INTRODUCTION

Colorectal cancer is the fourth most common cancer in the United Kingdom with over 40000 cases diagnosed each year[1]. At presentation, synchronous hepatic metastases are present in 20%-25% of patients with metachronous hepatic metastases developing in 40%-50%[2,3]. Up to 80% of patients who develop metachronous disease do so within the first 3 years[4,5]. About 10% of patients who have resection of the primary tumour with curative intent will develop metachronous lung metastases[6] with local recurrence having been reported to occur in 4%-10% of patients[7,8]. Recent decades have seen a significant improvement in early post-operative survival in patients undergoing lung or liver resection surgery for colorectal metastasis[9,10]. Intensive post-operative surveillance has shown to improve 5-year survival with recognition of early, asymptomatic recurrent disease[11]. Five-year survival has further improved with the advent of effective chemotherapy, especially for patients with resectable liver disease, seeing a rise from 35% to 50%[10,12]. Three meta-analyses[13-15]have shown improved, albeit modest, survival with aggressive surveillance, which has been proven to be within the National Health Service’s threshold of cost acceptability[16].

Despite the widespread use of screening programs for detection of colorectal cancer, a large number of cases in England are diagnosed in the acute or urgent setting either as an emergency presentation (26%) or following an urgent 2-wk referral (27%)[17]. Compared to elective resection, emergency surgery is associated with adverse postoperative outcomes (post-operative mortality 4.6% vs 16%), disease-free and overall longterm survival[18-20]. This may represent a multifactorial basis due to altered physiology, immunosuppression,advanced disease and aggressive tumour biology[21,22].

Surveillance after resection of the colorectal primary in the form of colonoscopy and computed tomography (CT) imaging with or without adjuncts such as positron emission tomography (PET/PET-CT)is generally considered the standard of care[4]. There is wide variation in follow-up protocols in randomised trials with no clear consensus about follow-up intensity[23].The Association of Coloproctologists of Great Britain and Ireland (ACPGBI) recommends a CT scan within the first 2 years after resection of the primary tumour to detect metastases as part of the follow up of these patients[24].Conversely, the American Society of Clinical Oncology(ASCO) has suggested an annual abdominal/chest CT scan for three years with more frequent scans for higher risk patients (defined as stage III or stage II with multiple high-risk features)[4]. The American National Comprehensive Cancer Network (NCCN) recommends an abdominal/pelvic and chest CT scan annually for up to five years[25]. Furthermore, it is clear that not all patients with colorectal cancer will benefit from intensive surveillance, incurring unnecessary costs. Identifying patients at high risk of developing early recurrence(within the first three years) will help to determine who would benefit from aggressive surveillance.

The aim of this study was to investigate the prognostic effects of histological factors on patterns of recurrent disease and survival in patients undergoing emergency resection surgery for colorectal cancer.

MATERIALS AND METHODS

A retrospective audit of patients undergoing surgery for colorectal cancer was carried out after institutional approval. Patients undergoing consecutive curative resection for histologically proven, primary colorectal adenocarcinoma in the absence of synchronous metastatic disease on presentation were included the study covering an eight-year period from January 2001 to December 2008. The study population was identified using procedure codes from the hospital database.

Demographic data on age, sex and mode of presentation was recorded. In the emergency surgery setting the presence of bowel obstruction or perforation was recorded. Histological data was retrieved for site of tumour, TNM staging was based on postoperative histological findings along with degree of tumour differentiation, lymphovascular invasion (LVI), perineural invasion (PNI), resection margin status (R). Lymph node ratio (LNR) was calculated as the ratio of disease positive nodes to the total number of lymph nodes retrieved. Clinic letters and correspondences within the computerised hospital database were accessed to gain information on presentation, mode of surgery and neoadjuvant and adjuvant therapies. Treatment decisions regarding neo-adjuvant and adjuvant therapies were carried out in multi-disciplinary team meetings based on patient fitness, symptoms, synchronous disease and post-operative recovery. Generally, patients with rectal tumour received neo-adjuvant therapy if the tumour was ＞ T3b or in presence of nodal disease on crosssectional imaging.

Surveillance following curative colorectal cancer resection incorporated 6 monthly clinical assessments for 3 years followed by annual reviews for a total of 5 years for patients without recurrent disease.This assessment was supplemented by 6 monthly CEA levels (Carcinoembroyic Antigen), CT of chest,abdomen and pelvis within 2 years of surgery and 5-yearly surveillance colonoscopy (following completion colonoscopy within a year where indicated) until the age of 75 years (or longer if life expectancy deemed longer than 10 years at this stage). Detection of new symptoms, increased CEA levels, and abnormal CT or colonoscopy findings warranted multidisciplinary team review during follow-up. Patients developing an extracolonic primary malignancy during the course of followup were excluded from the study to minimise bias.Survival data was obtained as all-cause mortality using the Demographics Batch Service (DBS) to access the national electronic database of the United Kingdom NHS.

Primary outcome was development of early recurrence disease within three years of curative resection.This was subdivided into liver, lung and local recurrence.Secondary outcomes were overall recurrence, three-year and overall survival.

Lymph node involvement, along with depth of bowel wall invasion, has represented an important prognostic indicator for metachronous metastasis[29]. This is in broad correlation with our study. Nodal status was noted to be an independent predictor in early all-site recurrence, but no independent predictive value was noted for early liver and lung recurrent disease. In the setting of emergency surgery, where adequate lymph node yield may be compromised, LNR may prove to be a more useful prognostic tool since the patient’s physiology might not tolerate prolonged surgery in order to attain a good lymph node yield.

RESULTS

The database identified 266 patients meeting the inclusion criteria during the study period. Median period of follow-up was 7.9 years (4.6 to 12.6 years). The median age at the time of surgery was 68 years (26 to 91 years) with a male to female ratio of 1.5:1.1.Surgery was undertaken as an elective procedure in 225 patients (84.6%) and as an emergency in 35 (13.2%)patients and remained unclear for 6 (2.2%) patients.The indication for emergency surgery was not identified in 3 patients. Bowel obstruction was the predominant indication for emergency surgery, undertaken in 28 patients compared to 9 patients with a diagnosis of perforation on presentation.

Of the total 266 patients, 151 were diagnosed with tumours situated in the colon and 115 within the rectum. Data on neo-adjuvant therapy was missing in 12 patients (7 colonic and 5 rectal cancers). None of the remaining patients with colon cancer received neo-adjuvant therapy before surgery. Of 115 patients with rectal cancer, 39 (33.91%) received pre-operative radiotherapy, 10 (8.69%) received pre-operative chemo-radiotherapy and 5 (4.31%) had pre-operative chemotherapy alone. Postoperatively, amongst patients with tumour sited in the colon, only 53 (35.10%)received adjuvant therapies (data missing in 6 patients).Amongst patients with rectal cancer, 54 (46.96%)received neo-adjuvant therapy and 14 of these patients proceeded to have further adjuvant therapies postoperatively. Overall, 30 (26.09%) patients with rectal cancer had adjuvant therapies post-operatively (missing data in 3).

The site and histological features of the primary colorectal tumour in all 266 patients are shown in Table 1.TNM staging is presented from postoperative histological assessment. Pre-operative radiological changes in staging before and after neo-adjuvant therapy were not collected. Although T stage was not recorded for 18 patients positive residual disease was identified in 16 of these patients. Lymph node status was missing in 17 patients.

Emergency surgery for colorectal cancer

Complete data was available from 35 patients undergoing emergency colorectal cancer resection.Detailed characteristics of patients undergoing emergency and elective colorectal resection for cancer are shown in Table 2. No significant differences were noted between the two groups in age, sex, tumour grade, nodal disease, LNR, LVI, PNI or resection margin status on univariate regression analysis. Right colon was more commonly the site of primary cancer in the emergency group and associated with higher rate of obstruction. More patients undergoing emergencysurgery had T4 disease stage on univariate analysis (OR= 4.33, 95%CI: 2.03-9.25, P ＜ 0.001) and a higher proportion received adjuvant therapies post-resection compared to elective resection (45.7% vs 28.8%, OR= 2.10, 95%CI: 1.01-4.37, P = 0.047). Multivariate modelling was not carried out as no other histological parameter reached significance of P ＜ 0.100.

Emergency resection was also positively associated with increased risk of recurrent disease on univariate analysis (48.57% vs 20.89%, OR = 3.60, 95%CI:1.69-7.64, P = 0.001) with liver being the commonest site of early recurrent disease (40.0% vs 11.6%, OR= 5.78, 95%CI: 2.66-12.55, P ＜ 0.001). A subset analysis demonstrated a greater proportion of patients undergoing emergency resection received adjuvant therapies compared to elective resection (45.7% vs 28.9%). In the emergency surgery group, patients with T4 disease were likely to received adjuvant therapies (P= 0.004). These patients receiving adjuvant therapies demonstrated an increased trend towards risk of liver metastasis but it failed to reach significance (P =0.089). No differences were seen in recurrence rates for lung and local disease in the two groups. Although,median period to recurrence in days was shorter in the emergency resection group, this did not reach significance (OR = 0.99, 95%CI: 0.99-1.00, P = 0.181).

No independent predictors were identified for early lung recurrence. Early local recurrence represented a very small number of patients (7) for detailed analyses.

回顾性分析2015年9月—2018年8月我院58例患者的肋骨骨折CT影像和临床内固定术后病历资料。其中男40例，女18例，年龄20～62岁，平均41岁。单侧肋骨骨折31例，双侧多发多段肋骨骨折27例，肋骨骨折数1～8根，胸壁塌陷6例，胸壁软化3例，合并血气胸5例，肺挫伤23例，呼吸困难6例。

你说交通拥堵，给你限号了；你说油不合格污染空气，给你把油价涨了；你说房价太高买不起，给你征税20%了；你说国产奶粉是垃圾，给香港下禁令了；你说出租车不好打，给你把车价涨了……

Patterns of recurrent disease and survival

Recurrent disease was observed in 67 out of 264 patients with available data (25.38%) during the median follow-up period of 7.9 years (range 4.6 to 12.6 years). Amongst patients with recurrence, liver was the commonest site in 49 out of 67 (73.13%) patients with isolated liver disease in 41 patients. This was followed by lung disease in 14 (20.90%) patients with isolated disease in 4. Local recurrence was seen in 10 (14.93%)patients and 6 of whom had isolated local disease.Ten patients developed recurrence at multiple sites; 7(10.45%) with concomitant liver and lung and 3 (4.58%)patients had lung metastasis with local recurrence.

Recurrence was predominantly early (＜ 3 years)affecting 55 patients (Table 3). The liver remained the commonest site of early recurrent disease with 35 outof 41 patients presenting with isolated liver disease.Early multi-site disease was seen in a small proportion of patients with liver disease (4 patients with liver and lung disease, 2 with liver and lung and local disease).In contrast, isolated lung disease was noted in only 3 out of 11 patients with early disease (4 patients had lung and liver disease, 2 had lung disease with local recurrence, 2 had lung, liver and local recurrence). Local recurrence was seen in 7 patients and was isolated in 3.

Recurrence between 3 to 5 years following curative resection represented 14.92% (10 patients) of overall recurrent disease. The liver remained the predominant site with 5 patients demonstrating isolated liver disease and 1 with liver and lung metastasis. Two patients presented with lung disease (1 isolated and 1 combined lung and liver disease) and 3 patients presented with isolated late local recurrence. Beyond the 5-year followup period, 1 patient developed isolated liver disease and 1 had liver and lung metastasis. No local recurrence was noted beyond 5-year follow-up.

Age, sex, tumour location, tumour differentiation and neo-adjuvant therapy did not show correlation with early all-site recurrent disease. Significant histological markers of early recurrence on univariate analyses included T4 stage (OR = 3.61, 95%CI: 1.88-6.96, P ＜0.001), N2 nodal status (OR = 4.18, 95%CI: 1.89-9.24,P ＜ 0.001), LVI (OR = 3.40, 95%CI: 1.79-6.46, P＜ 0.001), PNI (OR = 4.54, 95%CI: 1.51-13.60, P ＜0.007) and R1 resection margin (OR = 4.51, 95%CI:1.50-13.53, P = 0.007). LNR provided a strong correlation for early all-site recurrence on univariate analyses (OR = 25.55, 95%CI: 4.52-144.32, P ＜ 0.001)with an optimal cut-off at 0.015 (52.7% sensitivity and 68.4% specificity). In a multivariate predictive model for early all-site recurrence, emergency surgery with perforation was the strongest predictor amongst factors including T4 stage and LVI.

“三农”问题最早是由温铁军于1996年提出来的，主要指的是“农业农村农民”问题。[1]新世纪以来，一些学者开始从理论上阐释“三农”问题产生的根源，并寻求破解之策。

For early liver disease, no correlation was noted with age, sex, site of tumour or tumour differentiation on univariate analysis. Emergency surgery was associated with a higher risk of recurrent disease in the liver (OR= 5.13, 95%CI: 2.33-11.30, P ＜ 0.001), with an adverse outcome in the presence of perforation than obstruction alone (OR 4.78 vs 3.74). Histological factors demonstrating significance on univariate analysis included T4 stage (OR = 2.76, 95%CI: 1.32-5.76, P =0.007), N2 stage (OR = 3.32, 95%CI: 1.42-7.76, P =0.006), LVI (OR = 3.02, 95%CI: 1.49-6.10, P = 0.002),PNI (OR = 3.71, 95%CI: 1.17-11.80, P = 0.026) and R1 resection margin (OR = 3.70, 95%CI: 1.16-11.74,P = 0.027). LNR (OR = 11.69, 95%CI: 1.94-70.24, P= 0.007) provided AUC of 0.61 (95%CI: 0.51-0.71,P = 0.023) with the optimal cut-off at 0.015 (53.7%sensitivity and 67.3% specificity). A multivariate predictive model of presentation and histological features showed that perforation at the time of surgery was the strongest independent predictor of early liver recurrence amongst other markers of predictive value(Table 4).

Patients undergoing emergency resection also displayed adverse disease free survival (DFS) and overall survival compared to elective resections. Median DFS and overall survival were poorer in the emergency resection at 1155 days (Log rank P ＜ 0.001, Figure 1)and 1931 d (Log rank P = 0.027, Figure 2) respectively.

Long-term survival data was available from 262 patients with a median survival of 9.9 years. One-,three- and five-year survival in the study cohort was 96%, 82% and 72% respectively. Emergency surgery was associated with poorer survival (log rank P = 0.027)with 1, 3 and 5 year survival at 90%, 65% and 50%respectively (Figure 2). Multivariate Cox regression demonstrated T4 status to be a stronger predictor of adverse outcome than emergency surgery (HR 1.96, 95%CI: 1.27 to 3.02, P = 0.003). No significant difference in long-term survival was noted in patients with colonic or rectal disease (log rank P = 0.217).

Amongst histological features, T4 disease (HR= 1.65, 95%CI: 1.05-2.60, P = 0.031), PNI (HR =3.20, 95%CI: 1.72-5.97, P ＜ 0.001) and LNR were independent predictors of adverse outcome in a multivariate Cox regression model. LNR was associated with the greatest risk of early death (HR = 11.87,95%CI: 3.98-35.36, P ＜ 0.001).

Median survival with early recurrence was 2.62 years (95%CI: 1.92-3.31). In the presence of early liver recurrence, median survival was 2.78 years(95%CI: 2.27-3.39); early lung disease was 2.17 years(95%CI: 1.82-2.53) and early local recurrence was 1.80 years (95%CI: 1.27-2.33). For overall recurrence,isolated liver or lung only metastatic disease showed a better survival pattern than multi-site or local recurrent disease (Figure 3). Median survival in isolated liver disease was 2.87 years (95%CI: 2.39-3.35), which was not significantly different compared to 3.98 years(95%CI: 1.12-6.85) for isolated lung recurrence. Multisite disease and local disease were associated with significantly adverse survival compared to isolated liver disease.

DISCUSSION

Emergency resection for colorectal cancer presents a high risk group with increased risk of early recurrence and adverse long-term survival. Right colonic tumours and T4 stage are prognostic predictors for emergency colorectal cancer resection. T4 stage, LVI and emergency resection also offer a strong prognostic prediction for development of recurrent disease identifying high-risk patients for aggressive surveillance or adjuvant therapies.

Emergency colorectal resection constituted 13.2%of patients undergoing curative surgery and did not constitute all emergency presentations with symptomatic colorectal cancer. This is smaller than the reported national average of up to 30%[17,26] and may be the result of patient selection practices and the emerging role of self-expanding metal stent for acute malignant large bowel obstruction. Emergency surgery in our cohort was associated with poorer early and longterm survival. Hogan et al[20] concluded similarly that emergent surgery was associated with higher rates of local recurrence and poorer disease-free survival.Patients presenting in an emergency setting with advanced disease may have a distinct, aggressive tumour with unfavourable biology[22] and therefore these patients may be more prone to early recurrence.Furthermore, in the emergency setting patients have altered physiology and are immunosuppressed so that tumour dissemination in these circumstances occurs more easily[21]. Correlation between the increased morbidity of emergency surgery and timely or successful progression to adjuvant therapies was not specifically evaluated. The use of self-expanding colonic stents offers to address the associated high morbidity and mortality with emergency surgery[27,28].

Statistical analysis was performed using SPSS®version 20.0 (IBM, New York, NY, United States) using non-parametric tests (χ2 test and logistic regression).Continuous data in the text are reported as median(range), unless stated otherwise. P ＜ 0.050 was regarded as significant. Variables with P ＞ 0.100 on univariate analysis were excluded from multiple regression predictive model analyses. Models with multiple variables were assessed for interactions.Receiver operating characteristic (ROC) curves were plotted for continuous variables to estimate threshold values that differentiated groups. Survival analysis was carried out using the Kaplan-Meier method. Differences in survival curves were assessed using the log rank method.

这实在是一篇好散文，文辞优美，理情兼具，更难得的是，它所表达的，在当下看来毫无时代的隔膜，仍有棒喝之效。

LVI was also found to be an independent predictor of early all-site recurrence in a similar study by Huh et al[32] however they classified early recurrence as less than 1 year after operation. Lim et al[33] found that after attempted curative resection, patients with LVI-positive tumours had a higher rate of all-site recurrence than those without LVI. This is in correlation with our study.

对于高校的知识产权管理而言，主要的目标是对科研技术成果及其他智力成果的开发、利用、转让和发展进行系统化的管理。但是在目前的高校知识产权管理中，还存在以下方面的诸多问题。

壁层作成模块安在腔体内壁上，壁层向着等离子体方向的表层由铍组成，在于对快中子减速和再与快中子反应产生更多中子，能量较低的中子再经过重水减速，把能量带出腔体，这种热能可用于发电。灰份输出可进行磁流发电。作些改进，可生产氚。可参考西南核物理研究院设计的壁层。

这是本节复习课的最后一道例题，处理完问(1)距下课还有十多分钟的时间，之后对问(2)，教师引导学生思考、讨论、展示、交流．学生自主提出5个问题，在教师的引导下，又有4个新问题被提出．在解决的过程中，教师又引领学生深入研究．前两个问题解决后，发现最值取得时，四边形PAOB恰是正方形，顺势教师提出可以研究四边形PAOB何时为正方形；∠APB的最大值求出是90°时，教师又提出若∠APB=60°，那么点P的横坐标的范围如何等等，问题不断衍生，探究永不停止，从而让思维的教学更具穿透力、延展力．

Up to 50% of patients develop hepatic metastases within the first three years after curative resection[3].In our study, overall recurrence occurred in 25% of the patient population, with 82% of the recurrence diagnosed within three years after resection. This is commensurate with the reported literature[4,34];Meyerhardt et al[4] reports 80% of recurrences occur within the first three years. The liver was by far the most common site for early recurrence with 74% of cases occurring there. This is due to haematogenous spread via the portal venous system[35]. Pietra et al[36]also reported that 65% of recurrence occurred in the liver, in keeping with our observation.

Median survival of patients with early liver recurrence was 2.78 years. This compares favourably with patients presenting with early local recurrence who had a median survival of 1.8 years. This improved outcome may be a reflection of a more aggressive approach of isolated liver disease with the advent of improved liver parenchyma sparing techniques and advances in surgical techniques and perioperative care. The 5-year survival rate for patients that undergo curative metachronous resection of four or less hepatic lesions is 24%-58%[37-40]. A 5-year survival of 24% has also been reported for curative metachronous resection of ＞ 8 hepatic lesions[41]. Detection of metachronous disease as early as possible is imperative in limiting the extent of resection and improving survival. Renehan et al[15] highlighted the value of intensive follow-up by demonstrating a high detection of early metachronous disease by aid of CEA and computed tomography.This has delivered an opportunity for early detection and planning of definitive intervention. This may allow for more liver parenchymal-sparing techniques in the form of metastectomies and also improve the success of redo-hepatectomies[42]. The earlier the diagnosis is made, the more likely it is going to be resectable[43].

The lungs are the second most common location for metastatic spread of colorectal cancer[44]. It occurs in 5%-15% of patients and not all of these have concurrent liver metastases[45]. Only 4.1% of patients with synchronous pulmonary metastases are resectable, whereas 14.8% of patients with metachronous pulmonary metastases are resectable[46]with a 36%-40% 5-year survival rate in resected patients[47]. In our study, 14 (5.2%) patients developed lung metastases in the follow-up period with a median survival period of 2.17 years. Nodal status and Dukes stage were predictive of early lung recurrence on univariate analysis but not multivariate analysis. This result should be treated with caution due to the limited number of patients who developed lung metastases. This is in contrast to a similar study by Kim et al[48] that reported a 3 year overall survival rate of 54.6%, although their study included 105 patients. Our study only contained 14 patients who developed lung metastases and it is possible that increased survival may have occurred with more patients in this category.

Negative predictive features when considering a patient for pulmonary metastatectomy follow a similar pattern to metastasis elsewhere and include an unresectable primary tumour, extra-pulmonary metastases, resection margins (R1/2) and mediastinal lymph node disease[49]. Blackmon et al[50] concluded that more than three lung metastases present at the first metastatectomy and a preoperative disease free survival of less than three years predicts recurrence.This suggests that early pickup of metastases means more patients can be considered for a successful resection. However, due to a small number of patients with lung disease in our cohort, no meaningful analyses of multiple clinical and pathological factors could be carried out.

The value of early detection of metastatic disease in offering an absolute reduction in mortality is clear[15].Predictive tools can aid the clinician in identifying patients at higher risk of early metachronous metastasis as not all patients will benefit from aggressive surveillance. Our results suggest that there may be a subgroup of patients who would benefit from more intensive follow-up. As most tumours recur within the first three years after resection[34,51], it is imperative that the focus on follow-up occurs during this time frame.However, there is a lack of specific guidance for patients who may be at increased risk.

Current surveillance protocols consist of a combination of CEA testing, CT scans, and colonoscopy.Emergency surgery and the presence of specific histological features can inform the selection of patients at high-risk of early recurrence and should be factored into surveillance strategies. There is a substantial range in intensity of follow-up with the United Kingdom having noticeably less intensive follow-up in comparison to American collaborators[4,21,22]. A recent United Kingdom study of 1202 participants who had undergone curative surgery for primary colorectal cancer found no survival benefit from combined intensive monitoring groups compared to follow-up only if symptoms recurred[52]. This study was a randomised trial and so highlights the need to target the patients that would benefit from an intensive follow-up regimen. This has benefits for all stakeholders; earlier detection of recurrence in high-risk patients and a reduction of unnecessary investigations in the lowrisk group. Exciting developments in the availability of other prognostic markers in the future may enhance the efficacy of a risk-adapted follow-up strategy[53]. The overexpression of vascular endothelial growth factor[54]and interleukin-8[55] in colorectal carcinoma cells are two such examples.

Our study is limited, foremost by the retrospective approach of data gathering using the hospital coding process. The weaknesses of such a design are well known[56]. Secondly, relevant data on neoadjuvant and adjuvant therapies and cause of death was not available to afford reliable assessment of correlation. More patients in the emergency resection group received postoperative adjuvant therapies which may have been the result of a higher tumour stage (T4), early recurrence disease or palliative treatment. Indication for post-operative therapies and cause of death outcomes were not collected and survival was calculated on basis of all-cause mortality. The majority of recurrent disease occurred in the liver, leading to more reliable statistical conclusions here. However, this was limited in number for both lung and local recurrent disease reflecting differences in association of histological and clinical predictive features. Furthermore, low event rates in neo-adjuvant therapies and positive resection margins, missing data on total number of lymph nodes harvested, limited reliable evaluation of these factors in overall outcomes.

Although emergency presentation in the form of obstruction continues to represent a significant proportion of patients with initial diagnosis, self-expanding colonic metal stents are likely to play an increasingly important role in improving immediate postoperative outcomes,stoma rates and long-term outcomes without adverse oncological outcomes[28]. Proven survival benefit from primary and redo liver resections in isolated disease and emerging technologies for palliative control of local and distant metastatic disease mean that predictive clinicopathological markers could be used in a more intensive, targeted surveillance strategy to identify more patients with early recurrence. Emergency resection,tumour stage, lymphovascular invasion and lymph node ratio ＞ 0.015 represent a high-risk of recurrent disease and can inform surveillance strategies to enable early interventions.

ARTICLE HIGHLIGHTS

Research background

Colorectal cancer is the fourth most common cancer in the United Kingdom with over 40000 cases diagnosed each year. Despite the widespread use of screening programs, a large number of cases are diagnosed in the acute or urgent setting with adverse post-operative mortality, disease-free and overall long-term survival.

Research motivation

A large proportion of patients with colorectal cancer are diagnosed in the acute setting with an emergency presentation (26%) or following an urgent 2-wk referral (27%). Compared to elective resection, emergency surgery is associated with adverse postoperative outcomes (post-operative mortality 4.6% vs 16%), disease-free and overall long-term survival. The basis for this is multifactorial and may include altered physiology, immune-suppression,adverse tumour biology, advanced disease, peri-operative complications and lower progression to adjuvant therapies.

Research objectives

Adverse predictive factors for survival in colorectal cancer include emergency presentation with obstruction or perforation and histo-pathological features such as T4 disease, advanced nodal disease. Lymph node ratio offers to a new representation of nodal disease. Although it is affected directly but the lymph node yield, its utility as a predictive tool for recurrent disease has not been evaluated. We aimed to identify clinical and histological predictive factors for early recurrence disease and pattern to inform surveillance strategies and aid in early detection.

Research methods

首先，要想使学生真正学到英语，而不是在伪学习，教师要根据学生的不同层次和学情来设计教学活动。学生的知识水平、认知能力和性格特点有着很大的差异，所以教师应适当地进行分层教学，给每一个学生必要的自主表现和发展的空间、时间，促使有差异的学生共同发展。分层有很多内容，因为学生的基础不一致，所以学生需要分层；因为知识的难易程度有别，所以教学目标也要分层；学生和知识有差别，所以施教、作业和评价都需要分层。教师要根据情况的不同，在教学中采取不一样的教学策略，充分发挥学生在学习中的主体作用，让学生从英语教学中体会英语学习的乐趣，曾强学习英语的自信，从而提升英语教学的水平，促进学生发展。

Research results

Outcomes were evaluated in 266 consecutive patients following curative surgery with a median follow-up of 7.9 years. The proportion of patients undergoing emergency resection was 13.2%. Recurrent disease was detected in 67 patients (25.2%) during follow-up with the majority identified early within 3 years (82.1%). Liver was the predominant site of metastatic disease (73.1%).Emergency resection (OR = 3.60, P = 0.001), T4 stage (OR = 4.33, P ＜ 0.001)and lymphovascular invasion (LVI) (OR = 2.37, P = 0.032) were associated with higher risk of recurrent disease. Emergency resection, T4 disease and a high lymph node ratio (LNR) were strong independent predictors of adverse longterm survival.

社区大学的新教师要适应角色，需要向社区经验丰富的资深教师学习。资深教师可以用已有经验，帮助新教师成长得更快，专业发展之路更为顺畅。社区可以聘请资深教师做师傅，与新教师结对，分享教学经验，协助新进教师适应教学，提供教学与活动的管理和组织技巧。例如，社区大学教师师徒结对过程中，可以由资深的“师傅”讲述自己在社区大学的教学故事开始，进而讨论教学过程中的感受、困境与改变，也可以谈及社区大学教学的核心价值及未来期待。结对过程中，资深教师通过经验分享可以带给年轻教师深刻的学习经验，形成一种社区大学新教师的学习模式［4］。

Research conclusions

Our study reaffirms the independent predictive potential of histological and clinical features for recurrent disease in patients undergoing emergency resection for colorectal cancer. Furthermore, it introduces the independent utility of lymph node ratio (LNR) alongside T stage and lympho-vascular invasion in identifying patients with high risk of recurrent disease.

Research perspectives

Modified surveillance strategies should be evaluated in presence of adverse clinical and histological factors to improve early detection of recurrent disease in high-risk patients to offset adverse disease-free and overall long-term survival.

REFERENCES

1 Cancer Research UK. Bowel cancer incidence statistics. [accessed 2014 Jun]. Available from: URL: http://www.cancerresearchuk.org/cancer-info/cancerstats/types/bowel/incidence/

2 Tan EK, Ooi LL. Colorectal cancer liver metastases - understanding the differences in the management of synchronous and metachronous disease. Ann Acad Med Singapore 2010; 39:719-715 [PMID: 20957308]

3 Garden OJ, Rees M, Poston GJ, Mirza D, Saunders M,Ledermann J, Primrose JN, Parks RW. Guidelines for resection of colorectal cancer liver metastases. Gut 2006; 55 Suppl 3: iii1-iii8[PMID: 16835351 DOI: 10.1136/gut.2006.098053]

4 Meyerhardt JA, Mangu PB, Flynn PJ, Korde L, Loprinzi CL,Minsky BD, Petrelli NJ, Ryan K, Schrag DH, Wong SL, Benson AB 3rd; American Society of Clinical Oncology. Follow-up care, surveillance protocol, and secondary prevention measures for survivors of colorectal cancer: American Society of Clinical Oncology clinical practice guideline endorsement. J Clin Oncol 2013; 31: 4465-4470 [PMID: 24220554 DOI: 10.1200/JCO.2013.50.7442]

5 Scheele J, Stangl R, Altendorf-Hofmann A. Hepatic metastases from colorectal carcinoma: impact of surgical resection on the natural history. Br J Surg 1990; 77: 1241-1246 [PMID: 2253003 DOI: 10.1002/bjs.1800771115]

6 Nozawa H, Sunami E, Nakajima J, Nagawa H, Kitayama J.Synchronous and metachronous lung metastases in patients with colorectal cancer: A 20-year monocentric experience. Exp Ther Med 2012; 3: 449-456 [PMID: 22969910 DOI: 10.3892/etm.2011.443]

7 Landmann RG, Weiser MR. Surgical management of locally advanced and locally recurrent colon cancer. Clin Colon Rectal Surg 2005; 18: 182-189 [PMID: 20011301 DOI: 10.1055/s-2005-916279]

8 Read TE, Mutch MG, Chang BW, McNevin MS, Fleshman JW,Birnbaum EH, Fry RD, Caushaj PF, Kodner IJ. Locoregional recurrence and survival after curative resection of adenocarcinoma of the colon. J Am Coll Surg 2002; 195: 33-40 [PMID: 12113543 DOI: 10.1016/S1072-7515(02)01224-3]

9 Pastorino U, Buyse M, Friedel G, Ginsberg RJ, Girard P,Goldstraw P, Johnston M, McCormack P, Pass H, Putnam JB Jr;International Registry of Lung Metastases. Long-term results of lung metastasectomy: prognostic analyses based on 5206 cases. J Thorac Cardiovasc Surg 1997; 113: 37-49 [PMID: 9011700 DOI:10.1016/S0022-5223(97)70397-0]

10 Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM,Rougier P, Bechstein WO, Primrose JN, Walpole ET, Finch-Jones M, Jaeck D, Mirza D, Parks RW, Collette L, Praet M,Bethe U, Van Cutsem E, Scheithauer W, Gruenberger T; EORTC Gastro-Intestinal Tract Cancer Group; Cancer Research UK;Arbeitsgruppe Lebermetastasen und-tumoren in der Chirurgischen Arbeitsgemeinschaft Onkologie (ALM-CAO); Australasian Gastro-Intestinal Trials Group (AGITG); Fédération Francophone de Cancérologie Digestive (FFCD). Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983):a randomised controlled trial. Lancet 2008; 371: 1007-1016 [PMID:18358928 DOI: 10.1016/S0140-6736(08)60455-9]

11 Bruinvels DJ, Stiggelbout AM, Kievit J, van Houwelingen HC, Habbema JD, van de Velde CJ. Follow-up of patients with colorectal cancer. A meta-analysis. Ann Surg 1994; 219: 174-182[PMID: 8129488 DOI: 10.1097/00000658-199402000-00009]

12 House MG, Ito H, Gönen M, Fong Y, Allen PJ, DeMatteo RP,Brennan MF, Blumgart LH, Jarnagin WR, D’Angelica MI.Survival after hepatic resection for metastatic colorectal cancer:trends in outcomes for 1,600 patients during two decades at a single institution. J Am Coll Surg 2010; 210: 744-752, 752-755[PMID: 20421043 DOI: 10.1016/j.jamcollsurg.2009.12.040]

17 National Cancer Intelligence Network data briefing. Routes to diagnosis. NCIN, November 2010. [accessed 2015 Mar]. Available from: URL: http://www.ncin.org.uk/databriefings

（四）加强“谁执法谁普法”的资源整合。法治宣传主管部门要积极推动建立“谁执法谁普法”联席会议制度，定期召集各单位商议，并邀请人大代表、政协委员、社会团体，市民群众等列席会议，共同探讨协商解决问题，加强部门间的横向联动和资源整合；进一步夯实并丰富各类交流和宣传的载体和平台，加强对新媒体和融媒体的运用，做到“我搭台同唱戏”，开展更具生动性、有效性的普法宣传工作；切实运用好福建省法治宣传云平台，完善“谁执法谁普法”网上报备机制，各单位开展“谁执法谁普法”的工作情况实时利用平台上传报备，资源共享，形成工作合力。

14 Figueredo A, Rumble RB, Maroun J, Earle CC, Cummings B,McLeod R, Zuraw L, Zwaal C; Gastrointestinal Cancer Disease Site Group of Cancer Care Ontario’s Program in Evidence-based Care. Follow-up of patients with curatively resected colorectal cancer: a practice guideline. BMC Cancer 2003; 3: 26 [PMID:14529575 DOI: 10.1186/1471-2407-3-26]

这是教师针对性批改作文的做法，是“授之以渔”的一个重要方法。因为每一个学生的习作，在选材、内容、结构都不一定相同，甚至相同的题材，侧重点也不尽相同，好、中、差学生的习作也肯定不同。我们可以选择优良的习作面批面改，在全班范读，指出好在哪里，起典范作用。若为了全面提高，也要选一些其他层次的学生习作，和学生面对面地指导，教给学生修改的方法。

15 Renehan AG, Egger M, Saunders MP, O’Dwyer ST. Impact on survival of intensive follow up after curative resection for colorectal cancer: systematic review and meta-analysis of randomised trials. BMJ 2002; 324: 813 [PMID: 11934773 DOI: 10.1136/bmj.324.7341.813]

16 Renehan AG, O’Dwyer ST, Whynes DK. Cost effectiveness analysis of intensive versus conventional follow up after curative resection for colorectal cancer. BMJ 2004; 328: 81 [PMID:14715603 DOI: 10.1136/bmj.328.7431.81]

13 Jeffery M, Hickey BE, Hider PN. Follow-up strategies for patients treated for non-metastatic colorectal cancer. Cochrane Database Syst Rev 2007; CD002200 [PMID: 17253476 DOI:10.1002/14651858.CD002200.pub2]

Keum et al[30] concluded that high risk factors for recurrence include rectal cancer, T2 stage and an infiltrative growth pattern. However, this study only looked at patients who underwent resection for stage I colorectal cancer which may explain their finding of T2 stage compared with ours of T4 stage. It has been stated previously that rectal tumours and younger age at presentation have a higher recurrence risk[31].However, this was not the case in our study for reasons that are not clear to us.

18 Wong SK, Jalaludin BB, Morgan MJ, Berthelsen AS, Morgan A,Gatenby AH, Fulham SB. Tumor pathology and long-term survival in emergency colorectal cancer. Dis Colon Rectum 2008; 51:223-230 [PMID: 18097722 DOI: 10.1007/s10350-007-9094-2]

作为云南省大型进口企业,11月6日，云天化集团公司及联合商务与三井物产、TRAMMO(美商运安)、LUKOIL(鲁克石油)、ADM、CARGILL(嘉吉)等10家主流国际客户现场签约，签约金额超过10亿美元，成为云南省交易团进口签约的最大买家。

19 Morris EJ, Taylor EF, Thomas JD, Quirke P, Finan PJ, Coleman MP, Rachet B, Forman D. Thirty-day postoperative mortality after colorectal cancer surgery in England. Gut 2011; 60: 806-813[PMID: 21486939 DOI: 10.1136/gut.2010.232181]

20 Hogan J, Samaha G, Burke J, Chang KH, Condon E, Waldron D,Coffey JC. Emergency presenting colon cancer is an independent predictor of adverse disease-free survival. Int Surg 2015; 100:77-86 [PMID: 25594643 DOI: 10.9738/INTSURG-D-13-00281.1]

21 Vallejo R, Hord ED, Barna SA, Santiago-Palma J, Ahmed S.Perioperative immunosuppression in cancer patients. J Environ Pathol Toxicol Oncol 2003; 22: 139-146 [PMID: 14533877 DOI:10.1615/JEnvPathToxOncol.v22.i2.70]

22 Ghazi S, Berg E, Lindblom A, Lindforss U; Low-Risk Colorectal Cancer Study Group. Clinicopathological analysis of colorectal cancer: a comparison between emergency and elective surgical cases. World J Surg Oncol 2013; 11: 133 [PMID: 23758762 DOI:10.1186/1477-7819-11-133]

23 Baca B, Beart RW Jr, Etzioni DA. Surveillance after colorectal cancer resection: a systematic review. Dis Colon Rectum 2011; 54:1036-1048 [PMID: 21730795 DOI: 10.1007/DCR.0b013e31820db364]

24 The Association of Coloproctologists of Great Britain and Ireland. Guidelines for the Management of Colorectal Cancer.Third edition, 2007.

25 Benson AB, Arnoletti P, Bekaii-Saab T, Chan E, Chen YJ, Choti MA, Cooper HS, Dilawari RA, Engstrom PF, Enzinger PC,Fleshman JW, Fuchs CS, Grem JL, Knol JA, Leong LA, Lin E,May KS, Mulcahy MF, Murphy K, Rohren E, Ryan DP, Saltz L, Sharma S, Shibata D, Skibber JM, Small W, Sofocleous CT,Venook AP, Willett C. Clinical practice and guidelines in oncology(National Comprehensive Cancer Network Guidelines) Colon Cancer NCCN Version 3, 2014

26 Scott N, Hill J, Smith J, Kelly S, Fearnhead N. National Bowel Cancer Audit Annual Report. Association of Coloproctologist of Great Britain and Ireland. 2013

27 Tan CJ, Dasari BV, Gardiner K. Systematic review and metaanalysis of randomized clinical trials of self-expanding metallic stents as a bridge to surgery versus emergency surgery for malignant left-sided large bowel obstruction. Br J Surg 2012; 99:469-476 [PMID: 22261931 DOI: 10.1002/bjs.8689]

28 Hill J, Kay C, Morton D, Magill L, Handley K, Gray R. CREST Trial Collaborative Group CREST: Randomised phase III study of stenting as a bridge to surgery in obstructing colorectal cancer-Results of the UK ColoRectal Endoscopic Stenting Trial (CREST).J Clin Oncol 2016; 34 (suppl): Abstr 3507

29 Liang JL, Wan DS, Pan ZZ, Zhou ZW, Chen G, Li LR, Lu ZH,Wu XJ. [Multivariate regression analysis of recurrence following curative surgery for colorectal cancer]. Ai Zheng 2004; 23: 564-567[PMID: 15142455]

30 Keum MA, Lim SB, Kim SA, Yoon YS, Kim CW, Yu CS, Kim JC.Clinicopathologic factors affecting recurrence after curative surgery for stage I colorectal cancer. J Korean Soc Coloproctol 2012; 28:49-55 [PMID: 22413082 DOI: 10.3393/jksc.2012.28.1.49]

Following institutional approval, a retrospective study of clinical and histopathological parameters was carried out to study patterns of recurrence and survival in consecutive patients undergoing elective and emergency resection for colorectal cancer over an eight-year study period.

高职院校校友工作多是以学校需求为主导，开展校友值年返校、校友讲座、校友捐赠等活动，重“索取”、轻“交互”。而与校友企业开展人才培养、社会培训、技术服务等合作，既可以提升母校人才培养质量、社会服务能力，也可以为校友企业发展提供人才支撑和智力支持，从而实现学校与校友企业共赢发展。

31 Hellinger MD, Santiago CA. Reoperation for recurrent colorectal cancer. Clin Colon Rectal Surg 2006; 19: 228-236 [PMID:20011326 DOI: 10.1055/s-2006-956445]

32 Huh JW, Kim CH, Lim SW, Kim HR, Kim YJ. Early recurrence in patients undergoing curative surgery for colorectal cancer: is it a predictor for poor overall survival? Int J Colorectal Dis 2013; 28:1143-1149 [PMID: 23503665 DOI: 10.1007/s00384-013-1675-z]

33 Lim SB, Yu CS, Jang SJ, Kim TW, Kim JH, Kim JC. Prognostic significance of lymphovascular invasion in sporadic colorectal cancer. Dis Colon Rectum 2010; 53: 377-384 [PMID: 20305435 DOI: 10.1007/DCR.0b013e3181cf8ae5]

34 Sargent DJ, Wieand HS, Haller DG, Gray R, Benedetti JK, Buyse M, Labianca R, Seitz JF, O’Callaghan CJ, Francini G, Grothey A,O’Connell M, Catalano PJ, Blanke CD, Kerr D, Green E, Wolmark N, Andre T, Goldberg RM, De Gramont A. Disease-free survival versus overall survival as a primary end point for adjuvant colon cancer studies: individual patient data from 20,898 patients on 18 randomized trials. J Clin Oncol 2005; 23: 8664-8670 [PMID:16260700 DOI: 10.1200/JCO.2005.01.6071]

35 Bar-Gil Shitrit A, Shitrit D, Bakal I, Braverman D, Kramer MR. Endobronchial metastases from colon cancer without liver metastases: report of eight cases. Dis Colon Rectum 2007; 50:1087-1089 [PMID: 17347902 DOI: 10.1007/s10350-006-0880-z]

36 Pietra N, Sarli L, Costi R, Ouchemi C, Grattarola M, Peracchia A.Role of follow-up in management of local recurrences of colorectal cancer: a prospective, randomized study. Dis Colon Rectum 1998;41: 1127-1133 [PMID: 9749496 DOI: 10.1007/BF02239434]

37 Morris EJ, Forman D, Thomas JD, Quirke P, Taylor EF, Fairley L, Cottier B, Poston G. Surgical management and outcomes of colorectal cancer liver metastases. Br J Surg 2010; 97: 1110-1118[PMID: 20632280 DOI: 10.1002/bjs.7032]

38 de Jong MC, Pulitano C, Ribero D, Strub J, Mentha G, Schulick RD, Choti MA, Aldrighetti L, Capussotti L, Pawlik TM. Rates and patterns of recurrence following curative intent surgery for colorectal liver metastasis: an international multi-institutional analysis of 1669 patients. Ann Surg 2009; 250: 440-448 [PMID:19730175 DOI: 10.1097/SLA.0b013e3181b4539b]

39 Fernandez FG, Drebin JA, Linehan DC, Dehdashti F, Siegel BA, Strasberg SM. Five-year survival after resection of hepatic metastases from colorectal cancer in patients screened by positron emission tomography with F-18 fluorodeoxyglucose (FDGPET). Ann Surg 2004; 240: 438-447; discussion 447-450 [PMID:15319715 DOI: 10.1097/01.sla.0000138076.72547.b1]

40 Jamison RL, Donohue JH, Nagorney DM, Rosen CB, Harmsen WS, Ilstrup DM. Hepatic resection for metastatic colorectal cancer results in cure for some patients. Arch Surg 1997; 132:505-510; discussion 511 [PMID: 9161393 DOI: 10.1001/archsurg.1997.01430290051008]

41 Malik HZ, Hamady ZZ, Adair R, Finch R, Al-Mukhtar A, Toogood GJ, Prasad KR, Lodge JP. Prognostic influence of multiple hepatic metastases from colorectal cancer. Eur J Surg Oncol 2007; 33:468-473 [PMID: 17097260 DOI: 10.1016/j.ejso.2006.09.030]

42 Allen PJ, Jarnagin WR. Current status of hepatic resection. Adv Surg 2003; 37: 29-49 [PMID: 12953626]

43 Adam R, Lucidi V, Bismuth H. Hepatic colorectal metastases:methods of improving resectability. Surg Clin North Am 2004; 84:659-671 [PMID: 15062667 DOI: 10.1016/j.suc.2003.12.005]

44 McCormack PM, Attiyeh FF. Resected pulmonary metastases from colorectal cancer. Dis Colon Rectum 1979; 22: 553-556[PMID: 527448 DOI: 10.1007/BF02587003]

45 Tan KK, Lopes Gde L Jr, Sim R. How uncommon are isolated lung metastases in colorectal cancer? A review from database of 754 patients over 4 years. J Gastrointest Surg 2009; 13: 642-648[PMID: 19082673 DOI: 10.1007/s11605-008-0757-7]

46 Mitry E, Guiu B, Cosconea S, Jooste V, Faivre J, Bouvier AM.

Epidemiology, management and prognosis of colorectal cancer with lung metastases: a 30-year population-based study. Gut 2010;59: 1383-1388 [PMID: 20732912 DOI: 10.1136/gut.2010.211557]

47 Fiorentino F, Hunt I, Teoh K, Treasure T, Utley M. Pulmonary metastasectomy in colorectal cancer: a systematic review and quantitative synthesis. J R Soc Med 2010; 103: 60-66 [PMID:20118336 DOI: 10.1258/jrsm.2009.090299]

48 Kim CH, Huh JW, Kim HJ, Lim SW, Song SY, Kim HR, Na KJ,Kim YJ. Factors influencing oncological outcomes in patients who develop pulmonary metastases after curative resection of colorectal cancer. Dis Colon Rectum 2012; 55: 459-464 [PMID: 22426271 DOI: 10.1097/DCR.0b013e318246b08d]

49 Treasure T, Milošević M, Fiorentino F, Macbeth F. Pulmonary metastasectomy: what is the practice and where is the evidence for effectiveness? Thorax 2014; 69: 946-949 [PMID: 24415715 DOI:10.1136/thoraxjnl-2013-204528]

50 Blackmon SH, Stephens EH, Correa AM, Hofstetter W, Kim MP,Mehran RJ, Rice DC, Roth JA, Swisher SG, Walsh GL, Vaporciyan AA. Predictors of recurrent pulmonary metastases and survival after pulmonary metastasectomy for colorectal cancer. Ann Thorac Surg 2012; 94: 1802-1809 [PMID: 23063195 DOI: 10.1016/j.athor acsur.2012.07.014]

51 Berman JM, Cheung RJ, Weinberg DS. Surveillance after colorectal cancer resection. Lancet 2000; 355: 395-399 [PMID:10665570 DOI: 10.1016/S0140-6736(99)06552-6]

52 Primrose JN, Perera R, Gray A, Rose P, Fuller A, Corkhill A,

George S, Mant D; FACS Trial Investigators. Effect of 3 to 5 years of scheduled CEA and CT follow-up to detect recurrence of colorectal cancer: the FACS randomized clinical trial. JAMA 2014;311: 263-270 [PMID: 24430319 DOI: 10.1001/jama.2013.285718]

53 Rose J, Augestad KM, Cooper GS. Colorectal cancer surveillance:what’s new and what’s next. World J Gastroenterol 2014; 20:1887-1897 [PMID: 24587668 DOI: 10.3748/wjg.v20.i8.1887]

54 Toiyama Y, Inoue Y, Saigusa S, Okugawa Y, Yokoe T, Tanaka K,Miki C, Kusunoki M. Gene expression profiles of epidermal growth factor receptor, vascular endothelial growth factor and hypoxiainducible factor-1 with special reference to local responsiveness to neoadjuvant chemoradiotherapy and disease recurrence after rectal cancer surgery. Clin Oncol (R Coll Radiol) 2010; 22: 272-280[PMID: 20117921 DOI: 10.1016/j.clon.2010.01.001]

55 Lurje G, Zhang W, Schultheis AM, Yang D, Groshen S, Hendifar AE, Husain H, Gordon MA, Nagashima F, Chang HM, Lenz HJ.Polymorphisms in VEGF and IL-8 predict tumor recurrence in stage III colon cancer. Ann Oncol 2008; 19: 1734-1741 [PMID:18550579 DOI: 10.1093/annonc/mdn368]

56 Audit commission. PbR Data assurance Framework 2007/2008.Audit Commission London