In order to accurately monitor graft immunology, we have developed a method for performing intestine and abdominal wall transplantation heterotopically in miniature swine. The procedure consisted of ...simultaneous segmental terminal ileum and full-thickness abdominal wall transplantation in Lanyu miniature swine, with the intestinal and the abdominal wall grafts being placed on the recipient's bilateral rear flank. Five transplantations were technically successful. One animal died on the first post-transplant day due to anesthesia-related issues, three abdominal wall and four intestinal grafts survived, while one abdominal wall graft failed due to vascular thrombosis. Acute cellular rejection (ACR) of the intestinal graft could occur preceding, simultaneously with or following ACR of the abdominal wall graft. Our experimental model demonstrates the technical feasibility of heterotopic intestine and abdominal wall transplantation in miniature swine without grafting in gastrointestinal continuity. This model could be suitable for further studies of graft immunology.
Background
The aim of the present study was to determine which aspects of tumor histology influence postoperative early relapse and overall survival rates after radical resection of stage II ...colorectal cancer (CRC).
Methods
Data were collected for 425 patients with stage II CRC who began treatment at a single institution between January 2006 and October 2013. All the enrolled patients were followed up on until death or until December 2014. Clinically significant factors affecting postoperative early relapse and overall survival rates were analyzed.
Results
Using a multivariate analysis, tumor invasion depth (
P
= 0.008), vascular invasion (
P
= 0.029), postoperative carcinoembryonic antigen (CEA) level (
P
= 0.001), and retrieval of less than 12 lymph nodes (
P
= 0.002) were found to be independent predictors for postoperative early relapse. A combination of tumor invasion depth, vascular invasion, postoperative CEA level, and number of lymph nodes retrieved showed that the greater the number of predictors involved, the higher the likelihood of postoperative early relapse and the poorer the overall survival.
Conclusions
This study revealed that T4 invasion, vascular invasion, postoperative CEA level, and the number of examined lymph nodes may significantly affect the prognosis of stage II CRC patients after radical resection. The risks of postoperative early relapse and worse clinical outcome increase in proportion to the values of these four parameters.
Vascular endothelial growth factor (VEGF) is correlated with angiogenesis and early relapse of colorectal cancer (CRC). This study investigated the role of miR‐148a in the regulation of ...VEGF/angiogenesis and early relapse of CRC. We established a stable clone with miR‐148a expression in HCT116 and HT29 cell lines and created a hypoxic condition by using CoCl2 to determine the underlying mechanism of miR‐148a. The effects of miR‐148a on the phosphoryl‐ERK (pERK)/hypoxia‐inducible factor‐1α (HIF‐1α)/VEGF pathway were evaluated through Western blotting and the inhibitory effect of miR‐148a on angiogenesis was demonstrated through a tube formation assay. Sixty‐three CRC tissues (28 early relapse and 35 non‐early relapse) were analysed to assess the relationship between miR‐148a and HIF‐1α/VEGF. The protein expression of pERK/HIF‐1α/VEGF in HCT116 and HT29 cells was significantly decreased by miR‐148a (all P < 0.05). The protein expression of VEGF/HIF‐1α was strongly inversely associated with the expression of miR‐148a in the 63 CRC tissue samples (all P < 0.05). Tube formation assay demonstrated that miR‐148a significantly obliterated angiogenesis. miR‐148a suppresses VEGF through down‐regulation of the pERK/HIF‐1α/VEGF pathway and might lead to the inhibition of angiogenesis; miR‐148a down‐regulation increased the early relapse rate of CRC. This demonstrates that miR‐148a is a potential diagnostic and therapeutic target.
Patients with locally advanced colon cancer (LACC) have a relatively poor prognosis despite radical resection and adjuvant chemotherapy. This study investigated the treatment efficacy and toxicity of ...neoadjuvant chemoradiotherapy in patients with LACC.
We retrospectively reviewed 36 patients with LACC preoperatively treated with chemotherapy and radiotherapy. Patients were administered chemoradiotherapy, which comprised radiotherapy and neoadjuvant chemotherapy involving a 5-fluorouracil, leucovorin, and oxaliplatin regimen every 2 weeks.
Median age was 64 years (45-86 years) and median follow-up period was 23.5 months (5.0-49.1 months). Seven (19.4%) patients developed grade 3 or 4 adverse events during neoadjuvant concurrent chemoradiotherapy. Pathologic responses were not evaluated in two patients who did not undergo radical resection. Of the 34 patients who underwent surgery, nine (26.4%) achieved a pathologic complete response (pCR). The 2-year estimated overall survival and disease-free survival rates were 88.7% and 73.6%, respectively.
Our results demonstrated that neoadjuvant chemoradiotherapy is feasible and safe. A prominent pCR rate with an acceptable toxicity profile suggests that the multimodality therapy might be a treatment option for patients with LACC.
Purpose
To evaluate the 2-year efficacy and safety of micropulse transscleral cyclophotocoagulation (MP-TSCPC) in Taiwanese patients with glaucoma.
Methods
We included the patients who received ...standardized MP-TSCPC with follow-up examinations on a regular basis for 24 months. Treatment success was defined as the attainment of a postoperative intraocular pressure (IOP) between 6 and 21 mmHg or a ≥ 20% reduction in IOP from baseline without an increase in glaucoma medications.
Results
A total of 60 eyes from 56 patients who underwent MP-TSCPC for refractory glaucoma were included. The median age at MP-TSCPC intervention was 58.9 ± 12.4 years. The percentage of treatment success was 88.3% at 3 months, 83.3% at 6 months, 78.3% at 12 months, and 75.0% at 24 months. The mean baseline IOP prior to MP-TSCPC was 34 ± 11.9 mmHg (range 14–56 mmHg). The mean postoperative IOP decreased to 20.9 ± 10.0 mmHg, 18.0 ± 7.8 mmHg, 17.5 ± 6.4 mmHg, and 18.2 ± 7.1 mmHg after 3 months, 6 months, 12 months, and 24 months, respectively, in successful cases. The mean number of glaucoma medications at baseline was 3.8 ± 0.2, and the mean numbers of glaucoma medications at postoperative months 3, 6, 12, and 24 were 2.6 ± 0.7, 2.8 ± 0.6, 2.5 ± 1.4 and 2.6 ± 1.4, respectively, in successful cases. Younger age and prior CW-TSCPC significantly contributed to surgical failure in the multivariate model. Complications after MP-TSCPC included mild anterior chamber inflammation, conjunctival hemorrhage, hypotony, and mydriasis, and all subsided after treatment. None of the eyes developed vitreous hemorrhage, cystoid macular edema, or phthisis bulbi in the late postoperative period.
Conclusions
This study demonstrated that younger age and prior CW-TSCPC were risk factors for MP-TSCPC failure within 2 years. MP-TSCPC might be safe and effective for refractory glaucoma patients with maximal antiglaucoma medications.
Background:
The high prevalence of type 2 diabetes mellitus (DM) among patients with colorectal cancer (CRC) is becoming a serious public health concern worldwide. FOLFOX4 chemotherapy is one of the ...most widely used adjuvant therapies in patients with stage III colon cancer after surgical resection. However, chemotherapy resistance is associated with a poor prognosis. The prognostic impact of high blood sugar levels on oxaliplatin resistance in CRC patients is an unexplored topic.
Methods:
In total, 157 patients with stage III CRC were classified according to their fasting blood sugar level (⩾126 or <126 mg/dl). Clinicopathological features and oxaliplatin chemoresistance/survival outcome of the two groups were compared. In vitro cell proliferation assay was performed through d-(+)-glucose administration.
Results:
Multivariate analysis results revealed that high blood sugar level was a significantly independent prognostic factor of disease-free survival and overall survival (both p < 0.05), but not DM history. After metformin administration, enhanced proliferation of CRC cells (HT-29, HCT-116, SW480, and SW620) with d-(+)-glucose administration could be reversed and oxaliplatin chemosensitivity considerably increased (p < 0.05). Furthermore, phosphorylation of two glycolysis-related target proteins, SMAD3 and MYC, notably increased under high glucose concentration.
Conclusions:
Hyperglycemia can affect clinical outcomes in stage III CRC patients receiving adjuvant chemotherapy, and the mechanism underlying oxaliplatin resistance is possibly associated with increased phosphorylation of SMAD3 and MYC and upregulation of EHMT2 expression.
Locally advanced gastric cancer (LAGC) has a poor prognosis with surgical resection alone, and neoadjuvant treatment has been recommended to improve surgical and oncological outcomes. Although ...neoadjuvant chemotherapy has been established to be effective for LAGC, the role of neoadjuvant chemoradiotherapy (NCRT) remains under investigation. Clinical experience and research evidence on esophagogastric junction adenocarcinoma (e.g., cardia gastric cancers) indicate that the likelihood of achieving sustainable local control is higher through NCRT than through resection alone. Furthermore, NCRT also has an acceptable treatment-related toxicity and adverse event profile. In particular, it increases the likelihood of achieving an R0 resection and a pathological complete response (pCR). Moreover, NCRT results in higher overall and recurrence-free survival rates than surgery alone; however, evidence on the survival benefits of NCRT versus neoadjuvant chemotherapy (NCT) remains conflicting. For noncardia gastric cancer, the efficacy of NCRT has mostly been reported in retrospective studies, and several large clinical trials are ongoing. Consequently, NCRT might play a more essential role in unresectable LAGC, for which NCT alone may not be adequate to attain disease control. The continual improvements in systemic treatments, radiotherapy techniques, and emerging biomarkers can also lead to improved personalized therapy for NCRT. To elucidate the contributions of NCRT to gastric cancer treatment in the future, the efficacy, potential toxicity, predictive biomarkers, and clinical considerations for implementing NCRT in different types of LAGC were reviewed.
Abstract
The risks of misdiagnosing a healthy individual as glaucomatous or vice versa may be high in a population with a large majority of highly myopic individuals, due to considerable morphologic ...variability in high myopic fundus. This study aims to compare the diagnostic ability of the regular and long axial length databases in the RS-3000 Advance SD-OCT (Nidek) device to correctly diagnose glaucoma with high myopia. Patients with high myopia (axial length ≥ 26.0 mm) in Chang Gung Memorial Hospital, Taiwan between 2015 and 2020 were included. Glaucoma was diagnosed based on glaucomatous discs, visual field defects and corresponding retinal nerve fiber layer defects. The sensitivity, specificity, diagnostic accuracy and likelihood ratios of diagnosing glaucoma via mGCC thickness in both superior/inferior and GChart mapping using the regular and long axial length normative databases. The specificity and diagnostic accuracy of mGCC thickness for distinguishing glaucomatous eyes from nonglaucomatous eyes among highly myopic eyes were significantly improved using the long axial length database (p = 0.046). There were also significant proportion changes in S/I mapping as well as GChart mapping (37.3% and 48.0%, respectively; p < 0.01) from abnormal to normal in the myopic normal eye group when using the long axial length normative database. The study revealed that clinicians could utilize a long axial length database to effectively decrease the number of false-positive diagnoses or to correctly identify highly myopic normal eyes misdiagnosed as glaucomatous eyes.
Patients with cancer use low-molecular-weight fucoidan (LMF) as a supplement to therapy. However, most studies of LMF are in vitro or conducted using animals. Concurrent chemoradiotherapy (CCRT) is ...the gold standard for locally advanced rectal cancer (LARC). This study investigated the quality of life (QoL) and clinical outcomes of patients with LARC taking LMF as a supplement to neoadjuvant CCRT. This was a double-blind, randomized, placebo-controlled study. The sample comprised 87 patients, of whom 44 were included in a fucoidan group and 43 were included in a placebo group. We compared their QoL scores and clinical outcomes before treatment, and at 1 month, 2 months, and 3 months posttreatment. Pretreatment and posttreatment gut microbiota differences were also compared. Although enhanced physical well-being (PWB) at 2 months and 3 months posttreatment in the fucoidan group were observed (both P < .0125), the improvements of the Functional Assessment of Cancer Therapy for Patients with Colorectal Cancer (FACT-C) were nonsignificant (all P > .0125). Skin rash and itching and fatigue were less common in the fucoidan group (both P < .05). Posttreatment, the genus Parabacteroides was significantly more common in the gut microbiota of the fucoidan group. LMF administration improved the QoL, skin rash and itching, fatigue, and gut microbiota composition of the patients with LARC receiving CCRT.
Clinical Trial Registration: NCT04342949
Backover crashes cause considerable injuries especially among young children. Prior research on backover crashes has not assessed the joint effect of heavy vehicles and diminished light conditions on ...injuries. By analysing the United Kingdom STATS19 crash dataset from 1991 to 2020, this study focused on backover crashes involving paediatric cyclists or pedestrians aged ≤17 years and other motorised vehicles. By estimating the adjusted odds ratio (AOR) of multiple logistic regression models, pedestrians appeared to have 82.3% (95% CI: 1.78-1.85) higher risks of sustaining killed or serious injuries (KSIs) than cyclists. In addition, casualties involved in backover crashes with heavy vehicles were 39.3% (95% CI: 1.35-1.42) more likely to sustain KSIs than those involved in crashes with personal cars. The joint effect of heavy vehicles and diminished light conditions was associated with a 71% increased probability of sustaining KSIs (AOR = 1.71; 95% CI: 1.60-1.83). Other significant joint effects included young children (aged 0 to 5 years) as pedestrian (AOR = 1.92; 95% CI: 1.87-1.97), in diminished light conditions (AOR = 1.23; 95% CI: 1.15-1.31), and with heavy vehicle (AOR = 1.37; 95% CI: 1.28-1.47).
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