Automated Skeletal Classification with Lateral Cephalometry Based on Artificial Intelligence.

Lateral cephalometry has been widely used for skeletal classification in orthodontic diagnosis and treatment planning. However, this conventional system, requiring manual tracing of individual landmarks, contains possible errors of inter- and intravariability and is highly time-consuming. This study aims to provide an accurate and robust skeletal diagnostic system by incorporating a convolutional neural network (CNN) into a 1-step, end-to-end diagnostic system with lateral cephalograms. A multimodal CNN model was constructed on the basis of 5,890 lateral cephalograms and demographic data as an input. The model was optimized with transfer learning and data augmentation techniques. Diagnostic performance was evaluated with statistical analysis. The proposed system exhibited >90% sensitivity, specificity, and accuracy for vertical and sagittal skeletal diagnosis. Clinical performance of the vertical classification showed the highest accuracy at 96.40 (95% CI, 93.06 to 98.39; model III). The receiver operating characteristic curve and the area under the curve both demonstrated the excellent performance of the system, with a mean area under the curve >95%. The heat maps of cephalograms were also provided for deeper understanding of the quality of the learned model by visually representing the region of the cephalogram that is most informative in distinguishing skeletal classes. In addition, we present broad applicability of this system through subtasks. The proposed CNN-incorporated system showed potential for skeletal orthodontic diagnosis without the need for intermediary steps requiring complicated diagnostic procedures.

Effect of prolonged inspiratory time on gas exchange during robot-assisted laparoscopic urologic surgery.

BACKGROUND: Gas exchange disturbance may develop during urologic robotic laparoscopic surgery with the patient in a steep Trendelenburg position. This study investigated whether prolonged inspiratory time could mitigate gas exchange disturbances including hypercapnia. METHODS: In this randomized cross-over trial, 32 patients scheduled for robot-assisted urologic surgery were randomized to receive an inspiratory to expiratory time ratio (I:E) of 1:1 for the first hour of pneumoperitoneum followed by 1:2 for last period of surgery (group A, n = 17) or I:E of 1:2 followed by 1:1 (group B, n = 15). Arterial blood gas analysis, airway pressure and hemodynamic variables were assessed at four time points (T1: 10 min after induction of general anesthesia, T2: 1 h after the initiation of pneumoperitoneum, T3: 1 h after T2 and T4: at skin closure). The carry over effect of initial I:E was also evaluated over the next hour through arterial blood gas analysis. RESULTS: There was a significant decrease in partial pressure of oxygen in arterial blood (PaO2) for both groups at T2 and T3 compared to T1 but in group B the PaO2 at T4 was not decreased from the baseline. Partial pressure of carbon dioxide in arterial blood (PaCO2) increased with I:E of 1:2 but did not significantly increase with I:E of 1:1; however, there were no differences in PaO2 and PaCO2 between the groups. CONCLUSION: Decreased oxygenation by pneumoperitoneum was improved and PaCO2 did not increase after 1 h of I:E of 1:1; however, the effect of equal ratio ventilation longer than 1 h remains to be determined. There was no carryover effect of the two different I:E ratios.

Pharmacological interventions for protecting renal function after cardiac surgery: a Bayesian network meta-analysis of comparative effectiveness.

Many drugs have been investigated as potentially protective of renal function after cardiac surgery. However, their comparative effectiveness has not been established. We performed an arm-based hierarchical Bayesian network meta-analysis including 95 randomised controlled trials with 28,833 participants, which allowed us to compare some agents not previously compared directly. Renal outcomes, including: the incidence of postoperative renal dysfunction and haemodialysis; serum creatinine level at 24 hours postoperatively; all-cause mortality; and length of hospital and ICU stay, were compared. Exploratory meta-regression was conducted for potential effect modifiers. A random effects model was selected according to the evaluation of model fit by deviance information criteria. Atrial natriuretic peptide (odds ratio (95%CrI) 0.28 (0.17-0.48); moderate-quality evidence), B-type natriuretic peptide, dexmedetomidine, levosimendan and N-acetyl cysteine significantly decreased the rate of postoperative renal dysfunction compared with placebo. Atrial natriuretic peptide (OR (95%CrI) 0.24 (0.10-0.58); low-quality evidence), B-type natriuretic peptide, and dexamethasone significantly decreased the need for haemodialysis. Levosimendan significantly decreased mortality, OR (95%CrI) 0.49 (0.27-0.91); low-quality evidence). The benefit of atrial natriuretic peptide was still apparent when baseline renal function was normal. None of the potential effect modifiers were significantly correlated with our renal outcomes. Atrial natriuretic peptide was ranked best regarding renal dysfunction, haemodialysis and length of hospital stay. Levosimendan was ranked best regarding mortality and ICU stay. However, our results should be interpreted cautiously given the assumptions made about transitivity and consistency.

Quantitative proteomic analysis of HER2 expression in the selection of gastric cancer patients for trastuzumab treatment.

Background: A wide range of response rates have been reported in HER2-positive gastric cancer (GC) patients treated with trastuzumab. Other HER2-targeted therapies for GC have yet to show efficacy in clinical trials. These findings raise question about the ability of standard HER2 diagnostics to accurately distinguish between GC patients who would and would not benefit from anti-HER2 therapies. Patients and methods: GC patients (n = 237), including a subset from the Trastuzumab in GC (ToGA) trial were divided into three groups based on HER2 status and history of treatment with standard chemotherapy or chemotherapy plus trastuzumab. We applied mass spectrometry-based proteomic analysis to quantify HER2 protein expression in formalin-fixed tumor samples. Using HER2 expression as a continuous variable, we defined a predictive protein level cutoff to identify which patients would benefit from trastuzumab. We compared quantitated protein level with clinical outcome and HER2 status as determined by conventional HER2 diagnostics. Results: Quantitative proteomics detected a 115-fold range of HER2 protein expression among patients diagnosed as HER2 positive by standard methods. A protein level of 1825 amol/µg was predicted to determine benefit from the addition of trastuzumab to chemotherapy. Trastuzumab treated patients with HER2 protein levels above this cutoff had twice the median overall survival (OS) of their counterparts below the cutoff (35.0 versus 17.5 months, P = 0.011). Conversely, trastuzumab-treated patients with HER2 levels below the cutoff had outcomes similar to HER2-positive patients treated with chemotherapy. (Progression-free survival = 7.0 versus 6.5 months: P = 0.504; OS = 17.5 versus 12.6 months: P = 0.520). HER2 levels were not prognostic for response to chemotherapy. Conclusions: Proteomic analysis of HER2 expression demonstrated a quantitative cutoff that improves selection of GC patients for trastuzumab as compared with current diagnostic methods.

Increased Leptin and Leptin Receptor Expression in Dogs With Gallbladder Mucocele.

BACKGROUND: Leptin and its receptor play a role in several disease processes such as pancreatitis and heart disease. However, their association with gallbladder mucocele (GBM) in dogs has not been reported. HYPOTHESIS/OBJECTIVES: To evaluate differences in the expression of leptin and leptin receptor between dogs with and without GBM. ANIMALS: Twenty-five healthy dogs, including 9 laboratory beagle dogs, and 22 client-owned dogs with GBM. METHODS: Serum leptin concentration was determined in blood samples of all dogs by ELISA. Canine gallbladder samples were collected from 9 dogs with GBM that underwent surgery for therapeutic purposes and from 9 healthy laboratory beagle dogs as a normal control group. Samples were analyzed for leptin and leptin receptor mRNA by real-time polymerase chain reaction. RESULTS: Serum leptin concentration was significantly higher in dogs with GBM than in healthy dogs (medians of 7.03 and 2.18 ng/mL, respectively; P < .001). Patients with GBM that had undergone surgery had significantly higher serum leptin concentrations than those that had not (medians of 12.2 and 4.09 ng/mL, respectively; P = .001). However, no difference in serum leptin concentration was found between dogs with GBM with or without endocrinopathies. The mRNA expression levels of leptin and its receptor were significantly increased in the gallbladder tissues of dogs with GBM. CONCLUSIONS AND CLINICAL IMPORTANCE: Dysregulation of leptin might be involved in the pathophysiology of GBM, and leptin concentrations might be associated with GBM severity.

Elevated Microsatellite Alterations at Selected Tetranucleotide Repeats (EMAST) and Microsatellite Instability in Patients with Colorectal Cancer and Its Clinical Features.

PURPOSE: Recently, a different type of microsatellite instability (MSI) instability designated 'elevated microsatellite alterations at selected tetranucleotide repeats' (EMAST) has been reported in several neoplasms, but its clinical implications remain unclear. We aimed to determine the relationships among EMAST, MSI and clinicopathologic characteristics, including oncologic outcomes, in colorectal cancer (CRC). MATERIALS AND METHODS: We evaluated 100 sporadic CRC cases subjected to surgery using five markers (MYCL1, D9S242, D20S85, D8S321, and D20S82) for EMAST and the Bethesda panel for MSI status. Immunohistochemical detection of hMSH3, c-erbB2, EGFR and thymidylate synthase was performed. Clinical characteristics and prognostic relevance were assessed. RESULTS: We identified 22 EMAST-positive tumors (22.0%) and 32 MSI-high (MSI-H) tumors (32.0%). EMAST was more frequent in colon cancer than rectal cancer (p=0.033), and associated with MSI-H phenotype (p<0.001), low expression of hMSH3 (p=0.004), and overexpression of thymidylate synthase (p=0.006). Among the 38 MSI-L tumors, only one (4.5%) showed EMAST. Long-term oncologic results in terms of overall and disease-free survival were similar between EMAST and non-EMAST tumors. CONCLUSION: EMAST is more closely related to MSI-H than MSI-L or MSS status. The clinical and molecular characteristics of EMAST were distinct in terms of tumor location, thymidylate synthase expression, MSI status and hMSH3 expression. Our preliminary findings support the utility of EMAST as a new potential classifier in CRC.

Allogeneic adipose-derived stem cells for the treatment of perianal fistula in Crohn's disease: a pilot clinical trial.

AIM: Many perianal fistulae in Crohn's disease do not respond to conventional surgical and medical management and recurrence rates are high. The study evaluated the safety and feasibility of allogeneic adipose-derived stem cells for the treatment of perianal fistula in Crohn's disease. METHOD: A multicentre, open-label, dose escalation pilot study was performed. The first three patients (group 1) were administered 1 × 10(7) cells/ml based on the size of the fistula tract. Four weeks later, after which time this dose had been confirmed to be safe, the next three patients (group 2) were administered 3 × 10(7) cells/ml. The end-point was complete closure at 8 weeks after the injection. Patients who attended for the 8 week assessment were followed for an additional 6 months. RESULTS: There were no adverse events of Grade 3 or 4 severity and no adverse events related to the treatment with allogeneic adipose-derived stem cells. Two patients in group 1 achieved complete closure of the fistula at month 4 and month 6, and one patient in group 2 achieved complete closure at 8 weeks. The closure was sustained up to month 8 in all three of those patients. CONCLUSION: These data suggest that allogeneic adipose-derived stem cells may be a feasible treatment option for perianal fistula in Crohn's disease.

PHF2 histone demethylase acts as a tumor suppressor in association with p53 in cancer.

Plant homeodomain finger 2 (PHF2) has a role in epigenetic regulation of gene expression by demethylating H3K9-Me2. Several genome-wide studies have demonstrated that the chromosomal region including the PHF2 gene is often deleted in some cancers including colorectal cancer, and this finding encouraged us to investigate the tumor suppressive role of PHF2. As p53 is a critical tumor suppressor in colon cancer, we tested the possibility that PHF2 is an epigenetic regulator of p53. PHF2 was associated with p53, and thereby, promoted p53-driven gene expression in cancer cells under genotoxic stress. PHF2 converted the chromatin that is favorable for transcription by demethylating the repressive H3K9-Me2 mark. In an HCT116 xenograft model, PHF2 was found to be required for the anticancer effects of oxaliplatin and doxorubicin. In PHF2-deficient xenografts, p53 expression was profoundly induced by both drugs, but its downstream product p21 was not, suggesting that p53 cannot be activated in the absence of PHF2. To find clinical evidence about the role of PHF2, we analyzed the expressions of PHF2, p53 and p21 in human colon cancer tissues and adjacent normal tissues from patients. PHF2 was downregulated in cancer tissues and PHF2 correlated with p21 in cancers expressing functional p53. Colon and stomach cancer tissue arrays showed a positive correlation between PHF2 and p21 expressions. Informatics analyses using the Oncomine database also supported our notion that PHF2 is downregulated in colon and stomach cancers. On the basis of these findings, we propose that PHF2 acts as a tumor suppressor in association with p53 in cancer development and ensures p53-mediated cell death in response to chemotherapy.

Lateral spread response monitoring during microvascular decompression for hemifacial spasm. Comparison of two targets of partial neuromuscular blockade.

AIM: The aim of the present study was to determine (1) whether successful intraoperative electromyography monitoring for lateral spread response (LSR) is possible with partial neuromuscular blockade (NMB) in subjects undergoing microvascular decompression (MVD) for hemifacial spasm and (2) the adequate level of NMB to achieve that goal. MATERIAL AND METHODS: A total of 61 patients in whom LSR was monitored during MVD were enrolled in the study. Patients were randomly allocated to two groups: group TOF in which the NMB target was maintenance of two train-of-four (TOF) counts and group T1 in which the NMB target was maintenance of a T1/Tc ratio of 50 % (T1: first twitch height of TOF and Tc: control twitch height). The adductor pollicis brevis muscle was used to monitor TOF responses. The frequency of successful LSR monitoring, defined as successful baseline establishment and maintenance of LSR until surgical decompression, was compared between the two groups. RESULTS: Of the 61 patients 2 were excluded from the study so that 30 patients in group TOF and 29 patients in group T1 were analyzed. The success rate of LSR monitoring was clinically acceptable and significantly higher in group T1 than in group TOF, i.e. n = 15 (50.0 %) in group TOF versus n = 24 (82.8 %) in group T1 (P = 0.008), corresponding to a 32.8 % higher success rate in group T1 than group TOF (95 % CI: 13.9-51.7 %). Mean vecuronium infusion dose was smaller and mean TOF count was higher in group T1 than group TOF with a TOF count = 2 (1) in group TOF versus 3 (1) in group T1 (P = 0.003). Mean sevoflurane and remifentanil infusion doses were not different between groups. There was no incidence of spontaneous movement during microscopy in either group. CONCLUSION: Maintenance of partial NMB with a target T1/Tc ratio of 50 % resulted in a clinically acceptable success rate of LSR monitoring and surgical condition during MVD. Maintenance of partial NMB with a target T1/Tc ratio of 50 % rather than TOF count of two during LSR monitoring for MVD can therefore be recommended.

Evaluation of FOXP3 expression in canine mammary gland tumours.

The expression of the transcription factor forkhead box P3 (FOXP3) was examined in 62 canine mammary gland tumours via immunohistochemical analysis and association with the known expression of the oestrogen receptor-alpha (ERα), progesterone receptor (PR), c-erbB-2 receptor (HER2/neu), and survival. Positive staining for FOXP3 was present in 22.6% of the tumours and was associated with the histological type. Negative staining for FOXP3 was associated with positive ERα and PR expression (P < 0.001). The expression of FOXP3 in canine mammary gland tumours was significantly associated with the disease-free survival time (P = 0.029). The FOXP3 expression was not an independent prognostic factor in the multivariate analysis, though. The negative expression of FOXP3 in the canine mammary gland tumours was found to be related to histopathologic benignity and a longer survival time in canine mammary gland tumours.

The effects of prolonged inspiratory time during one-lung ventilation: a randomised controlled trial.

We evaluated the effects of a prolonged inspiratory time on gas exchange in subjects undergoing one-lung ventilation for thoracic surgery. One hundred patients were randomly assigned to Group I:E = 1:2 or Group I:E = 1:1. Arterial blood gas analysis and respiratory mechanics measurements were performed 10 min after anaesthesia induction, 30 and 60 min after initiation of one-lung ventilation, and 15 min after restoration of conventional two-lung ventilation. The mean (SD) ratio of the partial pressure of arterial oxygen to fraction of inspired oxygen after 60 min of one-lung ventilation was significantly lower in Group I:E = 1:2 compared with Group I:E = 1:1 (27.7 (13.2) kPa vs 35.2 (22.1) kPa, respectively, p = 0.043). Mean (SD) physiological dead space-to-tidal volume ratio after 60 min of one-lung ventilation was significantly higher in Group I:E = 1:2 compared with Group I:E = 1:1 (0.46 (0.04) vs 0.43 (0.04), respectively, p = 0.008). Median (IQR [range]) peak inspiratory pressure was higher in Group I:E = 1:2 compared with Group I:E = 1:1 after 60 min of one-lung ventilation (23 (22-25 [18-29]) cmH2O vs 20 (18-21 [16-27]) cmH2O, respectively, p < 0.001) and median (IQR [range]) mean airway pressure was lower in Group I:E = 1:2 compared with Group I:E = 1:1 (10 (8-11 [5-15]) cmH2O vs 11 (10-13 [5-16]) cmH2O, respectively, p < 0.001). We conclude that, compared with an I:E ratio of 1:2, an I:E ratio of 1:1 resulted in a modest improvement in oxygenation and decreased shunt fraction during one-lung ventilation.

A case of isolated bilateral pulmonary arterial calcification diagnosed in utero.

We report a very rare case of isolated multiple pulmonary arterial calcification with severe bilateral peripheral pulmonary arterial stenosis diagnosed in utero. Despite treatment with bisphosphonate for 6 months, systolic right ventricular pressure increased persistently and surpassed left ventricular pressure. After successful bilateral pulmonary arterioplasty at 13 months of age, the patient showed decreased systolic right ventricular pressure with normal interventricular septal configuration. This is the first case report for an isolated pulmonary artery calcification without other arterial calcification proven by non-contrast computed tomography of a living patient.

Prolonged inspiratory time produces better gas exchange in patients undergoing laparoscopic surgery: A randomised trial.

BACKGROUND: Laparoscopic surgery performed with a patient in the Trendelenburg position is known to have adverse effects on pulmonary gas exchange and respiratory mechanics. We supposed that prolonged inspiratory time can improve gas exchange at lower airway pressure. METHODS: One hundred patients undergoing gynaecologic laparoscopic surgery were randomly assigned to one of four groups: conventional inspiratory-to-expiratory (I : E) ratio (Group 1 : 2), I : E ratio of 1 : 1 (Group 1 : 1), 2 : 1 (Group 2 : 1), or 1 : 2 with external positive end-expiratory pressure (PEEP) of 5 cmH2 O (Group 1 : 2 PEEP). Tidal volume was set to 6 ml/kg, and I : E ratio was adjusted at the onset of pneumoperitoneum. Arterial blood gas analysis with measurements of partial pressure of arterial oxygen/fraction of inspired oxygen (PaO2 /FiO2 ), and physiologic dead space-to-tidal volume ratio (VD /VT ) was performed 15 min after anaesthetic induction (T1), and 30 (T2) and 60 min (T3) after onset of CO2 insufflation. RESULTS: PaO2 /FiO2 at T3 in Groups 1 : 1, 2 : 1, and 1 : 2 PEEP were higher than Group 1 : 2. The partial pressure of arterial carbon dioxide at T3 in Group 2 : 1 was lower than the other groups. The VD /VT at T2 and T3 were lower in Groups 1 : 1 and 2 : 1 than Groups 1 : 2 and 1 : 2 PEEP. Peak or plateau airway pressure was higher in Group 1 : 2 PEEP than the other groups. CONCLUSIONS: A prolonged inspiratory time demonstrated a beneficial effect on oxygenation. Furthermore, it showed better CO2 elimination without elevating the peak or plateau airway pressure compared with applying external PEEP. In terms of gas exchange and respiratory mechanics, a prolonged inspiratory time appears to be superior to applying external PEEP in patients undergoing laparoscopic surgery in the Trendelenburg position.

Arthroscopic shoulder surgery under general anesthesia with brachial plexus block: postoperative respiratory dysfunction of combined obstructive and restrictive pathology.

OBJECTIVE: Changes in respiratory parameters and pulmonary function tests were evaluated after shoulder arthroscopic surgery with brachial plexus block (BPB). The purpose of this study was to identify the mechanism of respiratory dysfunction after this type of surgery. METHODS: Patients undergoing arthroscopic rotator cuff repair under general anesthesia (GA) with BPB were enrolled in the arthroscopy group (n = 30) while those undergoing open reduction of a clavicle or humerus fracture under GA were enrolled in the control group (n = 30). Forced vital capacity (FVC) and forced expiratory volume 1 s (FEV(1)) were measured at the outpatient clinic stage (#1) before (#2) and 20 min after BPB (#3) and 1 h after extubation (#4). Respiratory variable measurements along with the cuff leak test were performed 5 min after surgical positioning (T1) and at the start of skin closure (T2). Respiratory discomfort was evaluated after extubation. The upper airway diameters and soft tissue depth of chest wall were also measured by ultrasonography at stages #3 and #4. RESULTS: Static compliance decreased significantly at T2 in the arthroscopy group (50 ± 11 at T1 vs. 44 ± 9 ml/cm H(2)O at T2, p =0.035) but not in the control group. The incidence of positive cuff leak tests at T2 was significantly higher in the arthroscopy group than in the control group (47% in the arthroscopy group vs. 17% in controls, p =0.010). While FEV(1) and FVC remained stable at stages #1 and #2, FVC and FEV(1) decreased at stages #3 and #4 only in the arthroscopy group (FVC in arthroscopy group, #2: 3.26 ± 0.77 l; #3: 2.55 ± 0.63 l, p =0.015 vs. #2; #4: 2.66 ± 0.41 l, p =0.040 vs. #2). The subglottic diameter decreased at #4 in the arthroscopy group, while no changes occurred in the control group (0.70 ± 0.21 cm vs. 0.85 ± 0.23 cm in the arthroscopy and control groups, respectively, p =0.011). Depth of skin to pleura increased at both intercostal spaces 1-2 and 3-4 in the arthroscopy group. There were three cases of hypoxia (S(p)O(2) < 95%) with room air in the arthroscopy group while none occurred in the controls. CONCLUSION: Shoulder arthroscopic surgery under GA with BPB induced both restrictive and obstructive pathologies. It is important to maintain a high level of awareness for the potential negative respiratory effects of this surgery especially for subjects with pre-existing cardiopulmonary disease. The measurements in this study would be useful to monitor the risk of respiratory dysfunction in these patients.

MET in gastric carcinomas: comparison between protein expression and gene copy number and impact on clinical outcome.

BACKGROUND: The aim of this study was to compare gene copy number (GCN) and protein expression of MET and to evaluate their prognostic roles in gastric carcinomas. METHODS: MET protein expression and gene amplification (GA) status were determined by immunohistochemistry (IHC) and silver in-situ hybridisation (SISH), respectively, in a large series of gastric carcinoma. RESULTS: Protein overexpression was observed in 104 of 438 cases, with IHC 2+ in 94 and IHC 3+ in 10, and high polysomy of chromosome 7 and GA were found in 61 and 13 of 381, respectively. Direct comparison revealed a significant correlation between high level of protein expression and increased GCN. All cases with GA showed protein overexpression. Furthermore, all with IHC 3+ showed GA except 1, even which could be categorised as GA according to the ASCO/CAP guideline for human epidermal growth factor receptor 2 assessment. IHC 3+ and GA were significantly associated with poor prognosis. CONCLUSION: MET IHC reflects well on GA, and therefore, it could be a primary screening test for patient selection for anti-MET therapy if GA is a major determinant of drug responsiveness. Also, the prognostic role of MET indicates that anti-MET therapy is a very promising modality in adjuvant treatment for gastric cancer.

Anatomical analysis of computed tomography images for determining the optimal oblique fluoroscope angle for percutaneous coeliac plexus block.

This retrospective study used abdominal computed tomography (CT) scan images to determine the optimal safe oblique angle for fluoroscopy in fluoroscope-assisted coeliac plexus block (CPB). Abdominal CT scans from 131 patients were included in the study: 42 patients with cancer of the pancreas head, 45 with cancer of the pancreas body and tail and 44 with chronic pancreatitis. The oblique angle and entry distance from the midline were measured at the T12 and L1 levels, and the safe angle range that avoided puncture of the organs was also measured. The optimal angle varied between the T12 and L1 levels, and between the right and left sides at the T12 level. There was no difference in the oblique angle between the patient groups. The optimal oblique angle for fluoroscopy was determined to be 17° for right T12, 18° for left T12, and 19° for both left and right L1.

High FOXP3+ regulatory T-cell density in the sentinel lymph node is associated with downstream non-sentinel lymph-node metastasis in gastric cancer.

BACKGROUND: We aimed to evaluate the immunologic nature of sentinel lymph nodes (SLNs) in gastric cancer patients and to determine whether it can predict non-SLN metastasis. METHODS: Sentinel lymph node samples were collected from 64 gastric carcinoma patients who had undergone gastrectomy with SLN biopsy. One representative SLN sample was selected from each patient and was subjected to immunostaining for CD8, CD57, FOXP3, and DC-LAMP. The numbers of marker-positive cells in each sample were counted. The relationships between various immune cell densities and clinicopathologic parameters or metastasis status of SLNs and non-SLNs were sought. RESULTS: High FOXP3+ Treg density of the SLN was found to be significantly associated with the presence of metastasis in either SLNs or non-SLNs. DC-LAMP+ cell density of the SLN was the highest at the isolated tumours cell level, and this decreased along with an increase in tumour metastasis in either SLNs or non-SLNs. Univariate and multivariate logistic regression models revealed that high FOXP3+ Treg density of the SLN was an independently significant predictor of non-SLN metastasis. CONCLUSIONS: This study is the first to indicate an important role of SLNs in metastatic dissemination of gastric cancer. Our findings suggest that Tregs could be a new therapeutic target for regulating the metastasis of gastric cancer.

Determinants of Epstein-Barr virus-positive gastric cancer: an international pooled analysis.

BACKGROUND: Meta-analyses of the published literature indicate that about 9% of gastric cancers contain Epstein-Barr virus (EBV), with consistent and significant differences by sex and anatomic subsite. This study aimed to identify additional determinants of EBV positivity and their joint effects. METHODS: From 15 international populations with consistent laboratory testing for EBV, we pooled individual-level data for 5081 gastric cancer cases including information on age, sex, subsite, histologic type, diagnostic stage, geographic region, and period of diagnosis. First, we combined population-specific EBV prevalence estimates using random effects meta-analysis. We then aggregated individual-level data to estimate odds ratios of EBV positivity in relation to all variables, accounting for within-population clustering. RESULTS: In unadjusted analyses, EBV positivity was significantly higher in males, young subjects, non-antral subsites, diffuse-type histology, and in studies from the Americas. Multivariable analyses confirmed significant associations with histology and region. Sex interacted with age (P=0.003) and subsite (P=0.002) such that male predominance decreased with age for both subsites. The positivity of EBV was not significantly associated with either stage or time period. CONCLUSION: Aggregating individual-level data provides additional information over meta-analyses. Distinguishing histologic and geographic features as well as interactions among age, sex, and subsite further support classification of EBV-associated gastric cancer as a distinct aetiologic entity.