Prevalence and risk factors for lymph node metastasis after noncurative endoscopic resection for early gastric cancer: a systematic review and meta-analysis

Background

Additional surgery for all patients with noncurative resection after endoscopic resection (ER) for early gastric cancer (EGC) may be excessive due to the relatively low rate of lymph node metastasis (LNM) in such patients. However, the prevalence and risk factors for LNM after noncurative ER have not been consistent across studies.

Methods

We performed a systematic review of electronic databases through August 10, 2018 to identify cohort studies with patients who underwent additional surgery after noncurative ER for EGC. The prevalence of LNM in such patients was extracted for all studies. Odds ratios (ORs) were combined using random-effects meta-analyses to assess the risk of LNM, when possible.

Results

We identified 24 studies comprising 3877 patients with 311 having LNM (pooled prevalence, 8.1%). The risk of LNM was significantly increased in lymphatic invasion (OR [95% confidence interval] = 4.22 [2.88–6.19]), lymphovascular invasion (LVI) (4.17 [2.90–5.99]), vascular invasion (2.38 [1.65–3.44]), positive vertical margin (2.16 [1.59–2.93]), submucosal invasion depth of ≥ 500 μm (2.14 [1.48–3.09]), and tumor size > 30 mm (1.77 [1.31–2.40]). In contrast, there was no significant association between undifferentiated-type or ulceration (scar) and LNM. When studies were restricted to those that evaluated the adjusted OR, the risk of vascular invasion for LNM did not reach statistical significance.

Conclusions

Several pathological factors, most notably lymphatic invasion and LVI, were associated with LNM in patients with noncurative resection after ER for EGC. Lymphatic and vascular invasion should be assessed separately instead of LVI (PROSPERO CRD42018109996).

     

OVA-bound nanoparticles induce OVA-specific IgG1, IgG2a,and IgG2b responses with low IgE synthesis

There is an urgent requirement for a novel vaccine that can stimulate immune responses without unwanted toxicity, including IgE elevation. We examined whether antigen ovalbumin (OVA) conjugated to the surface of nanoparticles (NPs) (OVA-NPs) with average diameter of 110 nm would serve as an immune adjuvant. When BALB/c mice were immunized with OVA-NPs, they developed sufficient levels of OVA-specific IgG1 antibody responses with low levels of IgE synthesis, representing helper T (Th)2-mediated humoral immunity. OVA-specific IgG2a and IgG2b responses (i.e., Th1-mediated immunity) were also induced by secondary immunization with OVA-NPs. As expected, immunization with OVA in alum (OVA-alum) stimulated humoral immune responses, including IgG1 and IgE antibodies, with only low levels of IgG2a/IgG2b antibodies. CD4-positive T cells from mice primed with OVA-NPs produced substantial levels of IL-21 and IL-4, comparable to those from OVA-alum group. The irradiated mice receiving OVA-NPs-primed B cells together with OVA-alum-primed T cells exhibited enhanced anti-OVA IgG2b responses relative to OVA-alum-primed B cells and T cells following stimulation with OVA-NPs. Moreover, when OVA-NPs-primed, but not OVA-alum-primed, B cells were cultured in the presence of anti-CD40 monoclonal antibody, IL-4, and IL-21, or LPS plus TGF-β in vitro, OVA-specific IgG1 or IgG2b antibody responses were elicited, suggesting that immunization with OVA-NPs modulates B cells to generate IgG1 and IgG2b responses. Thus, OVA-NPs might exert their adjuvant action on B cells, and they represent a promising potential vaccine for generating both IgG1 and IgG2a/IgG2b antibody responses with low IgE synthesis.     

Disruption of actin‐binding domain‐containing Dystonin protein causes dystonia musculorum in mice

The Dystonin gene (Dst) is responsible for dystonia musculorum (dt), an inherited mouse model of hereditary neuropathy accompanied by progressive motor symptoms such as dystonia and cerebellar ataxia. Dst‐a isoforms, which contain actin‐binding domains, are predominantly expressed in the nervous system. Although sensory neuron degeneration in the peripheral nervous system during the early postnatal stage is a well‐recognised phenotype in dt, the histological characteristics and neuronal circuits in the central nervous system responsible for motor symptoms remain unclear. To analyse the causative neuronal networks and roles of Dst isoforms, we generated novel multipurpose Dst gene trap mice, in which actin‐binding domain‐containing isoforms are disrupted. Homozygous mice showed typical dt phenotypes with sensory degeneration and progressive motor symptoms. The gene trap allele (Dst^Gt) encodes a mutant Dystonin‐LacZ fusion protein, which is detectable by X‐gal (5‐bromo‐4‐chloro‐3‐indolyl‐β‐D‐galactoside) staining. We observed wide expression of the actin‐binding domain‐containing Dystonin isoforms in the central nervous system (CNS) and peripheral nervous system. This raised the possibility that not only secondary neuronal defects in the CNS subsequent to peripheral sensory degeneration but also cell‐autonomous defects in the CNS contribute to the motor symptoms. Expression analysis of immediate early genes revealed decreased neuronal activity in the cerebellar‐thalamo‐striatal pathway in the homozygous brain, implying the involvement of this pathway in the dt phenotype. These novel Dst^Gt mice showed that a loss‐of‐function mutation in the actin‐binding domain‐containing Dystonin isoforms led to typical dt phenotypes. Furthermore, this novel multipurpose Dst^Gt allele offers a unique tool for analysing the causative neuronal networks involved in the dt phenotype.     

Anatomical correlates of quality of life: Evidence from voxel‐based morphometry

Quality of life (QOL) has been defined in many ways, and these definitions usually emphasize happiness and satisfaction with life. Health‐related problems are known to cause lower QOL. However, the neural mechanisms underlying individual differences in QOL measured by questionnaire (QOLMQ) in young healthy subjects are unknown. QOL is essential to our well‐being, and investigation of the neural mechanisms underlying QOL in uncompromised subjects is obviously of great scientific and social interest. We used voxel‐based morphometry to investigate the association between regional gray matter volume (rGMV) and QOLMQ across the brain in healthy young adults (age, 21.4 ± 1.8 years) men (n = 88) and women (n = 68) in humans. We found significant negative relationships between QOLMQ and rGMV in a region in the left rostrolateral prefrontal cortex and regions in the dorsal part of the anterior cingulate gyrus and contingent cingulate regions. These findings show that structural variations in regions associated with processing of negative emotions such as fear and anger as well as those associated with evaluation of internally generated information are associated with QOLMQ. These findings suggest that these processes might be related to QOLMQ in healthy young adults. Hum Brain Mapp 35:1834–1846, 2014. © 2013 Wiley Periodicals, Inc.     

A novel SCN1A mutation in a cytoplasmic loop in intractable juvenile myoclonic epilepsy without febrile seizures

Generalised (genetic) epilepsy with febrile seizures plus (GEFS+) is a familial epilepsy syndrome with various phenotypes. The majority of individuals with GEFS+ have generalised seizure types, in addition to febrile seizures (FS) or febrile seizures plus (FS+), defined as either continued FS after 6 years of age or afebrile seizures following FS. A 27‐year‐old man with no history of FS/FS+ experienced intractable generalised convulsive seizures. The patient's father had a history of similar seizures during puberty and the patient's siblings had only FS. No individual in the family had both generalised seizures and FS/FS+, although GEFS+ might be considered to be present in the family. Analysis of SCN1A, a sodium channel gene, revealed a novel mutation (c.3250A>T [S1084C]) in the cytoplasmic loop 2 of SCN1A in both the patient and his father. Most previously reported SCN1A mutations in GEFS+ patients are located in the conserved homologous domains of SCN1A, whereas mutations in the cytoplasmic loops are very rare. SCN1A gene analysis is not commonly performed in subjects with generalised seizures without FS. SCN1A mutation may be a clinically‐useful genetic marker in order to distinguish GEFS+ patients from those with classic idiopathic generalised epilepsy, even if they present an atypical clinical picture.     

Role of sodium channels in recovery of sciatic nerve‐stretch injury in rats

Introduction: To elucidate the mechanism of functional recovery after gradual nerve‐stretch injury, we used rats in which the femur length was increased by 15 mm at 1.5 mm/day. Methods: We performed electrophysiology, mRNA analysis of tetrodotoxin‐resistant voltage‐gated sodium channels (TTX‐R VGSCs) in dorsal root ganglia, and histology of unmyelinated sciatic nerve fibers and examined pain thresholds at 1, 10, 20, and 30 days after cessation of lengthening. Results: Electrophysiology revealed conduction block after cessation that recovered after 30 days. TTX‐R VGSC levels decreased immediately after cessation but were restored after 10 (Nav1.9) or 20 (Nav1.8) days. Histology revealed that injured unmyelinated nerve fibers regenerate 30 days after cessation. Pain threshold decreased gradually during lengthening but had not recovered to the control group level after 30 days. Conclusions: Early restoration of TTX‐R VGSC mRNA in dorsal root ganglia preceded functional recovery of stretched nerves before regeneration of injured unmyelinated nerve fibers. Muscle Nerve 50 : 425–430, 2014     

Fatigue and relating to others 3 months after the 2011 Great East Japan Earthquake

Most inhabitants of Tohoku district suffer from chronic fatigue after the 2011 Great East Japan Earthquake. Chronic fatigue following disasters may lead to serious illness, even death. Posttraumatic growth appears to counteract fatigue. We predicted that the chronic fatigue would be inversely related to the posttraumatic growth factor “relating to others,” as represented by mutual helping and a strong sense of connection with humanity. Young 59 healthy volunteers, residing in Miyagi prefecture, were recruited 3 months after the disaster. We measured the subjects? total scores on the Japanese version of the Checklist Individual Strength questionnaire (CIS), the Trait Anxiety (T-A) subscale of the State–Trait Anxiety Inventory (STAI), the Center for Epidemiologic Studies Depression Scale (CES-D), and four subscores on the posttraumatic growth inventory (PTGI). Stepwise regression analyses were conducted with score on the CIS as the dependent variable and other scores as independent variables. Scores on the “relating to others” factor of the PTGI showed a significant negative relationship with the CIS score, whereas the scores on the T-A subscale of the STAI and the CES-D were positively related to the CIS score. Human ties and mutual help were negatively related to the degree of the chronic fatigue.     

Effects of knee extensor muscle strength on the incidence of osteopenia and osteoporosis after 6 years

The association of knee extensor muscle strength with bone mineral density (BMD) has been reported in cross-sectional epidemiological studies, but it remains unclear whether or not this is the case with longitudinal change. Thus, we investigated whether or not the knee extension strength can predict the incidence of osteopenia or osteoporosis after 6 years, then compared the difference between sexes. Subjects were 1255 community-dwelling Japanese men and menopaused women, aged 40–81 years. BMD of lumbar spine and femoral neck was assessed by dual-energy X-ray absorptiometry twice at 6-year intervals. Subjects were divided into three groups, normal, osteopenia, and osteoporosis, depending on their young adult mean BMD % value. In the cross-sectional analysis the correlations between the knee extension strength and BMD of the two regions were examined, using Pearson’s correlation coefficient. Longitudinal analyses were then conducted to determine the odds ratio, controlled for age and BMI, given that those who were normal in the initial stage developed osteopenia or osteoporosis after 6 years, for every 1 SD decrease in knee extension strength, as well as those who first had normal or osteopenia and then developed osteoporosis. Cross-sectional analysis showed a statistically significant relation between knee extensor muscle strength and BMD at both the lumbar spine (p = 0.02) and the femoral neck (p < 0.0001) only in men. The longitudinal analysis showed the significant effect of muscle strength on the loss of femoral neck BMD from normal to osteopenia or osteoporosis both in men (OR 1.84, 95 % CI 1.36–2.48, p < 0.0001) and in women (OR 1.29, 95 % CI 1.002–1.65, p < 0.05), as well as on the loss of spinal BMD from normal or osteopenia to osteoporosis only in men (OR 2.97, 95 % CI 1.07–8.23, p < 0.05). The results suggest the importance of knee extension strength to maintain the bone health of the proximal femur and spine in aging particularly in men.