Effect of radiation therapy on lymph node fluorescence in head and neck squamous cell carcinoma after intravenous injection of indocyanine green: a prospective evaluation.

BACKGROUND: Indocyanine green (ICG)-guided surgery has proven effective in the identification of neoplastic tissues. The effect of radiation therapy (RT) on lymph node fluorescence after intravenous injection of ICG has not been addressed yet. The objective of this study was to evaluate the influence of RT on node fluorescence during neck dissection in head and neck squamous cell carcinoma (HNSCC). RESULTS: Twenty-four patients with planned neck dissection for HNSCC were prospectively enrolled. Eleven were included without previous radiation therapy and 13 after RT. ICG was intravenously administered in the operating room. The resected specimen was analyzed by the pathology department to determine the status of each resected lymph node (invaded or not). The fluorescence of each resected node was measured in arbitrary units (AU) on paraffin blocs. The surface area (mm2) of all metastatic nodes and of the invaded component were measured. The values of these surface areas were correlated to fluorescence values. A total of 707 nodes were harvested, the mean fluorescence of irradiated nodes (n = 253) was 9.2 AU and of non-irradiated nodes (n = 454) was 9.6 AU (p = 0.63). Fifty nodes were invaded, with a mean fluorescence of 22 AU. The mean fluorescence values in the invaded irradiated nodes (n = 20) and the invaded non-irradiated nodes (n = 30) were 19 AU and 28 AU (p = 0.23), respectively. The surface area of metastatic nodes and of the invaded component were correlated to fluorescence values even after previous RT (p = 0.02). CONCLUSION: No differences were observed between the fluorescence of irradiated and non-irradiated lymph nodes, including invaded nodes. ICG-guided surgery can be performed after failed RT. TRIAL REGISTRATION: EudraCT ref. 2013-004498-29, registered 29 November 2013. https://www.clinicaltrialsregister.eu/ctr-search/search?query=2013-004498-29.

Gradual withdrawal of remifentanil delays initial post-operative analgesic demand after thyroid surgery; double-blinded, randomized controlled trial.

BACKGROUND: Mismanagement of remifentanil leads to severe side effects such as opioid-induced tolerance and hyperalgesia. Recently studies revealed an alternative withdrawal method to limit these side effects. A gradual withdrawal of remifentanil seems to be associated with less pain. The hypothesis of this double-blinded, randomized controlled trial was that a gradual withdrawal of remifentanil would be associated with less immediate post-operative pain compared to after an abrupt discontinuation of remifentanil in patients who underwent thyroid surgery. METHODS: This double-blinded, randomized controlled trial was conducted in a tertiary level hospital in Brussels (Belgium) from April until August 2017. 34 patients undergoing thyroid surgery were randomized and 29 patients completed the study. After randomization, patients undergoing thyroid surgery were allocated to two groups: one with an abrupt discontinuation of remifentanil after surgery and one with a gradual withdrawal of remifentanil after surgery. The primary outcome was the initial post-operative demand of analgesic medication. RESULTS: Gradual withdrawal of remifentanil was associated with a delayed initial post-operative demand of analgesic medication (P = 0.006). The first morphine bolus was given after 76.3 +/- 89.0 min in the group with a gradual withdrawal of remifentanil versus after 9.0 +/- 13.5 min in the group with an abrupt discontinuation of remifentanil. However, overall morphine consumption, numeric rating scale scores, Ramsay Sedation Scale scores, and quality of recovery scores (QoR-40) were similar in both groups (P > 0.05). CONCLUSION: Though overall morphine consumption, numeric rating scale scores, Ramsay Sedation Scale scores, and quality of recovery scores (QoR-40) are not altered, a gradual withdrawal of remifentanil after thyroid surgery is safe and associated with a delayed initial post-operative demand of analgesic drugs. The withdrawal process does, however, require vigilance and training. TRIAL REGISTRATION: Clinicaltrials.gov NCT03110653 (PI: Luc Barvais; date of registration: 03/31/2017).

Treatment of solitary thyroid nodules according to size, preoperative fine-needle aspiration cytology and frozen section: a retrospective single centre study.

Background: In order to avoid unnecessary thyroidectomies, it is important to predict the nature of thyroid nodules the more accurately possible. The size of the nodule as a predictive factor for malignancy is very controversial. Another point of debate is the accuracy of preoperative fine-needle aspiration cytology (FNAC) and frozen section (FS). The aim of our study is to correlate the nodule size with the final histological diagnosis and to estimate the accuracy of preoperative FNAC and FS. Methods: Retrospective study including 387 operated patients with ultrasound-detected solitary thyroid nodules from 01 January 2001 to 31 December 2013. The following data were collected: patient age and sex, nodule size, FNAC, FS and final histology results. Results: The odds ratio for malignancy within nodules <40 mm was 2.12 (95% CI: 1.104-4.084). The specificity of FNAC was 97.78% and the negative predictive value (NPV) was 97.78% for nodules ≥40 mm and 93.2% and 96.5% for nodules <40 mm, respectively. The observed specificity and NPV of FS ranged from 98% to 100% and from 87.4% to 98%, respectively. When combining FNAC and FS, the specificity and the NPV were 99% and 98%, respectively. Conclusions: The nodule size is not a predictive factor for thyroid cancer and therefore nodules ≥40 mm should not be routinely resected. A lege artis preparation and performance of FNAC along with an expertise on cytological interpretation can considerably diminish false-negative rate. FS can offer additional accuracy on FNAC results and should, therefore, be a part of patient treatment.

Pulmonary Myofibroblastic Tumour Involving the Pericardium and Left Atrium in an 18 Month Infant.

Inflammatory myofibroblastic tumor (IMT) is the most frequent primary lung tumor in children and it may be locally aggressive. The management of a locally advanced pulmonary IMT in an 18 month-old female child is presented.A left pulmonary mass was incidentally found on the computerized tomography (CT) scan of a child with persistent systemic inflammatory syndrome. Biopsy confirmed the diagnosis; after preoperative corticotherapy, left pneumonectomy was performed. The pericardium and left atrium were invaded and resected, requiring pericardial reconstruction. There is no relapse at four years of follow-up.Steroids play a role in tumor size reduction, but marginal resection is the gold standard. Extended approaches are feasible and often required in advanced cases.

Phenotypic characteristics of human type II alveolar epithelial cells suitable for antigen presentation to T lymphocytes.

BACKGROUND: Type II alveolar epithelial cells (AECII) are well known for their role in the innate immune system. More recently, it was proposed that they could play a role in the antigen presentation to T lymphocytes but contradictory results have been published both concerning their surface expressed molecules and the T lymphocyte responses in mixed lymphocyte cultures. The use of either AECII cell line or fresh cells could explain the observed discrepancies. Thus, this study aimed at defining the most relevant model of accessory antigen presenting cells by carefully comparing the two models for their expression of surface molecules necessary for efficient antigen presentation. METHODS: We have compared by flow cytometry the surface expression of the major markers involved in the immunological synapse on the A549 cell line, the most popular model of type II alveolar epithelial cells, and freshly isolated cells. HLA-DR, CD80, CD86, ICOS-L, CD54, CD58 surface expression were studied in resting conditions as well as after IFN-γ/TNF-α treatment, two inflammatory cytokines, known to modulate some of these markers. RESULTS: The major difference found between the two cells types was the very low surface expression of HLA-DR on the A549 cell line compared to its constitutive expression on freshly isolated AECII. The surface expression of co-stimulatory molecules from the B7 family was very low for the CD86 (B7-2) and ICOS-L (B7-H2) and absent for CD80 (B7-1) on both freshly isolated cells and A549 cell line. Neither IFN-γ nor TNF-α could increase the expression of these classical co-stimulatory molecules. However CD54 (ICAM-1) and CD58 (LFA-3) adhesion molecules, known to be implicated in B7 independent co-stimulatory signals, were well expressed on the two cell types. CONCLUSIONS: Constitutive expression of MHC class I and II molecules as well as alternative co-stimulatory molecules by freshly isolated AECII render these cells a good model to study antigen presentation.

Different anesthetic techniques associated with different incidences of chronic post-thoracotomy pain: low-dose remifentanil plus presurgical epidural analgesia is preferable to high-dose remifentanil with postsurgical epidural analgesia.

OBJECTIVE: To investigate the relationships between 2 anesthetic techniques, or the extent of allodynia around the surgical wound, and the occurrence of chronic post-thoracotomy pain. DESIGN: Prospective, randomized study. SETTING: A single-institution, university hospital. PARTICIPANTS: Thirty-eight patients who underwent elective thoracotomy under general anesthesia. INTERVENTIONS: High-dose remifentanil (average effect-site concentration 5.61 +/- 0.84 ng/mL) with epidural analgesia started and at the end of surgery or low-dose remifentanil (average effect site concentration 1.99 +/- 0.02 ng/mL) with epidural analgesia with 0.5% ropivacaine started at the beginning of anesthesia. MEASUREMENTS AND MAIN RESULTS: Pain intensity and the extent of allodynia around the wound were measured during the hospital stay. The presence and intensity of residual pain were assessed 1, 3, and 6 months after surgery and at the end of the study (6-13 months, average 9 months). A DN4 neuropathic pain diagnostic questionnaire was conducted at the same times. In the high-dose group, the area with allodynia was three times larger than the area in the low-dose group. The increased allodynia was associated with a higher incidence of chronic pain (RR: 2.7-4.2) 3 and 6 months after surgery and at the end of the study (median follow-up: 9.5 months). CONCLUSIONS: High-dose remifentanil (0.14-0.26 microg/kg/min) without epidural analgesia during surgery is associated with a large area of allodynia around the wound. These patients develop a much higher incidence of chronic pain than those receiving low-dose remifentanil with epidural analgesia during surgery.

Accurate pre-operative localization of pathological parathyroid glands using 11C-methionine PET/CT.

OBJECTIVE: The pre-operative technique most routinely used to localize pathological parathyroid glands (PPG), prior to minimal access surgery (MAS), relies on 99mTc-sestamibi (MIBI) scintigraphy. Positron emission tomography (PET) using the radiolabelled amino acid 11C-methionine as the tracer agent offers a technological alternative to localize PPG. In this study we evaluated the sensitivity of 11C-methionine PET/CT (MET-PET/CT) for PPG detection and the extent to which MET-PET/CT images may contribute to the planning of surgical procedures. DESIGN: Thirty patients were included, 22 with primary hyperparathyroidism and eight with secondary hyperparathyroidism. Patients suspected of suffering from parathyroid hyperplasia underwent a complete surgical exploration of the neck region. In those suspected of parathyroid adenoma, surgery was limited to the presumed localization described by MET-PET/CT. To specifically address the additional benefit of the MET-PET/CT in terms of surgical planning and procedure, the surgeon classified the patients into two categories depending on the type of benefit, or the reason for the absence of benefit, occurring in each case. We also compared the sensitivity of MET-PET/CT and MIBI scintigraphy. RESULTS: The total number of lesions removed was 46 (24 adenomatous and 22 hyperplastic). Globally, MET-PET/CT provided additional benefit to surgery in 15 out of 30 cases (50%). The sensitivity of 11C-methionine PET/CT and MIBI scintigraphy was respectively 92% and 95% for adenoma, and 68% and 59% for hyperplasia, on the basis of available resected lesions. CONCLUSION: MET-PET/CT appears a reliable technique to guide MAS of parathyroid glands.

Gene expression in human thyrocytes and autonomous adenomas reveals suppression of negative feedbacks in tumorigenesis.

The cAMP signaling pathway regulates growth of many cell types, including somatotrophs, thyrocytes, melanocytes, ovarian follicular granulosa cells, adrenocortical cells, and keratinocytes. Mutations of partners from the cAMP signaling cascade are involved in tumor formation. Thyroid-stimulating hormone (TSH) receptor and Gsalpha activating mutations have been detected in thyroid autonomous adenomas, Gsalpha mutations in growth hormone-secreting pituitary adenomas, and PKAR1A mutations in Carney complex, a multiple neoplasia syndrome. To gain more insight into the role of cAMP signaling in tumor formation, human primary cultures of thyrocytes were treated for different times (1.5, 3, 16, 24, and 48 h) with TSH to characterize modulations in gene expression using cDNA microarrays. This kinetic study showed a clear difference in expression, early (1.5 and 3 h) and late (16-48 h) after the onset of TSH stimulation. This result suggests a progressive sequential process leading to a change of cell program. The gene expression profile of the long-term stimulated cultures resembled the autonomous adenomas, but not papillary carcinomas. The molecular phenotype of the adenomas thus confirms the role of long-term stimulation of the TSH-cAMP cascade in the pathology. TSH induced a striking up-regulation of different negative feedback modulators of the cAMP cascade, presumably insuring the one-shot effect of the stimulus. Some were down- or nonregulated in adenomas, suggesting a loss of negative feedback control in the tumors. These results suggest that in tumorigenesis, activation of proliferation pathways may be complemented by suppression of multiple corresponding negative feedbacks, i.e., specific tumor suppressors.

Vancomycin penetration of uninfected pleural fluid exudate after continuous or intermittent infusion.

Blood and pleural exudate samples were obtained from 16 patients receiving intermittent or continuous infusions of vancomycin after lung surgery. The areas under the concentration-time curves for blood and pleural exudates were identical for both administration schedules, while continuous infusion allowed the concentrations in pleural exudates to be more sustained (mean concentration, 12 mg/liter).