局部晚期肾盂输尿管癌单纯手术与术后辅助放疗疗效比较

目的 比较肾盂输尿管癌单纯手术与术后辅助放疗的疗效。方法 回顾分析2005—2008年间 103例肾盂输尿管移行细胞癌患者的临床资料,37例行术后辅助三维适形放疗,66例单纯手术。局部控制率、生存率用Kaplan-Meier法计算并Logrank法检验及单因素分析,多因素分析采用Cox回归模型。结果 单纯手术组、术后放疗组随访率分别为89%、92%,其中随访满 5年者分别为33、17例。单纯手术组1、3、5年局部控制率分别为89%、74%、72%,术后放疗组分别为94%、90%、90%(χ²=3.90,P=0.048)。单纯手术组1、3、5年无膀胱癌发生率分别为87%、60%、57%,术后放疗组分别为94%、79%、79%(χ²=4.50,P=0.037)。单纯手术组1、3、5年总生存率为90%、71%、65%,术后放疗组分别为84%、65%、62%(χ²=0.32,P=0.573)。单因素和多因素分析均显示分期、淋巴结转移、手术断端阳性与总生存率相关(χ²=7.91、64.69、40.20和5.08、17.23、8.22,P=0.005、0.000、0.000和0.024、0.000、0.004)。结论 术后辅助三维适形放疗能提高肿瘤控制率,降低膀胱癌发生率,但在改善患者生存方面尚未现优势。     

不能手术肾癌及肾盂输尿管癌放疗效果分析

目的 回顾性分析不能手术治疗的肾癌及肾盂输尿管癌放疗结果。方法 2006—2015年间 29例无法行肾癌及肾盂输尿管癌手术患者实行了放疗,其中男 18例、女 11例,年龄 41~95岁(中位数 76岁);肾癌 17例,肾盂输尿管癌 12例;临床血尿 14例,腰背痛 7例。采用剂量递增放疗模式,其中伽马刀治疗 17例、HT治疗 12例。伽马刀50%等剂量线为处方剂量线,3~5 Gy/次,PTV边缘 40~50 Gy,GTV边缘 60~70 Gy。HT 50、60、70 Gy分 15~20次。结果 原发灶CR率为17%(5/29)、PR率为69%(20/29),总有效率(CR+PR)为86%。血尿消失93%,腰背痛消失100%。3、5年样本量分别为15、11例,肾癌和肾盂输尿管癌3、5年生存率分别为81%、81%和69%、69%。治疗期间1、2级消化系统反应 25例,1、2级骨髓抑制 20例,给予药物对症治疗后好转。结论 肾癌和肾盂输尿管癌伽马刀和HT安全有效切可提高LC和OS率,为不能手术肾癌和肾盂输尿管癌患者提供了有效治疗手段。     

组织蛋白酶D在肾盂输尿管移行细胞癌中表达的意义

目的：探讨组织蛋白酶D在上尿路移行细胞癌中表达的临床意义。方法：应用免疫组织化学ABC法，对组织蛋白酶D在43例肾盂、输尿管移行细胞癌中的表达进行检测。结果：肿瘤细胞阳性表达19例（44．2％）；间质细胞阳性表达14例（32．6％）。两表达与肿瘤分级、分期无显差异（P＞0．05）。间质细胞组织蛋白酶D阳性表达的患术后肿瘤复发明显高于阴性表达（P＜0．05），且5年生存期明显低于阴性表达（P＜0．05）。结论：上尿路移行细胞癌间质细胞组织蛋白酶D的检测，对术后肿瘤复发、生存期的判断具有一定的临床价值，可能用作判断预后的指标之一。     

The prognostic value of KI-67 proliferation index in transitional cell carcinoma of renal pelvis and ureter

The investigation deals with Ki-67 immunoreactivity assay in upper urinary tract transitional cell carcinoma (TCC) with respect to grade, stage and survival after radical surgery. In a retrospective study (5yrs) of 37 patients with TCC of the renal pelvis and ureter, who had undergone radical nephroureterectomy and bladder resection, pT1-pT4 lesions and G1-G3 tumors were identified. Ki-67 expression was evaluated by immunohistological staining (1:100; MIB-1; Immunotech. Inc., Westbrook, USA). By using fifteen x600 visual fields, Ki-67 labeling index (number of positive cells per 100 tumor cells) was found (mean +SD--29.7 +/- 9.22). There was a correlation between the index and tumor stage (p < 0.001) and grade (p = 0.002). The Ki-67 values in excess of 27 corresponded to high risk of bladder recurrence (p < 0.001) and short duration of recurrence development (p = 0.067) whereas, for the index of under 22, five-year progression-free survival was more frequent (p < 0.001). Having been tested in that study, discriminative modeling yielded the following parameters: sensitivity and specificity for bladder recurrence was 93% and 79% while for 5-year progression-free survival- 89% and 100%.     

肾盂移行上皮细胞癌CT诊断

目的探讨肾盂移行上皮细胞癌CT特点, 评价CT在肾盂移行上皮细胞癌诊断中的价值。方法 报告经手术病理证实的肾盂移行上皮细胞癌32例, 回顾性分析CT表现。结果 32例中15例见肾盂、肾盏内1.5cm-4.0cm大的结节状软组织肿块影, 肾窦脂肪受压、变薄, 但间隙存在;8例见肾盂、肾盏内直径4.1cm-9.0cm肿块, 累及肾门, 肾窦脂肪间隙消失;4例沿肾盂壁浸润性生长, 肾盂壁不规则增厚, 经肾门蔓延至输尿管上端, 肾盂、肾盏轻度扩张积水;5例肿块浸润肾实质, 并侵犯邻近组织, 形成密度不均的团块, 分不清肾盂、肾盏和肾实质, 肾门和腹膜后淋巴结增大。平扫:32例CT值33Hu-50Hu, 其中25例等密度, 4例略高密度, 3例略低密度;密度均匀21例, 密度不均匀11例;瘤内伴有小斑片状高密度出血灶5例, 小点状钙化5例, 坏死囊变3例。增强:CT增强扫描21例中13例于皮质期见肿块呈轻度均匀强化, 轻度不均匀强化8例;21例于实质期及肾盂期病灶强化程度均无明显增加, 与邻近增强肾实质相比, 肿瘤略呈低密度。32例中CT直接诊断肾盂癌21例, 提示肾盂癌可能7例, 误诊2例, 漏诊2例。结论 肾盂移行上皮细胞癌在CT平扫以等密度, 增强以轻度强化为主要征象, 在病灶的发现及定性, 螺旋CT具有较高价值。     

The prognostic value of angiogenesis and metastasis-related genes for progression of transitional cell carcinoma of the renal pelvis and ureter.

PURPOSE: We reported previously that angiogenesis evaluated by intratumor microvessel density (MVD), expression of such angiogenic factors as vascular endothelial cell growth factor (VEGF) and basic fibroblast growth factor (bFGF), and the matrix metalloproteinase-9:E-cadherin ratio (M:E ratio) could identify patients with advanced transitional cell carcinoma (TCC) of the bladder for whom chemotherapy and cystectomy will be unsuccessful. In the present study, we evaluated the significance of the M:E ratio as a predictor for prognosis for patients with TCC in the upper urinary tract (TCC-UUT). EXPERIMENTAL DESIGN: We evaluated MVD by immunohistochemistry and the expression of angiogenic and metastasis-related factors by in situ hybridization in 55 nephroureterectomy specimens from patients who received no neoadjuvant therapy. The expression of angiogenesis, angiogenic and metastasis-related factors, and clinicopathological characteristics were evaluated for their correlation with metastasis, recurrence, and disease prognosis. RESULTS: We found that tumor grade and pathological stage were important predictors for metastasis and survival in these patients. The expression level of matrix metalloproteinase type 9 (MMP-9) and type 2 (MMP-2) and the M:E ratio correlated with MVD. Increased MVD, elevated expression levels of MMP-9 and MMP-2, and a higher M:E ratio were associated with poor prognosis. Moreover, lower expression levels of E-cadherin were associated with fewer recurrences in the urinary bladder. Multivariate analysis indicated that the M:E ratio and E-cadherin expression were independent prognostic factors for disease progression and intravesical recurrence, respectively. CONCLUSION: We suggest that the M:E ratio and E-cadherin expression may be targets for novel therapeutic strategies.     

Cyclin-dependent kinase inhibitor p27(Kip1) expression in transitional cell carcinoma of renal pelvis and ureter

We examined the expression and significance of p27^Kip1 protein in 79 patients with transitional cell carcinoma of the renal pelvis and ureter. Immunohistochemical staining of archival tissue specimens was done using a labeled streptavidin–biotin–peroxidase method. There was no significant association between p27^Kip1 labeling index and histologic grade or pathologic stage. Patients with p27^Kip1 labeling indices of 27 or greater had more favorable prognoses in comparison to those with p27^kip1 labeling indices less than 27 (P<0.01). Multivariate analysis indicated that p27^Kip1 had an independent predictive prognostic value (P<0.05). The p27^Kip1 may be a novel prognostic marker for transitional cell carcinoma of the renal pelvis and ureter.     

Recurrent transitional cell carcinoma of the renal pelvis presenting as diabetes insipidus

We present the case of a 61-year old man with intracranial recurrence of transitional cell carcinoma of the renal pelvis presenting as diabetes insipidus. Metastatic infiltration of the pituitary stalk was demonstrated by magnetic resonance imaging when cerebral computerized tomography scanning was unhelpful. Successful treatment followed, comprising radiotherapy and intranasal desmopressin.     

膀胱癌T3期的术前放疗

目的 比较术前放疗加全膀胱切除术和单纯全膀胱切除术在膀胱癌患者Ｔ３期治疗中的疗效。方法 ２６例Ｔ３期移行细胞膀胱癌患者为术前放疗组,术前放疗剂量为ＤＴ２０Ｇｙ／５次,共５日,放疗后一周内手术。中位随访时间为４８个月（２１～８４个月）。３６例Ｔ３期患者行单纯全膀胱切除术（单手术组）,中位随访时间４４个月（１３～８４个月）。全部病例随访率１００％。结果 术前放疗组３年盆腔复发率０％低于单手术组１９．４％（Ｐ〈０．０５）,５年盆腔复发率１１．５％及腹壁切口复发率０％低于单手术组的２５．０％和１１．１％,５年生存率术前放疗组５７．６％,单手术组４４．４％。结论 Ｔ３期膀胱癌患者接受术前放疗可以降低盆腔复发率。     

Adjuvant radiotherapy in early stage ovarian carcinoma

In a series of 228 women diagnosed with malignant ovarian tumors during the years 1980-87 radiotherapy was added as postoperative adjuvant therapy. Twenty-three cases with epithelial borderline carcinomas and 18 cases with nonepithelial tumors were excluded from the analysis. The remaining 187 cases of invasive epithelial ovarian carcinoma in FIGO stage I-II was a complete, consecutive, and total geographic series. After primary staging surgery lower abdomino-pelvic or whole abdominal radiotherapy was administered. The dose to the upper part of the abdomen was 20 Gy (fraction dose 1.0 Gy) and to the lower part and the pelvis 40 Gy (fraction dose 1.7 Gy). The patients were followed up for at least 10 years. During the follow-up 75 tumors (40%) recurred and were then treated with cisplatin-containing chemotherapy. Abdomino-pelvic (18%) and abdomino-pelvic-distant metastases (11%) were most frequent. Mean time to recurrence was 26 months. The 5-year overall survival of the complete series was 57% and the cancer-specific survival 66%. FIGO stage and tumor grade were the only independent and significant prognostic factors in a Cox multivariate analysis. Only cases in FIGO stage IA and grade 1 could be classified as low-risk cases with 5-year survival of 87%. All other cases showed a significantly worse prognosis and should be classified as intermediate or high-risk cases. Early radiation reactions were frequent (80%) but of little clinical significance. In 21 cases (11%) late radiation reactions were recorded. In 8 cases (4%) the reactions were regarded as severe and required surgical intervention or disabled the patient significantly. The results compare well with others reported in the literature.     

Primary mucinous adenocarcinoma of the renal pelvis with carcinoma in situ in the ureter

Primary epithelial tumor of the renal pelvis is rare and only 100 cases are reported in the literature [1]. Histological examination of the tumor showed glands, cysts, and papillae lined by pseudostratified columnar epithelium with hyperchromatic nuclei. Scattered signet ring-type cells were also seen floating in large pools of extracellular mucin. Sections from the ureter showed a component of adenocarcinoma in situ. No invasive tumor was identified in ureteric tissue. One case was reported with carcinoma in situ of the ureter (2).Immunohistochemically: The tumor showed positivity for CK7, CK20, CK8/18, GATA-3, MSH-2, MSH-6, MLH-1, Ber-EP4, and S-100-P with focal positivity for CDX-2, weak positivity for PMS-2 and negativity in TTF-1 and Her-2. Molecular pathological analysis revealed microsatellite stability and without mutation in K-ras-gene. Thus, a diagnosis of mucinous adenocarcinoma of the renal pelvis with in situ adenocarcinoma of the ureter was made.     

Cigarette smoking and cancers of the renal pelvis and ureter.

A population-based case-control study of renal pelvis and ureter cancers (502 cases, 496 controls) conducted in three areas of the United States found cigarette smoking to be associated with a 3.1-fold increase in risk, with long-term (greater than 45 years) smokers having a 7.2-fold increased risk. Statistically significant dose-response associations were observed for both cancer sites and in both sexes regardless of the measure used: cigarettes per day, duration of use, or pack years. A significant decreasing trend in risk with increasing years quit smoking was also demonstrated for these cancers. Attributable risk estimates indicate that approximately 7 of 10 cancers of the renal pelvis and ureter among men and almost 4 of 10 among women are caused by smoking. The results of this study, the largest to date, confirm that cigarette smoking is the major cause of cancers of the renal pelvis and ureter, and that cessation of smoking could eliminate a large proportion of these tumors.     

Adjuvant therapy in renal cell carcinoma

Localized renal cell carcinoma (RCC) has an associated risk of recurrence after nephrectomy. Several clinical risk models attempt to predict oncologic outcomes based on clinical and pathologic features. In addition, novel gene signatures have been developed to refine risk prediction based on tumor biology. Systemic therapies targeting angiogenic pathways that are effective in metastatic RCC failed to show an improvement in overall survival in the adjuvant setting. Immune checkpoint inhibitors have shown significant antitumor activity with prolonged and durable responses in metastatic RCC, which led to an interest in evaluating these agents in the adjuvant setting. In this review, clinical risk-predictive models, novel gene signatures, major clinical trials completed in the adjuvant setting, ongoing immune checkpoint inhibitor trials, and the perspective of adjuvant treatment in RCC are discussed.     

Adjuvant therapy in renal cell carcinoma

Several drugs have demonstrated clinical activity in metastatic renal cell carcinoma (mRCC). The identification of key metabolic pathways has led to the development of novel targeted therapies which have drastically changed the treatment paradigm of mRCC. Moreover, immune-checkpoint inhibitors have recently shown significant activity in advanced disease. Despite these advancements, the role of adjuvant therapy in localized, non-metastatic RCC remains unclear. The utility of many of these agents in the adjuvant setting is currently being actively explored. In this review, we will summarize the main clinical trials investigating adjuvant therapy in renal cell carcinoma, focusing primarily on immunotherapy and targeted agents.     

Adjuvant therapy of renal cell carcinoma

Metastatic renal cell carcinoma (RCC) has a highly variable natural history and carries a dismal prognosis. Unlike many other tumors, RCC is generally unresponsive to cytotoxic, hormonal, and radiation adjuvant therapies after cytoreductive surgery. Different modalities of treatment have been tried and tested with modest success. Until recently, only immunotherapies such as interleukin-2 and interferon- α have been shown to provide a response, albeit in a minority of patients and often with severe treatment-associated toxicities. Other adjuvant therapies, such as active specific immunotherapy with Bacillus Calmette-Guerin and autologous renal tumor cell vaccines, have not provided alternative solutions. Recent approaches include heatshock protein peptide complex 96 vaccine and cG250 monoclonal antibody therapy. Novel targeted therapies have been developed using our knowledge of the molecular genetics that belie RCC. This culminated in sorafenib and sunitinib, the first Food and Drug Administration- approved drugs for RCC in more than a decade in the United States. The future will see further trials being carried out in the development of targeted therapies with emphasis placed on patient selection. Staging systems will need to be updated to integrate molecular biomarkers, which could potentially act not just as diagnostic and prognostic predictors, but also as tools for appropriate patient selection for treatment. In the future, this could potentially lead us to our ultimate goal of personalized medicine.