Serum TLR2 and TLR4 levels in colorectal cancer and their association with systemic inflammatory markers,tumor characteristics,and disease outcome

Toll‐like receptors (TLRs) are involved in colorectal cancer (CRC) pathogenesis. However, the significance of serum TLR concentrations in CRC is unknown. We analyzed serum TLR2 and TLR4 concentrations with ELISA in preoperative samples from 118 patients with CRC and 88 matched controls. We also assessed tissue TLR expression with immunohistochemistry and by detecting serum determinants of systemic inflammation. Most participants (>70%) had undetectable serum TLR2. The mean serum TLR4 levels were lower in patients than in controls (1.1 vs 1.8 ng/mL; p = 0.015). Undetectable TLR4 was more common in stage I (39%) than in stages II–IV (11%, p < 0.001). TLR2 or TLR4 expression in tumor cells did not correlate with serum levels, but abundant TLR2 expression in normal colon epithelium was associated with detectable serum TLR2 (p = 0.034). Undetectable serum TLR2 was linked to high modified Glasgow prognostic scores (p = 0.010), high CRP levels (p = 0.013), blood vessel invasion (p = 0.013), and tended to be associated with worse 5‐year survival (p = 0.052). In conclusion, serum TLR2 levels were inversely associated with systemic inflammation in patients with CRC. Moreover, serum TLR2 levels might depend more on normal colorectal mucosa contributions than on tumor tissue contributions. Further studies are required to assess the prognostic value of serum TLR2.     

Estimating molar-incisor-hypomineralization among 8-year-olds based on 15-year public oral health practice-based data

Abstract

Background: A wide range in the prevalence of molar-incisor-hypomineralization (MIH) has been reported. Population-based studies are recommended. However, such studies are expensive and time-consuming.

Objectives: To estimate the magnitude of MIH condition among 8-year-olds based on routine oral health examinations and to associate first permanent molar (FPM) affection with that of other permanent teeth over time.

Materials and methods: This retrospective study, with cross-sectional and longitudinal components, was based on electronic oral health records; all 8-year-olds examined between 2002 and 2016 were included.

Results: The average estimated prevalence of MIH was 8.3%; yearly range was 4.8–15.9%. The mean number of affected teeth was 1.4; 62% had one affected tooth. One-surface defects were the most frequent (66%). Asymmetric distribution of affected teeth was observed. In follow-up, 10.7%, 8.4%, and 11.2% had at least one affected permanent canine, premolar, or second permanent molar, respectively. The proportion of children with other MIH-affected permanent teeth was higher in the group with ≥2 MIH-affected teeth than in group with one affected FPM at the age of 8.

Conclusions: The average prevalence of MIH was comparable to that reported elsewhere. The number of MIH-affected teeth at early mixed dentition predicts the affection of other permanent teeth over time, mainly that of permanent canines. Further screening of children with MIH is recommended to improve individually tailored early preventive and restorative dental care.     

Continuous Absorbable Intradermal Sutures Yield Better Cosmetic Results than Nonabsorbable Interrupted Sutures in Open Appendectomy Wounds: A Prospective,Randomized Trial

Background

Acute appendicitis is the most common reason for abdominal surgery in young adults and children. Open appendectomy is still the treatment often chosen because it is simple, safe, and effective. Our aim was to study whether cosmetic results of appendectomy wounds are better after using continuous absorbable intradermal (A) sutures compared with wound closure with interrupted nonabsorbable (NA) sutures.

Methods

A total of 206 adult patients with clinically suspected appendicitis were allocated to the study and prospectively randomized into two wound-closure groups: the interrupted NA suture group and the A suture group. Of these, 193 patients with sufficient data were invited to the outpatient clinic for cosmetic analysis. Cosmetic results were evaluated after a median of 14 months. For subjective scar assessment, the Vancouver scar scale, the patient and observer scar assessment scale (POSAS), and a visual analog scale (VAS) were used. Objective evaluation was carried out by measuring surface area, average width, and estimated concentration change (ECC) of hemoglobin and melanin in the scar using spectrocutometry. For statistical analyses we used the Mann–Whitney test and Student’s t test.

Results

Both objective and subjective analyses showed better cosmetic results for absorbable intradermal suturing. The difference between the two groups was statistically significant as regards POSAS in both patient (p = 0.032) and observer scales (p = 0.001), and VAS (p = 0.002). Scar surface area was significantly smaller in group A than in group NA (p = 0.002). ECC measurements showed higher values for melanin in group NA than in group A (p = 0.034).

Conclusion

Continuous intradermal absorbable suturing yields a better cosmetic result than interrupted nonabsorbable suturing in lower abdominal transverse appendectomy.     

Endoscopic Evaluation of Laparoscopic Nissen Fundoplication: 89 % Success Rate 10 Years After Surgery

Background

The surgical outcome of fundoplication can be evaluated by means of esophagogastroduodenoscopy (EGDS). The literature reveals only one prior long-term follow-up series with endoscopic evaluation of the fundoplication wraps after laparoscopic Nissen fundoplication (LNF). The results achieved at a university clinic showed LNF to be more durable than open fundoplication (ONF). Previously, in our community-based hospital, the results of ONF were somewhat poorer than those achieved at a university clinic. The objective of the present study was to describe the long-term results of LNF in our hospital as regards surgical and symptomatic outcomes.

Methods

In 1997–1999, 107 LNFs were performed in our hospital. A questionnaire with symptom evaluation was mailed to all patients. The patients who agreed to participate were interviewed and underwent EGDS.

Results

Of the 107 patients, 64 (59.8 %) participated in the study (40 men, mean age 61.9 years, range 28–85 years). The mean follow-up time was 9.8 years. Seven endoscopic examinations (10.9 %) showed a defective fundic wrap; three of the patients had undergone reoperation. Fifty-eight (90.6 %) patients had no or minimal heartburn and 61 (95.3 %) had no or minimal regurgitation. Twenty-three (35.9 %) patients had moderate or severe dysphagia, and 43 (67.2 %) patients had moderate or severe flatulence. Fifty-seven (89.1 %) patients would have opted for surgery again.

Conclusions

This study contributes to the previous notion that LNF is associated with fewer surgical failures than ONF. Our results indicate that LNF can well be performed in a community-based hospital with acceptable long-term results.     

Temperament,character and personality disorders

ObjectiveTo study, whether temperament and character remain stable over time and whether they differ between patients with and without personality disorder (PD) and between patients with specific PDs.MethodsPatients with (n = 225) or without (n = 285) PD from Jorvi Bipolar Study, Vantaa Depression Study (VDS) and Vantaa Primary Care Depression Study were interviewed at baseline and at 18 months, and in the VDS also at 5 years. A general population comparison group (n = 264) was surveyed by mail.ResultsCompared with non-PD patients, PD patients scored lower on self-directedness and cooperativeness. Cluster B and C PDs associated with high Novelty Seeking and Harm Avoidance, respectively. In logistic regression models, sensitivity and specificity of Temperament and Character Inventory (TCI) dimensions for presence of any PD were 53% and 75%, and for specific PDs from 11% to 41% and from 92% to 100%, respectively. The 18-month test-retest correlations of TCI-R dimensions ranged from 0.58 to 0.82.ConclusionsMedium-term temporal stability of TCI in a clinical population appears good. Character scores differ markedly between PD and non-PD patients, whereas temperament scores differ only somewhat between the specific PDs. However, the TCI dimensions capture only a portion of the differences between PD and non-PD patients.     

Short DNA sequences and bacterial DNA induce esophageal,gastric, and colorectal cancer cell invasion

Toll‐like receptor 9 (TLR9) recognizes both bacterial and self‐DNA and it is abundantly expressed in the gastrointestinal tract. In this study, we investigated the influences of both bacterial DNA and specific short DNA sequences on TLR9‐mediated gastrointestinal cancer cell invasion. We assessed the effect of various DNA ligands on cellular invasion and on TLR9 and matrix metalloproteinase expression of three gastrointestinal cancer cell lines. DNA‐ligands described in this study include CpG‐ODN M362, 9‐mer (hairpin), human telomeric sequence h‐Tel22 G‐quadruplex, and bacterial DNAs from Escherichia coli and Helicobacter pylori. All of the DNAs studied were demonstrated to induce invasion in the studied cells. The DNA‐induced invasion was inhibited with a broad‐spectrum MMP inhibitor and partly also with chloroquine suggesting that it could be mediated via MMP activation, endosomal signaling, and TLR9. Interestingly, H. pylori DNA was shown to induce a more pronounced invasion in a gastric cancer cell line than in the other cell lines. Our results suggest that bacterial DNA as well as deoxynucleotides having stable secondary structures (i.e. hairpins or G‐quadruplex structures) may serve as endogenous, invasion‐inducing TLR9‐ligands and promote local progression and metastasis of cancers in the alimentary tract.     

Expression of cancer‐related carbonic anhydrases IX and XII in normal skin and skin neoplasms

Purpose of the study was to evaluate the presence of hypoxia‐inducible, tumour‐associated carbonic anhydrases IX and XII in normal skin and a series of cutaneous tumours. Human tumour samples were taken during surgical operations performed on 245 patients and were immunohistochemically stained. A histological score value was calculated for statistical analyses which were performed using SPSS for Windows, versions 17.0 and 20.0. In normal skin, the highest expression of CA IX was detected in hair follicles, sebaceous glands, and basal parts of epidermis. CA XII was detected in all epithelial components of skin. Both CA IX and CA XII expression levels were significantly different in epidermal, appendigeal, and melanocytic tumour categories. Both CA IX and XII showed the most intense immunostaining in epidermal tumours, whereas virtually all melanocytic tumours were devoid of CA IX and XII immunostaining. In premalignant lesions, CA IX expression significantly increased when the tumours progressed to more severe dysplasia forms. Both CA IX and XII are highly expressed in different epithelial components of skin. They are also highly expressed in epidermal tumours, in which CA IX expression levels also correlate with the dysplasia grade. Interestingly, both isozymes are absent in melanocytic tumours.