根治性膀胱切除术中扩大淋巴结清扫术不可滥用

根治性膀胱全切+尿流改道术是目前肌层浸润性膀胱肿瘤的首选治疗,盆腔淋巴结清扫术是其中的必要步骤,其对进行肿瘤准确分期、判断患者预后、提高患者的生存率至关重要,而是否所有膀胱癌患者都应该行扩大淋巴结清扫术学界尚无定论。在此,作者结合文献报道和临床诊治体会,就根治性膀胱切除术中扩大淋巴结清扫术的意义与适应征作一简要探讨。     

Development and external validation of lymph node density cut‐off points in prospective series of radical cystectomy and pelvic lymph node dissection

Objective: To identify lymph node density thresholds and their prognostic role in patients who underwent radical cystectomy and pelvic lymph node dissection, and to validate findings in an external series. Methods: Between May 2001 and September 2009, data from 750 radical cystectomies carried out at “Regina Elena” National Cancer Institute (Rome, Italy) were collected in a prospectively‐maintained database. Once patients who had undergone neoadjuvant treatments and those who had undergone salvage radical cystectomy were excluded from the 210 pN+ patients, 156 patients with urothelial carcinoma were selected for analysis. Optimal cut‐off points for age, lymph node count and lymph node density were identified by considering these variables as continuous. External validation of findings was carried out by using data of 154 pN+ patients selected from two prospective series. Results: The optimal identified cut‐off points were 11% and 30% for lymph node density, nine and 30 nodes for lymph node count, and 73 years for age. Median cancer‐specific survival of patients were significantly different in patients with lymph node density <12%, between 12% and 30%, and >30% (71 months, 24 months and 11 months, respectively; P < 0.001). Cancer‐specific survival was independently predicted by lymph node density cut‐off points (12–30% vs <12%: hazard ratio 1.51, P = 0.047; >30% vs <12%: hazard ratio 2.89, P < 0.001). In the external series, the prognostic effect of lymph node density according to tertiary distribution of risk based on these lymph node density cut‐off points was confirmed at Cox multivariable analysis (12–30% vs <12%: hazard ratio 1.5, P = 0.048; >30% vs <12%: hazard ratio 2.5, P = 0.004). Conclusions: Lymph node density is the strongest predictor of cancer‐specific survival. Identified lymph node density thresholds have shown to be independent predictors of cancer‐specific survival in the external validation series.     

Cancer‐specific survival after radical cystectomy and standardized extended lymphadenectomy for node‐positive bladder cancer: prediction by lymph node positivity and density

OBJECTIVE

To investigate the associations between different overall or topographically restricted lymph node (LN) variables and cancer‐specific survival (CSS) after radical cystectomy (RC) and extended LN dissection (LND) with curative intent in patients with LN‐positive bladder cancer.

PATIENTS AND METHODS

Between 2001 and 2006, 152 patients had RC with standardized extended LND for bladder cancer with curative intent. Patients with positive LNs were stratified according to the median of the LN variables (LNs removed, number of positive LNs, LN density). CSS was related to overall and topographically restricted LN variables, e.g. different levels of LND, and relationships were tested by univariate and multivariate analyses. Level 1 LND comprised the regions of the external and internal iliac LNs and of the obturator LNs, level 2 the templates of common iliac and presacral LNs, and level 3 the para‐aortic and paracaval LNs up to the inferior mesenteric artery. The mean (range) follow‐up was 22 (1–84) months.

RESULTS

LN metastases were diagnosed in 46 of the 152 patients (30%) with extended LND. In these 46 patients, the median number of removed LNs was 33 (level 1, 15.5; level 2, 9.0; level 3, 7.0), the median number of positive LNs was 3 (1.5, 0.5 and 0.0, respectively) and the median LN density was 0.11 (0.10, 0.02 and 0.0, respectively). The CSS was 76% at 1 year and 23% at 3 years. There were significant correlations between the 3‐year CSS and the overall LN density (≤0.11 vs >0.11; 34% vs 8%, P = 0.008), and the total number of positive LNs (≤3 vs >3; 33% vs 8%; P = 0.05). Overall LN density (hazard ratio 0.33, 95% confidence interval 0.15–0.72; P = 0.006) was an independent predictor for CSS in multivariate analysis.

CONCLUSIONS

Overall LN density is an independent predictor of survival after RC and extended LND with curative intent. Evaluation of topographically restricted LN positivity and density for different regions and levels of LND does not improve the prediction of CSS compared with overall LN positivity and density. A low incidence of level 3 LN positivity questions the clinical relevance of removing para‐aortic and paracaval LNs. However, our data need to be confirmed by a prospective randomized trial.     

腹腔镜下膀胱癌根治术中膀胱切除前后标准淋巴结清扫效果比较

目的观察在腹腔镜膀胱癌根治术中膀胱切除前后进行标准盆腔淋巴结清扫术(PLND)两种手术方案的相关临床指标变化。方法回顾性分析2018年1月至2019年5月长海医院接受腹腔镜膀胱癌根治术加标准淋巴结清扫的63例肌层浸润性膀胱癌(MIBC)患者的临床资料,其中男性54例,女性9例;年龄41~85岁,平均(66±9)岁。由2位不同的主刀医生分别实施先清扫淋巴结组(A组)和后清扫淋巴结组(B组)。统计术中及术后的相关临床指标,结果用t检验、非参数检验和卡方分析进行统计分析。结果两组的年龄、体质指数和肿瘤分期等术前基线指标无统计学差异。A、B组清扫淋巴结总数分别为11.3±5.8和13.6±5.1(P>0.05),阳性淋巴结检出率分别为15.6%(5/32)和22.6%(7/31,P>0.05),并发症发生率分别为9.4%(3/32)和3.2%(1/31,P>0.05);术中出血量和手术前后血红蛋白、白蛋白以及肌酐变化值等无统计学差异(P>0.05)。结论腹腔镜下膀胱癌根治术在膀胱切除前后行标准PLND在淋巴结清扫数量、术后临床指标变化方面两组无显著性差异,两种手术方式在熟练掌握手术技巧后均安全、有效。     

The lymph node yield during robot-assisted radical cystectomy

OBJECTIVE

To evaluate the lymph node yield (LNY) during robot‐assisted radical cystectomy (RC), as it has been questioned as to whether robot assistance allows adequate pelvic LN dissection (LND), especially during the initial experience.

PATIENTS AND METHODS

In all, 67 consecutive patients were selected for robot‐assisted RC and LND with open urinary diversion from October 2005 to November 2007. Data was collected prospectively in a standard fashion as part of a quality assurance programme. Nine patients were excluded (three had unresectable disease and six underwent palliative cystectomy) and the remainder were divided into five groups. Data included demographics, operative variables, complications and pathological outcomes. Evidence of the LNY curve was examined using nonlinear regression to compare the number of LNs obtained.

RESULTS

The mean (range) patient age was 67 (36–90) years and the mean body mass index (BMI) was 27 (17–45) kg/m². The mean operative duration for the robot‐assisted pelvic LND was 44 (19–85) min. There was one postoperative complication that required exploration for vascular injury. The mean number of LNs retrieved was 18 (6–43). The mean LNY for each of the five groups was 13, 16, 21, 19 and 23, respectively, and neither BMI nor previous major abdominal surgery affected LNY.

CONCLUSION

Robot‐assisted RC with pelvic LND was performed safely. LNY was oncologically acceptable and increased with experience.     

Standardization of radical cystectomy and pelvic lymph node dissection for bladder cancer: a collaborative group report

PURPOSE: We propose standards for radical cystectomy and pelvic lymph node dissection in the surgical treatment of patients with invasive bladder cancer. MATERIALS AND METHODS: We compiled the consecutive cystectomy experience of 16 experienced surgeons during the last 3 years (2000 to 2002) from 4 institutions. We evaluated patient, tumor and surgical variables of margin status, extent of pelvic node dissection, number of nodes examined and surgeon volume associated with bladder cancer outcomes. RESULTS: A total of 1,091 cystectomy cases were evaluated. Surgical margins and number of nodes retrieved correlated with patient age, prior treatments, pathological tumor stage and extent of node dissection, but not surgeon volume. CONCLUSIONS: Standards for radical cystectomy can be established and achieved by experienced surgeons operating on patients presenting with diverse clinical situations.     

Robotic and laparoscopic high extended pelvic lymph node dissection during radical cystectomy: technique and outcomes

Background

With the increasing use of laparoscopic and robotic radical cystectomy (RC), there are perceived concerns about the adequacy of lymph node dissection (LND).

Objective

Describe the robotic and laparoscopic technique and the short-term outcomes of high extended pelvic LND (PLND) up to the inferior mesenteric artery (IMA) during RC.

Design, setting, and participants

From January 2007 through September 2009, we performed high extended PLND with proximal extent up to the IMA (n = 10) or aortic bifurcation (n = 5) in 15 patients undergoing robotic RC (n = 4) or laparoscopic RC (n = 11) at two institutions.

Surgical procedure

We performed robotic extended PLND with the proximal extent up to the IMA or aortic bifurcation. The LND was performed starting from the right external iliac, obturator, internal iliac, common iliac, preaortic and para-aortic, precaval, and presacral and then proceeding to the left side. The accompanying video highlights our detailed technique.

Measurements

Median age was 69 yr, body mass index was 26, and American Society of Anesthesiologists class ≥3 was present in 40% of patients. All urinary diversions, including orthotopic neobladder (n = 5) and ileal conduit (n = 10), were performed extracorporeally.

Results and limitations

All 15 procedures were technically successful without need for conversion to open surgery. Median operative time was 6.7 h, estimated blood loss was 500 ml, and three patients (21%) required blood transfusion. Median nodal yield in the entire cohort was 31 (range: 15-78). The IMA group had more nodes retrieved (median: 42.5) compared with the aortic bifurcation group (median: 20.5). Histopathology confirmed nodal metastases in four patients (27%), including three patients in the IMA group and one patient in the aortic bifurcation group. Perioperative complications were recorded in six cases (40%). During a median follow-up of 13 mo, no patient developed local or systemic recurrence. Limitations of the study include its retrospective design and small cohort of patients.

Conclusions

High extended PLND during laparoscopic or robotic RC is technically feasible. Longer survival data in a larger cohort of patients are necessary to determine the proper place for robotic and laparoscopic surgery in patients undergoing RC for high-risk bladder cancer.     

Extended versus limited lymph node dissection in radical cystectomy: impact on recurrence pattern and survival

Objectives: To compare recurrence patterns and survival of patients with carcinoma of the urinary bladder undergoing radical cystectomy and extended or limited lymph node dissection. Methods: From a consecutive series of 469 patients undergoing radical cystectomy, two different historical cohorts were constructed; one with 265 patients intentionally undergoing extended lymph node dissection and one with 204 patients undergoing limited lymph node dissection. Results: Early lymph node recurrences were more frequently located outside the pelvic region in patients from the extended lymph node dissection cohort, whereas the overall risk of recurrence was not reduced by carrying out an extended lymph node dissection compared with the limited lymph node dissection cohort (8% vs 6%, P = 0.5). However, positive node patients had a significantly better prognosis after extended lymph node dissection (5‐year disease‐specific survival 29% vs 8%, P = 0.002). Improved survival was also found in negative node patients with non‐organ confined tumors undergoing extended lymph node dissection compared with limited lymph node dissection (5‐year disease‐specific survival 76% vs 62%, P = 0.008). A total of 16 positive node patients (6%) in the extended lymph node dissection cohort were identified as possible stage migrators with metastasis exclusively in lymph nodes outside the limited template. A total of 5% of patients undergoing extended lymph node dissection had an evident survival benefit of an extended lymph node dissection compared with a limited lymph node dissection. Conclusions: Extended lymph node dissection provides more accurate nodal staging than a limited lymph node dissection. However, recurrence patterns are not significantly altered by extending the limits of lymph node dissection, suggesting a survival benefit only in a minority of patients. Improved survival is more likely in patients with locally advanced disease.     

Evaluation of different lymph node (LN) variables as prognostic markers in patients undergoing radical cystectomy and extended LN dissection to the level of the inferior mesenteric artery

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Different lymph node variables have been suggested as prognostic factors to improve substratification of lymph node positive patients undergoing cystectomy. In this uniform surgery only series the classical TNM classification still provided the most relevant stratification, whereas several other tested variables proved to have little or no relevant influence regarding prognosis.

OBJECTIVE

? To evaluate the prognostic impact of lymph node (LN) variables in patients undergoing radical cystectomy (RC) and extended LN dissection.

PATIENTS AND METHODS

? From January 2004 to January 2009, 167 patients with bladder cancer underwent RC and extended LN dissection to the level of the inferior mesenteric artery in a surgery‐only series with no neoadjuvant or adjuvant chemotherapy. ? Correlation to prognosis of different LN variables according to presence of LN metastasis, number, localization, extracapsular extension (ECE), size, volume, LN density and N‐stage according to two different Tumour‐Node‐Metastasis (TNM) classifications were analysed.

RESULTS

? In all, 43 patients (26%) had LN metastases. ? In univariate analysis, gender, T‐stage and several different LN variables stratified by presence of LN metastasis, number of positive LNs, anatomical localisation, ECE, LN density, size and volume of positive LNs, were significant prognostic predictors. ? Female gender, advanced T‐stage, presence of LN metastasis, non‐regional LN metastases (M‐positive) and number of positive LNs (1 vs >1) were significant adverse prognostic predictors in multivariate analysis, whereas the other LN variables were not. ? Inclusion of the common iliac LNs in the regional LNs as suggested in the seventh edition of the TNM classification was relevant regarding prognosis. However, subclassification based on location was not correlated to prognosis. The new N3 category therefore seems superfluous.

CONCLUSIONS

? LN‐positive patients have a poor prognosis, especially if >1 positive LN is present. ? Despite several different suggestions of new LN‐dependent prognostic factors, none of the tested variables were independently significant in the present series.     

Outcome of patients with grossly node positive bladder cancer after pelvic lymph node dissection and radical cystectomy

PURPOSE: Should the surgeon proceed with surgery when grossly positive nodes are found at cystectomy? To answer this question, we determine the outcome of patients after radical surgery alone for grossly node positive bladder cancer. MATERIALS AND METHODS: A total of 84 patients with grossly node positive (N2-3) bladder cancer found at cystectomy underwent extended pelvic lymph node dissection and have been followed for up to 10 years. The end point of study was disease specific survival. RESULTS: Of the 84 patients 20 (24%) survived and 64 (76%) died of disease. Median survival time was 19 months for all patients and 10 years for surviving patients. Of 53 patients with clinical stage T2 (organ confined) tumors 17 (32%) survived versus 3 of 31 (9.7%) with stage T3 (extravesical) tumors. CONCLUSIONS: A proportion of patients with grossly node positive bladder cancer can be cured with radical cystectomy and thorough pelvic lymph node dissection.     

Laparoscopic extended pelvic lymph node dissection during radical cystectomy: technique and clinical outcomes

Study Type – Therapy (case series)
Level of Evidence 4 What’s known on the subject? and What does the study add? Pelvic lymph node dissection (PLND) is an obligatory step for radical cystectomy and it provides staging information and potential survival benefits. This study shows extended PLND with proximal boundary of inferior mesentery artery is safe and feasible under laparoscopy. More positive nodes can be retrieved compared to standard template.

OBJECTIVE

? To study the surgical techniques and clinical results of laparoscopic extended pelvic lymph node dissection during radical cystectomy.

PATIENTS AND METHODS

? From July 2007 to October 2009, 43 patients with bladder carcinoma received laparoscopic radical cystectomy with extended pelvic lymphadenectomy and urinary diversion. ? Pelvic lymph node dissection (PLND) was first performed within extended template. ? The lower part of aorta and vena cava were isolated from the bifurcation of common iliac artery to the level of the inferior mesenteric artery. ? The standard template PLND was continued along the external iliac vessels, internal iliac vessels and obturator nerve. The bladder was then removed laparoscopically and urinary diversion was performed.

RESULTS

? All procedures were performed successfully and no open conversion occurred. The duration of the procedure for extended PLND was 90–185 min (mean 125 min) and total duration was 280–470 min (mean 329 min). ? Intra‐operative blood loss was 200–1500 mL (mean 325 mL) and eight cases received transfusion. Pathological study identified transitional cell carcinoma and a negative margin in all cases. A range of 19–53 lymph nodes were dissected in the patients with a mean of 31.3. ? In total, 17 positive nodes were confirmed in 11 cases. Postoperative complications included two cases of bowel obstruction, two cases of mild urine leakage and 17 cases of lymphatic leakage.

CONCLUSIONS

? Laparoscopic radical cystectomy with extended pelvic lymphadenectomy is indicated in selected patients with bladder cancer. ? It is safe, minimally invasive and more lymph nodes can be retrieved with a higher success rate by extended pelvic lymphadenectomy.     

Stage specific lymph node metastasis mapping in radical cystectomy specimens

PURPOSE: We provide an accurate map of lymph node (LN) metastasis in patients with bladder cancer undergoing radical cystectomy and pelvic lymph node dissection. MATERIALS AND METHODS: We analyzed data on 176 consecutive patients operated on by the same surgeon. The extent of node dissection included presacral, bilateral common iliac and pelvic, and perivesical. The number of LNs removed from each site and the number of metastases bearing nodes were recorded separately. Stage specific maps were constructed. RESULTS: The median number of LNs removed was 25 (range 2 to 80). Metastases were found in the lymph nodes of 43 patients (24.4%) and the median number of positive nodes was 3 (range 1 to 63). Of these patients 22 (51%) had lymph node involvement at more than 1 site. The mean number of positive/total LNs sampled +/- SD in LN positive cases was 26% +/- 28% and the median was 13% (range 1.9 to 100%). Only 1 of the patients with pT1 (3.6%) had LN metastases, which was in the pelvic region. Only 2 of the patients with pT2 (3%) had LN metastases outside of the true pelvis and perivesical sites. Of patients with pT3 or pT4 16% had LN metastases outside the common boundaries for standard LN dissection, namely the common iliac artery and at or above aortic bifurcation. CONCLUSIONS: We present a detailed map of regional LN involvement in patients treated with radical cystectomy and lymph node dissection for transitional cell cancer of the bladder. Extensive LN dissection is essential for the complete removal of disease and accurate staging.     

Combination chemotherapy of ifosfamide, 5‐fluorouracil,etoposide and cisplatin as perioperative treatment in lymph node positive bladder carcinoma patients treated by radical cystectomy

Objectives: To evaluate the efficacy and toxicity of perioperative combination chemotherapy with ifosfamide, 5‐fluorouracil, etoposide and cisplatin (IFEP) in bladder cancer patients with regional lymph node metastases treated by radical cystectomy. Methods: We reviewed the medical records of 183 consecutive patients who underwent radical cystectomy for invasive urothelial carcinoma of the bladder. Of those, 26 patients with regional lymph node metastasis who were regarded as being rendered surgically disease‐free (pT1‐4, N1‐2, cM0) and treated with perioperative IFEP chemotherapy were the subjects of the present study. Results: Median follow‐up of 26 patients was 49 months (range 4–150). Grade 3 and 4 bone marrow toxicities were seen in 15 and four patients, respectively. Neither chemotherapy‐related death nor febrile neutropenia occurred. The 5‐year overall and cancer‐specific survival rate was 60% and 68%, respectively. The overall survival rate of the patients with pT4 disease was significantly worse than that of patients with pT1‐3. There were four N2 patients who survived for over 5 years free of disease. Conclusions: Perioperative IFEP therapy appeared to be effective in the treatment of lymph node positive bladder cancer patients who underwent radical cystectomy. Further study may be warranted.