Distal Biliary Stent Migration in Patients with Irretrievable Bile Duct Stones: Long-Term Comparison Between Straight and Double-Pigtail Stents.

BACKGROUND: Prolonged biliary stenting may be considered in high-risk patients with irretrievable bile duct stones (IBDS). Distal stent migration (DSM) is a known complication, although data beyond the recommended interval of temporary stenting (3-6 months) are lacking. We compared the long-term incidence of DSM between straight and double-pigtail stents in patients with IBDS. METHODS: Consecutive patients with IBDS undergoing plastic biliary stenting (1/2009-12/2019) were retrospectively reviewed. DSM was confirmed on follow-up examination when the stent was no longer present at the papillary orifice nor fluoroscopically visible in the bile duct. Kaplan-Meier and Cox regression analyses were used to determine estimates and predictors of DSM. RESULTS: Overall, 618 biliary stenting procedures (410 patients) were included: 289 with a straight stent (group A) and 329 with a double-pigtail (group B). By Kaplan-Meier analysis, the DSM rates were 8.4 and 14.6% at 6 months, 21.4 and 27.7% at 12 months, 27 and 43.5% at 18 months, and 37.2 and 60.4% at 24 months, for groups A and B, respectively (p = 0.004). Double-pigtail stents were at higher risk for DSM (HR = 7.38, p = 0.04), whereas an inverse correlation was noted with age (HR = 0.97, p = 0.0001). Considering only temporary stenting procedures (≤ 6 months; n = 297), the probability of DSM was not significantly different between the two groups (p = 0.07). CONCLUSIONS: In a setting of prolonged stenting for IBDS, the probability of DSM appears to be higher when a double-pigtail stent is used and in younger patients. A relative anti-migratory advantage of double-pigtail over straight stents appears negligible in this study.

The role of M1 and M2 macrophage polarization in progression of medication-related osteonecrosis of the jaw.

OBJECTIVES: The aim of this study was to investigate the relationship between M1 and M2 macrophage polarization and clinical stage in patients with medication-related osteonecrosis of the jaw (MRONJ) who underwent treatment with bisphosphonates or denosumab. MATERIALS AND METHODS: M1 and M2 macrophage density and expression of interleukin (IL)-6 and IL-10 were assessed on biopsies of mucosal tissues surrounding necrotic bone in 30 MRONJ patients with stages 1-3 and controls. For identification of M1 and M2 macrophages, double CD68/iNOS and CD68/CD206 immunofluorescence staining was conducted, respectively. Computer-assisted immunofluorescence quantification of markers was performed. RESULTS: Early stage 1 MRONJ patients showed a switch toward the M2 phenotype, as indicated by the higher density of M2 macrophages, the decreased M1/M2 ratio, and the upregulation of IL-10. MRONJ patients with advanced stages 2 and 3 showed a shift toward M1-polarized macrophages, as suggested by the higher density of M1 macrophages, the increased M1/M2 ratio, and the overexpression of IL-6. The macrophage density of both M1 and M2 subsets was significantly enhanced in patients receiving bisphosphonates compared with those receiving denosumab. CONCLUSIONS: The M1-M2 macrophage polarization status in mucosal tissues bordering necrotic bone correlates with clinical stage of MRONJ. Patients with early-stage MRONJ show a switch toward M2-polarized macrophages, while MRONJ patients with advanced stage demonstrate a shift toward the M1 phenotype. CLINICAL RELEVANCE: Therapeutic molecules targeting the inflammatory microenvironment via the regulation of either M1 or M2 macrophage polarization may represent a novel strategy for treatment of MRONJ.

Atrial Fibrillation: Pathogenesis, Predisposing Factors, and Genetics.

Atrial fibrillation (AF) is the most frequent arrhythmia managed in clinical practice, and it is linked to an increased risk of death, stroke, and peripheral embolism. The Global Burden of Disease shows that the estimated prevalence of AF is up to 33.5 million patients. So far, successful therapeutic techniques have been implemented, with a high health-care cost burden. As a result, identifying modifiable risk factors for AF and suitable preventive measures may play a significant role in enhancing community health and lowering health-care system expenditures. Several mechanisms, including electrical and structural remodeling of atrial tissue, have been proposed to contribute to the development of AF. This review article discusses the predisposing factors in AF including the different pathogenic mechanisms, sedentary lifestyle, and dietary habits, as well as the potential genetic burden.

The use of crevicular fluid to assess markers of inflammation and angiogenesis, IL-17 and VEGF, in patients with solid tumors receiving zoledronic acid and/or bevacizumab.

PURPOSE: Crevicular fluid was used to assess interleukin-17 (IL-17) and vascular endothelial growth factor (VEGF) in cancer patients receiving zoledronic acid and/or bevacizumab. The markers were also assessed in the serum. METHODS: Twenty-five patients were included and comprised three groups: patients who received zoledronic acid (n = 9), patients who received bevacizumab (n = 9), and patients who received zoledronic acid combined with bevacizumab (n = 5). One patient received zoledronic acid and everolimus and another received zoledronic acid, bevacizumab, and temsirolimus. IL-17 and VEGF were measured by standard quantitative ELISA kits and assessed in two study points. RESULTS: Twenty-four patients maintained good periodontal health; one had asymptomatic osteonecrosis of the jaw. First assessment: 44 samples were collected; 21 from serum and 23 from crevicular fluid. Second assessment, 6 months later: 11 samples were collected; 6 from serum and 5 from crevicular fluid. IL-17 was detected in all samples, in serum and crevicular fluid, and remained unchanged at both time points. Serum VEGF in patients with bevacizumab alone or combined with zoledronic acid was significantly lower compared with that of patients who received zoledronic acid alone. VEGF was not detected in the crevicular fluid. CONCLUSIONS: Crevicular fluid might be an easy, non-invasive means to assess IL-17. The stable values of IL-17 in crevicular fluid and serum and the lack of VEGF in the crevicular fluid could be related to the good periodontal health of our patients. Further studies are needed to assess IL-17 and VEGF in the crevicular fluid in patients with and without periodontal disease.

Alveolar bone histological necrosis observed prior to extractions in patients, who received bone-targeting agents.

OBJECTIVE: We reported the alveolar bone histology prior to dental extractions in cancer patients, who received bone-targeting agents (BTA). SUBJECTS AND METHODS: Fifty-four patients were included. Patients underwent extractions, and bone biopsies were taken. RESULTS: Extractions were performed due to pain, swelling, purulence, fistula, and numbness, not responding to treatment, in 40 patients (group A); extractions due to asymptomatic, non-restorable teeth, were performed in 14 patients (group B). Complete alveolar jaw bone histological necrosis was observed in 28 of 40 (70%) patients of group A and none of group B (p < .001). The development of clinical osteonecrosis (MRON) was assessed in 44 patients; 10 patients, who were also treated with Low Level Laser Treatments-LLLT, were excluded from this analysis, as the alternative therapies were a confounding factor. Twelve patients, with alveolar bone histological necrosis prior to extraction, developed medication-related osteonecrosis of the jaw (MRONJ) compared with two patients with vital or mixed vital/non-vital bone (p < .0007). BTAs >1 year and concurrent targeted therapy were also significantly associated with MRONJ (p = .016 and p = .050). CONCLUSION: Pain, swelling, purulence, fistula, and numbness were significantly associated with complete bone histological necrosis prior to extractions and increased MRONJ development. Research is justified to explore whether histological necrosis represents an early stage of osteonecrosis.

Osteonecrosis of the jaw related to non-antiresorptive medications: a systematic review.

INTRODUCTION: The reporting of osteonecrosis of the jaw (ONJ) related to anticancer agents without known antiresorptive properties (non-antiresorptives), such as antiangiogenics, tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors, immune checkpoint inhibitors, and cytotoxic chemotherapy is increasing. OBJECTIVE: To review characteristics of ONJ in cancer patients receiving non-antiresorptives. METHODS: A systematic review of the literature between 2009 and 2017 was conducted by the Bone Study Group of MASCC/ISOO. RESULTS: Of 6249 articles reviewed and from personal communication, 42 ONJ cases related to non-antiresorptives were identified. No gender predilection was noted. Median age was 60 years and ONJ stage 2 was most common, with predilection for posterior mandible. Exposed bone, pain, and infection were common at diagnosis. In comparison to bone targeting agents (BTAs), radiology, histology, and management were similar, with medication often discontinued. Delayed diagnosis (median 8 weeks) was noted. Important differences included earlier time to ONJ onset (median 20 weeks), absence of trigger event (40%), and greater likelihood of healing and shorter healing time (median 8 weeks) as compared to BTA-related ONJ. Gastrointestinal cancers predominated, followed by renal cell carcinomas compared to breast, followed by prostate cancers in BTA-related ONJ, reflecting different medications. CONCLUSIONS: Data about non-antiresorptive-related ONJ is sparse. This type of ONJ may have better prognosis compared to the BTA-related ONJ, suggested by greater likelihood of healing and shorter healing time. However, the delay in diagnosis highlights the need for more education. This is the first attempt to characterize ONJ associated with different non-antiresorptives, including BRAF and immune checkpoint inhibitors.

Cold versus hot endoscopic mucosal resection for nonpedunculated colorectal polyps sized 6-10 mm: a randomized trial.

BACKGROUND AND STUDY AIMS: Cold snare polypectomy is an established method for the resection of small colorectal polyps; however, significant incomplete resection rates still leave room for improvement. We aimed to assess the efficacy of cold snare endoscopic mucosal resection (CS-EMR), compared with hot snare endoscopic mucosal resection (HS-EMR), for nonpedunculated polyps sized 6 - 10 mm. PATIENTS AND METHODS: This study was a dual-center, randomized, noninferiority trial. Consecutive adult patients with at least one nonpedunculated polyp sized 6 - 10 mm were enrolled. Eligible polyps were randomized (1:1) to be treated with either CS-EMR or HS-EMR. Both methods involved submucosal injection of a methylene blue-tinted normal saline solution. The primary noninferiority end point was histological eradication evaluated by postpolypectomy biopsies (noninferiority margin - 10 %). Secondary outcomes included occurrence of intraprocedural bleeding, clinically significant postprocedural bleeding, and perforation. RESULTS: Among 689 patients screened, 155 patients with 164 eligible polyps were included (CS-EMR n = 83, HS-EMR n = 81). The overall rate of histological complete resection was 92.8 % in the CS-EMR group and 96.3 % in the HS-EMR group (difference 3.5 %; 95 % confidence interval [CI] - 4.15 to 11.56), showing noninferiority of CS-EMR compared with HS-EMR. CS-EMR was shown to be noninferior both for polyps measuring 6 - 7 mm (CS-EMR 93.3 %; HS-EMR 100 %; 95 %CI - 7.95 to 21.3) and those of 8 - 10 mm (92.5 % vs. 94.7 %, respectively; 95 %CI - 7.91 to 13.16). Rates of intraprocedural bleeding were similar between the two groups (CS-EMR 3.6 %, HS-EMR 1.2 %; P  = 0.30). No clinically significant postprocedural bleeding or perforation occurred in either group. CONCLUSIONS: CS-EMR appears to be a valuable modification of the standard cold snare technique, obviating the need to use diathermy for nonpedunculated colorectal polyps sized 6 - 10 mm.

A systematic review of dental disease management in cancer patients.

INTRODUCTION: This systematic review aims to update on the prevalence of odontogenic-related infections and the efficacy of dental strategies in preventing dental-related complications in cancer patients since the 2010 systematic review. REVIEW METHOD: A literature search was conducted in the databases MEDLINE/PubMed and EMBASE for articles published between 1 January 2009 and 30 June 2016. Each study was assessed by 2 reviewers and the body of evidence for each intervention was assigned an evidence level. RESULTS: After examination of the abstracts and full-text articles, 59 articles satisfied the inclusion criteria. The weighted prevalence of dental infections and pericoronitis during cancer therapy was 5.4 and 5.3%, respectively. The frequency of dental-related infections during intensive chemotherapy after complete, partial, and minimal pre-cancer dental evaluation/treatment protocols ranged from 0 to 4%. Protocols involving third molars extractions had the highest complications (40%). CONCLUSIONS: In view of the low prevalence of infections and the potential for complications after third molar extractions, it is suggested that partial dental evaluation/treatment protocols prior to intensive chemotherapy; whereby minor caries (within dentin), asymptomatic third molars or asymptomatic teeth without excessive probing depth (<8 mm), mobility (mobility I or II) or with periapical lesions of <5 mm were observed; is a viable option when there is insufficient time for complete dental evaluation/treatment protocols. The use of chlorhexidine, fluoride mouth rinses as well as composite resin, resin-modified glass ionomer cement (GIC), and amalgam restorations over conventional GIC in post head and neck radiation patients who are compliant fluoride users is recommended.

Long-term recurrence of bile duct stones after endoscopic papillary large balloon dilation with sphincterotomy: 4-year extended follow-up of a randomized trial.

BACKGROUND: Endoscopic papillary large balloon dilation with biliary sphincterotomy (EPLBD + EBS) is safe and effective in patients with large common bile duct (CBD) stones. However, data on long-term outcomes after EPLBD + EBS remain limited. We sought to prospectively evaluate the long-term recurrence of CBD stones after EPLBD + EBS and to identify the associated factors. METHODS: We conducted an extended follow-up of a previous randomized trial (2009-2011) comparing the outcomes of 30- versus 60-s large balloon dilation. A total of 106 trial participants undergoing successful CBD stone clearance by EPLBD + EBS were prospectively followed up for up to 4 years (range 19-48 months). Various risk factors were analysed to assess predictors of long-term recurrence of stones. RESULTS: Recurrent CBD stones appeared in 8/106 (7.5 %) patients during a mean follow-up of 30.5 ± 5.5 months. The mean diameter of CBD was significantly higher in the recurrence versus non-recurrence group (2.0 ± 4.9 vs 1.6 ± 0.9 cm, p = 0.008). Multivariate analysis revealed that CBD diameter was the only predictor significantly associated with the long-term recurrence of stones (odds ratio 1.2, p = 0.01). CONCLUSIONS: EPLBD + EBS is associated with a low rate of long-term CBD stone recurrence. However, the risk is significantly higher in patients with a more dilated CBD.

MicroRNAs in Atrial Fibrillation: Mechanisms, Vascular Implications, and Therapeutic Potential.

Atrial fibrillation (AFib), the most prevalent arrhythmia in clinical practice, presents a growing global health concern, particularly with the aging population, as it is associated with devastating complications and an impaired quality of life. Its pathophysiology is multifactorial, including the pathways of fibrosis, inflammation, and oxidative stress. MicroRNAs (miRNAs), small non-coding RNA molecules, have emerged as substantial contributors in AFib pathophysiology, by affecting those pathways. In this review, we explore the intricate relationship between miRNAs and the aforementioned aspects of AFib, shedding light on the molecular pathways as well as the potential diagnostic applications. Recent evidence also suggests a possible role of miRNA therapeutics in maintenance of sinus rhythm via the antagonism of miR-1 and miR-328, or the pharmacological upregulation of miR-27b and miR-223-3p. Unraveling the crosstalk between specific miRNA profiles and genetic predispositions may pave the way for personalized therapeutic approaches, setting the tone for precision medicine in atrial fibrillation.

Endoscopic papillary large-balloon dilation with sphincterotomy for difficult common bile duct stones ≤12 mm: a prospective study.

Background: Stone recurrence is a significant complication following endoscopic bile duct clearance. Endoscopic papillary large-balloon dilation (EPLBD) with biliary sphincterotomy (EBS) has shown satisfactory results in preventing recurrence of "large" common bile duct stones (CBDS). However, data on outcomes after EPLBD+EBS for CBDS ≤12 mm remain scarce. The present study prospectively evaluated the mid- and long-term efficacy of EPLBD+EBS for CBDS recurrence among this group of patients. Methods: Consecutive patients with CBDS ranging from 8-12 mm, treated with EPLBD+EBS from June 2018 through June 2020, were prospectively followed-up for at least 36 months. CBDS recurrence was defined as recurrent stones confirmed by endoscopic retrograde cholangiopancreatography (ERCP) during the follow-up period. Results: Overall, 72 patients (mean age: 67 years, 52.8% male) were included, of whom 22 (30.5%) had multiple (≥3) CBDS, 23 (31.9%) had a history of cholecystectomy, 13 (18.1%) had a periampullary diverticulum and 22 (30.5%) had a previous EBS. The mean CBD diameter was 11.6±1 mm, while a tapered duct was noted in 7 (9.7%). Post-procedural bleeding and cholangitis occurred in 1 and 2 cases respectively. No cases of perforation and post-ERCP pancreatitis were observed. During a mean follow up of 46.4±6.2 months (range 37-60), no mid-term recurrence was observed, whereas CBDS recurred in 2/72 (2.7%) in the long term. Conclusions: EPLBD+EBS in patients with CBDS ≤12 mm was associated with a very low rate of mid- and long-term CBDS recurrence. Our results need to be further investigated with randomized controlled trials.

Long-term adenoma recurrence and development of colorectal cancer following endoscopic mucosal resection in large non-pedunculated colonic polyps ≥4 cm.

OBJECTIVES: Data of long-term follow up for large non pedunculated colorectal polyps (LNPCPs) ≥4 cm removed with piecemeal wide field endoscopic mucosal resection (PWF-EMR) are limited. We primarily evaluated the recurrence rates and secondarily the rates of post colonoscopic polypectomy colorectal cancer (PCPCRC) on a long-term basis. METHODS: We retrospectively reviewed a prospectively-stored electronic database of all patients who underwent PWF-EMR for LNPCPs at the Venizeleion General Hospital, between 2009 and 2020. Eligible patients were those with LNPCPs ≥4 cm, deemed completely removed by endoscopic means and followed-up for a minimum of 36 months with at least two surveillance colonoscopies, the first one (SC1) (4-6) months after the initial PWF-EMR procedure and the second one (SC2) after (12-18) months. In 2023, all cases were checked for PCPCRC development. RESULTS: Residual/early recurrent tissue was detected in 44 (31 %) cases among the 142 (82 males, 60 females) assessed during SC1. Late recurrent tissue was detected in 9 (6.6 %) cases among the 137 surveyed during SC2. Investigation did not reveal any case of PCPCRC . CONCLUSIONS: This historical cohort shows that the PWF-EMR for LNPCPs ≥4 cm is a safe and definitive removal method while it is not associated with the appearance of PCPCRC.

Atrial fibrillation post CABG and the risk of arrhythmia recurrence: the AFRODITE study.

BACKGROUND: New-onset postoperative atrial fibrillation (POAF) after coronary artery bypass surgery (CABG) occurs with an incidence of 20-40%. The clinical relevance of POAF remains a concern, and the need for further studies regarding the clinical management of POAF is necessary. AIM: The AFRODITE study, a prospective multicenter cohort study, had as its primary endpoint the evaluation of AF recurrence in patients post CABG over a one-year period. METHODS: Two hundred twenty-eight patients aged >50 years who underwent isolated CABG were included in the study. Patients were stratified into two groups, POAF and non-POAF, and followed for 12 months for AF recurrence, hospitalizations, and death. RESULTS: Two hundred twenty-eight patients (mean age 67 years, 88.6% male) were included in the study. 28.5% of patients experienced at least one episode of POAF during index hospitalization (POAF group) and were compared with the non-POAF group (n = 163). Multivariate stepwise logistic regression analysis showed that the strongest prognostic parameter for POAF was the CHA2DS2-VASc score (odds ratio = 1.61, p < 0.001). POAF patients had a worse in-hospital outcome, but the incidence of long-term AF recurrence was not statistically different (3.6% vs. 4.8%, p = 0.9). CONCLUSION: Interestingly, a one-year prospective follow-up of patients in the study did not reveal significant differences between POAF and non-POAF patients. A notable finding was that patients with a higher CHA2DS2-VASc score were more likely to develop POAF.

Orthodontic treatment as triggering factor of Medication Related Osteonecrosis of the Jaw in a breast cancer patient. Report of a rare case.

Background: Orthodontic treatment in adult patient is widely accepted nowadays. Therefore, orthodontists are needed to interact with more complex medical histories that may interfere with the orthodontic treatment. Antiresorptive medication is a widely used treatment for osteoporosis or malignancies that may affect the orthodontic movement and planning. Case presentation: A 53-year-old patient diagnosed with MRONJ one year after she started orthodontic treatment. Patients' medical history includes breast cancer and treatment with high doses of denosumab for over 2 years. The patient had a drug holiday period in the start of orthodontic treatment and then resumed antiresorptive medication until extreme tooth mobility was observed during the orthodontic treatment. After a long absence from denosumab and failure of conservative means to control the established MRONJ we proceeded in surgical management of the affected area. After two relapse the patient is now stable and prosthetically rehabilitated. Discussion: The affected area was the only one treated orthodontically and in lack of other triggering factors such as extraction or acute inflammation we consider the orthodontic movement as triggering factor of MRONJ. BPs are widely known to affect orthodontic treatment as they suppress bone remodeling but there is a lack of literature as far as patients treated with denosumab or high doses of antiresorptive medication concern. Conclusions: Patients treated with high doses of antiresorptive medication should considered at high risk of developing MRONJ during orthodontic movement. Although, more studies are needed to establish a protocol for the patients seeking orthodontic treatment and treated with denosumab. Key words:Medication Related Osteonecrosis of the Jaw, MRONJ, orthodontic treatment, bisphosphonates, denosumab, antiresorptive medication, surgical management.

A rare case of massive hepatic abscess 6 years after ERCP due to retained biliary stent.

BACKROUND: ERCP combined with the insertion of biliary endoprosthesis is considered a daily practice endoscopic intervention for the treatment of choledocholithiasis. Nevertheless, retained biliary stents for a prolonged period without follow up may cause serious complications. CASE PRESENTATION: We present the case of a 62-year-old man who was hospitalized with symptoms of vomiting, abdominal pain, fatigue and fever. Clinical examination and laboratory results were indicative of an intra abdominal infection. Ultrasound and CT scans were performed, identifying a 17x11.3x7.7 cm. The cause of this lesion was a retained stent in the common bile duct which was placed 6 years ago via endoscopic retrograde cholangiopancreatography. The patient did not attend his follow up appointments after his initial ERCP. Patient's clinical status deteriorated, and an urgent ERCP was performed replacing the retained stent, followed by ultrasound-guided pigtail stent insertion into the hepatic abscess and administration of antibiotics intravenously. Patient's clinical condition was improved and after two months of surveillance complete resolution of the hepatic abscess was achieved. CONCLUSION: The insertion of biliary stents is common endoscopic technique, but close follow up is of outmost importance. J. Med. Invest. 70 : 508-512, August, 2023.

Co-existence of Congenital Epidermoid Cyst and Ranula in a Newborn. Report of a Unique Case.

Background: Congenital cystic swellings involving the floor of the mouth include various lesions such as developmental cysts (e.g., dermoid and epidermoid cysts), ranulas, vascular malformations etc. However, coexistence of such conditions, possibly with a cause-and-effect- relationship, is rare. The purpose of this case report is to present a rare case of a congenital epidermoid cyst associated with a mucous retention cyst in a newborn. Methods: A 6-month-old female infant was referred to an Oral Medicine Clinic in Athens, Greece on October 2019 for evaluation of a swelling at the floor of the mouth, first noticed by her paediatrician just after birth. Clinically, a yellowish "pearly" nodule in close association with the orifice of the left submandibular duct, posteriorly transitioning to a diffuse bluish cystic swelling of the left floor of the mouth was observed. With a provisional diagnosis of a dermoid cyst and/or ranula, a surgical excision was performed under general anaesthesia. Results: Histopathologically, a well-defined, keratin-filled, cystic cavity lined by orthokeratinized stratified squamous epithelium was observed in the anterior aspect while posteriorly and in close proximity, a dilated salivary duct lined by cylindrical, cuboidal or pseudostratified epithelium was noted. A final diagnosis of an epidermoid cyst intimately associated with a mucus retention cyst (ranula) of the submandibular duct was rendered. Conclusions: The coexistence of two cystic lesions in the floor of the mouth with features of epidermoid and mucous retention cyst, respectively, is rare and its pathogenesis intriguing, especially in a newborn.

Experimental study of the effect of autologous platelet-rich plasma on the early phases of osteoinduction by allogenic demineralized bone matrix.

PURPOSE: To evaluate the effect of autologous platelet-rich plasma (PRP) on the early phases of osteoinduction by allogenic demineralized bone matrix (DBM) in rabbit intramuscular positions. MATERIALS AND METHODS: Allogenic DBM was produced from bones of 3 healthy rabbits. In each of 6 experimental animals, 0.3 mL autologous PRP was prepared and 2 muscle pouches were created, where 250 mg DBM + PRP (experimental sites) and 250 mg DBM without PRP (control sites) were randomly implanted. Animals were euthanized 3 weeks postoperatively. RESULTS: Histologic examination revealed uneventful healing in all cases, whereas remineralization of the periphery of the bone graft particles was a constant finding. In both control and experimental sites, fibroblasts and other mesenchymal cells (probably osteoprogenitor cells and preosteoblasts) were observed. The main histological difference was the recolonization of the empty lacunae of the bone graft particles by osteocytes at the control sites. The degradation of the graft at the control sites was statistically significantly quicker, although a statistically significant difference regarding the amount of the newly formed fibrous connective tissue was not observed. CONCLUSION: The present study demonstrated that in this experimental model, the addition of PRP to DBM had a negative effect on the early phases of osteoinduction at 3 weeks of observation.

Aplasia of the Major and Minor Salivary Glands: Report of a Rare Case.

Background: Aplasia of the salivary glands, either partial or involving all the major and possibly the minor salivary glands, is a very rare cause of hyposalivation. The aim of this case report is to present a case of aplasia of the major and minor salivary glands and discuss the relevant literature. Methods: A 23-year-old woman, with a non-contributory medical and family history was referred due to rampant caries, that could not be attributed to any obvious aetiology. No sicca symptoms, previous parotid gland swelling or general symptoms were reported. Clinically, oral mucosa dryness and extended dental erosions and caries were observed, while the orifices of the excretory ducts of the parotid and submandibular salivary glands were not evident. Unstimulated and stimulated saliva flow rates were severely diminished, while a diagnostic biopsy of the lower lip revealed absence of minor salivary glands. Detailed hematologic and immunological investigations to exclude systemic disorders were also within normal limits. Ultrasound and magnetic resonance imaging revealed the absence of all major salivary glands, confirming the clinical diagnosis of congenital aplasia of the salivary glands. Results: Oral hygiene instructions and dietary advice were given while dental products with fluoride and saliva substitutes were administered and appropriate dental treatment was implemented. Regular dental follow-up was also advised. Conclusions: Timely diagnosis of aplasia of the salivary glands is important, considering the detrimental effects of the absence of saliva on oral health. Management consists of the use of saliva substitutes, nutritional adaptation, maintenance of oral health and regular dental follow-ups.

Pharmacological Management of Neuropathic Pain after Radiotherapy in Head and Neck Cancer Patients: A Systematic Review.

Background: Neuropathic pain (NP) in head and neck cancer (HNC) patients represents a treatment challenge. Most studies investigating drugs against NP are conducted in patients suffering with diabetic neuropathy or postherpetic neuralgia, while data are limited in cancer pain management. Additionally, regarding cancer therapy-related NP, most of the studies do not focus on HNC patients. The aim of this review is to identify the studies on systematically administered medication for NP management that included HNC patients under radiotherapy. Methods: A systematic literature search was performed, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, in PubMed, Cochrane Library, Web of Science and ClinicalTrials.gov on 30 October 2021. The medical subject heading (MeSH) terms were ("head and neck cancer" OR "tumor") AND "neuropathic pain" AND "medication" AND "radiotherapy." The Cochrane Collaboration tool was used for quality assessment. Results: The search identified 432 articles. Three more articles were identified after searching the reference lists of the retrieved articles. A total of 10 articles met the eligibility inclusion criteria and were included in this review; 6 on gabapentin, 1 on pregabalin, 1 on nortriptyline, 1 on methadone, and 1 on ketamine. Statistically significant results in pain reduction compared to placebo or standard pain medication were found in the studies on pregabalin (p = 0.003), methadone (p = 0.03), ketamine (p = 0.012), and in two out of six gabapentin studies (p < 0.004). Two of the studies (both concerning gabapentin) had no comparison arm. Conclusions: Treatments including pregabalin, methadone, ketamine, and gabapentin were found to provide pain relief against HNC NP. While there is a plethora of pharmacological treatments available for the management of NP, only a few studies have been conducted regarding the pharmacological management of therapy-related NP in HNC patients. More studies should be conducted regarding the pharmacological approaches in HNC therapy-related NP so that specific treatment algorithms can be developed.