结直肠癌肝转移术后化疗远期疗效的Meta分析

目的用Meta分析的方法,评价化疗对可切除结直肠肝转移患者长期疗效的影响。方法检索1990-01-2013-12发表于PubMed、Embase、Cochrane Library和万方数据库中收集化疗对可切除结直肠肝转移患者长期疗效随机对照试验的文章,有2名评价员独立按照纳入及排除标准,筛选及提取数据并评估研究的方法学质量,利用Cochrane协作网提供的RevMan 5.1.4软件进行Meta分析。结果共纳入8篇随机对照试验,样本量885例,手术+化疗组409例,单纯手术组476例。Meta分析结果显示,与单纯手术组患者相比,手术+化疗组患者并不具备长期生存的优势,两组差异无统计学意义,HR=0.92,95%CI为0.80~1.06,P=0.25,I2=17%。但在亚组分析中,手术+静脉化疗组与单纯手术组相比,两组差异有统计学意义,HR=0.80,95%CI为0.63~1.00,P=0.05,I2=0;手术+肝动脉化疗组与单纯手术组相比,两者差异无统计学意义,HR=1.00,95%CI为0.84~1.21,P=0.96,I2=30%。在分析无疾病进展时间时,化疗组可以增加患者的无疾病进展时间,HR=0.77,95%CI为0.67~0.88,P=0.000 2,I2=25%。在亚组分析中,手术+静脉化疗组(HR=0.75,95%CI为0.62~0.92,P=0.004,I2=0)与单纯手术组相比差异有统计学意义,但手术+肝动脉化疗组与单纯手术组差异无统计学意义,HR=0.72,95%CI为0.51~1.02,P=0.07,I2=54%。结论全身静脉化疗对于提高和改善结直肠癌肝转移手术患者的长期生存及无疾病进展时间是有帮助的,但静脉化疗的时间及方案选择还需大样本前瞻性研究进一步证实。     

Hepatectomy and intraarterial infusion chemotherapy for liver metastasis from colorectal cancer

Hepatectomy and intraarterial chemotherapy for liver metastasis from colorectal cancer have been performed in our department. Intraarterial infusion chemotherapy has also been performed for unresectable liver metastasis. One hundred twenty-seven cases of liver metastasis from colorectal cancer were studied. The cases were divided into groups according to radicability of the original colorectal cancer, whether or not hepatectomy was performed, and whether or not they received intraarterial chemotherapy. Group I is cur C of origin. Group II is cur A or B without hepatectomy. Group III is cur A or B with hepatectomy. Each group was divided into a group without intraarterial chemotherapy (A) and a group with it (B). IA 23 cases, IB 13 cases, IIA 14 cases, IIB 21 cases, IIIA 28 cases, and IIIB 28 cases. The survival rate of group III was better than that of group II. The survival rate of group II was better than that of group I. There was no significant difference in survival rates between IA and IB. The survival rate of group IIB was significantly better than that of group IIA. The survival rate of group IIIB was significantly better than that of group III A. Hepatectomy and intraarterial chemotherapy after hepatectomy for liver metastasis from colorectal cancer were effective.     

Cryosurgery for resectable and unresectable hepatic metastases from colorectal cancer.

AIMS: Hepatic cryosurgery is useful for patients with hepatic metastases from colorectal cancer confined to the liver but considered unresectables because of the number and location of lesions. While encouraging results were reported following cryosurgery for unresectable liver metastases we considered particularly valuable to examine the safety and effectiveness of cryosurgery in patients with resectable and unresectable metastases from colorectal cancer. METHODS: Between January 1997 and September 2005, 53 patients with liver metastases from colorectal cancer underwent hepatic cryosurgery at our institution. Hepatic metastases were resectable in 31 (58.5%) patients and unresectable in 22 (41.5%). RESULTS: A total of 136 liver metastases were treated in 53 patients. The size of treated lesions ranged from 0.5 to 10 cm (mean 2.7). There were 2 postoperative deaths (3.8%) from massive bleeding and from cryoshock. The overall morbidity rate was 66%. The median follow-up was 24.8 months. The overall survival rate at 12 months was 86.1%, at 48 months it was 27%. No significant difference was found between survival rates in patients with resectable or unresectable metastases. Among 31 patients with resectable liver metastases 7 (22.6%) patients developed recurrence at the site of cryosurgery. CONCLUSION: Survival rates were comparables between patients with resectable and unresectable metastases but a high complication rate and a substantial rate of local recurrence following cryosurgery should caution against its use to treat resectable disease.     

可切除结直肠癌肝转移患者的术前和术后化疗

可切除结直肠癌肝转移患者术后约有75%的复发率.围手术期的氟尿嘧啶、亚叶酸、奥沙利铂(FOLFOX)化疗较单纯手术可以减少合格入组患者和手术患者的疾病进展风险.但术前化疗可导致肝血管改变和脂性肝炎从而增加手术风险.汇总分析显示与单纯手术相比,术后接受氟尿嘧啶和亚叶酸为基础的辅助化疗,有延长无疾病进展生存期的趋势.贝伐单抗无论术前还是术后使用可能均不会增加手术风险.如何合理地选择化疗时机及最佳持续时间等问题尚待解决.     

Borderline resectable pancreatic cancer - a definition and effective treatment strategy

The survival benefit of extended surgery for advanced pancreatic cancer has been denied by four randomized controlled trials. However, there still is confusion and conflict over the definition and effective treatment strategy for so-called locally advanced or borderline resectable pancreatic cancer. Although there are a number of reports that showed outcomes of preoperative chemotherapy or chemoradiotherapy for this disease, the definitions and treatment regimens described in these studies vary. Moreover, all of the studies were Phase I / II trials or retrospective analysis, and there is no Phase III trial currently focused on this issue. It is urgently necessary to establish an international consensus on the definition of borderline resectable pancreatic cancer. The usefulness of neoadjuvant treatment for this disease should also be elucidated in future clinical trials. In this review article, we discuss the current understanding and definition of borderline resectable pancreatic cancer, and the value of neoadjuvant treatment strategy for treating it.     

潜在可切除的结直肠癌同时性肝转移的治疗策略

肝转移是结直肠癌治疗的重点和难点,同时性肝转移接受根治性手术的机会更少,手术难度更大,因此预后更差.如何科学地判断肝转移灶的可切除性,有效地将潜在可切除肝转移灶转化为可切除病灶,对于治疗至关重要.本文就潜在可切除的结直肠癌同时性肝转移在临床治疗策略上的变革与发展进行综述.     

Intraoperative radiotherapy in colorectal cancer: Systematic review and meta-analysis of techniques,long-term outcomes,and complications

BackgroundThe precise contribution of IORT to the management of locally advanced and recurrent colorectal cancer (CRC) remains uncertain. We performed a systematic review and meta-analysis to assess the value of IORT in this setting.MethodsStudies published between 1965 and 2011 that reported outcomes after IORT for advanced or recurrent CRC were identified by an electronic literature search. Studies were assessed for methodological quality and design, and evaluated for technique of IORT delivery, oncological outcomes, and complications following IORT. Outcomes were analysed with fixed-effect and random-effect model meta-analyses and heterogeneity and publication bias examined.Results29 studies comprising 14 prospective and 15 retrospective studies met the inclusion criteria and were assessed, yielding a total of 3003 patients. The indication for IORT was locally advanced disease in 1792 patients and locally recurrent disease in 1211 patients. Despite heterogeneity in methodology and reporting practice, IORT is principally applied for the treatment of close or positive margins. When comparative studies were evaluated, a significant effect favouring improved local control (OR 0.22; 95% CI = 0.05–0.86; p = 0.03), disease free survival (HR 0.51; 95% CI = 0.31–0.85; p = 0.009), and overall survival (HR 0.33; 95% CI = 0.2–0.54; p = 0.001) was noted with no increase in total (OR 1.13; 95% CI = 0.77–1.65; p = 0.57), urologic (OR 1.35; 95% CI = 0.84–2.82; p = 0.47), or anastomotic complications (OR 0.94; 95% CI = 0.42–2.1; p = 0.98). Increased wound complications were noted after IORT (OR 1.86; 95% CI = 1.03–3.38; p = 0.049).ConclusionsDespite methodological weaknesses in the studies evaluated, our results suggest that IORT may improve oncological outcomes in advanced and recurrent CRC.     

Adjuvant chemotherapy of cancer: definition, prognosis, statistical aspects

Once the need for adjuvant chemotherapy has been defined with precision, it is important to specify when it may be employed. Two factors determine the decision to use this form of therapy: a) the notion of the presence of malignant tumor, sensitive to chemotherapy (breast, bone ovary), b) knowledge of the elements of prognosis. The probability of relapse is estimated on the basis of these two latter points. Adjuvant chemotherapy is prescribed in cases where the risk of relapse is quite important, attaining 40 to 50 per cent. Its effectiveness can be assessed only with rigorous statistical rules. Randomization only permits a comparison of adjuvant chemotherapy to a control group. Certain errors must be avoided in the interpretation of the results: inaccurate analysis of results such as median comparisons; comparison of the number of deaths or the number of relapses; exclusion of patients after randomization. Only the comparison of the remission duration curves by a test adapted to the form of the curves (Log rank test or Weibull's test) seems justified.     

Minimally invasive techniques for colorectal cancer

Laparoscopic approaches are increasingly being applied to colorectal surgical procedures. Initial concerns regarding the existence of benefits from the laparoscopic approach have now been addressed. Even as these were being addressed, however, further concerns arose regarding the appropriateness of this technique in malignancy. Colorectal cancer is the only intra-abdominal malignancy that is knowingly resected employing laparoscopic techniques. This controversy was highlighted by reports of early wound implants. With careful technique, training and experience, however, wound recurrences are rarely seen, suggesting that this phenomenon, in the clinical setting, is primarily technique-related. Lack of rigorous evidence either condemning or supporting the laparoscopic approach for colorectal cancer resulted in the establishment of several large-scale randomized, prospective trials, all currently in progress, that aim to determine if laparoscopic resection of colorectal cancer results in oncologic outcomes comparable to the open approach.     

Re-operation for recurrent colorectal cancer: the importance of early diagnosis for resectability and survival

Between 1978 and 1986, 179 patients with recurrent colorectal cancer were treated and 137 patients were operated a second time.82.1% of the patients showed elevated CEA levels (greater than or equal to 5 ng/ml) at the time of diagnosis. In 58.1% of the patients the CEA increase preceded the recognition of recurrence, and in 13.4% the diagnosis could be confirmed only by a second-look operation. In 46.7% of the re-operated patients a potentially curative resection of the locally recurrent or metastatic disease could be performed. The resectability was significantly lower in patients with symptomatic recurrent disease (34.5%) as compared to asymptomatic patients with CEA-directed positive imaging (52.7%) and the second-look patients (62.5%) respectively. A significant improvement in survival could be achieved especially in the second-look operated patients.     

可切除结直肠癌肺转移的预后因素分析

目的 探讨结直肠癌肺转移根治性切除术后的预后影响因素.方法 回顾性分析行根治性切除术的60例结直肠癌肺转移患者的临床资料.结果 全组患者肺转移瘤切除术后和结直肠癌切除术后的5年生存率分别为43.7%和74.0%.单因素分析结果显示,肺转移瘤数目和无瘤间期与结直肠癌术后患者的总生存率有关(均P＜0.05),肺转移瘤切除前癌胚抗原(CEA)水平、肺转移瘸数目、有无肺门和纵隔淋巴结转移与肺转移瘤切除术后患者的生存率有关(均P＜0.05).多因素分析结果显示,肺转移瘤数目和无瘤间期是结直肠癌术后患者预后的独立影响因素(OR=2.691,95% CI为1.072～6.754;OR=0.979,95% CI为0.963～0.994),肺转移瘤数目、有无肺门和纵隔淋巴结转移是肺转移瘤切除术后患者预后的独立影响因素(OR=3.319,95% CI为1.274～8.648;OR=3.414,95% CI为1.340～8.695).结论 经过严格选择的结直肠癌肺转移患者,尤其是单发肺转移及无肺门和纵隔淋巴结转移的患者,行根治性切除术后可获得长期生存.     

Inflammation and prognosis in colorectal cancer

Aim of the studyPrevious work has indicated that quantification of inflammatory cell reaction is of prognostic value in colorectal cancer. We evaluated the prognostic significance of inflammatory cell reaction patterns in colorectal cancer and developed a grading method which could be used in the routine assessment of tumours.MethodsThe intensity of overall inflammatory cell reaction, numbers of neutrophilic and eosinophilic granulocytes, lymphoid cells and macrophages in both the central region and the invasive margin were estimated in 386 colorectal cancer patients. Prognostic significance was analysed by uni- and multivariate analysis.ResultsOur method for classification of inflammatory reaction was reliable. High-grade inflammation at the invasive margin in Dukes’ stage A and B cancers (pT1-2N0 and pT3N0, respectively) was associated with better 5-year-survival (87.6%) than low-grade inflammation (47.0%).ConclusionsInflammatory cell response at the invasive border is a relevant prognostic indicator and could be easily incorporated into the routine evaluation of histopathological specimens.     

Expanding criteria for resectability of colorectal liver metastases

Surgical resection is the treatment of choice in patients with colorectal liver metastases, with 5-year survival rates reported in the range of 40%-58%. Over the past 10 years, there has been an impetus to expand the criteria for defining resectability for patients with colorectal metastases. In the past, such features as the number of metastases (three to four), the size of the tumor lesion, and a mandatory 1-cm margin of resection dictated who was "resectable." More recently, the criteria for resectability have been expanded to include any patient in whom all disease can be removed with a negative margin and who has adequate hepatic volume/reserve. Specifically, instead of resectability being defined by what is removed, decisions concerning resectability now center around what will remain after resection. Under this new paradigm, the number of patients with resectable disease can be expanded by increasing/preserving hepatic reserve (e.g., portal vein embolization, two-stage hepatectomy), combining resection with ablation, and decreasing tumor size (preoperative chemotherapy). The criteria for resectability have also expanded to include patients with extrahepatic disease. Rather than being an absolute contraindication to surgery, patients with both intra- and extrahepatic disease should potentially be considered for resection based on strict selection criteria. The expansion of criteria for resectability of colorectal liver metastases requires a much more nuanced and sophisticated approach to the patient with advanced disease. A therapeutic approach that includes all aspects of multidisciplinary and multimodality care is required to select and treat this complex group of patients.     

炎症与免疫指标在可切除性结直肠癌中的预后价值

结直肠癌是世界范围内常见的恶性肿瘤之一,在中国其发病率和病死率逐年增加,年轻化趋势也愈加明显.在肿瘤治疗过程中,免疫及炎症介导的抗肿瘤反应尤为重要,并在肿瘤的发生、发展过程中发挥重要作用.近年来研究发现,中性粒细胞与淋巴细胞比值(neutrophil-lymphocyte ratio,NLR)、血小板与淋巴细胞比值(p...     

Preoperative therapies for resectable and borderline resectable pancreatic cancer

In the era of multidetector high quality CT imaging, it is feasible and critical to use objective criteria to define resectable pancreatic cancer. This allows accurate pretreatment staging and the development of stage-specific therapy. Tumors of borderline resectability have emerged as a distinct subset and the definition has been expanded in the last few years. Borderline resectable tumors are defined as those with tumor abutment of <180degrees (< 50%) of the SMA or celiac axis, short segment abutment or encasement of the common hepatic artery typically at the gastroduodenal artery origin, SMV-PV abutment with impingement and narrowing or segmental venous occlusion with sufficient venous flow above and below the occlusion to allow an option for venous reconstruction. Most of the patients whose cancer meet these CT criteria are candidates for preoperative systemic chemotherapy followed by chemoradiation since they are at a high risk for margin positive resection with upfront surgery. Patients whose imaging studies show radiographic stability or regression proceed to pancreaticoduodenectomy (or pancreatectomy) and this may require vascular resection and reconstruction. Prospective biomarker and functional imaging enriched studies are warranted to determine the best overall treatment strategy for these patients.     

Patient-centered outcomes after therapy for colorectal cancer

In practical terms, clinicians can use the results of patient-centered outcome instruments to track patients' functional status and quality-of-life changes through treatment. Noting formalized results might help clinicians better communicate with patients at critical times during treatment, especially with regard to patient expectations.Although numerous clinical variables of uncertain value are regularly followed, validated functional and quality-of-life results have been put to use only rarely in the clinical setting. Clinicians' ability to interpret and apply quality-of-life results will surely improve with practice, and likely would be well worth the contribution to our patients' well-being.     

Impact of skeletal muscle mass on the prognosis of patients undergoing neoadjuvant chemotherapy for resectable or borderline resectable pancreatic cancer

International Journal of Clinical Oncology - Neoadjuvant chemotherapy is a common therapeutic procedure for patients with pancreatic cancer. This study aimed to investigate the association between...     

Defining patient outcomes in stage IV colorectal cancer: a prospective study with baseline stratification according to disease resectability status

Background:

Stage IV colorectal cancer encompasses a broad patient population in which both curative and palliative management strategies may be used. In a phase II study primarily designed to assess the efficacy of capecitabine and oxaliplatin, we were able to prospectively examine the outcomes of patients with stage IV colorectal cancer according to the baseline resectability status.

Methods:

At enrolment, patients were stratified into three subgroups according to the resectability of liver disease and treatment intent: palliative chemotherapy (subgroup A), conversion therapy (subgroup B) or neoadjuvant therapy (subgroup C). All patients received chemotherapy with capecitabine 2000 mg m^–2 on days 1–14 and oxaliplatin 130 mg m^–2 on day 1 repeated every 3 weeks. Imaging was repeated every four cycles where feasible liver resection was undertaken after four or eight cycles of chemotherapy.

Results:

Of 128 enrolled patients, 74, 22 and 32 were stratified into subgroups A, B and C, respectively. Attempt at curative liver resection was undertaken in 10 (45%) patients in subgroup B and 19 (59%) in subgroup C. The median overall survival was 14.6, 24.5 and 52.9 months in subgroups A, B and C, respectively. For patients in subgroups B and C who underwent an attempt at curative resection, 3-year progression-free survival was 10% in subgroup B and 37% for subgroup C.

Conclusions:

This prospective study shows the wide variation in outcome according to baseline resectability status and highlights the potential clinical value of a modified staging system to distinguish between these patient subgroups.