Expression of sarcosine metabolism-related proteins according to metastatic site in breast cancer

We aimed to evaluate the expression of sarcosine metabolism-related proteins according to site of metastatic breast cancer, and the clinical implications. Immunohistochemical staining for glycine N-methyltransferase (GNMT), sarcosine dehydrogenase (SARDH), and l-pipecolic acid oxidase (PIPOX) was performed on tissue microarrays from 162 metastatic breast cancer (bone metastases = 47, brain metastases = 39, liver metastases = 24, and lung metastases = 52). Sarcosine metabolism-related proteins showed variable expression with regard to metastatic sites. GNMT was expressed in brain and lung metastases, but not in bone and liver metastases (P = 0.016). In view of the sarcosine metabolic phenotype, high sarcosine and intermediate type were only found in the brain and lung metastases, and low sarcosine type was observed more frequently in bone and lung metastases (P = 0.047). By univariate analysis, PIPOX positivity was correlated with shorter overall survival (OS) (P = 0.031). In lung metastases, PIPOX positivity (P = 0.019) and stromal PIPOX positivity (P = 0.001) were associated with shorter OS. In conclusion, in metastatic breast cancer, sarcosine metabolism-related proteins are differently expressed according to the metastatic site. Expression of GNMT and high sarcosine type are predominantly observed in brain and lung metastases.     

Expression of sarcosine metabolism-related proteins in estrogen receptor negative breast cancer according to the androgen receptor and HER-2 status

The aim of this study is to investigate the expression of sarcosine metabolism related proteins according to androgen receptor (AR) and HER-2 status in estrogen receptor (ER) negative breast cancer and to analyze its clinical implications. Tissue microarray was constructed for a total of 334 cases of ER negative breast cancer. Immunohistochemical stain was conducted for sarcosine metabolism related proteins such as glycine N-methyltransferase (GNMT), sarcosine dehydrogenase (SARDH), and l-pipecolic acid oxidase (PIPOX). There were 131 AR positive, 205 AR negative cases and 143 HER-2 positive, 193 HER-2 negative cases. When subdividing into four groups according to AR and HER-2 status, there were 55 AR(+)/HER-2(-) cases, 76 AR(+)/HER-2(+) cases, 67 AR(-)/HER-2(+) cases and 138 AR(-)/HER-2(-) cases. GNMT and PIPOX expression was highest in the AR(+)/HER-2(-) group while expressed lowest in the AR(-)/HER-2(-) group (P<0.001). Stromal PIPOX expression was highest in the AR(-)/HER-2(+) group and lowest in the AR(-)/HER-2(-) group (P=0.010). GNMT and PIPOX expression was higher in the AR positive group compared with those of AR negative group (P=0.001, and P<0.001, respectively), while tumoral and stromal PIPOX expression showed a significant association with HER-2 positivity (P=0.006, and P=0.005, respectively). AR positive group had the highest ratio of low sarcosine type while the AR negative group had the highest ratio of null type (P<0.001). In conclusion, ER negative breast cancer showed different expression of sarcosine metabolism related proteins according to AR and HER-2 status. GNMT and PIPOX expression was high in the AR positive group while tumoral and stromal PIPOX expression was high in the HER-2 positive group.     

Risk Factors for Patients with Stage IVB Hepatocellular Carcinoma and Extension into the Heart: Prognostic and Therapeutic Implications

Purpose

To evaluate the risk factors of hepatocellular carcinoma (HCC) extension into the right atrium (RA) and determine poor prognostic factors for HCC extension to the heart.

Materials and Methods

A total of 665 patients who were newly diagnosed with HCC were analyzed retrospectively from January 2004 to July 2012. The patients were divided into two groups: 33 patients with HCC extending into the RA and 632 HCC patients during the same period. The patients with HCC extending into the RA were subdivided into shorter survival group (<2 months) and longer survival group (≥2 months).

Results

The prevalence of HCC extending to the RA was 4.96%. In multivariate analysis, a modified Union Internationale Contre le Cancer (UICC) stage higher than IVA, hepatic vein invasion, concomitant inferior vena cava and portal vein invasion, and multinodular tumor type were risk factors for HCC extending to the RA. In multivariate analysis, Cancer of the Liver Italian Program (CLIP) score >3 (p=0.016, OR: 13.89) and active treatment (p=0.024, OR: 0.054) were associated with prognostic factors in patients HCC extending into the RA. Active treatment such as radiation (n=1), transcatheter arterial chemoembolization (TACE) (n=11), Sorafenib (n=1), and combined modalities (n=2) were performed.

Conclusion

Modified UICC stage higher than IVA, vascular invasion and multinodular tumor type are independent risk factors for HCC extending to the RA. Active treatment may prolong survival in patients HCC extending into the RA.     

Microcalcification of Tumor is a Predictor of Response to Neoadjuvant Chemotherapy for Invasive Breast Carcinoma

Background

In recent years, neoadjuvant chemotherapy (NAC) is often performed for patients with unresectable breast carcinoma or without indication of breast conserving therapy. However, it is currently difficult to predict response to NAC with diagnostic imaging of breast carcinoma. In this study, we investigated imaging findings that could serve as a predictor of the response to NAC for patients with invasive breast carcinoma.

Methods

Twenty-six patients with invasive breast carcinoma who received NAC at the Division of Breast and Endocrine Surgery of Tottori University Hospital between January 2010 and May 2014 were retrospectively investigated. Their imaging findings from mammograms and ultrasonograms were reviewed. The association between findings on mammograms and ultrasonograms captured before NAC and response to treatment after NAC was examined.

Results

Of the 26 patients with invasive breast carcinoma, 19 (73%) responded well to treatment and 7 (27%) did not. Most notably, all 10 patients who had microcalcifications on mammogram responded well to treatment (53% of responders), and all patients who did not respond to treatment had no microcalcifications (P < 0.05). Of these 10 patients, 9 (90%) had microcalcifications of comedo type and one (10%) had non comedo type. As a distribution, 8 of the 10 (80%) had a clustered type of microcalcifications and the remaining 2 (20%) had a segmental type of them.

Conclusion

Microcalcifications of tumor observed in mammogram (particularly comedo type) could be a predictor of response to NAC for patients with invasive breast carcinoma.     

Overcoming the Limitations of Fine Needle Aspiration Biopsy: Detection of Lateral Neck Node Metastasis in Papillary Thyroid Carcinoma

Purpose

Ultrasound (US) and US-guided fine needle aspiration biopsies (FNAB) are considered the modalities of choice for assessing lymph nodes suspected of containing metastases, but the sensitivity of FNAB varies and is specific to the operator. We analyzed the risk of FNAB providing false negative results of lateral neck node metastasis, and evaluated diagnostic accuracy of FNAB, in patients with papillary thyroid cancer.

Materials and Methods

FNAB was performed in 242 patients suspected of having lateral neck node metastasis on preoperative imaging. Thyroglobulin in the fine-needle aspirate washout (FNA wash-out Tg) and computed tomography enhancement (Hounsfield units) were measured. Patients with negative results on FNAB were examined by intraoperative frozen section. The false negative and true negative groups were compared.

Results

Of the 242 patients, 130 were confirmed as having lateral neck node metastases. In 74 patients, the metastasis was identified by FNAB. False positive results were observed in 2 patients (0.8%) and false negatives in 58 (44.6%). Risk analysis showed that patient age <45 years (p=0.006), tumor size >1 cm (p=0.008) and elevated FNA wash-out Tg (p=0.004) were significantly associated with false negative results on FNAB. The accuracy of FNAB increased significantly when combined with FNA wash-out Tg (p=0.003).

Conclusion

To reduce the false negative rate of FNAB, patient age (<45 years), tumor size (>1 cm) and FNA wash-out Tg (>34.8 ng/mL) should be considered in preoperative planning. Accuracy may be improved by combining the results of FNAB and FNA wash-out Tg.     

Anti-Hyperglycemic and Anti-Hyperlipidemic Potential of a Polyherbal Preparation “Diabegon” in Metabolic Syndrome Subject with Type 2 Diabetes

Background

In the present study, “Diabegon” a poly-herbal preparation, with hypoglycemic activity, was evaluated for its preventive effect in metabolic syndrome subjects with type 2 diabetes and also to reveal its side effects, on liver and kidney.

Materials and Methods

Type 2 diabetic subjects with metabolic syndrome (N=58) were categorized on the basis of age and fasting blood glucose. The grouping was as follows: Group I (35–50 yrs), Group II (51–65 yrs), Group III >65 yrs, Group IV FBS<145.9, Group V FBS>145. Each group was administered 4 gm of diabegon daily. Blood glucose levels, lipid profile, liver and kidney function of the subjects were regularly monitored within 3 months of interval to 18 months.

Results

The reduction in fasting blood glucose level ranged from 12.3% (P<0.05) to 42% (P<0.001) after 18 month of therapy whereas in postprandial blood glucose, the decrease ranged from 28% (P<0.05) to 32% (P<0.05) after 18 month of therapy. Overall reductions in the individual parameters of the metabolic syndrome subjects were significantly higher in Group I. Cholesterol level decreased from 11% to 27.2% (P<0.001), triglyceride levels decreased from 24% to 55%, VLDL and LDL levels reduced by 60% & 54% respectively after 18 months of therapy. The HDL-C level increased in all groups. Moreover, diabegon administration for 1.5 years exhibited no alteration in liver and kidney function tests, which indicate its non-toxicity.

Conclusion

Our study suggests that diabegon could be included as a preventive treatment in metabolic syndrome subjects with type 2 diabetes especially for long term treatment as it efficiently shows anti-hyperglycemic and anti-lipidemic effects with no adverse impacts on the liver and kidney.     

Radiologic Outcomes According to Varus Deformity in Minimally Invasive Surgery Total Knee Arthroplasty

Purpose

To identify the accuracy of postoperative implant alignment in minimally invasive surgery total knee arthroplasty (MIS-TKA), based on the degree of varus deformity.

Materials and Methods

The research examined 627 cases of MIS-TKA from November 2005 to December 2007. The cases were categorized according to the preoperative degree of varus deformity in the knee joint in order to compare the postoperative alignment of the implant: less than 5° varus (Group 1, 351 cases), 5° to less than 10° varus (Group 2, 189 cases), 10° to less than 15° varus (Group 3, 59 cases), and 15° varus or more (Group 4, 28 cases).

Results

On average, the alignment of the tibial implant was 0.2±1.4°, 0.1±1.3°, 0.1±1.6°, and 0.3±1.7° varus, and the tibiofemoral alignment was 5.2±1.9°, 4.7±1.9°, 4.9±1.9°, and 5.1±2.0° valgus for Groups 1, 2, 3, and 4, respectively, in the preoperative stage, indicating no difference between the groups (p>0.05). With respect to the accuracy of the tibial implant alignment, 98.1%, 97.6%, 87.5%, and 86.7% of Groups 1, 2, 3, and 4, respectively, had 0±3° varus angulation, demonstrating a reduced level of accuracy in Groups 3 and 4 (p<0.0001). There was no difference in terms of tibiofemoral alignment, with 83.9%, 82.9%, 85.4%, and 86.7% of each group, respectively, showing 6±3° valgus angulation (p>0.05).

Conclusion

Satisfactory component alignment was achieved in minimally invasive surgery in total knee arthroplasty, regardless of the degree of varus deformity.     

Empirical Evidence for “Syndrome Z”: A Hierarchical 5-Factor Model of the Metabolic Syndrome Incorporating Sleep Disturbance Measures

Study Objective:

Sleep disturbances have been associated with individual components of the metabolic syndrome (“syndrome X”), and, although the concept has been proposed, it is not known whether sleep disturbances actually cluster with features of the metabolic syndrome to produce a unifying trait, “syndrome Z”. Therefore, we evaluated a second-order factor model, whereby syndrome Z was described by 5 first-order factors – insulin resistance, obesity, hypertension, dyslipidemia, and sleep disturbance – with the sleep disturbance factor defined using the apnea-hypopnea index, arousal index, percentage of sleep time with oxygen saturation less than 90%, and percentage of slow wave sleep.

Design:

Observational, cross-sectional study.

Setting:

Clinical research center.

Participants:

Five hundred thirty-three adults from the Cleveland Family Sleep Study who underwent polysomnography and were not treated by continuous positive airway pressure.

Measurements and Results:

When modeling syndrome Z as a second-order factor unifying 5 first-order factors, we observed good overall model fit (χ²/df = 3.20; CFI = 0.96; RMSEA = 0.06; SRMR = 0.05) and found that obesity was the most important determining factor (standardized loading = 0.85 ± standard error = 0.02; P < 0.01) followed by sleep disturbance (0.82 ± 0.03; P < 0.01), insulin resistance (0.67 ± 0.03; P < 0.01), hypertension (0.64 ± 0.04; P < 0.01), and dyslipidemia (0.60 ± 0.05; P < 0.01). Simultaneous multiple group analyses revealed that this model was essentially generalizable across age, race, and sex subgroups.

Conclusions:

Our results demonstrate that sleep disturbance co-aggregates with other metabolic features to represent a single unifying trait, syndrome Z. Although our model awaits validation in other populations, it provides a tool for better understanding the synergistic risk of syndrome Z, compared with syndrome X, on type 2 diabetes and cardiovascular disease in future studies.

Citation:

Nock NL; Larkin EK; Patel SR; Redline S. Empirical evidence for “Syndrome Z”: a hierarchical 5-factor model of the metabolic syndrome incorporating sleep disturbance measures. SLEEP 2009;32(5):615-622.     

Randomised controlled trial of intensive multifactorial treatment for cardiovascular risk in patients with screen-detected type 2 diabetes: 1-year data from the ADDITION Netherlands study

Background

A growing body of evidence suggests that earlier diagnosis and treatment of diabetes may be beneficial; however, definitive evidence is lacking.

Aim

To evaluate the effectiveness of an intensified multifactorial treatment on cardiovascular risk factors in patients with screen-detected type 2 diabetes.

Design of study

Randomised controlled trial.

Setting

Seventy-nine general practices in the southwestern region of the Netherlands.

Method

In this randomised trial, patients diagnosed with diabetes by screen-detection were assigned to intensified (n = 255) or routine treatment (n = 243), and followed over 1 year. Intensified treatment consisted of pharmacological treatment combined with lifestyle education to achieve haemoglobin A1c (HbA1c) <7.0%, blood pressure <135/85 mmHg, and cholesterol <5.0 mmol/l (4.5 mmol/l if cardiovascular disease was present). Health-related quality of life (HRQoL) was assessed using the Short Form (SF)-36. Analyses were performed using generalised estimating equations models.

Results

Changes in body mass index were 0.2 (routine care) versus −1.4 kg/m² (intensified treatment), P<0.001; systolic blood pressure −19 versus −33 mmHg, P<0.001; diastolic blood pressure −7 versus −12 mmHg, P<0.001; HbA1c −0.9% versus −1.1%, P = 0.03; cholesterol −0.5 versus −1.2 mmol/l, P<0.001; high-density lipoprotein cholesterol 0.1 versus 0.1 mmol/l, P = 0.26; low-density lipoprotein cholesterol −0.5 versus −1.0 mmol/l, P<0.001; triglycerides −0.3 versus −0.4 mmol/l, P = 0.71. No difference in HRQoL between the two groups was reported.

Conclusion

Intensified multifactorial treatment of patients with screen-detected diabetes in general practice reduces cardiovascular risk factor levels significantly without worsening HRQoL.     

Clinicopathlogic and immunohistochemical characteristics of triple negative invasive lobular carcinoma

Purpose

Our study is performed to find out clinicopathlogic and immunohistochemical (IHC) characteristics of triple negative invasive lobular carcinoma (ILC), as has been demonstrated in their invasive ductal counterparts.

Materials and Methods

Retrospective analysis of variable clinicopathlogic parameters and IHC stains for androgen receptor, estrogen receptor, progesterone receptor, p53, c-kit, galectin-3, cytokeratin 5 (CK5), CK5/6, vimentin, E-cadherin, epidermal growth factor receptor, and HER2 were performed in 117 cases of ILC.

Results

Eight cases (6.8%) were triple negative carcinoma (TNC), which showed higher incidence of high histologic grade than non-TNC (p = 0.019). Galectin-3 was expressed with higher incidence in tumor cells of TNC (62.5%) than those of non-TNC (7.3%) (p = 0.000). In contrast, galectin-3 was expressed with higher incidence in stromal cells of non-TNC (53.2%) than those of TNC (12.5%) (p = 0.029). CK5 and CK5/6 were not expressed in all ILCs.

Conclusion

TNC in ILC showed distinct clinicopathologic and IHC characteristics such as higher histologic grade and increased expression of galectin-3, compared to non-TNC in ILC. TNC in ILC was less frequent and did not show CK5 and CK5/6 expression when compared to TNC in invasive ductal carcinoma.     

Trace elements and Vitamin E status in Nigerian patients with prostate cancer

Background

Prostate cancer is the most common type of cancer among men.

Objectives

To investigate the trace elements (Se, Zn, Cu and Cd) and vitamin E status of some Nigerian prostate cancer (PCa) patients relative to their prostate-specific antigen (PSA) values.

Methods

Prostate cancer patients were assigned into groups 1, 2 and 3 with PSA of 5–10 ng/ml, 11–20 ng/ml and > 20 ng/ml, respectively.

Results

The results showed that the levels of whole blood superoxide dismutase (SOD) and serum Se and Zn were significantly lower (p< 0.05) in the PCa patients. Specifically, levels of SOD, Se and Zn decreased by 67%, 30% and 35%; 70%, 52% and 41%; 81%, 58% and 47%, in subjects with PSA of 5–10 ng/ml, 11–20 ng/ml and > 20 ng/ml, respectively. There were no significant differences (p> 0.05) in levels of Cu and Cd. Serum Cu/ Zn ratio were significantly higher in PCa patients. The Cu/ Zn ratios were 1: 1.2: 1.3 for subjects in groups 1, 2 and 3, respectively. Vitamin E levels in PCa patients were significantly lower and followed the order; normal > PSA (5–10) > PSA (11–20) > PSA (> 20).

Conclusions

Deficiency of vitamin E, Zn and Se may be risk factors for development of PCa.Key words: Lipid peroxidation, Prostate cancer, PSA values, Trace elements, Vitamin E     

Thoracic aortic atheroma severity predicts high-risk coronary anatomy in patients undergoing transesophageal echocardiography

Introduction

We hypothesized a relationship between severity of thoracic aortic atheroma (AA) and prevalence of high-risk coronary anatomy (HRCA).

Material and methods

We investigated AA diagnosed by transesophageal echocardiography and HRCA diagnosed by coronary angiography in 187 patients. HRCA was defined as ≥ 50% stenosis of the left main coronary artery or significant 3-vessel coronary artery disease (≥ 70% narrowing).

Results

HRCA was present in 45 of 187 patients (24%). AA severity was grade I in 55 patients (29%), grade II in 71 patients (38%), grade III in 52 patients (28%), grade IV in 5 patients (3%), and grade V in 4 patients (2%). The area under receiver operating characteristic curve for AA grade predicting HRCA was 0.83 (p = 0.0001). The cut-off points of AA to predict HRCA was > II grade. The sensitivity and specificity of AA > grade II to predict HRCA were 76% and 81%, respectively. After adjustment for 10 variables with significant differences by univariate regression, AA > grade II was related to HRCA by multivariate regression (odds ratio = 7.5, p< 0.0001). During 41-month follow-up, 15 of 61 patients (25%) with AA >grade II and 10 of 126 patients (8%) with AA grade ≤ 2 died (p= 0.004). Survival by Kaplan-Meier plot in patients with AA > grade II was significantly decreased compared to patients with AA ≤ grade II (p= 0.002).

Conclusions

AA > grade II is associated with a 7.5 times increase in HRCA and with a significant reduction in all-cause mortality.     

Clinicopathologic features and outcomes of metaplastic breast carcinoma: comparison with invasive ductal carcinoma of the breast

Purpose

Metaplastic breast carcinoma (MBC) is rare. Its clinicopathologic features and prognosis are uncertain. The aim of this study was to evaluate the clinicopathologic characteristics and outcomes in comparison with invasive ductal carcinoma (IDC).

Materials and Methods

We reviewed the data of 29 patients with MBC and 4,851 patients with IDC, who received surgery at Yonsei University Severance Hospital between 1980 and 2008. Various clinicopathologic features, recurrence free, and overall survival were investigated and compared to each other.

Results

Stage IV cases at diagnosis were more common in MBC (10.3%) than in IDC (0.9%). The incidence rates of triple negative breast cancer (TNBC) were significantly higher in MBC (84.0%) than in IDC (20.1%). Larger tumors (>2 cm) and lower tendency of axillary metastasis were frequently observed in MBC. Only one of 24 preoperative core needle biopsies (CNB) correctly diagnosed MBC. There was no significant difference in survival between the two groups.

Conclusion

MBC was characterized by a higher incidence of TNBC, larger tumor size, and lower tendency of axillary metastasis, and was difficult to diagnose with CNB. Although the incidence of stage IV disease at diagnosis was higher in MBC, the survival rates of stage I-III were comparable to those of IDC.     

Presence of a Nail in the Medullary Canal; Is It Enough to Prevent Femoral Neck Shortening in Trochanteric Fracture?

Purpose

Presence of a cephalomedullary nail (CMN) in the medullary canal has been thought as advantageous in the control of femoral neck shortening (FNS) and lag screw sliding in trochanteric fracture compared to extramedullary fixation system. However, researches on the factors that influence the degree of FNS after cephalomedullary nailing are lacking.

Materials and Methods

We observed 95 patients (mean age, 75±2.8 years) with trochanteric fractures who were treated with a CMN, and evaluated the relationship between FNS and patient factors including age, gender, fracture type (AO/OTA), bone mineral density, medullary canal diameter, canal occupancy ratio (COR=nail size/canal diameter), and tip-apex distance using initial, immediate postoperative, and follow-up radiography.

Results

Univariate regression analyses revealed that the degree of FNS was significantly correlated with fracture type (A1 versus A3, p<0.001), medullary canal diameter (p<0.001), and COR (p<0.001). Multiple regression analyses revealed that FNS was strongly correlated with fracture type (p<0.001) and COR (p<0.001).

Conclusion

Presence of a CMN in the medullary canal could not effectively prevent FNS in patients with low COR and in A3 type fracture.     

A 5′-flanking region polymorphism in toll-like receptor 4 is associated with gastric cancer in a Chinese population

Objective

Inflammation induced by H.pylori colonization in the stomach is related to the development of gastric cancer and the genetic variations of the genes involved in the immune responses modify the host response to the infection. The aim of this study was to evaluate whether polymorphisms in the toll-like receptor 4 (TLR4) gene, a key regulator of both innate and adaptive immunity, were related to the susceptibility to gastric cancer in a Chinese population.

Methods

Two variations in the 5′-flanking region of TLR4 (rs1927914 T > C and rs10759932 T > C) were genotyped by using the PCR-restriction fragment length polymorphism (RFLP) assay in a case-control study of 1,053 incident gastric cancer cases and 1,100 cancer-free controls in a Chinese population.

Results

Individuals carrying the C allele of rs10759932 had a significantly reduced risk of gastric cancer (adjusted OR = 0.81; 95%CI = 0.67-0.96), compared with the wild-type homozygote (TT), and the protective effect was not significantly different among subgroups stratified by age, sex, smoking, drinking and H.pylori infection status (P for heterogeneity > 0.05). No significant association was observed between rs1927914 and gastric cancer risk in this study population.

Conclusion

The T to C allele substitution of rs10759932 may play a protective role in gastric carcinogenesis in a Chinese population. Large studies with different ethnic populations are warranted to confirm these findings.     

Body Mass Index-Independent Metabolic Alterations in Narcolepsy with Cataplexy

Study Objectives:

To contribute to the anthropometric and metabolic phenotyping of orexin-A–deficient narcoleptic patients, and to explore a possible risk of their developing a metabolic syndrome.

Design:

We performed a cross-sectional study comparing metabolic alterations in patients with narcolepsy with cataplexy (NC) and patients with idiopathic hypersomnia without long sleep time.

Setting:

University hospital.

Patients:

Fourteen patients with narcolepsy with cataplexy and 14 sex and age-matched patients with idiopathic hypersomnia without long sleep time.

Interventions:

N/A.

Measurements and results:

Metabolic parameters were evaluated by measuring body mass index (BMI), waist circumference (also with abdominal computed tomography), blood pressure, and daily calorie intake (3-day diary). Chronotypes were assessed through the morningness-eveningness questionnaire. Lumbar puncture for cerebrospinal fluid orexin-A determination and HLA typing were performed. Patients with narcolepsy with cataplexy (all HLA DQB1*0602 positive and with cerebrospinal fluid orexin-A levels < 110 pg/mL) had a higher BMI and BMI-independent metabolic alterations, namely waist circumference, high-density lipoprotein cholesterol, and glucose/insulin ratio (an insulin resistance index), with respect to patients with idiopathic hypersomnia without long sleep time (cerebrospinal fluid orexin-A levels > 300 pg/mL). Despite lower daily food intake, patients with narcolepsy with cataplexy displayed significant alterations in metabolic parameters resulting in a diagnosis of metabolic syndrome in more than half the cases.

Conclusions:

BMI-independent metabolic alterations and the relative hypophagia of patients with narcolepsy with cataplexy, as compared with patients with idiopathic hypersomnia without long sleep time, suggest that orexin-A influences the etiology of this phenotype. Moreover, considering that these dysmetabolic alterations are present from a young age, a careful metabolic follow-up of patients diagnosed with narcolepsy with cataplexy is mandatory.

Citation:

Poli F; Plazzi G; Dalmazi GD; Ribichini D; Vicennati V; Pizza F; Mignot E; Montagna P; Pasquali R; Pagotto U. Body mass index-independent metabolic alterations in narcolepsy with cataplexy. SLEEP 2009;32(11):1491-1497.     

Outcomes of Gleason Score ≤8 among High Risk Prostate Cancer Treated with 125I Low Dose Rate Brachytherapy Based Multimodal Therapy

Purpose

To investigate the role of low dose rate (LDR) brachytherapy-based multimodal therapy in high-risk prostate cancer (PCa) and analyze its optimal indications.

Materials and Methods

We reviewed the records of 50 high-risk PCa patients [clinical stage ≥T2c, prostate-specific antigen (PSA) >20 ng/mL, or biopsy Gleason score ≥8] who had undergone ¹²⁵I LDR brachytherapy since April 2007. We excluded those with a follow-up period <3 years. Biochemical recurrence (BCR) followed the Phoenix definition. BCR-free survival rates were compared between the patients with Gleason score ≥9 and Gleason score ≤8.

Results

The mean initial PSA was 22.1 ng/mL, and mean D90 was 244.3 Gy. During a median follow-up of 39.2 months, biochemical control was obtained in 72% (36/50) of the total patients; The estimated 3-year BCR-free survival was 92% for the patients with biopsy Gleason scores ≤8, and 40% for those with Gleason scores ≥9 (p<0.001). In Cox multivariate analysis, only Gleason score ≥9 was observed to be significantly associated with BCR (p=0.021). Acute and late grade ≥3 toxicities were observed in 20% (10/50) and 36% (18/50) patients, respectively.

Conclusion

Our results showed that ¹²⁵I LDR brachytherapy-based multimodal therapy in high-risk PCa produced encouraging relatively long-term results among the Asian population, especially in patients with Gleason score ≤8. Despite small number of subjects, biopsy Gleason score ≥9 was a significant predictor of BCR among high risk PCa patients after brachytherapy.     

Expression of autophagy related proteins in invasive lobular carcinoma: comparison to invasive ductal carcinoma

The aim of this study is to compare the expression of autophagy related proteins in invasive lobular carcinoma (ILC) with that of autophagy related proteins in invasive ductal carcinoma (IDC), and to determinate its implication. Tissue microarray containing 114 ILC and 692 IDC was constructed, and immunohistochemistry was performed for autophagy related protein (beclin-1, LC3A, LC3B, p62) and Ki-67. No significant difference in expression of autophagy-related proteins between pleomorphic type (n = 12) and classic type (n = 102) of ILC was observed, whereas ILC and IDC showed distinguished features that tumoral beclin-1, stromal LC3A, tumoral LC3B, tumoral p62 were highly expressed in IDC and tumoral BNIP3 was highly expressed in ILC (P < 0.001). Beclin-1 expression was correlated with ER negativity (P = 0.016) and TNBC type (P = 0.024). BNIP3 expression was correlated with ER positivity (p = 0.040). Using multivariate Cox analysis, shorter overall survival was associated with tumoral beclin-1 positivity (hazard ratio: 21.19, 95% CI: 1.098-409.1, P = 0.043). In conclusion, ILC and IDC showed different expression pattern of autophagy-related proteins in tumor and stroma that demonstrated by higher expression of tumoral beclin-1, stromal LC3A, tumoral LC3B, tumoral p62 in IDC, and higher expression of tumoral BNIP3 in ILC.     

Cyclooxygenase-2 Polymorphisms and Susceptibility to Colorectal Cancer: A Meta-Analysis

Purpose

Four polymorphisms, -765G>C, -1195G>A, 8473T>C, and Val511Ala, in the cyclooxygenase-2 (COX-2) gene were identified to be associated with colorectal cancer (CRC) risk. However, the results are inconsistent. The objective of this meta-analysis was to evaluate the association between these four polymorphisms and the risk of CRC.

Materials and Methods

All eligible case-control studies published up to December 2012 on the association between the four polymorphisms of COX-2 and CRC risk were identified by searching PubMed and Web of Science. The CRC risk associated with the four polymorphisms of the COX-2 gene was estimated for each study by odds ratio (OR) together with its 95 % confidence interval (CI), respectively.

Results

A total of 15 case-control studies were included. Overall, no evidence has indicated that the -1195A allele, -765C allele, 8473C allele, and 511Ala allele are associated with susceptibility to CRC (-1195G>A: OR=1.11, 95 % CI: 0.82-1.51, p=0.78; -765G>C: OR=1.08, 95 % CI: 0.96-1.21, p=0.07; 8473T>C: OR=1.03, 95 % CI: 0.89-1.18, p=0.91; Val511Ala: OR=0.71, 95 % CI: 0.46-1.09, p=0.94). However, stratified analysis with ethnicity indicated that individuals with -765GC or GC/CC genotypes had an increased risk of CRC among Asian populations (GC vs. GG: OR=1.05, 95 % CI: 0.87-1.28, p=0.03; GC+CC vs. GG: OR=1.08, 95 % CI: 0.96-1.21, p=0.07).

Conclusion

This meta-analysis indicated that -765G>C polymorphism was significantly associated with susceptibility to CRC in Asian populations.     

Genotoxicity and cytotoxicity of sevoflurane in two human cell lines in vitro with ionizing radiation

Objective:

To determine the in vitro toxicity of different concentrations of sevoflurane in cells exposed to X-ray.

Methods:

The genotoxic effects of sevofluorane were studied by means of the micronucleus test in cytokinesis-blocked cells of irradiated human lymphocytes. Subsequently, its cytotoxic effects on PNT2 (normal prostate) cells was determined using the cell viability test (MTT) and compared with those induced by different doses of X-rays.

Results:

A dose- and time-dependent cytotoxic effect of sevofluorane on PNT2 cells was determined (p >0.001) and a dose-dependent genotoxic effect of sevofluorane was established (p >0.001). Hovewer, at volumes lower than 30 μL of sevofluorane at 100%, a non-toxic effect on PNT2 cells was shown.

Conclusion:

Sevofluorane demonstrates a genotoxic capacity as determined in vitro by micronucleus test in cytokinesis-blocked cells of irradiated human lymphocytes.