What Is the Role of Lateral Lymph Node Excision in Patients with Locally Advanced Rectal Cancer Who Received Preoperative Chemoradiotherapy?

In the era of preoperative chemoradiotherapy (CRT) for rectal cancer, the role of lateral pelvic lymph node dissection (LPLND) has become much more complicated because preoperative CRT affects both the lateral pelvic lymph nodes (LPLN) and the main tumor. Most previous studies do not demonstrate the benefits of LPLND following preoperative CRT in comparison with total mesorectal excision, although some authors have argued that selective LPLND is beneficial. LPLN treatment strategies differ depending on whether the disease was considered systemic metastatic disease or local disease which can be treated using surgical resection. The role of LPLND in rectal cancer is better evaluated on the basis of its oncologic impact rather than technical feasibility. Here, we review LPLN metastasis status in rectal cancer, whether LPLN metastasis is systemic or local disease, and studies on the use of LPLND to treat rectal cancer.     

直肠癌侧方淋巴结清扫的研究进展与相关争议

盆腔侧方淋巴结（lateral pelvic lymph node,LPLN）是中低位直肠癌常见的淋巴回流通路,有14%～30%的局部中晚期直肠癌患者同时合并LPLN转移。然而,术前诊断的遗漏和不规范的治疗是导致术后LPLN复发的常见原因,同时也是诊疗中的难点之一。目前,侧方淋巴结清扫术（lateral pelvic lymph node dissection,LPLND）的价值与意义,在国际上尚存争议。近些年来,新辅助放化疗（neoadjuvant chemoradiotherapy,nCRT）与LPLND相互替代的治疗模式趋于融合,逐渐形成了一套精确化、个体化的治疗策略。同时,随着外科器械设备的更新与淋巴结示踪剂技术的不断发展,使得以往制约LPLND的因素逐渐消失,可逐渐在临床推广开展。但针对直肠癌LPLN转移的治疗策略、nCRT后LPLND的适应证、预后价值、有效清扫范围、安全性仍存在诸多问题,需深入研究。      

102例直肠癌侧方淋巴结转移患者临床病理特点及生存预后分析

Objective To investigate the therapeutic effect and prognostic significance of lateral lymph node dissection (LPLND) in patients with lateral lymph node (LPLN) metastasis. Methods The clinicopathological data of rectal cancer patients who underwent total mesorectal excision (TME) combined with LPLND and pathologically confirmed as LPLN metastasis after operation were retrospectively analyzed. The clinicopathological characteristics and metastasis rules of patients with LPLN metastasis were discussed, and the survival prognosis after LPLND was analyzed. Results A total of 102 rectal cancer patients with pathologically confirmed LPLN metastasis were included. The common sites of LPLN metastasis were internal iliac vessels lymph nodes (n=68, 66.7%), followed by obturator lymph nodes (n=44, 43.1%), and common iliac vessels or external iliac vessels lymph nodes (n=12, 11.8%). There were 10 patients (9.8%) with bilateral LPLN metastases, and the mean number of LPLN metastases was 2.2±2.4, among which 16 patients (15.7%) had LPLN metastases number≥2. The 3-year OS (66.8% vs. 7.7%, P<0.001) and DFS (39.1% vs. 10.5%, P=0.012) of patients with LPLN metastases to the external iliac or common iliac lymph node were significantly lower than those with metastases to the internal iliac or obturator lymph node. The multivariate analysis showed that LPLN metastasis to external iliac or common iliac lymph node was an independent risk factor both for OS (HR=3.53; 95%CI: 1.50-8.31; P=0.004) and DFS (HR=2.40; 95%CI: 1.05-5.47; P=0.037). Conclusion LPLN mainly metastasizes to the internal iliac or obturator lymph node areas. The survival of patients with metastasis to the external iliac or common iliac lymph node cannot be improved by LPLND, and thus systemic comprehensive treatment is often the optimal treatment option. © 2023, CHINA RESEARCH ON PREVENTION AND TREATMENT. All rights reserved.     

局部治疗在直肠癌盆腔侧方淋巴结转移中的作用北大核心CSCD

盆腔侧方淋巴结(LPLN)转移是直肠癌预后不佳因素, 在低位、T3-T4期、直肠系膜淋巴结阳性情况下更常见, 但无准确预测转移的因素。高分辨率MRI是目前诊断LPLN转移的首选手段, 但阈值选择仍不明确。局部进展期直肠癌的侧方淋巴结转移治疗模式在全球存在分歧, 欧美国家主张放化疗联合直肠全系膜切除术, 而日本推荐直肠全系膜切除术联合LPLN清扫。放疗与手术联合可取得很好的局控, 利用放疗前、后MRI的侧方淋巴结信息, 可筛选出高危患者进行强化治疗, 如放化疗后行LPLN清扫或LPLN区放疗推量。目前各种手段在治疗LPLN转移方面的作用仍缺乏高质量证据, 尚需更多的研究来改善治疗策略。     

Preservation of bowel and urinary continence in the management of locally recurrent rectal cancer

BACKGROUND: The management of locally recurrent rectal cancer should achieve local tumor control and potentially improving disease-free and overall survival. Radical pelvic resection has traditionally been associated with permanent fecal and urinary diversion. However, as advanced techniques have evolved to allow restoration of intestinal and urinary continence, we reviewed the use of these techniques in patients with recurrent rectal cancer. METHODS: Patients with recurrent rectal cancer who underwent a resection at Norris Comprehensive Cancer Center between 1993 and 1999 were retrospectively reviewed. Data collected included demographic data, surgical and oncological history, patterns of recurrence, treatment modalities, and outcome. Follow-up data was obtained from the last clinic visit and/or tumor registry. RESULTS: Sixty-seven patients with locally recurrent rectal cancer (male/female 45/22, age 32-81 years) were included in the analysis. Continence was re-established in 22 (33%) patients, urinary continence was restored in 12 patients, and intestinal continuity in 14 patients (both in 4 patients). A temporary diverting ostomy was necessary in 5 out of 14 (36%) patients. Mortality was zero and morbidity was low and included two urinary leaks and one fecal leak all of which could be managed non-operatively. At a median follow-up of 16 months (range 5-55), 11 (50%) patients were still alive, 7 (31%) without evidence of disease. Comparison of the groups of patients either with or without continence preservation showed no statistically significant difference in disease-free survival and overall survival rates. High quality of life was achieved with restoration of continuity, no patient with restored continuity expressed a desire for a diversion. CONCLUSION: If an oncologically adequate resection of the recurrent rectal cancer can be performed without impairment of the pelvic floor integrity, continence preservation is feasible and results in good functional and oncological outcome.     

低位直肠癌选择性侧方淋巴结清扫研究进展

盆腔侧方淋巴结(Lateral pelvic lymph node,LPLN)是低位直肠癌患者常见的局部转移部位,同时也是术后局部复发的主要部位,然而目前对于LPLN转移的治疗方案仍没有明确的定论.同时LPLN的转移应被看作是局部而不是全身,新辅助放化疗(Chemoradiotherapy,CRT)并不能替代手术清扫,...     

Restaging rectal cancer following neoadjuvant chemoradiotherapy

Correct tumour restaging is pivotal for identifying the most personalised surgical treatment for patients with locally advanced rectal cancer undergoing neoadjuvant therapy, and works to avoid both poor oncological outcome and overtreatment. Digital rectal examination, endoscopy, and pelvic magnetic resonance imaging are the recommended modalities for local tumour restaging, while chest and abdominal computed tomography are utilised for the assessment of distant disease. The optimal length of time between neoadjuvant treatment and restaging, in terms of both oncological safety and clinical effectiveness of treatment, remains unclear, especially for patients receiving prolonged total neoadjuvant therapy. The timely identification of patients who are radioresistant and at risk of disease progression remains challenging.     

Role of Pelvic Exenteration in the Management of Locally Advanced Primary and Recurrent Rectal Cancer

Aim

A review of a single-centre experience of pelvic exenteration as a treatment modality for patients with locally advanced primary and recurrent rectal cancer. The perioperative outcomes, morbidity and long term oncological outcomes are reviewed.

Materials & Methods

Patients undergoing pelvic exenterations for recurrent and locally advanced rectal cancer between 1 January 2006 and 1 August 2012 were identified from a prospective database. All patients underwent pre-operative staging investigations with computed tomography (CT) scan of chest, abdomen and pelvis and pelvic magnetic resonance imaging (MRI). Patients with locally advanced primary rectal cancer were counselled for pre-operative chemoradiation. Structures such as the urinary bladder and female reproductive organs were resected en bloc where indicated with the lesion. Urological or plastic reconstructions were employed where indicated. The primary outcome measured was overall survival and secondary outcomes measured were time to local recurrence (LR) and systemic recurrence. Disease-free survival was examined by the Kaplan–Meier Method (Fig. 1).

Results

Pelvic exenterations were performed in 13 patients with a median age of 59 (range 26–81). The rate of major post-operative complications was 8 % (n?=?1), where the patient had anastomotic leakage. There were no mortalities in the perioperative period. All patients were operated with curative intent and negative circumferential margins were shown in 9 out of 13 patients (70 %). The DFS was 19.4 and the OS was 22.5 months.

Conclusion

An aggressive approach with en bloc resection of organs involved provides survival benefit to patients with locally advanced primary and recurrent rectal cancer with an acceptable morbidity profile.     

高位直肠癌辅助性放疗的问题与争议探讨

局部晚期直肠癌的治疗强调多学科综合治疗,除高质量的直肠全系膜切除术（total mesorectal excision,TME）之外,放化疗的加入也进一步降低了局部复发、延长了总生存,尤其是对于中低位直肠癌。但是,目前对于局部晚期高位直肠癌,放疗的价值仍未明确,国内外各共识指南对高位直肠癌的定义并不完全统一,关于是否放疗的推荐也存在一定差异,目前尚缺乏大型前瞻性随机对照试验,既往的研究结果也存在诸多矛盾之处。同时,盆腔放疗也不可避免的带来一系列不良反应。因此,局部晚期高位直肠癌的治疗应该如何决策,如何基于复发风险进行分层治疗,放疗是否能带来获益,均值得进一步探索。本文旨在针对高位直肠癌辅助放疗的问题与争议进行综述。      

Current issues in colorectal cancer surgery.

Increased understanding of the pathology and natural history of colorectal cancer has led to significant advances in the management of this disease. Surgical management of rectal cancer currently includes a spectrum of operative procedures ranging from radical operations to innovative sphincter-preserving techniques. At one end of the spectrum, 5% to 10% of patients present with small, superficially invasive rectal cancers amenable to a curative local excision. At the other end, a subset of patients present with locally advanced rectal cancers that require multimodality therapy, including sharp pelvic dissection with en-bloc resection of involved organs. However, the majority of rectal cancer patients present with nonfixed, yet deeply invasive, lesions requiring either a low anterior resection (LAR) or an abdominal perineal resection (APR). This report will address the controversies in the surgical management of colorectal cancer.     

Surgical management of extra-regional lymph node metastasis in colorectal cancer

One of the major problems in rectal cancer surgery is local recurrence, found in an average of 21% to 46% cases in 1990. However, the advent of chemo-radiotherapy (CRT) and total mesorectal excision (TME) improve local control and enhances survival rates in colorectal cancer (CRC). Regional lymph node involvement is determined to be an independent prognostic factor in local recurrence; however, extra-regional lymph node (ERLN) metastasis has a higher recurrence rate (up to 58.1%). Lack of supportive data in management of ERLN metastasis in CRC has added further strain and challenges to structure a unique treatment strategy. ERLN refers to extra-mesenteric involvement either in the para-aortic lymph node (PALN) or the lateral pelvic lymph node (LPLN). Treatment of ERLN metastasis is challenging because of the shortage of the resources. Here, we will outline and summarize approaches and management of ERLN metastasis. We also aim to clarify the role of surgical intervention in CRC     

Treatment of High Rectal Cancers: Do We Need Radiation?

Before total mesorectal excision (TME) and radiation therapy/chemoradiation therapy (RT/CRT) were widely adopted in the treatment of rectal cancer, surgery alone was the standard. Therapies have since evolved to neoadjuvant RT or CRT followed by TME as the established paradigm for locally advanced disease. More recently, issues of toxicity and systemic metastasis have risen to the forefront, prompting the exploration of individualized strategies in an attempt to maximize potential cure and local control yet minimize late toxicities. In this article, we will focus on the treatment of high rectal cancers, exploring the specific role of pelvic radiotherapy in this setting.     

Controversies in the multimodality management of locally advanced rectal cancer

Neoadjuvant radiotherapy previous to radical surgery, both as short-course radiotherapy and as long-course radiotherapy combined with 5-FU-based chemotherapy (LCRCT), is routinely used in the management of locally advanced rectal cancer, with consistent benefits in the reduction in the local relapse risk. Unfortunately, survival benefits have been elusive to demonstrate with this approach, especially in the setting of radical surgery in the form of total mesorectal excision (TME). Concerns about over-treating early-stage patients and about the possible long-term side effects have also cast more doubts in a blanket approach of treating all patients with neoadjuvant radiotherapy, especially with LCRCT. In this review of selected controversial topics in locally advanced rectal cancer, we examine the benefits and drawbacks for the use of both neoadjuvant approaches in the TME era, the role of the intensification of the neoadjuvant regimens with new chemotherapy agents and modifications of the radiotherapy regimen, the usefulness of adjuvant chemotherapy, especially after LCRCT and surgery, and the management of elderly and/or frail patients. Finally, we offer some future perspectives in the management of these patients.     

The importance of MRI for rectal cancer evaluation

Magnetic resonance imaging (MRI) has gained increasing importance in the management of rectal cancer over the last two decades. The role of MRI in patients with rectal cancer has expanded beyond the tumor-node-metastasis (TNM) system in both staging and restaging scenarios and has contributed to identifying “high” and “low” risk features that can be used to tailor and personalize patient treatment; for instance, selecting the patients for neoadjuvant chemoradiation (NCRT) before the total mesorectal excision (TME) surgery based on risk of recurrence. Among those features, the status of the circumferential resection margin (CRM), extramural vascular invasion (EMVI), and tumor deposits (TD) have stood out. Moreover, MRI also has played a role in surgical planning, especially when the tumor is located in the low rectum, when the relationship between tumor and the anal canal is important to choose the best surgical approach, and in cases of locally advanced or recurrent tumors invading adjacent pelvic organs that may require more complex surgeries such as pelvic exenteration. As approaches using organ preservation emerge, including transanal local excision and “watch-and-wait”, MRI may help in the patient selection for those treatments, follow up, and detection of tumor regrowth. Additionally, potential MRI-based prognostic and predictive biomarkers, such as quantitative and semi-quantitative metrics derived from functional sequences like diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE), and radiomics, are under investigation. This review provides an overview of the current role of MRI in rectal cancer in staging and restaging and highlights the main areas under investigation and future perspectives.     

Outcome after the introduction of a multimodality treatment program for locally advanced rectal cancer.

AIM: This prospective study reports the results of a multimodality treatment protocol in patients with locally advanced rectal cancer and assesses outcome after curative vs non-curative surgery and in relation to primary advanced vs locally recurrent cancer. METHODS: Between 1991 and 2002, 122 patients completed the protocol. Fifty-eight had primary advanced and sixty-four had locally recurrent rectal cancer. Median follow up was 82 months (5-143). RESULTS: A potentially curative resection was achieved in 59% of the patients with primary advanced and in 34% of patients with locally recurrent cancer. After curative resection, 53 and 59%, respectively, were free from recurrence during the observation time (median 82 months) and the overall 5-year survival was 34 and 40%. Overall 5-year survival in all patients with primary advanced cancer was 29 and 16% in all patients with locally recurrent rectal cancer. CONCLUSION: Multimodality treatment may cure at least a third of patients with locally advanced rectal cancer provided a radical resection is performed. As the post-operative morbidity is high, an optimised patient selection for neo-adjuvant treatment and surgery is essential. However, palliative surgery may benefit the patient if local control is achieved. Future studies should focus on the problem of distant metastasis.     

Significance of surgery in the multimodality treatment of rectal cancer

Since the NIH recommendations in 1990 the majority of patients with rectal cancer are treated by a multimodality approach. The last decade has seen considerable improvements in the overall management of rectal cancer, therefore a certain reorientation seems justified. Although many questions remain to be answered, some general recommendations for the treatment of rectal cancer focussed on the small pelvis can be given. Surgery with total mesorectal excision is the standard therapy for cancers of the middle and low rectum in stages T1/2 N0. Adjuvant radiochemotherapy and shortterm pre-operative radiotherapy are both feasible approaches for the treatment of stage II and stage III rectal carcinomas. The superiority of either concept awaits clarifying randomised trials. Patients with T4 rectal cancers should undergo long-term neoadjuvant radiochemotherapy with consecutive oncological resection. The exact mode of the neoadjuvant regimen combining high remission rates with low treatment-associated morbidity needs further refinements. Local excision should be restricted to patients with well-differentiated, less than semi-circumferential T1 carcinomas. Tumours with less favourable histologies should not be treated locally unless general patient conditions forbid oncological resections. In these instances, additional radiochemotherapy appears able to reduce the risk of local recurrence.     

Neoadjuvant and adjuvant therapy for rectal cancer

The currently available evidence from randomized clinical trials clearly supports the use of adjuvant therapy in general and preoperative combined modality therapy in particular as effective means of decreasing the rates of local recurrence, improving sphincter preservation rates, and probably im-proving overall survival when managing patients with locally advanced adenocarcinomas of the lower two thirds of the rectum. A radical surgical approach with adequately performed, sharp TME remains the standard of care for those patients. There is clearly a need to develop and validate surrogate biomarkers for the identification of patients who respond favorably to preoperative treatment. There is still a significant fraction of rectal cancer patients who ultimately die from their disease. The armamentarium of avail-able therapies is evolving rapidly, and hopefully local control rates and overall survival of rectal cancer patients will continue to improve in the near future.     

Results after change of treatment policy for rectal cancer--report from a single hospital in China.

BACKGROUND: Great changes have occurred in the management of rectal cancer. This study presents the outcome of total mesorectal excision (TME) for rectal cancer in a single Chinese institution and evaluates TME's role in the comprehensive management of rectal cancer. METHODS: We reviewed the data of rectal cancer patients surgically treated by three colorectal surgeons from January 2000 to August 2004. Patients who received surgical resection for rectal cancer from January 1996 to December 1999, before the introduction of TME, were chosen as controls. Data regarding characteristics of patients and tumors, surgical procedures, postoperative complications, and results of follow-up were collected for analysis. RESULTS: Three hundred and seventy-seven patients with rectal cancer were enrolled in our study, with 175 patients in the TME group and 202 as controls. Mortality and morbidity rates were 1% and 14% in TME patients and 1% and 31% in controls, respectively. The TME group had a shorter operation time and hospital stay, and less bleeding, wound and urinary complications. The local recurrence (LR) rate was 6% and 12% in the TME and the control groups, respectively (P<0.05). With a median follow-up of 35 months, the actuarial 5-year survival rate was 66%. Consistent with the univariate analysis result, multivariate analysis demonstrated that TNM stage, tumor grade, age, and surgeons were independent prognostic factors. TME was not an independent prognostic factor for patients' survival. CONCLUSIONS: TME is a safe and efficient option in reducing LR. However, it is not an independent predictor for patients' survival. In addition to the standardized usage of TME, further knowledge on the molecular mechanism of cancer is needed.     

低位直肠癌术前同步放化疗的远期疗效及安全性研究

目的评估术前口服卡培他滨（希罗达）与放疗联合治疗局部进展期低位直肠癌的远期疗效及安全性。方法对局部进展期（T3／T4）低位直肠腺癌（距肛缘≤9Ccm）患者51例,术前给予口服卡培他滨（希罗达）并联合放疗。放疗结束后休息3—4周,按TME原则进行手术。结果3例患者临床完全消退（cCR）,占5．88％,未行手术;其余48例患者均行根治性切除术（R0）,实际保肛率90．20％（46／51）,10例术后病理检查未见肿瘤细胞,为病理消退（pCR）,总消退率为25．49％（13／51）。肿瘤降期41例,占80．39％。5年无病生存率为70．59％,总生存率为80．39％。放化疗过程中出现3、4级不良反应5例,无疾病进展、手术死亡者。结论术前口服卡培他滨联合放疗治疗局部进展期低位直肠癌是有效安全的。     

Preoperative radiation with concurrent 5-fluorouracil continuous infusion for locally advanced unresectable rectal cancer

Background and Purpose: To determine the percentage of complete responders and the resectability rate for patients with locally advanced carcinoma of the rectum treated by 5-fluorouracil (5-FU) infusional chemotherapy and pelvic radiation.Materials and Methods: Between October 1992 and June 1996, 29 patients with a diagnosis of locally advanced unresectable rectal cancer received preoperative 5 FU by continuous intravenous infusion at a dose of 225 mg/m²/day concurrent with pelvic radiation (median 54 Gy/28 fractions). All patients were clinical stage T4 on the bases of organ invasion or tumor fixation. Median time for surgical resection was 6 weeks.Results: Median follow-up for the group was 28 months (range 5–57 months). Six patients were felt to be persistently unresectable or developed distant metastases and did not undergo surgical resection. Of the 29 patients, 23 proceeded to surgery, 18 were resectable for cure, 13 by abdominoperineal resection, 3 by anterior resection and 2 by local excision. Of the 29 patients, 4 (13%) had a complete response, and 90% were clinically downstaged. Of the 18 resected patients, 1 has died of his disease, 17 are alive, and 15 disease-free. The regimen was well tolerated; there was only one treatment-related complication, a wound dehiscence.Conclusion: The combination of 5 FU infusion and pelvic radiation in the management of locally advanced rectal cancer is well tolerated and provides a baseline for comparison purposes with future combinations of newer systemic agents and radiation.