A combination of radiomic features, clinic characteristics, and serum tumor biomarkers to predict the possibility of the micropapillary/solid component of lung adenocarcinoma.

BACKGROUND: Invasive lung adenocarcinoma with MPP/SOL components has a poor prognosis and often shows a tendency to recurrence and metastasis. This poor prognosis may require adjustment of treatment strategies. Preoperative identification is essential for decision-making for subsequent treatment. OBJECTIVE: This study aimed to preoperatively predict the probability of MPP/SOL components in lung adenocarcinomas by a comprehensive model that includes radiomics features, clinical characteristics, and serum tumor biomarkers. DESIGN: A retrospective case control, diagnostic accuracy study. METHODS: This study retrospectively recruited 273 patients (males: females, 130: 143; mean age ± standard deviation, 63.29 ± 10.03 years; range 21-83 years) who underwent resection of invasive lung adenocarcinoma. Sixty-one patients (22.3%) were diagnosed with lung adenocarcinoma with MPP/SOL components. Radiomic features were extracted from CT before surgery. Clinical, radiomic, and combined models were developed using the logistic regression algorithm. The clinical and radiomic signatures were integrated into a nomogram. The diagnostic performance of the models was evaluated using the area under the curve (AUC). Studies were scored according to the Radiomics Quality Score and Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis guidelines. RESULTS: The radiomics model achieved the best AUC values of 0.858 and 0.822 in the training and test cohort, respectively. Tumor size (T_size), solid tumor size (ST_size), consolidation-to-tumor ratio (CTR), years of smoking, CYFRA 21-1, and squamous cell carcinoma antigen were used to construct the clinical model. The clinical model achieved AUC values of 0.741 and 0.705 in the training and test cohort, respectively. The nomogram showed higher AUCs of 0.894 and 0.843 in the training and test cohort, respectively. CONCLUSION: This study has developed and validated a combined nomogram, a visual tool that integrates CT radiomics features with clinical indicators and serum tumor biomarkers. This innovative model facilitates the differentiation of micropapillary or solid components within lung adenocarcinoma and achieves a higher AUC, indicating superior predictive accuracy.

A new tool to predict aggressive lung cancer types before surgeryWe developed a tool to help doctors determine whether lung cancer is one of the more dangerous types, called micropapillary (MPP) or solid (SOL) patterns, before surgery. These patterns can be more harmful and spread quickly, so knowing they are there can help doctors plan the best treatment. We looked at the cases of 273 lung cancer patients who had surgery and found that 61 of them had these aggressive cancer types. To predict these patterns, we used a computer process known as logistic regression, analyzing CT scan details, health information, and blood tests for cancer markers. Based on CT scans, our tool was very good at predicting whether these patterns were present in two patient groups. However, predictions using only basic health information like the size of the tumor and whether the patient smoked needed to be more accurate. We found a way to make our predictions even better. Combining all information into one chart, known as a nomogram, significantly improved our ability to predict these dangerous cancer patterns. This combined chart could be a big help for doctors. It gives them a clearer picture of the cancer's aggressiveness before surgery, which can guide them to choose the best treatment options. This approach aims to offer a better understanding of the tumor, leading to more tailored and effective treatments for patients facing lung cancer.

Intraductal papillary bile duct adenocarcinoma and gastrointestinal stromal tumor in a case of neurofibromatosis type 1.

We report our experience with a synchronous case of gastrointestinal stromal tumor (GIST) and intraductal papillary neoplasm of the bile duct (IPNB) in an elderly woman with neurofibromatosis type 1 (NF-1). A 72-year-old woman presented with a 2-mo history of right upper abdominal pain unrelated to diet and indigestion. Fourteen years earlier, she had been diagnosed with NF-1, which manifested as café au lait spots and multiple nodules on the skin. Computed tomography (CT) revealed a multilocular low-density mass with septation, and mural nodules in the right hepatic lobe, as well as a 1.7-cm-sized well-demarcated enhancing mass in the third portion of the duodenum. The patient subsequently underwent right hepatectomy and duodenal wedge resection. We present here the first report of a case involving a synchronous IPNB and GIST in a patient with NF-1. Our findings demonstrate the possibility of various tumors in NF-1 patients and the importance of diagnosis at an early stage.

Circulating Epithelial Cells in Intraductal Papillary Mucinous Neoplasms and Cystic Pancreatic Lesions.

OBJECTIVES: Circulating epithelial cells (CECs) are identified in the blood of patients with intraductal papillary mucinous neoplasms (IPMNs) despite the absence of malignancy. We assessed the blood of patients undergoing resection for IPMN or other benign pancreatic lesions for CECs. METHODS: Peripheral blood was collected from 26 patients prior to pancreatic resection and filtered by the ISET (Isolation by Size of Epithelial Tumor Cells) method. Circulating epithelial cells were identified with antibodies to cytokeratin and Pdx1 (pancreas and duodenal homeobox protein 1), a pancreas marker. RESULTS: Nineteen patients underwent resection of an IPMN without associated malignancy. Eleven patients (58%) had cytokeratin-positive CECs. Circulating epithelial cells were significantly more likely to be found in patients with IPMNs with high-grade dysplasia (P = 0.04). In addition, 10 of the 11 patients with cytokeratin-positive CECs also had separate populations of cytokeratin-positive, Pdx1-positive CECs, suggesting a pancreatic source. Dual-staining CECs were more frequently found in patients with high-grade dysplasia (P = 0.04). Patients with IPMNs were significantly more likely to have pan-cytokeratin CECs in the blood compared with those without IPMNs (P = 0.01). CONCLUSIONS: Circulating epithelial cells staining with potential pancreas-specific markers have been found in patients with IPMNs, even without malignancy. Circulating epithelial cells may help to differentiate patients with high-grade IPMN from lower grades of dysplasia and other pancreatic cysts.

Association of PDCD1 gene markers with susceptibility to thyroid cancer.

PURPOSE: PD-1 receptor is a co-signaling molecule with an important role in regulation of T-lymphocyte activity. Correlation between PD-1 gene (PDCD1) polymorphisms and some immune-related diseases has been reported before. In current study, we aimed to investigate the association of PD-1 polymorphisms at positions +7146 G/A (PD-1.3) and +7785 C/T (PD-1.5), as well as the emerged haplotypes with susceptibility to thyroid carcinoma. METHODS: One hundred five patients with confirmed thyroid cancer and 160 healthy individuals as control group were enrolled. Genotypes were identified using PCR-RFLP and nested PCR-RFLP methods. Results were analyzed by Arlequin and SPSS software packages. RESULTS: Analysis revealed a significant increase in the frequency of PD-1.5 mutant T allele and heterozygous CT genotype in patients with thyroid cancer in comparison with controls [79 (37.7%) vs. 71 (22.2%), and 51 (48.6%) vs. 51 (31.9%), p = 0.0001 and p = 0.009, receptively]. CC genotype at this position observed to be significantly higher among controls than the patients [99 (61.9%) vs. 40 (38.1%), p = 0.0002]. There were no significant differences in the frequencies of genotypes and alleles at locus PD-1.3 between patients and control group. Despite this, GT haplotype emerged from both positions (PD-1.3 G and PD-1.5 T) has also been observed with significant increased frequency between patients and controls [70 (36.8%) vs. 71 (22.2%), p = 0.0005]. CONCLUSION: As the first study to investigate two mentioned polymorphisms in thyroid cancer, current study confirmed the association of PD-1.5 C/T polymorphism and a haplotype resulted from both loci, PD-1.3 and PD-1.5, with susceptibility of Iranians to thyroid cancer.

Verification of WFA-Sialylated MUC1 as a Sensitive Biliary Biomarker for Human Biliary Tract Cancer.

BACKGROUND: The diagnostic accuracy of biliary cytology is limited. A novel sandwich enzyme-linked immunosorbent assay that combined Wisteria floribunda agglutinin (WFA) and anti-sialylated mucin 1 (MUC1) monoclonal antibody to target bile samples was recently developed. This study was designed to verify the diagnostic accuracy of WFA-sialylated MUC1 as a sensitive biliary biomarker for human biliary tract cancer. METHODS: Bile samples from 27 patients with benign disease and 174 patients with biliary tract cancer were analyzed. A receiver-operated characteristic curve analysis for biliary WFA-sialylated MUC1 and serum CA19-9 levels was performed to determine the cutoff value for the prediction of the presence of biliary tract cancer. RESULTS: Biliary WFA-sialylated MUC1 levels were significantly higher in the biliary tract cancer group compared with the benign group (P < 0.001). The cutoff value of WFA-sialylated MUC1 for discriminating biliary tract cancer was 10.5. The sensitivity of WFA-sialylated MUC1 in discriminating biliary tract cancer was much higher (82.2 %) than that of cytology (23.6 %) when this cutoff value was used. The cutoff value of serum CA19-9 for discriminating biliary tract cancer was 38 IU/L in the same cohort. All patients with biliary WFA-sialylated MUC1 and serum CA19-9 above the cutoff values had biliary tract cancer, and no patient with benign disease was categorized in this group. CONCLUSIONS: Biliary WFA-sialylated MUC1 is a useful biomarker for the differentiation of biliary tract cancer. The sensitivity of WFA-sialylated MUC1 was clearly higher than that of biliary cytology. Further data collection is necessary to validate the clinical usefulness of this biomarker.

Serum levels of the progesterone induced blocking factor do not precipitously rise in women with gynecologic cancer in contrast to women exposed to progesterone.

PURPOSE: To determine if an immunomodulatory protein (progesterone induced blocking factor [PIBF]) that is progesterone induced and found in higher concentration during pregnancy is similarly found with increased levels in women with gynecologic cancers. MATERIALS AND METHODS: A newly developed enzyme linked immunoabsorbent assay (ELISA) assay was used to measure PIBF in the sera of six women with various gynecologic cancers and compare them to five controls (three with benign tumors and two having gynecologic procedures for non-tumors. RESULTS: The PIBF levels in women with gynecologic cancer did not rise precipitously as historical controls of women or men exposed to progesterone. The two highest PIBF levels of the 11 subjects were in women with gynecologic cancer. CONCLUSIONS: The data suggest that if PIBF helps cancer cells to evade immune surveillance, it probably operates through an intracytoplasmic presence. If an increase in sera PIBF could have been detected in women with gynecologic cancer, then this ELISA test could have been used to detect tumor recurrence. Future studies may concentrate on evaluating intracytoplasmic PIBF to possibly help determine which tumors may respond to progesterone antagonist receptors.

Expression of serum miR-200a, miR-200b, and miR-200c as candidate biomarkers in epithelial ovarian cancer and their association with clinicopathological features.

BACKGROUND: MicroRNAs (miRs) have been implicated in the etiology of various human cancers. The aim of this study was to investigate the association of the expression of three members--miR 200a, miR 200b, and miR 200c belonging to the miR-200 family with clinicopathological characteristics and their impact on the progression of epithelial ovarian cancer (EOC). MATERIALS AND METHODS: Total RNA from serum was isolated by Trizol method, polyadenylated, and reverse transcribed into cDNA. Expression levels of miR-200a, miR-200b, and miR-200c were detected by using miRNA qRT-PCR. We measured miR expression in 70 serum samples of EOC patients with matched controls using U6 snRNA as a reference. Levels of miR expression was compared with distinct clinicopathological features. RESULTS: Expression of miR-200a was found to be greater than six-fold (p = 0.01), miR-200b and miR-200c greater than three-fold (p = 0.01) in comparison with matched normal controls. Association of miRNA expression with clinicopathological factors and progression was statistically evaluated. The expression levels of miR-200a and miR-200c were found to be significantly associated with disease progression (p = 0.04 and p < 0.001, respectively). miR-200a overexpression was found be associated with tumor histology and stage. Patients with lymph node metastasis showed significant elevation of miR-200c (p = 0.006). The AUC in ROC curve also indicated that serum levels of miR-200a and miR-200c might be worthwhile as a diagnostic tool in the near future. CONCLUSION: Our findings suggest that miR-200a, miR-200b, and miR-200c overexpressions are associated with the aggressive tumor progression and be recognized as reliable markers to predict the prognosis and survival in EOC patients.

Interleukin 27 -964A > G genetic polymorphism and serum IL-27p28 levels in Chinese patients with papillary thyroid cancer.

The aim of this study was to investigate the association between a potentially functional polymorphism (rs153109, -964A > G) in the promoter region of interleukin-27 (IL-27) gene and the risk of papillary thyroid cancer (PTC) in a Chinese population. Genotype of IL-27 -964A > G polymorphism was determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Serum IL-27p28 levels were determined using enzyme-linked immunosorbent assay (ELISA). No significant difference was noticed in IL-27 -964A > G polymorphism between PTC patients and healthy controls in the overall analysis. However, analysis of clinical features showed that PTC patients carrying the GG genotype or G allele had significantly decreased risks for developing lymph node metastasis compared with those carrying the AA genotype or A allele (GG vs. AA: OR = 0.38, 95 % CI, 0.20-0.72; G vs. A: OR = 0.63, 95 % CI, 0.44-0.86). Furthermore, ELISA results demonstrated that serum IL-27p28 levels were significantly decreased in PTC patients compared with those in controls (P < 0.05). Serum IL-27p28 levels in healthy controls with the GG genotype were significantly high compared with those carrying AA genotype or the AG genotype (P < 0.05). In conclusion, our results suggest that IL-27 -964A > G polymorphism may be associated with the decreased risk for lymph node metastasis of PTC.

Prognostic significance of thyroglobulin antibody epitopes in differentiated thyroid cancer.

CONTEXT: Thyroglobulin antibodies (TgAbs) are surrogate markers of disease recurrence or persistence in differentiated thyroid cancer (DTC). However, the prognostic significance of TgAb heterogeneity in DTC has not been investigated. OBJECTIVE: To evaluate the relationship between TgAb epitope specificities and clinical outcomes in DTC patients. DESIGN: We studied 61 TgAb-positive patients with DTC, post-thyroidectomy and remnant ablation (7 males, 54 females; age-range 16-80 years, median follow-up duration 8.9 years). TgAb epitope reactivities were mapped using a panel of 10 thyroglobulin (Tg) monoclonal antibodies delineating six antigenic Tg clusters in competitive ELISA studies. Sera from 45 patients with Hashimoto's thyroiditis (HT) and 22 TgAb-positive healthy subjects served as autoimmune and healthy controls. Tg was measured by immunoradiometric assay (IRMA), electrochemiluminescence immunoassay (ECLIA), and RIA, while TgAbs was measured by ELISA and ECLIA methods. RESULTS: Samples from 26 DTC patients showed TgAb epitope restriction similar to HT patients, while 35 patients exhibited nonspecific reactivity comparable to healthy controls. DTC patients with epitope restriction had higher rates of recurrent/persistent disease (81% vs 17%, P < .001), higher median TgAb concentration (887.0 vs 82.0 kIU/L; P < .001), and a higher prevalence of thyroid lymphocytic infiltration (71.4% vs 26.8%; P < .001) compared to patients with nonspecific reactivity. Samples with epitope restriction also had a lower median Tg-IRMA/RIA ratio (3.0% vs 36.0%; P < .001) denoting greater degrees of Tg assay interference. CONCLUSIONS: TgAb epitope restriction is associated with a less favorable prognosis than nonspecific reactivity in DTC patients. TgAb epitope specificities may have prognostic value in DTC.

Markedly elevated thyroglobulin levels in the preoperative thyroidectomy patient correlates with metastatic burden.

BACKGROUND: Thyroglobulin (Tg) is a marker of tumor recurrence during thyroid cancer follow-up. While helpful in the postoperative setting, the clinical significance of preoperative Tg measurements remains unclear. The aim of the study was to determine if preoperative Tg levels are indicative of underlying malignancy or burden of metastatic disease. METHODS: A retrospective review of a prospectively collected database at an academic medical center of all thyroidectomy patients with a measured preoperative Tg level was conducted. Patients were grouped by Tg level into quartiles for initial univariate analysis, followed by multivariable analysis of variance. RESULTS: Between 2007 and 2012, 611 patients met criteria. Quartile breakdown was as follows: ≤19 ng/mL, 19.1-54 ng/mL, 54.1-151 ng/mL, and >151 ng/mL. Patients' age and gender were equivalent. Hashimoto's thyroiditis was most common in the lowest Tg group (24% versus 11%-12%, P < 0.01). While cancer was more common in the low Tg, metastatic disease was most common in the high Tg group. Specimen weight increased with increasing Tg levels (P < 0.01). Body mass index, gland weight, cancer, and Hashimoto's and metastatic disease were entered into a multivariable analysis. Only gland weight and metastatic disease correlated with Tg levels (both P < 0.001). All patients with Tg > 5000 ng/mL had metastatic disease (n = 6). CONCLUSIONS: Although preoperative Tg levels are not associated with a diagnosis of cancer, they are associated with the presence of metastatic disease. All patients with a Tg > 5000 ng/mL had significant disease burden. In patients with concern for metastatic disease, preoperative serum Tg may be a useful marker to aid decision making.

Usefulness of repeated recombinant human thyrotropin-stimulated thyroglobulin test in the post-surgical follow-up of very low-risk patients with differentiated thyroid carcinoma.

BACKGROUND: The European Thyroid Association (ETA) and the American Thyroid Association (ATA) guidelines identify subgroups of patients affected by thyroid carcinoma in whom, due to a low risk of recurrence, radioiodine ablation is not indicated. These patients are referred to as "very low-risk" according to the ETA consensus and "low-risk" patients according to the ATA guidelines. The recommended post-surgical follow-up of these patients is based upon periodical measurements of serum thyroglobulin (Tg) on levothyroxine therapy and neck ultrasound (US). AIM: To evaluate the usefulness of recombinant human (rh)-TSH Tg test and its repetition 2-3 yr afterwards in very low-risk patients. MATERIALS AND METHODS: We consecutively enrolled 32 patients with undetectable anti-Tg antibodies. Basal serum Tg levels was undetectable in all patients. RESULTS: Following rhTSH serum Tg remained undetectable in 23 (71.9%) patients (UP) and was >1.0 ng/ml in 9 (DP). US and whole body scan, revealed lymph node metastasis in 4/9 DP patients. A second rhTSH stimulation test (36.9±3.5 months later) was performed in all UP and in 5 DP patients without proven recurrences. All the UP and 4/5 formerly DP patients showed undetectable Tg stimulation. CONCLUSIONS: Our results suggest that rhTSH Tg test may be helpful in very low-risk patients, given its ability to differentiate those who may be considered "free of disease" from those who require further investigation and treatment. Repeated rhTSH Tg tests may be indicated only in patients with detectable serum Tg at prior stimulation testing.

Sustained platelet-sparing effect of weekly low dose paclitaxel allows effective, tolerable delivery of extended dose dense weekly carboplatin in platinum resistant/refractory epithelial ovarian cancer.

BACKGROUND: Platinum agents have shown demonstrable activity in the treatment of patients with platinum resistant, recurrent ovarian cancer when delivered in a "dose-dense" fashion. However, the development of thrombocytopenia limits the weekly administration of carboplatin to no greater than AUC 2. Paclitaxel has a well-described platelet sparing effect however its use to explicitly provide thromboprotection in the context of dose dense carboplatin has not been explored. METHODS: We treated seven patients with platinum resistant ovarian cancer who had previously received paclitaxel or who had developed significant peripheral neuropathy precluding the use of further full dose weekly paclitaxel. RESULTS: We were able to deliver carboplatin AUC 3 and paclitaxel 20 mg/m2 with no thrombocytopenia or worsening of neuropathic side-effects, and with good activity. CONCLUSIONS: We conclude that this regimen may be feasible and active, and could be formally developed as a "platinum-focussed dose-dense scaffold" into which targeted therapies that reverse platinum resistance can be incorporated, and merits further evaluation.

Endocrine effects of the tyrosine kinase inhibitor vandetanib in patients treated for thyroid cancer.

PURPOSE: The purpose of the study was to assess the endocrine effects of vandetanib, a multikinase inhibitor targeting RET, vascular endothelial growth factor receptor, and epidermal growth factor receptor, in 39 patients with progressive thyroid cancer included in two randomized placebo-controlled trials using vandetanib 300 mg/d. METHODS: Endocrine samplings were performed at baseline and then every 6 months. We compared differences in endocrine parameters between baseline and on vandetanib therapy or placebo. RESULTS: During vandetanib treatment, several changes were observed. 1) Calcium (P = 0.0004) and vitamin D (P = 0.001) mean replacement doses were increased; calcium level remained unchanged, but serum 25(OH) vitamin D level decreased (P = 0.001); and serum PTH (P = 0.01) and 1,25(OH)(2) vitamin D (P = 0.01) levels increased, suggesting a decreased intestinal absorption of vitamin D or lack of sun exposure as a result of photosensitization. 2) l-T(4) doses were increased (P < 0.0001) to maintain serum TSH within the normal range. 3) In male patients, total testosterone (P = 0.048), bioavailable testosterone (P = 0.03), and SHBG (P = 0.02) levels increased. Serum inhibin B decreased (P = 0.02) and stimulated FSH increased (P = 0.006), suggesting a Sertoli cells insufficiency. 4) Cortisol level increased (P = 0.007) as well as ACTH level (P = 0.03) and cortisol-binding globulin (P = 0.02), but free urinary cortisol levels remained in the normal range. None of these changes were observed in patients randomized to the placebo arm. CONCLUSION: In patients with locally advanced or metastatic thyroid cancer, the tyrosine kinase inhibitor vandetanib has several endocrine effects. Thyroid hormone, calcium, and vitamin D analog requirements increased, but consequences of the biological alterations on phosphocalcic metabolism and gonadotrope and adrenal functions are unknown.

Possible use of CA-125 level normalization after the third chemotherapy cycle in deciding on chemotherapy regimen in patients with epithelial ovarian cancer: brief report.

BACKGROUND: Cancer antigen (CA)-125 is a biomarker widely used in the monitoring of response to chemotherapy in patients with epithelial ovarian cancer (EOC). We hypothesize that normalization of the CA-125 after the third cycle of chemotherapy is an independent prognostic indicator of prolonged progression-free survival (PFS) and overall survival (OS). METHODS: A retrospective analysis of patients with a diagnosis of advanced-stage (III-IV) EOC who were treated with cytoreductive surgery and adjuvant platinum-based chemotherapy from January 1999 to June 2009 was conducted. Patient demographics and the prognostic significance of CA-125 level above the discrimination value of 35 U/mL were assessed by univariate and multivariate analyses. RESULTS: A total of 124 women met the study inclusion criteria. The median PFS for all patients with a CA-125 level of less than 35 U/mL (n = 72) after the third chemotherapy cycle was 18 months versus that of the patients with a CA-125 level of 35 U/mL or greater (n = 52) was 9 months (P < 0.0001). The median OS was 42 and 22 months, respectively (P < 0.0001). Optimal microscopically debulked patients with normalization of CA-125 after the third cycle did significantly better than those who did not normalize (PFS, 48 vs 8.3 months; OS, 59 vs 23.8 months; P < 0.0001). When patients with macroscopic disease and normalization of CA-125 after the third cycle were compared with those with CA-125 of 35 U/mL or greater, a significant difference in OS was seen between the 2 groups (47 vs 29 months, respectively; P < 0.0001). On multivariate analysis, only 2 variables were associated with poor prognosis: (1) the failure of CA-125 level to normalize after the third chemotherapy cycle (hazard ratio, 2.5; confidence interval, 1.3-4.6) and (2) the grade of the tumor (hazard ratio, 7.7; confidence interval, 1.6-37.6). CONCLUSIONS: Although hypothesis generating at this point, normalization of CA-125 level after the third chemotherapy cycle is an independent predictor of survival for patients with advanced EOC regardless of debulking status. We would propose future trials that consider switching regimens in patients who do not normalize their CA-125 after the third cycle to see if such a switch can improve PFS and OS.

Expression and prognostic significance of CEACAM6, ITGB1, and CYR61 in peripheral blood of patients with gastric cancer.

BACKGROUND: We examined CEACAM6, ITGB1, and cyr61 concentrations from patients with gastric cancers (GCs) to assess their clinical application for diagnosing and monitoring diseases. METHODS: Real-time reverse transcription-polymerase chain reaction was used to detect the expressions of CEA, CEACAM6, ITGB1, IGF1R, CK20, cyr61, and S100A4 in peripheral blood karyocyte from 82 patients with GC, 24 patients with recurrence, and 37 healthy volunteers. Receiver operating characteristics (ROC) curves were constructed. RESULTS: There were significant association between these CEACAM6, ITGB1, and cyr61 and TNM Stages and distant metastasis. The AUC of CEACAM6 was 0.884 ± 0.044 (P = 0.0001), the AUC of cyr61 was 0.833 ± 0.047 (P = 0.0001), and the AUC of ITGB1 was 0.838 ± 0.042 (P = 0.0001) by differentiating preoperative GC patients from healthy volunteers from ROC curve analysis. The AUC of CEACAM6 was 0.761 ± 0.066 (P = 0.001), the AUC of CYR61 was 0.762 ± 0.063 (P = 0.001), and the AUC of ITGB1 was 0.824 ± 0.051 (P = 0.0001), by differentiating recurrence of GC from healthy volunteers from ROC curve analysis. CONCLUSION: The method of detecting the expression of CEACAM6, ITGB1, and CYR61 in peripheral blood of GC patients was more sensitive than CEA, IGF1R, CK20, and S100A4 for the early diagnosis of metastasis and recurrence.

Risk-adapted management of differentiated thyroid cancer assessed by a sensitive measurement of basal serum thyroglobulin.

CONTEXT: Treatment and follow-up of patients thyroidectomized for differentiated thyroid carcinoma (DTC) mainly depends on the identification of the patient's risk of recurrence. Thyroglobulin (Tg) is the most important marker of persistent/recurrent disease. The recent introduction of a new, more sensitive Tg measurement allows for the early detection of the disease by measuring the basal (under L-T(4) therapy) serum Tg level without TSH stimulation. OBJECTIVE: The goal of this study is to identify the basal serum Tg threshold value that indicates recurrent disease by using a second-generation Tg assay. DESIGN AND PATIENTS: A continuous series of 425 DTC patients, all thyroidectomized and treated with (131)I after surgery and having basal Tg of no more than 1.0 ng/ml, negative anti-Tg antibodies, and a recombinant human TSH-stimulated Tg measurement was retrospectively analyzed. SETTING: The study took place at an academic hospital. RESULTS: The most accurate basal Tg value for predicting the presence of recurrent/residual disease was more than 0.15 ng/ml (sensitivity 87%, specificity 91%, negative predictive value 98.6%, and positive predictive value 47.8%). When the basal Tg level was no more than 0.15 ng/ml, the risk of disease presence was very low, even in patients classified at an intermediate or high risk. In contrast, when the basal Tg level was more than 0.15 ng/ml, the percentage of recurrent disease was relatively high (12.5% or one in eight cases) in low-risk patients. CONCLUSIONS: Basal Tg, measured using a second-generation Tg assay allows for the identification of DTC patients who are likely to remain disease free with great accuracy. This simple measurement, therefore, may be sufficient to assess the risk-adapted management of DTC patients.

Decreased 1-25 dihydroxyvitamin D3 concentration in peripheral blood serum of patients with thyroid cancer.

BACKGROUND AND AIMS: Vitamin D(3), in addition to its role in calcium homeostasis, has been recognized as playing a role in human cancer development. However, little is known about the association between vitamin D status and the development of thyroid cancer. This study aimed to investigate vitamin D metabolism by measuring 25(OH) D(3), 1-25 (OH)(2) D(3), PTH and calcium concentrations in the peripheral blood of patients with different forms of thyroid tumors. METHODS: The 25-hydroxyvitamin D(3) ,1-25- dihydoxyvitamin D(3), PTH and calcium serum levels of 50 consecutive patients with epithelial thyroid cancer 27 cases of papillary cancers (PTC), 16 follicular cancers (FTC), and seven cases of anaplastic cancers (ATC) and 34 multinodular nontoxic goiter (MNG) were measured by specific immunoassay. The control group consisted of 26 healthy volunteers. RESULTS: Our results revealed significantly lower 1-25 (OH)(2) D(3) concentration in the PTC group (22.67 pg/mL +/- 8.12; p <0.05), FTC group (16.09 pg/mL +/- 6.15; p <0.02) and ATC group (9.48 pg/mL +/- 5.18; p <0.02). Levels of 1-25 (OH)(2) D(3) varied by cancer stage and were also significantly different. A significant decrease in circulating 1-25 (OH)(2) D(3) concentration was found in patients with stage I (24.12 pg/mL +/- 6.77; p <0.05), stage II (16.93 pg/mL +/- 4.55; p <0.05), stage III (12.44 +/- 8.98; p <0.02) and in stage IVa (6.18 +/- 2.22; p <0.01). There were no significant differences when comparing serum levels of 25(OH) D(3), PTH or calcium concentrations among individuals with multinodular goiter, thyroid cancer and age- and sex-matched control volunteers. CONCLUSIONS: Our study revealed that impaired vitamin D(3) metabolism may play an important role in thyroid follicular cell oncogenesis.

The potential for serum p53 to predict the response to chemotherapy of patients with gastric cancer.

This study was designed to investigate the relationship between serum p53, tissue p53 and tissue permeability glycoprotein (P-gp) levels in gastric cancer. Serum levels of p53 were detected by enzyme-linked immunosorbent assay, and tissue p53 and P-gp levels were analysed by immunohistochemistry. In total, 63.0% of gastric cancer tissue samples tested positive for P-gp and 58.7% of samples tested positive for p53. Tissue P-gp immunoreactivity was significantly correlated with tissue p53 immunoreactivity, and both tissue p53 and P-gp immunoreactivity were significantly correlated to the degree of cancer cell differentiation. The percentage of gastric cancer patients with serum positive for p53 was 36.2%, which was significantly higher than the rate in non-cancerous gastric disease patients. Serum p53 was significantly correlated to tissue p53 and tissue P-gp, inferring that the presence of p53 in the serum could indicate the status of tissue p53 and P-gp. This could, therefore, be useful for screening for the most appropriate (lowest toxicity and highest effectiveness) drugs to use ahead of (neo)-adjuvant chemotherapy.

Features of papillary thyroid microcarcinoma in the presence and absence of lymphocytic thyroiditis.

It is known that the prevalence of lymphocytic thyroiditis (LT) is higher in patients with papillary thyroid carcinoma (PTC), that gender influences this association, and that certain features of PTC occur more frequently in patients who also have LT. These relationships have not been studied in patients with papillary thyroid microcarcinomas (PTMC), however. Therefore, we performed a study to compare the clinical and pathological features of patients with PTMC who did and did not have LT. We collected the 323 consecutive patients following excision of PTMC diagnosed as papillary carcinoma on preoperative needle aspiration cytology. We analyzed the demographic, serologic, and pathologic data of those cases with categorization into four groups based on presence of LT and neck lymph node metastasis. In all PTMC, the presence of LT did not influence the frequency of lymph node metastasis (27 of 105 [25.7%] vs. 48 of 218 [22.0%]). Among the patients with metastatic PTMC, LT was noted significantly more often in female than male patients (95.2% vs. 79.8%). In metastatic PTMC, multifocality and bilaterality was more frequent in with LT than without LT (44.4% vs. 29.2%; 29.6% vs. 14.6%). Both the presence of serum thyroglobulin antibody (TgAb; p = 0.016) and serum microsomal antibody (p = 0.013) were highly correlated with the presence of LT. Twenty-seven of 105 patients (25.7%) with PTMC with LT had nodal metastasis. Co-existing LT was noted predominantly in women, influenced more often multifocality and bilaterality of tumors, and higher frequency of metastasis to lateral compartment lymph nodes.

Serum endostatin levels in patients with metastatic and non-metastatic well-differentiated thyroid cancer.

INTRODUCTION: The growth of a tumour is limited by its neovascularisation. Angiogenesis is dependent on a dynamic balance between its activators and inhibitors. One of the most important antiangiogenic factors is endostatin. The aim of the study was to assess the usefulness of serum endostatin levels as a potential marker of metastases of well-differentiated thyroid cancer, and to estimate the effect of endogenous TSH stimulation on serum endostatin levels. MATERIAL AND METHODS: The study group consisted of 68 patients with differentiated thyroid cancer. We provided a cross-sectional analysis of the study group divided into patients with distant and/or locoregional metastases and patients with remission, and compared it with serum endostatin levels of healthy volunteers. Serum endostatin concentration was measured by ELISA kits (R & D Systems). RESULTS: Median endostatin concentration was significantly higher in patients with distant metastases than in patients with remission (141.95 v. 105.345 ng/ml, p < 0.05). This was not observed in patients with locoregional metastases. Serum endostatin levels were significantly higher in the study group, including patients with remission, than in the control group of healthy volunteers (remission v. healthy median 105.3 v. 88.1 ng/ml, p < 0.05). During endogenous TSH stimulation, endostatin levels significantly decreased (122.94 v. 93.60 ng/ml, p < 0.05). CONCLUSIONS: The study indicates that endogenous TSH stimulation plays a role in the regulation of endostatin secretion. Although median serum endostatin levels are higher in patients with distant metastases than in patients with remission, its clinical usefulness is limited due to the overlapping data between the study groups. (Pol J Endocrinol 2010; 61 (1): 7-12).