Conditional survival analysis and real-time prognosis prediction in stage III T3-T4 colon cancer patients after surgical resection: a SEER database analysis.

BACKGROUND: Conditional survival (CS) takes into consideration the duration of survival post-surgery and can provide valuable additional insights. The aim of this study was to investigate the risk factors associated with reduced one-year postoperative conditional survival in patients diagnosed with stage III T3-T4 colon cancer and real-time prognosis prediction. Furthermore, we aim to develop pertinent nomograms and predictive models. METHODS: Clinical data and survival outcomes of patients diagnosed with stage III T3-T4 colon cancer were obtained from the Surveillance, Epidemiology, and End Results (SEER) database, covering the period from 2010 to 2019. Patients were divided into training and validation cohorts at a ratio of 7:3. The training set consisted of a total of 11,386 patients for conditional overall survival (cOS) and 11,800 patients for conditional cancer-specific survival (cCSS), while the validation set comprised 4876 patients for cOS and 5055 patients for cCSS. Univariate and multivariate Cox regression analyses were employed to identify independent risk factors influencing one-year postoperative cOS and cCSS. Subsequently, predictive nomograms for cOS and cCSS at 2-year, 3-year, 4-year, and 5-year intervals were constructed based on the identified prognostic factors. The performance of these nomograms was rigorously assessed through metrics including the concordance index (C-index), calibration curves, and the area under curve (AUC) derived from the receiver operating characteristic (ROC) analysis. Clinical utility was further evaluated using decision curve analysis (DCA). RESULTS: A total of 18,190 patients diagnosed with stage III T3-T4 colon cancer were included in this study. Independent risk factors for one-year postoperative cOS and cCSS included age, pT stage, pN stage, pretreatment carcinoembryonic antigen (CEA) levels, receipt of chemotherapy, perineural invasion (PNI), presence of tumor deposits, the number of harvested lymph nodes, and marital status. Sex and tumor site were significantly associated with one-year postoperative cOS, while radiation therapy was notably associated with one-year postoperative cCSS. In the training cohort, the developed nomogram demonstrated a C-index of 0.701 (95% CI, 0.711-0.691) for predicting one-year postoperative cOS and 0.701 (95% CI, 0.713-0.689) for one-year postoperative cCSS. Following validation, the C-index remained robust at 0.707 (95% CI, 0.721-0.693) for one-year postoperative cOS and 0.700 (95% CI, 0.716-0.684) for one-year postoperative cCSS. ROC and calibration curves provided evidence of the model's stability and reliability. Furthermore, DCA underscored the nomogram's superior clinical utility. CONCLUSIONS: Our study developed nomograms and predictive models for postoperative stage III survival in T3-T4 colon cancer with the aim of accurately estimating conditional survival. Survival bias in our analyses may lead to overestimation of survival outcomes, which may limit the applicability of our findings.

A combination of silymarin and garlic extract enhances thyroid hormone activation and body metabolism in orally intoxicated male rats with atrazine: Impact on hepatic iodothyronine deiodinase type 1.

Atrazine is a widely applied herbicide to improve crop yield and maintain general health. It has been reported to impair thyroid function and architecture in experimental animals. Alterations in thyroid hormones disrupt normal body function and metabolism. Silymarin, a hepatoprotective flavonolignan, was found to improve thyroid function and body metabolism. Additionally, garlic displays several protective effects on body organs. Therefore, this study explored the prophylactic impact of natural compounds comprising silymarin and garlic extract on disrupted thyroid function, hepatic iodothyronine deiodinase type 1, and metabolic parameters in atrazine-intoxicated male rats. We found that daily pre- and co-treatment of atrazine-intoxicated male rats with silymarin (100 mg/kg, p.o) and/or garlic extract (10 mg/kg, p.o) significantly improved thyroid activation and hepatic functionality as evidenced by the re-establishment of T3, T3/T4, and TSH values as well as ALT and AST activities. Interestingly, individual or concurrent supplementation of the atrazine group with silymarin and garlic extract prevented the down-regulation in hepatic iodothyronine deiodinase type 1. These effects were coupled with the repletion of serum and hepatic antioxidants and the amelioration of lipid peroxidation. In addition, current natural products markedly alleviated weight gain, dyslipidemia, hyperglycemia, glucose intolerance, and insulin resistance. Notably, a cocktail of silymarin and garlic extract exerted superior protection against atrazine-triggered deterioration of thyroid, hepatic, and metabolic functioning to individual treatments. Present findings pinpoint the prophylactic and synergistic influence of silymarin and garlic extract combinatorial regimen on thyroid activation and body metabolism via enhancing antioxidant potential, maintaining hepatic function, and iodothyronine deiodinase type 1.

Different FT3/TSH correlation in acquired and congenital hypothyroid patients reveals a different hypothalamic set-point.

OBJECTIVE: To understand differences in thyroid hormone replacement therapy with levo-thyroxine (l-T4) between acquired and congenital hypothyroid (CH) patients. DESIGN: We compared biochemical thyroid parameters between euthyroid subjects (EU) and both CH adult patients and thyroidectomized patients (TP) under replacement therapy. PATIENTS AND MEASUREMENTS: A retrospective analysis was performed on a series of 98 consecutive adult CH patients (27 males and 71 females) with a median age of 24 years (range 18-58). Serum TSH, FT3, FT4, l-T4 dose and body weight were assessed. For comparison purposes, large series of 461 TP for thyroid cancer and 1852 EU followed at our Thyroid Clinic were used as control groups. RESULTS: The daily weight-based l-T4 dose was significantly higher in CH than TP group (1.9 vs. 1.7 mcg/kg, p = .03). FT3/FT4 ratio was significantly higher in the EU group, intermediate in CH and lower in TP groups (0.32, 0.28 and 0.24, respectively). Linear regression analysis displayed an inverse correlation between FT4 and TSH in all the groups. An inverse correlation between FT3 and TSH was observed in the TP group, but not in the EU and CH group suggesting that CH patients, under replacement therapy, display biochemical thyroid parameters similar to EU subjects. CONCLUSIONS: Adult CH patients require a higher daily l-T4 dose than adult TP. However, the different correlation of TSH and FT3 values between CH and TP patients suggests an adaptive and different hypothalamic-pituitary-thyroid axis regulation that may depend on the early timing of the onset of hypothyroidism in CH.

Triiodothyronine/Thyroxine Ratio as a Marker of Clinical Response to Levothyroxine Replacement in Patients With Hypothyroidism.

BACKGROUND:  Hypothyroidism is one of the most common endocrine disorders with a simple therapy, that is levothyroxine (LT4). A normal thyroid-stimulating hormone (TSH) measurement is used as a marker of optimal replacement. But, many patients still have symptoms. Triiodothyronine (T3), thyroxine (T4), and their ratio may correlate with clinical improvement. The study aims to assess the T3/T4 ratio as a marker of clinical response in patients with hypothyroidism.  Method: A cross-sectional study was conducted from June to November 2022 at Faiha Specialized Diabetes, Endocrine, and Metabolism Center, in Basrah, southern Iraq. We included 48 adult patients with primary hypothyroidism on LT4 treatment only and TSH within the target reference range for at least within the last six months. Each patient was subjected to a questionnaire that was designed to capture hypothyroidism-related complaints in the form of a five-point Likert scale. Biochemical assessments were done with the measurement of TSH, T3, and T4. RESULTS: Despite having a normal TSH level, nearly all the patients had persistent and varying severity of clinical complaints of hypothyroidism. Tiredness, hair problems, weight gain, and cold intolerance were the most severely persistent symptoms. Patients with scores of two and more for weight gain, cold intolerance, and skin problems had significantly lower T3/T4 ratios (P = 0.04, 0.002, and 0.02, respectively), while in the remaining clinical symptoms, the T3/T4 ratio did not differ significantly. CONCLUSION: A low T3/T4 ratio was significantly associated with resistant symptoms of hypothyroidism and may be used as a marker for treatment efficacy with TSH rather than TSH value alone.

Effect of thermal manipulation on embryonic development, hatching process, and chick quality under heat-stress conditions.

Thermal stress is a risk that threatens poultry welfare and productivity. Thermal manipulation during egg incubation is considered a prevention strategy used to mitigate the detrimental effects of high ambient temperatures on birds. This study aimed to investigate the impact of thermal manipulation, applied to chicken breeder's eggs during the incubation period, on embryonic development, hatching characteristics, and chick quality, as well as posthatch thermotolerance and performance. A total of 1,200 fertile eggs were randomly and equally assigned into 2 groups of 3 replicates (200 eggs/replicate), using a randomized experimental design followed by t test. The first group eggs (G1) were subjected to a commercial setter temperature of 37.5°C with 55% relative humidity (RH) throughout the incubation period (1-18 d) and served as a control, while the second group eggs (G2) were treated the same commercial setter conditions until the 11th day of the incubation, then the eggs were exposed to a higher temperature of 39.5°C with 60% RH for 4 h daily from the 12th to the 18th day of incubation. All eggs in both groups were exposed to the same temperature condition of 37.2°C with 70% RH from the 19th to the 22nd days of the incubation (hatching period). Three hundred hatched female chicks per each treatment group were transferred into a closed-system house and distributed randomly into 20 floor pens (15 birds per pen). At the 8th week of age, birds were exposed to a daily heat challenge by raising the temperature to 35°C for 6 h until the 18th week of the chick's age. According to the results, thermal manipulation at 12 to 18 d of egg incubation positively (P ≤ 0.05) affected several studied traits. It improved some embryonic development traits, such as embryonic weight and tibia length, as well as some hatching parameters, such as hatching time and pipped eggs. It also improved hatched chick quality traits, including the chick's weight, length, and activity. In addition, it enhanced the posthatch chick's thermotolerance and body weight. Hatched chicks of G2 had significantly (P ≤ 0.05) higher total protein, albumin, IgM, glucose, calcium, total antioxidant, and T3 than G1 chicks. They also had significantly (P = 0.001) higher body weight (23%) at the 18th week of age than G1, as well as a lower feed conversion ratio (20.71%) than G1 chicks at 8 to 18 wk of age. Therefore, it is recommended to apply thermal manipulation during egg incubation, particularly at 12 to 18 d, for its positive effects on the pre- and posthatch performance.

Low T3 vs low T3T4 euthyroid sick syndrome in septic shock patients: A prospective observational cohort study.

BACKGROUND: Both phases of euthyroid sick syndrome (ESS) are associated with worse prognosis in septic shock patients. Although there are still no indications for supplementation therapy, there is no evidence that both phases (initial and prolonged) are adaptive or that only prolonged is maladaptive and requires supplementation. AIM: To analyze clinical, hemodynamic and laboratory differences in two groups of septic shock patients with ESS. METHODS: A total of 47 septic shock patients with ESS were divided according to values of their thyroid hormones into low T3 and low T3T4 groups. The analysis included demographic data, mortality scores, intensive care unit stay, mechanical ventilation length and 28-day survival and laboratory with hemodynamics. RESULTS: The Simplified Acute Physiology Score II score (P = 0.029), dobutamine (P = 0.003) and epinephrine requirement (P = 0.000) and the incidence of renal failure and multiple organ failure (MOF) (P = 0.000) were significantly higher for the low T3T4. Hypoalbuminemia (P = 0.047), neutrophilia (P = 0.038), lymphopenia (P = 0.013) and lactatemia (P = 0.013) were more pronounced on T2 for the low T3T4 group compared to the low T3 group. Diastolic blood pressure at T0 (P = 0.017) and T1 (P = 0.007), as well as mean arterial pressure at T0 (P = 0.037) and T2 (P = 0.033) was higher for the low T3 group. CONCLUSION: The low T3T4 population is associated with higher frequency of renal insufficiency and MOF, with worse laboratory and hemodynamic parameters. These findings suggest potentially maladaptive changes in the chronic phase of septic shock.

Exploring The Link Between Obesity And Hypothyroidism.

BACKGROUND: Obesity and hypothyroidism are two common clinical conditions that are often connected. This connection is now more important because of an exceptional rise in the prevalence of obesity around the world. Both of these conditions have a noteworthy impact on human health and well-being. The main objective of this study was to determine the frequency of hypothyroidism in obese patients presenting at Ayub Teaching Hospital, Abbottabad. METHODS: This cross-sectional study was carried out on 242 patients in the Department of Medicine of Ayub Teaching Hospital, Abbottabad from 1st March to 31st August 2022. SPSS version 23.0 was used for data analysis. RESULTS: In this study, 242 obese patients were included. The mean age of the patients was 39.55±9.361 years. The mean BMI was 41.62±8.099kg/m2 ranging from 31 to 61kg/m2, the mean TSH level was 3.04±2.604mU/l, the mean T4 level was 8.53±2.215pmol/L and the mean T3 level was 1.2195±0.35795nmol/L. Out of a total of 242 patients, 34 (14.0%) were male and 208(86.0%) were female patients. Patients found with overt hypothyroidism were 11 (4.5%), subclinical hypothyroidism were 31 (12.8%) and euthyroid were 200 (82.6%). CONCLUSIONS: The proportion of hypothyroidism among the obese patients was quite less in our setup and not significantly associated with age and gender of the patients.

Relationship Between Rhinitis, Nasal Obstruction and Hypothyroidism: A Follow Up Study with Pre-post Treatment with Levothyroxine.

Hypothyroidism is the most common form of thyroid disorder in India, while, Rhinitis and Nasal obstruction are frequent complaints treated on regular basis in ENT OPD. Studies show that there is relationship between Rhinitis and Nasal obstruction with hypothyroidism. To assess the improvement in symptoms associated with Rhinitis and nasal obstruction in patients with hypothyroidism after treating with levothyroxine. 50 patients presenting in ENT OPD with rhinitis and nasal obstruction and diagnosed with hypothyroidism were selected. Complete history was taken and clinical examination was performed, Nasal Obstruction Symptom Evaluation Score, (NOSE) and Peak nasal inspiratory flow rate (PNIF) were noted. Biochemically proven hypothyroid patients were treated with adequate dosage of Levothyroxine. The patients were followed up and the above-mentioned tests were repeated at regular intervals (1 month and 3 month), Changes in these readings were recorded and maintained. Significant difference was found in TSH level, NOSE questionnaire, and PNIF reading in patients with hypothyroidism after treatment with levothyroxine (P value < 0.001). This was most commonly noted to occur in young and middle-aged population of age 15 years to 50 years (88%). In our study - An attempt was made to correlate the symptomatology with hypothyroidism. Treatment with levothyroxine in patients with rhinitis, nasal obstruction and biochemically proven hypothyroidism was found to be effective in improvement of symptoms. It was found that there is significant association between hypothyroid status and rhinitis with nasal obstruction.

Understanding anti-TNF treatment failure: does serum triiodothyronine-to-thyroxine (T3/T4) ratio predict therapeutic outcome to anti-TNF therapies in biologic-naïve patients with active luminal Crohn's disease?

BACKGROUND: During illness, adaptations of the hypothalamic-pituitary-thyroid axis reduce energy expenditure, protein catabolism and modulate immune responses to promote survival. Lower serum free triiodothyronine-to-thyroxine (fT3/fT4) ratio has been linked to non-response to treatment in a range of diseases, including in biologic-treated patients with inflammatory bowel disease. AIM: To assess whether baseline serum fT3/fT4 ratio predicted primary non-response (PNR) and non-remission to infliximab and adalimumab in patients with Crohn's disease METHODS: Thyroid function tests were undertaken in stored serum from biologic-naïve adult patients with active luminal Crohn's disease immediately prior to treatment with infliximab (427 originator; 122 biosimilar) or adalimumab (448) in the Personalised Anti-TNF Therapy in Crohn's Disease study (PANTS). RESULTS: Baseline median [IQR] fT3/fT4 ratios were lower in women than men (0.30 [0.27-0.34] vs 0.32 [0.28-0.36], p < 0.001), in patients with more severe inflammatory disease, and in patients receiving corticosteroids (0.28 [0.25-0.33] vs. 0.32 [0.29-0.36], p < 0.001). Multivariable logistic regression analysis demonstrated that fT3/fT4 ratio was independently associated with PNR at week 14 (odds ratio [OR] 0.51, 95% confidence interval [CI] 0.31-0.85, p = 0.009), but not non-remission or changes in faecal calprotectin concentrations at week 54. The optimal threshold to determine PNR was 0.31 (area under the curve 0.57 [95% CI 0.54-0.61], sensitivity 0.62 [95% CI 0.41-0.74], and specificity 0.53 [95% CI 0.42-0.73]). CONCLUSIONS: Lower baseline serum fT3/fT4 ratio was associated with female sex, corticosteroid use and disease activity. It predicted PNR to anti-TNF treatment at week 14, but not non-remission at week 54.

A breakthrough-like effect of metformin reduces peripheral resistance to triiodothyronine in euthyroid, non-insulin-resistant, type 2 diabetic patients.

BACKGROUND: Type 2 diabetes is characterized, beyond the insulin resistance, by polyhormonal resistance. Thyroid hormonal resistance has not yet been described in this population of patients. Metformin is used to decrease insulin resistance, and at present, it is assumed to influence the effect of triiodothyronine, as well. METHODS: In this open-label, pilot, hypothesis-generating, follow-up study, 21 patients were included; all of them were euthyroid with drug naïve, newly diagnosed type 2 diabetes. Before and after 4 weeks of metformin therapy, fructosamine, homeostasis model assessment for insulin resistance (HOMA-IR), thyroid hormones, T3/T4 ratio, and TSH, as well as blood pressure and heart rate using ambulatory blood pressure monitor were measured. We also conducted an in vitro study to investigate the possible mechanisms of T3 resistance, assessing T3-induced Akt phosphorylation among normal (5 mM) and high (25 mM) glucose levels with or without metformin treatment in a human embryonal kidney cell line. RESULTS: Metformin decreased the level of T3 (P < 0.001), the ratio of T3/T4 (P = 0.038), fructosamine (P = 0.008) and HOMA-IR (P = 0.022). All these changes were accompanied by an unchanged TSH, T4, triglyceride, plasma glucose, bodyweight, blood pressure, and heart rate. In our in vitro study, T3-induced Akt phosphorylation decreased in cells grown in 25 mM glucose medium compared to those in 5 mM. Metformin could not reverse this effect. CONCLUSION: Metformin seems to improve T3 sensitivity in the cardiovascular system in euthyroid, type 2 diabetic patients, the mechanism of which may be supracellular.

Rapid Differential Diagnosis of Thyrotoxicosis Using T3/T4 Ratio, FT3/FT4 Ratio and Color Doppler of Thyroid Gland.

CONTEXT: Establishing the etiology of thyrotoxicosis is of utmost importance to plan the appropriate line of therapy. However, certain scenarios such as absence of pathognomonic clinical features of Graves' disease in some patients, or non-availability of radionuclide scanning and newer generation TRAb assays especially in resource-poor settings, necessitates utilization of other, simple and effective measures to differentiate between the two common causes of thyrotoxicosis, Graves' disease (GD) and Destructive thyroiditis (DT). AIMS: The aim of this work was to study the role of FT3/FT4 ratio, T3/T4 ratio and color flow Doppler ultrasound in treatment-naïve patients with thyrotoxicosis, in comparison to Tc-99m pertechnetate thyroid scanning in the differentiation of thyrotoxicosis due to GD and DT. MATERIALS AND METHODS: Clinical data was collected from all study subjects. Thyroid function tests including FT3, FT4, T3, T4 and TSH, TSH Receptor Antibody (TRAb), Technetium Tc 99m pertechnetate scan and the mean peak systolic velocity in inferior thyroid artery (mean PSV-ITA) by color Doppler ultrasonography of thyroid gland was done in all patients. RESULTS: A total of 83 treatment-naïve patients with thyrotoxicosis (61 with GD and 22 with DT) were studied. Mean PSV-ITA, T3/T4 ratio and FT3/FT4 ratio showed a sensitivity of 85.2%, 73.8%, and 77.04%, and a specificity of 90.9%, 72.7%, and 59.09%, respectively. The three parameters in combination yielded a positive predictive value of 100% in the diagnosis of Graves' disease. CONCLUSION: Results of this study show that inferior thyroid artery blood flow, T3/T4 ratio and FT3/FT4 ratio are useful parameters in the differentiation between GD and DT.

The relationship between thyroid function tests and sleep quality: cross-sectional study.

INTRODUCTION: The relationship between sleep and hormones have long been recognized. Studies indicated that sleep quality is one of the major modulatory effects on the endocrine system. In this study, we aimed to assess the serum concentration of thyroid hormones in individuals who suffered from low quality sleep. MATERIAL AND METHODS: Based on the Pittsburgh Sleep Quality Index and ISMA Stress questionnaire, we divided 83 participants into two groups. Forty-one individuals with low quality sleep group and 42 with good quality sleep group, all from the male students of a medical school in Tehran, Iran, participated in this descriptive and cross-sectional study. Then, serum levels of thyroid hormones including free T3, free T4, and TSH were assessed and compared between two groups. RESULTS: There were a significant increase in serum levels of FT4 (p=0.01) and TSH (p=0.02). There were also meaningful correlations between sleep score and stress score (p=0.008) as well as stress score and FT4 (p=0.03) in the case group. CONCLUSIONS: The current study showed that thyroid function tests (T4 and TSH) significantly rose in the poor sleep condition. We also found correlations between sleep score, stress score, and FT4 in the poor sleep condition group that suggest low sleep quality can affect thyroid hormones.

The role of CSE1L expression in cervical lymph node metastasis of larynx tumors.

INTRODUCTION: According to international reports, 30-40% of all head and neck cancers are larynx cancers, comprising 1-2.5% of all cancer types. Cervical nodal involvement has been reported to be 40% and 65% in T3 and T4 cases, respectively. Five-year survival in patients with cervical lymph node metastasis has been demonstrated to be 50% lower compared to patients with no metastasis. Chromosome segregation like 1 protein; is a DNA fragment isolated by Brinkmann et al. in 1995 that corresponds to yeast chromosome segregation protein. Studies on the effect of chromosome segregation like 1 protein expression in head and neck tumors are rare and it has been shown that nuclear chromosome segregation like 1 protein is over-expressed in these studies where gastrointestinal and breast tumors over-expressed cytoplasmic chromosome segregation like 1 protein. OBJECTIVE: Chromosome segregation like 1 protein may regulate the proliferation and metastasis of T3-T4 glottic larynx cancer. The aim of this study is to show the relationship between chromosome segregation like 1 protein expression and cervical lymph node metastasis of T3-T4 glottic larynx cancer. METHODS: A total of 57 male patients who were operated for T3-T4 glottic cancer in a tertiary referral hospital was included in this study. There were 28 patients with cervical lymph node metastasis and 29 patients without lymph node metastasis. Immunohistochemistry was carried out on formalin-fixed, paraffin-embedded archival glottic larynx tumour tissue. According to the percentage of immunoreactive cells, chromosome segregation like 1 protein status was analyzed. RESULTS: Among the patients, who had no cervical lymph node metastasis, 15 patients showed weak nuclear staining, 12 patients showed moderate nuclear staining and only 2 patients showed high nuclear staining for chromosome segregation like 1 protein. Among the patients who had cervical lymph node metastasis, 18 patients showed high nuclear staining, 9 patients showed moderate staining and only one patient showed weak staining for chromosome segregation like 1 protein. None of the metastatic patients showed cytoplasmic staining and only one patient in the non-metastatic group showed cytoplasmic staining for chromosome segregation like 1 protein. There was a positive correlation between nuclear chromosome segregation like 1 protein expression and cervical lymph node metastasis (r = 0,668) and it was statistically significant (p < 0,001). CONCLUSION: Chromosome segregation like 1 protein expression is correlated with lymph node metastasis in T3-T4 glottic cancers. This may change the approach to cervical node treatment in patients with glottic cancers in future.

LT4 and Slow Release T3 Combination: Optimum Therapy for Hypothyroidism?

CONTEXT: Levothyroxine (LT4) is recommended as replacement therapy for thyroid hormone deficiency. However, some hypothyroid patients receiving LT4 therapy do not feel as well as healthy subjects. This article aimed to review current knowledge regarding LT4 monotherapy versus LT4+LT3 combination therapy and propose future directions regarding LT4+slow release T3 combination treatment for hypothyroidism. EVIDENCE ACQUISITION: We searched PubMed and Scopus using related keywords. RESULTS: The LT4 monotherapy causes higher serum free T4 (fT4), subnormal serum free T3 (fT3), and fT3/fT4 ratio in one-fourth of patients. The LT4+LT3 combination therapy increases serum T3 and fT3 concentrations and may normalize the fT3/fT4 ratio. However, the primary outcomes, including thyroid hormone deficiency, anxiety, depression, and quality of life, may not be better in LT4+LT3 combination therapy than in LT4 monotherapy. Recent surveys show that combination therapy is on the rise, in particular, due to patient demand. The LT4 plus slow-release LT3 preparation has shown promising results in improving serum thyroid hormone concentrations. CONCLUSIONS: The beneficial effect of LT4+LT3 combination therapy is not clear, and the safety of long-term therapy is yet under question. More scientific well-designed research projects are required in this field.

Lymph Nodes Dissection in Elderly Patients with T3-T4 Laryngeal Cancer.

OBJECTIVE: To explore the survival value of lymph node dissection (LND) in elderly patients with T3-T4 laryngeal cancer, analyze the risk factors of lymph node metastasis, and construct a preoperative prediction model. MATERIALS AND METHODS: The study included 996 patients aged ≥65 years with laryngectomy confirmed T3-T4 laryngeal cancer queried from Surveillance, Epidemiology and End Results (SEER) database between 2010 and 2017. Propensity score matching (PSM) was applied to balance the effects of confounding factors. Kaplan-Meier (K-M) analysis and competitive risk model were used to compare the overall survival (OS) and cancer-specific survival (CSS) between LND and no-LND (N-LND) group. Combined with risk factors of multivariate logistic regression, a nomogram was built to predict lymph node metastasis preoperatively. The performance was assessed in the training set and the validation set, and internal validation was assessed. RESULTS: Among the cohort, 822 patients underwent LND and 410 patients had positive lymph nodes. The OS and CSS of patients who underwent LND were not better than that of N-LND patients (P>0.05). The prognosis of patients with lymph node metastases was significantly worse than that of negative patients (P<0.05). On multivariate logistic regression, supraglottis cancer, tumor size >5cm and grade 3-4 classification were associated with significantly greater odds of lymph node metastasis. The nomogram showed favorable predictive efficacy and good calibration (in the training cohort C-index=0.700; in the validation cohort C-index=0.721). CONCLUSION: For elderly patients with T3-T4 laryngeal cancer, LND did not bring significant survival values. Supraglottis cancer, tumor size >5cm and grade 3-4 classification were independent risk factors of lymph node metastasis, which means poor prognosis. The nomogram developed was an easy-to-use tool for lymph node prediction.

Long-term prognostic analysis of different treatment strategies for T 3-T 4 nasal sinus adenocarcinoma / 中华放射肿瘤学杂志

Objective:To investigate the prognosis and influencing factors of different treatment strategies in T 3-T 4 nasal sinus adenocarcinoma. Methods:The data of 93 cases of T 3-T 4 stage nasal sinus adenocarcinoma diagnosed from 2006 to 2018 were retrospectively analyzed. All patients were divided into combined operation group and non-operation group. The survival status and failure mode after corresponding treatment were analyzed. The enumeration data were analyzed by Chi-square test or Fisher's exact test. Survival analysis was performed by Kaplan-Meier method. Univariate analysis was conducted by log-rank test. Multivariate prognostic analysis was performed by Cox model. Results:The average follow-up time in the whole cohort was 81.3 months (18-156 months). By the end of follow-up, a total of 38.7% (36/93) of patients had local recurrence, 14.0% (13/93) had distant metastasis, 17.2% (16/93) had local recurrence complicated with distant metastasis, and 28.0% (26/93) were stable. The overall 2-, 5-, and 10-year overall survival (OS) and progression free survival (PFS) rates were 83.5%, 59.3%, 31.8% and 73.6%, 40.7% and 25.3%, respectively. In univariate analysis, the PFS and OS of patients aged 46-64 years old (all P<0.001), male ( P=0.022, P=0.001), patients with lesions located in the maxillary sinus ( P=0.001, P<0.001), adenoid cystic carcinoma ( P=0.001, P<0.001), non-invasion of orbital / clivus ( P=0.041, P<0.001), GTV P dose>64 Gy ( P=0.003, P=0.006) and N 1 stage ( P=0.014, P=0.014) were statistically different among different treatment modes. Multivariate analysis showed that age ≥65 years old ( P=0.012, P=0.005), orbital / clival invasion ( P<0.001, P=0.005), and GTV p dose ≤64 Gy ( P<0.001, P=0.011) were the independent adverse prognostic factors affecting PFS and OS in T 3-T 4 stage nasal sinus adenocarcinoma. Conclusions:The local failure rate of T 3-T 4 stage nasal sinus adenocarcinoma is high after treatment. Age, orbital / clival invasion, and GTV p dosage are the independent adverse prognostic factors. Surgery based intervention is superior to other treatment strategies.

Scintigraphic Profile of Thyrotoxicosis Patients and Correlation with Biochemical and Sonological Findings.

INTRODUCTION: Thyrotoxicosis is a spectrum of disorder with a rather common clinical presentation with different aetiologies. The aetiological diagnosis is important as the management differs. It is essential to accurately diagnose the cause before starting treatment. Scintigraphy of thyroid helps in differentiating accurately the various causes. USG is routinely being advocated and T3/T4 ratio has also been used. AIM: This study aims to evaluate the scintigraphic profile of thyrotoxicosis patients and to correlate biochemical and USG findings with scintigraphy. MATERIALS AND METHODS: A total of 60 newly diagnosed thyrotoxicosis patients based on biochemical reports were included in the study. They underwent further evaluation with ultrasonography and 99mTc scintigraphy. RESULTS: Of 60 patients of thyrotoxicosis, 45 cases were of Grave's disease, 10 cases were of thyroiditis and five cases were of Toxic Multinodular Goiter (MNG). The clinical characteristics were helpful in establishing the diagnosis in only six (10%) patients who presented with classic features of Grave's disease with ophthalmopathy. T3/T4 ratio greater than 20 was seen only in 29 (66%) patients of Grave's disease and also in three (33.33%) of thyroiditis patients. USG had a sensitivity and specificity of 81.82% and 93.75% in diagnosing Graves' disease and 100% and 82.4% in diagnosing thyroiditis respectively. CONCLUSION: Clinical findings do not help in accurately delineating aetiological diagnosis of thyrotoxicosis. Serum T3/T4 ratio when used as a criterion has marked overlap between the various conditions causing thyrotoxicosis. USG has reasonable sensitivity however, misses many cases of early Grave's disease. Follow up scintigraphy helps in a small population with resolving thyroiditis or early Grave's disease where the initial scintiscan is normal or inconclusive.

Prospective serum metabolomic profile of prostate cancer by size and extent of primary tumor.

Two recent investigations found serum lipid and energy metabolites related to aggressive prostate cancer up to 20 years prior to diagnosis. To elucidate whether those metabolomic profiles represent etiologic or tumor biomarker signals, we prospectively examined serum metabolites of prostate cancer cases by size and extent of primary tumors in a nested case-control analysis in the ATBC Study cohort that compared cases diagnosed with T2 (n = 71), T3 (n = 51), or T4 (n = 15) disease to controls (n = 200). Time from fasting serum collection to diagnosis averaged 10 years (range 1-20). LC/MS-GC/MS identified 625 known compounds, and logistic regression estimated odds ratios (ORs) associated with one-standard deviation differences in log-metabolites. N-acetyl-3-methylhistidine, 3-methylhistidine and 2'-deoxyuridine were elevated in men with T2 cancers compared to controls (ORs = 1.38-1.79; 0.0002 ≤ p ≤ 0.01). By contrast, four lipid metabolites were inversely associated with T3 tumors: oleoyl-linoleoyl-glycerophosphoinositol (GPI), palmitoyl-linoleoyl-GPI, cholate, and inositol 1-phosphate (ORs = 0.49-0.60; 0.000017 ≤ p ≤ 0.003). Secondary bile acid lipids, sex steroids and caffeine-related xanthine metabolites were elevated, while two Krebs cycle metabolites were decreased, in men diagnosed with T4 cancers. Men with T2, T3, and T4 prostate cancer primaries exhibit qualitatively different metabolite profiles years in advance of diagnosis that may represent etiologic factors, molecular patterns reflective of distinct primary tumors, or a combination of both.

Alteration of thyroid hormone concentrations in juvenile Chinook salmon (Oncorhynchus tshawytscha) exposed to polybrominated diphenyl ethers, BDE-47 and BDE-99.

Polybrominated diphenyl ethers (PBDEs) have been used as flame-retardants in consumer products and are currently detected in salmon globally. The two most predominant PBDE congeners found in salmon are BDE-47 (2,2',4,4'-tetrabromodiphenyl ether) and BDE-99 (2,2',4,4',5-pentabromodiphenyl ether). In the present study, groups of juvenile Pacific Chinook salmon were fed five environmentally relevant concentrations of either BDE-47 (0.3-552 ng total PBDEs/g food), BDE-99 (0.3-580 ng total PBDEs/g food), or nearly equal mixtures of both congeners (0.7-690 ng total PBDEs/g food) for 39-40 days. The concentrations of circulating total thyroid hormones, thyroxine (T4) and 3,5,3'-triiodothyronine (T3), were measured using a hormone-specific time-resolved fluoroimmunoassay to determine if PBDE exposure disrupts the hypothalamic-pituitary-thyroid endocrine axis. The concentrations of both circulating T4 and T3 were altered in juvenile salmon by dietary uptake of BDE-99. Exposure to BDE-47 did not alter either T3 or T4 circulating hormone concentrations. However, exposure to a mixture of BDE-47 and BDE-99 reduced T3 in fish with lower concentrations of total whole body PBDEs than with either congener alone at equivalent PBDE whole body concentrations. Accordingly, the disruption of PBDEs on circulating thyroid hormone concentrations has the potential to impact a number of critical functions in juvenile salmon including growth, parr-smolt transformation, and immunological processes.

The impact of comorbidities on the benefits of prolonged androgen ablation in patients with T3-4 prostate cancer treated with external beam radiation therapy.

PURPOSE: To determine whether the survival benefit associated with prolonged androgen deprivation therapy (ADT) and radiotherapy (EBRT) varies with baseline estimates of overall survival in cT3-4 prostate cancer patients (PCa). METHODS AND MATERIALS: In 1997, the BC Cancer Agency adopted as standard a policy of prolonged ADT (>18months) with EBRT for locally advanced PCa. Two cohorts of cT3-T4 PCa treated with EBRT were selected: 1993-1995 (early: N=725) and 1999-2001 (late: N=584). Duration of ADT and baseline prognostic factors (age, clinical stage, grade, presenting PSA, and Charlson index (CCI)) were abstracted from charts. Estimates of 10-year (E10) survival using an age-adjusted CCI were calculated and patients were grouped into low (<60%), medium (60-90%) and high (>90%) E10. In each E10 group, actual overall survivals were compared by era using log rank test. RESULTS: There were 318 low, 544 medium, and 447 high E10 patients with median follow-up of 11.1years. Gleason grade and T stage were not statistically different between E10 groups. As expected, median age and baseline CCI were higher in lower E10 groups (p<0.0001). Overall survival was higher in the late era, but varied with E10 group: low (43% vs. 49%, p=0.54), medium (55% vs. 64%, p=0.02) and high (66% vs. 77%, p=0.01). CONCLUSION: The policy of prolonged ADT with EBRT provides a survival benefit that varies with baseline risk of death from other causes. Absolute benefit from ADT is largest in those with medium or high E10.