Hepatic resection for colorectal metastases: value for risk scoring systems?

INTRODUCTION: Predictors of outcome in patients with metastatic colorectal cancer remain inconsistent. We aimed to identify predictors of outcome in these patients, to develop a prognostic scoring system, and to assess the general applicability of the current major risk scoring systems. MATERIALS AND METHODS: Following IRB approval, medical records of 662 consecutive patients undergoing resection of colorectal metastases to the liver during 1960 to 1995 were reviewed. Clinicopathologic and outcome data were assessed from records and mailed questionnaire. Clinicopathologic variables were tested using univariate and multivariate analyses; best-fit models were then generated to study the effect of each independent risk factor on outcome. To validate existing scoring models, our independent data set was applied to those scores. The relative concordance probability estimates were calculated for these models and compared with that of the proposed Mayo model. RESULTS: The overall and disease-specific 5-year survival rates were 37% and 42%, respectively. The probability of recurrence at any site was 65% at 5 years. Perioperative blood transfusion and positive hepatoduodenal nodes were the major determinants of survival and recurrence. To assess the general applicability of the proposed risk scoring systems, we imported the data from our patient population into 3 other scoring systems. Neither survival nor recurrence among our patients was stratified discretely by any of the scoring systems. Based on probability estimates, all models were only marginally better than chance alone in predicting outcome. CONCLUSION: Broad application of risk scoring systems for patients with metastatic colorectal cancer has limited clinical value and refinement and external validation should be undertaken before utilization.     

Colorectal Liver Metastases: State of the Art Imaging

Colorectal cancer is a leading cause of death with mortality determined predominately by metastatic involvement of the liver. Treatment of liver metastases continues to evolve and imaging plays an essential role in initial staging, preoperative planning, and treatment monitoring. This review article discusses the current role of imaging in the management of patients with colorectal liver metastases. Particular challenges such as hepatic steatosis, disappearing metastases, and following treated lesions are addressed.     

Are academic hospitals better at treating metastatic colorectal cancer?

BackgroundThere is a strong association between hospital volume and surgical outcomes in resectable colorectal cancer. The purpose of our study was to investigate the association between hospital facility type and survival of patients with metastatic colorectal cancer.MethodsAdults from the National Cancer Database (2010–2015) with a primary diagnosis of colorectal metastases were included and stratified by facility type: community cancer program, comprehensive community cancer program, and academic/research program. The primary outcome was 5-year overall survival, analyzed using Kaplan-Meier survival curves, log-rank test, and the Cox proportional hazards regression model.ResultsAmong the 52,958 included patients, 13.72% were treated at a community cancer program, 49.89% at a comprehensive community cancer program, and 36.29% at an academic/research program. A significant increase in the proportion of patients being treated in an academic/research program has been observed from 2010 to 2015. An academic/research program tended to use more chemotherapy with colorectal radical resection and liver or lung resection and immunotherapy with chemotherapy. In adjusted analysis, the academic/research program had decreased risk of mortality in comparison to the community cancer program and the comprehensive community cancer program (hazard ratio 0.90, 95% confidence interval 0.86–0.94; 0.87, 0.85–0.90; each P < .001; respectively). Similar results were seen after stratifying by metastatic site and treatment type.ConclusionThe prognosis and overall survival of patients with metastatic disease is better in an academic/research program compared with a community cancer program or a comprehensive community cancer program, with this difference persisting across sites of metastatic disease and treatment types. Further studies are required to validate these results and investigate disparities in the management of metastatic colorectal cancer.     

转移性肝癌的治疗理念和策略

转移性肝癌是恶性肿瘤发展的终末阶段,是导致患者死亡的主要原因,其中胃肠道是常见的原发癌部位。人们正尝试通过根治转移性肝癌或控制其发展等多种治疗策略,延长患者生存期。手术治疗、全身化疗、分子靶向治疗、射频消融术、门静脉栓塞术、肝动脉导管栓塞术是转移性肝癌的有效治疗方法,其中手术治疗是转移性肝癌可能获得治愈的有效手段。相比结肠癌肝转移癌,胃癌肝转移癌的治疗正处于探索阶段,但是随着新型有效化疗药物及化疗方案的出现、肝转移癌手术适应证的拓展以及大规模多中心临床试验循证医学证据的涌现,包括胃癌肝转移在内的转移性肝癌的治疗必将朝着一个更加规范,更为有效的方向发展。     

Long-term outcome of familial adenomatous polyposis patients after restorative coloproctectomy

BACKGROUND: Restorative proctocolectomy (RPC) eliminates the risk of colorectal adenocarcinoma in familial adenomatous polyposis (FAP) patients, but desmoid tumors, duodenal, and ileal adenomas can still develop. Our aim was to assess the long-term outcome of FAP patients after RPC. PATIENTS AND METHODS: FAP patients who had RPC between 1983 and 1990 were contacted for interview and upper gastrointestinal (GI) and ileal pouch endoscopy. RESULTS: Sixty-two males and 48 females had undergone hand-sewn RPC during this period. One patient died postoperatively (0.9%). Among 96 patients available for a minimal follow-up of 11 years, 7 patients died: 3 from causes unrelated to FAP, 2 from metastatic colorectal cancer, and 2 from mesenteric desmoid tumor (MDT). Thirteen patients had a symptomatic MDT (13.5%). Of 73 patients who had an upper GI endoscopy, 52 developed duodenal and/or ampullary adenomas. Four patients required surgical treatment of their duodenal lesions. Among 54 patients who underwent ileal pouch endoscopy, pouch adenomas were noted in 29. No invasive duodenal or ileal pouch carcinoma were detected. Functional results of RPC were significantly worse in MDT patients. CONCLUSIONS: RPC eliminates the risk of colorectal cancer, and close upper GI surveillance may help prevent duodenal malignancy. MDTs are the principal cause of death, once colorectal cancer has been prevented, and the main reason for worsening functional results.     

Does the literature support an indication for hepatic metastasectomy other than for colorectal primary?

Hepatic resection for colorectal hepatic metastatic disease has been demonstrated to have a significant outcome benefit for selected patients. Advances in anesthetic and surgical technique have resulted in a significantly reduced morbidity and mortality for this procedure, and this management approach has become widely practiced. This hepatic resection paradigm is also being applied to hepatic metastatic disease of noncolorectal origin. The purpose of this report is to review and summarize the reported literature in order to define if the current data support an indication for hepatic metastasectomy. Thespecific cancer primaries that this analysis evaluated include breast, melanoma, gynecologic, neuroendocrine, sarcoma, and gastric cancer. Based on the data examined, we propose that although hepatic metastasectomy for noncolorectal cancer may be a promising component of overall oncologic treatment, the role of surgical resection cannot be generalized and at present should be individualized based on the patient’s clinical course and by the biologic behaviors of specific malignancies.     

Peritonealkarzinose

Colorectal cancer is a common malignant disease with increasing incidence and a significant cause of death in cancer patients. More than 10% of patients with colorectal cancer show peritoneal carcinomatosis at initial diagnosis. Moreover, peritoneal metastasis is a common sign of recurrence. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are a new treatment strategy for highly selected patients with peritoneal carcinomatosis. Numerous studies show prolonged survival after CRS and HIPEC with acceptable morbidity and mortality rates. Accurate preoperative diagnostics and patient selection play a pivotal role in postoperative patient outcome. This promising treatment strategy is discussed regarding surgical technique, intraperitoneal chemotherapy, and patient outcome.     

Peritoneal carcinomatosis. Surgical treatment, including hyperthermal intraperitoneal chemotherapy]

Colorectal cancer is a common malignant disease with increasing incidence and a significant cause of death in cancer patients. More than 10% of patients with colorectal cancer show peritoneal carcinomatosis at initial diagnosis. Moreover, peritoneal metastasis is a common sign of recurrence. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are a new treatment strategy for highly selected patients with peritoneal carcinomatosis. Numerous studies show prolonged survival after CRS and HIPEC with acceptable morbidity and mortality rates. Accurate preoperative diagnostics and patient selection play a pivotal role in postoperative patient outcome. This promising treatment strategy is discussed regarding surgical technique, intraperitoneal chemotherapy, and patient outcome.     

Advances in systemic chemotherapy and immunotherapy for metastatic colorectal cancer

Colorectal cancer is the second leading cause of cancer related death in the United States. Approximately 25% of patients are diagnosed with metastatic colorectal cancer (mCRC) and the 5-year survival rate in mCRC is low at 14%. Primary treatment for mCRC is systemic therapy, which includes chemotherapy, immunotherapy, and targeted agents. With advances in genomic profiling, we can now tailor treatment to unique patient populations and improve overall survival. In this review, we discuss treatment strategies for mCRC patients based on tumor sidedness, KRAS/BRAF wild-type versus mutant tumors, and review the benefit of immunotherapy in microsatellite unstable and mismatch repair deficient tumors.     

Prognostic Models for Predicting Death after Hepatectomy in Individuals with Hepatic Metastases from Colorectal Cancer

BACKGROUND: Appropriate cancer treatment policies should include an accurate estimate of a patient's baseline risk of death, determined by the tumor load. Few prognostic models have reached the stage at which they can be used to select patients who would benefit from hepatectomy for metastatic colorectal cancer. Establishing the prognosis of patients with hepatic metastases from colorectal cancer is an important part of their evaluation and treatment. METHODS: Pre- and post-treatment prognostic nomograms were developed using Cox regression and multiple imputation from 578 patients with hepatic metastases from colorectal cancer who were candidates for hepatectomy. RESULTS: The preoperative nomogram included the following prognostic factors: primary histology, number of metastatic lymph nodes associated with the primary lesion, number of hepatic tumors, extrahepatic disease, and prehepatectomy carcinoembryonic antigen level. Plots of predicted versus actual outcomes suggested that the nomogram was well calibrated for predicting death after hepatectomy. The concordance index of the nomogram was 0.66, higher than those of other models for hepatic metastatic colorectal cancer in the literature. A postoperative nomogram was also prepared. CONCLUSIONS: These models have improved predictive ability in individuals with hepatic metastases from colorectal cancer, which may be helpful in counseling patients and making treatment decisions.     

Outcome of treatment of 160 patients with squamous cell carcinoma of the neck staged N3a.

One hundred sixty patients with N3a neck disease were studied to evaluate the overall treatment outcome. Of these, 54 received palliative radiotherapy and 106 patients were treated with treated with curative intent. Twenty patients (19%) died of intercurrent disease (13 at less than 2 years), and 13 of 93 patients followed for 2 or more years are alive with no evidence of disease. Thus, 73 patients died directly from cancer, with metastatic disease being the leading cause of death. Almost one third of the patients failed to complete treatment.     

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??Progression of targeted therapy for colorectal cancer LIN Feng, LI Yong. Guangdong Provincial People's Hospital ?? Guangdong Province Academy of Medical Sciences, Guangzhou 510080, China
Corresponding author??LIN Feng??E-mail: liyong-lucky@21cn.com
Abstract Colorectal cancer is one of the most common malignant tumors but the results of conventional chemotherapy have been discouraging. The recent successful development of targeted therapy has brought new hope for patients with colorectal cancer. Two monoclonal antibodies, bevacizumab and cetuximab, that block vascular endothelial growth factor and epithelial growth factor receptor are available widely in clinical practice. The addition of cetuximab or bevacizumab to the chemotherapy for metastatic colorectal cancer further improves the outcome. The combination of chemotherapy with cetuximab or bevacizumab has become standard regimens in advanced colorectal cancer and makes a striking step to prolong the survival time in the past few years. The major achievement for the cetuximab targeted therapy of mCRC is the correlation between k-ras status and the efficacy of anti-EGFR therapy. Molecular targeted therapy plays a more important role in treatment for colorectal cancer.     

Targeted biotherapy in metastatic colorectal carcinoma: Current practice

Targeted therapy has become an indispensable tool in the management of metastatic colorectal cancer (mCRC). The combination of monoclonal antibodies with conventional polychemotherapy has proven its efficacy as the median overall survival now exceeds 24 months: these novel molecules act by targeting circulating vascular endothelial growth factor (VEGF) and the receptor of epidermal growth factor (EGFR). At the present time, no factor has been identified to predict the efficacy of bevacizumab, an inhibitor of circulating VEGF. On the other hand, mutation of the KRAS oncogen has been proven to be a factor of non-response, or even of deleterious response to the use of EGFR, therefore limiting its use to patients whose tumors bear the wild type KRAS oncogen. Treatment toxicity for these molecules is moderate, specific, and is not cumulative with chemotherapy-related toxicity. On the other hand, combined targeted therapy (association of several targeted therapy drugs) has not been shown to be of any benefit. Other biotherapies continue to be developed, but there is not yet a consensus of how to best target the tumor nor which anti-tumoral molecules to use in the treatment of mCRC.     

Additive Chemotherapie bei Lebermalignomen zur Verbesserung der Operabilität

Complete tumor resection is the only curative option for patients with colorectal liver metastases. Hepatic resection is frequently not possible for technical reasons: because of large tumors, multiple or bilateral metastases, or tumors that are too close to vessels. In these cases chemotherapy might downstage the tumor volume and facilitate secondary curative resection in patients initially not eligible for curative surgery. Treatment with fluorouracil (5-Fu) alone has resulted in disappointing response rates of about 10-20% in patients with colorectal liver metastases, which make these protocols useless in the neoadjuvant setting. Because regional chemotherapy into the hepatic arteria results in significantly higher response rates (40-50%), some studies have documented some success in secondary curative surgery after regional chemotherapy of initially unresectable colorectal liver metastases. However, regional chemotherapy is invasive and therefore not standard therapy for every patient with colorectal liver metastases. Recently new exciting treatment options have become available for colorectal cancer. Combinations of chemotherapy consisting of irinotecan and 5-Fu/FA or oxaliplatin and 5-Fu/FA result in response rates of 50% and can be considered a new standard first-line chemotherapy for patients with metastatic colorectal cancer. Recently, two encouraging retrospective studies have been published with chronomodulated chemotherapy of oxaliplatin and 5-Fu/FA in the setting of neoadjuvant chemotherapy for patients with unresectable colorectal liver metastases. With this multidisciplinary approach, antitumor activity of chemotherapy appears to be translated into a long-term survival benefit and some patients with initially unresectable colorectal liver metastases can potentially be cured. As a consequence, on the premises of close cooperation between surgeons and internists, more patients with metastatic colorectal cancer will be cured in the future.     

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??Treatment strategies for management of colorectal cancer liver metastases YE Ying-jiang, WANG Shan. Department of Gastroenterology Surgery, Peking University People’s Hospital, Beijing 100044, China Corresponding author:YE Ying-jiang, E-mail:yjye101@yahoo.com.cn Abstract Liver metastases is the most common distant metastasis of colorectal cancer. Surgical resection is believed the only effective treatment for metastatic hepatic cancer currently. With increased experience and multiple disciplines development, the surgical indication for metastatic liver cancer has been expanded gradually, and the standard of hepatic surgery has also been improved constantly. Importantly, multidisciplinary team (MDT) model remains the fundamental for optimal treatment for liver metastasis from colorectal cancer. The participation of MDT brings more opportunities for metastatic liver cancer, and improves the surgery outcomes indirectly. Diagnostic radiology is an important way for R0 resection of metastatic liver cancer; the intraoperative ultrasound increases metastatic liver cancer detection rate and surgery safety. Preoperative chemotherapy brings operation opportunity for those patients with initially unresectable lesions, and postoperative adjuvant therapy contributes to reduce the post-operation recurrence and metastasis. Radiofrequency ablation combined with hepatic resection provides unresectable metastatic liver cancer the best opportunity for long term survival.     

Advances and directions in chemotherapy using implantable port systems for colorectal cancer: a historical review

With the recent advances in chemotherapy for colorectal cancer, the prognosis for patients with metastatic colorectal cancer has been significantly improved. The development of the implantable port system has also enabled patients to receive multiagent chemotherapy with a more satisfactory quality of life. Historically, chemotherapy using implantable port systems was begun to obtain an oncological benefit in the treatment of locoregional cancer. In the 1950s, there was an increasing interest in perfusion techniques for the application of chemotherapeutic agents, such as nitrogen mustard, in the locoregional treatment of metastatic cancer. Among them, the treatment of liver metastasis has interested oncologists for many years. On the other hand, implantable devices were developed during the intervening decades that have enabled patients with colorectal cancer with liver metastases to be treated effectively using hepatic arterial infusion; which became more common in the 1980s. The treatment of metastatic colorectal cancer increasingly requires a multimodal approach and multiple treatment options based not on convenience, but in terms of personalization and efficacy. Therefore, it is important to optimize the pharmacokinetics of chemotherapeutic agents. Implantable port systems for colorectal cancer patients have been essential for oncological practice, and the importance of these systems will remain unchanged in the near future.     

Surgical resection of pulmonary metastases from colorectal cancer: a systematic review of published series

The treatment of patients with pulmonary metastases from colorectal cancer continues to evolve. Recently the use of novel agents as a first-line treatment in metastatic colorectal disease has generated cautious optimism in the oncological community. However, pulmonary metastasectomy remains a mainstay in a multidisciplinary concept for a highly selected subset of patients. A selected group of patients with metastases limited to the lungs may benefit from pulmonary metastasectomy with a 5-year survival rate of up to more than 50%. This review evaluates the current status of surgical resection in pulmonary metastases from colorectal cancer, with special emphasis on prognostic factors that influence survival, as well as on surgical approach and lymph node dissection and its impact on the management of patients with metastatic colorectal disease.     

Young-onset colorectal cancer: Diagnosis and management

In the U.S., colorectal cancer (CRC) has become the second most incident cancer among adults younger than age 50, and is a leading contributor to cancer deaths in this age group. Young-onset CRC is a heterogeneous disease entity that encompasses etiologies arising from a mix of genetic and environmental factors. Germline predisposition through major hereditary cancer syndromes account for 10–19% of these patients, while familial clustering of risk can be observed in another 23%. The majority of the patients have sporadic CRCs that predominate the left colon and rectum and are typically already nodally or systemically metastatic at diagnosis. The key components of their management include multidisciplinary oncologic care, clinical genetics care, and multidimensional survivorship care. We herein review the epidemiology, the etiologies, and other considerations surrounding the diagnosis and treatment of young-onset CRC.     

结直肠癌腹膜转移的诊治策略与挑战

腹膜是结直肠癌常见的转移部位,与其他转移部位相比预后较差。早期的观点认为,腹膜转移是疾病的终末状态,全身化疗为主的姑息性治疗是其主要治疗手段。随着肿瘤细胞减灭术(CRS)+腹腔热灌注化疗(HIPEC)的治疗模式逐渐得到外科医生的认可,以及靶向治疗和免疫药物的应用,结直肠癌腹膜转移患者的预后得到了很大改善。然而,结直肠癌腹膜转移的诊治仍面临很多挑战和争议。本文从对结直肠癌腹膜转移的认识演变出发,讨论了腹膜转移可能的机制,包括"寡转移"学说和"种子-土壤"学说;进一步探讨了结直肠癌腹膜转移的诊治策略及面临的挑战,包括影像学检查的局限性、腹腔镜探查的争议、腹膜转移负荷评估困难、术后复发监测和疗效评估手段有限以及中国不同地区间诊治水平差异较大等问题。同时强调了CRS+HIPEC围手术期多学科管理的重要性,并提出应加强腹膜转移的基础与临床转化研究,推广腹膜转移的规范化诊治是提高结直肠癌腹膜转移患者预后的根本。     

Survival After Hepatic Resection for Colorectal Metastases: A 10-Year Experience

Background Metastatic colorectal cancer is a major cause of cancer death in North America. Hepatic resection offers the potential for cure in selected patients. We report the long-term outcomes of patients who underwent hepatic resection for colorectal metastases over a 10-year period at a single hepatobiliary surgical oncology center. Methods All patients who underwent liver resection for metastatic colorectal cancer between 1992 and 2002 were identified. Data were retrospectively obtained through chart review. Major outcome variables were disease-free survival and overall survival. Risk factors for disease recurrence and mortality were identified by multivariate analysis by using the Cox proportional hazard method. Results A total of 423 hepatectomies were performed for metastatic colorectal cancer. Most operations (n = 276; 65%) were major (four or more segments) hepatectomies. Perioperative morbidity occurred in 74 (17%) patients. There were seven (1.6%) perioperative deaths. The disease-free survival at 1, 5, and 10 years was 64%, 27%, and 22%, respectively. The overall survival at 1, 5, and 10 years was 93%, 47%, and 28%, respectively. Multivariate analysis identified four negative predictive factors for overall survival (hazard ratio; 95% confidence interval): a positive surgical margin (2.9; 1.5–5.3), large metastases (>5 cm; 1.5; 1.1–2.0), multiple metastases (1.4; 1.1–1.9), and age >60 years (1.4; 1.1–1.9). Conclusions Hepatic resection for metastatic colorectal cancer is safe and provides good long-term overall survival rates of 47% at 5 years and 28% at 10 years. An aggressive approach is justified by the low operative mortality rate and good long-term survival, even in individuals with multiple bilobar metastases.