Are Breast Cancer Nomograms Still Valid to Predict the Need for Axillary Dissection?

BACKGROUND: Nomograms can help in estimating the nodal status among clinically node-negative patients. Yet their validity in external cohorts over time is unknown. If the nodal stage can be estimated preoperatively, the need for axillary dissection can be decided. OBJECTIVES: The aim of this study was to validate three existing nomograms predicting 4 or more axillary lymph node metastases. METHOD: The risk for ≥4 lymph node metastases was calculated for n = 529 eligible breast cancer patients using the nomograms of Chagpar et al. [Ann Surg Oncol. 2007;14:670-7], Katz et al. [J Clin Oncol. 2008;26(13):2093-8], and Meretoja et al. [Breast Cancer Res Treat. 2013;138(3):817-27]. Discrimination and calibration were calculated for each nomogram to determine their validity. RESULTS: In this cohort, the AUC values for the Chagpar, Katz, and Meretoja models were 0.79 (95% CI 0.74-0.83), 0.87 (95% CI 0.83-0.91), and 0.82 (95% CI 0.76-0.86), respectively, showing good discrimination between patients with and without high nodal burdens. CONCLUSION: This study presents support for the use of older breast cancer nomograms and confirms their current validity in an external population.

Excess of Radiation Burden for Young Testicular Cancer Patients using Automatic Exposure Control and Contrast Agent on Whole-body Computed Tomography Imaging.

BACKGROUND: The aim of the study was to assess patient dose from whole-body computed tomography (CT) in association with patient size, automatic exposure control (AEC) and intravenous (IV) contrast agent. PATIENTS AND METHODS: Sixty-five testicular cancer patients (mean age 28 years) underwent altogether 279 whole-body CT scans from April 2000 to April 2011. The mean number of repeated examinations was 4.3. The GE LightSpeed 16 equipped with AEC and the Siemens Plus 4 CT scanners were used for imaging. Whole-body scans were performed with (216) and without (63) IV contrast. The ImPACT software was used to determine the effective and organ doses. RESULTS: Patient doses were independent (p < 0.41) of patient size when the Plus 4 device (mean 7.4 mSv, SD 1.7 mSv) was used, but with the LightSpeed 16 AEC device, the dose (mean 14 mSv, SD 4.6 mSv) increased significantly (p < 0.001) with waist cirfumference. Imaging with the IV contrast agent caused significantly higher (13% Plus 4, 35% LightSpeed 16) exposure than non-contrast imaging (p < 0.001). CONCLUSIONS: Great caution on the use of IV contrast agent and careful set-up of the AEC modulation parameters is recommended to avoid excessive radiation exposure on the whole-body CT imaging of young patients.

Health-related quality of life during adjuvant radiotherapy in breast cancer.

OBJECTIVE: In this study, health- related quality of life (HRQoL) and its determinants were assessed in breast cancer patients undergoing postoperative adjuvant radiotherapy. The aim was to improve our understanding of patient's situation at the end of adjuvant treatment, as the return to every day life approaches after breast cancer surgery and adjuvant chemo- and radiotherapy. METHODS: Health- related quality of life was measured by the 15D instrument. Self-administered questionnaires were distributed to patients undergoing postoperative radiotherapy. Out of 389 consecutive breast cancer patients, 273 comprised the final study group. The results were compared to 15D results for an age-standardized sample of the female general population in Finland (n = 3,335). Determinants of HRQoL were assessed by a multivariate model. RESULTS: In patients <53 years, but not in older patients, the total 15D score was lower than in age-standardized controls. Both younger and older patients differed significantly from the controls on specific 15D dimensions of sleeping, depression, distress, vitality, and sexual activity. When clinical and treatment variables were assessed by a multivariate model, depressive symptoms had a negative effect on HRQoL. Further, having undergone breast conserving surgery instead of mastectomy was associated with poorer HRQoL. CONCLUSIONS: Impairment of HRQoL was observed during adjuvant radiotherapy in breast cancer. This finding calls for action to develop supportive and preventive means to smoothen the return to normal activities after completion of adjuvant treatment for breast cancer.

Opioids in pain management of mesothelioma and lung cancer patients.

BACKGROUND: Lung cancer and mesothelioma are malignant tumors with generally dismal prognosis and therefore palliative pain treatment constitutes a challenge for the clinician. OBJECTIVES: The aim of this study was to compare the outcomes of pain treatment with opioids among mesothelioma and lung cancer patients treated for palliation and assess factors which confound to optimal treatment. PATIENTS AND METHODS: A sub-cohort of 373 lung cancer and 22 mesothelioma patients was identified in multi-center European Pharmacogenetic Opioid Study (EPOS) cohort. A nested case-control (1:4) setting was designed to estimate the pain and other covariates distinguishing 22 mesothelioma- (= cases) and 88 lung cancer patients (controls), analyzed using univariate- and multivariate conditional (fixed-effects) logistic regression models. RESULTS: The mean total daily dose of opioids varied from 30.0 to 960.0 mg (mean 275, median 160 mg, SD 293) in mesothelioma, and from 10 to 5072 mg (mean 414, median 175, SD 788) in lung cancer patients (p = 0.420). In both groups, pain was mostly experienced as moderate and severe and it was frequently accompanied by depression, poor sleep, anxiety and fatigue. Four mesothelioma patients (18%) and seven lung cancer patients (10%) experienced complete pain relief with opioids by self-assessment. Assessments of pain severity by the patients and their physicians deviated significantly in mesothelioma (p = 0.039 McNemar test), as well as in lung cancer (p = 0.0001). In conditional logistic regression, no significant differences were found in distribution of pain covariates between lung cancer and mesothelioma patients. CONCLUSION: Pain perception by the patients was associated frequently with other symptoms and complete pain control with opioids was achieved only with minority of patients both with mesothelioma and advanced lung cancer. Adequate pain control requires continuous monitoring and tailoring the dose to patient's individual needs and tolerance, recognition of accompanying symptoms such as depression and poor sleep, and their management.

State of the art in research into the risk of low dose radiation exposure--findings of the fourth MELODI workshop.

The fourth workshop of the Multidisciplinary European Low Dose Initiative (MELODI) was organised by STUK-Radiation and Nuclear Safety Authority of Finland. It took place from 12 to 14 September 2012 in Helsinki, Finland. The meeting was attended by 179 scientists and professionals engaged in radiation research and radiation protection. We summarise the major scientific findings of the workshop and the recommendations for updating the MELODI Strategic Research Agenda and Road Map for future low dose research activities.

Long-term Outcome With Prolonged Use of Interferon-alpha Administered Intermittently for Metastatic Renal Cell Carcinoma: A Phase II Study.

BACKGROUND/AIM: Interferon-alpha (IFN-alpha) has shown survival benefits in metastatic renal cell carcinoma (mRCC), but the knowledge about long-term outcome is sparse. Additional knowledge is beneficial because IFN-alpha usage in combination therapy such as immune checkpoint inhibitor for mRCC is an area of interest. This is the longest follow-up concerning IFN-alpha treatment. PATIENTS AND METHODS: A total of 117 metastatic renal cell cancer (mRCC) patients without prior chemotherapy were enrolled between 1994-2002 and followed-up until January 2022. The median follow-up was 18 months. After progression to IFN-alpha, the patients were not treated with tyrosine kinase, mTOR inhibitors or bevacizumab as these were not standard therapies at that time or the patients' performance status was too poor. Mean treatment duration was 11 months. RESULTS: Median overall survival was 19.0 months, 5-year survival rate 16.2%, and 10-year survival rate 9.0%. There were statistically significant differences in survival in response to treatment (log-rank test, p<0.001): median overall survival was 52.0 months for objective responses, 25.0 months for stable disease and 5.0 months for progressive disease. Proportion of 5-year survivors was 29% in low, 20% in intermediate, and 7% in high-risk groups, respectively (p=0.001). CONCLUSION: With prolonged INF-alpha treatment stable and responding patients can obtain late objective responses, long-lasting complete responses, and long-term outcome with acceptable toxicity. IFN-alpha is an alternative therapy when multiple treatment lines are used for mRCC and an interesting option to study for combined therapies such as immune checkpoint inhibitor-based therapies.

Effect of a low dose of sea buckthorn berries on circulating concentrations of cholesterol, triacylglycerols, and flavonols in healthy adults.

BACKGROUND: Epidemiological studies indicate beneficial effects of flavonoids on cardiovascular disease (CVD) risk. AIM OF THE STUDY: To study the effect of flavonoid-rich sea buckthorn berry (SBB) on circulating lipid markers associated with CVD risk and plasma flavonol concentration. Also investigated was whether changes in the circulating flavonol concentrations correlate with the SBB induced changes in C-reactive protein (CRP) concentration observed previously. SUBJECTS AND METHODS: In all 229 healthy participants completed the randomized double-blind study and consumed daily 28 g of SBB or placebo for 3 months. Fasting blood samples for the analysis of lipid markers and flavonols were obtained at the beginning and end of the study. RESULTS: Compared to the placebo, the consumption of SBB increased the plasma concentration of the flavonols quercetin and isorhamnetin significantly [treatment differences 3.0 ng/ml (P = 0.03) and 3.9 ng/ml (P < 0.01), respectively]. The increase of kaempferol concentration was not significant [treatment difference 0.7 ng/ml (P = 0.08)]. SBB did not affect the serum total, HDL, LDL cholesterol, or the serum triacylglycerol concentrations. There was no correlation between the changes in flavonol and CRP concentrations of participants. CONCLUSIONS: The consumption of SBB significantly increased the fasting plasma concentration of quercetin and isorhamnetin indicating that it is a good dietary source of flavonols. However, this did not convert to affecting the circulating concentrations of lipid markers in healthy, normolipidemic adults having healthy diets.

Qualitative and quantitative analyses of the bifidobacterial microbiota in the colonic mucosa of patients with colorectal cancer, diverticulitis and inflammatory bowel disease.

AIM: To characterize the bifidobacterial microbiota of the colonic mucosa in patients with colon cancer, inflammatory bowel disease or diverticuitis. METHODS: A sample of the distal colonic mucosa was taken during surgery from a total of 34 patients, twenty-one with diagnosed colorectal cancer, nine with diverticulitis and four with inflammatory bowel disease, requiring surgery for their condition. Bacterial DNA was extracted from the resected mucosal samples and bifidobacterial mucosa-associated microbiota was qualitatively and quantitatively determined by means of qualitative and quantitative PCR. RESULTS: Bifidobacteria were found in 100% of the samples from patients with diverticulitis or IBD and a 76% of those suffering colon cancer. The species B. longum and B. bifidum were the most widely found, followed by B. animalis, B. catenulatum and B. adolescentis. B. breve, B. dentium and B. angulatum were not detected in any sample. A significantly higher occurrence of B. longum was observed in patients with diverticulitis than in those with colon cancer or IBD (100%, 62% and 75%, respectively, P < 0.05). Similar results were obtained for B. animalis (56%, 0% and 25%, P < 0.05), while B. adolescentis was only found in the mucosa from patients with colon cancer (5 out of 21, 24%). At the quantitative level, patients with colon cancer or IBD showed lower counts of total Bifidobacterium (4.94 and 5.91 vs 6.96 log cells/sample, respectively, P < 0.05) and of the species B. longum (4.05 and 4.79 vs 6.76, P < 0.05) than those with diverticulitis. CONCLUSION: Aberrancies in mucosa associated microbiota are present in different intestinal diseases. This may indicate a role of the microbiota in the pathogenesis of these diseases.

Cancer Death Risk Related to Radiation Exposure from Computed Tomography Scanning Among Testicular Cancer Patients.

BACKGROUND: A study of the computed tomography (CT) imaging related effective doses and radiation-related cancer death risk. PATIENTS AND METHODS: Estimate effective doses were computed from CT scans of testicular cancer patients treated and followed-up in Turku University Hospital, South Western Finland. Association between effective doses from follow-up CT scans and radiation-induced cancer death was examined using United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) 2008 formula. RESULTS: Mean effective dose per CT abdomen was 9.32 (standard deviation, SD 3.89) mSv and for whole-body CT it was 14.24 (SD 6.84) mSv. During follow-up of 6 years, the patients were estimated to undergo 12 to 14 abdominal/whole-body CTs and the corresponding risk estimates were 0.11 and 1.14, respectively. The risk of estimated radiation-induced cancer deaths (RICD in %) computed for mean effective doses was lower in patients diagnosed at older age, being 0.61 for 10-19 years age and 0.04 for 40-49 years age at the diagnosis. CONCLUSION: Patient radiation exposure in CT imaging is associated with the type of CT device and imaging protocols, which should be periodically updated and reviewed to minimize individual exposure. Using the UNSCEAR modelling 2 % risk for radiation related cancer death was attributed to diagnostic exposure of study patients. Age at the diagnosis was associated with CT imaging related radiation exposure. The highest exposure was estimated to the youngest patients.

The Sentinel Node with Isolated Breast Tumor Cells or Micrometastases. Benefits and Risks of Axillary Dissection.

BACKGROUND/AIM: Sentinel lymph node (SLN) biopsy has become the standard procedure to identify metastases in axillary nodes in breast cancer. Even after careful SLN examination additional micrometastases and isolated tumor cells (ITCs) are sometimes found, resulting in a need for delayed axillary lymph node dissection (ALND). This study was undertaken to assess prognostic factors identifying additional axillary lymph node (ALN) metastases at delayed ALND. PATIENTS AND METHODS: To define the impact of late ALND regarding their outcome, 162 breast cancer patients with 169 operated breasts treated between 2010 and 2012 were evaluated, with follow-up through 2016. Data were collected on the patients, histology and biologic profile of the cancer, lymph node involvement, recurrence of breast cancer and adverse effects of ALND. RESULTS: With thorough examination and immunohistochemical stainings twenty-nine of 168 SLN biopsies (28 patients, 17% of the patients) showed micrometastases or ITC, and a full ALND was performed at a later time. During these ALNDs 13 to 31 lymph nodes were removed. Additional ALN metastases were found in three (10%) patients. Two (7%) of the 28 patients with triple-negative cancer deceased of metastatic breast cancer. Three patients (11%) reported adverse effects of ALND requiring physiotherapy due to pain, stiffness, swelling or arm oedema. Tumor factors such as molecular subtype (p=0.002), tumor size (p=0.004), and proliferation index (Ki-67) (p=0.003) correlated with higher numbers of ALN metastases. CONCLUSION: Since most patients with micrometastases found in the primary operation showed no additional positive lymph nodes, completion ALND may not be required in patients with micrometastases or ITCs in the SLN. In our study, the predictive factors for additional ALN metastases were tumur size, molecular subtype and proliferation index. It is conceivable that the features of the primary tumor, rather than the amount of cancer cells in the SLN, might serve to identify patients in whom ALDN can be avoided.

Probiotic supplementation reduces a biomarker for increased risk of liver cancer in young men from Southern China.

BACKGROUND: In vitro and in vivo studies suggest that selected strains of probiotic bacteria can form tight complexes with aflatoxin B(1) and other carcinogens. OBJECTIVE: The aim of the present study was to determine whether administration of probiotic bacteria could block the intestinal absorption of aflatoxin B(1) and thereby lead to reduced urinary excretion of aflatoxin B(1)-N(7)-guanine (AFB-N(7)-guanine), a marker for a biologically effective dose of aflatoxin exposure. Elevated urinary excretion of this aflatoxin-DNA adduct is associated with an increased risk of liver cancer. DESIGN: Ninety healthy young men from Guangzhou, China, were randomly assigned to 2 groups; one group received a mixture of Lactobacillus rhamnosus LC705 and Propionibacterium freudenreichii subsp. shermanii strains 2 times/d for 5 wk, and the other group received a placebo preparation. The subjects provided 4 urine samples: at baseline, at 3 and 5 wk after starting the supplementation, and at the end of the 5-wk postintervention period. RESULTS: The percentage of samples with negative AFB-N(7)-guanine values tended to be higher in the probiotic group than in the placebo group during the 5-wk intervention period (odds ratio: 2.63, P = 0.052), and a statistically significant decrease in the concentration of urinary AFB-N(7)-guanine was observed in the probiotic group. The reduction was 36% at week 3 and 55% at week 5. The geometric means for the probiotic and placebo groups were 0.24 and 0.49 ng AFB-N(7)-guanine/mL, respectively, during the intervention period (P = 0.005). CONCLUSION: A probiotic supplement reduces the biologically effective dose of aflatoxin exposure and may thereby offer an effective dietary approach to decrease the risk of liver cancer.

Impact of radiotherapy in the risk of esophageal cancer as subsequent primary cancer after breast cancer.

PURPOSE: To assess the risk of esophageal cancer as second cancer among breast-cancer patients treated with radiotherapy. METHODS AND MATERIALS: The records of the Finnish Cancer Registry from 1953 to 2000 were used to assess the risk of esophageal cancer as second cancer among 75,849 breast-cancer patients. Patients were treated with surgery (n = 33,672), radiotherapy (n = 35,057), chemotherapy and radiotherapy (n = 4673), or chemotherapy (n = 2,447). The risk of a new primary cancer was expressed as standardized incidence ratio (SIR), defined as the ratio of observed to expected cases. RESULTS: By the end of 2000, the number of observed cases esophageal cancers was 80 vs. 72 expected cases (standardized incidence ratio (SIR) = 1.1, 95% Confidence Interval (CI) = 0.9 to 1.5). Among patients followed for 15 years and treated with radiotherapy, the SIR for esophageal cancer was 2.3 (95% CI = 1.4 to 5.4). No increase in risk was seen for patients treated without radiotherapy. The risk of esophageal cancer was increased among patients diagnosed during 1953 to 1974, although age at the treatment did not have marked effect on the risk estimate. CONCLUSION: Increased risk of second cancer in the esophagus was observed for breast-cancer patients in Finland, especially among patients with over 15 years of follow-up and treated in the earliest period, which may relate to the type of radiotherapy.

The association of immunoreactive p53 and Ki-67 with T-stage, grade, occurrence of metastases and survival in renal cell carcinoma.

BACKGROUND: The aim of this study was to clarify the association of p53 and Ki-67 protein expressions with tumor characteristics and survival in renal cell carcinoma (RCC). MATERIALS AND METHODS: One hundred and seventeen patients were included in the study, 101 (86%) with conventional RCC according to the Heidelberg classification. Patients were divided into three groups with either primary metastases (pm), later metastases (lm), or no metastases (nm) during 7.5 years follow-up. Paraffin-embedded tissues were examined by immunohistochemistry utilizing anti-p53 and anti-Ki-67 antibodies, with a positive reaction cut-off of 10%. RESULTS: In conventional RCC, there was more Ki-67 positivity in high T(tumor)-stage compared to low T-stage (p = 0.036) and in pm patients compared to nm patients (p = 0.007); p53 was not associated with T-stage or metastatic category. Coexpression of p53/Ki-67 was more common in pm patients than in lm patients, but was not observed in nm patients (p = 0.001). In the pm/lm group, p53 and Ki-67 expressions were associated with decreased survival (log-rank, p = 0.030 and p = 0.031, respectively). In lm patients, high T-stage (T3, T4) was associated with metastases-free survival (p = 0.034) and overall survival (p = 0.006). CONCLUSION: p53 and Ki-67 expressions are associated with aggressive tumor phenotype and decreased survival in metastatic RCC. Ki-67 alone was a stronger prognostic marker than p53 for development of metastases. Double positivity for p53 and Ki-67 expression in RCC patients seems to indicate a high metastatic probability.

Symptom Assessment for Patients with Non-small Cell Lung Cancer Scheduled for Chemotherapy.

AIM: This study assessed the symptoms and health-related quality of life (HRQOL) of patients with advanced non-small cell lung cancer (NSCLC) and examined the symptom-associated characteristics. PATIENTS AND METHODS: The symptoms of 122 patients with NSCLC scheduled for chemotherapy before starting treatment were surveyed using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire and Edmonton Symptom Assessment Scale (ESAS). RESULTS: The most prevalent symptoms were coughing (EORTC score 41.7), dyspnea (33.9), fatigue (31.9), insomnia (30.3) and pain (21.8). The mean EORTC score for global QoL was 56.9 (SD=23.5). Physical, cognitive and emotional functioning, insomnia, diarrhea, and dyspnea had a significant influence on the HRQOL (p<0.05). ESAS assessment correlated with these results and thus was an easy-to-use tool for symptom assessment (correlation coefficient range=0.546-0.865, p<0.0001 for all symptoms). CONCLUSION: Patients with advanced NSCLC suffer from multiple symptoms influencing HRQOL. ESAS provides a symptom assessment tool that is as reliable as but simpler to use than the EORTC questionnaire.

Positron emission tomography is superior to computed tomography scanning for response-assessment after radical radiotherapy or chemoradiotherapy in patients with non-small-cell lung cancer.

PURPOSE: To prospectively study the capacity of positron emission tomography (PET) and computed tomography (CT) to determine response soon after radical radiotherapy or chemoradiotherapy and, thereby, predict survival. PET is known to provide a more accurate estimate of true extent of disease than CT when used to stage non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Seventy-three patients with NSCLC underwent [(18)F]fluorodeoxyglucose PET and CT scans before and after radical radiotherapy (n = 10) or chemoradiotherapy (n = 63). Follow-up PET scans were performed at a median of 70 days after radiotherapy. The median PET-CT interval was 1 day. Each patient had determinations of response to therapy made with PET and CT, categorized as complete response, partial response, no response, progressive disease, or nonassessable. Responses were correlated with subsequent survival. RESULTS: Median survival after follow-up PET was 24 months. There was poor agreement between PET and CT responses (weighted kappa = 0.35), which were identical in only 40% of patients. There were significantly more complete responders on PET (n = 34) than CT (n = 10), whereas fewer patients were judged to be nonresponders (12 patients on PET v 20 on CT) or nonassessable (zero patients on PET v six on CT) by PET. Both CT and PET responses were individually significantly associated with survival duration; but on multifactor analysis that included the known prognostic factors of CT response, performance status, weight loss, and stage, only PET response was significantly associated with survival duration (P <.0001). CONCLUSION: In NSCLC, a single, early, posttreatment PET scan is a better predictor of survival than CT response, stage, or pretreatment performance status.

Phase III study of letrozole versus tamoxifen as first-line therapy of advanced breast cancer in postmenopausal women: analysis of survival and update of efficacy from the International Letrozole Breast Cancer Group.

PURPOSE: To analyze overall survival (OS) and update efficacy data for letrozole versus tamoxifen as first-line therapy in postmenopausal women with locally advanced or metastatic breast cancer. PATIENTS AND METHODS: This multicenter phase III trial randomly assigned 916 patients with hormone receptor-positive or unknown tumors letrozole 2.5 mg (n = 458) or tamoxifen 20 mg (n = 458) daily until disease progression. Optional cross-over was permitted at the treating physician's discretion. This report updates efficacy at a median follow-up of 32 months. RESULTS: The superiority of letrozole to tamoxifen was confirmed for time to progression (median, 9.4 v 6.0 months, respectively; P <.0001), time to treatment failure (median, 9 v 5.7 months, respectively; P <.0001), overall objective response rate (32% v 21%, respectively; P =.0002), and overall clinical benefit. Median OS was slightly prolonged for the randomized letrozole arm (34 v 30 months, respectively). Although this difference in OS is not significant, survival was improved in the randomized letrozole arm over the first 2 years of the study. Approximately one half of the patients in each arm crossed over. Total duration of endocrine therapy ("time to chemotherapy") was significantly longer (P =.005) for patients initially on letrozole (median, 16 months) than for patients initially on tamoxifen (median, 9 months). Time to worsening of Karnofsky performance score was significantly delayed with letrozole compared with tamoxifen (P =.001). CONCLUSION: This study documents the superiority of letrozole over tamoxifen in first-line endocrine therapy in postmenopausal women with advanced breast cancer.

Associations between serum testosterone fall and cognitive function in prostate cancer patients.

Data on the association between cognition and testosterone levels in elderly men are inconclusive. Androgen deprivation therapy is commonly used in the treatment of prostate cancer with the aim of achieving castration levels of serum testosterone. The study group comprised 26 elderly men (mean age 65 years) with newly diagnosed prostate cancer. Cognitive testing was done at baseline and at 6 and 12 months on androgen deprivation therapy. Cognitive performances were evaluated using verbal, visuomotor, and memory tests as well as tests of processing speed and attention. Castration levels of testosterone were achieved in all patients by 6 months. Significant associations between cognitive performances and testosterone decline were documented: visuomotor slowing, slowed reaction times in some attentional domains including working memory and impaired hit rate in a vigilance test, impaired delayed recall and recognition speed of letters, but improvement in object recall. The results suggest selective associations between testosterone decline and cognition. Documentation of cognitive performance with changes in serum testosterone levels has substantial implications for informed patient support in prostate cancer.

Increased proliferation activity measured by immunoreactive Ki67 is associated with survival improvement in rectal/recto sigmoid cancer.

AIM: To assess the expression of Ki67 as prognosticator in rectal/recto sigmoid cancer. METHODS: Samples from 146 patients with rectal and recto sigmoid cancer were studied for expression of Ki67 and its prognostic significance in comparison with clinico-pathological predictors of survival. Formalin-fixed, paraffin-embedded tissues from 6 (4.1%) patients with T1, 26 (17.8%) with T2, 94 (64.4%) with T3, and 20 (13.7%) with T4 tumors were studied. Ki67 expression was determined immunohistochemically. Samples were divided according to mean value into high (>40%) and low (< or =40%) expression. Areas of extensive proliferation (>50%) were defined as "hot spot" areas. RESULTS: Hot spot areas were present in samples regardless of histopathological grade. Lower TNM and Dukes stage and higher expression of Ki67 and presence of Ki67 hot spot areas in histopathological samples were associated with better survival, whereas no association was observed with histopathological grade (P = 0.78). In Cox multivariate regression analysis, significant prognostic factors were Dukes stage (P<0.001), presence of lymph node metastases (P = 0.015), age (P = 0.035) and presence of Ki67 hot spot areas (P = 0.044). CONCLUSION: Proliferative activity as measured by Ki67 in rectal cancer is associated with survival improvement compared with patients with low Ki67. Areas of prognostically significant increased proliferation were found independently of histopathological tumor grade.

Relationship between proliferative activity of cancer cells and clinicopathological factors in patients with esophageal squamous cell carcinoma.

AIM: To assess whether the molecular markers of malignant tumors could improve the understanding of tumor characteristics, and to observe the characteristics of expression of cell cycle markers Ki-67 and cyclin A in esophageal carcinoma and to analyze the relationship between proliferative activity of cancer cells and clinicopathological factors. METHODS: Seventy of surgically resected esophageal squamous cell carcinoma (SCC) were examined by immunohistochemistry utilizing commercially available antibodies. Nuclear staining was regarded as a positive result. At least 50 fields in each tumor and non-tumor section were evaluated at a medium power (X200) to determine the proportion of tumor cells and the staining intensity of nuclei in the entire sections. RESULTS: Ki-67 and cyclin A were only expressed in base cells of normal esophageal mucosa. The positive immuno-staining of nuclei of SCC was significantly higher than that in normal esophageal mucosa (t=13.32 and t=7.52, respectively, P<0.01). The distribution of positively stained was more diffuse and stronger in poorly differentiated SCC. Both Ki-67 and cyclin A expressions were related to histological grades of tumors (t=3.5675 and t=3.916; t=2.13, respectively, P<0.05) but not to the sex and age of the patients, tumor size, lymphatic invasion, location, or stage grouping. CONCLUSION: The proliferative activity of cancer cells may be understood by immunohistochemistry of Ki-67 and cyclin A in Chinese patients with esophageal SCC. These cell cycle markers may serve as an indicator of cancer cell proliferation rate. The overexpression of cell cycle markers Ki-67 and cyclin A suggests the poor SCC differentiation in patients with esophageal carcinoma.