| 1. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 2. |
- Fraser, Sheila, et al.
(författare)
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Incidence and Risk Factors for Occult Level 3 Lymph Node Metastases in Papillary Thyroid Cancer
- 2016
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Ingår i: Annals of Surgical Oncology. - : Springer Science and Business Media LLC. - 1068-9265 .- 1534-4681. ; 23:11, s. 3587-3592
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Tidskriftsartikel (refereegranskat)abstract
- Papillary thyroid cancer (PTC) frequently disseminates into cervical lymph nodes. Lateral node involvement is described in up to 50 % patients undergoing prophylactic lateral neck dissection. This study aimed to assess this finding and identify which factors predict for occult lateral node disease. Patients with fine needle aspiration-confirmed PTC (Bethesda V or VI), without evidence of cervical lymph node metastases, underwent a total thyroidectomy with prophylactic ipsilateral central and level 3 dissection. Level 3 nodes were removed by compartmental dissection or by sampling the sentinel nodes overlying the jugular vein, according to surgeon preference. Data were collected prospectively from January 2011 to August 2014. Statistical analysis was performed by SPSS software. A total of 137 patients underwent total thyroidectomy with prophylactic ipsilateral central and level 3 dissection for PTC. The incidence of occult level 3 disease was 30 % (41/137 patients). A total of 48 % of patients (66/137) harbored occult central neck disease. A total of 80.5 % of patients with pN1b disease had macrometastases (aeyen2 mm), and 15 % exhibited skip metastases with central compartment sparing. In patients with pN1b disease, a median of 6 level 3 nodes were retrieved, with an average involved nodal ratio of 0.29. Multivariate regression demonstrated risk factors for occult lateral neck metastasis include tumor size (odds ratio 1.1), upper pole tumors (odds ratio 6.6), and vascular invasion (odds ratio 3.2) (p < 0.05). PTC is associated with a significant incidence of occult central and lateral nodal metastases. In patients undergoing prophylactic central neck dissection, inclusion of level 3 dissection should be considered in patients with large upper lobe cancers.
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| 3. |
- Glover, Anthony R, et al.
(författare)
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Use of the Nerve Integrity Monitor during Thyroid Surgery Aids Identification of the External Branch of the Superior Laryngeal Nerve.
- 2015
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Ingår i: Annals of Surgical Oncology. - : Springer Science and Business Media LLC. - 1068-9265 .- 1534-4681. ; 22:6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The external branch of the superior laryngeal nerve (EBSLN) is at risk during thyroid surgery. Despite meticulous dissection and visualization, the EBSLN can be mistaken for other structures. The nerve integrity monitor (NIM) allows EBSLN confirmation with cricothyroid twitch on stimulation.AIMS: The aim of this study was to assess any difference in identification of EBSLN and its anatomical sub-types by dissection alone compared to NIM-aided dissection.METHODS: Routine intra-operative nerve monitoring (IONM) was used, when available, for 228 consecutive thyroid operations (129 total thyroidectomies, 99 hemi-thyroidectomies) over a 10-month period. EBSLN identification by dissection alone (with NIM confirmation of cricothyroid twitch) and by NIM-assisted dissection was recorded prospectively. Anatomical sub-types were defined by the Cernea classification.RESULTS: Of 357 nerves at risk, 97.2 % EBSLNs (95 % confidence interval [CI], 95.5-98.9) were identified by visualization and NIM-aided dissection compared to 85.7 % (95 % CI, 82.1-89.3) identified by dissection alone (<0.001). EBSLN frequency was 34 % for type 1, 55 % for type 2a, and 11 % for type 2b. All identified EBSLNs were stimulated to confirm a cricothyroid twitch after superior thyroid vessel ligation.CONCLUSION: Using the NIM and meticulous dissection of the upper thyroid pole improves EBSLN identification. As the EBSLN is at risk during thyroidectomy and can lead to voice morbidity, the NIM can aid identification of the EBSLN and provide a functional assessment of the EBSLN after thyroid resection.
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| 4. |
- Loch-Wilkinson, Thorbjorn J., et al.
(författare)
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Nerve stimulation in thyroid surgery : is it really useful?
- 2007
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Ingår i: ANZ journal of surgery. - : Wiley. - 1445-1433 .- 1445-2197. ; 77:5, s. 377-380
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Monitoring of the recurrent laryngeal nerve (RLN) has been claimed in some studies to reduce rates of nerve injury during thyroid surgery compared with anatomical dissection and visual identification of the RLN alone, whereas other studies have found no benefit. Continuous monitoring with endotracheal electrodes is expensive whereas discontinuous monitoring by laryngeal palpation with nerve stimulation is a simple and inexpensive technique. This study aimed to assess the value of nerve stimulation with laryngeal palpation as a means of identifying and assessing the function of the RLN and external branch of the superior laryngeal nerve (EBSLN) during thyroid surgery. METHODS: This was a prospective case series comprising 50 consecutive patients undergoing total thyroidectomy providing 100 RLN and 100 EBSLN for examination. All patients underwent preoperative and postoperative vocal cord and voice assessment by an independent ear, nose and throat surgeon, laryngeal examination at extubation and all were asked to complete a postoperative dysphagia score sheet. Dysphagia scores in the study group were compared with a control group (n = 20) undergoing total thyroidectomy without nerve stimulation. RESULTS: One hundred of 100 (100%) RLN were located without the use of the nerve stimulator. A negative twitch response occurred in seven (7%) RLN stimulated (two bilateral, three unilateral). Postoperative testing, however, only showed one true unilateral RLN palsy postoperatively (1%), which recovered in 7 weeks giving six false-positive and one true-positive results. Eighty-six of 100 (86%) EBSLN were located without the nerve stimulator. Thirteen of 100 (13%) EBSLN could not be identified and 1 of 100 (1%) was located with the use of the nerve stimulator. Fourteen per cent of EBSLN showed no cricothyroid twitch on EBSLN stimulation. Postoperative vocal function in these patients was normal. There were no instances of equipment malfunction. Dysphagia scores did not differ significantly between the study and control groups. CONCLUSION: Use of a nerve stimulator did not aid in anatomical dissection of the RLN and was useful in identifying only one EBSLN. Discontinuous nerve monitoring by stimulation during total thyroidectomy confers no obvious benefit for the experienced surgeon in nerve identification, functional testing or injury prevention.
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| 5. |
- Meyer-Rochow, Goswin Y., et al.
(författare)
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MicroRNA profiling of benign and malignant pheochromocytomas identifies novel diagnostic and therapeutic targets
- 2010
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Ingår i: Endocrine-Related Cancer. - 1351-0088 .- 1479-6821. ; 17:3, s. 835-846
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Tidskriftsartikel (refereegranskat)abstract
- MicroRNAs (miRNAs) are small RNAs (similar to 22 bp) that post-transcriptionally regulate protein expression and are found to be differentially expressed in a number of human cancers. There is increasing evidence to suggest that miRNAs could be useful in cancer diagnosis, prognosis, and therapy. We performed miRNA microarray expression profiling on a cohort of 12 benign and 12 malignant pheochromocytomas and identified a number of differentially expressed miRNAs. These results were validated in a separate cohort of ten benign and ten malignant samples using real-time quantitative RT-PCR; benign samples had a minimum follow-up of at least 2 years. It was found that IGF2 as well as its intronic miR-483-5p was over-expressed, while miR-15a and miR-16 were under-expressed in malignant tumours compared with benign tumours. These miRNAs were found to be diagnostic and prognostic markers for malignant pheochromocytoma. The functional role of miR-15a and miR-16 was investigated in vitro in the rat PC12 pheochromocytoma cell line, and these miRNAs were found to regulate cell proliferation via their effect on cyclin D1 and apoptosis. These data indicate that miRNAs play a pivotal role in the biology of malignant pheochromocytoma, and represent an important class of diagnostic and prognostic biomarkers and therapeutic targets warranting further investigation.
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| 6. |
- Nylén, Carolina, et al.
(författare)
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Prophylactic central lymph node dissection informs the decision of radioactive iodine ablation in papillary thyroid cancer
- 2021
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Ingår i: American Journal of Surgery. - : Elsevier BV. - 0002-9610 .- 1879-1883. ; 221:5, s. 886-892
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundProphylactic central lymph node dissection (CLND) in papillary thyroid cancer (PTC) is controversial. We aimed to investigate if prophylactic CLND aids risk stratification and contributes to the decision for postoperative RAI ablation.MethodsPatients undergoing thyroidectomy for PTC and prophylactic CLND were identified from an endocrine surgical unit database. Pathology reports where reviewed for number and size of lymph nodes and patients stratified by risk according to the ATA guidelines.Results426 patients were identified with PTC ≤4 cm and prophylactic CLND. 96 patients (23%) had central lymph node metastasis (CLNM) that qualified them for the intermediate risk group. In 17 patients (4%), the CLNM data led to upgrading independently of other histopathological characteristics. Correcting for multiple variables, CLNM was an independent factor contributing to RAI treatment.ConclusionProphylactic CLND provides information to aid the selection of RAI ablation independent of primary cancer histology for risk stratification in 4% of patients. This benefit should be carefully balanced with the risk of CLND and patient treatment choice when deciding on management of PTC ≤4 cm.
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| 7. |
- Sarkis, Leba M, et al.
(författare)
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Bilateral recurrent laryngeal nerve injury in a specialized thyroid surgery unit : would routine intraoperative neuromonitoring alter outcomes?
- 2017
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Ingår i: ANZ journal of surgery. - : Wiley. - 1445-1433 .- 1445-2197. ; 87:5, s. 364-367
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Bilateral recurrent laryngeal nerve (RLN) palsy following total thyroidectomy is a rare complication, however, poses significant morbidity to the patient when it does occur. The purpose of this paper was to determine the incidence of bilateral RLN palsy in a specialized thyroid unit and determine whether the routine use of intraoperative nerve monitoring (IONM) would alter the outcome.METHODS: This is a retrospective review of prospectively gathered data. A total of 7406 patients underwent total thyroidectomy at the University of Sydney Endocrine Surgical Unit between January 1990 and February 2014. IONM was utilized on a selective basis and we sought to assess whether IONM would have altered outcome in those patients who developed bilateral RLN palsy.RESULTS: Of the 7406 patients who underwent total thyroidectomy, seven patients (0.09%) developed bilateral RLN palsy during the study period. There was one permanent RLN palsy (0.01%) and routine IONM may have prevented one death and altered the outcome in two of the seven patients.CONCLUSION: Bilateral RLN palsy is a rare entity occurring in one out of 1000 cases in a specialized thyroid unit. IONM may facilitate the decision to pursue delayed surgery where the signal is lost on the first surgical side and has the potential to avoid bilateral RLN palsy following total thyroidectomy.
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| 8. |
- Sywak, Mark S., et al.
(författare)
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A randomized controlled trial of minimally invasive thyroidectomy using the lateral direct approach versus conventional hemithyroidectomy
- 2008
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Ingår i: Surgery. - : Elsevier BV. - 0039-6060 .- 1532-7361. ; 144:6, s. 1016-21; discussion 1021
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The role of minimally invasive thyroid surgery (MITS) is currently in evolution. The aim of this study is to compare the outcomes of MITS using the direct approach through a lateral incision with conventional hemithyroidectomy (CHT) for the management of atypical thyroid nodules. METHODS: A prospective, single-blinded, randomized controlled trial involving patients presenting with atypical thyroid nodules of 3-cm diameter or less was performed. Patients were randomized to MITS through a lateral 2.5-cm incision or CHT through a traditional 5- to 6-cm cervicotomy. Pain was measured using a 7-point visual analog scale on the 1st and 10th postoperative days. Serum C-reactive protein was measured on postoperative days 1 and 10. Satisfaction with cosmetic outcome was measured at 3 months. RESULTS: One-hundred patients were randomized to undergo MITS or CHT. The 2 groups were equivalent in terms of age and thyroid nodule size. Mean operative times were longer for the MITS group (56 vs 46 min, P < .001). Mean pain scores were less in the MITS group on the 1st postoperative day (2.67 vs 3.43, P = .032). Pain scores at 10 days were equivalent (1.5 vs 1.8, P = .36). Serum C-reactive protein levels were equivalent postoperatively. At 3 months, patients undergoing MITS reported a greater mean cosmetic satisfaction score (6.3 vs 5.0, P = .002). Incision lengths measured at 3 months were 2.6 cm for MITS and 5.4 cm for CHT group, P < .001. CONCLUSION: In the management of small, atypical thyroid nodules, MITS through a direct lateral approach results in less early postoperative pain and superior cosmetic results when compared with conventional thyroidectomy.
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