Nodules Less Than 20 mm and Vascular Invasion are Predictors of Survival in Small Hepatocellular Carcinoma

Background: The aims of this study were to analyze the overall survival of patients with cirrhosis and small hepatocellular carcinoma (HCC) and identify independent pretreatment predictors of survival in Brazil. Methods: Between 1998 and 2003, 74 patients with cirrhosis and small HCC were evaluated. Predictors of survival were identified using the Kaplan-Meier survival curves and the Cox model. Results: The overall survival rates were 80%, 41%, and 17% at 12, 36, and 60 months, respectively. The mean length of follow-up after HCC diagnosis was 23 months (median 22 mo, range: I to 86 mo) for the entire group. Univariate analysis showed that model for endstage liver disease (MELD) score (P = 0.016), Child-Pugh classification (P = 0.007), alpha-fetoprotein level (P = 0.006), number of nodules (P = 0.041), tumor diameter (P = 0.009), and vascular invasion (P < 0.0001) were significant predictors Of Survival. Cox regression analysis identified vascular invasion (relative risk = 14.60, confidence interval 95% = 3.3-64.56, P < 0.001) and tumor size > 20 mm (relative risk = 2.14, confidence interval 95% = 1.07-4.2, P = 0.030) as independent predictors of decreased survival. Treatment of HCC was related to increased overall survival. Conclusions: Identification of HCC smaller than 20 mm is associated with longer survival. Presence of vascular invasion, even in small tumors, maybe associated with poor prognosis. Treatment of small tumors Of LIP to 20 mm diameter is related to increased survival.

Peritumoural, but not intratumoural, lymphatic vessel density and invasion correlate with colorectal carcinoma poor-outcome markers

To evaluate whether lymphatic vessel density (LVD) and lymphatic vessel invasion (LVI) are useful markers of worse outcome in colorectal carcinoma and if LVD and LVI correlate to the classical clinical-pathological parameters, we analysed 120 cases of colorectal carcinomas selected from the files of Division of Pathology, Hospital das Clinicas, Sao Paulo University, Brazil. Assessment of LVD and LVI was performed by immunohistochemical detection of lymphatic vessels, using the monoclonal antibody D2-40. Higher LVD was found in the intratumoural area, when comparing with normal and peritumoural areas (p < 0.001). However, peritumoural LVD, but not intratumoural, correlated with both colonic-wall-invasion depth (p=0.037) and liver metastasis (p=0.012). Remarkably, LVI was found associated with local invasion (p=0.016), nodal metastasis (p=0.022) and hepatic metastasis (p < 0.001). Peritumoural LVD and LVI are directly related to histopathological variables indicative of poor outcome such as lymph-node status and liver metastasis.

Deregulated expression of superoxide dismutase-2 correlates with different stages of cervical neoplasia

Objective: Superoxide dismutase-2 (SOD2) is considered one of the most important antioxidant enzymes that regulate cellular redox state in normal and tumorigenic cells. Overexpression of this enzyme may be involved in carcinogenesis, particularly in lung, gastric, colorectal and breast cancer. Methods: In the present study, we have evaluated SOD2 protein levels by immunohistochemistry (IHC) in 331 cervical histological samples including 31 low-grade cervical intraepithelial neoplasia (LSIL), 51 high-grade cervical intraepithelial neoplasia (HSIL), 197 squamous cervical carcinomas (SCC) and 52 cervical adenocarcinomas (ADENO). Results: We observed that SOD2 staining increases with cervical disease severity. Intense SOD2 staining was found in 13% of LSIL, 25.5% of HSIL and 40% of SCC. Moreover, 65.4% of ADENO exhibited intense SOD2 staining. Conclusions: Differences in the expression of SOD2 could potentially be used as a biomarker for the characterization of different stages of cervical disease.

Extent of Pelvic Lymphadenectomy in Women With Squamous Cell Carcinoma of the Uterine Cervix: Is There Any Prognostic Value?

Background and Objectives: Some authors states that the removal of lymph node would only contribute towards assessing the lymph node status and regional disease control, without any benefit for the patients` survival. The aim of this paper was to assess the influence of the number of surgically dissected pelvic lymph nodes (PLN) on disease-free Survival. Methods: Retrospective cohort study on 42 women presenting squamous cell carcinoma (SCC) of the uterine cervix, with metastases in PLN treated by radical surgery. The Cox model was used to identify risk factors for recurrence. The model variables were adjusted for treatment-related factors (year of treatment, surgical margins and postoperative radiotherapy). The cutoff value for classifying the lymphadenectomy as comprehensive (15 PLN or more) or non-comprehensive (<15 PLN) was determined from analysis of the ROC curve. Results: Fourteen recurrences (32.6%) were recorded: three pelvic, eight distant, two both pelvic and distant, and one at an unknown location. The following risk factors for recurrence were identified: invasion of the deep third of the cervix and number of dissected lymph nodes <15. Conclusions: Deep invasion and non-comprehensive pelvic lymphadenectomy are possible risk factors for recurrence of SCC of the uterine cervix with metastases in PLN. J. Surg. Oncol. 2009;100:252-257. (C) 2009 Wiley-Liss, Inc.

Percutaneous vertebroplasty for multiple myeloma of the cervical spine

Spinal involvement is a common presentation of multiple myeloma (MM); however, the cervical spine is the least common site of myelomatous involvement. Few studies evaluate the results of percutaneous vertebroplasty (PV) in the treatment of MM of the spine. The purpose of this series is to report on the use of PV in the treatment of MM of the cervical spine and to review the literature. From January 1994 to October 2007, four patients (three men and one woman; mean age, 45 years) who underwent five PV for painful MM in the cervical spine were retrospectively reviewed. The pain was estimated by the patient on a verbal analogic scale. Clinical follow-up was available for all patients (mean, 27.5 months; range, 1-96 months). The mean volume of cement injected per vertebral body was 2.3 +/- 0.8 mL (range, 1.0-4.0 mL) with a mean vertebral filling of 55.0 +/- 12.0% (range, 40.0-75.0%). Analgesic efficacy was achieved in all patients. One patient had a spinal instability due to a progression of spinal deformity noted on follow-up radiographs, without clinical symptoms. Cement leakage was detected in three (60%) of the five treated vertebrae. There was no clinical complication. The present series suggests that PV for MM of the cervical spine is safe and effective for pain control; nonetheless, the detrimental impact of the disease on bone quality should prompt close radiological follow-up after PV owing to the risk of spinal instability.

Association between ultrasound findings and extent of trophoblastic invasion into the tubal wall in ampullary pregnancy

Objective Predictive factors of damage to the Fallopian tube may guide the treatment of Patients with tubal pregnancy. The aim of the present study was to investigate the association between the depth of trophoblastic invasion into the tubal wall, assessed on postoperative histological examination, with the findings obtained on transvaginal sonograpby (TVS) in women with ampullary Methods Women with ampullary pregnancy undergoing salpingectomy were enrolled into the study. Only women with a finding of either an embryo with cardiac activity or a tubal ring on TVS were included in the analysis, a total of 8.5 patients. Trophoblastic invasion was assessed postoperatively and was histologically classified as Stage I when limited to the tubal mucosa, Stage II when extending to the muscle layer and Stage III in the case of complete tubal wall infiltration. The association between findings on TVS and the stage of trophoblastic invasion was evaluated. Results There was a significant association between the findings on TVS and the depth of trophoblastic invasion (P < 0.001). All patients in whom an embryo with cardiac activity bad been identified were found to have Stage II (17.9%) or Stage III (82.1%) invasion, whereas in those patients who showed a tubal ring on TVS, Stage I invasion was the most frequent finding (41.3%). Conclusions In ampullary pregnancy, the finding on TVS of an embryo with cardiac activity is associated with deeper penetration of trophoblastic tissue into the tubal wall than is the finding of a tubal ring. Copyright (C) 2009 ISUOG, Published by John Wiley & Sons, Ltd.

Intra- and inter-observer reliability of MRI examination of intervertebral disc abnormalities in patients with cervical myelopathy

Purpose: Intervertebral cervical disc herniation (CDH) is a relatively common disorder that can coexist with degenerative changes to worsen cervicogenic myelopathy. Despite the frequent disc abnormalities found in asymptomatic populations, magnetic resonance imaging (MRI) is considered excellent at detecting cervical spine myelopathy (CSM) associated with disc abnormality. The objective of this study was to investigate the intra- and inter-observer reliability of MRI detection of CSM in subjects who also had co-existing intervertebral disc abnormalities. Materials and methods: Seven experienced radiologists reviewed twice the MRI of 10 patients with clinically and/or imaging determined myelopathy. MRI assessment was performed individually, with and without operational guidelines. A Fleiss Kappa statistic was used to evaluate the intra- and inter-observer agreement. Results: The study found high intra-observer percent agreement but relatively low Kappa values on selected variables. Inter-observer reliability was also low and neither observation was improved with operational guidelines. We believe that those low values may be associated with the base rate problem of Kappa. Conclusion: In conclusion, this study demonstrated high intra-observer percent agreement in MR examination for intervertebral disc abnormalities in patients with underlying cervical myelopathy, but differing levels of intra- and inter-observer Kappa agreement among seven radiologists. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

Cervical Mobility in Women With Migraine

Objective.-To contrast the cervical range of motion (CROM) in women with episodic migraine (EM), transformed migraine (TM), and controls without migraine headaches. Background.-Migraineurs often complain about neck pain. Furthermore, neck problems can worsen the headaches in individuals with migraine. Individuals with neck pain usually have reduced CROM. Nonetheless, studies assessing the CROM in migraineurs are scarce. Methods.-Our sample was selected in an outpatient headache clinic, and consisted of 45 women aged 20-54 years old, 15 per group. Cervical mobility was evaluated in movements of flexion, extension, right lateral flexion, left lateral flexion, right rotation, and left rotation using the CROM technique, and was contrasted among the groups. Migraine clinical patterns were also evaluated ( frequency, duration of migraine, pain in the moment of evaluation, pain in movement, and pain localization) as a function of CROM. Results.-Compared with controls, individuals with TM had numerically inferior CROM in all parameters, and significant reduction in 3 of them: extension (59.3 vs 68.1, P = .02), left lateral flexion (44.5 vs 49.1, P = .03), and right rotation (62.2 vs 69.6, P = .02). Compared with individuals with migraine, the TM group presented significantly reduced mobility only for extension ( 59.3 vs 68.4, P = .02). Migraineurs also had numerically inferior ROM, contrasted to controls, in 5 of the 6 parameters, although significance was seen just for right rotation (60.8 vs 68.6 P < .01). There was no correlation between cervical mobility and migraine parameters. The CROM was not reduced for the symptomatic side of migraine, in cases of unilateral pain. Conclusion.-Contrasted to controls, individuals with episodic and TM have decreased cervical range of motion.

Classical and non-classical HLA molecules and p16(INK4a) expression in precursors lesions and invasive cervical cancer

Objectives: Viruses and turnout cells may regulate the expression of HLA molecules on the cell surface to escape immune system surveillance. Absence of classical HLA class I molecules may impair the action of specific cytotoxic cells, whereas non-classical HLA class I molecules may regulate innate and adaptive immune cells. We assess here the possible associations between classical/non-classical class I HLA and p16(INK4a) molecule expression in cervical biopsies of women infected with HPV, stratified according to grade of the lesion and HPV type. Study design: Cervical biopsies (N = 74) presenting cervical intraepithelial neoplasia grade 1 (CIN1) (n = 31), CIN2-3 (n = 19), and invasive cancer (n = 14) were evaluated alongside 10 normal cervical specimens. Results: HLA-A/B/C/G staining was observed in the early stages of HPV infection. A significant association was detected between HLA-A/B/C staining and HPV16/18 infection (OR = 0.12, 95%CI: 0.0163-0.7899; p = 0.04). HLA-E expression increased with the progression of the lesion (chi(2)-test for trend = 4.01; p = 0.05), and a significant association was found between HLA-E staining and HPV16/18 infection (OR = 11.25, 95%CI: 2.324-54.465; p = 0.003). Irrespective of the grade of the lesion, HLA-A/B/C staining and p16(INK4a) presented a good concordance (Kappa: 0.67). Conclusions: HLA-E overexpression seemed to be associated with invasive cancer and HPV16/18 infection. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

A pilot case-control association study of cytokine polymorphisms in Brazilian women presenting with HPV-related cervical lesions

Objective and study design: A case-control study was conducted on 42 Brazilian women presenting with human papilloma virus (HPV) infection and cervical lesion and 87 HPV-negative women to evaluate single nucleotide polymorphisms observed in TNF-alpha, TGF-beta, IL-10, IL-6, and IFN-gamma genes. Results and conclusion: No significant association was observed on the cytokine polymorphisms analyzed in this series. Larger studies using cytokine polymorphisms may be useful for providing further information regarding their influence or not in HPV-related cervical lesions. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Low Expression of Human Histocompatibility Soluble Leukocyte Antigen-G (HLA-G5) in Invasive Cervical Cancer With and Without Metastasis, Associated With Papilloma Virus (HPV)

Human leukocyte antigen-G (HLA-G) is a non-classical major histocompatibility complex class lb molecule that acts as a specific immunosuppressor. Some studies have demonstrated that human papillomavirus (HPV) seems to be involved in lower or absent HLA-G expression, particularly in cervical cancer. In this study, we performed a cross-sectional study, systematically comparing the qualitative expression of the HLA-G5 isoform in invasive cervical carcinoma (ICC), stratifying patients according to the presence [ICC with metastasis (ICC(W))) and absence [ICC without metastasis (ICC(WT))] of metastasis, correlating these findings with interference of HPV and demographic and clinical variables. Seventy-nine patients with a diagnosis of ICC were stratified into two groups: ICC(WT) (n=52 patients) and ICC(W) (n=27). Two biopsies were collected from each patient (one from the tumor lesion and one from a lymph node). Immunohistochemistry analyses were performed for the HLA-G5 isoform, for HPV detection, and virus typing. HLA-G5 isoform molecules were detected in 25 cases (31.6%), 17 (32.7%) without metastasis and 8 (29.6%) with metastasis. HPV was detected in the cervical lesions of 74 patients (93.7%), but low expression of the HLA-G5 isoform was observed in all HPV-related cases. These findings are important; however, additional studies are necessary to identify the influence of HPV with HLA-G5 isoform expression on invasive cervical malignancies. (J Histochem Cytochem 58:405-411, 2010)

Local profile of cytokines and nitric oxide in patients with bacterial vaginosis and cervical intraepithelial neoplasia

Objective: To evaluate the local immune response in patients with bacterial vaginosis (BV) and cervical intraepithelial neoplasia (CIN), as assessed by cytokine and nitric oxide (NO) concentrations. Study design: Patients attending for routine gynaecological examination were prospectively enrolled in groups: BV (n = 25) diagnosed by clinical criteria, CIN graded I to III (n = 35, 6 CIN 1, 8 CIN 11 and 21 CIN 111) by histological analysis, and controls (n = 15) without clinical and cytological findings. Randomly selected patients within CIN group at grades 11 or III (n = 15) were re-evaluated at 60 days after surgical treatment. Endocervical (EC) and vaginal secretion samples were collected by cytobrush and the levels of cytokines (ELISA) and NO metabolite (Griess reaction) were assayed. Results: NO was assessed in all subjects, and cytokines in all controls, 15 BV and 30 CIN patients. Interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10) and nitrite levels were higher in EC than in vaginal secretions in BV and CIN groups. In CIN group, IL-8, IL-10 and nitrite concentrations were greater in EC and/or vaginal secretions than in BV or controls. Surgical treatment reduced IL-8 levels in EC and vaginal secretions. Conclusion: A similar local immune profile was found in BV and CIN groups. The increased local production of IL-8, IL-10 and NO in CIN suggests a role for these mediators in the immune response against tumour or tumour development. (c) 2007 Elsevier Ireland Ltd. All rights reserved.