Fabrication of a complete,removable dental prosthesis from a digital intraoral impression for a patient with an excessively tight reconstructed lip after oral cancer treatment: A clinical report

This clinical report describes the management of a patient who had an excessively tight reconstructed lip because of oral cancer surgery and postoperative radiotherapy. The presented technique used an intraoral scanner for a preliminary impression and computer-aided design and computer-aided manufacturing (CAD-CAM) technology for preliminary laboratory procedures. This digital impression technique may reduce patient discomfort.     

Role of vascular density and normalization in response to neoadjuvant bevacizumab and chemotherapy in breast cancer patients

Preoperative bevacizumab and chemotherapy may benefit a subset of breast cancer (BC) patients. To explore potential mechanisms of this benefit, we conducted a phase II study of neoadjuvant bevacizumab (single dose) followed by combined bevacizumab and adriamycin/cyclophosphamide/paclitaxel chemotherapy in HER2-negative BC. The regimen was well-tolerated and showed a higher rate of pathologic complete response (pCR) in triple-negative (TN)BC (11/21 patients or 52%, [95% confidence interval (CI): 30,74]) than in hormone receptor-positive (HR)BC [5/78 patients or 6% (95%CI: 2,14)]. Within the HRBCs, basal-like subtype was significantly associated with pCR (P = 0.007; Fisher exact test). We assessed interstitial fluid pressure (IFP) and tissue biopsies before and after bevacizumab monotherapy and circulating plasma biomarkers at baseline and before and after combination therapy. Bevacizumab alone lowered IFP, but to a smaller extent than previously observed in other tumor types. Pathologic response to therapy correlated with sVEGFR1 postbevacizumab alone in TNBC (Spearman correlation 0.610, P = 0.0033) and pretreatment microvascular density (MVD) in all patients (Spearman correlation 0.465, P = 0.0005). Moreover, increased pericyte-covered MVD, a marker of extent of vascular normalization, after bevacizumab monotherapy was associated with improved pathologic response to treatment, especially in patients with a high pretreatment MVD. These data suggest that bevacizumab prunes vessels while normalizing those remaining, and thus is beneficial only when sufficient numbers of vessels are initially present. This study implicates pretreatment MVD as a potential predictive biomarker of response to bevacizumab in BC and suggests that new therapies are needed to normalize vessels without pruning.Ten drugs that target VEGF or its receptors have been approved for the treatment of various malignant diseases (1). However, bevacizumab, an anti-VEGF antibody, and other antiangiogenic agents (AAs) that target the VEGF pathway have failed to provide an overall survival benefit to metastatic breast cancer (BC) patients (2). Preoperative (neoadjuvant) therapy is an effective way of treating certain BC patients, because this strategy leads to survival rates similar to those from postoperative therapy (3) while reducing the extent of surgery. Moreover, a favorable pathologic response to neoadjuvant therapy is associated with longer disease-free survival (4, 5). Recent studies report significant increases in the percentage of patients with no detectable residual disease—referred to as pathologic complete response (pCR)—with the addition of bevacizumab to neoadjuvant chemotherapy in human epidermal growth factor receptor 2 (HER2)-negative BC. The GeparQuinto, the CALGB 40603, and the ARTemis trials demonstrated a significant increase in pCR with the addition of bevacizumab in patients with triple-negative BC (TNBC) (6–8). However, the National Surgical Adjuvant Breast and Bowel Project B-40 study demonstrated a higher pCR rate in hormone receptor-positive BC (15.1% without bevacizumab vs. 23.2% with bevacizumab, P = 0.007) but no statistically significant difference in TNBC (9). Moreover, two postoperative (adjuvant) trials of bevacizumab, BEATRICE and E5103, demonstrated no improvement in disease-free survival with the addition of bevacizumab to standard anthracycline- and taxane-based chemotherapy (2, 10). These inconsistent results underscore the need to identify mechanistic biomarkers of response to bevacizumab therapy.There are two major hypotheses concerning AAs’ mechanism of action in tumors: (i) starving the tumor by blocking its blood supply and (ii) alleviating hypoxia by normalizing the function of tumor vasculature (1). Emerging functional imaging data in glioblastoma, nonsmall-cell lung cancer, and BC patients suggests that improved vascular function and the resulting increase in tumor oxygenation are associated with response to AAs (1, 11–15). However, there are no structural features of tumor vessels that can be used to predict the response (16), and the vascular changes induced by AAs to increase vessel function remain unclear. To complement the previous functional imaging studies with histological analysis of in situ changes in vascular structure in response to AA, we conducted a phase II trial of HER2-negative BC to investigate the neoadjuvant use of bevacizumab combined with standard of care dose-dense chemotherapy, which consists of doxorubicin and cyclophosphamide followed by paclitaxel (ACP). Neoadjuvant treatment enables pre- and posttherapy biopsies to explore potential mechanisms of action and biomarkers that may help select patients likely to benefit from AAs. In this exploratory correlative study, we evaluated biomarkers in serial biopsies, blood samples, and a functional marker of vascular normalization—tumor interstitial fluid pressure (IFP)—before and after a single dose of bevacizumab. Our results suggest that a high baseline microvascular density (MVD) in breast tumors may be necessary to benefit from bevacizumab-induced vascular normalization.     

Genetic Variants in the SAMM50 Gene Create Susceptibility to Nonalcoholic Fatty Liver Disease in a Chinese Han Population

Background:

Genome-wide association studies have shown that rs738491, rs2143571, and rs3761472 in the sorting and assembly machinery component 50 homolog (SAMM50) gene are significantly associated with susceptibility to nonalcoholic fatty liver disease (NAFLD).

Objectives:

The present study evaluated the association between the three genetic variants in the SAMM50 gene and susceptibility to NAFLD in a Chinese Han population.

Patients and Methods:

Genotypes for 3 single nucleotide polymorphisms (SNPs), viz rs738491, rs2143571, and rs3761472, in the SAMM50 gene were determined using an improved multiplex ligation detection reaction technique in 340 B-type ultrasonography-diagnosed NAFLD patients and 452 healthy controls. Meanwhile, serum lipid profiles and liver enzymes were estimated using standard clinical laboratory methods. The SNP-SNP interactions were analyzed by performing multifactor dimensionality reduction (MDR) and generalized multifactor dimensionality reduction (GMDR).

Results:

The genotype and allele frequencies of the SAMM50 polymorphisms between the NAFLD group and the control group were significantly different (all Ps < 0.05). In the multivariate analysis adjusted for gender, age, and body mass index, the carriers of the rs738491 T allele, rs2143571 A allele, and rs3761472 G allele had significantly increased susceptibility to NAFLD (OR, 1.507; 95% CI, 1.035 to 2.195; P = 0.032; OR, 1.761; 95% CI, 1.232 to 2.517; P = 0.002; OR, 1.483; 95% CI, 1.039 to 2.115; P = 0.030, respectively). Moreover, the rs738491 T allele carriers had significantly higher levels of alanine aminotransferase (ALT) (P = 0.017) than did the noncarriers. However, differences in the levels of serum triglyceride (TG) and aspartate aminotransferase (AST) were not statistically significant (P = 0.123; P = 0.107). The Rs2143571 A allele and the rs3761472 G allele were both deeply associated with increased levels of serum TG, ALT, and AST (all Ps < 0.05). Furthermore, the MDR and GMDR showed that a synergistic relationship might exist between rs738491, rs2143571, and rs3761472 in the SAMM50 gene and the pathophysiology and genetics of NAFLD.

Conclusions:

We first demonstrated that the rs738491 T allele, rs2143571 A allele, and rs3761472 G allele in the SAMM50 gene created susceptibility to NAFLD in a Chinese Han population. The combination of the three SNPs in the SAMM50 gene may have synergism to predict the predisposition to NAFLD.     

A novel non-invasive score for the prediction of advanced fibrosis in patients with chronic hepatitis B

Introduction and objectivesEvaluation of liver fibrosis is important for treatment decisions, complications and to predict prognosis in patients with chronic hepatitis B (CHB). Our aim was to develop a new non-invasive fibrosis scoring method and prove its accuracy in the differentiation of no/low grade and advanced fibrosis in patients with CHB.Patients and methodsOur study included 273 chronic hepatitis B patients who underwent liver biopsy from February, 2007 to February, 2019 with medical records retrospectively reviewed. Preparations of these patients were divided into two groups as ≤ 3 no-low grade fibrosis (n=236) and ≥ 4 advanced fibrosis (n=37) according to histological ISHAK fibrosis scoring system.ResultsThe newly developed AGAP score and other non-invasive fibrosis scores; Fibrosis-4 index, Aspartate aminotransferase to platelets ratio, Gamma glutamyl transpeptidase to platelet ratio, Goteborg University Cirrhosis Index, King's score, Albumin-bilirubin index, Fibrosis cirrhosis index, Fibrosis index, Fibrosis quotient, Lok score and mean and/or median values of Fibroindex were significantly higher in the advanced fibrosis group compared to the no/low grade fibrosis group (p<0.001). However, there was no significant difference in AAR score among the groups (p=0.265). With cut-off value of 4.038, AUROC value of 0.803, sensitivity of 75.7%, specificity of 73.7% and accuracy of 0.740, AGAP score showed the best performance in advanced fibrosis differentiation compared to 12 other non-invasive fibrosis scoring methods.ConclusionsThe newly developed AGAP score showed better performance in patients with CHB compared to 12 other non-invasive fibrosis scores in differentiation of no/low grade fibrosis and advanced fibrosis.