Saliva protein biomarkers to detect oral squamous cell carcinoma in a high-risk population in Taiwan.

Most cases of oral squamous cell carcinoma (OSCC) develop from visible oral potentially malignant disorders (OPMDs). The latter exhibit heterogeneous subtypes with different transformation potentials, complicating the early detection of OSCC during routine visual oral cancer screenings. To develop clinically applicable biomarkers, we collected saliva samples from 96 healthy controls, 103 low-risk OPMDs, 130 high-risk OPMDs, and 131 OSCC subjects. These individuals were enrolled in Taiwan's Oral Cancer Screening Program. We identified 302 protein biomarkers reported in the literature and/or through in-house studies and prioritized 49 proteins for quantification in the saliva samples using multiple reaction monitoring-MS. Twenty-eight proteins were successfully quantified with high confidence. The quantification data from non-OSCC subjects (healthy controls + low-risk OPMDs) and OSCC subjects in the training set were subjected to classification and regression tree analyses, through which we generated a four-protein panel consisting of MMP1, KNG1, ANXA2, and HSPA5. A risk-score scheme was established, and the panel showed high sensitivity (87.5%) and specificity (80.5%) in the test set to distinguish OSCC samples from non-OSCC samples. The risk score >0.4 detected 84% (42/50) of the stage I OSCCs and a significant portion (42%) of the high-risk OPMDs. Moreover, among 88 high-risk OPMD patients with available follow-up results, 18 developed OSCC within 5 y; of them, 77.8% (14/18) had risk scores >0.4. Our four-protein panel may therefore offer a clinically effective tool for detecting OSCC and monitoring high-risk OPMDs through a readily available biofluid.

The potential effects of cholecalciferol on bone regeneration in dogs.

OBJECTIVES: The aim of this investigation was to evaluate the potential effects of the systemically delivered combination of calcium supplementation and cholecalciferol and of the locally applied biphasic calcium alloplast on the surgically produced alveolar sockets at the early healing stage in a dog model. MATERIALS AND METHODS: The mandibular pre-molars of nine Beagle dogs were extracted first. Three months later, four standardized sockets with a 4 mm in diameter and 6 mm deep cylinder were created bilaterally at healed extraction sites. The sockets on one side were grafted with biphasic calcium phosphate alloplast, whereas the defects on the other side were left un-grafted. The dogs were then randomly divided into two groups; five dogs received oral calcium and cholecalciferol combination (Vit.D/Ca) and were assigned to the test group (Vit.D/Ca Group). The other four dogs without Vit.D/Ca supplement were distributed to the control group (Non-Vit.D/Ca Group). The bone density (Density) and the implant stability quotient (ISQ) at prepared sites were measured 4 weeks later. The drawn bone cores were examined by a histomorphometric analysis for measurement of new bone formation (NBF). The amount of vertical ridge resorption (VRR) was evaluated. RESULTS: The Vit.D/Ca-treated subjects revealed significantly more NBF (P < 0.05), higher bone density (P < 0.05) and significantly less vertical ridge reduction (P < 0.05) in the healing sockets than those without Vit.D/Ca treatment. The non-grafted sockets demonstrated significantly more NBF (P < 0.05), higher bone density (P < 0.05), better ISQ value (P < 0.05) and more vertical ridge reduction (P < 0.05) than those in the grafted sockets. There was no significant difference between the serum data determined before and 4 weeks after experiment in Vit.D/Ca Group or Non-Vit.D/Ca Group. However, the changed value (post-op vs. pre-op) between the two groups was significant in the serum level of phosphate and parathyroid hormone (P = 0.05). CONCLUSION: The results of the present study indicated that the examined calcium phosphate alloplast may perform a function in alveolar ridge preservation while reducing the potential of NBF potential in the healing extraction socket. Also, the combination of calcium supplementation and cholecalciferol may have systemic effects on accelerating bone regeneration.

Maintenance of pegylated liposomal doxorubicin/carboplatin in patients with advanced ovarian cancer: randomized study of an Asian Gynecologic Oncology Group.

OBJECTIVES: An Asian Gynecologic Oncology Group phase III randomized trial was conducted to determine whether maintenance chemotherapy could improve progression-free survival (PFS) in stages III/IV ovarian cancer. METHODS: Between 2007 and 2014, 45 newly-diagnosed ovarian cancer patients were enrolled after complete remission and randomized (1:1) to arm A (4-weekly carboplatin area under the curve 4 and pegylated liposomal doxorubicin [PLD] 30 mg/m², n=24) for 6 cycles or arm B (observation, n=21). The primary end-point was PFS. A post hoc translational study was conducted to deep sequence BRCA/homologous recombination deficiency (HRD) genes, because BRCA/HRD mutations (BRCA/HRDm) are known to be associated with better prognosis. RESULTS: Enrollment was slow, accrual was closed when 7+ years had passed. With a median follow-up of 88.9 months, the median PFS was significantly better in arm A (55.5 months) than arm B (9.2 months) (hazard ratio [HR]=0.40; 95% confidence interval [CI]=0.19-0.87; p=0.020), yet the median overall survival was not significantly different in arm A (not reached) than arm B (95.1 months) (p=0.148). Overall grade 3/4 adverse events were more frequent in arm A than arm B (60.9% vs 0.0%) (p<0.001). Quality of life was generally not significantly different. Distribution of BRCA1/2m or BRCA/HRDm was not significantly biased between the two arms. Wild-type BRCA/non-HRD subgroup seemed to fare better with maintenance therapy (HR=0.35; 95% CI=0.11-1.18; p=0.091). CONCLUSIONS: Despite limitations in small sample size, it suggests that maintenance carboplatin-PLD chemotherapy could improve PFS in advanced ovarian cancer.

Severity of chronic periodontitis and risk of gastrointestinal cancers: A population-based follow-up study from Taiwan.

The present study aimed to assess the association between the severity of chronic periodontitis and the risk of gastrointestinal (GI) cancers by investigating whether severe chronic periodontitis (CP), rather than mild CP, correlates with an increased risk of total or individual GI cancers.Adults (≥18 years) with mild and severe CP were identified from a random sample of 2 million insured patients in the National Health Insurance Research Database (2001-2010). After propensity score matching, 25,485 individuals, each with mild or severe CP, were included for comparison. The primary endpoint was the incidence of total or individual GI cancers, including cancers of the esophagus, stomach, small intestine, colon/rectum, and pancreas. Cox proportional hazard models with the robust aggregated sandwich estimator were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) after adjusting for known risk factors.GI cancers occurred in 275 individuals with mild CP and 324 individuals with severe CP. After adjusting for known risk factors, severe CP was not associated with an increased risk of total GI cancer relative to mild CP (HR: 0.99, 95% CI: 0.84-1.16) or individual GI cancers, including esophageal (HR: 1.15, 95% CI: 0.62-2.15), gastric (HR: 1.01, 95% CI: 0.68-1.49), small intestinal (HR: 0.70, 95% CI: 0.22-2.22), colorectal (HR: 0.95, 95% CI: 0.78-1.16), and pancreatic cancers (HR: 0.90, 95% CI: 0.47-1.75).Severe CP was not associated with an increased risk of total or individual GI cancers when compared with mild CP.

Clinical evaluation of silicone gel in the treatment of cleft lip scars.

Upper lip scars are at risk of hypertrophy. Our center therefore uses microporous tape and silicone sheeting for postoperative scar care following cleft lip repair. However, some babies have previously ingested their silicone sheeting, which has the potential for respiratory compromise or gastrointestinal obstruction. Self-dry silicone gel is reportedly also effective for preventing hypertrophic scars. Hence, we sought to test whether silicone gel, which cannot be ingested whole, might be non-inferior to silicone sheeting for controlling against upper lip scar hypertrophy. This was a mixed prospective and retrospective case-controlled clinical trial involving patients undergoing unilateral cleft lip repair, 29 of whom received standard postoperative silicone sheeting (control group) and another 33 age-matched consecutive patients who received self-dry silicone instead. The Vancouver scar scale, visual analogue scale and photographically assessed scar width assessments were the same in both groups at six months after surgery. In conclusion, silicone gel appears to be non-inferior to silicone sheeting for postoperative care of upper lip scars as judged by scar quality at six months, but silicone sheeting has the safety disadvantage that it can be swallowed whole by babies. It is thus recommended that silicone gel be used for upper lip scar management in babies.

Patient and parent reported outcome measures in cleft lip and palate patients before and after secondary alveolar bone grafting.

European and Northern American healthcare authorities increasingly encourage the use of Patient Reported Outcome Measures (PROMs) that complement clinical and laboratory assessments to help holistically evaluate reconstructive outcomes. This is the first study to evaluate PROMs in cleft lip/palate patients who have, or have not, undergone secondary alveolar bone grafting (SABG).A PROMs study was conducted; 40 consecutive consenting cleft lip/palate children between 8 and 14 years old were included. Twenty patients did, and 20 patients did not, have SABG. PROMs scores from children and parents in the 2 groups were compared.Forty patients completed the trial. No significant differences in total score from the Chang Gung Short Form-15 (CGSF-15) were found between children and their parents. Children with SABG reported no more oral-nasal regurgitation than children without SABG, but tended to report more nasal obstruction. There were no statistically significant differences in parent reported outcomes between the 2 groups.Cleft lip/palate patients who underwent SABG reported significantly less nasal regurgitation and more nasal obstruction compared to those patients who did not undergo SABG.

Dental Procedures and the Risk of Infective Endocarditis.

Infective endocarditis (IE) is an uncommon but potentially devastating disease. Recently published data have revealed a significant increase in the incidence of IE following the restriction on indications for antibiotic prophylaxis as recommended by the revised guidelines. This study aims to reexamine the basic assumption behind the rationale of prophylaxis that dental procedures increase the risk of IE.Using the Longitudinal Health Insurance Database of Taiwan, we retrospectively analyzed a total of 739 patients hospitalized for IE between 1999 and 2012. A case-crossover design was conducted to compare the odds of exposure to dental procedures within 3 months preceding hospitalization with that during matched control periods when no IE developed.In the unadjusted model, the odds ratio (OR) was 0.93 for tooth extraction (95% confidence interval [CI] 0.54-1.59), 1.64 for surgery (95% CI 0.61-4.42), 0.92 for dental scaling (95% CI 0.59-1.42), 1.69 for periodontal treatment (95% CI 0.88-3.21), and 1.29 for endodontic treatment (95% CI 0.72-2.31). The association between dental procedures and the risk of IE remained insignificant after adjustment for antibiotic use, indicating that dental procedures did not increase the risk of IE.Therefore, this result may argue against the conventional assumption on which the recommended prophylaxis for IE is based.

Major Adverse Cardiovascular Events in Treated Periodontitis: A Population-Based Follow-Up Study from Taiwan.

BACKGROUND: The aim of the present study was to identify the long-term major adverse cardiovascular events (MACE) in treated periodontitis patients in Taiwan. METHODS: From the National Health Insurance Research Database (2001-2010), adult patients (≥ 18 years) with treated periodontitis were identified. Comparison was made between patients with mild form and severe form of treated periodontitis after propensity score matching. The primary end point was the incidence of MACE. RESULTS: A total of 32,504 adult patients with treated periodontitis were identified between 2001 and 2010. After propensity score matching, 27,146 patients were preserved for comparison, including 13,573 patients with mild form and 13,573 patients with severe form of treated periodontitis. During follow-up, 728 individuals in mild treated periodontitis group and 1,206 individuals in severe treated periodontitis group had at least 1 MACE event. After adjustment for gender, hyperlipidemia, hypertension and diabetes mellitus, severe treated periodontitis was associated with a mildly but significantly increased risk of MACE among older patients > 60 years of age (incidence rate ratio, 1.26; 95% confidence interval, 1.08-1.46). No association was found among younger patients ≤ 60 years of age. CONCLUSIONS: Severe form of treated periodontitis was associated with an increased risk of MACE among older Taiwanese patients, but not among younger Taiwanese patients. We should put more efforts on the improvement of periodontal health to prevent further MACE.