Systemic combining inflammatory score (SCIS): a new score for prediction of oncologic outcomes in patients with high-risk non-muscle-invasive urothelial bladder cancer

BackgroundAn accurate and early diagnosis of bladder cancer (BC) is essential to offer patients the most appropriate treatment and the highest cure rate. For this reason, patients need to be best stratified by class and risk factors. We aimed to develop a score able to better predict cancer outcomes, using serum variables of inflammation.MethodsA total of 1,510 high-risk non-muscle invasive bladder cancer (NMIBC) patients were included in this retrospective observational study. Patients with pathologically proven T1 HG/G3 at first TURBT were included. Systemic combined inflammatory score (SCIS) was calculated according to systemic inflammatory markers (SIM), modified Glasgow prognostic score (mGPS), and prognostic nutritional index (PNI) dichotomized (final score from 0 to 3).ResultsAfter 48 months of follow-up (IQR 40.0–73.0), 727 patients recurred (48.1%), 485 progressed (32.1%), 81 died for cancer (7.0%), and 163 died for overall causes (10.8%). Overall, 231 (15.3%) patients had concomitant Cis, 669 (44.3%) patients had multifocal pathology, 967 (64.1%) patients had tumor size >3 cm. Overall, 357 (23.6%) patients received immediate-intravesical therapy, 1,356 (89.8%) received adjuvant intravesical therapy, of which 1,382 (91.5%) received BCG, 266 (17.6%) patients received mitomycin C, 4 (0.5%) patients received others intravesical therapy. Higher SCIS was independently predictive of recurrence (hazard ratio HR 1.5, 1.3 and 2.2) and cancer specific mortality for SCIS 0 and 3 (HR: 1.61 and 2.3), and overall mortality for SCIS 0 and 3 (HR: 2.4 and 3.2). Conversely, SCIS was not associated with a higher probability of progression.ConclusionsThe inclusion of the SCIS in clinical practice is simple to apply and can help improve the prediction of cancer outcomes. It can identify patients with high-grade BC who are more likely to experience disease mortality.     

膀胱癌特异性核基质蛋白-4在膀胱癌患者尿液中的表达及其临床意义

目的 探讨膀胱癌特异性核基质蛋白-4(BLCA-4)在膀胱癌患者早期诊断及术后监测肿瘤复发中的意义.方法 采用酶联免疫吸附试验(ELISA)法检测良性病变组、对照组和实验组患者术前及术后1、6个月和1年尿液中BLCA-4的表达.结果 实验组患者尿液中BLCA-4的含量中位数为39.48 A/μg protein,敏感性为93.33％,良性病变组和对照组分别为2.19 A/μg protein和0.965 A/μg protein,特异性为100％,2例复发患者术后1年复发时尿液中BLCA-4的含量均明显高于术后6个月时的含量.结论 BLCA-4作为一种新的膀胱肿瘤检测指标,有助于膀胱肿瘤的早期诊断及术后随访.     

Recommendations for follow-up of muscle-invasive bladder cancer patients: A consensus by the international bladder cancer network

Rationale

Several guidelines exist that address treatment of patients with nonmetastatic muscle-invasive bladder cancer (MIBC). However, most only briefly mention follow-up strategies for patients and hence the treating physician is often left to infer on what the preferred follow-up schema would be for an individual patient. Herein, we aim to synthesize recommendations for follow-up of patients with MIBC for easy reference.

术前外周血中淋巴细胞与单核细胞比值对高危非肌层浸润性膀胱癌预后的评估价值

目的探讨术前外周血中淋巴细胞与单核细胞比值（LMR）对高危非肌层浸润性膀胱癌（NMIBC）预后的评估价值。 方法回顾性分析2014年1月至2020年1月本院收治的120例高危NMIBC患者,收集术前血常规检测结果中淋巴细胞、单核细胞计数,按照LMR中位值将120例患者分为高低两组,术后随访,比较高LMR组和低LMR组的临床特征及1~5年无复发生存率情况,并应用Logistic多因素回归分析风险模型分析影响高危非肌层浸润性膀胱癌预后的独立危险因素,评估两组LMR指标与高危NMIBC预后的关系。 结果根据LMR中位值将患者分为低LMR组（<3.14,52例）和高LMR组（≥3.14,68例）,分析表明高LMR组和低LMR组的NLR、PLR、年龄、病理分级、肿瘤分期、肿瘤复发、分化程度之间差异有统计学意义（P<0.05）。低LMR组患者3~5年无复发生存率均明显低于高LMR组（P<0.05）。多因素分析表明LMR是影响肿瘤无复发生存率的独立相关因素（P<0.05）。 结论术前LMR与高危NMIBC患者的预后相关,可以作为判断预后的一项指标。     

Changing pattern in the clinical presentation of breast cancer in the absence of a screening program over a period of thirty-three years in Iran

ObjectiveTo survey the proportion of stages at the presentation of the disease without a screening program, among a population of breast cancer patients that is as a representative sample of the country in a distinct period.Materials and methodsThe population of the current study is found among the female breast cancer patients who were referred to oncology centers in northeastern Iran over a thirty-three-year period from 1980 to 2012.ResultsFour thousand patients were divided into three time periods consisting of 521 cases from 1980 to 1990, 1178 cases from 1991 to 2001, and 2302 cases from 2002 to 2012. While there was no difference in the proportions of T1 and T3 tumors, T2 tumors showed an increase (P = 0.001) and T4 tumors a decrease (P = 0.000) during these periods. There was no change in the proportion of stage I, however the proportion of stage II had risen (P = 0.000), while that of stage III (P = 0.002), and stage IV (P = 0.000) had fallen. The study's urban and rural populations experienced a similar trend in this respect, with the exception that the rural population exhibited more striking changes during the study's recent years.ConclusionAfter a thirty-three-year follow up on breast cancer in northeastern Iran, it is obvious that this disease is now presented in its earlier stages even in the absence of a screening program. In spite of this, the proportion of T1 disease and those tumors are discovered by a screening program has not significantly changed.     

The value of the UroVysion assay for surveillance of non-muscle-invasive bladder cancer

OBJECTIVE: Patients with non-muscle-invasive bladder cancer are traditionally followed by repeat cystoscopy and urine cytology. A fluorescence in situ hybridisation technique called UroVysion((R)) (UV) is now available for clinical diagnosis of urothelial cancer cells. The aim of the present study was to compare UV analysis with routine follow-up methods. METHODS: We studied an unselected cohort of patients undergoing cystoscopy follow-ups at two Swedish centres in 2004-2005. All patients were investigated by cystoscopy, cytology, and UV assay. The UV assay was evaluated with regards to sensitivity, specificity, and positive predictive value for tumour recurrence. RESULTS: In all, 159 cases were analysed. UV had a 30% overall sensitivity for the 27 biopsy-proven recurrences and 70% sensitivity for high-risk tumours (pT1 and carcinoma in situ [CIS]). The specificity of UV was 95%. UV detected all six CIS cases in the study and was predictive in two additional patients who developed CIS within 1 yr of inclusion. Cytology was positive in four of those eight CIS cases and atypical in the other four. CONCLUSIONS: The UV assay cannot replace cystoscopy for surveillance of patients with non-muscle-invasive bladder cancer, but it may be valuable as a supplement to traditional measures for detecting CIS. Before any conclusions can be drawn regarding the efficacy of novel markers of bladder cancer, they must be studied in bladder cancer patients undergoing endoscopic surveillance.     

Breast cancer in a county hospital population: Impact of breast screening on stage of presentation

Background: Indigent patients in a county hospital setting typically present with breast cancer at a later stage than do patients in the private sector. In the early 1980s, 50% of all breast cancers diagnosed in our county hospital were stages III and IV. This contrasted markedly with the findings of an American College of Surgeons study, which showed <15% of breast cancers diagnosed as stages III and IV. Methods: Recognizing this disparity, we instituted a breast screening project in the county teaching hospital targeted at women who routinely received medical care in the county hospital clinics. Between 1985 and 1992, 14,567 mammograms were performed. Results: Two hundred eighty-nine breast biopsies were performed and 76 cancers were identified (26%). Ninety-five patients advised to have surgical consultation for biopsy declined further evaluation. The stage distribution of cancers diagnosed was as follows: stage 0, 20%; stage I, 43%; stage II, 28%; stage III, 8%; and stage IV, 1%. This compares favorably with National Cancer Data Base statistics for 1988. In contrast, symptomatic nonscreened patients diagnosed at the county hospital in 1992 presented at a significantly more advanced stage: stage 0, 1%; stage I, 14%; stage II, 45%; stage III, 26%; and stage IV, 13%. Conclusions: Mammographic screening has lowered the stage of cancers diagnosed in the screened indigent population. However, a significant percentage of patients are presenting to our hospital with stage III and IV disease. Problems identified in the screening project included noncompliance with recommendations for follow-up of abnormal studies and noncompliance with appointments. In order to broaden the impact of our breast screening project, we have instituted outreach programs with community-based clinics and the American Cancer Society.The results of this study were presented at the 46th Annual Cancer Symposium of the Society of Surgical Oncology, Los Angeles, California, March 18–21, 1993.     

Impact of symptomatic recurrence on oncological outcomes in patients with primary high-risk non-muscle-invasive bladder cancer

ObjectivesTo evaluate the impact of symptomatic recurrence on oncological outcomes in patients with primary high-risk non-muscle invasive bladder cancer (NMIBC) who underwent transurethral resection of bladder tumor (TURBT).Materials and MethodsWe retrospectively evaluated 428 patients with primary high-risk NMIBC who underwent TURBT from November 1993 to April 2019. Of the 428 patients, 140 had experienced recurrence at any site and were divided into 2 groups: patients who had experienced recurrence detected by the surveillance (asymptomatic group) and patients who had experienced recurrence detected by a symptom-driven investigation (symptomatic group). Background-adjusted multivariable analyses with the inverse probability of treatment weighting method were performed to evaluate the impact of symptomatic recurrence on cancer-specific survival and overall survival after first recurrence in patients who had experienced recurrence. Moreover, multivariable analysis was performed to identify predictive factors of symptomatic recurrence in the entire cohort.ResultsMedian age and follow-up periods were 72 (interquartile range [IQR] 64–79) years and 55 (IQR 29–96) months, respectively. Of the 140 patients who experienced recurrence, 106 (76%) were diagnosed by the surveillance (asymptomatic group) and 34 (24%) were diagnosed by a symptom-driven investigation (symptomatic group). In the background-adjusted multivariable analyses with the inverse probability of treatment weighting model, symptomatic recurrence was significantly associated with shorter cancer-specific survival along with shorter overall survival after first recurrence. In the multivariable analysis, only tumor grade was selected as a significant predictive factor of symptomatic recurrence after TURBT.ConclusionsSymptomatic recurrence was significantly associated with poor oncological outcomes in patients with primary high-risk NMIBC. Patients with grade 3 tumors may require more intensive surveillance after TURBT.     

Four years experience in bladder preserving management for muscle invasive bladder cancer

OBJECTIVES: To evaluate the bladder preservation strategy in invasive bladder cancer particularly relapse, progression and complications. MATERIALS AND METHODS: From January 2000 to May 2004 a total of 24 patients (mean age of 81 years; range 68-92) with muscle invasive bladder cancer who had refused or were not eligible for cystectomy were followed up for a period of up to four years. RESULTS: 24 (21 M/3 F) patients were followed up for a mean time of 680 (182-1253) days. All patients complained of frequency, urgency and severe nocturia. The second most frequent complication was bleeding which required a salvage cystectomy in 7 cases. Other major complications were intestinal occlusion in three cases, an enterovesical fistula, brain metastasis requiring neurosurgical intervention and radiation therapy of the brain, bone metastasis in the cervical spinal column and chronic renal failure. The mean re-admission rate was 8 per patient and the mean time spent at the hospital was 109 (range 13-253) days. CONCLUSION: In our series the bladder preserving strategy does not confirm the optimistic results of other authors. The complications forced us to carry out a salvage cystectomy in nearly half of the cases. The other half of the patients complained of other severe complications reducing the quality of life of the remaining life span.     

Urinary markers in screening patients with hematuria

Hematuria is a common presenting symptom of urothelial malignancy. Although conventional urine analysis is very sensitive in detecting the presence of hematuria, it is not specific in detecting bladder cancer or other urinary-tract cancers. The noninvasive urinary tests NMP22 and UroVysion have been approved by the U.S. Food and Drug Administration for bladder cancer screening. These tests have better sensitivity than cytology for detecting bladder cancer in patients who present with hematuria. The positive predictive values of both tests increase in individuals with hematuria who have risk factors for bladder cancer. Evaluating hematuria with sensitive markers, such as NMP22 and UroVysion, in high-risk populations offers an opportunity to develop effective strategies for bladder cancer screening.     

Intravesical pharmacotherapy for non-muscle-invasive bladder cancer: a critical analysis of currently available drugs, treatment schedules, and long-term results

OBJECTIVES: Review adjuvant intravesical pharmacotherapy for non-muscle-invasive bladder cancer (NMIBC), emphasising treatment schedules and long-term results. METHODS: Search of published literature on conventional treatment of NMIBC, emerging drugs, and device-assisted therapies. RESULTS: In low-risk NMIBC patients an immediate instillation with chemotherapy is sufficient. For patients with intermediate- or high-risk tumours, additional adjuvant instillations are needed. For intermediate-risk patients chemotherapeutic instillations, usually with mitomycin C or epirubicin, are safe and effective in reducing the risk of recurrence in the short term, but efficacy is only marginal in the long term. Newer drugs have promising results, but long term follow-up is limited or lacking. In these patients bacillus Calmette-Guérin (BCG) does not seem to be more effective, only more toxic. In high-risk NMIBC, or patients in whom chemotherapy fails, BCG is the best choice with lower rates of recurrence and progression. For BCG failures cystectomy is therapy of choice, although the combination of BCG and interferon-alpha can be considered, just as device-assisted therapies such as thermochemotherapy and electromotive drug administration. CONCLUSIONS: Risk-adapted first-line adjuvant therapy for NMIBC after TURBT is well established but has its limitations because recurrences are still numerous. Some new drugs and second-line therapies are promising, but efficacy should be confirmed.     

Bladder cancer risk: Use of the PLCO and NLST to identify a suitable screening cohort

PurposeBladder cancer (BC) screening is not accepted in part owing to low overall incidence. We used the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) and National Lung Cancer Screening Trial (NLST) to identify optimal high-risk populations most likely to benefit from screening.Materials and methodsData were extracted from PLCO and NLST to stratify risk of BC by overall population, sex, race, age at inclusion, and smoking status. Incidence rates between groups were compared using chi-square test.ResultsBC was identified in 1,430/154,898 patients in PLCO and 439/53,173 patients in NLST. BCs were grade III/IV in 36.8% and 41.3%. Incidence rates were significantly higher in men than in women (PLCO: 1.4 vs. 0.31/1,000 person-years and NLST: 1.84 vs. 0.6/1,000 person-years, both P<0.0001). In proportional hazards models, male sex, higher age, and duration and intensity of smoking were associated with higher risk of BC (all P<0.0001). In men older than 70 years with smoking exposure of 30 pack-years (PY) and more, incidence rates were as high as 11.92 (PLCO) and 5.23 (NLST) (per 1,000 person-years). In current high-intensity smokers (≥50 PY), the sex disparity in incidence persists in both trials (0.78 vs. 2.99 per 1,000 person-years in PLCO and 1.12 vs. 2.65 per 1,000 person-years in NLST).ConclusionsMen older than 60 years with a smoking history of>30 PY had incidence rates of more than 2/1,000 person-years, which could serve as an excellent population for screening trials. Sex differences in the incidence of BC cannot be readily explained by the differences in exposure to tobacco, as sex disparity persisted regardless of smoking intensity.     

Survivin: a promising biomarker for detection and prognosis of bladder cancer

Survivin is a 16.5 kDa member of the inhibitor of apoptosis protein family that is overexpressed in many malignancies but rarely detected in normal differentiated adult tissues. Functionally, Survivin inhibits apoptosis, promotes cell proliferation, and induces/enhances angiogenesis. In transitional cell carcinoma of the urinary bladder, Survivin has been shown to be a promising biomarker for cancer diagnosis, prognosis and prediction of response to intravesical or systemic therapies. Moreover, in pre-clinical bladder tumor models, inhibition of Survivin expression and/or function has been shown to impede tumor cell proliferation, and markedly induce spontaneous or chemotherapy induced apoptosis. These preliminary findings should now be confirmed in large prospective trials. Furthermore, simplified, quantitative and reproducible assays need to be developed and validated for the detection of Survivin and its different isoforms.     

Hybrid SPECT-CT: an additional technique for sentinel node detection of patients with invasive bladder cancer

OBJECTIVES: To explore the feasibility of performing lymphoscintigraphy combined with computed tomography (CT) for preoperative detection of sentinel lymph nodes in patients with invasive bladder cancer. MATERIALS: Six consecutive patients scheduled for radical cystectomy underwent lymphoscintigraphy after transurethral injection of Albures-technetium 99m in the detrusor muscle peritumourally both with planar imaging and with single-photon emission computed tomography/CT (SPECT/CT). CT for anatomic fusion was performed directly after the SPECT/CT and both investigations were combined to a fused image. Radical cystectomy started with extended lymphadenectomy and intraoperative detection of sentinel nodes with both Geiger probe and dye marker. The conventional planar lymphoscintigraphies and the fused SPECT/CT were compared with each other and with the outcome of intraoperative sentinel node detection and final histopathologic analyses. RESULTS: The method allowed anatomically detailed preoperative visualisation of 21 sentinel nodes in five of the six patients, whereas planar pictures only visualised two sentinel nodes in two of six patients. Two patients had lymph node metastases and in the other four the nodes were negative. The combined method visualised all metastatic sentinel nodes, whereas planar lymphoscintigraphy detected only one of six node metastases. CONCLUSIONS: The combination of lymphoscintigraphy with CT enhanced preoperative anatomic localisation of sentinel nodes in bladder cancer and aided in the identification of sentinel nodes during surgery. The yield of detected sentinel nodes, both metastatic and nonmetastatic, was markedly increased using the combined method compared to conventional planar lymphoscintigraphy.     

Rectal cancer surgery in the elderly: analysis of consecutive 158 patients with stage III rectal cancer

Background It is difficult to establish a clear-cut indication for rectal surgery in elderly patients because of greater risk. We tried to clarify the factors associated with the short-term and long-term outcomes between elderly and younger patients. Materials and methods We clarified the potential predictors of the cancer-related and disease-free survivals after surgery, the factors associated with the elderly, preoperative comorbid conditions, and postoperative complications in 158 patients with stage III rectal cancer who underwent surgery, including 33 elderly patients (≥75 years) and 125 younger patients (<75 years). Results An old age and macroscopic types 3 and 4 were independent poor prognostic factors of cancer-related survival, whereas the disease-free survival of the younger patients was not longer than for the elderly patients. Interestingly, the survival rate in the elderly patients with recurrence was shorter than that in the younger patients. Histopathological type except well differentiated and without chemotherapy were significant tumor characteristics associated with the elderly patients. On preoperative comorbid conditions, elderly patients have more cardiovascular diseases than younger patients, whereas there were no significant differences in the postoperative complications. Conclusion Strength of the adjuvant and intensive therapies after recurrence may contribute to gain long-term survival in the elderly rectal cancer patients.     

Prognostic impact of comorbidity in patients with bladder cancer

OBJECTIVE: To determine the impact of comorbidity on survival of bladder cancer patients. METHODS: The population included 675 patients with newly diagnosed bladder cancer whose medical information was abstracted from a hospital cancer registry. Adult Comorbidity Evaluation-27, a validated instrument, was used to prospectively categorize comorbidity. Independent variables assessed include comorbidity, American Joint Committee on Cancer (AJCC) stage, grade, age, gender, and race. Outcome measure was overall survival. We analyzed the entire cohort, patients with noninvasive disease, and patients requiring cystectomy. Cox proportional hazards analysis was used to assess impact of independent variables on survival. RESULTS: Median age at diagnosis for the entire cohort was 71 yr and median follow-up was 45 mo. Of 675 patients, 446 had at least one comorbid condition and 301 died during follow-up. On multivariable analysis for the entire cohort, comorbidity (p=0.0001), AJCC stage (p=0.0001), age (p=0.0001), and race (p=0.0045) significantly predicted overall survival. On subset analysis of noninvasive bladder cancer patients, comorbidity (p=0.0001) and age (p=0.0001) independently predicted overall survival, whereas stage, grade, race, and gender did not. On subset analysis of cystectomy patients, comorbidity (p=0.0053), stage (p=0.0001), and race (p=0.0449) significantly predicted overall survival. CONCLUSIONS: Comorbidity is an independent predictor of overall survival in the entire cohort of bladder cancer patients, the subset with noninvasive disease, and the subset treated with cystectomy.     

Improved rates of colorectal cancer screening in an equal access population

Background

National colorectal cancer (CRC) screening averages 50% to 60%. We aimed to identify screening prevalence in select Department of Defense (DOD) beneficiaries with equal access to care.

Methods

December 2007 cross-sectional data of patients over 50 years of age included patient demographics, screening modality, and compliance.

Results

Of 17,252 patients (52% male; mean age 63.2 ± 8.1 years), 12,229 (71%) were up-to-date with national screening guidelines. Modalities included colonoscopy (83.0%), flexible sigmoidoscopy with fecal occult blood testing (FOBT) (32.2%), and air-contrast barium enema (0.7%). African American or Hispanic background (70% African American, 68% Hispanic vs 73% Caucasian), younger patients (66.1% <65 years vs 78.6% >65 years), and male gender (69.9% vs 72.1%; all P < .001) all had lower rates. Compared to 2005, more patients were current with guidelines (71% vs 64%) and colonoscopic screening (83% vs 71%).

Conclusions

Although ethnicity-, gender-, and age-related disparities were observed, screening rates are improved in an equal access healthcare system.     

FISH studies of urinary cells of patients with bladder cancer

Generally, bladder cancers are characterized by complex and numerous chromosome changes that vary from tumor to tumor. Nevertheless, certain chromosome changes recur with a consistency, (eg, +7, +8, −9, and −Y). In applying fluorescence in situ hybridization (FISH) studies to urinary cells in bladder cancer we chose probes for these chromosomes as well as those for chromosomes 10 and 11. A probe for the X chromosome was used for female patients in place of the Y. In the present study, we show that FISH of urine samples can detect the presence of cancer cells in transitional cell carcinoma (TCC) of the bladder of any grade and stage, including carcinomas in situ (CIS). We analyzed 27 samples from 25 patients (three were from the same patient); 24 samples were recurrent or newly diagnosed TCC and 3 were CIS. Our results show that FISH of urine samples is a reliable test for the detection of bladder cancer cells, regardless of the grade and stage of the tumor, and that a correlation appeared to exist between invasiveness of the tumor and the number of abnormalities in such tumor.     

极低密度脂蛋白受体基因促进膀胱癌细胞迁移的作用及机制

目的:探讨极低密度脂蛋白受体(VLDLR)对人膀胱癌细胞迁移活性的影响及机制。方法:采用实时荧光定量反转录-聚合酶链反应(RT-qPCR)检测人源膀胱癌细胞(J82、UMUC3与T24)与正常尿路上皮细胞(SV-HUC-1)VLDLR的表达水平;采用小干扰RNA(siRNA)建立VLDLR敲低T24细胞模型,通过划痕实...