低位直肠癌直肠系膜、盆腔侧方淋巴结转移规律分析

目的研究低位直肠癌直肠系膜、盆腔侧方淋巴结转移和微转移规律。方法联合运用大组织切片与组织芯片技术,研究67例全直肠系膜切除（total mesorectal excision,TME）、盆腔侧方淋巴结清扫手术标本。结果直肠系膜淋巴结癌转移30例,微转移10例,29.6%转移淋巴结位于直肠系膜外带。肿瘤远端、肿瘤旁和肿瘤近端直肠系膜内淋巴结转移的检出例数分别为4、32和19例,与肿瘤分化程度相关。9例标本存在环周切缘癌浸润（circumferential resection margin involvement,CRMI）,2例见微转移。盆腔侧方淋巴结癌转移、微转移分别为12例和10例,与肿瘤分化程度、浸润深度相关。结论按照TME原则手术,完整切除包裹在盆腔筋膜内的直肠系膜,可提高局部肿瘤廓清率,降低CRMI发生率。低位直肠癌盆腔侧方淋巴结转移较常见,应合理制定手术范围。     

低位直肠癌侧方转移和微转移的临床病理学研究

目的探讨低位直肠癌盆腔侧方淋巴结转移、微转移规律及其对预后的预测价值。方法运用大组织切片、组织芯片研究67例低位直肠癌手术标本,并分析其随访资料。结果12例标本检获盆腔侧方淋巴结癌转移,另有10例存在微转移,82．9％的转移淋巴结直径〈5mm。髂内血管、闭孔、髂内远端内侧分支等处淋巴结受累率较高。侧方转移、微转移病例术后复发多,生存时间短。结论低位直肠癌存在盆腔侧方转移,各区域受累率不一。侧方转移病例预后差,提示术前／术后辅助治疗的价值。     

中下段直肠癌直肠系膜转移的研究

目的探讨中下段直肠癌系膜转移与临床病理特征的关系。方法对56例行直肠系膜全切除的中下段直肠癌采用病理大切片法检测直肠系膜转移情况,并分析其与临床病理特征的关系。结果中下段直肠癌直肠系膜转移率为64．3％（36／56）。直肠系膜淋巴结转移率为51．8％（29／56）;直肠系膜癌巢阳性率44．6％（25／56）。直肠系膜转移病灶距肿瘤远端最远有5cm。肿瘤直径35cm中下段直肠癌系膜转移率为83．3％（15／18）,而肿瘤直径＜5cm仅为55．3％（21／38）（P=0．041）。T1、T2和T3期直肠癌直肠系膜转移率分别为1／6、56．6％（13／23）和81．5％（22／27）（P=0．007）。高分化、中分化和低分化直肠癌直肠系膜转移率分别为1／5、63．2％（23／37）和85．7％（12／14）（P=0．028）。I期、Ⅱ期和Ⅲ期直肠癌直肠系膜转移率分别为1／5、27．3％（6／22）和100％（29／29）（P=0．000）。直肠系膜转移率与性别、年龄、肿瘤侵袭肠壁周径、Ming分型无关（P＞0．05）。结论中下段直肠癌直肠系膜转移与肿瘤直径、浸润深度、分化程度和分期密切相关。中下段直肠癌应行直肠系膜全切除或远端直肠系膜切除至少5cm。     

中低位直肠癌系膜浸润程度的临床研究

目的探讨中低位直肠癌直肠系膜浸润程度与临床病理特征及预后的关系。方法采用大组织切片技术,测量行全直肠系膜切除术的49例中低位直肠癌标本的肿瘤浸润深度及直肠系膜厚度,计算直肠系膜浸润程度;并分析其临床病理特征和随访结果。结果本组中低位直肠癌术后局部复发率为12．2％（6／49）,远处转移率为26．5％（13／49）。直肠癌直肠系膜浸润程度Ⅰ度20例（40．8％）,Ⅱ度13例（26．5％）,Ⅲ度16例（32．7％）,Ⅰ、Ⅱ、Ⅲ度者术后局部复发率分别为0、7．7％和31．3％（X^2=7．357,P=0．015）;远处转移率分别为10％、23．1％和50％（X^2=7．405,P=0．025）;5年生存率则分别为90．9％、69．2％和28．6％（p=0．013）。直肠系膜浸润程度与肿瘤直径（X^2=6．849,P=0．033）、T分期（X^2=34．845,P=0．000）、N分期（X^2=17．266,P=0．002）有关。结论直肠系膜浸润程度是影响直肠癌预后的重要因素。     

462例中下段直肠癌淋巴转移规律与淋巴清扫范围的分析

目的 探讨中下段直肠癌的淋巴转移规律和淋巴清扫范围。方法 对1990－1999年行传统直肠癌根治术的373例和行传统直肠癌根治术加盆腔侧方淋巴清扫术（简称侧方清扫术）的89例中下段直肠癌患者进行回顾性分析。结果 全组淋巴转移率为41．8％,患者年龄、癌灶浸润深度、大体分型、癌灶大小是影响淋巴转移率的重要因素（P＜0．05）。89例侧方清扫术的盆腔侧方淋巴转移率为15．7％,其中85．7％位于癌灶同侧。有盆腔侧方淋巴结转移者均为浸润深度T3、T4者;癌灶＞3cm、溃疡型或浸润型、年龄＜60岁者盆腔侧方淋巴结转移较高。侧方清扫术组的盆腔复发率为5．6％,明显低于传统直肠癌根治术组的17．7％（P＜0．05）;侧方清扫术组和传统直肠癌根治术组的5年生存率分别为46．7％和47．9％（P＞0．05）。结论 应提高对中下段直肠癌淋巴转移规律的认识,对怀疑或证实有淋巴结转移、癌灶侵犯浆膜或穿透肠壁、癌灶＞3cm、溃疡型或浸润型、年龄＜60岁者建议行侧方清扫术。     

侧方淋巴结清扫对进展期低位直肠癌预后的影响

目的 应用治疗指数(therapeutic index,TX)(TX=肿瘤相关5年生存率×区域淋巴结转移的概率)评估侧方淋巴结清扣对于改善进展期低位直肠癌预后的价值.方法 回顾性分析直肠癌行根治性切除+全直肠系膜切除+侧方淋巴结清扫的96例进展期低位直肠癌患者的临床资料.结果 进展期低位直肠癌直肠系膜淋巴结、直肠上动脉旁淋巴结、肠系膜下动脉旁淋巴结和侧方淋巴结转移率分别为21%(20/96),13%(12/96),10%(10/96)和15%(14/96).检出直肠系膜淋巴结、直肠上动脉旁淋巴结、肠系膜下动脉旁淋巴结和侧方淋巴结转移阳性的进展期低位直肠癌患者5年生存率分别为35%,25%,20%和36%.TX:清扫直肠系膜淋巴结和侧方淋巴结的TX分别为7.4和5.4,明显高于清扫直肠上动脉和肠系膜下动脉旁淋巴结的3.3和2.0.侧方淋巴结转移阳性者术后局部复发率为64%(9/14),TX明显高于侧方淋巴结转移阴性者的11%(9/82)(x2=22.308/P=0.000).Kaplan-Meier生存分析显示,侧方淋巴结转移阳性患者平均生存期为(38.0±6.7)个月(95%置信区间:24.8～51.2个月),明显短于侧方淋巴结转移阴性的(80.9±2.1)个月(95%置信区间:76.7～85.1个月),两者差异有统计学意义. 结论侧方淋巴结清扫可降低进展期低位直肠癌根治性切除术后局部复发率以及改善预后.除全直肠系膜切除外,进展期低位直肠癌术中还应进行侧方淋巴结清扫.     

超低位直肠癌新辅助治疗后淋巴结分布及转移规律

目的探讨新辅助治疗对超低位直肠癌淋巴结转移及其微转移规律及分布的影响,为手术方式的选择提供依据。方法运用大组织切片苏木精．伊红染色和组织芯片CK20染色方法,研究超低位直肠癌新辅助治疗组（21例）与直接手术组（23例）行Miles手术后的大体标本。结果新辅助治疗组21例患者直肠系膜共检获淋巴结138枚．其中转移淋巴结39枚,微转移12枚：7例为淋巴结癌转移。2例为淋巴结微转移,6例为病理完全缓解。直接手术组23例患者的直肠系膜共检获淋巴结415枚,其中转移淋巴结169枚,微转移59枚：12例为淋巴结癌转移,4例为淋巴结微转移。两组直肠系膜外带与前区的转移淋巴结分别占21．5％（11／51）与29．0％（49／169）、17．6％（9／51）与17．2％（29／169）。坐骨直肠窝转移淋巴结分别占该区总淋巴结的25．0％（3／12）与22．2％（8／36）,该区淋巴结转移或微转移者分别占总病例数的4．8％（1／21）与13．0％（3／23）。结论新辅助治疗影响超低位直肠癌区域淋巴结的转移与分布．新辅助治疗组肛门括约肌累及较直接手术组显著降低。坐骨直肠窝内极少发生淋巴结转移,Miles手术作为超低位直肠癌新辅助治疗后标准术式的价值应重新评估。     

中下段直肠癌血管内皮生长因子表达与直肠系膜转移的关系

目的分析中下段直肠癌血管内皮生长因子（VEGF）表达与临床病理特征的关系。初步探讨中下段直肠癌直肠系膜转移的分子机制。方法采用病理大切片前瞻性研究56例中下段直肠癌直肠系膜转移情况，采用免疫组织化学技术检测肿瘤组织VEGF表达。结果57．1％（32／56）中下段直肠癌VEGF表达阳性；T3直肠癌VEGF表达阳性率为74．1％。明显高于配和T1直肠癌的43．5％和33．3％（P〈0．05）；淋巴结转移阳性的中下段直肠癌VEGF表达阳性率为72．4％明显高于淋巴结转移阴性的40．7％（P〈0．05）；中下段直肠癌直肠系膜转移率为64．3％（36／56）。36例系膜转移阳性直肠癌25例（69．4％）VEGF表达阳性，而20例系膜转移阴性直肠癌仅7例（35％）VEGF表达阳性，两者差异有统计学意义（P〈0．05）。结论中下段直肠癌VEGF表达与浸润深度和淋巴结转移密切相关。VEGF可能参与中下殷盲肠癌盲肠系膊转移的发生．     

中下段直肠癌基质金属蛋白酶-2表达与直肠系膜转移的关系

目的分析基质金属蛋白酶-2（MMP-2）在中下段直肠癌的表达及与直肠系膜转移的关系。方法采用病理大切片技术前瞻性研究56例中下段直肠癌直肠系膜转移的情况，免疫组织化学技术检测肿瘤组织MMP-2的表达。结果75％（42／56）的中下段直肠癌MMP-2表达阳性；T2、T3期直肠癌MMP-2表达阳性率分别为69．6％和88．9％，明显高于T1期直肠癌的33．3％（P=0．013）。Ming分型中，浸润型直肠癌MMP-2表达阳性率为91．2％，明显高于膨胀型直肠癌的40．0％（P=0．001）。中下段直肠癌直肠系膜转移率为64．3％（36／56）。系膜转移阳性的36例中有31例（86．1％）MMP-2表达阳性，而系膜转移阴性的20例中仅11例（55．0％）MMP-2表达阳性（P=0．01）。结论中下段直肠癌MMP-2表达与浸润深度和Ming分型密切相关。MMP-2可能参与中下段直肠癌直肠系膜转移的发生。     

中下段直肠癌盆腔侧方淋巴转移情况与转归

目的探讨中下段直肠癌盆腔侧方淋巴结转移(简称侧方转移)的规律和预后。方法对1990～2001年经根治性切除证实侧方转移的20例中下段直肠癌患者的临床资料进行回顾性分析。结果85.0%(17/20)的患者为直肠系膜和/或根部淋巴转移加侧方转移,15.0%(3/20)的患者为单纯侧方转移。侧方转移率依次为闭孔动脉45.0%(9/20)、髂内动脉40.0%(8/20)、髂总动脉20.0%(4/20)、髂外动脉15.0%(3/20)和腹主动脉分叉淋巴结5.0%(1/20)。75.0%的患者发生术后远处转移或远处转移合并盆腔局部复发,其中83.3%发生于术后2年内。患者平均生存期21.6个月,术后3年、5年生存率分别为16.7%和0。结论中下段直肠癌侧方转移不仅是盆腔局部病变,还可能是属于全身病变的一部分,提示直肠癌远处转移发生的可能性。     

Prognostic determinants of patients with lateral nodal involvement by rectal cancer

OBJECTIVE: To clarify the characteristics related to long-term survival in patients with lateral nodal involvement. SUMMARY BACKGROUND DATA: Few reports have addressed the prognostic determinants in patients with actual lateral nodal involvement, which are important in determining treatment. METHODS: Review of a prospective colorectal database at a single institution for a 10-year period (1987-1996) identified 53 patients with lateral nodal involvement. RESULTS: All nine patients who underwent resection of synchronous distant metastases developed recurrence and died within 3 years. Of the 44 patients without distant metastases, 25 (57%) developed locoregional recurrence, and the overall 5-year survival rate was 32%. Multivariate analysis showed that age, total number of involved nodes (mesorectal and lateral), and circumferential surgical margin involvement had independently predicted postoperative survival. Patients with three or fewer nodes involved accounted for one third of lateral-positive patients, with a 5-year survival rate of 75%, whereas the 18 patients with four or more involved nodes had a 5-year survival rate of 4%. All eight patients with circumferential margin involvement died of carcinoma, and seven developed locoregional recurrences. Involvement of other pelvic organs had no effect on prognosis, nor were adverse prognostic outcomes noted by the region of lateral involvement. CONCLUSIONS: For patients with lateral involvement, the most important prognostic variables are distant metastases, the total number of nodes involved, circumferential margin involvement, and age. Selection of patients based on these variables may lead to the identification of a subgroup for whom lateral nodal dissection could be the first treatment choice.     

Efforts to improve local control in rectal cancer compromise survival by the potential morbidity of optimal mesorectal excision

BACKGROUND: The technique of total mesorectal excision (TME) increases the risk of anastomotic leakage. The impact of postoperative morbidity of TME on longterm survival has never been described. We retrospectively analyzed factors that might influence survival after TME for rectal cancer, including postoperative morbidity. STUDY DESIGN: From 1994 to 2001, 300 patients (192 men and 108 women; mean age, 64 years) had TME for rectal cancer. Preoperative radiotherapy was given in 202 patients. Age, gender, tumor height, size and circular invasion of the tumor, pathologic tumor and nodal status, distal and circumferential margins, number of lymph nodes analyzed, type of surgery, postoperative pelvic sepsis, preoperative radiotherapy, and adjuvant chemotherapy were examined; their association with overall and disease-free survival was evaluated by the log-rank test in univariate analysis and by multivariable Cox proportional hazards analysis. RESULTS: Postoperative morbidity was 38% (113 of 300 patients) and included 18% (54 of 300 patients) pelvic sepsis. The local recurrence rate was 6% (18 of 300 patients), and the distant metastasis rate was 24% (73 of 300 patients). Recurrence was three times more frequent distally than locally, including patients with pelvic sepsis The 5-year overall and disease-free survival rates were 72% and 60%, respectively. Independent predictors of overall survival were age older than 64 years (odds ration [OR]=2.19, 95% CI 1.32 to 4.17), pelvic sepsis (OR=2.06, 95% CI 1.10 to 3.87), circumferential surgical margin (OR=3.19, 95% CI 1.67 to 6.09), pathologic tumor (OR=2.69, 95% CI1.23 to 5.88), and nodal status (OR=3.18, 95% CI 1.79 to 5.64). Independent predictors of disease-free survival were pelvic sepsis (OR=2.17, 95% CI 1.31 to 3.58), circumferential surgical margin (OR=2.61, 95 CI 1.52 to 4.49), pathologic tumor (OR=1.82, 95% CI 1.04 to 3.20), and nodal status (OR=2.67, 95% CI 1.68 to 4.23). Patients with pelvic sepsis had a 5-year disease-free survival of 39% compared with 65% without pelvic sepsis (p<0.001). CONCLUSIONS: After TME for rectal cancer, pelvic sepsis is a common complication that is associated with increased risk of distant recurrence and decreased longterm survival. Efforts are necessary to decrease postoperative morbidity in surgical treatment of rectal cancer.     

Potential prognostic benefit of lateral pelvic node dissection for rectal cancer located below the peritoneal reflection

OBJECTIVE: To identify the parameters related to the effective selection of patients who could receive prognostic benefit from lateral pelvic node dissection. BACKGROUND: Accurate preoperative diagnosis of lateral nodal involvement (LNI) remains difficult, and the indications for lateral lymph node dissection have been controversial. PATIENTS AND METHODS: A total of 244 consecutive patients who underwent potentially curative surgery with lateral dissection for advanced lower rectal cancer (1985-2000) were reviewed. Patients were stratified into groups based on various parameters, and the therapeutic value index for survival benefit was compared among groups. The therapeutic index of lateral dissection was calculated by multiplying the frequency of metastasis to the lateral area and the cancer-related 5-year survival rate of patients with metastasis to the lateral area, irrespective of metastasis to other areas (mesorectal, superior rectal artery [SRA], and inferior mesenteric artery [IMA] areas). RESULTS: LNI was observed in 41 patients (17%); and 88% of them had nodal involvement in the region along the internal iliac/pudendal artery or in the obturator region ("vulnerable field"). The cancer-related 5-year survival rate among the patients with LNI was 42%; the therapeutic index for lateral dissection was calculated as 7.0 patients, which was much higher than that of lymphadenectomy of the SRA area (1.6 patients) and the IMA area (0.4 patients), and almost comparable to that of lymphadenectomy of the upward mesorectal area (6.9 patients). Although it was possible to select groups at high and low risk for LNI based on several parameters related to tumor aggressiveness, such as tumor differentiation in biopsy specimens, the therapeutic value index was not significantly different between these groups. Unlike these parameters, the diameter of the largest lymph node in the "vulnerable field," which was positively correlated with the rate of LNI but irrelevant to the prognosis, was able to successfully stratify patients by therapeutic index. CONCLUSIONS: Advanced lower rectal cancer patients having LNI in the lateral pelvic area are likely to receive prognostic benefit from lymphadenectomy. The most efficient means of determining the effectiveness of lateral dissection preoperatively is to estimate the nodal diameter in the "vulnerable" lateral regions by diagnostic imaging.     

Comparative outcome between chemoradiotherapy and lateral pelvic lymph node dissection following total mesorectal excision in rectal cancer

OBJECTIVE: To evaluate comparative outcome between adjuvant postoperative chemoradiotherapy (postoperative CRT) and lateral pelvic lymph node dissection (LPLD) following total mesorectal excision (TME) in rectal cancer patients. BACKGROUND: Although TME results in lower rate of locoregional recurrence compared with conventional surgery, these 2 treatment modalities following TME have not adequately been appraised until the present trend of preoperative chemoradiotherapy. PATIENTS AND METHODS: Between 1995 and 2000, patients with stage II and III rectal cancer underwent TME plus postoperative CRT (n = 309) or LPLD (n = 176). Patients in the postoperative CRT group received 8 cycles of 5-fluorouracil plus leucovorin and 45 Gy pelvic radiotherapy. Patients in the LPLD group underwent lateral lymph node dissection outside the pelvic plexus. RESULTS: The 5-year overall and disease-free survival rates were 78.3% and 67.3% in the postoperative CRT group, respectively, and 73.9% and 68.6% in the LPLD group, respectively, without significant differences between these groups. Patients in the LPLD group with stage III lower rectal cancer had a locoregional recurrence rate 2.2-fold greater than those in the postoperative CRT group (16.7% vs. 7.5%, P = 0.044). Multivariate analysis showed that APR and advanced T-category (T4) were significantly associated with locoregional recurrence, whereas lymph node metastases, high preoperative serum carcinoembryonic antigen, and APR were significantly associated with shortening of disease-free survival. CONCLUSIONS: Postoperative-CRT and LPLD following TME resulted in comparable survival rates, but the locoregional recurrence rate was higher in the LPLD group. These findings suggest that initial surgery is appropriate for rectal cancer patients who are candidates for low anterior resection without extensive local disease (T1-T3), regardless of lymph node status.     

Survival benefit of lateral lymph node dissection according to the region of involvement and the number of lateral lymph nodes involved

Purpose

The effectiveness of lateral lymph node dissection for extending the survival of patients with advanced lower rectal cancer remains unclear. The purpose of this study was to clarify the survival benefit of lateral lymph node dissection according to the region of involvement and the number of lateral lymph nodes involved.

Methods

We reviewed 131 consecutive patients with advanced lower rectal cancer, who had undergone curative resection with total mesorectal excision plus extended lateral lymph node dissection at Wakayama Medical University Hospital. Twenty-six (19.1 %) of these patients had lateral lymph involvement. We performed univariate and multivariate analyses for the 3-year disease-free and overall survival of these patients.

Results

Multivariate analysis revealed that the number (>1) and the region (common iliac artery region or external iliac artery region) of lateral lymph node metastasis are independent predictive factors for recurrence and survival. The Kaplan–Meier analysis demonstrated that patients with one lymph node metastasis in the internal iliac artery or obturator region had better survival.

Conclusions

Lateral lymph node dissection resulted in survival benefit for patients with single lateral lymph node involvement in the internal iliac artery region or the obturator region.     

Incidence and prognostic significance of lateral lymph node metastasis in patients with advanced low rectal cancer

BACKGROUND: Lateral lymph node metastases occur in some patients with low rectal cancer and may cause local recurrence after total mesorectal excision. The aims of this study were to identify risk factors for lateral node metastases in patients with pathological tumour (pT) stage 3 or pT4 low rectal adenocarcinoma, and to evaluate the prognostic significance of lateral node metastases. METHODS: A retrospective analysis was performed of the outcome of 237 patients with pT3 or pT4 low rectal adenocarcinoma who underwent R0 resection with systematic lateral node dissection. RESULTS: Lateral lymph node metastases were found in 41 patients (17.3 per cent). Increased risk of lateral lymph node metastases was associated with a distal tumour margin close to the anal margin, histological type other than well or moderately differentiated adenocarcinoma, and the presence of mesenteric lymph node metastases. Patients with lateral node metastases had a significantly shorter postoperative survival (5-year survival rate 42 versus 71.6 per cent; P < 0.001) and an increased risk of local recurrence (44 versus 11.7 per cent; P < 0.001) compared with those without lateral node metastases. CONCLUSION: Tumour site, histological type and the presence of mesenteric lymph node metastasis are factors predicting the risk of lateral node metastasis. The poor prognosis of patients with lateral lymph node metastases after systematic lateral dissection suggests the need for adjuvant therapy.     

Predictors of disease‐free survival in rectal cancer patients undergoing curative proctectomy

Objective To identify the factors that affect the disease‐free survival (DFS) of rectal cancer patients. Method Patients from an IRB approved rectal cancer database were reviewed (1990–2000). All patients underwent either abdominoperineal resection or low anterior resection using total mesorectal excision with curative intent. Univariate and multivariate analyses were performed to analyse the factors that influenced DFS. Results A total of 304 patients were reviewed (mean age 64, 52% male). Seventy‐seven per cent of patients received neoadjuvant therapy (28.6% short‐course radiation therapy (RT), 35.5% long‐course RT, 12.5% chemo‐RT). The radial margin was involved with tumour in 5.2% of patients (final pathology). The overall survival rate was 85.2% with a mean follow‐up time of 33 ± 26 months. The mean time to death was 34.8 ± 26.8 months. Local recurrence (± distant recurrence) occurred in 4%. Anastomotic leaks occurred in 3.6% of patients. Overall pathologic stage, pathologic T stage, nodal status, the use of adjuvant chemotherapy, tumour fixation, involvement of the radial margin, the presence of mucin, and lymphatic and perineural invasion (PNI) were predictors of DFS by univariate analysis. Of note, anastomotic leaks and obstructing cancers did not influence DFS. Using multivariate analysis with backward elimination, overall pathologic stage, radial margin status, adjuvant chemotherapy, and PNI predicted the DFS. Conclusion Major predictors of DFS in rectal cancer are the overall pathologic stage, adjuvant chemotherapy, radial margin status and PNI. Radial margin status may be a marker of tumour aggressiveness and should be considered in deciding on adjuvant chemotherapy.