Postoperative Sigmoidoscopy and Biopsy After Elective Endovascular and Open Aortic Surgery for Preventing Mortality by Colonic Ischemia (PSB-Aorta-CI): Protocol for a Prospective Study.

BACKGROUND: Endovascular aortic repair is considered the standard procedure in treating patients diagnosed with pathologies of the abdominal aorta with suitable anatomy. Open surgery remains an option mostly for patients not suitable for endovascular surgery. Colonic ischemia is an important and life-threatening postoperative complication of these procedures. OBJECTIVE: The aim of this study is to evaluate the clinical value and safety of performing a planned sigmoidoscopy and biopsy for detection of colonic ischemia in patients undergoing elective aortic surgery. We also aim to develop prediction scores which could identify patients at risk for colonic ischemia and facilitate their timely treatment. METHODS: The trial is designed as a prospective study. The decision for aortic surgery and eligibility for these procedures will be ascertained according to current guidelines. Afterward, screening of the patient for the remaining inclusion and exclusion criteria will occur. If eligibility for study inclusion is confirmed, the patient will be informed about the aims of the study and all study-specific procedures (sigmoidoscopy and biopsy) and asked to provide informed consent. RESULTS: The primary end point is the proportion of patients diagnosed endoscopically with subclinical and clinically relevant colonic ischemia among all patients undergoing aortic surgery. Patient recruitment started on June 2021. The final patient is expected to be treated by the end of June 2023. Institutional Review Board review has been completed at the University of Halle (Saale; reference #052-2021). CONCLUSIONS: this shows that sigmoidoscopy can be performed safely and is effective for the timely diagnosis of colonic ischemia in these patients, this could result in its routine implementation in both elective and emergency settings. TRIAL REGISTRATION: German Clinical Trials Register DRKS00025587; https://www.drks.de/drks_web/navigate.do?navigationId =trial.HTML&TRIAL_ID=DRKS00025587. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/39071.

Comparison of percutaneous and cutdown access­related minor complications after endovascular aortic repair.

The aim of the present study was to compare the open surgical and percutaneous access for thoracic/endovascular aortic repair (T/EVAR) regarding in-hospital and post-hospital minor-complications. Percutaneous (pEVAR) and cutdown (cEVAR) techniques for femoral vessel access for T/EVAR were compared regarding their minor complications. The basic population of this retrospective cohort study consisted of 44 percutaneous and 215 cutdown accesses for endovascular aortic repair (T/EVAR-procedure) conducted between August 2008 and October 2019. The primary outcome consisted of conservatively treatable minor complications until hospital discharge and during follow up. Secondary outcomes comprised postoperative pain and complications requiring invasive treatment. Minor complications were observed in 11.4% (pEVAR) vs. 9% (cEVAR) of cases throughout index hospital stay and 10 vs. 13.7% during follow-up. No significant differences were noticed regarding overall complication rate between pEVAR and cEVAR. Only bleedings treatable through compression occurred significantly more often in the pEVAR-group (6.8 vs. 0.5%; P=0.02). In conclusions, the percutaneous technique represents a safe and quickly executable alternative to cutdown access. A significant difference in overall minor complications could not be observed. In both techniques, complications may occur even months after surgery. In order to demonstrate the superiority of the percutaneous technique compared with cutdown access, possible predictors for the use of the percutaneous technique should be defined in the future.

Acute and chronic mesenteric ischemia: single center analysis of open, endovascular, and hybrid surgery.

BACKGROUND: The aim of the study was to analyse the outcome of open surgical, endovascular, and hybrid interventions in the treatment of acute (AMI) and chronic (CMI) mesenteric ischemia. METHODS: Retrospective review of a cohort of mesenteric ischemia patients at a single tertiary referral center from 2015 to 2021. Primary end point was postoperative in-hospital mortality. Secondary end points were the number of bowel resections, duration of the procedure, length of postoperative intensive care treatment, length of hospital stay, revision surgery (number and type), and the nature and severity of postoperative complications according to Dindo-Clavien. RESULTS: A total of 64 patients, 20 with CMI and 44 with AMI, underwent open, hybrid or endovascular surgery. Bowel resection was performed in 45.5% of the patients with AMI (29.5% small intestine, 2.3% colon and 13.6% both). There was no in-hospital mortality in the CMI cohort as compared to 29.5% in the AMI cohort (p = 0.03), with no differences regarding endovascular and open surgery (29.6 vs 29.4%). Severe postoperative morbidity (Dindo-Clavien ≥ 3) was also significantly more frequent in the AMI group when compared to the CMI group (20 vs 77.3%, p < 0.001). ASA classification and intensive care stay were identified as factors associated with mortality in AMI patients. CONCLUSIONS: Morbidity and in-hospital mortality are low in CMI patients, but substantial in AMI patients. Early diagnosis and open or endovascular treatment may be decisive for the outcome of these patients.

Recurrent Laryngeal Nerve Preservation Strategies in Pediatric Thyroid Oncology: Continuous vs. Intermittent Nerve Monitoring.

(1) Background: Pediatric thyroidectomy is characterized by considerable space constraints, thinner nerves, a large thymus, and enlarged neck nodes, compromising surgical exposure. Given these challenges, risk-reduction surgery is of paramount importance in children, and even more so in pediatric thyroid oncology. (2) Methods: Children aged ≤18 years who underwent thyroidectomy with or without central node dissection for suspected or proven thyroid cancer were evaluated regarding suitability of intermittent vs. continuous intraoperative neuromonitoring (IONM) for prevention of postoperative vocal cord palsy. (3) Results: There were 258 children for analysis, 170 girls and 88 boys, with 486 recurrent laryngeal nerves at risk (NAR). Altogether, loss of signal occurred in 2.9% (14 NAR), resulting in six early postoperative vocal cord palsies, one of which became permanent. Loss of signal (3.5 vs. 0%), early (1.5 vs. 0%), and permanent (0.3 vs. 0%) postoperative vocal cord palsies occurred exclusively with intermittent IONM. With continuous nerve stimulation, sensitivity, specificity, positive and negative predictive values, and accuracy reached 100% for prediction of early and permanent postoperative vocal cord palsy. With intermittent nerve stimulation, sensitivity, specificity, positive and negative predictive values, and accuracy were consistently lower for prediction of early and permanent postoperative vocal cord palsy, ranging from 78.6% to 99.8%, and much lower (54.2-57.9%) for sensitivity. (4) Conclusions: Within the limitations of the study, continuous IONM, which is feasible in children ≥3 years, was superior to intermittent IONM in preventing early and permanent postoperative vocal cord palsy.

Prediction of Postoperative Vocal Fold Function After Intraoperative Recovery of Loss of Signal.

OBJECTIVES/HYPOTHESIS: This multicenter study aimed to 1) evaluate early postoperative vocal fold function in relation to intraoperative amplitude recovery, and 2) determine optimal absolute and relative thresholds of intraoperative amplitude recovery heralding normal early postoperative vocal fold function, both after segmental type 1 and after global type 2 loss of signal (LOS). STUDY DESIGN: Prospective outcome study. METHODS: This study, encompassing nine surgical centers from four countries, correlated intraoperative amplitude recovery with early postoperative vocal fold function using receiver operating characteristic analysis. RESULTS: Included in this study were 68 patients, 48 women and 20 men, who sustained transient recurrent laryngeal nerve injury during thyroid surgery under continuous intraoperative nerve monitoring. Early transient vocal fold palsy was seen in 18 (64%) of 28 patients with ipsilateral segmental LOS type 1, and in 10 (25%) of 40 patients with ipsilateral global LOS type 2. On receiver operating characteristic analysis, relative amplitude thresholds were superior to absolute amplitude thresholds in predicting vocal fold function after LOS type 2 (area under the curve [AUC]: 0.83 vs. 0.65; P = .01 vs. P = .15; Youden index 44% and 253 µV) and LOS type 1 (AUC: 0.96 vs. 0.97; P < .001 each; Youden index 49% and 455 µV). Amplitude recovery ≥50% of baseline after LOS always indicated intact vocal fold function. CONCLUSIONS: When the nerve amplitude recovers ≥50% of baseline after segmental LOS type 1 or global LOS type 2, it is appropriate to extend completion thyroidectomy to the other side during the same session. LEVEL OF EVIDENCE: 2b Laryngoscope, 129:525-531, 2019.

Prospective study of vocal fold function after loss of the neuromonitoring signal in thyroid surgery: The International Neural Monitoring Study Group's POLT study.

OBJECTIVES/HYPOTHESIS: Intraoperative neuromonitoring identifies recurrent laryngeal nerve (RLN) injury and gives prognostic information regarding postoperative glottic function. Loss of the neuromonitoring signal (LOS) signifies segmental type 1 or global type 2 RLN injury. This study aimed at identifying risk factors for RLN injury and determining vocal fold (VF) function initially and 6 months after definitive LOS. STUDY DESIGN: Prospective study encompassing 21 hospitals from 13 countries. METHODS: Included in this study were patients with persistent intraoperative LOS. RESULTS: At first postoperative laryngoscopy, early VF palsy was present in 94 of all 115 patients with LOS (81.7%): in 53 of 56 patients (94.6%) with type 1 injury and 41 of 59 patients (69.5%) with type 2 injury. In LOS type 1, women outnumbered men >5-fold. Traction produced LOS type 1 in 38 of 56 patients (67.9%) and LOS type 2 in 54 of 59 patients (91.5%). Course of the RLN posterior and/or anterior to the inferior thyroid artery, extralaryngeal branching, or tuberculum of Zuckerkandl did not increase VF palsy rates. Permanent VF palsy rates were also lower (P = .661) after LOS type 2 than after LOS type 1: 6.8% (four of 59 patients) versus 10.7% (six of 56 patients). Intraoperative administration of steroids did not diminish postoperative VF palsy rates. CONCLUSIONS: LOS type 1 entails more severe nerve damage than LOS type 2, affecting women disproportionately. Both LOS types, being primarily associated with traction injury, are unaffected by variant neck anatomy in expert hands and unresponsive to steroids. LEVEL OF EVIDENCE: 2b Laryngoscope, 126:1260-1266, 2016.

Dynamics of loss and recovery of the nerve monitoring signal during thyroidectomy predict early postoperative vocal fold function.

BACKGROUND: The characteristics of segmental type 1 and global type 2 injuries to the recurrent laryngeal nerve (RLN) and the extent and dynamics of nerve recovery are poorly understood. METHODS: This investigation of 785 patients who underwent thyroidectomy under continuous intraoperative nerve monitoring aimed at exploring the dynamics of loss and recovery of the nerve monitoring signal and its relationship to early postoperative vocal fold palsy. RESULTS: Persistent complete loss of signal and signal recovery <50% identified all (based on 12 and 4 patients with type 1 injuries) or most (based on 9 of 12 and 4 of 6 patients with global type 2 injuries) early unilateral vocal fold palsies. Signal recovery ≥50% (based on 7 patients) always signified normal vocal fold function. CONCLUSION: These data, including the observation that global type 2 injuries may entail less severe nerve injury, require validation in independent series before being adopted more widely. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1144-E1151, 2016.

Phosphorylation of pyruvate kinase M2 and lactate dehydrogenase A by fibroblast growth factor receptor 1 in benign and malignant thyroid tissue.

BACKGROUND: Lactate dehydrogenase A (LDHA) and Pyruvate Kinase M2 (PKM2) are important enzymes of glycolysis. Both of them can be phosphorylated and therefore regulated by Fibroblast growth factor receptor 1 (FGFR1). While phosphorylation of LDHA at tyrosine10 leads to tetramerization and activation, phosphorylation of PKM2 at tyrosine105 promotes dimerization and inactivation. Dimeric PKM2 is found in the nucleus and regulates gene transcription. Up-regulation and phosphorylation of LDHA and PKM2 contribute to faster proliferation under hypoxic conditions and promote the Warburg effect. METHODS: Using western blot and SYBR Green Real time PCR we investigated 77 thyroid tissues including 19 goiter tissues, 11 follicular adenomas, 16 follicular carcinomas, 15 papillary thyroid carcinomas, and 16 undifferentiated thyroid carcinomas for total expression of PKM2, LDHA and FGFR1. Additionally, phosphorylation status of PKM2 and LDHA was analysed. Inhibition of FGFR was performed on FTC133 cells with SU-5402 and Dovitinib. RESULTS: All examined thyroid cancer subtypes overexpressed PKM2 as compared to goiter. LDHA was overexpressed in follicular and papillary thyroid cancer as compared to goiter. Elevated phosphorylation of LDHA and PKM2 was detectable in all analysed cancer subtypes. The highest relative phosphorylation levels of PKM2 and LDHA compared to overall expression were found in undifferentiated thyroid cancer. Inhibition of FGFR led to significantly decreased phosphorylation levels of PKM2 and LDHA. CONCLUSIONS: Our data shows that overexpression and increased phosphorylation of PKM2 and LHDA is a common finding in thyroid malignancies. Phospho-PKM2 and Phospho-LDHA could be valuable tumour markers for thyroglobulin negative thyroid cancer.

Results of intraoperative neuromonitoring in thyroid surgery and preoperative vocal cord paralysis.

BACKGROUND: Systematic studies of intermittent intraoperative neuromonitoring (IONM) have shown that IONM enhances recurrent laryngeal nerve (RLN) identification via functional assessment, but does not significantly reduce rates of vocal cord (VC) paralysis (VCP). The reliability of functional nerve assessment depends on the preoperative integrity of VC mobility. The present study was therefore performed to analyze the validity of IONM in patients with pre-existing VC paralysis. METHODS: Of 8,128 patients, 285 (3.5 %) with preoperative VCP underwent thyroid surgery using standardized IONM of the RLN and vagus nerves (VNs). VC function was assessed by pre- and postoperative direct videolaryngoscopy. Quantitative parameters of IONM in patients with VCP were compared with IONM in patients with intact VC function. Clinical symptoms and surgical outcomes of patients with pre-existing VCP were analyzed. RESULTS: A total of 244 patients revealed negative, and 41 revealed positive IONM on the side of the VCP. VCP with positive IONM revealed significantly lower amplitudes of VN and RLN than intact VN (p = 0.010) and RLN (p = 0.011). Symptoms of patients with VCP included hoarseness (25 %), dyspnea (29 %), stridor (13 %), and dysphagia (13 %); 13 % were asymptomatic. New VCP occurred in five patients, ten needed tracheostomy for various reasons, and one patient died. CONCLUSIONS: Patients with pre-existing VCP revealed significantly reduced amplitude of ipsilateral VN and RLN, indicating retained nerve conductivity despite VC immobility. Preoperative laryngoscopy is therefore indispensable for reliable IONM and risk assessment, even in patients without voice abnormalities.

Continuous intraoperative vagus nerve stimulation for identification of imminent recurrent laryngeal nerve injury.

BACKGROUND: Conventional intraoperative nerve monitoring, predicated on intermittent stimulation, can predict recurrent laryngeal nerve (RLN) palsy only after the damage has been done. METHODS: Fifty-two patients (52 nerves at risk) who underwent continuous intraoperative nerve monitoring (CIONM) for thyroid surgery via vagus nerve stimulation had their electromyographic (EMG) tracings recorded and correlated with surgical maneuvers and postoperative RLN function. RESULTS: There was 1 imminent loss of signal (LOS) with intraoperative signal recovery and there were 4 losses of signal with corresponding unilateral transient RLN palsy. When EMG amplitude decreased >50% and EMG latency increased >10%, LOS and postoperative RLN palsy were noted in 4 of 8 patients (50%) who had multiple combined events. In 9 of 13 patients (70%) who developed adverse EMG changes, modification of the causative surgical maneuver resulted in recovery of those EMG changes and aversion of impending RLN palsy. CONCLUSION: CIONM reliably signaled impending nerve injury, enabling immediate corrective action.

Molecular epidemiology of multiple endocrine neoplasia 2: implications for RET screening in the new millenium.

OBJECTIVE: Twenty years ago, the groundbreaking discovery that rearranged during transfection (RET) mutations underlie multiple endocrine neoplasia 2 (MEN2) and familial medullary thyroid cancer (FMTC) ushered in the era of personalized medicine. MEN2-associated signs, taking time to manifest, can be subtle. This study sought to clarify to what extent conventional estimates of 1:200 000-500 000 underestimate the incidence of RET mutations in the population. DESIGN: Included in this retrospective investigation were 333 RET carriers born between 1951 and 2000 and operated on at the largest German surgical referral center (286 carriers) or elsewhere (47 carriers). METHODS: To estimate the incidence of RET mutations, the number of RET carriers born in Germany in five decades (1951-1960, 1961-1970, 1971-1980, 1981-1990, and 1991-2000) was divided by the corresponding number of German live births. RESULTS: Owing to improved diagnosis and capture of FMTC and MEN2 patients, minimum incidence estimates increased over time: overall from 5.0 (1951-1960) to 9.9 (1991-2000) per million live births and year (P=0.008), and by American Thyroid Association/ATA class from 1.7 to 3.7 for ATA class C (P=0.008); from 1.8 to 2.7 for ATA class A (P=0.017); from 1.5 to 2.2 for ATA class B (P=0.20); and from 0 to 1.4 for ATA class D mutations per million live births and year (P=0.008). Based on 1991-2000 incidence estimates the prevalence in Germany is ∼1:80 000 inhabitants. CONCLUSIONS: The molecular minimum incidence estimate of ≈1:100 000 was two- to fivefold greater than conventional estimates of 1:200 000-500 000.

Thyroid cancer surgery in Germany: an analysis of the nationwide DRG statistics 2005-2006.

PURPOSE: In 2004, a Diagnosis Related Groups (DRG)-based hospital reimbursement system became mandatory in Germany. The aim of this study was to provide nationwide data on the surgery of thyroid cancer by analyzing DRG statistics of the years 2005 and 2006. METHODS: The unit of analysis was hospital admission with a diagnosis of thyroid cancer. We assessed the influence of age, sex and region on the relative frequency of thyroid cancer-related hospitalisations with surgery of the thyroid and we measured the association between hospitalisation rates and incidence rates of thyroid cancer among the Federal States of Germany. RESULTS: Over the period 2005 to 2006, 11,107 thyroid cancer-associated hospitalisations included surgical treatment of the thyroid. The age-standardised DRG-based hospitalisation rates and the corresponding cancer registry-based incidences of thyroid cancer were positively associated. Overall, 68% of the hospitalisations with thyroid surgery included a total thyroidectomy. The percentage of surgery of the thyroid with a total thyroidectomy was nearly identical among men and women, decreased among men aged over 60 and varied considerably by region (minimum, 48% in Saarland; maximum, 78% in Saxony-Anhalt). CONCLUSIONS: Our analyses of DRG statistics provide for the first time representative population-based data of the surgical management of thyroid cancer patients in Germany. Despite an identical health care system all over Germany and existing guidelines for surgical treatment of thyroid cancer, we observed a considerable regional variation in the proportion of total thyroidectomies performed in Germany.

Latencies shorter than 3.5 ms after vagus nerve stimulation signify a nonrecurrent inferior laryngeal nerve before dissection.

OBJECTIVE: Quantitative electromyographic signals recorded after vagus nerve stimulation during intraoperative neuromonitoring (IONM) were analyzed for their clinical usefulness to identify and track a nonrecurrent inferior laryngeal nerve (NRLN) before dissection. BACKGROUND: A NRLN is anatomically shorter than a recurrent inferior laryngeal nerve (RLN). This disparity should cause differential latencies after vagus nerve stimulation during IONM, which may aid in distinguishing a NRLN from a RLN. Failure to identify a NRLN early on entails a great risk of nerve injury. METHODS: Included in this IONM case-control study were 18 cases with a NRLN and 36 controls with RLN anatomy matched for gender, age, body size, and underlying thyroid and parathyroid disease. RESULTS: All 18 NRLN were found in the right neck only. Cases with a NRLN had significantly shorter latencies than controls (medians of 2.7 vs. 4.6 ms; P < 0.001) but comparable amplitude and duration after stimulation of the right vagus nerve. With a latency threshold of <3.5 ms, sensitivity, specificity, positive and negative predictive value, and accuracy, respectively, were 100%, 94%, 100%, 97%, and 98% for diagnosis of a NRLN. CONCLUSIONS: A latency threshold of 3.5 ms after ipsilateral vagus nerve stimulation during IONM was able to discriminate well between a NRLN and a RLN in adults, helping avoid injury to the aberrant nerve. Additional studies should explore latency thresholds in children and adolescents who have shorter inferior laryngeal nerves and conceivably shorter latencies than adults.

Impact of extent of resection for thyroid cancer invading the aerodigestive tract on surgical morbidity, local recurrence, and cancer-specific survival.

BACKGROUND: The appropriate resection for thyroid cancer invading the aerodigestive tract remains controversial. METHODS: A total of 174 patients underwent resections for aerodigestive tract invasion from differentiated thyroid cancer (103 patients), medullary thyroid cancer (40 patients), and undifferentiated thyroid cancers/unusual thyroid neoplasms (31 patients). In all, 82 patients submitted to transmural resections (window resection, sleeve resection, or cervical evisceration), 65 patients underwent nontransmural resections (shaving or extramucosal esophageal resections), and 27 patients had grossly incomplete resections. The measures of outcome included surgical morbidity, locoregional recurrence, and disease-specific survival. RESULTS: Surgical morbidity was 38% after transmural and 25% after nontransmural resection (P = .02). On histopathologic examination, surgical margins were microscopically involved in 9% of patients after transmural and 23% of patients after nontransmural resection (P = .014). At a mean follow-up of 35.3 months, locoregional recurrence developed in 10 (46%) of 22 patients with microscopically incomplete and 18 (15%) of 121 patients with microscopically complete resection (P = .001). After grossly complete resection, the mean disease-specific survival was 101.2, 69.8, and 25.5 months for differentiated thyroid cancer, medullary thyroid cancer, and undifferentiated thyroid cancer/unusual neoplasms, respectively (P < .001). This outcome was independent of the type of resection. CONCLUSION: The type of cancer and resection are key determinants of outcome among thyroid cancer patients with aerodigestive tract invasion.

What are normal quantitative parameters of intraoperative neuromonitoring (IONM) in thyroid surgery?

PURPOSE: This study aimed at definition of normal quantitative parameters in intraoperative neuromonitoring during thyroid surgery. Only few and single center studies described quantitative data of intraoperative neuromonitoring. Definition of normal parameters in intraoperative neuromonitoring is believed to be a prerequisite for interpretation of results and intraoperative findings when using this method. Moreover, these parameters seem important in regard to the prognostic impact of the method on postoperative vocal cord function. MATERIAL AND METHODS: In a prospective multicenter study, quantitative analysis of vagal nerve stimulation pre- and postresection was performed in thyroid lobectomies. A standardized protocol determined set up and installation of neuromonitoring and defined assessment of quantitative parameters. Data of intraoperative neuromonitoring were respectively print-documented and centrally analyzed. RESULTS: In six participating centers a total of 1,289 patients with 1,996 nerves at risk underwent surgery for benign and malignant thyroid disease. Median amplitude was significantly larger for the right vs. left vagal nerve, latency was significantly longer for left vs. right vagal nerve and duration of the left vs. right vagal nerve significantly longer. Age disparities were only present in form of significantly higher amplitude in patients below 40 years; however, there is no continuous increase with age. Regarding gender, there was significantly higher amplitude and smaller latency in women compared to men. Duration of surgery revealed a reduction of amplitude with operative time; contrarily, latency and signal duration remained stable. The type of underlying thyroid disease showed no influence on quantitative parameters of intraoperative neuromonitoring. CONCLUSIONS: Systematic data of multicenter evaluation on quantitative intraoperative neuromonitoring parameters revealed differences between left and right vagal nerves in regard to amplitude, latency and duration of signal, gender, and age. The nature of thyroid disease showed no significant influence on quantitative parameters of intraoperative neuromonitoring. This study presents for the first time collective data of a large series of nerves at risk in a multicenter setting. It seems that definitions of "normal" parameters are prerequisite for the interpretation of quantitative changes of intraoperative neuromonitoring during thyroid surgery to enable interpretation of influence on surgical strategy and prediction of postoperative vocal cord function.

Management of lymph fistulas in thyroid surgery.

PURPOSE: Postoperative lymphatic leakage following thyroid surgery represents a management problem with considerate potential morbidity, psychological, and economical impact. Conservative and surgical management strategies for high- and low-output lymph fistulas are inconsistent. Reliable criteria to predict outcome of conservative versus surgical treatment in clinically evident lymph fistula are lacking. MATERIAL AND METHODS: A retrospective single-center chart review of consecutively quality-control-documented thyroid surgeries from January 1998 to December 2009 was performed to identify reported postoperative lymph fistulas. Documentation of surgical procedures, drainage, medical, and nutritional management was analyzed to identify risk factors for occurrence and criteria for management of evident lymph fistulas. RESULTS: There were 29 patients identified with postoperative clinical evidence of lymph fistulas following thyroid surgery; incidence was 0.5%. Indication to surgery comprised benign nodular goiter, recurrent nodular goiter, and thyroid carcinoma or local and lymphonodal carcinoma recurrences. There were 12 (41%) primary and 17 (59%) redo surgeries performed. Surgical procedures performed included thyroidectomy, completion thyroidectomy, and primary and redo central and lateral systematic microdissection of lymphatic compartments. All patients were initially submitted to fasting diet and medical treatment, successfully in 19 (66%), whereas ten (34%) patients underwent surgical intervention for fistula closure after failure of conservative treatment. Complications were one wound infection and fistula recurrence in five (26%) patients in the conservative group and two (20%) in the surgical group. Hospital stay was exceedingly prolonged in both groups with a median of 21 and 11 versus 6 days in patients with regular postoperative course following thyroid surgery. CONCLUSIONS: Data of this series support definition of the two categories of high- and low-output fistulas according to drainage collection with >300 versus <200 ml/day. Fasting in low-output fistula facilitates conservative treatment with closed drainage, whereas in high-output fistulas surgical intervention should be sought. Attendant criteria for treatment stratification are equally important, like patient's compliance, nutritional, and general health status as well as evidence for wound infection. Surgical closure of lymph fistula may be demanding when identification of the secreting fistula is limited and even muscle flap fortification may fail. Ultimately, in unsuccessfully reoperated fistula recurrences, open drainage may become necessary. Lymph fistulas cause significantly prolonged hospital stay, possible critical clinical decay, and unfavorable cosmetic and oncologic outcome while the superior management remains to be defined.

Proteomic approach reveals novel targets for retinoic acid-mediated therapy of thyroid carcinoma.

Our previous studies demonstrated that retinoic acid (RA)-induced reduction of both, the key glycolytic enzyme ENO1 and proliferation-promoting c-Myc, resulted in decreased vitality and invasiveness of the follicular thyroid carcinoma cell lines FTC-133 and FTC-238. By employing two-dimensional electrophoresis and mass spectrometry, we identified proteins affected by RA treatment. In addition to previously reported decrease in ENO1 expression, we found that RA led to significantly reduced levels of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase isoenzymes M1/M2 (PKM1/M2), peptidyl-prolyl cis-trans isomerase A (PPIA), transketolase (TKT), annexin A2 (ANXA2), glutathione S-transferase P (GSTP1) and peroxiredoxin 2 (PRDX2) as compared to untreated control. The same proteins investigated on thyroid tissues were found to be significantly up-regulated in follicular, papillary and undifferentiated thyroid carcinomas when compared with goiter and adenoma tissues. These findings identify new target proteins for RA-mediated anti-tumor and re-differentiation therapies and provide novel insights into treatments for thyroid carcinoma.

Importance of gender-specific calcitonin thresholds in screening for occult sporadic medullary thyroid cancer.

Men and women differ in thyroidal C-cell mass and calcitonin secretion. This difference may have implications for the definition of calcitonin thresholds to distinguish sporadic C-cell hyperplasia from occult medullary thyroid cancer. This retrospective study examined the hypothesis that gender-specific calcitonin thresholds predict occult medullary thyroid cancer more accurately among patients with increased basal calcitonin levels than unisex thresholds. A total of 100 consecutive patients were evaluated with occult sporadic C-cell disease no larger than 10 mm who were referred for increased basal calcitonin levels and underwent pentagastrin stimulation preoperatively at this institution. Altogether, gender-specific calcitonin thresholds predicted medullary thyroid cancer better than unisex thresholds. At lower (

The role of AUF1 in thyroid carcinoma progression.

AUF1/heterogeneous nuclear ribonucleoprotein D is an adenylate-uridylate-rich elements (AREs) -binding protein, which regulates the mRNA stability of many genes related to growth regulation, such as proto-oncogenes, growth factors, cytokines, and cell cycle-regulatory genes. Several studies demonstrated AUF1 involvement in the processes of apoptosis, tumorigenesis, and development by its interactions with ARE-bearing mRNAs. We report here that AUF1 may be involved in thyroid carcinoma progression. Investigations on thyroid tissues revealed that cytoplasmic expression of AUF1 in malignant tissues was increased when compared with benign thyroid tissues. In thyroid carcinoma cell lines, AUF1 was mostly detectable in the nucleus; however, in dividing cells, its increased production was also observed in the cytoplasm. We found AUF1 in complexes with ARE-bearing mRNAs, previously described to be crucial for proliferation and cell cycle of thyroid carcinoma. Total or exon-selective knockdown of AUF1 led to growth inhibition accompanied by induction of cell cycle inhibitors and decreased levels of cell cycle promoters. Our data demonstrate the existence of a complex network between AUF1 and mRNAs encoding proteins related to cell proliferation. AUF1 may control the balance between stabilizing and destabilizing effects, both of which are exerted on cell cycle machinery in thyroid carcinoma. Although we cannot exclude participation of other factors, thyroid carcinoma may recruit cytoplasmic AUF1 to disturb the stability of mRNAs encoding cyclin-dependent kinase inhibitors, leading to uncontrolled growth and progression of tumor cells. Thus, AUF1 may be considered as a new, additional marker for thyroid carcinoma.