Cell cycle analysis can differentiate thin melanomas from dysplastic nevi and reveals accelerated replication in thick melanomas

Cell replication integrates aberrations of cell cycle regulation and diverse upstream pathways which all can contribute to melanoma development and progression. In this study, cell cycle regulatory proteins were detected in situ in benign and malignant melanocytic tumors to allow correlation of major cell cycle fractions (G1, S-G2, and G2-M) with melanoma evolution. Dysplastic nevi expressed early cell cycle markers (cyclin D1 and cyclin-dependent kinase 2; Cdk2) significantly more (p?<?0.05) than common nevi. Post-G1 phase markers such as cyclin A, geminin, topoisomerase IIα (peaking at S-G2) and aurora kinase B (peaking at G2-M) were expressed in thin (≤1 mm) melanomas but not in dysplastic nevi, suggesting that dysplastic melanocytes engaged in the cell cycle do not complete replication and remain arrested in G1 phase. In malignant melanomas, the expression of general and post-G1 phase markers correlated well with each other implying negligible cell cycle arrest. Post-G1 phase markers and Ki67 but none of the early markers cyclin D1, Cdk2 or minichromosome maintenance protein 6 (Mcm6) were expressed significantly more often in thick (>1 mm) than in thin melanomas. Marker expression did not differ between metastatic melanomas and thick melanomas, with the exception of aurora kinase A of which the expression was higher in metastatic melanomas. Combined detection of cyclin A (post-G1 phase) with Mcm6 (replication licensing) and Ki67 correctly classified thin melanomas and dysplastic nevi in 95.9 % of the original samples and in 93.2 % of cross-validated grouped cases at 89.5 % sensitivity and 92.6 % specificity. Therefore, cell cycle phase marker detection can indicate malignancy in early melanocytic lesions and accelerated cell cycle progression during vertical melanoma growth.     

Controversial association results for INSIG2 on body mass index may be explained by interactions with age and with MC4R

Among the single-nucleotide polymorphisms (SNPs) previously reported to be associated with body mass index (BMI) and obesity, we focus on a common risk variant rs7566605 upstream of the insulin-induced gene 2 (INSIG2) gene and a rare protective variant rs2229616 on the melanocortin-4 receptor (MC4R) gene. INSIG2 is involved in adipogenesis and MC4R effects hormonal appetite control in response to the amount of adipose tissue. The influence of rs2229616 (MC4R) on BMI and obesity has been confirmed repeatedly and insight into the underlying mechanism provided. However, a main effect of rs7566605 (INSIG2) is under debate because of inconsistent replications of association. Interaction of rs7566605 with age may offer an explanation. SNP–age and SNP–SNP interaction models were tested on independent individuals from three population-based longitudinal cohorts, restricting the analysis to an observed age of 25–74 years. KORA S3/F3, KORA S4/F4 (Augsburg, Germany, 1994–2005, 1999–2008), and Framingham-Offspring data (Framingham, USA, 1971–2001) were analysed, with a total sample size of N=6926 in the joint analysis. The effect of interaction between rs7566605 and age on BMI and obesity status is significant and consistent across studies. This new evidence for rs7566605 (INSIG2) complements previous research. In addition, the interaction effect of rs7566605 with the MC4R variant rs2229616 on BMI was observed. This effect size was three times larger than that in a previously reported single-locus main effect of rs2229616. This leads to the conclusion that SNP–age or SNP–SNP interactions can mask genetic effects for complex diseases if left unaccounted for.     

Applicability of strain measurements on a contra angle handpiece for the determination of alveolar bone quality during dental implant surgery

Alveolar bone quality is considered to be an important prognostic factor in dental implant stability. Although numerous methods have been described, no technique allows for reliable diagnostics. The purpose of this study was to determine if strain measurements on the shaft of a contra angle handpiece during implant bed preparation could be used for the determination of bone quality. Experiments in polyurethane foam and human cadaver bone were conducted to investigate whether strain measurements could be correlated with other diagnostic parameters, such as the surgeon's tactile sensation during drilling, implant insertion torque, implant stability, elastic modulus of bone and bone quality as assessed radiographically. Tests were also performed to determine if strain measurements could be used to distinguish various types of bone. As axial feed and contact pressure during the drilling process could not be standardized under simulated clinical conditions, substantial deviations in the time needed to complete the drilling occurred. Under controlled circumstances using polyurethane foam, this problem could be addressed by a normalization procedure, but great variations occurred in human cadaver bone. As bone quality could not be reliably determined, especially when a cortical layer was present, strain measurements on a contra angle handpiece appears to be inappropriate for this purpose.     

Possibilities and limitations of implant placement by virtual planning data and surgical guide templates

The use of computer-aided surgical systems for dental implant bed preparation and implant placement results in an average precision within 1 mm of implant position and within 5 degrees of deviation for implant inclination. The accuracy of axis and implant position is significantly more precise with the three-dimensional surgical guide than with the free-hand method. The three-dimensional assessment of the restorative goal (radiopaque simulation of prosthesis with scanning template) allows virtual planning of implants, which enables optimized positioning of implants with surgical guide templates in oral surgery. If there is a clear indication for three-dimensional diagnostics, it should always be checked whether the data can be used as planning data for a surgical guide template, otherwise the chance for guided surgery remains unused. Since uncertainties still exist despite the use of a drilling template, it is recommended that the minimum safety distance from adjacent structures be maintained. The successful use of surgical guide templates requires comprehensive knowledge of and experience in using three-dimensional information for the virtual planning of implant position.     

Acute and Elective Laparoscopic Resection for Complicated Sigmoid Diverticulitis: Clinical and Histological Outcome

Background

Surgical treatment of acute complicated sigmoid diverticulitis is still under debate while elective treatment of recurrent diverticulitis has proven benefits. The aim of this study was to evaluate the clinical and histological outcome of acute and elective laparoscopic sigmoid colectomy in patients with diverticulitis.

Methods

A retrospective review was conducted where 197 patients were analyzed undergoing laparoscopic sigmoid resection for acute complicated diverticulitis and recurrent diverticulitis. Single-stage laparoscopic resection and primary anastomosis were routinely performed using a 3-trocar technique. Recorded data included age, sex, American Society of Anesthesiologists (ASA)-score, operative time, duration of hospital stay, complications, and histological results.

Results

Ninety-one patients received laparoscopy for acute diverticular disease (group I) and 93 patients underwent elective laparoscopic sigmoid resection for diverticulitis (group II). M/F ratio was 49:42 for group I and 37:56 for group II. Mean operative time and hospital stay was similar in both groups. Majority of patients were ASA II in both groups. Rate of minor complications was 14.3 % in group I and 7.5 % in group II. Major complications were 2.2 % for acute treatment and 4.3 % for elective resections. No anastomotic leakage and no mortality occurred. In 32.3 % of the patients of elective group II, destruction of the colonic wall with pericolic abscess, fistulization, or fibrinoid purulent peritonitis were identified.

Conclusions

Laparoscopic surgery for acute diverticular disease is safe and effective. Continuing bowl inflammations in histological specimens justify sigmoid resection in elective patients, but more effective pre-operative parameters need to be found to identify patients that would benefit from surgery during the initial episode.