Prognostic value of the immunohistochemical expression of: Ki67, p53, PCNA and Bcl2 in the superficial tumors of the bladder

AIM: To study a serie of superficial tumors of the bladder and to assess the prognostic significance of p53, Ki67, PCNA and bcl2 in these tumors. METHODS: We studied 59 bladder tumors: 43 pTa and 16 pT1. All Patients had cystoscopy 3 months after the resection and tumors that did not recur had a minimum follow up of 5 years. RESULTS: Age more than 65 years (p = 0,001), multifocality (p=0,022) and tumoral size > or = 3 cm (p = 0,022) were correlated with the recurrence. The expression of p53 was correlated with the recurrence in the year following the tumoral resection (p = 0,035). That of of Ki67 was correlated with the histological grade (p = 0,03) and stage (p=0,002). CONCLUSION: Our results suggest to practise regular endoscopic controls during the first year following the resection of the primitive tumor if it expresses p53. The immunohistochemical expression of Ki67 being correlated with the grade, this marker could help to better classify the tumors of intermediate grade.     

Prognostic value of clinicopathologic factors in superficial bladder tumors: a retrospective analysis

OBJECTIVE: To study, through a series of superficial bladder tumors, the prognostic factors of recurrence and tumoral progression. MATERIALS AND METHODS: This is a retrospective study of a series of 59 urothelial tumors of the bladder at stage pTa or pT1. The following parameters were considered: age, sex, treatment, stage and grade. The chi square test was used in search of a correlation between the different parameters and the course (recurrence and progress) of the disease. A multivariate analysis was undertaken by integrating factors correlated with the course. RESULTS: Thirty two tumors (54 %) had recured versus 27 (46%) without recurrence. Eight tumors (25 %) progressed in grade and 4 (12,5 %) had become infiltrative. Age beyond 65 years, tumoral size > 3 cm and multifocality were predictive factors of recurrence with a relative risks of 2,36, 3,28 and 3,88 respectively. In a multivariate analysis, these factors remained significant with adjusted relatif risks respectively of 1,36, 1,6 and 1,7.     

吡柔比星膀胱灌注预防膀胱肿瘤复发的有效性和药理分析

目的观察吡柔比星膀胱灌注预防膀胱肿瘤复发的有效性,并对其药理作用展开分析。方法以2009年5月至2011年4月在我院接受治疗的膀胱肿瘤术后患者85例为研究对象,进行随机分组。所有患者均于术后1周开始进行膀胱灌注。A组42例患者给予丝裂霉素膀胱灌注,B组43例患者给予吡柔比星膀胱灌注治疗。术后随访1年,观察两组患者复发率、死亡率和治疗期间膀胱刺激征发生率的差异。结果与A组相比较,B组复发率、死亡率均明显较低,有统计学差异(P<0.05)。两组治疗期间膀胱刺激征发生率比较,无统计学差异(P>0.05)。结论采用吡柔比星膀胱灌注预防膀胱肿瘤复发效果满意,可在今后的临床工作中加以应用。     

Efficient scheduling of cystoscopies in monitoring for recurrent bladder cancer

Proper timing for repeated evaluations is difficult to assess. The authors analyzed scheduling of cystoscopy to monitor patients for detection of recurrent bladder cancer assuming that 1) minimizing tumor detection delay helps prevent cancer morbidities; 2) only limited numbers of cystoscopies are available; 3) prediction of recurrence or progression to invasive cancer is uncertain; 4) future tumors recur according to a Poisson process. Assumptions 3 and 4 permit estimation of each patient's recurrence rate. Thus, patients may be compared according to their relative risks of future tumors. With these assumptions, nonlinear optimization theory was used to calculate monitoring schedules for a model practice. Given 5.4 available visits per week per 100 patients, cystoscopy was recommended in 9-11 weeks for high-risk patients and in 30-40 weeks for low-risk patients, depending on stages, grades, and numbers of previous tumors. In contrast, standard cystoscopy was recommended in 13, 26, or 52 weeks, depending only on time elapsed since last recurrence. The calculated schedule implied an average detection delay for potentially invasive tumors of eight weeks, while standard practice led to detection delays of 11 weeks (38% worse). These results suggest that inclusion of each patient's tumor history in an optimization approach may improve follow-up care for patients who have superficial bladder cancers. This approach is being evaluated in a larger clinical setting.     

Dose effects of flaxseed and its lignan on N-methyl-N-nitrosourea-induced mammary tumorigenesis in rats

Dietary supplementation with flaxseed or its lignan secoisolariciresinol diglycoside (SDG) has reduced dimethylbenz[a]anthracene-induced mammary tumor size and number in rats. The objective of this study was to determine whether flaxseed has a dose-dependent effect on N-methyl-N-nitrosourea (MNU)-induced mammary tumor promotion and whether this effect can be attributed to its SDG. Two days after injection with MNU (50 mg/kg body wt i.p.), female Sprague-Dawley rats were fed a high-fat (20% soybean oil) AIN-93G basal diet alone (BD) or supplemented with flaxseed (2.5% F and 5% F) or SDG by gavage [SDG in 2.5% F (LSDG) and SDG in 5% F (HSDG)] for 22 weeks. Although tumors tended to be smallest in the 5% F group throughout the experimental period, flaxseed feeding did not significantly affect tumor size, multiplicity, or incidence in comparison to BD. However, there was a dose-dependent effect of SDG on tumor multiplicity. Tumor multiplicity was lowest in the HSDG group and highest in the LSDG group throughout treatment (p < 0.05), indicating that HSDG inhibited, whereas LSDG promoted, MNU-induced mammary tumor development. Tumor invasiveness and grade were decreased in all treatment groups compared with the BD (p < 0.032). Thus, although flaxseed feeding had no significant effect on tumor growth indexes, flaxseed and SDG treatment, regardless of dose, appeared to delay the progression of MNU-induced mammary tumorigenesis. Disparities between this study and previous studies on flaxseed may be related to differences in experimental design, the use and dose of a different carcinogen, and protective effects by the alpha-linolenic acid present in the BD.     

Differences between Hispanic and non-Hispanic white women with breast cancer for clinical characteristics and their correlates

PurposeBody size and ethnicity may influence breast cancer tumor characteristics at diagnosis. We compared Hispanic and non-Hispanic white (NHW) cases for stage of disease, estrogen receptor (ER) status, tumor size, and lymph node status, and the associations of these with body size in the 4-Corners Breast Cancer Study.MethodsOne thousand five hundred twenty-seven NHW and 798 Hispanic primary incident breast cancer cases diagnosed between October 1999 and May 2004 were included. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by multiple logistic regression.ResultsHispanic women were more likely to have larger (>1 cm) ER? tumors and more than four positive lymph nodes (P < .003). Lymph node status was not associated with body size. However, among NHW women, obesity (body mass index >30) and increased waist circumference (>38.5 inches) were significantly positively associated with ER? tumor status (OR, 1.87; 95% CI, 1.24–2.81 and OR, 2.59; 95% CI, 1.58–4.22, respectively). In contrast, among Hispanic women, obesity and waist circumference had inverse associations with ER? tumor status (OR, 0.49; 95% CI, 0.29–0.84 and OR, 0.56; 95% CI, 0.30–1.05, respectively).ConclusionsHispanic ethnicity may modify the association of body size and composition with ER? breast cancer. This finding could have relevance to clinical treatment and prognosis.     

Dietary Berries and Ellagic Acid Diminish Estrogen-Mediated Mammary Tumorigenesis &isin; ACI rats

Estrogen acts as a complete mammary carcinogen in ACI rats. Prevention studies in this model allowed us to identify agents that are effective against estrogen-induced mammary carcinogenesis. In this study, we investigated efficacy of dietary berries and ellagic acid to reduce estrogen-mediated mammary tumorigenesis. Female ACI rats (8–9 wk) were fed either AIN-93M diet (n = 25) or diet supplemented with either powdered blueberry (n = 19) and black raspberry (n = 19) at 2.5% wt/wt each or ellagic acid (n = 22) at 400 ppm. Animals received implants of 17β-estradiol 2 wk later, were palpated periodically for mammary tumors, and were euthanized after 24 wk. No differences were found in tumor incidence at 24 wk; however, tumor volume and multiplicity were reduced significantly after intervention. Compared with the control group (average tumor volume = 685 ± 240 mm3 and tumor multiplicity = 8.0 ± 1.3), ellagic acid reduced the tumor volume by 75% (P < 0.005) and tumor multiplicity by 44% (P < 0.05). Black raspberry followed closely, with tumor volume diminished by > 69% (P < 0.005) and tumor multiplicity by 37% (P = 0.07). Blueberry showed a reduction (40%) only in tumor volume. This is the first report showing the significant efficacy of both ellagic acid and berries in the prevention of solely estrogen-induced mammary tumors.     

Clinical Presentation of Retinoblastoma in Ethiopia: A Case of Jimma University Medical Center Pediatric Oncology Unit,Southwest Ethiopia

BackgroundRetinoblastoma (RB) is one of the most curable childhood cancers if early detected and treated. Late presentation complicates the management of RB results in dismal treatment outcome. Objective: The aim of this study is to report the clinical presentation pattern of retinoblastoma patients seen at Jimma University Medical center (JUMC).MethodsThe study was a retrospective review of retinoblastoma cases managed at JUMC between August 2016 and July 2020.ResultsAmong pediatric oncology cases registered retinoblastoma, accounting 8.5 % (36/423) of all childhood cancer patients in the study period, 29 (90.6%) of them had unilateral retinoblastoma and 3(9.4%) of them had bilateral retinoblastoma. The average age at presentation for bilateral and unilateral retinoblastoma patients was 17 (range 3–30) months and 37.5 months (range 8–84) respectively. The first symptom observed by the family was leukocoria in 21 (65.6%) of the patients but 24(75%) of the patients presented with advanced stage (proptosis and fungating orbital mass) of the disease. The longest and the shortest lag time of presentation from the first symptom was 17 months and 2 weeks respectively with the mean lag time of 1.4 months in bilateral and 6 months in unilateral cases. Clinically, the majority of the eyes 24/35(68.6%) were extraocular tumors involving orbital tissues at presentation.ConclusionMost of retinoblastoma patients presented at advanced stage of the disease and presented very late after the family observed the disease. Early detection strategies must be designed by the government and responsible stakeholders in mitigating the effects of late presentation.     

动脉化疗栓塞对膀胱癌组织中Ki-67表达的影响

目的 探讨术前动脉化疗栓塞对膀胱癌组织中核增殖相关抗原(gi-67)表达的影响.方法 对30例动脉化疗栓塞前后的膀胱癌组织,应用免疫组化方法测定Ki-67的表达,并分析Ki-67与膀胱癌病理分级和临床分期的关系.结果 动脉化疗栓塞前后Ki-67阳性和强阳性表达率分别为70.00%、26.67%,差异有统计学意义(P＜0.01).30例患者平均随访24.6个月,复发率为16.67%.Ki-67阳性表达及动脉化疗栓塞前后降低幅度与膀胱癌的病理分级、临床分期和患者术后复发率关系密切.结论 Ki-67的表达可作为膀胱癌预后评估的指标.     

3种方法经膀胱镜治疗膀胱肿瘤

目的:探讨膀胱镜下治疗膀胱肿瘤的几种方法。方法:总结比较膀胱镜下3种治疗方法:肿瘤蒂部注射复方硫酸铝、经尿道膀胱肿瘤电切(TURBT)、应用钬激光治疗膀胱肿瘤。结果:瘤蒂部注射复方硫酸铝治疗膀胱癌1174例,操作简单,经济实用,无闭孔神经反射,肿瘤无原位复发,但对大而且无蒂的肿瘤并不合适;TURBT700例,需要有一定的操作技术及设备,过程中需注意止血及闭孔神经反射,有部分原位复发;应用钬激光治疗膀胱肿瘤34例,有3例异位复发,无原位复发,需钬激光操作设备。结论:3种方法在膀胱镜下对膀胱肿瘤治疗均有效但各有利弊,应视病人具体病情选择最佳治疗方案,具体操作时交叉使用互补以获取最好的疗效。     

Initial phase I/IIa trial results of an autologous tumor lysate,particle-loaded,dendritic cell (TLPLDC) vaccine in patients with solid tumors

IntroductionTumor vaccines use various strategies to generate immune responses, commonly targeting generic tumor-associated antigens. The tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine is produced from DC loaded with autologous tumor antigens, creating a patient-specific vaccine. Here, we describe initial phase I/IIa trial results.MethodsThis trial includes patients with any stage solid tumors, ECOG ≤1, and >4 months life-expectancy. A personalized vaccine is created using 1 mg of tumor and 120 ml blood (to isolate DC). Primary vaccination series (PVS) is four monthly inoculations. Patients are followed per standard of care (SOC). Endpoints include safety and tumor response (RECIST v1.1).Results44 patients were enrolled and vaccinated consisting of 31 late stage patients with residual/measurable disease, and 13 disease-free patients after SOC therapies. While 4 patients progressed before completing the PVS, 12/31 (39%) demonstrated clinical benefit (2 complete responses, 4 partial responses, 6 stable disease). In the adjuvant setting, 46% of late stage patients remain disease free at a median of 22.5 months.ConclusionsThe TLPLDC vaccine is scalable, generates a personalized DC vaccine, and requires little autologous tumor tissue and few DC. The vaccine is safe, with primarily grade 0–2 toxicities, and nearly 40% clinical benefit rate in varied tumors, warranting further study.Trial Registration: ISRCTN81339386, Registered 2/17/2016.     

Dietary berries and ellagic acid diminish estrogen-mediated mammary tumorigenesis in ACI rats

Estrogen acts as a complete mammary carcinogen in ACI rats. Prevention studies in this model allowed us to identify agents that are effective against estrogen-induced mammary carcinogenesis. In this study, we investigated efficacy of dietary berries and ellagic acid to reduce estrogen-mediated mammary tumorigenesis. Female ACI rats (8-9 wk) were fed either AIN-93M diet (n = 25) or diet supplemented with either powdered blueberry (n = 19) and black raspberry (n = 19) at 2.5% wt/wt each or ellagic acid (n = 22) at 400 ppm. Animals received implants of 17beta-estradiol 2 wk later, were palpated periodically for mammary tumors, and were euthanized after 24 wk. No differences were found in tumor incidence at 24 wk; however, tumor volume and multiplicity were reduced significantly after intervention. Compared with the control group (average tumor volume = 685 +/- 240 mm3 and tumor multiplicity = 8.0 +/- 1.3), ellagic acid reduced the tumor volume by 75% (P < 0.005) and tumor multiplicity by 44% (P < 0.05). Black raspberry followed closely, with tumor volume diminished by > 69% (P < 0.005) and tumor multiplicity by 37% (P = 0.07). Blueberry showed a reduction (40%) only in tumor volume. This is the first report showing the significant efficacy of both ellagic acid and berries in the prevention of solely estrogen-induced mammary tumors.     

丝裂霉素与卡介苗膀胱灌注预防浅表膀胱癌术后复发比较

目的比较丝裂霉素(MMC)与卡介苗(BCG)膀胱灌注预防浅表膀胱癌术后复发的疗效及毒副作用。方法回顾分析1996年8月~2006年8月间在我院手术的132例浅表性膀胱癌患者的临床资料。结果128例患者获随访,中位随访时间62.7(6.6~122.0)个月,总的复发率为21%,从手术到肿瘤局部复发的平均时间为13.8月(3.6~71.8)个月。5年和10年总的无复发生存率为80.7%和71.3%。MMC组与BCG组的总复发率分别为21.8%和18.5%,两组之间无显著差异(P=0.087)。对于高分级肿瘤,MMC组的复发率(24.0%)显著高于BCG组(17.5%),BCG膀胱灌注能显著降低高分级膀胱肿瘤的术后复发率(P=0.046)。BCG组患者出现膀胱炎等毒副作用的机率较高(P=0.0316)。结论BCG膀胱灌注预防浅表性膀胱癌术后复发较MMC无明显优势,且出现膀胱炎等毒副作用的机率较高,但可显著降低高分级膀胱肿瘤的术后复发率。     

Intravesical chemotherapy prophylaxis in primary superficial bladder cancer: a meta-analysis of 3703 patients from 11 randomized trials

The impact of intravesical chemotherapy prophylaxis on recurrence of superficial transitional cell carcinoma of the bladder is poorly defined. The objective of this report is to present a meta-analysis of the available clinical trial data to quantify the effect of intravesical chemotherapy on tumor recurrence following complete transurethral resection (TURB) in patients with newly diagnosed superficial bladder cancer. A prospective protocol outlining the above meta-analysis was initially developed followed by a thorough search of the existing published literature using strict eligibility criteria. Eleven randomized trials were found that met protocol specifications. These studies contained data on 3703 patients that were statistically combined using a fixed effects model (Peto). The outcome of interest was the proportion of patients recurring at 1, 2, and 3 years post-TURB. Combining all 11 studies using 1-year recurrence as the outcome measure yielded a Peto odds ratio (ORp) of 0.56, demonstrating a 44% reduction in 1-year recurrence among patients treated with intravesical chemotherapy versus those treated with TURB alone. A statistical test for heterogeneity (Q) showed these data to be heterogenous (the studies are not measuring an effect of the same size). Sensitivity analyses were performed to determine sources of heterogeneity. These tests suggest that chemotherapy treatment schedule may account for the wide variation in tumor recurrence rates across studies. When the available clinical trial data were stratified by duration of treatment, the meta-analysis showed that intravesical chemotherapy decreased tumor recurrence from 30% to 80% depending on the outcome of interest (i.e., recurrence at 1, 2, or 3 years post-TURB). Intravesical chemotherapy appears to have a major impact on decreasing the chance of recurrence of superficial transitional cell carcinoma of the bladder. This is in contrast to prior analyses suggesting only modest efficacy in this clinical setting (i.e., on the order of a 14% reduction in recurrence).     

β-carotene regulates cancer stemness in colon cancer in vivo and in vitro

BACKGROUND/OBJECTIVESColorectal cancer (CRC) is the third most common cancer worldwide and has a high recurrence rate, which is associated with cancer stem cells (CSCs). β-carotene (BC) possesses antioxidant activity and several anticancer mechanisms. However, no investigation has examined its effect on colon cancer stemness.MATERIALS/METHODSCD133⁺CD44⁺ HCT116 and CD133⁺CD44⁺ HT-29 cells were isolated and analyzed their self-renewal capacity by clonogenic and sphere formation assays. Expressions of several CSCs markers and Wnt/β-catenin signaling were examined. In addition, CD133⁺CD44⁺ HCT116 cells were subcutaneously injected in xenograft mice and analyzed the effect of BC on tumor formation, tumor volume, and CSCs markers in tumors.RESULTSBC inhibited self-renewal capacity and CSC markers, including CD44, CD133, ALDH1A1, NOTCH1, Sox2, and β-catenin in vitro. The effects of BC on CSC markers were confirmed in primary cells isolated from human CRC tumors. BC supplementation decreased the number and size of tumors and delayed the tumor-onset time in xenograft mice injected with CD133⁺CD44⁺ HCT116 cells. The inhibitory effect of BC on CSC markers and the Wnt/β-catenin signaling pathway in tumors was confirmed in vivo as well.CONCLUSIONSThese results suggest that BC may be a potential therapeutic agent for colon cancer by targeting colon CSCs.     

Expression of progestrone receptor and proliferative marker ki 67 in various grades of meningioma

Meningiomas are slow-growing neoplasms which recur locally, their morphologic grading is simple but do not always correlate with patient outcome. The aim of present study is to evaluate the status of progesterone receptor (PR) and proliferation marker Ki67 in various grades of meningioma in a group of Iranian patients. 78 cases of meningioma were selected from the file of a hospital university. All archival H&E stained sections were reviewed and regraded according to WHO criteria. Immunohistochemical analysis for PR and Ki67 was performed on formalin-fixed, paraffin-embedded samples. PR status considered positive if >10% of tumor cell's nuclei were strongly immunoreactive, or if >50% of nuclei were stained with medium intensity. The Ki67 labeling index (LI) is defined as the percentage area with strongest immunostaining. PR were positive in 61/63 (96.8%) of grade I tumors, 2/10 (20%) of grade II, and 0/5 (0%) of grade III tumors. Ki67 LI was %2.98 +/- 2.27 in grade I tumors, %9.30 +/- 5.79 in grade II tumors and %34.00 +/- 5.47 in grade III tumors. For both markers, differences between grade I, II and III tumors were significant (P < 0.001). There was a reverse relationship between mean of Ki67 LI and PR status, with increasing grade of tumor. Evaluation of PR status and Ki67 LI together with conventional histologic evaluation can help in providing more information about the biologic behaviour of meningiomas, especially for those that histological grading is not straightforward.     

Clinical experience of hyperthermia in malignant tumors

Results in 44 cases of malignant tumors treated by localized radiofrequency hyperthermia are presented. All patients had either one or more failed attempts at conventional therapy or had such advanced disease at presentation that control with conventional modalities was considered unlikely. Hyperthermia were used together with radiation in 42 patients with chemotherapy in 1 patient, and alone in 1 patient. The overall response (CR plus PR) was 50% including a 18% complete response. Tumor response was somewhat better for superficial tumors. We retrospectively have analyzed the association between tumor response and histology, tumor size, temperature, radiation dose and total number of heat sessions. Clinical factors influencing the tumor response were initial tumor size and intratumor temperature. The incidence of overall response increased with a decrease in initial tumor size and an increase of intratumor temperature.     

经尿道绿激光汽化术治疗表浅膀胱肿瘤(附33例报告)

[目的]探讨经尿道绿激光汽化术治疗浅表膀胱肿瘤的手术方法、安全性与疗效。[方法]2004年9月~2007年12月,33例浅表膀胱肿瘤患者接受经尿道绿激光汽化术治疗,回顾手术时间,治疗效果。[结果]手术时间平均为12min(单发肿瘤5~9min,多发10~35min),术中无闭孔神经反射、无膀胱穿孔、无TUR综合征、几乎无出血、无输血病例。术后留置双腔气囊尿管3d,不需膀胱冲洗,术后膀胱肿瘤复发率0%,术后均行正规膀胱灌注化疗和膀胱镜定期检查,所有患者均存活,未发生死亡病例。其中1例由于肿瘤巨大改为TURBT术。[结论]经尿道绿激光汽化术治疗表浅膀胱肿瘤,疗效确切,安全可靠,此术式有望成为治疗浅表膀胱肿瘤的主要方法。     

A Multigene Prognostic Assay for Selection of Adjuvant Chemotherapy in Patients with T3, Stage II Colon Cancer: Impact on Quality-Adjusted Life Expectancy and Costs

ObjectivesUncertainty exists regarding appropriate and affordable use of adjuvant chemotherapy in stage II colon cancer (T3, proficient DNA mismatch repair). This study aimed to estimate the effectiveness and costs from a US societal perspective of a multigene recurrence score (RS) assay for patients recently diagnosed with stage II colon cancer (T3, proficient DNA mismatch repair) eligible for adjuvant chemotherapy.MethodsRS was compared with guideline-recommended clinicopathological factors (tumor stage, lymph nodes examined, tumor grade, and lymphovascular invasion) by using a state-transition (Markov) lifetime model. Data were obtained from published literature, a randomized controlled trial (QUick And Simple And Reliable) of adjuvant chemotherapy, and rates of chemotherapy use from the National Cooperative Cancer Network Colon/Rectum Cancer Outcomes study. Life-years, quality-adjusted life expectancy, and lifetime costs were examined.ResultsThe RS is projected to reduce adjuvant chemotherapy use by 17% compared with current treatment patterns and to increase quality-adjusted life expectancy by an average of 0.035 years. Direct medical costs are expected to decrease by an average of $2971 per patient. The assay was cost saving for all subgroups of patients stratified by clinicopathologic factors. The most influential variables affecting treatment decisions were projected years of life remaining, recurrence score, and patients' disutilities associated with adjuvant chemotherapy.ConclusionsUse of the multigene RS to assess recurrence risk after surgery in stage II colon cancer (T3, proficient DNA mismatch repair) may reduce the use of adjuvant chemotherapy without decreasing quality-adjusted life expectancy and be cost saving from a societal perspective. These findings need to be validated in additional cohorts, including studies of clinical practice as assay use diffuses into nonacademic settings.