Clinical significance of thrombospondin-1 expression in relation to vascular endothelial growth factor and interleukin-10 expression at the deepest invasive tumor site of advanced colorectal carcinoma

Various angiogenic and angiostatic factors regulate angiogenesis. Tumor angiogenesis is a complicated process for which the detailed mechanisms remain unclear. The aim of this study was to elucidate the clinical significance of TSP-1 expression in relation to expression of VEGF and IL-10 and angiogenesis at the deepest invasive tumor site as a predictor of invasive/metastatic potential and prognosis of advanced colorectal carcinoma (CRC). Patients (n=152) who had undergone surgical resection for advanced CRC were entered in this study. Expression of TSP-1, VEGF, and IL-10 was examined immunohistochemically with specific antibodies. Tumor microvessel density (MVD) was also determined immunohistochemically with anti-CD34 antibody (NU-4A1). Expression of TSP-1, VEGF, and IL-10 at the deepest invasive tumor site was detected in 46 (30.3%), 62 (40.8%), and 39 (25.7%) of 152 lesions, respectively. TSP-1, VEGF, and IL-10 expression at the superficial part was detected in 60 (39.5%), 35 (23.0%), and 46 (30.3%) of 152 lesions, respectively. Although there was no significant difference between the incidence of TSP-1 and IL-10 expression at the deepest invasive site or at the superficial part, there was a significant difference between the incidence of VEGF expression at the deepest invasive site and that at the superficial part. Expression of TSP-1 and IL-10 at the deepest invasive tumor site was inversely correlated with metastatic potential and prognosis in relation to MVD. Furthermore, lesions that were TSP-1-negative and VEGF-positive at the deepest invasive tumor site showed the strongest association with MVD. The 5-year survival rate for patients with TSP-1-negative or IL-10 negative lesions at the deepest invasive tumor site was significantly poorer than that for patients with TSP-1-positive or IL-10-positive lesions, respectively. The 5-year survival rate for patients with VEGF expression at the deepest invasive tumor site was significantly poorer than that for patients without VEGF expression. The 5-year survival rate for patients with TSP-1-negative, VEGF-positive lesions at the deepest invasive site were significantly poorer than that for patients with lesions without these characteristics. Multivariate analysis with logistic regression for 5-year survival in patients with curative surgery showed that lymph node metastasis and VEGF expression were significant prognostic factors. Although lack of TSP-1 or IL-10 expression was associated significantly with poorer prognosis, this may be less important in poorer prognosis than the presence of VEGF expression.     

RAF1–MEK/ERK pathway-dependent ARL4C expression promotes ameloblastoma cell proliferation and osteoclast formation

Ameloblastoma is an odontogenic neoplasm characterized by slow intraosseous growth with progressive jaw resorption. Recent reports have revealed that ameloblastoma harbours an oncogenic BRAFV600E mutation with mitogen-activated protein kinase (MAPK) pathway activation and described cases of ameloblastoma harbouring a BRAFV600E mutation in which patients were successfully treated with a BRAF inhibitor. Therefore, the MAPK pathway may be involved in the development of ameloblastoma; however, the precise mechanism by which it induces ameloblastoma is unclear. The expression of ADP-ribosylation factor (ARF)-like 4c (ARL4C), induced by a combination of the EGF–MAPK pathway and Wnt/β-catenin signalling, has been shown to induce epithelial morphogenesis. It was also reported that the overexpression of ARL4C, due to alterations in the EGF/RAS–MAPK pathway and Wnt/β-catenin signalling, promotes tumourigenesis. However, the roles of ARL4C in ameloblastoma are unknown. We investigated the involvement of ARL4C in the development of ameloblastoma. In immunohistochemical analyses of tissue specimens obtained from 38 ameloblastoma patients, ARL4C was hardly detected in non-tumour regions but tumours frequently showed strong expression of ARL4C, along with the expression of both BRAFV600E and RAF1 (also known as C-RAF). Loss-of-function experiments using inhibitors or siRNAs revealed that ARL4C elevation depended on the RAF1–MEK/ERK pathway in ameloblastoma cells. It was also shown that the RAF1–ARL4C and BRAFV600E–MEK/ERK pathways promoted cell proliferation independently. ARL4C-depleted tumour cells (generated by knockdown or knockout) exhibited decreased proliferation and migration capabilities. Finally, when ameloblastoma cells were co-cultured with mouse bone marrow cells and primary osteoblasts, ameloblastoma cells induced osteoclast formation. ARL4C elevation in ameloblastoma further promoted its formation capabilities through the increased RANKL expression of mouse bone marrow cells and/or primary osteoblasts. These results suggest that the RAF1–MEK/ERK–ARL4C axis, which may function in cooperation with the BRAFV600E–MEK/ERK pathway, promotes ameloblastoma development. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Usefulness of polyethylene glycol solution with dimethylpolysiloxanes for bowel preparation before capsule endoscopy

Background and Aim:  Capsule endoscopy (CE) is widely used for diagnosing small intestinal diseases. In some cases, however, observation of target sites is very poor during CE because of residues etc. Herein we report the usefulness of a preparation comprised of polyethylene glycol solution (PEG) for CE.
Methods:  This was a prospective, randomized, and single-blind study. Forty subjects, fasted for 12 h before CE, were randomized into two groups: 20 subjects in Group A were fasted only, whereas 20 in Group B received 1 liter (L) PEG with 200 mg dimethylpolysiloxane 3 h before CE. For evaluation, the observation period of the small intestine was divided into first and second halves. Subsequently, four investigators, blinded as to which group received the preparation, assessed the condition of the intestine using four rating scales in terms of 'residue' and 'intraluminal gas bubbles'. The effects of the preparation were statistically compared.
Results:  CE images were better in Group B than in Group A with respect to 'intraluminal gas bubbles' ( P  = 0.0038) in the first half of the observation period, as well as residue ( P  = 0.0087) and intraluminal gas bubbles ( P  = 0.0011) in the second half.
Conclusion:  Bowel preparation using 1 L PEG with dimethylpolysiloxane 3 h before CE significantly reduced residue and intraluminal gas bubbles, and was considered to be a useful method for CE.     

Wedging of vertebral bodies at the thoracolumbar junction in asymptomatic healthy subjects on magnetic resonance imaging

Purpose

Wedging of the vertebral body on radiological examination is a valuable indicator of a vertebral compression fracture, although it can also be observed in subjects with no history of trauma. The purpose of this study was to elucidate the normative value of vertebral wedging at the thoracolumbar junction in asymptomatic healthy subjects for differential diagnosis of vertebral compression fractures using MRI.

Methods

A total of 115 subjects without back pain at the time of the examination and without history of spinal trauma was included (68 males, 47 females, mean age 49.5?years). They underwent MRI of the thoracic and lumbar spine, and the ratio of anterior vertical height to posterior vertical height of the vertebral body (APR) was determined from T10 to L2 on T2 weighted sagittal images.

Results

APR was 0.92?±?0.08 at T10, 0.92?±?0.08 at T11, 0.90?±?0.06 at T12, 0.89?±?0.06 at L1, and 0.90?±?0.07 at L2, indicating that vertebral bodies at the thoracolumbar junction appear wedge-shaped rather than rectangular. Males, thinner subjects, smokers, and subjects with abnormalities of the endplates such as a Schmorl nodule had a significantly smaller APR than females, fatter subjects, non-smokers, and those without endplate abnormalities.

Conclusion

The normative values of APR obtained in the present study can represent a valuable reference in the diagnosis of vertebral compression fracture to help prevent confusion with physiological vertebral wedging.     

Bladder cancer develops 6 years earlier in current smokers: Analysis of bladder cancer registry data collected by the cancer registration committee of the Japanese Urological Association

Objectives:   It is generally recognized that cigarette smoking is the most important risk factor for bladder cancer. The present study was undertaken to examine the relationships between smoking history of bladder cancer patients and the age of onset of bladder cancer and tumor characteristics.
Methods:   The present study examined the data for 5959 cases (4728 males and 1231 females) collected in the bladder cancer database of the Japanese Urological Association from 1999 to 2001. Patients were divided by smoking history into three categories as current non-smokers, current smokers and unknown smoking history. Relationship between smoking history and the age at diagnosis of bladder cancer, gender, T stage, grade, tumor size, tumor number and initial symptoms was analyzed
Results:   In both males and females the onset of bladder cancer is about 6 years (6.1 years in males and 5.9 years in females) earlier for current smokers than for current non-smokers. At the time of diagnosis, tumor stage was significantly higher in the current smokers group. The current smokers group tended to have larger tumor size.
Conclusions:   The finding of 6-year-earlier onset of bladder cancer among current smokers is of great importance to both health care and medical economics. It is essential to make people better informed concerning the need to quit smoking.     

Clinical outcome of tumor recurrence for Ta, T1 non-muscle invasive bladder cancer from the data on registered bladder cancer patients in Japan: 1999–2001 report from the Japanese Urological Association

Objective:   To characterize the clinical outcome in a large contemporary series of Japanese patients with newly diagnosed Ta, T1 non-muscle invasive bladder cancer who underwent transurethral bladder tumor resection with or without intravesical chemotherapy or Bacillus Calmette-Guérin (BCG) therapy.
Methods:   We developed a database incorporating newly diagnosed non-muscle invasive bladder cancer data and outcomes from a Japanese bladder cancer registry between 1999 and 2001 and identified a study population of 3237 consecutive patients who had complete data based on pathological features. Median patient age was 69.9 years.
Results:   The 1-year, 3-year, and 5-year overall recurrence-free survival rates were 77.0%, 61.3%, and 52.8%, respectively. In multivariate analyses, the multiplicity of bladder tumors, tumor size greater than 3 cm, pathological stage T1, tumor grade G3, and the absence of adjuvant intravesical instillation were independent risk factors for tumor recurrence. Overall, 1710 patients (52.8%) received intravesical instillation; chemotherapy in 1314 (76.8%) and BCG treatment in 396 (23.2%). In patients treated with intravesical chemotherapy in which an anthracycline chemo-agent was used in 90.5% of the cases, multivariate analyses demonstrated that male gender, multiple bladder tumors, a tumor size greater than 3 cm, and pathological stage T1 were associated with tumor recurrence.
Conclusions:   The accumulation and analysis of data from the Japanese National Bladder Cancer Registry made it possible to determine the clinical characteristics, management trends, and survival rates for the period studied. Further study with a dataset created from longer follow-up data would be warranted to analyze tumor progression and disease survival.     

Blue Mode Imaging may Improve the Detection and Visualization of Small-Bowel Lesions: A Capsule Endoscopy Study

Background/Aims:Diagnostic miss rate and time consumption are the two challenging limitations of small-bowel capsule endoscopy (SBCE). In this study, we aimed to know whether using of the blue mode (BM) combined with QuickView (QV) at a high reviewing speed could influence SBCE interpretation and accuracy.Results:In study A, the total number of the vascular (P < 0.001) and the inflammatory lesions (P = 0.005) detected by BM was significantly higher than that detected by the white light. No lesion was found using the white light that was not detected by the BM. Moreover, the BM highly improved the image quality of all the vascular lesions and the erythematous ones from the nonvascular lesions. In study B, the total number of only the vascular lesions, detected by the BM on a rapid speed of viewing at 20 fps was significantly higher than that detected by the white light (P = 0.035). However, the true miss rate for the BM was 4%.Conclusion:BM imaging is a new method that improved the detection and visualization of the vascular and erythematous nonvascular lesions of SB as compared with the conventional white light imaging. Using of the BM at a slow viewing speed, markedly reduced the diagnostic miss rate of CE.     

Assessment of ablative margin after radiofrequency ablation for hepatocellular carcinoma; comparison between magnetic resonance imaging with ferucarbotran and enhanced CT with iodized oil deposition

Background and purpose

Our aim was to investigate whether magnetic resonance imaging (MRI) with ferucarbotran administered prior to radiofrequency ablation could accurately assess ablative margin when compared with enhanced computed tomography (CT) with iodized oil marking.

Materials and methods

We enrolled 27 patients with 32 hepatocellular carcinomas in which iodized oil deposits were visible throughout the nodule after transcatheter arterial chemoembolization. For these nodules, radiofrequency ablation was performed after ferucarbotran administration. We then performed T2-weighted MRI after 1 week and enhanced CT after 1 month. T2-weighted MRI demonstrated the ablative margin as a low-intensity rim. We classified the margin into three grades; margin (+): high-intensity area with a continuous low-intensity rim; margin zero: high-intensity area with a discontinuous low-intensity rim; and margin (−): high-intensity area extending beyond the low-intensity rim.

Results

In 28 (86%) of 32 nodules, there was agreement between MRI and CT. The overall agreement between for the two modalities in the assessment of ablative margin was good (κ = 0.759, 95% confidence interval: 0.480–1.000, p < 0.001). In four nodules, ablative margins on MRI were underestimated by one grade compared with CT.

Conclusion

MRI using ferucarbotran is less invasive and allows earlier assessment than CT. The MRI technique performed similarly to enhanced CT with iodized oil marking in evaluating the ablative margin after radiofrequency ablation.