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Real-life estimations of survival by stage in colorectal cancer are scanty. We estimated population-based net survival by pathological stage and location, and for rectal cancer by patterns of evolution according to clinical and pathological stage with regard to neoadjuvant therapy. Age-standardized net survival was estimated on 19,630 colorectal cancers diagnosed between 2009 and 2015. Five-year net survival was 64 % for colon and 62 % for rectal cancer. The highest absolute difference between colon and rectum was 12 % for stage II women aged 75 (91% vs. 79 %). Among patients with clinical stage III rectal cancer, 67 % no longer had pathological node involvement after neoadjuvant treatment. Survival was similar in clinical stage I, II or III and pathological stage III after neoadjuvant treatment and in pathological stage III without neoadjuvant treatment (between 67 % and 72 %). It ranged between 80 and 82 % in pathological stage II, without neoadjuvant treatment or with clinical stage I, II or III before neoadjuvant treatment. Survival ranged between 93 % and 95 % in pathological stage I, treated with surgery only or with clinical stage II or III before neoadjuvant treatment. Prognosis is associated with stage determined on surgical specimens rather than stage at the initial workup. [ABSTRACT FROM AUTHOR]

This study explored the predictors of upstaging and multiple sites of extension, and constructed a predictive model based on perioperative characteristics to calculate the risk of upstaging of cT1 renal cell carcinoma to pT3. We retrospectively reviewed 1012 patients diagnosed with cT1 renal cell carcinoma who underwent surgical treatment at the Affiliated Hospital of Qingdao University between June 2016 and August 2021. The continuous and categorical variables were analyzed using the Mann–Whitney U test and Chi-square test, respectively. After randomly dividing patients into a training set and an internal validation set with a ratio of 7:3, univariate and multivariate logistic regression analyses were used to explore the predictors of upstaging and multiple sites of extension. A nomogram model was established based on the predictors of upstaging and was validated. Ninety-one cases (8.99%) of renal cell carcinoma were upstaged to pT3. In the training set, multivariate logistic regression identified the following predictors of upstaging: maximum tumor diameter, hilus involvement, tumor necrosis, tumor edge irregularity, symptoms, smoking, and platelet–lymphocyte ratio. A nomogram model was established based on the predictors. The area under the receiver operating characteristic curve was 0.810 in the training set, and 0.804 in the validation set. A 10-fold internal cross-validation conducted 200 times showed that the mean area under the curve was 0.797. The calibration curve and decision curve analysis suggested that the nomogram had robust clinical predictive power. Analyses showed higher neutrophil–lymphocyte ratio and tumor necrosis were associated with multiple sites of extrarenal extension in patients with pT3a renal cell carcinoma. We identified 7 predictors of upstaging to pT3 and 2 predictors of multiple sites of extension. A nomogram model was constructed with satisfactory accuracy for predicting upstaging to pT3. This retrospective study analyzed 1012 patients diagnosed with cT1 renal cell carcinoma who underwent surgical treatment. Using univariate and multivariate logistic regression analyses, we identified the risk factors, constructed a predictive model and validated it. Our research contributes to assessing the risk of upstaging in patients with cT1 renal cell carcinoma and offering more assistance in the selection of surgical approaches. [ABSTRACT FROM AUTHOR]

Malnutrition is associated with the prognosis of malignant disease. The geriatric nutritional risk index (GNRI), based on serum albumin (ALB) levels and the present and ideal body weight, is a simple screening tool with which to predict the risk of malnutrition and mortality in patients. We hypothesised that nutritional markers could predict the prognosis of patients with oral squamous cell carcinoma (OSCC). The primary predictor variable was the GNRI score and the primary outcome variable was overall survival (OS). Univariate and multivariate analyses were performed using a Cox proportional hazard model to identify independent prognostic factors. The sample comprised 155 patients, of whom 17 presented with a low GNRI score (≤98) and 138 with a high GNRI score (≥ 98). There was a significant difference in OS when patients were stratified according to GNRI scores, with OS rates of 29.2% and 76.4% for scores of 98 and under and scores of over 98, respectively (p < 0.001). Univariate analyses showed that OS was significantly associated with GNRI score, age, T classification, N classification, stage, body mass index (BMI), prognostic nutrition index, and ALB levels. Analysis identified three independent predictive factors for OS: age (hazard ratio (HR) 2.184; 95% confidence interval (CI) 1.119 to 4.261; p = 0.022), stage (HR 2.684; 95% CI 1.457 to 5.367; p = 0.011), and GNRI score (HR 4.559; 95% CI 2.172 to 9.570; p <0.001). The results suggest that the GNRI score (>98 vs ≤98) is a good prognostic marker in patients with OSCC, along with age and stage. [ABSTRACT FROM AUTHOR]

• Nasopharyngeal carcinoma (NPC) may easily invade the prevertebral space. • Prevertebral space involvement (PSI) predicts poor prognosis in NPC. • Prognosis is particularly poor when tumor spread extends behind prevertebral muscle. • It might be reasonable to classify patients with PSI as T4 stage. To evaluate how prevertebral space involvement (PSI) and degree of tumor extension within the space affects prognosis in nasopharyngeal carcinoma (NPC). Data of patients with newly-diagnosed nonmetastatic NPC (n = 757) were retrospectively analyzed. Patients were separated into groups according to presence or absence of PSI and degree of tumor spread. Overall survival (OS), failure-free survival (FFS), local relapse–free survival (LRFS), and distant metastasis–free survival (DMFS) were compared between the groups. Prevalence of PSI, simple prevertebral muscle involvement (PMI), and behind prevertebral muscle involvement (BPMI) were 44.9% (340/757), 22.5% (170/757), and 22.5% (170/757), respectively. OS, FFS, LRFS, and DMFS for patients with and without PSI were 64% vs. 84.8%, 68% vs. 85.6%, 85.8% vs. 94.4%, and 78.5% vs. 92.8%, respectively (all P < 0.001). PSI was an independent predictor of OS, FFS, LRFS, and DMFS. OS, FFS, and DMFS for patients with simple PMI and with BPMI were 72.7% vs. 54.8% (P = 0.002), 75.8% vs. 59.8% (P = 0.003), and 85.5% vs. 71.2% (P = 0.002), respectively. Degree of PSI extension was related to OS, FFS, and DMFS. OS, FFS, LRFS, and DMFS were significantly poorer in patients with PSI in T2–3 stage than in patients without PSI in T3 stage (P < 0.05), but comparable to those in patients with T4 stage (P > 0.05). PSI predicts poor prognosis in NPC. Survival is poorer in patients with BPMI than in those with simple PMI. NPC with PSI should be classified as T4 stage. [ABSTRACT FROM AUTHOR]

To probe the utility of diffusion-weighted imaging (DWI) and 3D arterial spin labeling (ASL) in assessing the clinical stage of nasopharyngeal carcinoma (NPC). This prospective study included sixty-five newly diagnosed NPC patients who underwent DWI and 3D ASL scans on a 3.0-T magnetic resonance imaging (MRI) system. The apparent diffusion coefficient (ADC) and the tumor blood flow (TBF) of NPC were measured. Tumors were classified as low or high T, N and American Joint Committee on Cancer (AJCC) stages. Student's t -test was used to evaluate the differences between tumors with low and high clinical stages. Pearson correlation analyses were performed to determine the correlation between MRI parameters and clinical stages. Receiver operating characteristic (ROC) curves were then used to evaluate diagnostic capability. High T stage (T3/4) NPC showed significantly lower ADC min (P = 0.000) and higher TBF max (P = 0.003) and TBF mean (P = 0.008) values than low T stage (T1/2) NPC. High N stage (N2/3) NPC showed significantly lower ADC min values (P = 0.023) than low N stage (N0/1) NPC. High AJCC stage (III/IV) NPC showed significantly lower ADC min (P = 0.000) and higher TBF max (P = 0.005) and TBF mean (P = 0.011) values than low AJCC stage (I/II) NPC. ADC min values showed moderate negative correlations with T stage (r = −0.512, P = 0.000), N stage (r = −0.281, P = 0.023), and AJCC stage (r = −0.494, P = 0.000). TBF max values showed moderate positive correlations with T stage (r = 0.369, P = 0.003) and AJCC stage (r = 0.346, P = 0.005). Compared with ADC min and TBF max alone, the combination of ADC min and TBF max improved the accuracy from 72.3% and 75.4% to 78.5%, respectively, for T staging, as well as from 72.3% and 69.2% to 83.1% for AJCC staging. ADC min and TBF max values in patients with NPC could help evaluate clinical stages. ADC min and TBF max values combined could clearly improve the accuracy in the assessment of AJCC stage. • DWI and ASL are non-invasive imaging methods for assessing NPC clinical stages. • ADC min from DWI is inversely correlated with NPC clinical stages. • TBF max from ASL shows the greatest positive correlations with NPC clinical stages. • Combination of ADC min and TBF max provides more accurate T- and AJCC-staging results. • The accuracy improves more markedly for AJCC-staging than for T-staging. [ABSTRACT FROM AUTHOR]

To observe the clinical efficacy of fire needle combined with filiform needle for different clinical stage frozen shoulders, and to choose the best treatment opportunity for clinical treatment of frozen shoulder. 120 patients with frozen shoulders who met the inclusion criteria were numbered according to the visiting order. They were randomized into control group (60 cases) and treatment group (60 cases) according to the random number table. Both groups were treated with filiform needles once every other day and 3 times a week, and a course of treatment included 6 times and 2 courses were taken. The treatment group was treated by applying a fire needling point bloodletting on the local tender points once a week. Jiānyú (肩髃 LI 15), Jiānliáo (肩髎 TE 14), Jiānzhēn (肩贞 SI 9), Tiáokŏu (条口 ST 38), and local tender points were taken according to different meridian pains. The clinical efficacy of the frozen shoulder patients in the two groups in different clinical stages was compared. The evaluation indicators were scores of pain, joint activity range and activities of daily living, as well as clinical efficacy of traditional Chinese medicine. After treatment, the total scores of hundred-mark five-grade in both groups were significantly higher than those before treatment, and the differences were statistically significant (Treatment group 82.02 ± 14.23 vs 43.37 ± 22.10, Control group 66.80 ± 18.98 vs 42.67 ± 23.03, both P < 0.01), and the total score of the treatment group was significantly higher than the control group (P < 0.01). The hundred-mark five-grade assessment scores after treatment in the treatment group during the frozen stage were significantly higher than the control group (77.2 ± 14.40 vs 68.43 ± 16.94, P < 0.01); as to the clinical efficacy, the total effective rate of the treatment group was higher than the control group, and the difference was statistically significant (91.67% vs 76.67%, P < 0.01); The total effective rate of the control group in the acute stage and functional recovery stage was compared with the frozen stage, and the difference was statistically significant (100% vs 60%, P < 0.01), and there was no significant difference between each phase of the treatment group (P > 0.05). Single filiform therapy and the therapy of filiform needle combined with fire needle were effective in treating frozen shoulder patients, and the effect of the filiform needle combined with fire needle was significantly better than single filiform needle. The effect of fire needle combined with filiform needle on the frozen shoulder in frozen stage was significantly better than single filiform needle. [ABSTRACT FROM AUTHOR]

Objective: Although partial nephrectomy (PN) is the standard treatment for localized clinical T1a renal cell carcinoma (RCC), treatment of larger renal tumors is controversial. We evaluated the oncological outcomes and perioperative complications after radical and PN for RCC ≥4cm.Patients and Methods: We retrospectively analyzed the data of 2,373 patients surgically treated for nonmetastatic RCC with clinical T1b or T2 (≥4cm). The propensity scores for surgery type were calculated, and the partial group was matched to the radical group in a 1:3 ratio. The oncological outcomes were compared using Kaplan-Meier analysis and multivariate Cox regression models were used to identify the independent predictors of progression-free, cancer-specific, and overall survival.Results: All differences in preoperative clinical characteristics disappeared after matching. There were no significant differences in progression-free, cancer-specific, or overall survival between the partial and radical groups in the matched cohort. The patients' age, tumor size, cellular grade, and pathologic stage were independent predictors for all 3 survival outcomes. However, early complications (<30d postoperative) were significantly more common in the partial group (P<0.001). In a subgroup analysis of the patients with clinical T2 stage, there were no significant differences in all 3 survival outcomes.Conclusions: The partial and radical nephrectomy groups had equivalent oncological outcomes. Although the early complication rate was significantly higher after PN, it should be considered as a valuable treatment option even in patients with clinical T1b or higher RCC. [ABSTRACT FROM AUTHOR]

Schizophrenia (SZ) is a neuroprogressive disorder presenting with biochemical, functional, and structural changes, which differ from early to late stages of the illness. We explored the differences in serum levels of soluble intercellular cell adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) between early and late stages of SZ, in regard to clinical characteristics and treatment application. Serum levels of sICAM-1 and sVCAM-1 were measured in 80 patients with SZ (40 early stage; 40 late stage), and compared with 80 healthy controls, matched by age, gender, body mass index, and smoking habits with each SZ group. Serum levels of sICAM-1 and sVCAM-1 were measured using ELISA. The severity of psychopathology was assessed using the Clinical Global Impression Scale and five-factor Positive and Negative Symptoms in Schizophrenia Scale. After adjustment for confounders, we noticed normal levels of sICAM-1 in the early stage, and elevated levels of sICAM-1 in the late stage of SZ. sVCAM-1 levels were decreased in both stages of SZ. Higher sICAM-1 levels have been related to more pronounced cognitive deficit and excitement symptoms in the early stage of SZ and to favorable characteristics of treatment application in both stages. SZ is associated with changes in the levels of adhesion molecules that vary from early to late stages of the illness. This implies that the concept of biochemical staging is applicable in SZ, at least for markers of cellular adhesion. [ABSTRACT FROM AUTHOR]

In this study, the performance of 8 commercially available treponemal antibody tests was evaluated. Higher specificity was achieved in the automated chemiluminescence immunoassays(CIA assays) than enzyme-linked immunosorbent (ELISA) assays, but no significant differences were found in terms of the sensitivity levels. The levels of test sensitivity did not differ by HIV status and TRUST titer but did differ by clinical stage. The results of WB-IgG revealed that the level of antibodies against the 4 antigens showed an upward trend with the development of the clinical stages of syphilis, reaching a peak in tertiary syphilis and then decreasing. The present results supported the good performance of CIA tests used in the blood source screening of syphilis, which reduced the waste of plasma. The reaction intensities of anti-TP17 and TP47 antibodies in past treated syphilis samples were considerably weak and were expected to be used for monitoring the therapeutic effect of syphilis. [ABSTRACT FROM AUTHOR]

Purpose: The utility of the apparent diffusion coefficient (ADC) in patients with clear-cell renal cell carcinoma (RCC) for distinguishing between the four clinical stages was assessed. Methods: Forty-nine patients with pathologically proven RCCs (I, II, III, IV; 27, 5, 10, 7) were included. The ADC was compared between each stage. Results:Thedifferenceof ADCbetweenstageI and the more advanced stages (III and IV) was statistically significant. Conclusions: When ADC in primary tumor site of clear-cell RCC would be higher than the cutoff level, the stage might not be an advanced stage (III or IV). [ABSTRACT FROM AUTHOR]

Leishmaniosis is a zoonotic disease with a very complex pathogenesis modulated by the interaction between the parasite, the vector and the host. Although the pathological characteristics have been extensively studied in the typically affected organs, some locations such as muscles and reproductive organs have been less studied. The objective of this study was to evaluate the presence of lesions in the temporal muscle and the male reproductive organs (testicle and epididymis) and correlate their characteristics with the presence of the parasite and with the clinical status of the dogs. The temporal muscle was studied in 25 infected beagle dogs (nine females and 16 males) and five uninfected control dogs (two females and three males) and the testicle and epididymis in the 19 males. Dogs were euthanized one year after infection and clinical signs, anti- Leishmania serum antibodies, and lymph node parasite load were assessed. Muscular and reproductive lesions were characterized by H&E and immunohistochemistry (IHC). The presence of the parasite in the lesions was evaluated using IHC and molecular techniques. Myositis was observed in 72% (18/25) of the dogs and was characterized by lymphoplasmacytic or histiocytic lesions. Mild and severe lesions were detected, the latter being statistically associated with the presence of the parasite and with the clinical status of the dogs. Orchitis was observed in 50% (8/16) of the dogs and was mainly mild and lymphoplasmacytic. No statistical relationship was found between testicular lesions and the presence of the parasite or the clinical status. Epididymitis was observed in 87.5% (14/16) of the dogs, and the lesions were often infiltrated by numerous histiocytes and neutrophils. Epididymal lesions were statistically associated with the clinical status of the dogs and with the presence of the parasite in the lesions. IgG and IgM immunoglobulins were found in all lesions, suggesting a local immune response with reactivation of the infection. Leishmania was more frequently detected in severe and histiocytic lesions, although some lesions had no detectable parasites. These results have shown that lesions in the temporal muscle, epididymis, and testicles are common in dogs infected by Leishmania infantum and that dogs may show a different response to infection. This response is characterized by varying degrees of cellular and immune responses associated with a variable presence of the parasite. • Myositis, epididymitis and orchitis are common in Leishmania-infected dogs. • Epididymitis is more frequent than orchitis and predominantly histiocytic. • Testicular lesions are usually mild and lymphoplasmacytic in nature. • Leishmania amastigote presence is frequently associated with epididymitis but not with orchitis. • Neutrophils and IgM are present in lesions after one year of Leishmania infection. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: The transcription factor E2F3 plays an important role in controlling cell cycle progression and proliferation, and is overexpressed in various human cancers. The present study was undertaken to examine the expression of E2F3 and investigate its relevance in clinical and pathological features of pediatric Wilms’ tumors. Methods: Twenty-six Wilms’ tumor samples collected at the First Affiliated Hospital of Harbin Medical University underwent immunohistochemical staining for E2F3 protein expression by measuring the percentage of E2F3-positive cells and integrated optical density (IOD), and quantitative real-time polymerase chain reaction (qRT-PCR) for E2F3 mRNA expression. Results: The expression of E2F3 protein and mRNA was detectable in all the Wilms’ tumor samples with big variations (The average percentage of positive cells was 30.2%±23.5%, range 0.3%–75.6%; average IOD was 6.61×104 ±3.92×104, range 2.32×104–13.84×104; average relative mRNA unit was 0.54±0.38, range 0.03–1.31), but not in fetal kidney tissues. Wilms’ tumors with aggressive features, such as higher stage, unfavorable histology and higher risk level, expressed higher levels of E2F3 protein and mRNA. Conclusions: The preliminary data indicate that E2F3 is frequently expressed in pediatric Wilms’ tumors examined in the present study. E2F3 expression may be associated with Wilms’ tumors, particularly those that have more aggressive features. However, further studies are needed to validate these pilot observations and to clarify the functional and mechanistic significance of this association. [Copyright &y& Elsevier]

Abstract: Objectives: Polo-like kinase 1 (Plk1) has been widely pursued as an oncology target because it is overexpressed in several human tumor types. To investigate whether Plk1 plays a general role in bladder urothelial carcinoma, we examined the expression of Plk1 protein in bladder urothelial carcinoma and cell lines, and analyzed the relationship among Plk1 protein expression, metastasis, and recurrence of urinary bladder urothelial carcinoma. Methods: Immunohistochemistry was used to detect the expression of Plk1 in 120 bladder urothelial carcinoma. Moreover, the expression of Plk1 was analyzed by Western blot in 60 bladder urothelial carcinoma and 21 normal epithelial tissues. MTT assay and flow cytometry and transwell assay were used to examine the proliferative and invasive ability of bladder cancer cells with the treatment of scytonemin (the inhibitor of Plk1). Statistical analysis was used to discuss the association between Plk1 expression and clinicopathologic parameters, tumor metastasis and recurrence, and the proliferative and invasive ability and cell cycle process of the bladder cancer cells. Results: There was a significantly higher Plk1expressions in bladder urothelial carcinoma and highly invasive bladder T24 cells than those in bladder normal tissues and the superficial bladder BIU-87 cells. Plk1 expression was positively correlated with histologic grade, pT stage, recurrence, and metastasis. With the increasing concentration of scytonemin, we found that not only the cell proliferation and invasion activity decreased significantly, but also the cell cycle was blocked at G2/M stage. Conclusion: Plk1 expression status was closely correlated with important histopathologic characteristics (grades and stages) and the recurrence and metastasis of bladder urothelial carcinomas. Furthermore, Plk1 played an important function on the bladder cancer cells' proliferation by regulating the cancer cell cycle from G1/S to G2/M and probably promoted the invasion and metastasis of bladder cancer. [Copyright &y& Elsevier]

Objectives: To analyze whether differences between the interval from suspicion or clinical diagnosis to treatment onset (IClinDT) and the interval from certainty diagnosis to treatment onset (ICertDT) varied by tumor site, stage, and mode of hospital admission. Study Design and Setting: From our hospital cancer registry, we selected all 8,814 patients with breast, colorectal, lung, prostate, or cervical cancer diagnosed between 1992 and 2006. We compared IClinDT and ICertDT with density plots and logistic regression. Results: IClinDT was up to three times higher than ICertDT. There were very large differences among stages and within each stage in IClinDT and ICertDT. Tumor stage significantly influenced the difference between the two intervals in three of the five locations (breast, lung, and prostate cancer); as stage worsened, the difference between IClinDT and ICertDT became smaller. In all tumor sites, the difference was larger in scheduled than in emergency admissions. Overall, therapeutic delays--even when measured by ICertDT--were disturbingly common for important subgroups of patients. Conclusion: The difference between IClinDT and ICertDT varied highly by tumor site, stage, and mode of hospital admission. More standardized definitions and procedures to calculate time intervals between cancer diagnosis and treatment onset are needed. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: Both preoperative computed tomography (CT) staging and postoperative surgical Masaoka clinical staging are of great clinical importance for diagnosing thymomas. Our study aimed to investigate the relationships between these two staging systems. Materials and Methods: This was a retrospective review of 129 patients who had undergone thymoma surgery. Helical CT and 16-slice CT were performed preoperatively. Surgical findings were evaluated according to the Masaoka clinical staging system. Results: A significant association was shown between Masaoka clinical staging and CT staging, especially of features including tumor size (P = .004), tumor shape (P < .001), tumor density (P < .001), capsule completeness (P < .001), and involvement of surrounding tissues (P < .001). Based on the CT findings, there were 35.09% of Masaoka stage I patients who had a tumor size <5 cm as compared to 14.81% of stage IV patients. Only 8.77% of Masaoka stage I patients had a tumor size ≥10 cm as compared to 40.74% of stage IV patients. In stages III and IV, most tumors were irregularly shaped with an uneven density and incomplete capsule. Invasive tumors were more frequently found in stages III (81.48%) and IV (88.89%) than in stages I (0%) and II (38.89%). The incidence of myasthenia gravis was comparable in different stages. Consistency between CT and Masaoka clinical stages was higher in stage I (37.98%) than other stages (approximately 10%). Conclusion: This study documented a close relationship between preoperative CT thymoma staging and postoperative Masaoka clinical staging. Thus, preoperative CT findings can be beneficial for determining the proper management and prognosis of thymoma patients. [ABSTRACT FROM AUTHOR]

Abstract: Although the role of the non-classical human leukocyte antigen E (HLA-E) was originally thought to be limited to the development of a maternal tolerance to a semiallogeneic fetal graft, it is now known that HLA-E exerts multiple immunoregulatory functions. The significance of the presence of HLA-E in neoplastic cells and/or backround microenvironment cells in classical Hodgkin lymphoma (cHL) is not well characterized. In our study, we evaluated the presence of HLA-E in both neoplastic and background cells in 40 cases of cHL. We found HLA-E in both neoplastic and background cells. There was a positive statistical correlation between the expression of HLA-E in neoplastic cells and the clinical stage of the disease, which indicates an immune-tolerogenic property of this multiple-purpose molecule. The presence of HLA-E in background cells seems to be prognostically neutral but its significance still needs to be determined. The mechanisms regulating the immunopathology of cHL neoplastic cells with respect to the presence of these molecule deserve further studies. [Copyright &y& Elsevier]

Abstract: Objective: To examine the associations of measured anthropometric factors, including general and central adiposity, with epithelial ovarian cancer (EOC) risk in the Malmö Diet and Cancer Study. Methods: In 93 incident EOC cases from a Swedish population-based prospective cohort study, seven anthropometric factors; height, weight, BMI, body fat percentage, waist- and hip circumference, and waist-hip ratio (WHR), were categorized by tertiles of baseline anthropometric measurements and relative risks were calculated using multivariate Cox regression models. Results: A high WHR (<0.77, ≥0.77 to <0.81, ≥0.81cm/cm) was associated with a statistically significantly lower overall risk for EOC (RR 0.60; 0.36–1.00; p-trend=0.04), particularly tumours of differentiation grades 1 and 2 (RR 0.27; 0.09–0.81; p-trend=0.03) and clinical stages 1 and 2 (RR 0.32; 0.10–0.97; p-trend=0.03) and these associations were stronger in postmenopausal women. Neither height, weight, BMI, body fat percentage, waist- or hip circumference were associated with overall risk, nor with risk for different subtypes, differentiation grade or stage. Conclusions: These results demonstrate that a high WHR is associated with a decreased risk of EOC. Other anthropometric factors were not associated with EOC risk. [Copyright &y& Elsevier]

Abstract: A significant proportion of recurrent pregnancy loss (RPL) is associated with immune etiologies. The immunological environment is different between decidua basalis and decidua parietalis, and also different between RPL cases with normal fetal chromosomes and those with abnormal fetal chromosomes. Recent data show that the immune system in a late-stage abortion is completely different from that in an early-stage abortion. If immunocompetent cells can cause RPL, the immunological environment may be a causative factor, especially in an early-stage abortion, and/or at decidua basalis and/or in the cases of RPL with a normal embryo. Careful examination of the immune system at the decidua basalis in an early-stage abortion in RPL cases with normal fetal chromosome may reveal useful information. [Copyright &y& Elsevier]

Abstract: Background: The diagnosis of Rett syndrome (RTT) is based on a set of clinical criteria, irrespective of mutation status. The aims of this study were (1) to define the clinical differences existing between patients with Rett syndrome with (Group I) and without a MECP2 mutation (Group II), and (2) to characterize the phenotypes associated with the more common MECP2 mutations. Patients and methods: We analyzed 87 patients fulfilling the clinical criteria for RTT. All were observed and videotaped by the same paediatric neurologist. Seven common mutations were considered separately, and associated clinical features analysed. Results: Comparing Group I and II, we found differences concerning psychomotor development prior to onset, acquisition of propositive manipulation and language, and evolving autistic traits. Based on age at observation, we found differences in eye pointing, microcephaly, growth, number of stereotypies, rigidity, ataxia and ataxic-rigid gait, and severity score. Patients with truncating differed from those with missense mutations regarding acquisition of propositive words and independent gait, before the beginning of the disease, and microcephaly, growth, foot length, dystonia, rigidity and severity score, at the time of observation. Patients with the R168X mutation had a more severe phenotype, whereas those with R133C showed a less severe one. Patients with R294X had a hyperactive behaviour, and those with T158M seemed to be particularly ataxic and rigid. Conclusion: A clear regressive period (with loss of prehension and language, deceleration of growth) and the presence of more than three different stereotypies, rigidity and ataxic-rigid gait seemed to be very helpful in differentiating Group I from Group II. [Copyright &y& Elsevier]

Abstract: The interplay between mycobacteria and host determines the outcome of infection. After uptake of mycobacteria by macrophages, several possible scenarios may emerge; mycobacteria may be destroyed immediately or there is establishment of persistent infection. This review is focused around mycobacteria–host interactions with reference to Mycobacterium avium subspecies paratuberculosis (MAP) infection and highlights protective mechanisms involved in order to design vaccines and other control strategies. [Copyright &y& Elsevier]

Abstract: Background: Targets set by health care organizations on time intervals between cancer diagnosis and treatment often go unmet. The objective of the study was to analyse the interval from diagnosis to treatment onset, and related factors, in the six most incident cancers in Catalonia (Spain), a developed European region with universal free access to health care. Methods: Twenty-two hospitals contributed 1023 incident cancer patients (198 lung, 253 colorectal, 95 prostate, 109 urinary bladder, 266 breast, 102 endometrial). Information was gathered from hospital medical records. The dependent variable was the length of the diagnosis to treatment interval (DTI). Independent variables were age, sex, disease stage, hospital level, mode of admission to hospital, and type of physician seen before admission. Multivariate-adjusted odds ratios were calculated by unconditional logistic regression for each cancer site. Results: The median DTI (in days) was 39 for lung cancer, 25 for colorectal, 108 for prostate, 69 for bladder, 35 for breast and 40 for endometrial cancer. In prostate and bladder cancers, over 78% of patients showed a DTI >30 days, while in colorectal the figure was 42%. Disseminated stage (distant metastases) was associated with a lower DTI in all sites. Patients admitted to third-level hospitals and with an elective admission were more likely to have a DTI >30 days. Conclusions: In Catalonia, a substantial proportion of cancer patients experience treatment delays that may impact negatively on psychological well-being, quality of life, and probably survival as well. [Copyright &y& Elsevier]

Abstract: Hypermethylation of tumor-suppressor genes has been implicated in the pathogenesis of human cancers. This study was designed to examine the methylation profiles of a selected group of p53 target genes (APAF-1, CASP-8, DAPK-1, IGFBP-3) and to correlate the findings with the histopathological characterization of testicular germ cell tumors (TGCT). Promoter methylation status was analysed by highly sensitive real-time methylation-specific PCR in 46 primary TGCTs (26 seminomas and 20 nonseminomas) and 15 normal testicular tissue samples. APAF-1 methylation was detected in all of the seminomatous and nonseminomatous TGCTs as well as in 60% of normal testicular tissue. Methylation of DAPK-1 was frequent in seminomas (50%) and nonseminomas (20%), but not in normal testicular tissue (6%). The degree of DAPK-1 methylation correlated with the clinical stage of the disease (P=0.05) and was useful in differentiating seminomatous from nonseminomatous, and malignant from nonmalignant testicular tissue (P=0.04 and 0.02, respectively). The APAF-1 methylation index achieved a highly significant differentiation between seminomatous or nonseminomatous tissue and nonmalignant testicular tissue (P=0.0001). In testicular tumorigenesis, promoter methylation of specific p53 target genes occurs at early stage but to varying degrees. Methylation also occurs in normal testicular tissue, which is in contrast to findings in other urogenital malignancies. Further studies will be necessary to determine whether the methylation level may be used as marker for risk estimation, especially in clinical stage I disease. [Copyright &y& Elsevier]

Survivin is a new member of the inhibitor of apoptosis family of anti-apoptotic proteins. It has been reported that survivin is expressed during fetal development and in cancer tissues. Because suppression of apoptosis is important for carcinogenesis and tumor growth, we investigated the expression of survivin in human endometrial carcinomas. We analyzed serial frozen sections for survivin protein expression in 31 cases of endometrial carcinoma and 20 cases of normal endometria by fluorescent immunohistochemistry. We analyzed the relationship between the percentages of survivin-stained cells and the patient''s characteristics, including clinical stage, histological grade, presence of invasion to >1/2 myometrium, clinical outcome, and survival rate. Survivin was weakly detected in some normal endometria in the proliferative phase (0–5.1%) and in the secretory phase (0–15.8%). There was, however, abundant survivin immunoreactivity in the nucleus and/or cytoplasm of the endometrial carcinoma cells. Scoring on the basis of the percentage of positive cells indicated that survivin expression was significantly associated with proliferating cell nuclear antigen-labeling index, clinical stage, histological grade, the presence of invasion to >1/2 myometrium, clinical outcome, and survival rate (P<0.01, respectively). We conclude that the survivin protein is a defining diagnostic marker for endometrial carcinomas that may also yield prognostic information. [Copyright &y& Elsevier]

Ca2+/calmodulin-dependent protein kinase IV (CaMKIV) is a multifunctional protein kinase expressed abundantly in the central nervous system. Because changes in intracellular Ca2+ concentrations affect progression through the mitotic cell cycle, enhanced expression of CaMKIV has been reported in small cell lung carcinoma and hepatocellular carcinoma. To elucidate the involvement of CaMKIV in epithelial ovarian carcinogenesis, we analyzed serial frozen sections for CaMKIV protein expression in 26 patients with ovarian epithelial carcinoma and ten patients with benign cystadenoma of the ovary by fluorescent immunohistochemistry. We analyzed the relationship between the percentages of CaMKIV-stained cells and the patient''s characteristics, including histological classification, clinical stage, histological grade, and clinical outcome. In the benign ovarian cystadenoma, CaMKIV was detected in none of the cases examined. Most of the CaMKIV proteins were found in the nucleus of epithelial ovarian cancer tissue. CaMKIV expression was significantly associated with clinical stage (P<0.01), histological grade (P<0.01), and clinical outcome (P<0.01). Survival data were available for all patients, and univariate Cox regression analysis showed that CaMKIV expression was significantly associated with poor prognosis (P<0.05). Our results demonstrate that CaMKIV expression in epithelial ovarian cancer correlates with the malignant potential of this tumor. [Copyright &y& Elsevier]

This paper aims to assess diet and lifestyle by designing a healthy behavior index (HBI) related to the educational level and time of breast cancer (BC) diagnosis. 241 female breast cancer survivors treated at Centro Estatal de Cancerología (State Cancer Center) in Mexico were assessed based on dietary pattern, physical activity, smoking, alcohol consumption, body size and shape, sleep disorders with increasing scores that represent less healthy characteristics. The odds ratios (OR) and quartiles of the healthy behavior index and the time of diagnosis were estimated. The regression model was used to assess the association between HBI and the BC covariates. The healthy behavior index for the two first quartiles was that of p < 0.001. The graphic behavior of correspondence with the covariates (age, schooling and moderate physical activity) showed a different three-dimensional effect on healthy behaviors. According to diagnosis time ≤ three years, the following covariates were significant: socioeconomic status, (OR: 4.34 CI 95% 1.2-9.5), sleep disturbances (p = 020) and protective intake of fruits and vegetables (p = 0.001). In the multivariate analysis, survivors with a high level of education are significantly more likely to show a healthy behavior (OR: 0.3 95% CI 0.12 - 0.8); as well as the early clinical stages (OR: 0.4 95% CI 0.2–0.9). In breast cancer survivors, both the high level of education and early clinical stages were important healthy behavior modifiers. Since diets are potentially modifiable, the findings may have further implications to promote a careful dietary pattern to prevent breast cancer. These variables should be assessed as a strategy in cancer survivor preventive programs. • The level of education played a key role when adopting a healthy behavior. • Sleep disorders were also more evident in the first years after the diagnosis. • Women with early clinical stages were the healthiest. • The survivors diagnosed before three years have an adequate quality of diet. [ABSTRACT FROM AUTHOR]