Background
Esophagectomy with lymph node dissection is a choice of additional treatment after noncurative endoscopic resection (ER) of T1N0 esophageal squamous cell carcinoma (ESCC). The efficacy and ...safety of esophagectomy in this situation remain unclear when compared with upfront esophagectomy.
Methods
We investigated the short- and long-term outcomes of 321 patients with clinical T1N0M0 ESCC who underwent curative esophagectomy, and compared the status of lymph node metastasis, surgical results, and the prognosis between the ER and non-ER groups.
Results
The ER group consisted of 57 patients (17.8%), while the non-ER group consisted of 264 patients (82.2%). The incidence of lymph node metastasis was not significantly different between the ER (24.6%) and non-ER groups (30.7%), and there was no significant difference in surgical outcomes between the groups. The distribution of metastatic lymph nodes was very similar between the groups. However, 13 of 14 patients (93%) with lymph node metastasis in the ER group and 63 of 82 patients (77%) with lymph node metastasis in the non-ER group had pN1 disease, while the remaining 18 patients (23%) with lymph node metastasis in the non-ER group had pN2 or N3 disease. Overall and relapse-free survival rates were significantly better in the ER group than in the non-ER group (
p
< 0.05 and
p
< 0.01, respectively). To date, no patients in the ER group experienced disease recurrence.
Conclusions
Additional esophagectomy is a safe and effective treatment modality for patients after noncurative ER.
When activated by viral infection, plasmacytoid dendritic cells (pDCs) play a primary role in the immune response through secretion of IFN-α. Lactococcus lactis subsp. lactis JCM5805 (JCM5805) is a ...strain of lactic acid bacteria (LAB) that activates murine and human pDCs to express type I and type III interferons (IFNs). JCM5805 has also been shown to activate pDCs via a Toll-like receptor 9 (TLR9) dependent pathway. In this study, we investigated the anti-viral effects of oral administration of JCM5805 using a mouse model of murine parainfluenza virus (mPIV1) infection. JCM5805-fed mice showed a drastic improvement in survival rate, prevention of weight loss, and reduction in lung histopathology scores compared to control mice. We further examined the mechanism of anti-viral effects elicited by JCM5805 administration using naive mice. Microscopic observations showed that JCM5805 was incorporated into CD11c+ immune cells in Peyer's patches (PP) and PP pDCs were significantly activated and the expression levels of IFNs were significantly increased. Interestingly, nevertheless resident pDCs at lung were not activated and expressions levels of IFNs at whole lung tissue were not influenced, the expressions of anti-viral factors induced by IFNs, such as Isg15, Oasl2, and Viperin, at lung were up-regulated in JCM5805-fed mice compared to control mice. Therefore expressed IFNs from intestine might be delivered to lung and IFN stimulated genes might be induced. Furthermore, elevated expressions of type I IFNs from lung lymphocytes were observed in response to mPIV1 ex vivo stimulation in JCM5805-fed mice compared to control. This might be due to increased ratio of pDCs located in lung were significantly increased in JCM5805 group. Taken together, a specific LAB strain might be able to affect anti-viral immunological profile in lung via activation of intestinal pDC leading to enhanced anti-viral phenotype in vivo.
A variety of eye-related symptoms due to the overuse of digital devices is collectively referred to as computer vision syndrome (CVS). In this study, a web-based survey about mind and body functions, ...including eye strain, was conducted on 1998 Japanese volunteers. To investigate the biological mechanisms behind CVS, a multi-trait genome-wide association study (GWAS), a multivariate analysis on individual-level multivariate data, was performed based on the structural equation modeling methodology assuming a causal pathway for a genetic variant to influence each symptom via a single common latent variable. Twelve loci containing lead variants with a suggestive level of significance were identified. Two loci showed relatively strong signals and were associated with TRABD2B relative to the Wnt signaling pathway and SDK1 having neuronal adhesion and immune functions, respectively. By utilizing publicly available eQTL data, colocalization between GWAS and eQTL signals for four loci was detected, and a locus on 2p25.3 showed a strong colocalization (PPH
> 0.9) on retinal MYT1L, known to play an important role in neuronal differentiation. This study suggested that the use of multivariate questionnaire data and multi-trait GWAS can lead to biologically reasonable findings and enhance our genetic understanding of complex relationships among symptoms related to CVS.
Background
Squamous cell carcinoma antigen (SCC-Ag) is a widely used tumor marker of SCC. However, the clinical significance of serum SCC-Ag levels in recurrent esophageal SCC (ESCC) remains unclear. ...This study aimed to investigate the clinical relevance of serum SCC-Ag levels in patients with recurrent ESCC after surgery.
Methods
This study retrospectively analyzed 208 patients who experienced recurrence after curative resection for ESCC. Serum SCC-Ag levels at the time of recurrence were collected from the patients’ records. The patients were classified into tertiles based on the serum SCC-Ag values (low, middle, and high), and the clinical characteristics and outcomes were compared among the groups.
Results
Significant differences in sex (
p
= 0.001), pathologic T (
p
= 0.034), and N stages of primary cancer (
p
= 0.015) were observed among the groups. Although the recurrence patterns did not differ significantly, a high SCC-Ag was significantly associated with multiple recurrences (
p
= 0.019). The high-SCC-Ag group patients demonstrated a shorter time to recurrence than the other groups (
p
= 0.044). The SCC-Ag levels were significantly associated with overall survival after recurrence (
p
= 0.036). Multivariate analysis showed that serum SCC-Ag value at recurrence was an independent poor prognosticator (
p
= 0.031).
Conclusion
Elevated serum SCC-Ag levels at recurrence were significantly associated with a reduced time to recurrence, multiple recurrences, and a poor prognosis after recurrence. An alternative to the current standard treatment is required to improve the outcome for patients with high serum SCC-Ag levels at recurrence.
The resistance force generated when the locked-wheel acts on the soil is critical for deciding the traveling performance of push–pull locomotion. The resistance force depends on the tangential force ...of the sliding soil wedge beneath the wheel, and the tangential force depends on the forces of the soil and the wheel perpendicular to the tangential direction. Hence, the normal stress distribution of the locked-wheel can affect the resistance force. Previous studies indicated different insights that describe either a uniform or non-uniform shape of the normal stress distribution. The distribution of the locked-wheel still needs to be examined experimentally. This study measured the normal stress distribution using the wheel sensor system, and the variation of the contact area and slip surface beneath the wheel were also observed in PIV analysis. Those results showed that the normal stress distribution was non-uniform along the wheel contact area, and the change of the distribution was confirmed with the change of the contact area and slip surface. Then, the resistance force calculated by a preliminary model based on the measured data was compared with the total resistance force of the wheel measured by a separate sensor. This comparison provided a theoretical consideration for the measured data.
Background
Endoscopic resection (ER) has been widely implemented for cT1N0 esophageal squamous cell carcinoma (ESCC). Additional therapy, including esophagectomy and chemoradiotherapy (CRT), is ...sometimes required after noncurative ER.
Methods
We retrospectively reviewed 108 patients who received any additional treatment following noncurative ER (positive vertical margins, lymphovascular invasion, or invasion depth of submucosa or more), and compared the short- and long-term outcomes between the two treatment modalities.
Results
Of 108 patients, 56 underwent esophagectomy (E group), and 52 received CRT (CRT group). A positive vertical margin was observed in 17 (14.8%) patients and high risks of occult lymph node metastasis were observed in 91 (85.2%) patients, as well as lymphovascular invasion in 35 (32.4%) patients, invasion depth of the submucosa or more in 27 (25.0%) patients, and both in 29 (26.9%) patients. The E group patients were significantly younger (
p
= 0.046) and tended to present with larger tumors than those in the CRT group (
p
= 0.057). Lymphatic invasion was more frequent in the E group (
p
= 0.019), and, furthermore, one treatment-related death was observed in the E group. There were no significant differences between the groups in overall and disease-specific survival (
p
= 0.406 and 0.151, respectively), however, recurrence was only observed in the CRT group.
Conclusion
Both esophagectomy and CRT are safe and effective as additional treatments after noncurative ER in patients with ESCC. Esophagectomy is oncologically safe, whereas a risk of postoperative morbidity and mortality remains. Although the adverse events are acceptable, CRT has a certain degree of risk of disease recurrence.
In this study, we designed and synthesized organelle-targeted cell-penetrating peptide (CPP)-conjugated boron compounds to increase their cellular uptake and to control the intracellular locations ...for the induction of sophisticated anticancer biological activity in boron neutron capture therapy (BNCT), leading to anticancer effects with ATP reduction and apoptosis when irradiated with neutrons in an in vitro BNCT assay.
Background
Chronic obstructive pulmonary disease (COPD) is known to be a risk factor of pneumonia after esophagectomy. In this study, we investigated the relationship of airflow limitation with the ...occurrence and the severity of pneumonia in esophageal cancer patients who underwent esophagectomy.
Methods
We enrolled 844 patients who underwent curative esophagectomy between 2009 and 2018. The airflow limitation was evaluated using the percent-predicted forced expiratory volume at 1 s (%FEV1) with spirometry.
Results
There were 597 (70.7%), 141 (16.7%), 68 (8.1%), and 38 patients (4.5%) with %FEV1 of ≥ 90%, 80–90%, 70–80%, and < 70% categories, respectively. One hundred and ninety-one patients (22.6%) occurred pneumonia, and the incidences of pneumonia in each category of patients were 18.8%, 28.4%, 29.4%, and 50.0%, respectively. In multivariate analysis, the categories of 80%–90%, 70–80%, and < 70% were significantly associated with a higher incidence of postoperative pneumonia (OR 1.57; 95% CI 1.02–2.43, OR 1.87; 95% CI 1.04–3.36, OR 3.34; 95% CI 1.66–6.71, respectively), with the %FEV1 category of ≥ 90% as reference. The incidence of severe pneumonia of Clavien–Dindo grade III or higher was also significantly associated with the %FEV1. In patients without COPD, the incidence of pneumonia was significantly higher in those with %FEV1 < 90% than in those with %FEV1 ≥ 90% (32.2% versus 17.5%,
p
< 0.001).
Conclusions
The airflow limitation can help predict the occurrence of pneumonia after esophagectomy in patients with and without COPD. Exclusive preventive measures should be considered in patients with reduced %FEV1 undergoing esophagectomy.
Background
Anastomotic leakage (AL) is one of the most common complications after esophagectomy. Although some patients have a history of peptic ulcers or other prior stomach diseases, the influence ...of a damaged stomach (DS) on AL incidence remains unclear. Therefore, we investigated the association between DS and incidence of AL in patients who underwent esophagectomy.
Patients and Methods
Between 2015 and 2019, a total of 447 consecutive patients who underwent cervical esophagogastrostomy using gastric tube following esophagectomy were enrolled. DS was defined on the basis of endoscopic findings of ulcers or scars due to medical history or prior treatment. We compared the incidence of AL between patients with DS and those with a healthy stomach (HS). Univariate and multivariate logistic regression analyses were used to identify factors that could predict AL incidence.
Results
Fifty-one patients (11.4%) had DS. Causes of DS included peptic ulcer (
n
= 36), endoscopic resection for early gastric cancer (
n
= 9), percutaneous endoscopic gastrostomies (
n
= 5), and post-chemotherapy scar for gastric malignant lymphoma (
n
= 1). Overall, AL occurred in 35 patients (7.8%). The incidence of AL in the DS group was significantly higher than in the HS group (15.7 vs. 6.8%,
p
= 0.03). DS was one of the independent predictive factors for AL (odds ratio, 2.75; 95% confidence interval, 1.10–6.92;
p
= 0.03) on multivariate analysis. Further, the diseases in the lower third of the conduit were associated with AL.
Conclusions
Presence of DS can predict AL in patients who underwent cervical esophagogastrostomy after esophagectomy.
Activation of SIRT1, an NAD+-dependent protein deacetylase, ameliorates muscular pathophysiology of δ-sarcoglycan-deficient TO-2 hamsters and dystrophin-deficient mdx mice. We found that SIRT1 was ...highly expressed beneath the cellular membranes of muscle cells. To elucidate functional roles of SIRT1 on muscles, skeletal muscle-specific SIRT1 knockout mice (SIRT1-MKO) were generated. SIRT1-MKO mice showed muscular pathology similar to mild muscular dystrophies with increased numbers of centrally nucleated small myofibers and decreased numbers of middle-sized (2000-3001 μm2) myofibers compared to those of wild-type (WT) mice. Accordingly, SIRT1-MKO mice showed significantly decreased exercise capacity in treadmill and inverted hanging tests with higher levels of serum creatine kinase activities compared with those in WT mice. Evans blue dye uptake after exercise was greater in the muscles of SIRT1-MKO than those of WT mice, suggesting membrane fragility in SIRT1-MKO mice. Because SIRT1 was dominantly localized beneath the membranes of muscular cells, SIRT1 may have a new role in the membranes. We found that levels of fluorescent FM1-43 dye intake after laser-induced membrane disruption in C2C12 cells were significantly increased by SIRT1 inhibitors or Sirt1-siRNA compared with those of control cells. Inhibition of SIRT1 or SIRT1-knockdown severely disturbed the dynamic aggregation of membrane vesicles under the injured site but did not affect expression levels of membrane repair proteins. These data suggested that SIRT1 had a critical role in the resealing of membrane-ruptured muscle cells, which could affect phenotypes of SIRT1-MKO mice. To our knowledge, this report is the first to demonstrate that SIRT1 affected plasma-membrane repair mechanisms.
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