局部复发直肠癌综合治疗的时机及合理选择

随着原发性直肠癌治疗手段的不断改进,尤其是全直肠系膜切除和新辅助治疗的出现,直肠癌局部复发率显著降低。但由于受到病人曾经接受过的相关治疗的限制,局部复发直肠癌（locally recurrent rectal cancer,LRRC）的治疗一直以来是备受争议的问题。手术是其主要的治疗手段,但仅有少数病人可以获得根治。因此,针对不同治疗史的病人采取合理有效的多学科综合治疗模式是LRRC治疗的重要原则,而综合治疗时机及合理选择已成为目前研究的热点。     

Surgery for locally recurrent rectal cancer

After the diagnosis of a locally recurrent rectal cancer, imaging is the first step to estimate the extent and location of the local tumour growth and the presence or absence of distant metastases. The aim of the treatment is a R0 resection (microscopically tumour free circumferential margin) by multimodality treatment consisting of pre‐operative radiation, extended resection and intra‐operative radiotherapy by either electron beam irradiation or with high dose rate brachytherapy. Filling the pelvic cavity with vital tissue such as an omentoplasty should considered carefully. With this treatment the overall three‐year survival rate of a group of 33 patients was 60% with a local control rate of 73%. The combination of chemotherapy as a radiosensitizer resulted in an increase of R0 resections by 20%. Introduction of TME surgery and pre‐operative radiotherapy has created a new situation with limited possibilities due to dose‐accumulation toxicity of the radiotherapy and extensive scarring of the tissues making estimation of the extent of the tumour growth more difficult. The prevention of local recurrence by proper selection of primary cases, the training of experienced surgeons and the optimal use of pre‐operative radiotherapy is the way forward to improve results.     

Surgical oncology issues in locally advanced rectal cancer

The management of locally advanced (T3/4) rectal cancer is evolving. Randomized trials have shaped the current adjuvant treatment options, but yet there remain many unanswered questions. These include how best to define which patients to treat and choosing between short-course radiotherapy and long-course chemoradiotherapy. With respect to surgery, the optimal timing, the surgical approach in abdominoperineal resections and the role of laparoscopic surgery remain active areas of research. The possibility of avoiding surgery in selected patients is also a topic of great interest. A multidisciplinary team approach in managing rectal cancer patients is popular where possible and recommended in some guidelines.     

Preoperative chemotherapy and radiotherapy for locally advanced rectal cancer

BACKGROUND: The adjuvant treatment of rectal cancer is a rapidly evolving field. The standard approach is a combination of chemotherapy and radiotherapy, with the optimal treatment combination and sequencing yet to be determined. Here, we report our early experience of preoperative chemotherapy and radiotherapy (CRT) in locally advanced rectal cancer at Radiation Oncology Victoria to determine its efficacy and the rate of sphincter preservation. METHODS: Sixty-nine patients (46 men and 23 women) with locally advanced rectal cancer (T3-4 or N1) were treated with preoperative CRT followed by surgical resection of disease. Chemotherapy consisted of either bolus or continuous venous infusion of 5-fluorouracil (5-FU). Radiotherapy to a dose of 45 Gy was delivered to the pelvis followed by a boost of 5.4-14.4 Gy in the majority of patients. Surgical resection was carried out 4-8 weeks following completion of preoperative CRT. Univariate and multivariate analyses were performed to examine variables that may influence local recurrence and overall survival rates. RESULTS: All patients underwent a complete macroscopic resection, including the three patients that had unrecognized distant metastases discovered at the time of operation. Only two patients had microscopic residual disease. Sphincter preservation was achieved in 16 of 25 patients who were thought to require an abdominoperineal resection. Tumour and/or nodal downstaging were achieved in 47 patients (68%), with a pathological complete response in 12 (17%). At a median follow up of 29 months post-surgery, five patients (7.2%) have developed a local recurrence. Overall 21 patients (30%) have progressed and 12 (18%) have died. Treatment-related toxicity was acceptable and there was no treatment-related mortality. There was no significant relationship found between the pathological response to treatment and any clinical endpoint. CONCLUSIONS: Our results confirm the high response rates and acceptable toxicity of preoperative treatment. Further studies are required to better define the impact of preoperative chemotherapy and radiotherapy on long-term outcomes.     

Use of adjuvant,preoperative chemo-radiotherapy in patients with locally advanced rectal cancer

Background: The objective of this study was to perform a non‐randomised prospective examination of the efficacy of adjuvant, preoperative chemo‐radiotherapy in patients with locally advanced rectal cancer. Methods: Between 1996 and 2001, patients presenting with biopsy‐proven, locally advanced, rectal cancers within 12 cm of the anal verge were referred for a long course of adjuvant chemo‐radiotherapy prior to their surgery. Locally advanced lesions were defined by either: (i) endoanal ultrasound showing at least full thickness penetration of the rectal wall (i.e. T3, T4); (ii) abdominal computed tomography scan showing infiltration of adjacent structures, or; (iii) clinical examination demonstrating a fixed lesion. All patients were followed through the hospital colorectal unit. A Kaplan?Meier survival analysis was used to determine survival and local recurrence rates. Results: There were 60 patients with a mean age of 61.5 years (range 33?77 years) with a sex distribution of males to females of 1.7?1.0. Curative resections were performed in 81% of these patients. The remainder (n = 12) were found to have either metastatic disease at operation (n = 5), inoperable disease (n = 2), or had positive resection margins on histology (n = 7). The mean follow up was 2.1 years (maximum 5.1 years). The overall 2‐year survival rate was 86.1% (95% CI ±5.4%). In patients undergoing curative resections, the overall 2‐year survival rate was 91.4% (95% CI ±4.8%), and the 2‐year disease free survival rate was 85.1% (95% CI ±6.2%). The 2‐year local recurrence rate was 7.5%. Conclusions: The use of adjuvant, preoperative, chemo‐radiotherapy in patients with locally advanced rectal cancer is associated with high short‐term survival and a low recurrence rate.     

局部进展期直肠癌新辅助化放疗的疗效观察

目的观察新辅助治疗对局部进展期直肠癌的疗效。方法2003年5月至2008年12月,我院临床分期为T3／T4期的局部进展期直肠癌病例32例,术前接受化疗一放疗一化疗,化放疗结束4～6周后手术。术后用Dworak分级评估新辅助治疗的组织学反应。所有患者术后接受随访,观察并发症发生率、局部复发率和临床结局。结果本组32例皆为R0切除,其中21例低位前切除术（Dixon术）,11例腹会阴联合切除术（MiLe术）,保肛率为65．6％。术后病检：5例Dworak分级3级,3例Dworak分级2级,24例Dworak分级1级。32例术后全部随访,随访时间24～91个月,中位随访时间52个月。全组无局部复发病例,皆无瘤生存至今。结论局部进展期直肠癌术前新辅助治疗有益,但对术后生存率的影响有待进一步观察。     

Accurate staging, selective preoperative therapy and optimal surgery improves outcome in rectal cancer: a review of the recent evidence

OBJECTIVE: The current optimal management of locally advanced rectal cancer has evolved from surgical excision followed by postoperative therapy in patients with involved margins, to an increasing use of a preoperative strategy to 'down-stage and/or down-size' the tumour. This treatment strategy is based on the relationship of the tumour to the mesorectal fascia, the optimal surgical circumferential resection margin that can be achieved by total mesorectal excision. We have reviewed the recent evidence for this strategy. METHOD: An electronic literature search using PubMed identified articles on the subject of rectal cancer between January 2000 and December 2005. The search was limited to English language publications with secondary references obtained from key articles. Articles published in high impact factor journals formed the basis of the review, together with articles related to national programmes on the management of rectal cancer. This does lead to a selection bias, particularly as the articles identified had a European bias. CONCLUSION: The UK NHS Cancer Plan has outlined the basis for the multidisciplinary team (MDT) management of rectal cancer. Advances in preoperative assessment through accurate staging and the recognition of the importance of the relationship of the tumour to the mesorectal fascia has allowed the selection of patients for a preoperative strategy to down-size/down-stage the tumour if this fascial layer is involved or threatened. Improvements in the quality of surgical resection through the acceptance of the principle of total mesorectal excision have ensured that optimal surgery remains the cornerstone to successful treatment. Further refinements of the MDT process strive to improve outcome. Accurate radiological staging, optimal surgery and detailed histopathological assessment together with consideration of a preoperative neoadjuvant strategy should now form the basis for current treatment and future research in rectal cancer.     

局部复发直肠癌放射治疗

局部复发是直肠癌,尤其是Ⅱ/Ⅲ期直肠癌手术治疗失败的主要原因,且术后复发病例预后差。20世纪70年代开始局部进展期直肠癌手术前后辅助放化疗的相关研究。大量临床试验结果显示,术后或术前辅助性放化疗较单纯手术可降低局部复发率、提高保肛率和存活率,已经成为I类循证医学证据,作为局部进展期直肠癌的标准治疗方案。而术后局部复发的直肠癌放化疗,目前尚未取得较高级别的循证医学证据。美国国家癌症综合网络（NCCN）指南建议对复发直肠癌病人应该采用多学科合作的综合治疗方案。孤立的盆腔或吻合口复发,如果之前未接受过全量放疗,最适合的处理就是行术前放疗,同期化疗。有条件的医疗机构,可考虑行术前新辅助放化疗+手术切除+术中放疗。     

直肠癌患者新辅助放化疗期间营养状况调查分析

目的了解直肠癌患者新辅助放化疗期间的营养状况及变化规律,为制定有效的管理方案提供参考。方法对66例直肠癌新辅助放化疗患者,采用营养风险筛查量表、患者主观整体评估量表于放疗定位时、开始放疗及放疗第1~5周7个时间点进行测评。结果体质量随治疗进程而下降(P<0.01);33.3%~57.6%患者存在营养风险,中、度重营养不良分别为18.2%~54.5%及0~34.8%;发生体质量丢失51例(77.3%);同步双药化疗者体质量丢失率显著高于单药化疗者(P<0.01);体质量丢失明显者放化疗不耐受率显著高于体质量丢失较轻者(P<0.01)。结论直肠癌患者放化疗前即存在营养风险,随治疗进程重度营养不良者增多,导致其难以耐受治疗。应制定针对性干预方案,改善患者营养状况,确保放化疗的顺利实施。     

术前短期放射治疗在进展期中低位直肠癌治疗中的应用

对进展期直肠癌术前短期放疗的效果、与此有关的副作用及一些相关的热点问题进行综述。目前相关研究结果显示术前短期放疗可明显降低术后局部复发率,提高生存率,并有可能降低肿瘤分期,相对于其他辅助治疗手段来讲,术前放疗是安全而有效的。     

Short-course preoperative radiation therapy for operable rectal cancer

BACKGROUND: Short course neoadjuvant radiation has been shown to provide improved local control of rectal cancer in a clinical trial population even in the presence of standardized surgical techniques. However, this use of hypofractionated radiotherapy has been limited in North America owing to concerns over toxicity.METHODS: Patients considered to have locally advanced rectal carcinoma received a radiation dose of 25 Gy given in five fractions to the posterior pelvis. Definitive surgery was then performed within 2 weeks. Retrospective analysis was performed. RESULTS: Sixty-three patients, of whom 60 were assessable, were treated with preoperative short course radiotherapy at the British Columbia Cancer Agency between 1991 and 1998, and 97% proceeded to R0 resection. Local recurrence developed in 3 patients (5%). Five-year actuarial overall and relapse-free survival rates for the group were 71% and 69%, respectively. The actuarial rates of relapse-free survival by stage at 5 years were stage 1 83%, stage II 75%, stage III 62%, and stage 4 0%. Eleven patients (18%) experienced a postoperative complication.CONCLUSION: Short course preoperative radiotherapy for operable rectal cancer can be delivered to a general population and produce high pelvic control rates with acceptable toxicity.     

Palliative resection of the primary tumour in stage IV rectal cancer

Aim The aim of this study was to investigate the use of resection in a cohort of palliatively treated patients with stage IV rectal cancer. To avoid selection bias, particular attention was paid to correction for comorbidity and extent of disease. Method Patients with stage IV rectal cancer in two hospitals in Groningen were consecutively included over a 5‐year period. Comorbidity was defined as major (dementia, cardiac failure or left ventricle ejection fraction < 30%, or severe chronic obstructive pulmonary disease), minor (diabetes, hypertension, mild renal disease or mild pulmonary disease) or none. The effect of patient and disease characteristics on survival was assessed using Kaplan–Meier and Cox regression analyses. Results Of 88 patients, 11 (13%) underwent elective surgical resection without chemotherapy, 15 (17%) received both elective resection and chemotherapy, 21 (24%) underwent palliative chemotherapy only and 41 (47%) had supportive care only. The extent of disease (P < 0.01), hospital (P = 0.02) and comorbidity (P = 0.04) were correlated with worse survival. Patients treated surgically survived for longer than patients treated nonsurgically, when the data were corrected for age, comorbidity, extent of disease and hospital [hazard ratio (HR) = 0.4 (95% CI = 0.2–0.7)]. Perioperative morbidity was seen in 38% of the patients, and 30‐day mortality was 0%. Conclusion In this retrospective cohort, resection was associated with longer survival independently of the extent of distant metastases, age and comorbidity.     

Complete pathologic response after preoperative rectal cancer chemoradiotherapy

Background: Following preoperative treatment of rectal cancer with chemoradiotherapy (CRT), a complete pathological response (CPR) can be seen in the surgical specimen. The aim of this study was to assess the outcome of these patients as compared with those who did not have a complete response. Methods: A retrospective study of the outcome of patients managed with preoperative CRT for their rectal cancer was conducted. Results: Between November 1998 and July 2004, there were 530 new presentations of rectal cancer at The Queen Elizabeth and Royal Adelaide hospitals. Forty of these patients (7.5%) were treated with long‐course preoperative CRT. After resection, a CPR was seen in seven patients (17.5%). These patients were all disease free at January 2006 after a median follow‐up of 6.0 years (range 1.42–7.02 years). One patient had died from non‐tumour‐/surgery‐related causes. Tumour recurrence, but not mortality, in this group was superior to the comparison group of patients without a CPR. Conclusions: None of our patients who had a CPR after preoperative CRT have recurred or died from their disease.     

Combined endoscopic laser and radiotherapy palliation of advanced rectal cancer

Background : In the palliative treatment of patients with advanced, inoperable rectal cancer, combined endoscopic laser and radiotherapy have been claimed to be more effective than laser therapy alone. The number of laser treatments, laser energy used, relapse rate, treatment of relapse, morbidity and survival in consecutive patients who were treated either by laser therapy alone or laser plus radiotherapy was compared. Methods : Prospective data were analysed with regard to number of treatments, laser energy used, relapse rate, morbidity and survival for 56 consecutive patients. Results : The crude relapse rate was significantly higher in the laser only group than in the laser plus radiotherapy group (58 and 15%, respectively; P = 0.002). There was no difference between the groups in the median total number of laser treatments or the mean total laser energy used. In patients experiencing a relapse, there was no difference in the median number of relapses, the number of laser treatments post‐relapse or the total energy used post‐relapse. Survival did not differ between the groups and there were no treatment‐related deaths. Conclusions : These findings demonstrate a clear reduction in relapse after using combined laser and radiotherapy to palliate patients with advanced rectal cancer with no appreciable additional morbidity and have encouraged continuing use of this treatment.     

中低位直肠癌的综合治疗

随机临床研究已证实辅助放化疗的作用,德国研究证实术前新辅助放化疗较术后化疗的优势。荷兰的TEM研究中显示肿瘤位置是影响治疗疗效的预后因素。但在具体化疗的实施和与化疗的联合应用,目前没有统一的共识。术前放疗的分割剂量,同期化疗应用和病人的选择存有差异。在治疗选择时需注意综合分析,多学科治疗模式。     

Watch and wait approach to rectal cancer: A review

In 2014, there were an estimated 136800 new cases of colorectal cancer, making it the most common gastrointestinal malignancy. It is the second leadingcause of cancer death in both men and women in the United States and over one-third of newly diagnosed patients have stage Ⅲ(node-positive) disease. For stage Ⅱ and Ⅲ colorectal cancer patients, the mainstay of curative therapy is neoadjuvant therapy, followed by radical surgical resection of the rectum. However, the consequences of a proctectomy, either by low anterior resection or abdominoperineal resection, can lead to very extensive comorbidities, such as the need for a permanent colostomy, fecal incontinence, sexual and urinary dysfunction, and even mortality. Recently, trends of complete regression of the rectal cancer after neoadjuvant chemoradiation therapy have been confirmed by clinical and radiographic evaluationthis is known as complete clinical response(cC R). The "watch and wait" approach was first proposed by Dr. Angelita Habr-Gama in Brazil in 2009. Those patients with c CR are followed with close surveillance physical examinations, endoscopy, and imaging. Here, we review management of rectal cancer, the development of the "watch and wait" approach and its outcomes.     

A prospective case series assessing the Imperial College London intraoperative radiotherapy protocol for advanced rectal cancer: an IDEAL phase 2a study

Aim

Intraoperative radiotherapy (IORT) decreases local recurrence rates for advanced rectal cancer. Nevertheless, utilization of IORT is limited due to the associated logistical and financial challenges. The aim of this study is to describe the development and delivery of a novel IORT protocol for advanced rectal cancer that overcomes these difficulties in the context of the early phase of an IDEAL 2a study. The primary outcome measure was the ability to deliver IORT using this novel protocol with IORT-related toxicity as the secondary outcome measure.

Method

Consecutive patients with advanced rectal cancer expected to have involved (R1) resection margins were enrolled. After resection, 12 Gy low-energy photon IORT was delivered using the Axxent device with a custom-designed elliptical spherical balloon applicator.

Results

Six patients with a median age of 47 years (range 33–88 years; five women) were enrolled between 2018 and 2019. The indication was advanced cancer in four patients and atypical invasive pelvic side wall lymph nodes in two. IORT was successfully delivered in all cases. No toxicity was encountered. Three advanced cancer patients had R1 resection and one had complete resection (R0); resection margin status could not be established for the two lymph node cases. Five patients were alive at 3.4 (2.9–4.1) year follow-up. None of the R1 cases recurred.

Conclusion

This is the first study to describe a novel IORT protocol using low-energy photon IORT for advanced rectal cancer. IORT could be delivered in all cases and no IORT-related toxicity was encountered. Available oncological outcome data are encouraging, but further studies will be necessary to determine the oncological effectiveness of this protocol.     

Developments in the use of chemoradiotherapy in rectal cancer

This paper reviews the current evidence available from phase III trials of combination pre‐operative chemoradiotherapy (CRT) in the treatment of rectal cancer. There is clear evidence that CRT is superior to long‐course radiotherapy (LRT). However, the end‐points and definitions used must be standardized for future clinical trials of combination CRT.     

直肠癌治疗术后勃起功能障碍的发病机制

直肠癌是常见的消化道恶性肿瘤之一,近年来发病率逐年上升。目前治疗方法包括手术治疗、放化疗以及多种方式联合的综合治疗。性功能障碍尤其是勃起功能障碍(ED)是男性直肠癌治疗术后最常见的并发症之一,严重降低了患者术后的生活质量,既往公认其主要原因是损伤了盆腔自主神经。近年的研究发现其发病机制不仅如此,而是一个复杂的病理生理过程,包括神经、血管、心理因素等。现就直肠癌治疗术后ED的发病机制作一综述,为临床上预防和治疗术后ED提供理论依据,从而降低其发生率,提高患者的生活质量。