Fructosamine and glycated hemoglobin as biomarkers of glycemic control in people with type 2 diabetes mellitus and cancer (GlicoOnco study).

INTRODUCTION: Glycemic control is important to avoid diabetes complications in individuals with cancer. There is no evidence for HbA1c and fructosamine as reliable biomarkers in these conditions. There are particularities in caring for patients with diabetes and cancer that can alter these biomarkers. OBJECTIVE: The aim of this study was to evaluate HbA1c and fructosamine as glycemic biomarkers in people with type 2 diabetes and cancer, undergoing clinical or surgical oncological treatment. METHODS: The authors conducted a single-center, retrospective analysis with people who have cancer and diabetes. Comparison of glycemic biomarkers (HbA1c, fructosamine, and Self-Monitoring of Blood Glucose [SMBG]) was performed including evaluation in individuals undergoing chemotherapy, using glucocorticoids, with anemia, hypoproteinemia or with reduced estimated Glomerular Filtration Rate (eGFR). RESULTS: There was a strong positive correlation between fructosamine and HbA1c (n = 318, r = 0.66, p < 0.001) in people with diabetes and cancer even in those under chemotherapy (n = 101, r = 0.61, p < 0.001) or using glucocorticoids (n = 96, r = 0.67, p<0.001). There was a strong correlation between HbA1c and fructosamine in subjects with anemia (n = 111, r = 0.66, p < 0.001), hypoproteinemia (n = 54, r = 0.67, p < 0.001), or with eGFR ≥ 60 mL/min/1.73 m2 (n = 189, r = 0.70, p < 0.001), and moderate correlation with hypoalbuminemia (n = 21, r = 0.54, p = 0.001) and with reduced eGFR (n = 67, r = 0.57, p < 0.001). The correlations between fructosamine and HbA1c with SMBG were moderate (n = 164, r = 0.49, p < 0.001; n = 111, r = 0.55, p < 0.001, respectively), strong in subjects undergoing chemotherapy, with hypoalbuminemia or hypoproteinemia, and at least moderate, if eGFR < 60 mL/min/1.73 m2 or with anemia. CONCLUSIONS: Fructosamine and HbA1c can be used as glycemic biomarkers in people with diabetes and cancer, even in those with anemia, hypoproteinemia, or undergoing chemotherapy.

Fructosamine and glycated hemoglobin as biomarkers of glycemic control in people with type 2 diabetes mellitus and cancer (GlicoOnco study)

Abstract Introduction Glycemic control is important to avoid diabetes complications in individuals with cancer. There is no evidence for HbA1c and fructosamine as reliable biomarkers in these conditions. There are particularities in caring for patients with diabetes and cancer that can alter these biomarkers. Objective The aim of this study was to evaluate HbA1c and fructosamine as glycemic biomarkers in people with type 2 diabetes and cancer, undergoing clinical or surgical oncological treatment. Methods The authors conducted a single-center, retrospective analysis with people who have cancer and diabetes. Comparison of glycemic biomarkers (HbA1c, fructosamine, and Self-Monitoring of Blood Glucose [SMBG]) was performed including evaluation in individuals undergoing chemotherapy, using glucocorticoids, with anemia, hypoproteinemia or with reduced estimated Glomerular Filtration Rate (eGFR). Results There was a strong positive correlation between fructosamine and HbA1c (n = 318, r= 0.66, p < 0.001) in people with diabetes and cancer even in those under chemotherapy (n = 101, r= 0.61, p < 0.001) or using glucocorticoids (n = 96, r= 0.67, p<0.001). There was a strong correlation between HbA1c and fructosamine in subjects with anemia (n = 111, r= 0.66, p < 0.001), hypoproteinemia (n = 54, r= 0.67, p < 0.001), or with eGFR ≥ 60 mL/min/1.73 m2 (n = 189, r= 0.70, p < 0.001), and moderate correlation with hypoalbuminemia (n = 21, r= 0.54, p = 0.001) and with reduced eGFR (n = 67, r= 0.57, p < 0.001). The correlations between fructosamine and HbA1c with SMBG were moderate (n = 164, r= 0.49, p < 0.001; n = 111, r= 0.55, p < 0.001, respectively), strong in subjects undergoing chemotherapy, with hypoalbuminemia or hypoproteinemia, and at least moderate, if eGFR < 60 mL/min/1.73 m2 or with anemia. Conclusions Fructosamine and HbA1c can be used as glycemic biomarkers in people with diabetes and cancer, even in those with anemia, hypoproteinemia, or undergoing chemotherapy.

Variability of high-dose melphalan exposure on oral mucositis in patients undergoing prophylactic low-level laser therapy.

The present study outlines the clinical impact and risk factors of oral mucositis in 79 patients with multiple myeloma following high-dose melphalan for autologous transplant. All patients underwent daily prophylactic low-level indium gallium aluminum phosphate diode laser therapy (660 nm, 15 mW, 3.75 J/cm2, 10 s per point) from the beginning of the conditioning regimen up to day +2. Oral mucositis assessments were made daily until hospital discharge. For analysis, oral mucositis was divided into two groups according to severity: group 1, patients with oral mucositis grade

Altered expression of apoptosis-regulating miRNAs in salivary gland tumors suggests their involvement in salivary gland tumorigenesis.

Salivary gland tumors comprise a heterogeneous group of lesions with different histological features and diverse clinical pathophysiology. They account for about 3% of all head and neck tumors. Apoptosis plays an important role during morphogenesis of glandular structures, including that of the salivary gland. Recent studies have demonstrated that several microRNAs (miRNAs) are involved in the control of apoptosis. The aim of the present study was to determine the expression of apoptosis-related miRNAs (miR-15a, miR-16, miR-17-5p, miR-20a, miR-21, miR-29, and miR-34) and their target mRNAs in 25 pleomorphic adenomas, 23 mucoepidermoid carcinomas, and 10 non-neoplastic salivary gland samples by real-time RT-PCR. We observed upregulation of miR-15a, miR-16, miR-17-5p, miR-21, miR-29, and miR-34a in pleomorphic adenomas. The expression of miR-21 and miR-34a was upregulated in 91 and 74% of mucoepidermoid carcinomas, respectively. Downregulation of miR-20a was observed in 75% of pleomorphic adenomas and in 57% of mucoepidermoid carcinomas. APAF1, BAX, BCL2, BID, CASP2, CASP8, DIABLO , and TP53 transcripts were upregulated in both tumor types. BAD transcripts were upregulated in pleomorphic adenomas. CASP3 and CASP6 transcripts were upregulated in mucoepidermoid carcinomas. BCL2, CASP2, CASP6, and CASP8 proteins were mostly absent in mucoepidermoid carcinomas but expressed in few cells in pleomorphic adenomas. Our study provides evidence of alterations in the expression of apoptosis-regulating miRNAs in salivary gland tumors, suggesting possible involvement of these microRNAs in salivary gland tumorigenesis.

Expression of stem cell markers in oral cavity and oropharynx squamous cell carcinoma.

OBJECTIVES: The aim of this study was to analyze the expression of CD24, CD44, CD133, ALDH1, CD29 (integrin-ß1), and Ki-67 in squamous cell carcinoma of the oral cavity and oropharynx. STUDY DESIGN: Fifty-two tumors and 21 metastatic lymph nodes were evaluated by using immunohistochemistry. RESULTS: Seven of 52 cases (13.5%) showed positive cytoplasmic staining of aldehyde dehydrogenase 1; integrin-ß1 was expressed in 45 of 50 cases (90%); 30 of 52 cases (57.7%) had positive membranous staining of CD44; CD24 was expressed in 44 of 50 cases (88%); and three of 52 cases (5.8%) stained positively for membranous CD133. Median proliferation rate, measured by Ki-67, was 37.1% for tumors. Five-year cancer-specific survival rates for the CD44-negative and CD44-positive groups were 74% and 38%, respectively, although this difference did not reach statistical significance (P = .052). CONCLUSIONS: Our study demonstrated the expression of putative stem cell markers in squamous cell carcinoma of the oral cavity and oropharynx, with participation of CD44-positive cells in association with poor survival outcome.

Profile of apoptotic proteins in oral squamous cell carcinoma: A cluster analysis of 171 cases

Oral squamous cell carcinoma (OSCC) is the eighth most prevalent cancer worldwide. In recent large-scale studies, by immunohistochemistry and cluster analysis, several markers were associated with patient survival in various tumors. The aim of this study was to analyze the expression profiles of 23 proteins that have been linked to the inhibition (Bcl-2, Bcl-x, Bcl-xL, Bcl-2-related protein A1, BAG-1, and survivin) and promotion (Bak, Bax, Bim/Bod, Bim-Long, Bad, Bid, PUMA, Apaf-1, caspase-2, caspase-3, caspase-6, caspase-7, caspase-8, caspase-9, caspase-10, Smac/DIABLO, and cytochrome c) of apoptosis in OSCC. METHODS: Two-hundred and twenty nine cases of OSCC, arranged in a tissue microarray, were immunohistochemically analyzed, and the results were quantified on an automated imaging system. The data were analyzed using a random forest clustering method. RESULTS: Overall protein expression patterns defined two chief clusters: an anti-apoptotic cluster (142 cases) and a pro-apoptotic cluster (29 cases). These groups could not be explained by any clinical or pathological characteristic, and overall and disease-free survival did not differ between them. CONCLUSIONS: Although there was no association with survival, the cluster analysis demonstrated specific protein profiles that could be of interest for using targeted therapies: in one of the clusters, the expression of pro-apoptotic proteins was more prominent, demonstrating a pro-apoptotic profile and highlighting the importance of apoptosis during OSCC development.

Expression of stem cell-regulating miRNAs in oral cavity and oropharynx squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common tumor worldwide and is histologically heterogeneous. Studies have demonstrated the presence of stem cell markers in HNSCC, and microRNAs (miRNAs) have emerged as powerful regulators of differentiation, controlling the self-renewal of stem cells. miRNAs are non-coding RNA molecules that regulate gene expression post-transcriptionally. Many miRNAs have been described as regulators of stem cells in different types of cancer. METHODS: We have analyzed the expression of let-7a, miR-34, miR-125b, miR-138, miR-145, miR-183, miR-200b, miR-203, and miR-205 by real-time RT-PCR (qPCR), in 35 oral cavity and oropharynx squamous cell carcinoma (SCC) samples and 10 non-neoplastic oral mucosa controls, to determine possible associations between the expression of these miRNAs and clinical and pathological features of these tumors. RESULTS: We observed downregulation of miR-200b and miR-203 in 60.0% and 71.4% of the samples, respectively. Upregulation of miR-138 and miR-183 was observed in 50.0% of the samples. Downregulation of let-7a was associated with perineural invasion. Upregulation of miR-138, miRNA-145, and miR-205 was associated with advanced tumor stages, vascular invasion, and lymph node metastasis, respectively. CONCLUSIONS: Our study provides evidence of the expression of miRNAs associated with stem cell regulation in oral cavity and oropharynx SCC and the association of these miRNAs with clinical and pathological features of these tumors.

Metastatic area ratio can help predict nonsentinel node positivity in melanoma patients.

Several studies suggest that melanoma patients with a positive sentinel node biopsy (SNB) can avoid having complete nodal dissection on the basis of pathological features of the node. The aim of the study was to determine the value of metastatic area ratio as a predictive factor for nonsentinel node (NSN) positivity. A retrospective analysis was carried out of melanoma patients who underwent SNB in a single institution between 2000 and 2010. A total of 697 patients were evaluated. In 155 patients (22.2%), the SNB was positive; 146 lymphadenectomies were performed, and 23 patients in whom this was performed (15.8%) had positive NSN. In multivariate analyses, Breslow thickness of more than 2 mm, perinodal vascular invasion, and metastatic area ratio were significantly related to NSN positivity in the complete nodal dissection. Metastatic area ratio of a positive SNB can be valuable in predicting the risk of NSN positivity.

Evaluation of melanoma features and their relationship with nodal disease: the importance of the pathological report.

BACKGROUND: The pathological features of melanoma biopsies can provide significant prognostic information that can help the surgeon evaluate the risk of nodal disease. The aim of this study was to attempt to determine the relationship between pathological features of primary melanoma and nodal disease, by sentinel node biopsy (SNB) and complete node dissection (CND). METHODS: A retrospective analysis was completed of patients who underwent SNB at AC Camargo Cancer Center, São Paulo, Brazil, between 2000 and 2010. RESULTS: A total of 697 patients were evaluated. By univariate analysis, it was found that histology, Clark level, Breslow depth, mitotic index, ulceration, regression, lymphatic and perineural invasion and satellitosis were significantly associated with SNB positivity. In the multivariate analysis, it was found that Breslow depth, mitotic index, ulceration, regression, lymphatic invasion and satellitosis were significant factors. In patients with a positive SNB, the primary tumor site, Clark level and Breslow depth greater than 2 mm were significantly related to non-sentinel node (NSN) positivity by univariate analysis. By multivariate analysis, Breslow depth greater than 2 mm was the only primary tumor feature that was significantly related (p = 0.038). CONCLUSIONS: The indication of SNB should not be based solely on Breslow depth and ulceration or mitotic index. A complete evaluation of the pathological report should improve the identification of high-risk patients.

Benefits of an intraoral stent in decreasing the irradiation dose to oral healthy tissue: dosimetric and clinical features.

OBJECTIVE: To determine whether an intraoral stent may decrease radiation dose to health tissues during intensity-modulated radiotherapy (IMRT) and to evaluate the effect on mucositis. STUDY DESIGN: A total of 33 patients with tongue or floor of the mouth cancer were retrospectively evaluated and divided into 2 groups: group 1 (with stent, n = 19) and group 2 (without stent, n = 14). Data were collected on dosimetric and mucositis outcomes. RESULTS: The mean dose to the maxilla was significantly lower in group 1 (20.9 Gy) than in group 2 (35.8 Gy) (P = .05). The mean dose to the ipsilateral parotid was 35.0 Gy in group 1 vs 41.8 Gy in group 2 (P = .05). No difference was seen in the severity of mucositis between groups (P = .82). However, grade III mucositis was present in group 1 at 4 weeks after IMRT, 1 week after its occurrence in group 2. CONCLUSIONS: A stent was effective in decreasing doses to healthy structures and delaying the emergence of mucositis.

Is DWI/ADC a useful tool in the characterization of focal hepatic lesions suspected of malignancy?

OBJECTIVE: Apparent diffusion coefficient (ADC) values calculated through magnetic resonance imaging have been proposed as a useful tool to distinguish benign from malignant liver lesions. Most studies however included simple cysts in their analysis. Liver cysts are easy to diagnose, have very high ADC values and their inclusion facilitates differentiation in the ADC values between benign and malignant liver lesions groups. We prospectively evaluated the ability of ADC values to differentiate metastatic liver lesions from all benign or only solid benign liver lesions. MATERIAL AND METHODS: Sixty-seven adult cancer patients with 188 liver lesions were evaluated. Lesions were categorized as metastatic or benign throughout imaging and clinical evaluation. One hundred and five (105) metastatic lesions and 83 benign lesions including hemangiomas (37), cysts (42), adenomas (2) and focal nodular hyperplasias (2) were evaluated. ADC values were calculated for each lesion utilizing two b values (0 and 600 sec/mm2). RESULTS: The average ADC value for cysts was 2.4×10(-3) mm2/sec (CI: 2.1-2.6), for solid benign lesions was 1.4×10(-3) mm2/sec (CI: 1.1-1.7) and for metastases was 1.0×10(-3) mm2/sec (CI: 0.8-1.3). There was a difference between the ADC values of metastases and benign solid lesions (p<0.0001). With the ADC value of 1.5×10(-3) mm2/sec as a cut off it is possible to distinguish metastatic from benign liver lesions, including cysts, with an accuracy of 78%. But to distinguish metastatic from benign solid liver lesions the best ADC cut off value was 1.2×10(-3) mm2/sec and the accuracy drops to 71%. CONCLUSIONS: ADC values proved to be helpful in the distinction between metastasis and benign solid hepatic lesions. But the exclusion of cysts in the analysis point out to a lower cut off value and lower accuracy than previously reported.

Diffusion-weighted magnetic resonance imaging: biomarker for treatment response in oncology / Ressonância magnética com difusão: biomarcador de resposta terapêutica em oncologia

The authors report a case where a quantitative assessment of the apparent diffusion coefficient (ADC) of liver metastasis in a patient undergoing chemotherapy has shown to be an effective early marker for predicting therapeutic response, anticipating changes in tumor size. A lesion with lower initial ADC value and early increase in such value in the course of the treatment tends to present a better therapeutic response.

Relatamos um caso no qual a avaliação quantitativa do coeficiente de difusão aparente (ADC) de metástases hepáticas submetidas a quimioterapia se mostrou um bom preditor e marcador precoce de resposta terapêutica, antecipando alterações de tamanho. Lesão com valor inicial do ADC mais baixo e com aumento precoce deste valor no curso do tratamento tende a apresentar melhor resposta terapêutica tardia.

Interobserver agreement rate of the spontaneous breathing trial.

PURPOSE: During the mechanical ventilation weaning process, the spontaneous breathing trial (SBT) is the confirmatory test of patients' capability to breathe unassisted. However, the SBT interobserver agreement rate (its reliability) is unknown, and our objective was to evaluate it. MATERIALS AND METHODS: This is a prospective, multicentric and observational study. Patients were included when the SBT criteria were fulfilled. Two physicians and 2 respiratory therapists (RTs) rated each SBT. The SBT interobserver agreement was measured using κ statistic and also the percentage of agreement with its 95% credible interval (CrI) calculated by a Bayesian inference. RESULTS: Ninety-three distinct physicians and 91 distinct RTs rated 130 SBTs. The κ coefficient was 0.46 for physicians and 0.57 for RT, indicating a moderate interobserver agreement rate. The percentage of agreement was 87.7% between physicians (95% CrI, 81.0%-92.3%) and 86.2% between RT (95% CrI, 79.2%-91.1%). The physicians' and RT' percentage of agreement were not statistically different (P = .71). CONCLUSIONS: The SBT interobserver agreement rate is only moderate for physicians and RT. The percentage of agreement between 2 different SBT observers is 79.2% to 92.3%. Therefore, a relevant percentage of patients will have different extubation decisions depending on the SBT observer.