Application of indocyanine green-enhanced near-infrared fluorescence-guided imaging in laparoscopic lateral pelvic lymph node dissection for middle-low rectal cancer

BACKGROUND As one effective treatment for lateral pelvic lymph node(LPLN)metastasis(LPNM),laparoscopic LPLN dissection(LPND)is limited due to the complicated anatomy of the pelvic sidewall and various complications after surgery.With regard to improving the accuracy and completeness of LPND as well as safety,we tried an innovative method using indocyanine green(ICG)visualized with a near-infrared(NIR)camera system to guide the detection of LPLNs in patients with middle-low rectal cancer.AIM To investigate whether ICG-enhanced NIR fluorescence-guided imaging is a better technique for LPND in patients with rectal cancer.METHODS A total of 42 middle-low rectal cancer patients with clinical LPNM who underwent total mesorectal excision(TME)and LPND between October 2017 and March 2019 at our institution were assessed and divided into an ICG group and a non-ICG group.Clinical characteristics,operative outcomes,pathological outcomes,and postoperative complication information were compared and analysed between the two groups.RESULTS Compared to the non-ICG group,the ICG group had significantly lower intraoperative blood loss(55.8±37.5 mL vs 108.0±52.7 mL,P=0.003)and a significantly larger number of LPLNs harvested(11.5±5.9 vs 7.1±4.8,P=0.017).The LPLNs of two patients in the non-IVG group were residual during LPND.In addition,no significant difference was found in terms of LPND,LPNM,operative time,conversion to laparotomy,preoperative complication,or hospital stay(P>0.05).CONCLUSION ICG-enhanced NIR fluorescence-guided imaging could be a feasible and convenient technique to guide LPND because it could bring specific advantages regarding the accuracy and completeness of surgery as well as safety.     

直肠癌侧方淋巴结清扫的再思考

直肠淋巴流向的研究从1895年D. Gerota的研究开始,提出了直肠淋巴流向可以分为上、中、下三个方向,经过很多学者的进一步研究修正,现普遍认为侧方淋巴流向可以分为4个方向：1.前方,由膀胱下动脉,前列腺动脉,经闭孔动脉到髂总动脉;2.沿直肠中动脉到髂内动脉;3.沿着骶中动脉和骶外侧动脉到腹主动脉分叉部位;4.沿着直肠下动脉到髂内动脉。侧方淋巴结转移主要发生在低位直肠癌,浸润深度大于肌层者,而转移的侧方淋巴结并不包括在直肠癌全直肠系膜切除术（TME）范围之内。NCCN直肠癌诊疗指南中没有提及侧方淋巴结的概念,日本大肠癌规约则认为有适应证的低位直肠癌应行侧方淋巴结清扫术。西方学者认为直肠癌侧方淋巴结转移是全身疾病,侧方淋巴结清扫难以改善总体临床结局;日本学者则认为是局部疾病,对低位直肠癌规范手术为TME＋侧方淋巴结清扫。西方学者认为术前放化疗可替代侧方淋巴结清扫;东方学者则认为对于术前放化疗不敏感的直肠癌患者,侧方淋巴结清扫术仍不失为一个可供选择的治疗方案。低位直肠癌患者是否应行预防性盆腔侧方淋巴结清扫仍存在争议,但治疗性侧方淋巴结清扫术则是日本的直肠癌规范治疗。不少研究报道了腹腔镜侧方淋巴结清扫术的初步探索结果,认为其是安全有效的,但其与开放手术的远期肿瘤学结果对比仍需多中心随机对照研究验证。     

Long-Term Cure in Surgery for Extrarectal Pelvic Recurrence of Rectal Cancer

Purpose Survival benefit of radical surgery for locally recurrent rectal cancer depends on whether disease is cured rather than whether death is delayed. Cured patients gain decades of life and are spared from sufferings with recurrence. Unfortunately, the majority of patients undergoing surgery, particularly those with extrarectal pelvic recurrence, have poor outcomes with occult disseminated disease. This study was designed to identify which of these patients are curable. Methods Of 61 patients with pelvic recurrence treated by radical reexcision more than nine years before, 36 patients whose initial surgery was abdominoperineal resection were examined retrospectively. We used the logistic regression and Gamel-Boag regression models to estimate curability and identify predictors of cure. Results Ten patients survived five years and seven survived ten years. The cumulative disease-specific mortality curve leveled off 6.5 years after reexcision and remained at 74 percent (95 percent confidence interval, 60–89), indicating that the remaining 26 percent are curable. This value is comparable with the 23 percent curability estimated by the Gamel-Boag model, which also found that the disease-free interval from the initial surgery to the first recurrence is the best predictor of cure (P = 0.005). Of 11 patients with disease-free interval three years or more, 6 survived ten years, whereas 8 of 9 patients with disease-free interval less than one year died of second recurrence within three years of reexcision. Conclusions Even patients with extrarectal pelvic recurrence may have isolated disease that is amenable to complete eradication. As a biologic marker, the disease-free interval serves to predict curability and may distinguish isolated disease from occult disseminated disease.     

Isolated tumor cell in lateral lymph node has no influences on the prognosis of rectal cancer patients

BACKGROUND AND AIMS: The aim of this study was to determine the incidence of isolated tumor cells (ITC) and micrometastasis in lateral lymph nodes of patients with rectal cancer and its possible correlation with prognosis. MATERIALS AND METHODS: One hundred seventy-seven rectal cancer patients who underwent curative resection with lateral lymph node dissection were enrolled. Dissected lymph nodes were examined using hematoxylin-eosin staining (HE) and immunohistochemistry (IHC) with anti-keratin antibody (AE1/AE3). States of lymph node metastasis were divisible into three groups: detectable with HE (HE+), detectable with only IHC (HE-/IHC+), and undetectable even with IHC (IHC-). Almost all the HE-/IHC+ group was classified as ITC consisting of a few tumor cells according to the UICC criteria (ITC+). Survival rates were compared among HE+, ITC+, and IHC-. RESULTS: ITC+ were detected in 24.1% of patients with HE-negative lateral lymph nodes. No significant difference in overall 5-year survival was observed between ITC+ and IHC- patients (76.1 and 82.9%, respectively, p = 0.25). Multivariate analysis showed that perirectal HE+ lymph nodes, but not ITC+ lateral lymph nodes, was an independent prognostic factor. CONCLUSIONS: ITC in lateral lymph nodes does not contribute to the prognosis of rectal cancer in patients who undergo extended lateral lymph node dissection, unlike HE+ lateral lymph node metastasis.     

Risk factors of lateral pelvic lymph node metastasis in advanced rectal cancer

Background  To clarify the risk factors of lateral pelvic lymph node (LPLN) metastasis of rectal cancer, we examined associations between LPLN status and clinicopathological factors including LPLN status diagnosed by computed tomography (CT). Methods  We reviewed a total of 210 patients with advanced rectal cancer, of which the lower margin was located at or below the peritoneal reflection, who underwent preoperative CT with 5-mm-thick sections and lateral pelvic lymph node dissection at the National Cancer Center Hospital between February 1998 and March 2006. Results  Forty-seven patients (22.4%) had LPLN metastasis. Multivariate analysis showed that LPLN status diagnosed by CT, pathological regional lymph node status, tumor location, and tumor differentiation were significant risk factors for LPLN metastasis. Among 45 patients with well-differentiated adenocarcinoma who were LPLN-negative and in whom CT had found no regional lymph node metastasis, none had LPLN metastasis. On the other hand, among 13 patients with moderate or less differentiated lower rectal adenocarcinoma who were LPLN-positive and in whom CT had revealed regional lymph node metastasis, 12 (92.3%) had LPLN metastasis. Conclusions  LPLN status diagnosed by CT, pathological regional LN status, tumor location, and tumor differentiation are significant risk factors for LPLN metastasis. Using these factors, patients can be classified as having a low or high risk of LPLN metastasis.     

Evaluation of lateral lymph node dissection with preoperative chemo-radiotherapy for the treatment of advanced middle to lower rectal cancers

Background and aims This study examined rectal cancers with lateral lymph node (LN) metastases and whether lateral lymph node dissection (LLD) with or without preoperative chemo-radiotherapy (XRT) benefits patients with rectal cancer.Patients and methods A total of 452 consecutive cases of curatively resected pT2, pT3, and pT4 middle to lower rectal cancers were retrospectively analyzed. Of these, 265 patients underwent curative LLD and 155 XRT. Data were evaluated with respect to the cumulative percentage of survival.Results Lateral LN metastases were identified in 7.7% of patients. Of the pT3/pT4 extraperitoneal cancer patients 13.5/18.8% had lateral LN metastases. In the treatment of middle rectal cancers and pT2 extraperitoneal cancers LLD either with or without XRT did not improve survival rate. For the treatment of pT3/pT4 extraperitoneal tumors prior to the introduction of total mesorectal excision (TME) in 1994 LLD plus XRT yielded significantly better survival and local control than conventional surgery without LLD or XRT, although LLD alone did not improve either survival or local recurrence rates. Since 1995 TME with or without subsequent LLD has yielded favorable results for the treatment of extraperitoneal tumors.Conclusion For the treatment of middle rectal cancers and pT2 extraperitoneal cancers LLD either with or without XRT does not improve survival rate. For pT3/pT4 extraperitoneal tumors, which are associated with a high incidence of lateral node metastasis, combining treatment modalities such as TME followed by LLD or XRT followed by TME may be considered.This work was partially supported by a grant-in-aid for scientific research from the Japanese Ministry of Education (no. 11671149)An invited commentary on this paper is available at     

Technical feasibility of laparoscopic extended surgery beyond total mesorectal excision for primary or recurrent rectal cancer

Relatively little is known about the oncologic safety of laparoscopic surgery for advanced rectal cancer.Recently, large randomized clinical trials showed that laparoscopic surgery was not inferior to open surgery, as evidenced by survival and local control rates. However, patients with T4 tumors were excluded from these trials. Technological advances in the instrumentation and techniques used by laparoscopic surgery have increased the use of laparoscopic surgery for advanced rectal cancer. High-definition, illuminated, and magnified images obtained by laparoscopy may enable more precise laparoscopic surgery than open techniques, even during extended surgery for T4 or locally recurrent rectal cancer. To date, the quality of evidence regarding the usefulness of laparoscopy for extended surgery beyond total mesorectal excision has been low because most studies have been uncontrolled series, with small sample sizes, and long-term data are lacking. Nevertheless, laparoscopic extended surgery for rectal cancer, when performed by specialized laparoscopic colorectal surgeons, has been reported safe in selected patients, with significant advantages, including a clear visual field and less blood loss. This review summarizes current knowledge on laparoscopic extended surgery beyond total mesorectal excision for primary or locally recurrent rectal cancer.     

Ultrastaging of Rectal Cancer Based on Identification of Micrometastases in Sentinel Lymph Node

AbstractBackground and Purpose: Almost one third of patients with node-negative rectal carcinoma develop systemic disease. This implies that these patients have occult disease that is inadequately treated by surgery alone. In this study sentinel lymph node (SLN) mapping and a focused pathologic examination were combined to detect occult nodal metastases in rectal carcinoma.Patients and Methods: Since 1999, SLN mapping has been performed in 53 consecutive patients undergoing surgery for rectal carcinoma. Peritumoral injection of 0.5–1.0 ml of patent blue dye was performed to demonstrate the SLNs. All lymph nodes in the resected specimen were examined by routine hematoxylin-eosin (HE) staining. In addition, a focused examination of multiple sections of the negatively stained HE lymph node was performed using anti-carcinoembryonic antigen and monoclonal anti-cytokeratin.Results: Overall, lymphatic mapping was successful in 47 patients (88.7%). The number of patients with negative SLN and positive non-SLN amounted to four (skip lesion), two of them detected by HE staining and the others by immunostaining. Sensitivity was 81.6%, specificity 80%, and negative predictive value 63.2%. Negative HE staining and positive immunostaining were observed in 13 of 28 patients (stage B; 46%), nine SLN and four non-SLN. SLN detection proved to be successful when there was no evident lymph node involvement. Focused examination of the SLN identified seven cases (17.5%) of additional upstaging disease for stage pT1–3 N0 M0 tumor.Conclusion: Upstaging by combination of immunostaining and SLN mapping may have important implications for adjuvant treatment in future protocols.     

直肠癌侧方淋巴结清扫中国临床开展的现状

尽管目前东西方对于直肠癌侧方淋巴结清扫仍存争议,但中国学术界依据现有的循证医学证据制定了符合中国国情的侧方淋巴结清扫相关共识、指南和规范。相较于日本,国内侧方淋巴结清扫指征把握更加严格,仅当有明确影像学证据疑诊存在侧方淋巴结转移时,才会选择性进行清扫,常规清扫区域也仅限于髂内和闭孔周围。基于全面了解盆腔解剖结构的前提下,以筋膜为导向的两间隙清扫现已成为中国侧方淋巴结清扫的主流方案,该术式在明确清扫边界、保护神经功能、彻底清除侧方淋巴结等方面具有明显优势。未来随着更多的高质量侧方淋巴结清扫研究的进行,将会有更多的证据来规范直肠癌侧方淋巴结清扫的临床应用。     

Validity of Pelvic Autonomic Nerve Stimulation With Intraoperative Monitoring of Bladder Function Following Total Mesorectal Excision for Rectal Cancer

PURPOSE This prospective study was designed to clarify whether the results of the intraoperative stimulation of parasympathetic pelvic nerves performed in 31 patients after mesorectal excision for rectal carcinoma allowed predictions in terms of the postoperative bladder function of the patients.METHODS After monopolar stimulation of the splanchnic pelvic nerves using a constant voltage stimulator (Screener 3625®), intravesical pressure increase was measured manometrically. The results were related to the postoperative residual urine volume, requirement of recatheterization and long-term catheterization, just as to the results of the validated International Prostatic Symptom Scores and the Quality of Life Index caused by urinary symptoms. The median follow-up period was nine (range, 2–14) months.RESULTS Parasympathetic nerve stimulation was performed at 61 sites and results in intravesical pressure increase up to 6 cm water column in median. In 11 patients (33.3 percent), a negative test result was achieved: 5 with unilateral and 6 with bilateral pressure increases of 2 cm water column. Recatheterization was necessary in four patients, and all of them showed negative neuromonitoring results. Two of these patients were discharged with an in situ urinary bladder catheter. Postoperative increased residual urine volumes (100 ml) resulted more frequently in the group with negative test results (63.6 vs. 21.1 percent; P = 0.047), and the International Prostatic Symptom Score and Quality of Life Index showed the worst results (9.9 ± 6.7 vs. 3 ± 4.9, P = 0.021; 2.4 ± 1.7 vs. 0.7 ± 1.3, P = 0.021).CONCLUSIONS Intraoperative neurostimulation and manometric measurement of bladder pressure may contribute to the identification of parasympathetic pelvic nerves during total mesorectal excision. This method is suitable for intraoperative recording of nerve preservation and therefore associated with postoperative bladder function.© The American Society of Colon and Rectal SurgeonsPublished online: 28 January 2005.     

Outcome After Curative Resection for Locally Recurrent Rectal Cancer

Purpose Few biologic markers have been studied as prognostic factors in recurrent rectal carcinoma patients. We sought to determine the influence of clinical, pathologic, and biologic (p53, bcl-2, and ki-67) variables on survival after curative resection of locally recurrent rectal cancer. Methods Retrospective review of patients with locally recurrent rectal cancer who received surgery with curative intent. Results From 1988 to 1998, 134 patients with locally recurrent rectal cancer underwent operative exploration. Curative resection was performed in 85 patients. Median follow-up was 43 (range, 1.3–149) months. On multivariate analysis, negative predictors of overall survival included an elevated carcinoembryonic antigen level (P = 0.02; hazard ratio 2.41; 95 percent confidence interval, 1.19–4.89) and an R1 resection margin (P = 0.01; hazard ratio, 2.81; 95 percent confidence interval, 1.27–6.21). In 26 patients for whom biologic variables were available, p53, bcl-2, and ki-67 did not significantly impact disease-specific survival or overall survival. Five-year disease-specific survival, overall survival, and pelvic control rates were 46, 36, and 51 percent respectively. Of the 50 patients who relapsed, time to second local recurrence was longer than time to development of metastasis (median, 16.5 vs. 9 months). Median survival for patients with metastatic recurrence was 26.l vs. 41.5 months for those with a subsequent local recurrence alone. Conclusions Approximately two-thirds of patients with locally recurrent rectal cancer can be resected for cure. Preoperative carcinoembryonic antigen and an R0 resection margin were the only significant predictors of overall survival. p53, bcl-2, and ki-67 did not impact survival outcomes.     

Rectal lymphoscintigraphy

Regional lymph nodes of the rectum are not demonstrable by pedal lymphoscintigraphy. We have evaluated the technique of rectal lymphoscintigraphy, using a technique similar to that which has been used in the assessment of lymph nodes in breast and prostatic cancer. Thirty-five patients were studied: ten normal subjects and 25 patients with rectal cancer. In normal subjects, the lymph nodes accompanying the superior hemorrhoidal artery and the inferior mesenteric artery are demonstrable in succession; after three hours the aortic lymph nodes are demonstrable. The 25 patients with rectal cancer underwent resection of their primary tumor and the stage was defined according to Dukes (1932). In five patients (stage A) no alteration was demonstrable. In 11 patients (stage B) the demonstration of regional lymph nodes was delayed vs. the control group. In nine cases (stage C) the demonstration of regional lymph nodes was delayed and defective versus the control group. A preliminary report read at the First Congress of the European Society of Surgical Oncology, Athens, Greece, November 26 to 27, 1982. Read at the International Congress on Colon Cancer, Rotterdam, May 26 to 27, 1983. Supported in part by CNR Progetto Finalizzato Controllo della Crescita Neoplastica.     

Impact of Pelvic Radiotherapy on Morbidity and Durability of Sphincter Preservation After Coloanal Anastomosis for Rectal Cancers

Purpose This study was designed to assess the impact of pelvic radiotherapy on the incidence of complications and colostomy-free survival of patients after a coloanal anastomosis for rectal cancer. Methods A total of 192 patients underwent a coloanal anastomosis between 1982 and 2001: 87 patients did not receive pelvic radiotherapy; 105 patients received pelvic radiotherapy (39 preoperative and 66 postoperative). Early and late complications requiring surgical intervention and the colostomy-free survival rate were assessed by retrospective review of patient records. Results After a median follow-up of 62 months, 151 patients were alive. The most frequent complication was development of an anastomotic stricture (5-year rate of a stricture, 16 percent; 95 percent confidence interval, 10–21). Patients receiving pelvic radiotherapy had a higher rate of complications other than anastomotic strictures, including fecal incontinence, fistulas, abscesses, and bowel obstructions compared with patients not receiving pelvic radiotherapy (5-year rate: 20 percent (95 percent confidence interval, 10–29) vs. 5 percent (95 percent confidence interval, 0–10); P = 0.001). Patients receiving pelvic radiotherapy had a lower colostomy-free survival than did patients not receiving pelvic radiotherapy (5-year colostomy-free rate: 72 percent (95 percent confidence interval, 62–84) vs. 92 percent (95 percent confidence interval, 86–98); P < 0.001). There was no significant difference in the colostomy-free survival of patients receiving preoperative and postoperative pelvic radiotherapy. Conclusions After coloanal anastomosis, a significant number of patients will have complications requiring surgical intervention, and some will require a permanent colostomy. Pelvic radiotherapy, whether it is administered preoperatively or postoperatively, significantly increases the need for a permanent colostomy.     

Total Mesorectal Excision for Rectal Cancer: Difference in Outcome for Low and High Rectal Cancer

PURPOSE This prospective study was designed to assess the outcome through the first five years after the introduction of total mesorectal excision in 1993 in a Norwegian central hospital, with special regard to the difference between low (≤6 cm from anal verge) and high (>6 cm) rectal cancers. METHODS A total of 140 patients (81 males; median age, 64 (range, 29–87) years) underwent surgery for rectal cancer under curative intention. RESULTS Local recurrence rates were 8 of 44 (18 percent) for the low cancers and 5 of 96 (5 percent) for the high, a statistically significant difference (P = 0.0014). Corresponding numbers when the R1 resections are excluded were 5 of 36 (13 percent) for the low and 4 of 92 (4 percent) for the high cancers (P = 0.002). The five-year survival after R0 resections of cancers <6 cm was significantly reduced compared with those >6 cm. The five-year overall survival for the whole material was 72 percent. CONCLUSIONS Surgery alone for rectal cancer can achieve overall good results, with five-year overall survival of 72 percent. The prognosis of the cancers of the lower rectum seems to be inherently different from the tumors of the higher level, both concerning local recurrence and five-year survival, suggesting different biologic behavior of the two cancers. Presented at the meeting of the Norwegian Surgical Society, Oslo, Norway, October 18 to 22, 2004.     

精准医疗时代低位直肠癌选择性侧方淋巴结清扫价值与策略

随着生物分析技术、基因测序以及大数据分析工具的出现,医学进入了精准医疗时代。临床影像等技术的进步和发展,肿瘤患者术前精准临床分期判断及分子生物学信息的获得使得个体化的精准医疗成为可能,精准医疗时代对直肠癌的诊治提出了新的要求,不同部位的直肠癌治疗方案亦有所差异。手术治疗仍然是当今治疗直肠癌的主要方式,对于侧方淋巴结清扫问题一直存有争议,究其原因侧方淋巴结转移（lateral pelvic lymph node metastasis,LPLM）是全身系统性转移还是局部转移。笔者认为,低位直肠癌诊治应在充分推广诊疗规范的基础上,通过对数据的分析,筛选行侧方淋巴结手术治疗的获益人群,根据精确的诊断分期控制手术指征与范围,减少不必要的创伤及过度治疗从而真正实现精准医疗。     

Morbidity and Mortality of Laparoscopy-Assisted Gastrectomy with Extraperigastric Lymph Node Dissection for Gastric Cancer

Gastrectomy with extraperigastric lymph node dissection has not been generally acceptable because of increased morbidity and mortality in some Western countries. Recently, many surgeons have become interested in laparoscopic gastric surgery for malignant disease as well as benign lesions because laparoscopic surgery itself has been shown to have many advantages over open surgery. The aims of this study are to evaluate the incidence and nature of operative morbidity and mortality after laparoscopy-assisted gastrectomy (LAG) with extraperigastric lymph node dissection with respect to surgical experience and to identify factors predictive of complications and death. We reviewed the surgical outcomes of LAG with extraperigastric lymph node dissection in 140 consecutive gastric cancer patients. Clinicopathologic characteristics, operative outcomes, and postoperative morbidities and mortalities were compared after dividing the 140 patients into early (1–70) and late (71–140) groups. And risk factors for morbidity and mortality were identified by multivariate logistic regression analysis. The overall operative morbidity and mortality rates were 18.6% and 0.7%, respectively. Thirty postoperative complications occurred in 26 patients. The minor surgical complication rate in the late group was significantly lower than that in the early group (P = 0.0349). According to univariate and multivariate analyses to evaluate the independent predictor of a higher operative morbidity rate, no factor was significantly associated with operative morbidity. We conclude that LAG with extraperigastric lymph node dissection is a technically feasible and acceptable surgical modality for gastric cancer and low morbidity and mortality rates for this procedure can be accomplished by experienced laparoscopic gastric surgeons at large-volume hospitals.     

吲哚菁绿荧光造影辅助腹腔镜个体化侧方淋巴清扫策略治疗中低位直肠癌五例报告

中低位直肠癌的侧方淋巴结清扫(LLND)是一个热点和难点,东西方的治疗策略也一直有很大的区别.由于LLND存在不确定的肿瘤学效果和并发症高发生率,如何将其变得个体化、简单化,成为近年来的研究热点之一.目前吲哚菁绿(ICG)已经广泛应用于检测各种类型恶性肿瘤中转移性淋巴结,然而国内少有采用吲哚菁绿荧光造影(ICG-FI)...     

中日韩中低位直肠癌术前放化疗的理念与策略

关于术前放化疗在中低位直肠癌治疗中选择的理念和策略,中日韩三个国家的医生有些不同。中国的指南接近于美国国立综合癌症网络（National Comprehensive Cancer Network,NCCN）指南,建议对于T3和（或）N＋以上的可切除直肠癌患者,推荐术前放化疗;日本大多数医生对可切除的中低位直肠癌并不积极推荐术前放化疗,根据日本指南推荐,对于腹膜返折下局部进展期直肠癌的标准治疗方式为全直肠系膜切除术＋侧方淋巴结清扫术;韩国的结直肠癌临床实践指南对术前放化疗的推荐与中国和美国指南类似,与中国不同的是,源于韩国政府的法定政策,韩国医生针对直肠癌患者术前放化疗开展的更为积极。