Prognostic significance of erythrocyte protein band 4.1-like5 expression in upper urinary tract urothelial carcinoma

Objectives

The erythrocyte protein band 4.1-like5 (EPB4.1L5) regulates E-cadherin in cancer invasion and metastasis inducing epithelial-to-mesenchymal transition. This study aimed to investigate the biological significance of EPB4.1L5 in upper urinary tract urothelial carcinoma (UTUC).

Improved outcomes after aggressive surgical resection of hilar cholangiocarcinoma: a critical analysis of recurrence and survival

Background

Hilar cholangiocarcinoma (HC) is invariably fatal without surgical intervention. The primary aim of the current study was to report overall survival and recurrence-free survival outcomes after surgical resection of HC.

Methods

Between December 1992 and December 2009, 85 patients were evaluated; of these, 42 patients underwent potentially curative surgery. These patients are the principal subjects of this study. Patients were assessed monthly for the first 3 months and then at 6-month intervals after treatment. Recurrence-free survival and overall survival were determined; 18 clinicopathologic and treatment-related factors associated with recurrence-free survival and overall survival were evaluated through univariate and multivariate analyses.

Results

No patient was lost to follow-up evaluation. The median follow-up period was 20 months (range, 0–106 mo). The median recurrence-free survival and overall survival after resection was 15 and 28 months, respectively. The 5-year survival rate was 24%. Two factors were associated with overall survival: histologic grade (P = .002) and margin status (P = .033). Only histologic grade (P = .029) was associated with recurrence-free survival.

Conclusions

Surgical resection is an efficacious treatment for HC. Patient selection based on identified prognostic factors can improve treatment outcomes.     

Risk factors and outcomes of urethral recurrence following radical cystectomy

Background

Conflicting data exist regarding predictors of urethral recurrence (UR) following radical cystectomy (RC) as well as variables associated with survival in patients who experience UR.

Objective

To evaluate the incidence, risk factors, and outcomes of patients with UR.

Design, setting, and participants

We reviewed 1506 patients who underwent RC to identify patients with UR. Median follow-up after RC was 13.5 yr (interquartile range [IQR]: 10.5–18.4).

Intervention

Urethrectomy.

Measurements

Cox proportional hazard regression models were used to analyze predictors of UR and evaluate factors associated with death from urothelial carcinoma (UC) in patients who experienced UR. Cancer-specific survival (CSS) for patients with UR, stratified according to the mode of diagnosis (abnormal urethral cytology vs symptoms), was estimated using the Kaplan-Meier method and compared with the log-rank test.

Results and limitations

UR was identified in 85 patients (5.6%) at a median of 13.3 mo (IQR: 6.1–23.2) after RC, including 80 of 1243 (6.4%) who underwent cutaneous urinary diversion and 5 of 242 (2.1%) who received an orthotopic neobladder (p = 0.002). On multivariate analysis, prostate involvement with UC (hazard ratio [HR]: 4.89; p < 0.0001), bladder tumor multifocality (HR: 2.34; p = 0.001), and orthotopic diversion (HR: 0.34; p = 0.02) were significantly associated with the risk of UR. The 5-yr CSS after UR diagnosed by cytology was 80% versus 41% for patients who presented with symptoms (p < 0.0001). Patients with symptomatic UR were noted to have significantly higher stage disease at urethrectomy (p = 0.04) and tended toward an increased risk of death from UC (HR: 1.94; p = 0.08). Limitations included retrospective study design.

Conclusions

Prostate involvement with UC, tumor multifocality, and type of urinary diversion are significantly associated with UR following RC. Although UR is relatively uncommon, the detection of asymptomatic UR was associated with significantly lower stage disease and improved patient survival, suggesting the importance of continued postoperative evaluation of the urethra.     

Comparison of Laparoscopic,Hand-Assisted,and Open Surgical Nephroureterectomy

Background and Objectives:

The aim of this study was to compare oncologic outcomes after laparoscopic nephroureterectomy, hand-assisted laparoscopic nephroureterectomy, and open nephroureterectomy for upper urinary tract urothelial cancer.

Methods:

Between April 1995 and August 2010, 189 patients underwent laparoscopic nephroureterectomy, hand-assisted laparoscopic nephroureterectomy, or open nephroureterectomy for upper urinary tract urothelial cancer. Of these patients, 110 with no previous or concurrent bladder cancer or any metastatic disease were included in this study. Cancer-specific survival, recurrence-free survival, and intravesical recurrence-free survival rates were analyzed by the Kaplan-Meier method and compared with the log-rank test. The median follow-up period for the cohort was 70 months (range, 6–192 months).

Results:

The 3 groups were well matched for tumor stage, grade, and the presence of lymphovascular invasion and concomitant carcinoma in situ. The estimated 5-year cancer-specific survival rates were 81.1%, 65.6%, and 65.2% for laparoscopic nephroureterectomy, hand-assisted laparoscopic nephroureterectomy, and open nephroureterectomy, respectively (P = .4179). The estimated 5-year recurrence-free survival rates were 33.8%, 10.0%, and 41.2% for laparoscopic nephroureterectomy, hand-assisted laparoscopic nephroureterectomy, and open nephroureterectomy, respectively (P = .0245). The estimated 5-year intravesical recurrence-free survival rates were 64.8%, 10.0%, and 76.2% for laparoscopic nephroureterectomy, hand-assisted laparoscopic nephroureterectomy, and open nephroureterectomy, respectively (P < .0001).

Conclusion:

Although there was no significant difference in cancer-specific survival rate among the laparoscopic nephroureterectomy, hand-assisted laparoscopic nephroureterectomy, and open nephroureterectomy groups, hand-assisted laparoscopic nephroureterectomy may be inferior to laparoscopic nephroureterectomy or open nephroureterectomy with regard to recurrence-free survival and intravesical recurrence-free survival rates.     

Prognostic value of lymph node yield during nephroureterectomy for upper tract urothelial carcinoma

Introduction

Lymph node dissection (LND) performed during radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) remains controversial and difficult to evaluate. The aim of this study was to investigate whether removal of more lymph nodes during RNU is safe and improves oncologic outcomes.

CXCR4 Expression Predicts Patient Outcome and Recurrence Patterns after Hepatic Resection for Colorectal Liver Metastases

Background

The purpose of this study was to determine if the expression of the chemokine receptors, CXCR4 and CCR7, and the chemokine ligand, CXCL12, in completely resected colorectal cancer hepatic metastases are predictive of disease-specific survival, recurrence-free survival and patterns of recurrence.

Methods

Immunohistochemical analysis of CXCR4, CCR7 and CXCL12 expression within resected hepatic metastases was performed and correlated with clinicopathological variables, disease-specific survival, recurrence-free survival and patterns of recurrence.

Results

Seventy-five patients who underwent partial hepatectomy with curative intent were studied. CXCR4 expression (hazard ratio [HR] 3.6, 95% confidence interval [95% CI] 1.4–9.1) and clinical risk score >2 (HR 2.3, 95% CI 1.1–4.7) were independently associated with disease-specific survival by multivariate analysis. The 5-year estimated disease-specific survival rates for positive and negative CXCR4 tumor expression were 44 and 77%, respectively (P = 0.005). CXCR4 expression (HR 2.2, 95% CI 1.2–4.2) and clinical risk score >2 (HR 1.9, 95% CI 1.1–3.4) were independently associated with recurrence-free survival by multivariate analysis. The five year estimated recurrence-free survival rates for positive and negative CXCR4 tumor expression were 20 and 50%, respectively (P = 0.004). Neither CXCL12 nor CCR7 expression in tumors predicted disease-specific survival or recurrence-free survival. Forty-nine patients (65%) developed recurrent disease after initial hepatectomy. Negative CXCR4 tumor expression was associated with favorable recurrence patterns amenable to salvage resection and/or ablation.

Conclusions

Negative CXCR4 expression in resected colorectal cancer hepatic metastases is independently associated with improved disease-specific and recurrence-free survival and favorable patterns of recurrence.

     

Preoperative prognostic factors after radical nephroureterectomy in patients with upper urinary tract urothelial carcinoma

Purpose

To evaluate the clinical significance of preoperative biomarkers such as laboratory data, Eastern Cooperative Oncology Group Performance Status (ECOG PS) and clinicopathological factors in patients undergoing radical nephroureterectomy for upper urinary tract urothelial carcinoma.

Methods

Between 1995 and 2011, a total of 99 patients treated at our institution for upper urinary tract urothelial carcinoma were enrolled in this study. The prognostic significance of various preoperative data and clinicopathological factors were analyzed. Univariate and multivariate analyses were performed using the Kaplan–Meier method with the log-rank test and a Cox proportional hazards regression model.

Results

Median patient age was 73 years (range 44–86 years), and the median follow-up period after radical nephroureterectomy was 37.9 months (range 6.6–171.4 months). The 5-year intravesical recurrence-free survival and cancer-specific survival estimates were 47.1 and 70.0 %, respectively. On multivariate analysis, concomitant bladder carcinoma was an independent predictor of intravesical recurrence (hazard ratio 3.689; P = 0.002), and infiltration (hazard ratio 14.842; P = 0.002), preoperative serum creatinine level (hazard ratio 9.992; P = 0.005), preoperative serum hemoglobin level (hazard ratio 6.370; P = 0.018) and ECOG PS (hazard ratio 4.326; P = 0.037) were associated with worse cancer-specific survival. This study is limited by biases associated with its retrospective design.

Conclusions

This study indicates that not only clinicopathological factors, but also preoperative biomarkers, such as serum creatinine and hemoglobin levels and ECOG PS, predict a poor survival in patients with upper urinary tract urothelial carcinoma.     

Galectin-9 as a prognostic and predictive biomarker in bladder urothelial carcinoma

Purpose

Galectin-9, a member of the “tandem repeat” type galectins performing as animal lectins with an affinity for β-galactosides, has been well documented to exert crucial functions in immunomodulation, survival, and growth of various tumors. This study aims to reveal the clinical significance of galectin-9 in urothelial carcinoma of the bladder (UCB) postoperatively.

Preoperative controlling nutritional status (CONUT) score as a novel predictive biomarker of survival in patients with localized urothelial carcinoma of the upper urinary tract treated with radical nephroureterectomy

Objective

The purpose of this study was to investigate the correlation between the controlling nutritional status (CONUT) score and survival of patients with localized urothelial carcinoma of the upper urinary tract treated with radical nephroureterectomy (RNU).

The effect of AB0 and Rhesus blood grouping systems on oncological outcome in patients undergoing radical nephroureterectomy for upper tract urothelial carcinoma

Objectives

To investigate the effect of AB0 and Rhesus factor expression blood group systems on outcomes of upper tract urothelial carcinoma patients treated with radical nephroureterectomy.

Prognostic factors for survival after salvage surgery for locoregional recurrence of colon cancer

Background

Although locoregional recurrence after rectal cancer resection has been extensively investigated, studies of salvage surgery for locoregionally recurrent colon cancer are scarce. This study aimed to determine the predictors of postsalvage survival for locoregionally recurrent colon cancer.

Methods

We studied 45 consecutive patients who underwent macroscopically complete resection of locoregionally recurrent colon cancer between April 1988 and December 2007. The primary end point was cancer-specific survival, and 20 clinical variables were analyzed for their prognostic significance.

Results

Cancer-specific 5-year survival for the entire cohort of 45 patients was 46%. Multivariate survival analysis showed that margin status (P = .0311), number of locoregional recurrent tumors (P = .0002), pathological grade (P = .0416), largest tumor diameter (P = .0247), and distant metastasis (P = .0006) were independently associated with cancer-specific survival.

Conclusions

Salvage surgery for locoregional recurrence of colon cancer can provide a chance for long-term survival in selected patients.     

Clinical significance of lymphovascular invasion in upper urinary tract urothelial cancer

OBJECTIVES

To clarify the significance of lymphovascular invasion (LVI) in patients with pT3N0M0 upper urinary tract (UUT) urothelial carcinoma (UC) relative to prognosis in terms of disease‐specific survival, as LVI, which implies both blood vessel and lymph vessel involvement, is reportedly a poor prognostic factor in patients with UUT‐UC.

PATIENTS AND METHODS

The clinical records of 90 patients who had surgery for UUT‐UC were reviewed retrospectively. The median patient age was 71 years and the median follow‐up was 42 months. The prognostic significances of LVI (with vs without), T stage (<1 vs 2–4), grade (1–2 vs 3), N stage (0 vs 1–2), age (≤70 vs >70 years), gender and tumour location (renal pelvis vs ureter) for survival time were evaluated.

RESULTS

LVI of UUT‐UC was found in 34 patients (37.8%). There were significantly higher frequencies of LVI with advancing stage and lymph node metastasis. Kaplan‐Meier analysis showed that LVI was strongly associated with disease‐specific survival in all patients (P < 0.001) and in patients with pT3N0M0 disease (P < 0.001). Univariate analyses showed that LVI, T stage, N stage and tumour grade were significantly related to disease‐specific survival in all patients (P < 0.001, <0.001, 0.003 and 0.007, respectively). Multivariate analysis using Cox proportional hazards model showed that LVI was the only prognostic factor with independent significance for disease‐specific survival (P < 0.001).

CONCLUSIONS

LVI appears to be an important and independent prognostic factor for UUT‐UC in patients treated by nephroureterectomy. Our data suggest that the LVI status might be a predictive marker for disease‐specific survival in patients with T3N0M0 UTT‐UC.     

Androgen receptor expression is associated with adverse pathological features in ureteral but not in pelvicalyceal urothelial carcinomas of the upper urinary tract

Purpose

This study aims to determine the significance of androgen receptor (AR) expression in urothelial carcinoma of the upper urinary tract (UTUC).

Methods

AR expression was assessed on tissue microarrays containing specimens of 737 patients with UTUC who underwent radical nephroureterectomy with curative intent. AR expression was correlated with clinical and pathological tumor features as well as recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS).

Results

Overall, AR was expressed in 11 % of tumors. AR expression was significantly associated with tumor necrosis as well as sessile and multifocal tumor growth but not with RFS, CSS or OS. AR was detected nearly twice as often in tumors of the ureter than of the pelvicalyceal system (p = 0.005). Subgroup analyses showed that the significant associations of AR with unfavorable pathologic features were exclusively attributable to tumors located in the ureter. However, in both ureteral and pelvicalyceal tumors, AR status was independent of RFS, CSS and OS.

Conclusions

In this cohort of patients treated with RNU, AR expression was found in approximately 10 % of UTUCs, twice as often in ureteral than in pelvicalyceal tumors. While AR expression had no impact on postoperative prognosis, it was significantly associated with unfavorable pathologic features in ureteral tumors. Steroid hormone signaling might be relevant for future investigations of differences between ureteral and pelvicalyceal tumors.

     

Caveolin-1 as prognostic factor of disease recurrence and survival in patients treated with radical cystectomy for bladder cancer

Purpose

Overexpression of Caveolin-1 has been associated with cancer growth, migration, and metastases in several malignancies, but only few data are available on its role in bladder cancer (BCa). The aim of this study is to validate Caveolin-1 as a prognosticator of recurrence-free survival (RFS), overall survival (OS) and cancer-specific survival (CSS) in a large cohort of patients treated with radical cystectomy (RC) for BCa.

Prognostic role of ECOG performance status in patients with urothelial carcinoma of the upper urinary tract: an international study

Study Type – Prognosis (inception cohort series) Level of Evidence 2a What's known on the subject? and What does the study add? ECOG Performance Status has gained wide popularity as an integral part of the assessment of patients with upper urinary tract carcinoma. Our findings indicate that ECOG‐PS is strongly associated with perioperative and overall survival and should be considered carefully in our decision‐making process.

OBJECTIVE

• ? To evaluate the prognostic role of ECOG Performance status (ECOG‐PS) in a large multi‐institutional international cohort of patients treated with radical nephroureterectomy for upper tract urothelial carcinoma.

MATERIALS AND METHODS

• ? Data of 427 patients treated with radical nephroureterectomy at five international institutions in Asia, Europe and Northern America were collected retrospectively from 1987 to 2008.
• ? Logistic and Cox regression models were used for univariable and multivariable analyses.

RESULTS

• ? ECOG‐PS was 0 in 272 of 427 (64%) patients. The median follow‐up of the whole cohort was 32 months.
• ? The five‐year recurrence‐free (RFS), cancer‐specific (CSS) and overall (OS) survival estimates were 71.7%, 74.9% and 68.5%, respectively, in patients with ECOG‐PS 0 compared with 60.1%, 67.8%, and 51.4% respectively, in patients with ECOG‐PS ≥1 (P value 0.08 for RFS, 0.43 for CSS, and <0.001 for OS, respectively).
• ? On multivariable Cox regression analyses, ECOG‐PS was not an independent predictor of either RFS (hazard ratio 1.4; P = 0.107) or CSS (hazard ratio 1.2; P = 0.426) but was an independent predictor of OS (hazard ratio 1.5; P = 0.03).

CONCLUSIONS

• ? In this large multicentre international study, ECOG‐PS was not significantly associated with RFS and CSS.
• ? Conversely we find a strong association with survival 1‐month after surgery and OS. Further research is needed to ascertain the additive prognostic role of ECOG‐PS in well‐designed prospective multicentre studies.

     

Comparison of oncological outcomes after segmental ureterectomy or radical nephroureterectomy in urothelial carcinomas of the upper urinary tract: results from a large French multicentre study

Study Type – Therapy (multi‐centre retrospective cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Upper urinary tract urothelial carcinomas (UUT‐UCs) are rare tumours. Because of the aggressive pattern of UC, radical nephroureterectomy (RNU) with bladder cuff removal remains the ‘gold‐standard’ treatment. However, conservative strategies, such as segmental ureterectomy (SU) or endourological management, have also been developed in patients with imperative indications. Some teams are now advocating the use of conservative management more commonly in cases of elective indications of UUT‐UCs. Due to the paucity of cases of UUT‐UC, only limited data are available on the oncological outcomes afforded by conservative management. We retrospectively investigated the oncological outcomes after SU and RNU in a large multi‐institutional database. Overall, 52 patients were treated with SU and 416 with RNU. There was no statistical difference between the RNU and SU groups for the 5‐year probability of cancer‐specific survival, recurrence‐free survival and metastasis‐free survival. The type of surgery was not a significant prognostic factor in univariate analysis. The results were the same in a subgroup analysis of only unifocal tumours of the distal ureter with a diameter of <2 cm and of low stage (≤T2). Our results suggest that oncological outcomes after conservative treatment with SU are comparable to RNU for the management of UUT‐UC in select cases.

OBJECTIVE

• ? To compare recurrence‐free survival (RFS), metastasis‐free survival (MFS) and cancer‐specific survival (CSS) after segmental ureterectomy (SU) vs radical nephroureterectomy (RNU) for urothelial carcinoma (UC) of the upper urinary tract (UUT‐UC) located in the ureter.

PATIENTS AND METHODS

• ? We performed a multi‐institutional retrospective review of patients with UUT‐UC who had undergone RNU or SU between 1995 and 2010.
• ? Type of surgery, Tumour‐Node‐Metastasis status, tumour grade, lymphovascular invasion and positive surgical margin were tested as prognostic factors for survival.

RESULTS

• ? In all, 52 patients were treated with SU and 416 with RNU. The median (range) follow‐up was 26 (10–48) months.
• ? The 5‐year probability of CSS, RFS and MFS for SU and RNU were 87.9% and 86.3%, respectively (P= 0.99); 37% and 47.9%, respectively (P= 0.48); 81.9% and 85.4%, respectively (P= 0.51).
• ? In univariable analysis, type of surgery (SU vs RNU) failed to affect CSS, RFS and MFS (P= 0.94, 0.42 and 0.53, respectively).
• ? In multivariable analyses, pT stage and pN stage achieved independent predictor status for CSS (P= 0.005 and 0.007, respectively); the positive surgical margin and pT stage were independent prognostic factors of RFS and MFS (P= 0.001, 0.04, 0.009 and 0.001, respectively).
• ? The main limitation of the study is its retrospective design, which is due to the rarity of the disease.

CONCLUSIONS

• ? Short‐term oncological outcomes after conservative treatment with SU are comparable to RNU for the management of UUT‐UC in select cases and should be considered an option.
• ? In every other case, RNU still represents the ‘gold standard’ for the treatment of UUT‐UC.