Alleviative effects of glutamate against chemotherapeutic agent-induced intestinal mucositis.

5-Fluorouracil (5-FU) is one of the most widely used chemotherapeutic agents; however, it often causes intestinal mucositis with severe diarrhea. An efficient treatment strategy to reduce this side effect is lacking. Glutamate (Glu), a nonessential amino acid, is the most important energy source in the small intestine and has been shown to maintain intestinal morphology, barrier function, and antioxidative capacity. However, the effects of Glu on intestinal mucositis induced by chemotherapeutic agents have not been explored. This study aimed to demonstrate the alleviative effects of Glu on 5-FU-induced intestinal mucositis. Mucositis was induced in C57B/6N mice by intraperitoneal injection of 5-FU (50 mg/kg) for 6 days and assessed by histological and physiological analyses. Glu (500 or 1000 mg/kg) was orally administered as a pretreatment twice daily for 7 days before the initial treatment of 5-FU. Cellular proliferation and apoptosis were assessed using Ki-67 immunostaining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, respectively. Furthermore, fluorescein isothiocyanate-dextran infiltration was assessed to measure intestinal permeability. In vitro experiments using rat intestinal epithelial cells (IEC-6 cells) were performed to clarify the effect of Glu on 5-FU-induced barrier dysfunction. Glu alleviated 5-FU-induced intestinal mucositis by reducing villi shortening, enhancing cell proliferation, and suppressing apoptosis. It also alleviated the 5-FU-induced increased intestinal permeability. In vitro studies revealed significantly increased trans-epithelial electrical resistance (TEER) in Glu-pretreated IEC-6 cells compared to that in 5-FU-treated and control cells. In conclusion, the findings of this study provide evidence for the potential of Glu to protect against 5-FU-induced intestinal mucositis in patients with cancer.

New proposal to revise the classification for squamous cell carcinoma of the external auditory canal and middle ear.

BACKGROUND: The prognosis of patients with advanced squamous cell carcinoma of the external auditory canal and middle ear has been improved by advances in skull base surgery and multidrug chemoradiotherapy during the last two decades. METHODS: Ninety-five patients with squamous cell carcinoma of the external auditory canal and middle ear who were treated between 1998 and 2017 were enrolled. The number of patients with tumour stages T1, T2, T3 and T4 was 15, 22, 24 and 34, respectively. Oncological outcomes and prognostic factors were retrospectively investigated. RESULTS: Among patients with T4 disease, invasion of the brain (p = 0.024), carotid artery (p = 0.049) and/or jugular vein (p = 0.040) were significant predictors of poor prognosis. The five-year overall survival rate of patients with at least one of these factors (T4b) was significantly lower than that of patients without these factors (T4a) (25.5 vs 65.5 per cent, p = 0.049). CONCLUSION: It is proposed that stage T4 be subclassified into T4a and T4b according to the prognostic factors.

Functional Regulatory Mechanisms Underlying Bone Marrow Mesenchymal Stem Cell Senescence During Cell Passages.

Mesenchymal stem cell (MSC) transplantation is an effective periodontal regenerative therapy. MSCs are multipotent, have self-renewal ability, and can differentiate into periodontal cells. However, senescence is inevitable for MSCs. In vitro, cell senescence can be induced by long-term culture with/without cell passage. However, the regulatory mechanism of MSC senescence remains unclear. Undifferentiated MSC-specific transcription factors can regulate MSC function. Herein, we identified the regulatory transcription factors involved in MSC senescence and elucidated their mechanisms of action. We cultured human MSCs (hMSCs) with repetitive cell passages to induce cell senescence and evaluated the mRNA and protein expression of cell senescence-related genes. Additionally, we silenced the cell senescence-induced transcription factors, GATA binding protein 6 (GATA6) and SRY-box 11 (SOX11), and investigated senescence-related signaling pathways. With repeated passages, the number of senescent cells increased, while the cell proliferation capacity decreased; GATA6 mRNA expression was upregulated and that of SOX11 was downregulated. Repetitive cell passages decreased Wnt and bone morphogenetic protein (BMP) signaling pathway-related gene expression. Silencing of GATA6 and SOX11 regulated Wnt and BMP signaling pathway-related genes and affected cell senescence-related genes; moreover, SOX11 silencing regulated GATA6 expression. Hence, we identified them as pair of regulatory transcription factors for cell senescence in hMSCs via the Wnt and BMP signaling pathways.

Addition of low-dose liraglutide to insulin therapy is useful for glycaemic control during the peri-operative period: effect of glucagon-like peptide-1 receptor agonist therapy on glycaemic control in patients undergoing cardiac surgery (GLOLIA study).

AIM: To test the hypothesis that the addition of a glucagon-like peptide-1 receptor agonist that can decrease glucose levels without increasing the hypoglycaemia risk will achieve appropriate glycaemic control during the peri-operative period. METHODS: We studied 70 people with Type 2 diabetes who underwent elective cardiac surgery. Participants were randomized to either an insulin-alone or an insulin plus liraglutide 0.6 mg/day group. We evaluated average M values, which indicated the proximity index of the target glucose level from day 1 to day 10. RESULTS: The average M value in the liraglutide plus insulin group was significantly lower than that in the insulin-alone group (liraglutide plus insulin 5.8 vs insulin-alone 12.3; P < 0.001). The frequency of insulin dose modification in the liraglutide plus insulin group was significantly lower than that in the insulin-alone group (odds ratio 0.19, 95% CI 0.08-0.49; P < 0.001). The frequency of hypoglycaemia in the liraglutide plus insulin group tended to be lower than that in the insulin-alone group (odds ratio 0.57, 95% CI 0.15-2.23; P = 0.21). CONCLUSIONS: The results of this study showed that the addition of low-dose liraglutide to insulin achieved lower M values than insulin alone, suggesting that the addition of low-dose liraglutide may achieve better glycaemic control during the peri-operative period. (Clinical trials registry no.: UMIN 000008003).

An anatomical hypothesis: a "concentric-structured model" for the theoretical understanding of the surgical anatomy in the upper mediastinum required for esophagectomy with radical mediastinal lymph node dissection.

Understanding the surgical anatomy is the key to reducing surgical invasiveness especially in the upper mediastinal dissection for esophageal cancer, which is supposed to have a significant impact on curability and morbidity. However, there is no theoretical recognition regarding the surgical anatomy required for esophagectomy, although the surgical anatomy in abdominal digestive surgery has been developed on the basis of embryological findings of intestinal rotation and fusion fascia. Therefore, we developed a hypothesis of a 'concentric-structured model' of the surgical anatomy in the upper mediastinum based on human embryonic development. This model was characterized by three factors: (1) a concentric and symmetric three-layer structure, (2) bilateral vascular distribution, and (3) an 'inter-layer potential space' composed of loose connective tissue. The concentric three-layer structure consists of the 'visceral layer', the 'vascular layer', and the 'parietal layer': the visceral layer containing the esophagus, trachea, and recurrent laryngeal nerves as the central core, the vascular layer of major blood vessels surrounding the visceral core to maintain the circulation, and the parietal layer as the outer frame of the body. The bilateral vascular distribution consists of the inferior thyroid arteries and bronchial arteries originating from the bilateral dorsal aortae in an embryo. This bilateral vascular distribution may be related to the formation of the proper mesentery of the esophagus and frequent lymph node metastasis observed in the visceral layer around recurrent laryngeal nerves. The three concentric layers are bordered by loose connective tissue called the 'inter-layer potential space'. This inter-layer potential space is the fundamental factor of our concentric-structured model as the appropriate surgical plane of dissection. The peripheral blood vessels, nerves, and lymphatics transition between each layer, thereby penetrating this loose connective tissue forming the inter-layer potential space. Recurrent laryngeal nerves also transition from the vascular layer after branching off from the vagal nerves and then ascend consistently in the visceral layer. We investigated the validity of this concentric-structured model, confirming the intraoperative images and the surgical outcomes of thoracoscopic esophagectomy in a prone position (TSEP) before and after the introduction of this hypothetical anatomy model. A total of 226 patients with esophageal cancer underwent TSEP from January 2015 to December 2016. After the introduction of this model, the surgical outcomes in 105 patients clearly improved for the operation time of the thoracoscopic procedure (160 min vs. 182 min, P = 0.01) and the incidence of recurrent laryngeal nerve palsy (19.0% vs. 36.4%, P = 0.004). Moreover, we were able to identify the concentric and symmetric layer structure through surgical dissection along the inter-layer potential space between the visceral and vascular layers ('viscero-vascular space') in all 105 cases after introduction of the hypothetical model. The concentric-structured model based on embryonic development is clinically beneficial for achieving less-invasive esophagectomy by ensuring a theoretical understanding of the surgical anatomy in the upper mediastinum.

Terminal Ileac Ulcers Mimicked Post-transplantation Lymphoproliferative Disorder in a Heart Recipient Treated With Everolimus: A Case Report.

Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized and potentially fatal complication of cardiac transplantation that commonly involves the gastrointestinal tract. Herein, we report a case of life-threatening gastrointestinal bleeding from recurrent terminal ileac ulcers mimicking PTLD in a heart recipient treated with everolimus (EVL). A 40-year-old man underwent heart transplantation for dilated cardiomyopathy 3 years prior to the current admission and was treated with tacrolimus and EVL. He was admitted to a local hospital because of fever, abdominal pain, and diarrhea. His symptoms persisted and, 3 weeks later, hematochezia occurred; thus, he was transferred to our hospital. As computed tomography and 18F-fluorodeoxyglucose positron emission tomography showed bowel-wall thickening of the terminal ileum, gastrointestinal PTLD was initially suspected. However, although colonoscopy- performed after switching EVL to mycophenolate mofetil (MMF)-showed terminal ileac ulcers, the histologic examination revealed no findings corresponding to PTLD. As EVL may delay ulcer healing, MMF was maintained for 3 months. After repeated colonoscopy showed ulcer healing, MMF was switched back to EVL for cardiac allograft vasculopathy prevention. Three weeks later, he was emergently admitted to a local hospital for life-threatening gastrointestinal bleeding from a recurrent terminal ileal ulcer, which required hemostatic forceps hemostasis. As EVL is suspected to be associated with recurrent ileal ulcers, EVL was again switched back to MMF. The ileal ulcers resolved, without recurrence in 3 months of clinical follow-up. This case demonstrates that cases of life-threatening gastrointestinal bleeding from recurrent terminal ileac ulcers can mimic PTLD in a heart recipient treated with EVL.

Condyloma Acuminata of the Urethra in a Male Renal Transplant Recipient: A Case Report.

BACKGROUND: Condyloma acuminatum (CA) is a common sexually transmitted disease associated with human papilloma virus (HPV). CA occurring in the urethra is rare and has not been reported in male renal transplant recipients. In addition, despite immunosuppressive conditions and increased risk of HPV-related malignant neoplasms in transplant recipients, HPV testing in male transplant recipients has been uncommon. Here we report a case of urethral CA in a male deceased donor renal transplantation recipient and discuss the importance of HPV testing in male transplant recipients. CASE PRESENTATION: A 33-year-old male deceased donor renal transplant recipient presented with miction pain 5 years after the transplantation. He reported repeated urinary tract infections with no sexual contact since the renal transplantation. Multiple papillary tumors in his penile urethra were detected by cystoscopy, and a biopsy sample was pathologically diagnosed with CA. Transurethral tumor resection was performed, and the tumors were completely resected. Additional HPV risk type screening with a urethral smear sample showed the prevalence of low-risk HPV. Although tacrolimus was switched to everolimus and imiquimod cream was administered, the tumors recurred 6 months after the resection, and a second resection was performed. No further recurrence has been observed for 1 year to date. CONCLUSION: As the urethral CA was possibly related to immunosuppressive conditions and a risk for HPV-related malignant neoplasm, the case required careful diagnosis, including HPV risk type. The methodology of sampling for HPV testing in men has not been established. This case suggests the necessity for further discussion about HPV testing in male transplant recipients.

Partial Cystectomy of Paraganglioma of the Urinary Bladder Before Living Kidney Transplantation: Case Report.

BACKGROUND: Paraganglioma (extra-adrenal pheochromocytoma) of the bladder is a very rare disease, accounting for 0.06% of all bladder tumors. Optimal management of bladder paraganglioma before kidney transplantation is unknown. We report a case of partial cystectomy for urinary bladder paraganglioma before living kidney transplantation. CASE PRESENTATION: A 59-year-old man with a 27-year history of hemodialysis was referred to our department for further examination of a bladder tumor detected during pre-transplantation testing. Cystoscopy revealed a submucosal tumor on the right side of the bladder. The patient experienced a hypertensive crisis during transurethral resection of the bladder tumor. Endocrinologic and pathologic examinations confirmed the diagnosis of paraganglioma in the urinary bladder. A partial cystectomy was performed before kidney transplantation. Nine months after partial cystectomy, the patient underwent AB0-incompatible living kidney transplantation from his spouse. No disease recurrence or graft rejection was observed 12 months after the transplantation. CONCLUSIONS: To our knowledge, this is the 1st report on the management of paraganglioma in the urinary bladder before living kidney transplantation. Kidney transplantation after partial cystectomy is an option that may be considered in patients with paraganglioma of the urinary bladder, with careful observations of bladder function and vesicoureteral reflux to the grafts.

Reparative bone-like tissue formation in the tooth of a systemic sclerosis patient.

AIM: To report a case of reparative bone-like tissue formation in the tooth of a patient with systemic sclerosis. SUMMARY: A 58-year-old Japanese female patient with systemic sclerosis was referred because of tooth fracture. Cone beam computerized tomography (CBCT) revealed multiple root resorption and the unclear transition from alveolar bone to root profile. A sample from a fractured tooth was analysed histologically. Haematoxylin and eosin-stained sections revealed the irregular replacement of pulp and dentine by bone-like tissue. Calcinosis was noted in various parts of the body and a histological analysis identified it as dystrophic calcification on sclerosed fibrous connective tissue. Bite force and the occlusal area were markedly weaker than the means for female of the same age. KEY LEARNING POINTS: CBCT may be more useful than dental radiography for diagnosing multiple root resorption in systemic sclerosis patients. When systemic sclerosis patients have calcinosis, their root status must be examined carefully. When root resorption is present in systemic sclerosis patients, reparative bone-like tissue formation in teeth needs to be taken into account prior to the initiation of dental treatment.

The induced RNA-binding protein, HuR, targets 3'-UTR region of IL-6 mRNA and enhances its stabilization in periodontitis.

RNA-binding proteins (RBPs) regulate mRNA stability by binding to the 3'-untranslated region (UTR) region of mRNA. Human antigen-R (HuR), one of the RBPs, is involved in the progression of diseases, such as rheumatoid arthritis, diabetes mellitus and some inflammatory diseases. Interleukin (IL)-6 is a major inflammatory cytokine regulated by HuR binding to mRNA. Periodontal disease (PD) is also an inflammatory disease caused by elevations in IL-6 following an infection by periodontopathogenic bacteria. The involvement of HuR in the progression of PD was assessed using in-vitro and in-vivo experiments. Immunohistochemistry of inflamed periodontal tissue showed strong staining of HuR in the epithelium and connective tissue. HuR mRNA and protein level was increased following stimulation with Porphyromonas gingivalis (Pg), one of the periodontopathogenic bacteria, lipopolysacchride (LPS)-derived from Pg (PgLPS) and tumour necrosis factor (TNF)-α in OBA-9, an immortalized human gingival epithelial cell. The luciferase activity of 3'-UTR of IL-6 mRNA was increased by TNF-α, Pg and PgLPS in OBA-9. Luciferase activity was also increased in HuR-over-expressing OBA-9 following a bacterial stimulation. Down-regulation of HuR by siRNA resulted in a decrease in mRNA expression and production of IL-6. In contrast, the over-expression of HuR increased IL-6 mRNA expression and production in OBA-9. The HuR inhibitor, quercetin, suppressed Pg-induced HuR mRNA expression and IL-6 production in OBA-9. An oral inoculation with quercetin also inhibited bone resorption in ligature-induced periodontitis model mice as a result of down-regulation of IL-6. These results show that HuR modulates inflammatory responses by regulating IL-6.

Reversible Cerebral Vasoconstriction Syndrome After Heart Transplantation: A Case Report.

BACKGROUND: Reversible cerebral vasoconstriction syndrome (RCVS) is a transient cerebrovascular disorder putatively caused by some immunosuppressive agents. CASE REPORT: We recently encountered a 47-year-old female patient diagnosed with dilated cardiomyopathy who developed RCVS after heart transplantation. A triple-drug regimen consisting of tacrolimus, mycophenolate mofetil, and a corticosteroid was started after surgery. On postoperative day (POD) 11, the patient developed a severe headache, although computed tomography of the head demonstrated no signs of hemorrhage or infarction. At first, both a painkiller and migraine drugs were regularly administered to the patient. On POD 21, however, she developed an unbearable headache with a visual field defect and mild hemiparesis of the right hand. Magnetic resonance imaging (MRI) of the brain revealed a cerebral infarction in the left occipital lobe with diffuse vasoconstriction of both the middle and posterior cerebral arteries. A diagnosis of RCVS was made and tacrolimus, a drug suspected to cause RCVS, was discontinued. In its place, two doses of basiliximab followed by everolimus, both of which are alternatives for tacrolimus, were given. The corticosteroid dose was also increased. Furthermore, to release vasoconstriction, both verapamil and diltiazem were administered. On POD 27, cerebrovascular constrictions were shown to be relieved on brain MRI and the patient's neurological symptoms subsequently almost completely diminished. CONCLUSION: RCVS should always be considered as a cause of headache in heart transplant recipients because tacrolimus, an immunosuppressive agent, may trigger RCVS. This will allow rapid intervention that is essential for avoiding irreversible neurological deficits.

Urinary WT1-positive cells as a non-invasive biomarker of crescent formation.

OBJECTIVE: The purpose of this study was to assess the relationship between urinary WT1-positive cells (podocytes and active parietal epithelial cells) and WT1-positive cells in renal biopsy to investigate whether urinary WT1-positive cells are useful for detection of crescent formation. METHODS: Fifty-two patients with kidney disease were investigated (15 cases with crescentic lesions and 37 cases with non-crescentic lesions) for immunoenzyme staining using anti-WT1 antibody for urine cytology and renal biopsy. Numbers of WT1-positive cells in urine and renal biopsy were counted. RESULTS: There was no correlation between urinary WT1-positive cells and WT1-positive cells in renal biopsy. However, the number of urinary WT1-positive cells in patients with crescentic lesions was significantly higher than in patients with non-crescentic lesions. In addition, the best cut-off value to detect patients with crescentic lesions using urinary was 5 cells/10-mL (area under the concentration-time curve=0.735). CONCLUSIONS: The results of our study suggest urinary WT1-positive cells can be used to detect patients with crescent formation using 5 cells/10-mL cutoff value. WT1-positive glomerular podocytes and parietal epithelial cells may be shed into urine in active glomerular disease. This study, investigating the relationship between WT1-positive cells in urine and in the renal biopsy found no correlation; however, the results do suggest that, using a cutoff value of 5 cells/10 mL, WT1 positive urinary cells can be used to detect patients with crescent formation.

MSC/ECM Cellular Complexes Induce Periodontal Tissue Regeneration.

Transplantation of mesenchymal stem cells (MSCs), which possess self-renewing properties and multipotency, into a periodontal defect is thought to be a useful option for periodontal tissue regeneration. However, developing more reliable and predictable implantation techniques is still needed. Recently, we generated clumps of an MSC/extracellular matrix (ECM) complex (C-MSC), which consisted of cells and self-produced ECM. C-MSCs can regulate their cellular functions in vitro and can be grafted into a defect site, without any artificial scaffold, to induce bone regeneration. Accordingly, this study aimed to evaluate the effect of C-MSC transplantation on periodontal tissue regeneration in beagle dogs. Seven beagle dogs were employed to generate a premolar class III furcation defect model. MSCs isolated from dog ilium were seeded at a density of 7.0 × 104 cells/well into 24-well plates and cultured in growth medium supplemented with 50 µg/mL ascorbic acid for 4 d. To obtain C-MSCs, confluent cells were scratched using a micropipette tip and were then torn off as a cellular sheet. The sheet was rolled up to make round clumps of cells. C-MSCs were maintained in growth medium or osteoinductive medium (OIM) for 5 or 10 d. The biological properties of C-MSCs were evaluated in vitro, and their periodontal tissue regenerative activity was tested by using a dog class III furcation defect model. Immunofluorescence analysis revealed that type I collagen fabricated the form of C-MSCs. OIM markedly elevated calcium deposition in C-MSCs at day 10, suggesting its osteogenic differentiation capacity. Both C-MSCs and C-MSCs cultured with OIM transplantation without an artificial scaffold into the dog furcation defect induced periodontal tissue regeneration successfully compared with no graft, whereas osteogenic-differentiated C-MSCs led to rapid alveolar bone regeneration. These findings suggested that the use of C-MSCs refined by self-produced ECM may represent a novel predictable periodontal tissue regenerative therapy.

Percutaneous Coronary Intervention and Coronary Artery Bypass Grafting in Heart Transplant Recipients With Transplant Coronary Arterial Vasculopathy.

BACKGROUND: Transplant coronary arterial vasculopathy (TCAV) is a major cause of death after heart transplantation (HTx). Palliative coronary revascularization has been attempted in patients with severe TCAV; however, the outcome has not been fully elucidated. METHODS: Ninety-six patients who were treated after HTx at our institute between 1999 and 2015 were screened for TCAV. TCAV was defined as >70% stenosis on coronary angiography (CAG) or a maximal intimal thickness of >0.5 mm in the right or left coronary arteries on intracoronary ultrasonography (IVUS). In the present study, the outcomes of patients with severe TCAV who underwent percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) were investigated. RESULTS: TCAV containing donor-transmitted atherosclerosis was cumulatively found in 69 patients (71.9% of the total; mean age, 34.6 ± 13.1 years; 52 men; mean follow-up duration, 83.0 ± 60.4 months). Five (7.2%) and 64 (92.8%) of the 69 patients were diagnosed as having TCAV by use of CAG and IVUS, respectively. All 5 patients diagnosed by with the use of CAG underwent coronary revascularization between 1 and 236 months after HTx. Three patients underwent PCI with drug-eluting stents, with a primary success rate of 100%. No angiographic restenosis occurred in 2 patients at 31 and 36 months after PCI, respectively. Meanwhile, 2 patients underwent CABG. No peri-operative complications occurred, and all grafts were patent as assessed by use of CAG at 34 and 5 months after CABG. CONCLUSIONS: Coronary revascularization was feasible and effective for severe TCAV with middle-term follow-up.

Thermogenesis induced by amino acid administration prevents intraoperative hypothermia and reduces postoperative infectious complications after thoracoscopic esophagectomy.

Minimally invasive thoracoscopic esophagectomy has potential advantages in minimizing the impairment of respiratory function and reducing surgical stress. However, thoracoscopic esophagectomy occasionally results in anesthesia-induced hypothermia, particularly in cases involving artificial pneumothorax with CO2. Thermogenesis induced by amino acid administration has been reported during anesthesia. Here, we tested the efficacy of amino acid treatment for the prevention of hypothermia, and we investigated the potential of this treatment to reduce postoperative infectious complications after thoracoscopic esophagectomy. We conducted a randomized trial in patients with esophageal cancer who underwent thoracoscopic esophagectomy in the prone position in two groups and analyzed the incidences of hypothermia and surgical complications. One-hundred and thirty patients were randomized. Administration of amino acids resulted in a significant increase in core body temperature. In the saline (n = 60) and amino acid (n = 70) administration groups, 30% and 14.2% of patients, respectively, experienced infectious surgical complications (P = 0.029), and 21.6% and 22.8% of patients, respectively, experienced noninfectious surgical complications (P = 0.86). Univariate analysis revealed that blood loss and amino acid administration were significant factors for infectious surgical complications. Multivariate analysis revealed that amino acid administration was an independent factor reducing infectious surgical complications (P = 0.025, 95% confidence interval: 0.105-0.864). Administration of amino acids prevents hypothermia and reduces postoperative infectious complications after thoracoscopic esophagectomy.

Optimization of steroid injection intervals for prevention of stricture after esophageal endoscopic submucosal dissection: A randomized controlled trial.

BACKGROUND: Esophageal endoscopic submucosal dissection enables en bloc resection of large superficial esophageal cancer; however, this procedure may induce severe stricture. Intralesional steroid injection is an effective treatment for prevention of stricture after endoscopic resection; however, there have been no studies assessing the duration of such treatment. The aim of this study was to reduce treatment duration and to evaluate the effectiveness of weekly and biweekly steroid injections in preventing esophageal stricture after endoscopic resection. PATIENTS METHOD: We performed a randomized controlled trial comparing patients receiving weekly or biweekly intralesional triamcinolone injections. Patients with a mucosal defect greater than 75% (3/4) of the luminal circumference after esophageal endoscopic submucosal dissection for superficial esophageal cancers were enrolled. The primary endpoint was the duration of steroid injection treatment. RESULTS: The median duration of treatment was 37.0 days in the weekly group and 34.2 days in the biweekly group (P = 0.059). Among patients with a mucosal defect larger than 50 mm, there was a significant difference in the median duration of treatment between the weekly and biweekly groups (42.5 days vs 29.0 days, P = 0.013). CONCLUSION: Biweekly steroid injection of triamcinolone reduces treatment duration, particularly in those with mucosal defects larger than 50 mm. (Acta gastro-enterol. belg., 2016, 79, 315-320).

Prognostic value of tumor-infiltrating lymphocytes differs depending on histological type and smoking habit in completely resected non-small-cell lung cancer.

BACKGROUND: T-cell infiltration in tumors has been used as a prognostic tool in non-small-cell lung cancer (NSCLC). However, the influence of smoking habit and histological type on tumor-infiltrating lymphocytes (TILs) in NSCLC remains unclear. PATIENTS AND METHODS: We evaluated the prognostic significance of TILs (CD4+, CD8+, CD20+, and FOXP3+) according to histological type and smoking habit using automatic immunohistochemical staining and cell counting in 218 patients with NSCLC. RESULTS: In multivariate survival analyses of clinical, pathological, and immunological factors, a high ratio of FOXP3+ to CD4+ T cells (FOXP3/CD4) [hazard ratio (HR): 4.46, P < 0.01 for overall survival (OS); HR: 1.96, P < 0.05 for recurrence-free survival (RFS)] and a low accumulation of CD20+ B cells (HR: 2.45, P = 0.09 for OS; HR: 2.86, P < 0.01 for RFS) were identified as worse prognostic factors in patients with adenocarcinoma (AD). In non-AD, a low number of CD8+ T cells were correlated with an unfavorable outcome (HR: 7.69, P < 0.01 for OS; HR: 3.57, P < 0.02 for RFS). Regarding smoking habit in AD, a high FOXP3/CD4 ratio was poorly prognostic with a smoking history (HR: 5.21, P < 0.01 for OS; HR: 2.38, P < 0.03 for RFS), whereas a low accumulation of CD20+ B cells (HR: 4.54, P = 0.03 for OS; HR: 2.94, P < 0.01 for RFS) was confirmed as an unfavorable factor in non-smokers with AD. CONCLUSIONS: A low number of CD8+ T cells in non-AD, a high FOXP3/CD4 ratio in smokers with AD, and a low number of CD20+ B cells in non-smokers with AD were identified as independent unfavorable prognostic factors in resected NSCLC. Evaluating the influence of histological type and smoking habit on the immunological environment may lead to the establishment of immunological diagnosis and appropriate individualized immunotherapy for NSCLC.

A multi-centre retrospective study of mandibular fractures: do occlusal support and the mandibular third molar affect mandibular angle and condylar fractures?

This retrospective study was performed to investigate the influence of occlusal support and the presence, state, and position of mandibular third molars on the incidence of mandibular angle and condylar fractures. The following variables were investigated: age, sex, cause of fracture, presence and state (impaction, angulation, and the number of roots) of the mandibular third molars, site of the mandibular fracture, presence of occlusal support, duration of intermaxillary fixation, and postoperative complications. Various risk factors for mandibular angle and condylar fractures were investigated by univariate analysis. The risk of mandibular angle fracture was significantly higher in patients with occlusal support and mandibular third molars. The risk of condylar fracture was significantly higher in patients without occlusal support or mandibular third molars. The position and angulation of the mandibular third molars were not significant risk factors in mandibular angle and condylar fractures. This study demonstrated the influence of occlusal support and the presence of mandibular third molars on the incidence of mandibular angle and condylar fractures. The presence of occlusal support may be a more important factor affecting mandibular angle or condylar fractures than the position of the mandibular third molars.

Association Between the Polyomaviruses Titers and Decoy Cell Positivity Rates After Renal Transplantation.

BACKGROUND: Urinary decoy cells develop after renal transplantation and their appearance is attributable primarily to the proliferation of polyomavirus types BK and JC. We measured the levels of these 2 viruses that cause decoy cells to appear in the urine. PATIENTS AND METHODS: BK and JC virus levels were quantified in 1182 urine samples from 335 renal transplant patients using a multiplex Taqman real-time polymerase chain reaction assay. Forty-four samples were excluded from analyses because both viruses were present at ≥10(4) copies/mL. We analyzed the relationship between viral load and the presence of urinary decoy cells. RESULTS: Decoy cells were observed in 237 of 1138 urine samples (21%) and the BK and JC viruses were positive in 205 (18%) and 455 (40%) samples, respectively. Decoy cells were observed in 0%, 21%, 67%, 87%, 100%, and 96% of urine samples when the BK viral load was <10(4), 10(4)-10(5), 10(5)-10(6), 10(6)-10(7), 10(7)-10(8), and ≥10(8) copies/mL, respectively; and in 1%, 13%, 41%, 59%, 87%, and 97% of urine samples when the JC viral load was <10(4), 10(4)-10(5), 10(5)-10(6), 10(6)-10(7), 10(7)-10(8), and ≥10(8) copies/mL, respectively. CONCLUSIONS: BK virus more frequently triggered the appearance of decoy cells than did JC virus at equivalent viral titers.