Immunohistochemical Localization of p53 in Human Thyroid Neoplasms: Correlation with Biological Behavior

Molecular analyses of thyroid tumors have documented mutations in the tumor suppressor p53 gene almost exclusively in anaplastic carcinomas. In contrast, immunohistochemistry has localized p53 in differentiated papillary and follicular thyroid cancers. To establish the significance of p53 immunolocalization in these lesions, 78 thyroid tumors of follicular derivation were examined. All tumors were classified by strict criteria and the extent of tumor was determined morphologically. Immunohistochemical staining for p53 was performed on paraffin sections of formalin-fixed tumor tissue. The results of staining were correlated with diagnosis, tumor extent and clinical outcome. Immunopositivity for p53 was diffuse and strong in all five anaplastic carcinomas examined. There was no staining in five of six follicular adenomas. Four of nine follicular carcinomas had some degree of nuclear staining, but this was focal; all nine tumors were confined to the thyroid at the time of examination. Of 49 papillary carcinomas, 26 were intrathyroidal, and 7 of these were occult; there was no p53 positivity in any occult lesion and only 5 of the 19 palpable lesions stained. In contrast, among 23 papillary carcinomas with extrathyroidal extension or metastases, only 9 were negative for p53 immunoreactivity. Five of seven tall cell papillary carcinomas and one of two insular carcinomas had p53 immunopositivity and this correlated with aggressive behavior. These results support the tumorigenic role of p53 mutations postulated for anaplastic thyroid carcinomas and indicate that localization of p53 by immunohistochemistry is a useful prognostic index of clinical behavior in differentiated thyroid carcinomas of follicular cell derivation.     

Comparison of microscopic (pT3a) and gross extravesical extension (pT3b) in pathological staging of bladder cancer: analysis of patient outcomes

Objective

To determine the prognostic value of pT3 bladder urothelial carcinoma substaging in patients without lymphatic involvement.

Patients and methods

Pathologic and clinical data were reviewed on patients who underwent radical cystectomy for urothelial carcinoma between 1991 and 2010. Of the 460 reviewed patients, 74 patients were diagnosed with pathologic T3No urothelial carcinoma of the bladder. The impact of pathologic substaging (pT3a vs. pT3b) was examined to determine the effect on overall and disease-specific survival.

Results

Five years disease-specific and overall survival rates were 46.9 % and 39.6 % for patients with pT3aNo tumor, whereas these ratios were 34.4 and 30.3 %, respectively, for patients with pT3bNo tumor (p > 0.05). Mean disease-specific survival time was 43.94 ± 6.50 months for pT3aNo, while it was 39.01 ± 7.19 months for pT3bNo (p = 0.539). In multivariate cox regression analysis, age (p = 0.459), gender (p = 0.710), urinary diversion type (p = 0.088), and pT3 substaging (p = 0.554) were not noticed as an independent predictive factor for survival.

Conclusion

Macroscopic extravesical extension (pT3b) is not associated with a worse outcome than pT3a disease in lymph node-negative cases of bladder urothelial carcinoma.     

Is there any association between disturbed gastrointestinal visceromotor and sensory function and impaired quality of life in functional dyspepsia?

Background Functional dyspepsia (FD) is now categorized into the epigastric pain syndrome (EPS) and the postprandial distress syndrome (PDS). However, the role of disturbed gastric emptying and sensory function for the reduction of health‐related quality of life (HRQOL) has not yet been studied in EPS and PDS. Methods A total of 300 refractory FD patients and 450 healthy blood donors (BD) were studied. BD were stratified in subjects with (BD+) and without (BD?) concomitant FD symptoms. Gastric motor and sensory function, generic and disease‐specific HRQOL [physical (PCS) and mental component summary (MCS)] and affective disorders were assessed. Twenty randomly selected BD?, 50 BD+ (36 PDS, 72%), and 110 FD (95 PDS, 86.4%) patients had additional function testing. Key Results Health‐related quality of life was significantly reduced in FD patients (PCS = 40.7 ± 8.8, MCS = 39.7 ± 11.3, both P < 0.0001) compared to BD+ (PCS = 52.0 ± 7.6, MCS = 49.0 ± 9.4) and BD? (PCS = 56.0 ± 4.3, MCS = 52.8 ± 7.2). GET (t_½, min) was significantly (both P < 0.0001) longer in FD patients (143.0 ± 7.3) compared to BD+ (101.1 ± 6.3) and BD? (73.8 ± 7.6). FD patients scored significantly higher for ‘pain’ (P < 0.0001) and ‘nausea’ (P = 0.023), there was no difference for ‘fullness’ compared to BD. Impairment of GET was not associated with HRQOL. In FD patients, an augmented symptom response to the test meal (fullness, nausea) was associated with MCS, there was no difference between FD patients with EPS or PDS. Conclusions & Inferences In EPS and PDS, delayed gastric empting and altered sensory function are disease markers but not directly linked to the severity of HRQOL impairment or clinical presentation of FD.     

Urinary neutrophil gelatinase-associated lipocalin is associated with preeclampsia in a cohort of Turkish women

Purpose: We investigated the optimal cut-off level for urinary neutrophil gelatinase-associated lipocalin (NGAL) in preeclamptic patients to confirm the diagnosis.

Methods: Urinary NGAL concentrations were measured by specific enzyme-linked immunosorbent assay (ELISA).

Results: Patients with preeclampsia had significantly higher urinary NGAL concentrations than controls (mean: 387 ng/ml vs. 188 ng/ml, respectively; P< 0.001). Using a cutoff value 252 ng/ml for urinary NGAL to confirm diagnosis of preeclampsia, sensitivity, and specificity were 92% and 91%, respectively.

Conclusion: Urinary NGAL concentrations were significantly elevated in women with preeclampsia versus normotensive controls.     

Induction chemotherapy with cisplatin and 5-fluorouracil followed by chemoradiotherapy or radiotherapy alone in the treatment of locoregionally advanced resectable cancers of the larynx and hypopharynx: results of single-center study of 45 patients

BACKGROUND: Induction chemotherapy with cisplatin and fluorouracil and radiotherapy is an effective alternative to surgery in patients with carcinoma of the larynx and hypopharynx who are treated for organ preservation. METHODS: We designed a protocol to evaluate the possibility of organ preservation in patients with advanced, resectable carcinoma of the larynx and hypopharynx. Forty-five eligible patients who were followed up between April 1999 and May 2001 were enrolled. Initially, these patients were treated with two cycles of induction chemotherapy consisting of cisplatin, 20 mg/m2/day on days 1 to 5, and 5-fluorouracil, 600 mg/m2/day by continuous infusion on days 1 to 5. Patients who had a complete response to chemotherapy were treated with definitive radiotherapy; patients who had a partial response to chemotherapy were treated with chemoradiotherapy. Cisplatin, 35 mg/m2/week, was introduced throughout the duration of radiotherapy. Patients who had no response or progressive disease underwent surgery with postoperative radiotherapy. Patients with N2 or N3 positive lymph nodes underwent neck dissection after the treatment. RESULTS: The mean age was 56.6 years (range, 34-75 years). The overall response rate to induction chemotherapy was 71.1%, with a 17.8% complete response rate and 53.3% partial response rate. With a median follow-up of 13.7 months, 23 (51.1%) of all patients and 63.3% of surviving patients have had a preservation of the larynx or hypopharynx and remain disease free. The most common toxicities were nausea and vomiting and mucositis. CONCLUSION: Organ preservation, with multimodality treatment, may be achievable in some of the patients with resectable, advanced larynx or hypopharynx cancers without apparent compromise of survival.     

The effects of tonsillectomy and adenoidectomy on serum IGF-I and IGFBP3 levels in children

OBJECTIVE: Obstructive adenoid and tonsillar hyperplasia may present with retardation of growth. Interruption of growth hormone-insulin-like growth factor I axis resulting from abnormal nocturnal growth hormone secretion is among the postulated causes. Growth hormone (GH) mediates its anabolic effects on tissues through insulin-like growth factor I (IGF-I). Most of the circulating IGF-I is bound to insulin-like growth factor binding protein 3 (IGFBP3). The objective of this study is to determine blood serum levels of IGF-I and IGFBP3 in patients with adenoid and tonsillar hypertrophy. Furthermore, we want to investigate the effect of tonsillectomy and adenoidectomy (T&A) on these levels. STUDY DESIGN: The blood serum levels of IGF-I and its binding protein IGFBP3 were examined in 41 randomly selected children with a diagnosis of upper airway obstruction resulting from hypertrophic tonsils and adenoids. METHODS: Blood samples were taken preoperatively and repeated at 3 to 6 months (mean, 4.3 mo) following T&A operation. Coated-tube immunoradiometric assay (IRMA) method was used to analyze IGF-I and IGFBP3 levels. RESULTS: Thirty-two of 41 children were eligible for the analysis. When the preoperative and postoperative results were compared, it was found that there was a statistically significant increase in serum IGF-I and IGFBP3 levels in these 32 children (P <.001). In 7 of the 32 patients, the preoperative serum IGF-I levels were below normal. Postoperatively these levels increased within normal range. This was also statistically significant (P = .016). CONCLUSION: These findings revealed that obstructive adenoid and tonsillar hypertrophy may cause decreased serum IGF-I levels by affecting the GH-IGF-I axis, and T&A is an effective therapeutic measure in these patients.     

A novel method for prediction of stone composition: the average and difference of Hounsfield units and their cut-off values

Purpose

The purpose of the study was to investigate the predictive value of stone measurements by including a novel method on non-contrast computed tomography (NCCT) images for stone composition.

Methods

We retrospectively evaluated patients who had stone analysis, NCCT images, and underwent percutaneous nephrolithotomy between 2013 and 2016. Patient characteristics, stone measurements on NCCT images, and stone analysis results were evaluated. Hounsfield unit (HU) values (maximum (HU_max), minimum (HU_min), and average (HU_ave) of HU values) were investigated on NCCT images. HU_diff was calculated as the difference between the HU_max and the HU_min values. Patients were divided into seven stone groups and data were compared. Then patients were separately divided into two groups according to mineral complexity (mono-mineral and multi-mineral groups) and calcium-based (calcium and other stone groups) evaluation.

Results

In the study, 115 patients were evaluated. Age, gender, HU_min, HU_max, and HU_ave were significantly different between the stone groups. HU_diff and HU_ave were found to be 341.5 HU (AUC?=?0.719, p?=?0.017) and 1051.5 HU (AUC?=?0.701, p?=?0.029) as cut-off, respectively. Seventy of 72?>?341.5 HU_diff patients and 64 of 67?>?1051.5 HU_ave patients had multi-mineral stones (p?=?0.001, OR 9.26, and p?=?0.028, OR 4.27), respectively. In multivariate analysis, >?341.5 HU_diff rate was significantly higher in multi-mineral and calcium stone groups; HU_ave was also significantly higher in the calcium stone group.

Conclusions

HU_diff and HU_ave were significant predictors of mineral complexity. HU_diff of <?341.5 HU showed 81.8% sensitivity and 67.2% specificity for identification of mono-mineral stones.

     

Differential effects of STAT5 and PI3K/AKT signaling on effector and memory CD8 T-cell survival

During viral infection, effector CD8 T cells contract to form a population of protective memory cells that is maintained by IL-7 and IL-15. The mechanisms that control effector cell death during infection are poorly understood. We investigated how short- and long-lived antiviral CD8 T cells differentially used the survival and cell growth pathways PI3K/AKT and JAK/STAT5. In response to IL-15, long-lived memory precursor cells activated AKT significantly better than short-lived effector cells. However, constitutive AKT activation did not enhance memory CD8 T-cell survival but rather repressed IL-7 and IL-15 receptor expression, STAT5 phosphorylation, and BCL2 expression. Conversely, constitutive STAT5 activation profoundly enhanced effector and memory CD8 T-cell survival and augmented homeostatic proliferation, AKT activation, and BCL2 expression. Taken together, these data illustrate that effector and memory cell viability depends on properly balanced PI3K/AKT signaling and the maintenance of STAT5 signaling.