Galectin-8 predicts postoperative recurrence of patients with localized T1 clear cell renal cell carcinoma

BackgroundGalectin-8 (Gal-8), belonging to a family of the “tandem repeat”–type galectins that contain 2 carbohydrate recognition domains, serves to retain cell surface residency and signaling of glycoproteins including cytokine and growth factor receptors, and thereby promoting development and progression of various malignancies. This study aims to evaluate the effect of Gal-8 expression on postoperative recurrence of patients with localized pathologic T1 (pT1) clear cell renal cell carcinoma (ccRCC).Patients and methodsIn this retrospective study, we enrolled 244 patients (122 in group A and 122 in group B) with localized pT1 ccRCC undergoing nephrectomy at a single institution. Specimens from patients were collected from January 2003 to December 2008. Median follow-up was 71 months (range: 12–120 mo) in group A and 70 months (range: 12–119 mo) in group B. Overall, 14 patients experienced recurrence in group A (n = 122) and 22 patients had recurrence in group B (n = 122). Gal-8 expression was assessed by immunohistochemistry in clinical specimens. Kaplan-Meier method with log-rank test was performed to compare survival curves. Cox regression models were used to evaluate the prognostic values of variables on recurrence-free survival. Concordance index was calculated to assess prognostic accuracy.ResultsIn both groups, patients with high expression of Gal-8 were significantly inclined to have high rates of necrosis. High Gal-8 expression indicated early recurrence of patients with localized pT1 ccRCC. Gal-8 expression was determined to be an independent adverse prognostic indicator for recurrence. The accuracy of The Mayo Clinic Stage, Size, Grade, and Necrosis score and University of Los Angeles Integrated Staging System prognostic models was improved when Gal-8 expression was added.ConclusionsGal-8 expression is a potential independent unfavorable prognostic indicator for postoperative recurrence of patients with localized pT1 ccRCC.     

Outcome of surgical treatment of isolated local recurrence after radical nephrectomy for renal cell carcinoma

PURPOSE: Isolated local recurrences after radical nephrectomy for renal cell carcinoma occur in 2% to 3% of cases. Today local recurrences can be detected at an early stage due to modern imaging techniques. It remains controversial whether an aggressive surgical approach to this problem can prolong survival. MATERIALS AND METHODS: We retrospectively analyzed 16 patients who were treated surgically at our institution for suspected isolated local renal cell carcinoma recurrence during the last 10 years. All patients had undergone extensive staging and had no evidence of distant metastases with the local recurrence. Surgical exploration confirmed carcinoma recurrence in 13 of the 16 cases and all 13 patients underwent complete resection of the local recurrence. Three patients were found to have had false-positive computerized tomography findings on surgical exploration. RESULTS: Mean time to recurrence was 45.5 months (range 7 to 224). Only 2 patients were symptomatic, while in 11 disease had been detected at routine followup. Mean size of the recurrent tumor was 5.92 cm. (range 2 to 10). All patients survived surgery without major complications. Of the patients 7 died of metastatic disease after a mean survival of 23.1 months (range 4 to 68) following recurrence removal and 6 are alive with a mean survival of 53.0 months (range 18 to 101) (p = 0.09). Time to recurrence after nephrectomy was significantly longer (p <0.05) and size of recurrence significantly smaller (p <0.04) in the patients still alive. In 1 surviving patient evidence of metastatic disease developed 9 months after surgery for recurrence. CONCLUSIONS: Careful followup after radical nephrectomy for renal cell carcinoma allows the diagnosis of small local recurrences before they become symptomatic in the majority of cases. Although most of these patients will eventually have and die of metastatic disease, an aggressive surgical approach is justified and can result in prolonged survival.     

Extranodal extension in regional lymph nodes is associated with outcome in patients with renal cell carcinoma

PURPOSE: The 2002 American Joint Committee on Cancer pN classification for renal cell carcinoma is based on the number of positive regional lymph nodes. We examined the associations of pathological features of lymph node metastases with patient outcome to improve the prognostic accuracy of the current classification. MATERIALS AND METHODS: We studied the records of 2,076 patients treated with radical nephrectomy for unilateral, sporadic pM0 renal cell carcinoma between 1970 and 2000. There were 34 patients with metastasis in a single regional lymph node (pN1) and 35 with metastases in more than 1 lymph node (pN2). Pathological features of lymph node metastases, including the number and percent of positive lymph nodes, total number of lymph nodes removed, grade, necrosis, extranodal extension, and largest dimension and surface area of metastases were determined by 2 urological pathologists (HHD and JCC). RESULTS: There was no statistically significant association between the pN classification and death from renal cell carcinoma (pN2 vs pN1 RR 1.05, 95% CI 0.62 to 1.79, p = 0.846). However, patients with extranodal extension were twice as likely to die of renal cell carcinoma than patients in whom metastases did not extend outside of the lymph node capsule (RR 2.02, 95% CI 1.18 to 3.45, p = 0.010). The 5-year cancer specific survival rate was 18% and 35% in patients with and without extranodal extension, respectively. CONCLUSIONS: We believe that a pN classification based on the presence or absence of lymph node metastases with a notation regarding the presence or absence of extranodal extension represents a significant improvement in the prognostic accuracy of the current pN classification.     

Second primary malignancies associated with renal cell carcinoma histological subtypes

PURPOSE: Renal cell carcinoma has been linked to numerous secondary malignancies. We evaluated the risk of secondary malignancies by renal cell carcinoma histological subtype in patients with clear cell, papillary and chromophobe renal cell carcinoma. MATERIALS AND METHODS: We studied 2,722 patients who underwent nephrectomy for sporadic renal cell carcinoma at our institution between 1970 and 2000. All specimens were reviewed by a single urological pathologist for histological subtype. Associations of second primary malignancies by histological subtype were evaluated using the chi-square and Fisher exact tests. RESULTS: Of the patients studied 2,188 (80.4%) had clear cell, 378 (13.9%) had papillary and 128 (4.7%) had chromophobe renal cell carcinoma. Patients with papillary renal cell carcinoma were significantly more likely to have colon cancer (p = 0.041), prostate cancer (p = 0.003), any second malignancy (p <0.001) and multiple malignancies (p <0.001) compared with patients with clear cell renal cell carcinoma. In addition, patients with chromophobe renal cell carcinoma were significantly more likely to have colon cancer than patients with clear cell renal cell carcinoma (p = 0.020). Although patients with papillary renal cell carcinoma were more likely to have bladder cancer, the incidence did not differ significantly compared with that in patients harboring clear cell and chromophobe renal cell carcinoma (p = 0.193). We did not find a significant difference in the incidence of breast cancer, lung cancer, rectal cancer or lymphoma among histological subtypes. CONCLUSIONS: Our data indicate that patients with papillary renal cell carcinoma are more likely to harbor secondary malignancies, including colon and prostate cancer, than patients with clear cell renal cell carcinoma. These results may have important implications for patient education and followup evaluation, and they should prompt mechanistic investigations.     

A postoperative prognostic nomogram predicting recurrence for patients with conventional clear cell renal cell carcinoma

PURPOSE: Few published studies have simultaneously analyzed multiple prognostic factors to predict recurrence after surgery for conventional clear cell renal cortical carcinomas. We developed and performed external validation of a postoperative nomogram for this purpose. We used a prospectively updated database of more than 1,400 patients treated at a single institution. MATERIALS AND METHODS: From January 1989 to August 2002, 833 nephrectomies (partial and radical) for renal cell carcinoma of conventional clear cell histology performed at Memorial Sloan-Kettering Cancer Center were reviewed from the center's kidney database. Patients with von Hippel-Lindau disease or familial syndromes, as well as patients presenting with synchronous bilateral renal masses, or distant metastases or metastatic regional lymph nodes before or at surgery were excluded from study. We modeled clinicopathological data and disease followup for 701 patients with conventional clear cell renal cell carcinoma. Prognostic variables for the nomogram included pathological stage, Fuhrman grade, tumor size, necrosis, vascular invasion and clinical presentation (ie incidental asymptomatic, locally symptomatic or systemically symptomatic). RESULTS: Disease recurrence was noted in 72 of 701 patients. Those patients without evidence of disease had a median and maximum followup of 32 and 120 months, respectively. The 5-year probability of freedom from recurrence for the patient cohort was 80.9% (95% confidence interval 75.7% to 85.1%). A nomogram was designed based on a Cox proportional hazards regression model. Following external validation predictions by the nomogram appeared accurate and discriminating, and the concordance index was 0.82. CONCLUSIONS: A nomogram has been developed that can be used to predict the 5-year probability of freedom from recurrence for patients with conventional clear cell renal cell carcinoma. This nomogram may be useful for patient counseling, clinical trial design and effective patient followup strategies.     

Multiple primary malignancies in Japanese patients with renal cell carcinoma

AIM: To evaluate the incidence, nature and prognosis of multiple primary malignancies involving renal cell carcinoma (RCC) in Japan. METHODS: Between 1975 and 1998, 319 patients underwent an operation for RCC at Hokkaido University, Sapporo, Japan. The incidence of other primary malignancies was determined and classified as antecedent, synchronous or subsequent. Follow-up was obtained by thorough chart review or telephone interview, and ranged from 0 to 276 months (median 49.0 months). To analyze the influence of other primary malignancies on prognosis, overall and cause-specific survival rates of the patients with an antecedent or synchronous malignancy were compared to the remaining patients. RESULTS: Of the 319 patients there was at least one other malignancy in 38 patients (12%). Four patients had two other malignancies. The other malignancies were antecedent in 13, synchronous in 19 and subsequent in 10 patients. Twenty-two patients had gastrointestinal cancer. In cases of antecedent or synchronous diagnosis of other primary malignancies, RCC was commonly incidental, small or low-stage. Multivariate analysis using Cox's proportional hazards model showed that, for overall survival, the presence of other antecedent or synchronous malignancies was the second most significant prognostic factor, following the pathological stage of RCC. CONCLUSIONS: In Japanese patients with RCC, the incidence of other primary malignancies was not uncommon and these malignancies contributed to the prognosis of these patients. Therefore, the malignant potential of individual tumors should be paid careful attention in the management of these patients.     

凝血功能与肾癌肿瘤分期及转移的相关性研究

目的探讨凝血功能与肾癌肿瘤分期及转移的关系。方法回顾性分析我院2011～2012年收治的150例肾癌患者的临床资料。男95例,女55例。平均年龄（51．41±19．68）岁。病理类型：透明细胞癌120例、乳头状癌11例、嫌色细胞癌6例、囊性肾癌8例,其他类型5例。TNM分期：Ⅰ期87例（T1a45例,T1b42例）,Ⅱ期24例、Ⅲ期22例、Ⅳ期17例。N0111例、N1 17例、N2 22例,M0 133例、M1 17例。病理明确诊断为肾良性肿瘤132例纳入对照组。比较两组患者术前纤维蛋白原（Fib）、凝血酶原时间（PT）、部分活化凝血酶原时间（APTT）及国际标准化比值（INR）水平。结果肾癌组患者术前Fib值（4．08±1．12）g／L,对照组（3．23±0．52）g／L,两组比较差异有统计学意义（P〈0．01）;肾癌组PT（10．65±1.38）s、APTT（31．11±3．56）s、INR（0．95±0．72）,对照组分别为（11．02±7．44）s、（31．24±3．05）s、（O．96士o．64）,两组比较差异均无统计学意义（P〉0．05）。肾癌5个亚组术前Fib分别为（3．75±0．59）g／L、（3．31±0．64）g／L、（4．34±0．52）g／L、（4．99±0．38）g／L、（6．04±1．06）g／L,其中T1a、T1b组与对照组比较差异无统计学意义（P〉0．05）,其余组与对照组比较差异有统计学意义（P〈0．01）。肾癌组高纤维蛋白原血症（Fib＞4．0g／L）者68例（24．1％）。结论肾癌伴淋巴结及远处转移者血清Fib升高,肿瘤分期为Ⅱ期、Ⅲ期、Ⅳ期发生转移的可能性较大。血清Fib对肾癌预后具有独特的预测价值。     

Multiple primary malignancies in patients with renal cell carcinoma: a national population-based cohort study

OBJECTIVE: To determine the possibly greater occurrence of multiple malignancies in patients with renal cell carcinoma (RCC). PATIENTS AND METHODS: In the 7-year period 1987-93, all 1425 patients aged 15-70 years with registered histopathologically verified RCC in Norway were included in the study. All clinical and histopathology reports were checked manually, to verify the registered diagnosis and to ensure that no tumour was a metastasis from another. After this process, 257 patients (287 tumours other than RCC) with multiple primary malignancies were identified. The primary tumours other than RCC were classified as antecedent, synchronous and subsequent. For the subsequently occurring tumours, the expected number of different tumour types was calculated according to age group, gender and observation time. RESULTS: Of the 1425 patients, 228 (16%) had one, 23 (1.6%) had two, three (0.2%) had three and one (0.07%) had four other primary malignancies. In all, 100 (34.8%) of the other tumours were diagnosed as antecedent, 53 (18.7%) as synchronous and 134 (46.7%) as subsequent to the RCC. Cancer in the prostate, bladder, lung, breast, colon and rectal cancer, malignant melanomas (MM) and non-Hodgkin's lymphomas (NHL) were the most common other malignancies. The observed overall number of subsequent other malignant tumours was 22% higher than the expected number. The observed number of subsequent tumours was significantly higher for bladder cancer, NHL and MM. The estimated 15-year cumulative risk for patients with RCC and no previous or synchronous other malignancy for developing a later second cancer was 26.6% in men, and 15.5% in women (statistically significant, P = 0.04). Patients with antecedent or synchronous other cancer had significantly poorer overall survival than those without. CONCLUSIONS: Patients with RCC seem to have a significantly higher risk of developing other subsequent primary malignancies. This should be considered during the follow-up of patients with RCC.     

Impact of tumor size on the predictive ability of the pT3a primary tumor classification for renal cell carcinoma

PURPOSE: The accuracy of the pT3a primary tumor classification for renal cell carcinoma has been questioned recently. We investigated the association of perinephric and renal sinus fat invasion with death from renal cell carcinoma independent of tumor size. MATERIALS AND METHODS: We identified 2,165 patients treated with open radical nephrectomy or nephron sparing surgery for clinically localized, sporadic pT1a, pT1b, pT2 or pT3a renal cell carcinoma between 1970 and 2002. Patients with pT3a disease were then subdivided into 3 groups according to tumor size to match the size definitions for the pT1a, pT1b and pT2 tumor classifications. RESULTS: There were 834 patients with pT1a RCC, 674 with pT1b, 494 with pT2 and 163 with pT3a RCC. At last followup 317 patients died of RCC at a median of 3.8 years following surgery. The median followup among the 1,087 patients still alive at last followup was 7.8 years (range 0 to 34). The risk ratios (95% CI) for the association between fat invasion and death from RCC among patients with tumors 4 cm or smaller, 4 to 7 cm and more than 7 cm were 6.15 (1.84-20.50, p = 0.003), 4.12 (2.50-6.78, p <0.001) and 2.13 (1.53-2.97, p <0.001), respectively. These associations remained statistically significant in a multivariate analysis that included nuclear grade and histological coagulative tumor necrosis. CONCLUSIONS: Peripheral perinephric and renal sinus fat invasion was associated with death from RCC independent of tumor size. Our data contradict reports suggesting that pT3a tumors should be reclassified according to tumor size only.     

Stage-specific effect of nodal metastases on survival in patients with non-metastatic renal cell carcinoma

OBJECTIVE

To quantify the survival disadvantage related to the presence of exclusive nodal metastases (eNM) in patients with otherwise non‐metastatic (M0) renal cell carcinoma (RCC).

PATIENTS AND METHODS

Data were retrieved from 12 institutional databases and yielded 3507 patients with T1‐3N1‐2M0 RCC treated with partial or radical nephrectomy. Cox regression analyses relied on T stage, Fuhrman grade and presence of eNM. Data were analysed using univariable, multivariable and stratified analyses.

RESULTS

Overall 165 (4.7%) patients had eNM; of 2023 patients of stage T1, 23 (1.1%) had eNM, vs 20 of 448 (4.5%) for T2 and 122 of 993 (12.3%) for T3. In univariable analyses the presence of eNM increased the rate of cancer specific mortality (CSM) by 7.1 times. After adjusting for T stage and Fuhrman grade, in all patients eNM increased the rate of CSM by 3.2 times. In stratified analyses adjusted for Fuhrman grade, the increase in CSM related to the presence of eNM was 28.9, 4.3 and 2.5 times (all P < 0.001) for stages T1, T2 and T3, respectively.

CONCLUSIONS

From the prognostic perspective, staging lymphadenectomy appears of most value in patients with T1‐2 RCC, but the low prevalence of eNM questions the practical applicability of nodal staging in those patients. Conversely, in patients with T3 RCC, the prevalence and the prognostic impact of eNM might make a staging lymphadenectomy worthwhile.     

舒尼替尼在晚期肾细胞癌治疗中的运用

目的：探讨苹果酸舒尼替尼对晚期肾细胞癌治疗的安全性和有效性。方法：晚期肾细胞癌患者22例,男18例,女4例,平均年龄56岁,均为转移性或难以手术的肾细胞癌患者。采用舒尼替尼治疗,其中18例为一线治疗,4例为二线治疗。均为单一服药,口服50mg／d,每4周停药2周者16例;口服37．5mg／d,连续服药者6例。持续用药至肿瘤进展或出现不可耐受的并发症。以6周为1个治疗周期,至少每2个治疗周期进行疗效评价。结果：1例患者服药不足2周期内死亡,可评价病例21例。部分缓解6例（28．6％）,疾病稳定13例（61．9％）,疾病进展2例（9．5％）,无完全缓解病例。常见的不良反应包括手足皮肤反应、皮疹、疲劳乏力、骨髓抑制、味觉变化等。结论：舒尼替尼治疗晚期肾癌患者效果确切,不良反应多数可控制,但对于KPS评分较低,一般情况差,肿瘤负荷大的患者,运用时需慎重。