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Purpose: The aim of this work was to evaluate the bone-repair process after implantation of homogenous demineralized dentin matrix (HDDM) slices in surgical defects created in the parietal bones of rabbits with alloxan-induced diabetes. Materials and Methods: Forty-eight rabbits were selected and divided into 4 groups of 12 rabbits: the control group, diabetic rabbits (D), diabetic rabbits with a PTFE barrier (D-PTFE), and diabetic rabbits with a PTFE barrier and with slices of homogenous demineralized dentin matrix (D-PTFE+HDDM). The diabetic animals received a single dose of alloxan monohydrate (90 mg/kg) intravenously on the marginal ear vein, and their blood glucose was verified daily. The rabbits were sacrificed after 15, 30, 60, and 90 days. The histologic findings show both better bone structure and significantly greater bone density, as determined by histomorphometric analysis, for the D-PTFE + HDDM group than for the other 3 groups (P < .01). It was also observed that the mean bone density increased gradually from 15 to 90 days (except in the D-PTFE group). Conclusion: It was concluded that the HDDM was biocompatible with the bone repair of diabetic rabbits and that HDDM slices stimulated bone tissue formation. Facilitation of bone repair with HDDM could be useful in diabetic patients. [ABSTRACT FROM AUTHOR]

Introduction: Mucosal melanoma is a rare neoplasm. Late diagnosis is caused by occult anatomic sites and scarcity of symptoms. Novel biological therapies have now become available. Demographic, therapeutical and survival records on mucosal melanoma are scarce., Objectives: To provide an 11-year retrospective clinical review of real-world data on mucosal melanomas managed in a tertiary referral center in Italy., Methods: We included patients with histopathological mucosal melanoma diagnoses from January 2011 to December 2021. Data were collected until the last known follow-up or death. Survival analysis was performed., Results: Among 33 patients, we found 9 sinonasal, 13 anorectal and 11 urogenital mucosal melanomas (median age 82, females 66.7%). Eighteen cases (54.5%) presented with metastasis (p<0.05). In the urogenital subgroup, only 4 patients (36.4%) had metastasis at diagnosis, all in regional lymph nodes. Sinonasal melanomas were surgically managed with a debulking procedure (44.4%); every case of anorectal and urogenital melanomas underwent radical surgery (30.8% and 45.5%). Fifteen patients were treated with biological therapy (p<0.05). Radiation therapy was used in all melanomas of the sinonasal region (p<0.05). Overall survival was longer for urogenital melanomas (26 months). Univariate analysis showed an increased hazard ratio for death in patients with metastasis. A negative prognostic value of metastatic status was reported by the multivariate model, while administration of first-line immunotherapy demonstrated a protective role., Conclusions: At diagnosis, the absence of metastatic disease is the most relevant factor that influences the survival of mucosal melanomas. Moreover, the use of immunotherapy might prolong the survival of metastatic mucosal melanoma patients.

Importance: In the pivotal Bevacizumab-Avastin Adjuvant (AVANT) trial, patients with high-risk stage II colon cancer (CC) had 5-year and 10-year overall survival (OS) rates of 88% and 75%, respectively, with adjuvant fluorouracil and oxaliplatin-based chemotherapy; however, the trial did not demonstrate a disease-free survival (DFS) benefit of adding bevacizumab to oxaliplatin-based chemotherapy in stage III CC and suggested a detrimental effect on OS. The Long-term Survival AVANT (S-AVANT) study was designed to collect extended follow-up for patients in the AVANT trial., Objective: To explore the efficacy of adjuvant bevacizumab combined with oxaliplatin-based chemotherapy in patients with high-risk, stage II CC., Design, Setting, and Participants: This prespecified secondary end point analysis of the AVANT and S-AVANT studies included 573 patients with curatively resected high-risk stage II CC and at least 1 of the following criteria: stage T4, bowel obstruction or perforation, blood and/or lymphatic vascular invasion and/or perineural invasion, age younger than 50 years, or fewer than 12 nodes analyzed. The AVANT study was a multicenter randomized stage 3 clinical trial. Data were collected from December 2004 to February 2019, and data for this study were analyzed from March to September 2019., Intervention: Patients were randomly assigned to receive 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX4), FOLFOX4 with bevacizumab, or capecitabine and oxaliplatin (XELOX) with bevacizumab., Main Outcomes and Measures: The primary end points of this secondary analysis were DFS and OS in patients with high-risk stage II CC., Results: The AVANT study included 3451 patients, of whom 573 (16.6%) had high-risk stage II CC (192 [33.5%] randomized to FOLFOX4 group; 194 [33.9%] randomized to FOLFOX4 with bevacizumab group; 187 [32.6%] randomized to XELOX with bevacizumab group). With a median (interquartile range) age of 57.0 (47.2-65.7) years, the study population comprised 325 men (56.7%) and 248 women (43.3%). After a median (interquartile range) follow-up of 6.9 (6.1-11.3) years, the 3-year DFS and 5-year OS rates were 88.2% (95% CI, 83.7%-93.0%) and 89.7% (95% CI, 85.4%-94.2%) in the FOLFOX4 group, 86.6% (95% CI, 81.8%-91.6%) and 89.7% (95% CI, 85.4%-94.2%) in the FOLFOX4 with bevacizumab group, and 86.7% (95% CI, 81.8%-91.8%) and 93.2% (95% CI, 89.6%-97.0%) in the XELOX with bevacizumab group, respectively. The DFS hazard ratio was 0.94 (95% CI, 0.59-1.48; P = .78) for FOLFOX4 with bevacizumab vs FOLFOX4 and 1.07 (95% CI, 0.69-1.67; P = .76) for XELOX with bevacizumab vs FOLFOX4. The OS hazard ratio was 0.92 (95% CI, 0.55-1.55; P = .76) for FOLFOX4 with bevacizumab vs FOLFOX4 and 0.85 (95% CI, 0.50-1.44; P = .55) for XELOX with bevacizumab vs FOLFOX4., Conclusions and Relevance: In this secondary analysis of data from the AVANT trial, adding bevacizumab to oxaliplatin-based chemotherapy was not associated with longer DFS or OS in patients with high-risk stage II CC. The findings suggest that the definition of high-risk stage II CC needs to be revisited., Trial Registration: ClinicalTrial.gov Identifiers: AVANT (NCT00112918); S-AVANT (NCT02228668).

Adenomas are the easily identifiable precursors of the vast majority of colorectal cancers. Some of their morphological features, such as dysplasia, are predictive of their biological evolution toward adenocarcinomas. A large body of evidence has demonstrated that the epidermal growth factor receptor (EGFR) signaling pathway is commonly activated in colorectal cancer and EGFR-target therapies have improved the outcome for colorectal cancer patients. Nevertheless, the mechanisms underlying the role of EGFR in the adenoma-carcinoma sequence are not entirely clear. We retrospectively analyzed EGFR gene copy number by fluorescence in situ hybridization (FISH) in paraffin-embedded tissue from 215 patients recruited through a prospective colorectal cancer screening procedure and undergoing surgical colectomy. We observed that in human colorectal carcinogenesis, EGFR copy number increases progressively, from adenomas with high-grade dysplasia to locally advanced adenocarcinomas, through early invasive adenocarcinomas, suggesting that deregulation of EGFR may correlate with the malignant progression., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: The reconstruction of the maxillary bone frequently represents a real challenge for maxillofacial surgeons especially regarding the best choice of a suitable material to produce the required bone augmentation., Aim: In this study, we summarize our clinical experience on 47 sinus lifts with lateral approach using a mixture of aragonitic calcium carbonate and autologous platelet-rich plasma compared with that of a previous published study in which bovine bone (LADDEC) and autologous bone were used in 50 sinus lift operations (Br J Oral Maxillofac Surg 2005;43:309-313)., Materials and Methods: We subjected 34 patients to sinus lift operation, for a total of 47 sinus lifts, using natural coral as osteoconductive material. This material, combined with autologous platelet-rich plasma, was placed onto the maxillary sinus floor, after carefully lifting the endosteum. Cases were clinically, radiographically, and histologically analyzed. Histomorphometrical analysis, tests of microhardness, and x-ray microanalysis were conducted comparing the various sample to controls obtained from the same patients., Results and Conclusions: Histomorphometrical analysis, microhardness test, and x-ray microanalysis demonstrated that the newly formed bone showed morphologic and structural characteristics that were similar for all the grafting materials compared (bovine bone, autologous bone, and coral). Although all the grafting materials did yield good results of maturation of the newly formed bone, best results were achieved using autologous bone.

This paper reports on a 4-year-old male who had dyskeratosis congenita and who acquired severe aplastic anemia. The patient developed hyperpigmentation of the face, neck and chest region, arms, shoulders and legs. In addition, he had dry skin, deformed fingernails and toenails, sparse hair and eyebrows and hyperkeratosis of the dorsum of the hands and feet. Laboratory and histological analysis revealed severe pancytopenia and dyserythropoiesis of red blood cells, hypocellularity of white blood cells and decreased megakaryocytes with dysplasia. The intraoral examination identified bleeding gums; petechiae of the palate, tongue and cheek mucosa; and an atrophic, smooth and shining dorsal surface of the tongue. There were deep carious lesions in the deciduous mandibular molars and maxillary anterior teeth; as well as mobility of mandibular left canine, which had bone loss. The treatment for oral lesions included diet changes, improved oral hygiene, and extraction of the deciduous teeth destroyed by caries.

Background: To evaluate the changes in the biological features of breast cancer cells induced by primary chemotherapy (PCT) and their possible relationship with the response to therapy we performed an extensive immunohistochemical study before and after PCT., Patients and Methods: PCT was administered to 29 women with breast cancer. On specimens obtained by tru-cut and post-chemotherapy surgery we analyzed the following parameters: histology, histologic grade, apoptotic index, hormone receptor levels, Ki67, PCNA, EGFr, bcl-2, p53, p170. The significance of the changes induced by PCT and their correlations with the type of response were evaluated., Results: Twelve patients achieved a partial response with PCT. No baseline biological parameter correlated with the type of response. After PCT we observed a significant increase in the apoptotic index (p = 0.000), PCNA (p = 0.036), EGFr (p = 0.005), and p170 expression (p = 0.001), regardless of the type of chemotherapy administered (anthracyclines, 25 cases, or CMF, 4 cases). Responder patients displayed a significant decrease in ER levels (p = 0.015), whereas in non responders there was an increase in PCNA (p = 0.008) and EGFr expression (p = 0.002). The apoptotic index and p170 expression rose after PCT regardless of the type of response., Conclusions: PCT induced significant variations in the phenotype of breast cancer cells. These changes might reflect the selection of new neoplastic clones with different biological properties and so could facilitate the choice of appropriate chemotherapy agents.

A karyotype was obtained from 755 fetuses with structural anomalies detected by sonography between 13 and 40 weeks' gestation. Gestational age was found to have no influence on the prevalence of chromosomal aberrations. The incidence in the second and third trimesters of pregnancy was 15.7 and 17.5 per cent, respectively. The contribution of the different malformations to such proportions did, however, change throughout gestation. Cystic hygroma was by far predominant in the early second trimester, cardiac defects in the late second trimester, and duodenal atresia in late pregnancy. Our findings confirm that karyotyping of malformed fetuses is highly advisable; the importance of chromosomal investigation is not dependent on the gestational age at detection of the structural defect as the likelihood of finding a chromosomal anomaly during the second and third trimesters is quite similar. Spontaneous intrauterine selection of chromosomally abnormal fetuses is most likely counterbalanced by the limited accuracy of prenatal ultrasound in recognizing many fetal anomalies early in pregnancy.