Luis Barbier

Sentinel Node Biopsy in Head and Neck Cancer: Preliminary Results of a Multicenter Trial

Background: The aim was to determine the reliability and reproducibility of sentinel node biopsy (SNB) as a staging tool in head and neck squamous cell carcinoma (HNSCC) for T1/2 clinically N0 patients by means of a standardized technique.Methods: Between June 1998 and June 2002, 227 SNB procedures have been performed in HNSCC cases at six centers. One hundred thirty-four T1/2 tumors of the oral cavity/oropharynx in clinically N0 patients were investigated with preoperative lymphoscintigraphy (LSG), intraoperative use of blue dye/gamma probe, and pathological evaluation with step serial sectioning and immunohistochemistry, with a follow-up of at least 12 months. In 79 cases SNB alone was used to stage the neck carcinoma, and in 55 cases SNB was used in combination with an elective neck dissection (END).Results: In 125/134 cases (93%) a sentinel node was identified. Of 59 positive nodes, 57 were identified with the intraoperative gamma probe and 44 with blue dye. Upstaging of disease occurred in 42/125 cases (34%): with hematoxylin-eosin in 32/125 (26%) and with additional pathological staging in 10/93 (11%). The sensitivity of the technique with a mean follow-up of 24 months was 42/45 (93%). The identification of SNB for floor of mouth (FOM) tumors was 37/43 (86%), compared with 88/91 (97%) for other tumors. The sensitivity for FOM tumors was 12/15 (80%), compared with 30/30 (100%) for other tumor groups.Conclusion: SNB can be successfully applied to early T1/2 tumors of the oral cavity/oropharynx in a standardized fashion by centers worldwide. For the majority of these tumors the SNB technique can be used alone as a staging tool.

Sentinel European Node Trial (SENT): 3-year results of sentinel node biopsy in oral cancer

PURPOSE Optimum management of the N0 neck is unresolved in oral cancer. Sentinel node biopsy (SNB) can reliably detect microscopic lymph node metastasis. The object of this study was to establish whether the technique was both reliable in staging the N0 neck and a safe oncological procedure in patients with early-stage oral squamous cell carcinoma. METHODS An European Organisation for Research and Treatment of Cancer-approved prospective, observational study commenced in 2005. Fourteen European centres recruited 415 patients with radiologically staged T1-T2N0 squamous cell carcinoma. SNB was undertaken with an average of 3.2 nodes removed per patient. Patients were excluded if the sentinel node (SN) could not be identified. A positive SN led to a neck dissection within 3 weeks. Analysis was performed at 3-year follow-up. RESULTS An SN was found in 99.5% of cases. Positive SNs were found in 23% (94 in 415). A false-negative result occurred in 14% (15 in 109) of patients, of whom eight were subsequently rescued by salvage therapy. Recurrence after a positive SNB and subsequent neck dissection occurred in 22 patients, of which 16 (73%) were in the neck and just six patients were rescued. Only minor complications (3%) were reported following SNB. Disease-specific survival was 94%. The sensitivity of SNB was 86% and the negative predictive value 95%. CONCLUSION These data show that SNB is a reliable and safe oncological technique for staging the clinically N0 neck in patients with T1 and T2 oral cancer. EORTC Protocol 24021: Sentinel Node Biopsy in the Management of Oral and Oropharyngeal Squamous Cell Carcinoma.

Does Tumor Depth Affect Nodal Upstaging in Squamous Cell Carcinoma of the Head and Neck

Purpose: The aim of this study was to determine whether tumor depth affects upstaging of the clinically node‐negative neck, as determined by sentinel lymph node biopsy with full pathologic evaluation of harvested nodes including step‐serial sectioning (SSS) and immunohistochemistry (IHC).

Sentinel node biopsy in relation to survival in floor of the mouth carcinoma

Promising results have been obtained with sentinel node biopsy (SNB) in early oral carcinoma, but the floor of the mouth remains a site at risk of misdiagnosis. A retrospective and prospective study was designed to test the safety of SNB by comparing survival among patients with early stage carcinoma of the floor of the mouth (FOM) undergoing SNB, to a control group managed traditionally by a combination of clinical observation and elective neck dissection (END). A total of 63 patients with early stage carcinoma of the FOM were treated between 1991 and 2005. In the control group, 26 patients were managed with END and nine by close observation. In the test group, 28 patients were managed prospectively with SNB. Regional recurrence occurred in 23% (8/35) of control patients and 25% (7/28) of test patients. Approximately 25% of patients were successfully treated by salvage surgery. Disease-specific survival was 65.5% for control patients and 85% for SNB patients; the difference was not statistically significant. The use of SNB in the management of cancers of the FOM did not adversely affect survival and prevented 69.5% of patients undergoing unnecessary neck dissections, while clinical progress was better in the SNB group than in controls.

Metastasis of a malignant melanoma to the region of an impacted mandibular third molar: A case report☆

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Sentinel node in oral cancer: the nuclear medicine aspects. A survey from the sentinel european node trial

Purpose Nuclear imaging plays a crucial role in lymphatic mapping of oral cancer. This evaluation represents a subanalysis of the original multicenter SENT trial data set, involving 434 patients with T1-T2, N0, and M0 oral squamous cell carcinoma. The impact of acquisition techniques, tracer injection timing relative to surgery, and causes of false-negative rate were assessed. Methods Three to 24 hours before surgery, all patients received a dose of 99mTc-nanocolloid (10–175 MBq), followed by lymphoscintigraphy. According to institutional protocols, all patients underwent preoperative dynamic/static scan and/or SPECT/CT. Results Lymphoscintigraphy identified 723 lymphatic basins. 1398 sentinel lymph nodes (SNs) were biopsied (3.2 SN per patient; range, 1–10). Dynamic scan allowed the differentiation of sentinel nodes from second tier lymph nodes. SPECT/CT allowed more accurate anatomical localization and estimated SN depth more efficiently. After pathological examination, 9.9% of the SN excised (138 of 1398 SNs) showed metastases. The first neck level (NL) containing SN+ was NL I in 28.6%, NL IIa in 44.8%, NL IIb in 2.8%, NL III in 17.1%, and NL IV in 6.7% of positive patients. Approximately 96% of positive SNs were localized in the first and second lymphatic basin visualized using lymphoscintigraphy. After neck dissection, the SN+ was the only lymph node containing metastasis in approximately 80% of patients. Conclusions Best results were observed using a dynamic scan in combination with SPECT/CT. A shorter interval between tracer injection, imaging, and surgery resulted in a lower false-negative rate. At least 2 NLs have to be harvested, as this may increase the detection of lymphatic metastases.

Survey of Spanish dentists on the prescription of antibiotics and antiseptics in surgery for impacted lower third molars

Background This study explored the attitude of registered dentists in Biscay towards prescribing antibiotics and/or antiseptics to prevent potential infections after surgical extraction of completely bone-impacted third molars in otherwise healthy individuals, with no history of infection. Material and Methods We sent letters to 931 registered dentists in Biscay, with an explanation of the study objectives, description of a case of lower third molar impaction, including a panoramic radiograph, and a questionnaire. The questionnaire asked whether they would prescribe antibiotics and/or antiseptics, in the hypothetical case of lower third molar extraction surgery presented, and if so, when, what type, at what dose and how long for. Results The questionnaire was completed by 261 dentists (28%), with a mean age of 44.3 years old (SD 11.05) and mean of 18.7 years working as a dentist (SD 9). A total of 216 dentists (82.7%) considered it necessary to prescribe antibiotics. Of these, 126 (58.3%) would prescribe amoxicillin and 74 (34.5%) amoxicillin/clavulanic acid, while 129 dentists (59%) would prescribe antibiotics both before and after surgery and 10 (4.6%) only after surgery. The most common doses were amoxicillin 500 mg or 750 mg every 8 hours, and amoxicillin/clavulanic acid 875/125 mg every 8 hours, in both cases for a mean of 7 days. Further, 74 dentists (28%) said they would use immediate post-extraction socket irrigation with chlorhexidine, while 211 (81%) would prescribe antiseptics in the postoperative period, of whom 97% recommended chlorhexidine. We did not find significant differences in the use of antibiotics or antiseptics by dentist age (ANOVA p=0.22 and p=0.53, respectively), or professional experience (ANOVA p=0.45 and p=0.62). Conclusions In our sample, the prophylactic prescription of antibiotics and/or chlorhexidine is widespread in clinical practice, in most cases amoxicillin and amoxicillin/clavulanic acid for a week, starting the treatment before surgery. Key words:Extraction, lower third molar, survey, antibiotics, antiseptics.

Efficacy of amoxicillin and amoxicillin/clavulanic acid in the prevention of infection and dry socket after third molar extraction. A systematic review and meta-analysis

Background Prophylactic use of amoxicillin and amoxicillin/clavulanic acid, although controversial, is common in routine clinical practice in third molar surgery. Material and Methods Our objective was to assess the efficacy of prophylactic amoxicillin with or without clavulanic acid in reducing the incidence of dry socket and/or infection after third molar extraction. We conducted a systematic review and meta-analysis consulting electronic databases and references in retrieved articles. We included double-blind placebo-controlled randomized clinical trials published up to June 2015 investigating the efficacy of amoxicillin with or without clavulanic acid on the incidence of the aforementioned conditions after third molar extraction. Relative risks (RRs) were estimated with a generic inverse-variance approach and a random effect model using Stata/IC 13 and Review Manager Version 5.2. Stratified analysis was performed by antibiotic type. Results We included 10 papers in the qualitative review and in the quantitative synthesis (1997 extractions: 1072 in experimental groups and 925 in controls, with 27 and 74 events of dry socket and/or infection, respectively). The overall RR was 0.350 (p< 0.001; 95% CI 0.214 to 0.574). We found no evidence of heterogeneity (I2=0%, p=0.470). The number needed to treat was 18 (95% CI 13 to 29). Five studies reported adverse reactions (RR=1.188, 95% CI 0.658 to 2.146, p =0.567). The RRs were 0.563 for amoxicillin (95% CI 0.295 to 1.08, p=0.082) and 0.215 for amoxicillin/clavulanic acid (95% CI 0.117 to 0.395, p<0.001). Conclusions Prophylactic use of amoxicillin does not significantly reduce the risk of infection and/or dry socket after third molar extraction. With amoxicillin/clavulanic acid, the risk decreases significantly. Nevertheless, considering the number needed to treat, low prevalence of infection, potential adverse reactions to antibiotics and lack of serious complications in placebo groups, the routine prescription of amoxicillin with or without clavulanic acid is not justified. Key words:Meta-analysis, amoxicillin, infection, removal, dry socket, third molar.

Plasma variations in stress markers: Clinical trial of two anesthetics used in regional block in the extraction of impacted inferior third molars

Objectives: Was to evaluate the effect of different regional anesthetics (articaine with epinephrine versus prilocaine with felypressin) on stress in the extraction of impacted lower third molars in healthy subjects. Sutdy Desing: A prospective single-blind, split-mouth cross-over randomized study was designed, with a control group. The experimental group consisted of 24 otherwise healthy male volunteers, with two impacted lower third molars which were surgically extracted after inferior alveolar nerve block (regional anesthesia), with a fortnight’s interval: the right using 4% articaine with 1:100.000 epinephrine, and the left 3% prilocaine with 1:1.850.000 felypressin. Patients were randomized for the first surgical procedure. To analyze the variation in four stress markers, homovanillic acid, 3-methoxy-4-hydroxyphenylglycol, prolactin and cortisol, 10-mL blood samples were obtained at t = 0, 5, 60, and 120 minutes. The control group consisted of 12 healthy volunteers, who did not undergo either extractions or anesthetic procedures but from whom blood samples were collected and analyzed in the same way. Results: Plasma cortisol increased in the experimental group (multiple range test, P<0.05), the levels being significantly higher in the group receiving 3% prilocaine with 1:1.850,000 felypressin (signed rank test, p<0.0007). There was a significant reduction in homovanillic acid over time in both groups (multiple range test, P<0.05). No significant differences were observed in homovanillic acid, 3-methoxy-4-hydroxyphenylglycol or prolactin concentrations between the experimental and control groups. Conclusions: The effect of regional anesthesia on stress is lower when 4% articaine with 1:100,000 epinephrine is used in this surgical procedure. Key words:Stress markets, epinephrine versus felypressin.

Autologous dental pulp mesenchymal stem cells for inferior third molar post-extraction socket healing: a split-mouth randomised clinical trial

Background Since the discovery of adult mesenchymal stem cells extensive research has been conducted to determine their mechanisms of differentiation and effectiveness in cell therapy and regenerative medicine. Material and Methods To assess the efficacy of autologous dental pulp mesenchymal stem cells delivered in a collagen matrix for post-extraction socket healing, a single-centre, double-blind, randomised, split-mouth, controlled clinical trial was performed. Both impacted mandibular third molars were extracted from 32 patients. Dental pulp was collected and dissociated; the resulting cell suspension, obtained by centrifugation, was incorporated into a resorbable collagen matrix and implanted in 32 experimental post-extraction sockets. Collagen matrices alone were implanted in 32 contralateral, control post-extraction sockets. Two neuroradiologists independently assessed the extent of bone repair at 6 months after the extractions. Computed tomography (CT, Philips Brilliance) and an advanced display platform (IntelliSpace Portal) was used to record extraction socket density, expressed as Hounsfield units (HU) and height (mm) of the distal interdental bone septum of the second molar. Measurements at 6 months post-extraction were compared with measurements obtained immediately after extraction. Data were analysed with the statistical program STATA 14. Results Two patients dropped out of the study. The final sample consisted of 22 women and 8 men (mean age, 23 years; range: 18–30 years). Clinical, radiological, and surgical characteristics of impacted third molars of the control and experimental groups were homogeneous. Measurements obtained by the two neuroradiologists showed agreement. No significant differences were found in the extent of bone repair during analyses of density (p=0.4203 neuroradiologist 1; p=0.2525 neuroradiologist 2) or interdental septum height (p=0.2280 neuroradiologist 1; p=0.4784 neuroradiologist 2). Conclusions In our clinical trial, we were unable to demonstrate that autologous dental pulp mesenchymal stem cells reduce socket bone resorption after inferior third molar extraction. Key words:Clinical trial, autologous, pulpal stem cells, extraction socket healing.