Proposed treatment strategy for reactive hypoglycaemia.

Background/aim: Managing reactive hypoglycaemia (RH) poses challenges due to limited and often ineffective treatment options. We report a case series and draw on this to propose a stepwise treatment approach consisting of lifestyle modifications, metformin, GLP-1 analogues, and the use of flash glucose monitoring technology. Method: A retrospective review was conducted to analyse the management of 11 cases presenting with recurrent RH symptoms. Result: Two patients experienced successful resolution of symptoms through lifestyle modifications. Metformin alone was effective in treating seven out of nine patients who received pharmacological treatment. Two patients with previous upper gastrointestinal surgery showed a partial response to metformin and benefited further from additional long-acting GLP-1 analogue. Pharmacological intervention led to significant reductions in insulin and C-peptide levels in repeat mixed meal tolerance tests (P-values 0.043 for insulin and 0.006 for C-peptide). Finally, flash glucose monitoring technology was useful in early detection and preventing episodes of hypoglycaemia in one of these patients with persistent symptoms. Conclusion: These findings highlight the potential efficacy of escalated treatment strategies for RH, including the use of metformin, GLP-1 analogues, and flash glucose monitoring technology.

Use of thyroid hormones in hypothyroid and euthyroid patients: A THESIS questionnaire survey of UK endocrinologists.

OBJECTIVE: Management of hypothyroidism is controversial because of medication cost pressures and scientific uncertainty on how to address treatment dissatisfaction experienced by some patients. The objective was to investigate the experience and preferences of UK endocrinologists in use of thyroid hormones. DESIGN: Web-based survey. PATIENTS: UK endocrinologists were invited to participate. MEASUREMENTS: Responses to questionnaire. RESULTS: The response rate was 21% (272/1295). While levothyroxine monotherapy is regarded as the treatment of choice for hypothyroidism, 51% of respondents stated that combined treatment with levothyroxine and liothyronine could be considered for levothyroxine-treated patients whose symptoms persist despite normalisation of serum thyroid stimulating hormone (TSH) concentration. However, only 40% are currently prescribing such treatment, and just 23% would consider taking it themselves. A small minority prescribe desiccated thyroid extract, and those most likely to do so are aged over 60 years. Most respondents stated that they have no influence over brand or formulation of levothyroxine dispensed to their patients and expect no major differences in efficacy between different formulations. A total of 9% would prescribe levothyroxine for euthyroid enlarging goitre, and 29% for euthyroid female infertility with high titre thyroid peroxidase antibodies, despite recent trials finding no benefit. CONCLUSIONS: UK endocrine practice in management of hypothyroidism is broadly in line with international guidance. However, a minority of respondents would consider thyroid hormone supplementation in euthyroid individuals for female infertility, enlarging goitre, and other indications in which evidence of efficacy is lacking. Willingness to consider prescribing combined levothyroxine and liothyronine, for hypothyroid symptoms which persist despite normalised TSH, has increased in comparison to previous international surveys, despite inconsistent evidence of benefit.

Three-dimensional radiographic assessment of the mandibular interforaminal donor site in different vertical facial growth types.

PURPOSE: To assess volumetrically, the impact of vertical facial growth types (VFGT) on the mandibular interforaminal region as a potential bone donor site. MATERIAL AND METHODS: 60 cone beam computed tomography (CBCT) scans of adult individuals were classified in three groups according to their SN-GoGn angle: hypodivergent group (hG) (N=20), normodivergent group (NG) (N=19) and hyperdivergent group (HG) (N=21). Total harvestable bone volume (TBV), cortico-cancellous bone volume (CBV-cBV), and cortical bone surface (CBS) were evaluated. ANOVA test followed by Tukey post hoc tests were used to compare the mean continuous outcomes according to their VFGT. RESULTS: The whole sample showed a mean TBV of 1376.32±541.01mm3, CBV of 468.52±121.54mm3 and cBV of 908.73±474.71mm3. The mean CBS amounted to 782.58±146.80mm2. The comparison between the groups stated a significantly different mean TBV and cBV (-p-value<0.001). The mean CBS was significantly different (-p-value=0.015): the smallest for the NG, but not significantly different (-p-value<0.001): the highest for the HG, intermediate for the NG and the smallest for the hG. CONCLUSION: Hypodivergent individuals have the thickest cancellous bone suitable for an onlay bone graft, while hyperdivergent individuals have the thinnest bone ideal for a 3D grafting approach.

Meta-analysis of colorectal cancer follow-up after potentially curative resection.

BACKGROUND: After potentially curative resection of primary colorectal cancer, patients may be monitored by measurement of carcinoembryonic antigen and/or CT to detect asymptomatic metastatic disease earlier. METHODS: A systematic review and meta-analysis was conducted to find evidence for the clinical effectiveness of monitoring in advancing the diagnosis of recurrence and its effect on survival. MEDLINE (Ovid), Embase, the Cochrane Library, Web of Science and other databases were searched for randomized comparisons of increased intensity monitoring compared with a contemporary standard policy after resection of primary colorectal cancer. RESULTS: There were 16 randomized comparisons, 11 with published survival data. More intensive monitoring advanced the diagnosis of recurrence by a median of 10 (i.q.r. 5-24) months. In ten of 11 studies the authors reported no demonstrable difference in overall survival. Seven RCTs, published from 1995 to 2016, randomly assigned 3325 patients to a monitoring protocol made more intensive by introducing new methods or increasing the frequency of existing follow-up protocols versus less invasive monitoring. No detectable difference in overall survival was associated with more intensive monitoring protocols (hazard ratio 0·98, 95 per cent c.i. 0·87 to 1·11). CONCLUSION: Based on pooled data from randomized trials published from 1995 to 2016, the anticipated survival benefit from surgical treatment resulting from earlier detection of metastases has not been achieved.

Biotribocorrosion (tribo-electrochemical) characterization of anodized titanium biomaterial containing calcium and phosphorus before and after osteoblastic cell culture.

The purpose of this study was to investigate the relationship between the osteoblastic cells behavior and biotribocorrosion phenomena on bioactive titanium (Ti). Ti substrates submitted to bioactive anodic oxidation and etching treatments were cultured up to 28 days with MG63 osteoblast-like cells. Important parameters of in vitro bone-like tissue formation were assessed. Although no major differences were observed between the surfaces topography (both rough) and wettability (both hydrophobic), a significant increase in cell attachment and differentiation was detected on the anodized substrates as product of favorable surface morphology and chemical composition. Alkaline phosphatase production has increased (≈20 nmol/min/mg of protein) on the anodized materials, while phosphate concentration has reached the double of the etched material and calcium production increased (over 20 µg/mL). The mechanical and biological stability of the anodic surfaces were also put to test through biotribocorrosion sliding solicitations, putting in evidence the resistance of the anodic layer and the cells capacity of regeneration after implant degradation. The Ti osteointegration abilities were also confirmed by the development of strong cell-biomaterial bonds at the interface, on both substrates. By combining the biological and mechanical results, the anodized Ti can be considered a viable option for dentistry.

Role of adenosine deaminase and the influence of age on the diagnosis of pleural tuberculosis.

OBJECTIVE: 1) To determine factors affecting adenosine deaminase (ADA) levels in pleural fluid (PF), and 2) to establish the optimal ADA cut-off level for a Brazilian population. DESIGN: ADA levels in PF of 309 patients were analysed to investigate pleural effusion. All patients were evaluated for age, sex and presence of tuberculosis (TB) based on a positive pleural biopsy. Differences in ADA levels between groups were analysed using Kruskal-Wallis one-way analysis of variance. Logistic regression analysis was also carried out to predict the occurrence of TB. ADA cut-off levels were selected using the receiver operating characteristic (ROC) curve. RESULTS: The mean PF ADA level was significantly higher in the tuberculous pleural group than in non-tuberculous pleural patients (63.3 ± 29 IU/l vs. 19 ± 31 IU/l, P < 0.001). There was a significant correlation between PF ADA levels and age: for patients aged ⩾45 years, the ROC curve for ADA had an area under the curve of 0.91. An ADA level of 29 IU/l resulted in a sensitivity of 88.6% and specificity of 91.5%. CONCLUSIONS: There is a significant negative correlation between PF ADA level and age. The use of a lower ADA cut-off reduces the number of false-negative results.

Impact of adjuvant chemotherapy in completely resected stage IIIA non-small cell lung cancer.

AIM: Outcome of patients with locally advanced non-small-cell lung cancer (NCSLC) is generally poor, with five-year survival rate of only 23%, when patients are treated with surgery only. The presentation of positive adjuvant therapy trials in NSCLC has changed clinical practice, doubling the number of patients with completely resected NSCLC referred for adjuvant chemotherapy since 2004. Furthermore, few large studies described a large number of stage III patients in non-Asiatic patients and they showed controversial results about survival in completely resected stage IIIA NSCLC. The objective of this study was to evaluate the impact of adjuvant chemotherapy in completely resected stage IIIA NCSLC, administered on a routine basis, outside clinical trials. METHODS: This is a retrospective study of patients with stage IIIA NCSLC treated between 1990 and 2008, and included in a continuous, consecutive database. Inclusion criteria were: age >18 years, complete surgical resection, and pathologically confirmed as stage IIIA. The following clinical data were obtained: age, gender, performance status, histological type, chemotherapy regimens, status at last follow-up and hospital where the treatment occurred. Kaplan-Meier's method was used to determine actuarial survival. Differences in survival were determined by Breslow and log rank analyses. RESULTS: According to these inclusion criteria, 415 patients were considered for the present study. The median follow-up time of all patients was 38.2 months. The adjuvant chemotherapeutic treatment affected survival significantly (P <0.001). Also the type of chemotherapeutic treatment affected survival (P ≤0.001). CONCLUSION: Cisplatin-based adjuvant chemotherapy was beneficial in patients who had a completed resected stage IIIA carcinoma.

Pulmonary metastasectomy for colorectal cancer: long-term survival and prognostic factors.

BACKGROUND: Despite the development of novel chemotherapy and biological agents, surgery is still an important option for patients with pulmonary metastases. Predictors of survival usually include disease-free interval, histology of the primary tumor, number of metastases and complete resection. The aim of this study was to report the outcomes of patients with pulmonary metastases from colorectal carcinoma submitted to surgical resection, and to identify prognostic factors that significantly affect overall survival. METHODS: We retrospectively analyzed 120 patients with previously treated colorectal carcinoma that had developed pulmonary metastases, admitted between 1990 and 2006. Overall survival was estimated using Kaplan-Meier analysis. The log-rank and Breslow tests were used to compare survival differences for each variable. Multivariate analyses to determine the independent prognostic factors for overall survival were performed using the Cox proportional hazard model as identified by the univariate analyses. RESULTS: The median follow-up was 20.3 months (range: 3.27-134.2 months). The patients included in this study underwent a total of 165 thoracotomies (mean of 1.37 thoracotomies/patient). The median overall survival for all patients was 34.73 months, with an estimated 5-year survival rate of 24.39%. Multivariate analyses identified unilateral lesions, neoadjuvant chemotherapy at lung resection and complete resection as independent prognostic factors for overall survival. CONCLUSIONS: These results indicate that prognostic factors identified in studies on pulmonary metastasectomy for all primary tumors should be interpreted carefully for patients with possibility of pulmonary metastasectomy from colorectal carcinoma.

Pulmonary metastasectomy from head and neck tumors.

AIM: Isolated pulmonary metastases from head and neck cancer occur in 20%-30% of patients affected by head and neck neoplasms. Surgical resection is well accepted as a standard approach to treat metastases from head and neck cancer isolated to the lungs. Many studies reported overall five-year survival ranging from 20% to 30%. The aim of this study is to determine demographics and clinical treatment-related variables associated with long-term (60-month) overall survival in patients with lung metastases undergoing pulmonary metastasectomy from head and neck tumors. METHODS: A retrospective review was performed of patients who were admitted with lung metastases and underwent thoracotomy for resection after treatment of the primary tumor. Data were collected regarding primary tumor features, demographics, treatment, and outcome. RESULTS: Median follow-up time of all patients was 36.4 months (range: 0-288 months). The postoperative complication rate was 14.4%, and the 30-day mortality rate was 0%. The 60-month overall survival rate for all patients was 35.5%. Multivariate analysis identified the number of nodules at CT scan, the disease-free interval, and histological type as independent prognostic factors for overall survival. CONCLUSION: Lung metastasectomy is a safe and potentially curative procedure for patients with treated primary tumors. A select group of patients can achieve long-term survival after lung resection.

Imaging and lung cancer.

Lung cancer remains the most common cause of cancer-related mortality in Scotland, accounting for 28.9% of all cancer deaths in 2007. Current guidelines recommend assessment of patient fitness and operability by a multidisciplinary team when selecting management options. Two of the most important prognostic markers are the stage of disease and ECOG performance status. In 1996, the International Association for the Study of Lung Cancer (IASLC) launched a worldwide TNM staging project to create international databases that would be used to continue the excellent efforts of Dr. Cliff Mountain, who pioneered this approach to lung cancer staging in 1973. Successive iterations of tumor, nodule, metastasis (TNM) staging for lung cancer have addressed shortcomings identified by the oncology community. Similarly, the IASLC recognized that it is important that further revisions continue to be made to ensure that the international staging system for lung cancer remains fit for its purpose. The last work of the International Staging Committee (ISC) was the conduct of the study that informed the seventh edition of the international staging system for lung cancer, in 2010. This review of image and staging in non small cell lung cancer (NSCLC), includes a summary of the different noninvasive tests currently available for staging non small cell lung cancer.

ErbB receptors and fatty acid synthase expression in aggressive head and neck squamous cell carcinomas.

SUMMARY: Overexpression of ErbB receptors is frequent in head and neck squamous cell carcinomas (HNSCC) and seems to be correlated with tumor progression and metastasis. Fatty acid synthase (FASN), the key lipogenic enzyme responsible for the endogenous synthesis of fatty acids, is regulated by ErbB2 and overexpressed in several human malignancies. METHODS: This study was performed to examine the immunohistochemical expression patterns of ErbB1, ErbB2, ErbB3, ErbB4, and FASN in a tissue microarray, containing 33 representative areas from aggressive primary HNSCC (whose patients had distant metastasis), and 21 matched lung metastasis. RESULTS: Strong correlation among the expression of ErbB family receptors was found (ErbB1-ErbB2 P = 0.008, ErbB1-ErbB4 P = 0.018, EbB2-ErbB3 P = 0.001, ErbB2-ErbB4 P = 0.006, ErbB3-ErbB4 P=0.012) in the HNSCC. FASN expression was significantly associated with ErbB2 (P = 0.024). Lymphatic permeation was correlated with ErbB3 (P = 0.033) and histological grade with ErbB4 staining (P = 0.050). ErbB1 and ErbB2 were found mainly in patients with smoking habit (P = 0.011 and P = 0.027), and ErbB2 was associated with alcohol consumption and clinical stage (P = 0.014 and P = 0.031). Finally, FASN was overexpressed in lung metastasis, in comparison with matched HNSCC samples (P = 0.006). CONCLUSIONS: The results showed that high FASN immunohistochemical expression is a feature of HNSCC lung metastasis, and ErbB1-ErbB2, ErbB1-ErbB4, ErbB2-ErbB3, ErbB2-ErbB4, and ErbB3-ErbB4 expression levels are correlated in the respective primary tumors, being ErbB2 the preferred coexpression partner of all the other ErbB receptors.

Pertinent cell population to characterize periodontal disease.

The purpose of this in situ study is to quantify the inflammatory cell subsets and the area fraction (AA%) occupied by collagen fibers in human healthy and diseased (four different stages) gingival connective tissue in order to establish a possible correlation between periodontal disease resulting in collagen breakdown and specific inflammatory cell subsets. Paraffin gingival tissue sections from eight healthy controls (group 0), 10 patients with gingivitis (group 1), 10 patients with moderate periodontitis (group 2) and 10 patients with severe periodontitis (group 3) were immunohistochemically investigated using antibodies against CD-45+, CD-3+, CD-8+, CD-20+, CD-68+, and EMA+ (plasma cells). The AA% occupied by gingival collagen fibers significantly decreased from 54.12% in group (0) to 38.58% in group (1), to 31.87% in group (2), and to 25.46% in group (3). In progressive lesions of periodontal disease, CD-3(+) and CD-8+ cell numbers were increased in early stages within the connective tissue, while CD-20+ cell numbers were increased only in late stages. On the other hand, EMA+, CD-68+ and CD-45+ cell numbers were progressively increased from group (0) to group (3). We demonstrated that CD-68+ monocyte/macrophages, CD-45+ leukocyte common antigen and notably EMA+ plasma cells are pertinently correlated with the severity of periodontal disease and related collagen breakdown.

The defensive role of lysozyme in human gingiva in inflammatory periodontal disease.

BACKGROUND AND OBJECTIVE: The presence of lysozyme in human gingiva has not previously been demonstrated. In this study, we looked for evidence for the potential role of lysozyme as a protector of gingival elastic fibres. The objective of this study was also to determine the ex vivo susceptibility to hydrolysis of gingival elastic fibres from patients with or without periodontal disease by human leukocyte elastase and by human cathepsin G. MATERIALS AND METHODS: Using gingival tissue sections from eight control, 10 gingivitis and 10 periodontitis patients, we evaluated the area fraction occupied by gingival elastic fibres (after selective staining) by the use of automated image analysis. In the ex vivo experiments, serial tissue sections from four control, four gingivitis, four young periodontitis and four aged periodontitis patients were submitted to the action of human leukocyte elastase and cathepsin G, after which enzymatic activities were determined by image analysis. Indirect immunodetection of lysozyme was also done on tissue sections for all patients included in this study. RESULTS: Large variations of the area fraction occupied by elastic fibres were observed in human gingiva from young and aged patients with and without periodontal disease. In control and gingivitis patients, leukocyte elastase and cathepsin G had high comparable elastin solubilizing activities. With young and aged periodontitis patients, the two serine proteinases had weak elastin solubilizing activities. Lysozyme appeared to be present at the periphery of gingival elastic fibres in periodontitis patients. CONCLUSION: Lysozyme can be considered an important natural protector of elastic fibres in pathological gingiva.

Management of neuroendocrine tumors: a meeting of experts from Latin America.

A panel of experts from Latin America convened in Brazil, in May of 2007, for consensus recommendations regarding the management of neuroendocrine tumors (NETs) of the gastrointestinal tract and pancreas. The recently introduced World Health Organization classification of NETs represents a step forward, but the former classification of carcinoids into foregut, midgut and hindgut is still likely to be useful in the near future. Macroscopic description of the tumor should be followed by light microscopic examination and immunohistochemical staining, whereas other techniques might not be widely available in Latin America. Surgery remains the mainstay of treatment for patients with potentially curable tumors, and adequate selection is paramount in order to optimize treatment results. Regarding systemic therapy, patients with well-differentiated tumors or islet-cell carcinomas may be categorized as having indolent disease, while patients with poorly differentiated, anaplastic, and small-cell carcinomas, or with atypical carcinoids, may be approached initially as having aggressive disease. Somatostatin analogues play a cytostatic role in indolent tumors, and chemotherapy may play a role against other, more aggressive NETs. Obviously, there is an urgent need for novel therapies that are effective against NETs.

High frequency of immature dendritic cells and altered in situ production of interleukin-4 and tumor necrosis factor-alpha in lung cancer.

INTRODUCTION: Antigen-presenting cells, like dendritic cells (DCs) and macrophages, play a significant role in the induction of an immune response and an imbalance in the proportion of macrophages, immature and mature DCs within the tumor could affect significantly the immune response to cancer. DCs and macrophages can differentiate from monocytes, depending on the milieu, where cytokines, like interleukin (IL)-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF) induce DC differentiation and tumor necrosis factor (TNF)-alpha induce DC maturation. Thus, the aim of this work was to analyze by immunohistochemistry the presence of DCs (S100+ or CD1a+), macrophages (CD68+), IL-4 and TNF-alpha within the microenvironment of primary lung carcinomas. RESULTS: Higher frequencies of both immature DCs and macrophages were detected in the tumor-affected lung, when compared to the non-affected lung. Also, TNF-alpha-positive cells were more frequent, while IL-4-positive cells were less frequent in neoplastic tissues. This decreased frequency of mature DCs within the tumor was further confirmed by the lower frequency of CD14-CD80+ cells in cell suspensions obtained from the same lung tissues analyzed by flow cytometry. CONCLUSION: These data are discussed and interpreted as the result of an environment that does not oppose monocyte differentiation into DCs, but that could impair DC maturation, thus affecting the induction of effective immune responses against the tumor.

Expression of a dendritic cell maturation marker CD83 on tumor cells from lung cancer patients and several human tumor cell lines: is there a biological meaning behind it?

The present paper shows, for the first time, the membrane expression of the dendritic cell maturation marker CD83 on tumor cells from lung cancer patients. CD83 was also detected on freshly cultured fibroblast-like cells from these tissues and on several adherent human tumor cell lines (lung adenocarcinomas P9, A459 and A549, melanomas A375 and C81-61, breast adenocarcinomas SKBR-3 and MCF-7 and colon carcinoma AR42-J), but not in the non-adherent MOT leukemia cell line. CD83 may have immunosuppressive properties and its expression by cancer cells could have a role in facilitating tumor growth.

In vitro breast cancer cell lethality of Brazilian plant extracts.

In this study we screened the cytotoxicity of 1220 plant extracts obtained from 351 plants belonging to 74 families occurring in the Amazon and Atlantic rain forests against MCF-7 human breast adenocarcinoma cell lines. All extracts were tested at a dose of 100 microg/mL. Only 11 aqueous or organic extracts belonging to the Annonaceae, Apocynaceae, Araceae, Clusiaceae, Flacourtiaceae, Leguminosae, Olacaceae and Violaceae showed marked lethal activity. Vismia guianensis and Annona hypoglauca extracts showed the greatest lethal activity.

In vitro prostate cancer cell growth inhibition by Brazilian plant extracts.

In the present study, 1220 plant extracts obtained from 352 plants belonging to 73 families that grow in the Amazon and Atlantic rain forests were screened for cytotoxicity against PC-3 prostate cancer cell lines. Extracts were tested in the single dose of 100 microg/mL. Activity was observed in 17 aqueous or organic extracts belonging to Annonaceae, Apocynaceae, Araceae, Capparaceae, Commelinaceae, Flacourtiaceae, Lecythidaceae, Leguminosae, Passifloraceae, Rutaceae, and Violaceae.

Response to chemotherapy in patients with lung metastases: how many nodules should be measured?

OBJECTIVE: With the introduction of cross-sectional imaging methods the number of lesions per patient that can be evaluated is frequently large and most oncologists and study protocols use only one lesion or a few 'representative' lesions to evaluate chemotherapy response. Intra-patient response variability can therefore affect evaluation reproducibility. This study evaluates intra-individual variation in response to chemotherapy in patients with multiple lung metastases. METHODS: We prospectively studied chest CT images of patients with solid tumors and pulmonary metastases under systemic chemotherapy being evaluated for tumor response. The response of 566 pulmonary nodules in 41 evaluations was determined by both WHO and RECIST criteria in order to determine intra-individual tumor response variation. RESULTS: There was almost perfect agreement between the WHO and the RECIST criteria for the evaluation of tumor response. High intra-individual variability of tumor response was observed in a significant proportion of the evaluations. A new nodule was the main criterion for determination of disease progression. A mean of 35% of the total number of nodules of a patient have a response evaluation different from that calculated with all the nodules together. CONCLUSIONS: Intra-individual variation in tumor response of pulmonary metastases is elevated in some patients. Selecting any or some nodules for response evaluation could significantly influence therapeutic response perception.