Arterial chemotherapy of 5—fluorouracil and mitomycin Cin the treatment of liver metastases of colorectal cancer

AIM：Regional chemotherapy using hepatic artery catheters is a good method of treating patients with colorectal cancer liver metastases.We investigated the survival of patients with liver metastases from colorectal cancer using 5-fluorouracil(5-FU)and mitomycin C Cthrough implantable hepatic arterial infusion port.METHODS:Seventy-five patents with inoperable liver metastases forom colorectal cancer were included between March,1992 and November,2001,We placed implantable hepatic arterial cathter(HAC)port by laparotomy,5-FU,1000mg/m^2/d continuors infusion for five days every four weeks,was delivered in the hepatic arterial catheter through the port.Mitomycin C,30mg/m^2/d infusion in the first day every cycel through the port.Response to the treatment was evaluated by serial determinations of plasma CEAand imaping techniques consisting of computerized tomography and sonography of liver.RESULTS:Sixty-eight were performed hepatic artery chemotherapy and fifty-six were followed up among seventy-five HAC patients.Twenty-six patients(46.4%)have responded and4complete remission were achieved.Eight patients(14.3%)had stable liver metastases.Twenty-two patients(39.3%)were progressed with increased tumor size and number.Twenty-nine patients(51.8%)had a decreased serum CEAlevel.while10patients(17.9%) were stable and 17patients(30.4%)had an increased serum CEAlevel.There were no operative death in this serise.Complications,which occurred in 18patients(32.1%),were as followed:hepatic artery thrombosis in11,Upper gastric and intestinal bleeding in3,liver abscess in1,pocket infection in1,cholangitis in1,and hepatic artery pseudo-aneurysm in one patient.CONCLUSION:Combined infusion of 5-FU and mitomycin C by hepatic artery catheter port is an effective treatment for liver metastases from colorectal cancer.The high response and lower complication rater prove the adjuvant treatment of colorectal cancer with this treatment.     

Surgical approaches of resectable synchronous colorectal liver metastases： Timing considerations

AIM: To compare the safety and efficacy of simultaneous versus two stage resection of primary colorectal tumors and liver metastases. METHODS: From January 1996 to May 2004, 103 colorectal tumor patients presented with synchronous liver metastases. Twenty five underwent simultaneous colorectal and liver surgery and 78 underwent liver surgery 1-3 mo after primary colorectal tumor resection. Data were retrospectively analyzed to assess and compare the morbidity and mortality between the surgical strategies. The two groups were comparable regarding the age and sex distribution, the types of liver resection and stage of primary tumors, as well as the number and size of liver metastases. RESULTS: In two-stage procedures more transfusions were required (4 ± 1.5 vs 2 ± 1.8, pRBCs, P < 0.05). Chest infection was increased after the two-stage approach (26% vs 17%, P < 0.05). The two-stage procedure was also associated with longer hospitalization (20 ± 8 vs 12 ± 6 d, P < 0.05). Five year survival in both groups was similar (28% vs 31%). No hospital mortality occurred in our series. CONCLUSION: Synchronous colorectal liver metastases can be safely treated simultaneously with the primary tumor. Liver resection should be prioritized over colon resection. It is advisable that complex liver resections with marginal liver residual volume should be dealt with at a later stage.     

Long-term outcomes of hepatectomy vs percutaneous ablation for treatment of hepatocellular carcinoma ≤ 4 cm

AIM: To determine which treatment modality--hepatectomy or percutaneous ablation--is more beneficial for patients with small hepatocellular carcinoma (HCC) (< or =4 cm) in terms of long-term outcomes. METHODS: A retrospective analysis of 149 patients with HCC < or =4 cm was conducted. Eighty-five patients underwent partial hepatectomy (anatomic in 47 and non-anatomic in 38) and 64 underwent percutaneous ablation (percutaneous ethanol injection in 37, radiofrequency ablation in 21, and microwave coagulation in 6). The median follow-up period was 69 mo. RESULTS: Hepatectomy was associated with larger tumor size (P<0.001), whereas percutaneous ablation was significantly associated with impaired hepatic functional reserve. Local recurrence was less frequent following hepatectomy (P<0.0001). Survival was better following hepatectomy (median survival time: 122 mo) than following percutaneous ablation (median survival time: 66 mo; P=0.0123). When tumor size was divided into < or =2 cm vs >2 cm, the favorable effects of hepatectomy on long-term survival was seen only in patients with tumors>2 cm (P=0.0001). The Cox proportional hazards regression model revealed that hepatectomy (P=0.006) and tumors < or =2 cm (P=0.017) were independently associated with better survival. CONCLUSION: Hepatectomy provides both better local control and better long-term survival for patients with HCC < or =4 cm compared with percutaneous ablation. Of the patients with HCC < or =4 cm, those with tumors >2 cm are good candidates for hepatectomy, provided that the hepatic functional reserve of the patient permits resection.     

Complications and treatment of migrated biliary endoprostheses： A review of the literature

Endoscopic biliary stent insertion is a well-established procedure. It is especially successful in treating postoperative biliary leaks, and may prevent surgical intervention. A routine change of endoprostheses after 3 mo is a common practice but this can be prolonged to 6 too. We reported a colonic perforation due to biliary stent dislocation and migration to the rectosigmoid colon, and reviewed the literature.     

Folic acid supplementation inhibits recurrence of colorectal adenomas： A randomized chemoprevention trial

AIM： To determine whether folic acid supplementation will reduce the recurrence of colorectal adenomas, the precursors of colorectal cancer, we performed a double-blind placebo-controlled trial in patients with adenomatous polyps.
METHODS： In the current double-blind, placebocontrolled trial at this VA Medical Center, patients with colorectal adenomas were randomly assigned to receive either a daily 5 mg dose of folic acid or a matched identical placebo for 3 years. All polyps were removed at baseline colonoscopy and each patient had a follow up colonoscopy at 3 years. The primary endpoint was a reduction in the number of recurrent adenomas at 3 years.
RESULTS： Of 137 subjects, who were eligible after confirmation of polyp histology and run-in period to conform compliance, 94 completed the study; 49 in folic acid group and 45 in placebo group. Recurrence of adenomas at 3-year was compared between the two groups. The mean number of recurrent polyps at 3-year was 0.36 （SD, 0.69） for folic acid treated patients compared to 0.82 （SD, 1.17） for placebo treated subjects, resulting in a 3-fold increase in polyp recurrence in the placebo group. Patients below 70 years of age and those with left-sided colonic adenomas or advanced adenomas responded better to folic acid supplementation.
CONCLUSION： High dose folic acid supplementation is associated with a significant reduction in the recurrence of colonic adenomas suggesting that folic acid may be an effective chemopreventive agent for colorectal neoplasia.     

Brain metastasis of hepatocellular carcinoma： A case report and review of the literature

INTRODUCTION Hepatocellular carcinoma (HCC) is one of the most frequent malignancies in the world.     

Irinotecan therapy and molecular targets in colorectal cancer： A systemic review

Irinotecan is the second line chemotherapy for advanced stage colorectal cancer （CRC） after failure of first line chemotherapy with oxaliplatin and 5-fluorouracil. The aim of this review is to analyse the data on irinotecan as second line chemotherapy for advanced CRC and the potential roles of the molecular markers, p53 and vascular endothelial growth factor （VEGF） in the management of advanced CRC. Thus, the English literature from 1980 to 2008 concerning irinotecan, p53, VEGF and CRC was reviewed. On review, Phase Ⅱ and Ⅲ clinical trials showed that irinotecan improves pain-free survival, quality of life, 1-year survival, progression-free survival and overall survival in advanced CRC. p53 and VEGF were expressed in CRC and had a predictive power of aggressive clinical behaviour in CRC. Irinotecan sensitizes p53 wild type, mutant and null cells to Fas- mediated cell apoptosis in CRC cells. Wild type p53 cells were more sensitive to irinotecan than mutated p53. Irinotecan has an anti-VEGF effect inhibiting endothelial cell proliferation, increasing apoptosis and reducing microvascular density which is only limited by irinotecan toxicity levels. To conclude, irinotecan improves the patient＇s quality of life and the survival rates of patients with advanced CRC. p53 and VEGF status of the patients＇ tumour is likely to affect the responsiveness of CRC to irinotecan. It is recommended that studies of the expression of these molecular markers in relation to chemoresponsiveness of irinotecan should be carried out for better management of patients with advanced CRC.     

Graft-verse-host disease after liver transplantation： A report of two cases and review of literature

Graft-verse-host disease （GVHD） is an uncommon fatal complication following liver transplantation （LTx）. In mainland China, only six cases have been reported with a morbidity rate up to 1%-2%. Definitive diagnosis was achieved by molecular techniques （HLA typing or PCR-STR） in only two cases and the remaining cases were diagnosed based on typical clinical features with exclusion of other possible causes. All patients died of septic shock or multiple organ failure even after administration of increased corticosteroids and supportive therapy, and reduced immunosuppressive agents. In our center, two cases of GVHD were found among 128 （1.56%） patients. One case was diagnosed by detecting lymphocyte macrochimerism through DNA-STR. Both of them died even after aggressive treatment. In China, the incidence of GVHD is similar to that reported by foreign centers except for an extremely bad prognosis. Rapid diagnosis is crucial for a better prognosis. In China, only 37.5% of cases are diagnosed by molecular methods. We recommend detecting lymphocyte macrochimerism through DNA-STR to get a rapid diagnosis, and interleukin 2-receptor antibody （basiliximab or daclizumab） therapy seems to be a good choice for the disease.     

Radioembolization for the treatment of unresectable hepatocellular carcinoma： A clinical review

Hepatocellular carcinoma （HCC） is the sixth most common cancer in the world. The majority of patients with HCC present with unresectable disease. These patients have historically had limited treatment options secondary to HCC demonstrating chemoresistance to the currently available systemic therapies. Additionally, normal liver parenchyma has shown intolerance to tumoricidal radiation doses, limiting the use of external beam radiation. Because of these limitations, novel percutaneous liver-directed therapies have emerged. The targeted infusion of radioactive microspheres （radioembolization） represents one such therapy. Radioembolization is a minimally invasive transcatheter therapy through which radioactive microspheres are infused into the hepatic arteries that supply tumor. Once infused, these microspheres traverse the hepatic vascular plexus and selectively implant within the tumor arterioles. Embedded within the arterioles, the ^90y.impregnated microspheres emit high energy and low penetrating radiation doses selectively to the tumor. Radioembolization has recently shown promise for the treatment of patients with unresectable HCC. The objective of this review article is to highlight two currently available radioembolic devices ^90Y, ^188Rh） and provide the reader with a recent review of the literature.     

Rectal carcinosarcoma： A case report and review of literature

A 60-years old male was admitted to our department for investigation of constipation and hypogastric discomfort intensified during defecation of a few weeks duration. The cause proved to be a rectal carcinosarcoma that was treated by abdominoperineal resection and postoperative chemo-radiotherapy. The patient died 6 months later due to hepatic failure, showing evidence of disseminated disease. In general colonic carcinosarcomas constitute a rare category of malignant neoplasms whose nature is still incompletely understood. No specific treatment guidelines exist. Surgery is the mainstay of treatment and regardless of the addition of adjuvant therapy the prognosis is very poor. Systematic genetic analysis may be the clue for understanding the pathogenesis of these mysterious tumors.     

原发性肝癌术后复发的综合防治

原发性肝癌(以下简称肝癌)是世界第六大癌症,癌症死因顺位第三位.中国是肝癌的高发区,全世界每年的新发患者我国占一半以上.手术切除仍是目前治疗肝癌的首选手段,然而较高的术后复发率已成为影响患者疗效和获得长期生存的瓶颈.如何有效地预防及治疗术后复发,成为能否进一步提高肝癌治疗效果的关键,也是目前临床研究的热点和难点.本文结合本单位的临床工作实践探讨肝癌术后复发的预防和治疗对策.     

Surgical treatment of pulmonary recurrence after hepatectomy for colorectal liver metastases

BACKGROUND/AIMS: Although pulmonary recurrence is frequent among the extrahepatic recurrences after hepatectomy, the efficacy of surgical treatment for pulmonary recurrence after hepatectomy has not been confirmed. Surgical resection of pulmonary recurrence after hepatectomy for colorectal metastases was reviewed retrospectively to evaluate the survival benefit. METHODOLOGY: From 1990 to 1995, 10 of the 17 patients with pulmonary recurrence after hepatectomy for colorectal metastases underwent surgical treatment. Ten patients underwent resection of pulmonary recurrence. RESULTS: Operative mortality was 0%, and a postoperative complication was observed in 1 patient after pulmonary metastasectomy. The overall 5-year survival rate after pulmonary metastasectomy was 10.0%, and the median survival was 21.7 (range: 2.4-77.9) months. One patient underwent resection two times for remnant lung recurrence after first lung metastasectomy, and is alive with no evidence of recurrence 77.9 months after the first pulmonary resection, and 50.7 months after the third pulmonary resection. In 3 patients with well-differentiated adenocarcinoma, the median survival time was 6.2 months (range: 2.4-9.7). The other hands, 7 patients with moderately differentiated adenocarcinoma have a longer median survival time of 29.2 months (range: 16.0-77.9). CONCLUSIONS: Pulmonary metastasectomy after hepatectomy for metastases from colorectal cancer is a safe treatment, and might offer prolonged survival for highly selected patients.     

Peventive treatments for recurrence after curative resection of hepatocellular carcinoma - A literature review of randomized control trials

To review the inhibitory effect of preventive approaches on recurrence after operation in patients with hepatocellular carcinoma (HCC), we summarized all available publications reporting randomized control trial indexed in PubMed. The treatment approaches presented above included preoperative transcatheter arterial chemoembolization (TACE),post-operative TACE, systemic or locoregional chemotherapy,immunotherapy, Interferons and acyclic retinoic acid.Although no standard treatment has been established,several approaches presented promising results, which were both effective and tolerable in post-operative patients. Preoperative TACF was not effective on prolonging survivals,while post-operative TACE was shown with both diseasefree survival and overall survival benefits in some papers,however, it was also questioned by others. Systemic chemotherapy was generally not effective on prolonging survival but also poorly tolerated for its significant toxicities.Adoptive immunotherapy using LAK cells was proved to be beneficial to patients′ survival in a recent paper. Interferon α and Interferon β can inhibit recurrence in HCC patients with HCV infection background, though the mechanism is not fully understood. Acyclic retinoic acid was shown to decrease multi-centric recurrence after operation, which was reported by only one group. In conclusion, several adjuvant approaches have been studied for their efficacy on recurrence in HCC patients in randomized control trials; however, multicentric randomized control trial is still needed for further evaluation on their efficacy and systemic or local toxicities;in addition, new adjuvant treatment should be investigated to provide more effective and tolerable methods for the patients with HCC after operation.     

Preventive treatments for recurrence after curative resection of hepatocellular carcinoma--a literature review of randomized control trials

To review the inhibitory effect of preventive approaches on recurrence after operation in patients with hepatocellular carcinoma (HCC), we summarized all available publications. reporting randomized control trial indexed in PubMed. The treatment approaches presented above included preoperative transcatheter arterial chemoembolization (TACE),post-operative TACE, systemic or locoregional chemotherapy,immunotherapy, Interferons and acyclic retinoic acid Although no standard treatment has been established,several approaches presented promising results, which were both effective and tolerable in post-operative patients. Preoperative TACE was not effective on prolonging survivals,while post-operative TACE was shown with both diseasefree survival and overall survival benefits in some papers,however, it was also questioned by others. Systemic chemotherapy was generally not effective on prolonging survival but also poorly tolerated for its significant toxicities.Adoptive immunotherapy using LAK cells was proved to be beneficial to patients‘ survival in a recent paper. Interferon and Interferon β can inhibit recurrence in HCC patients with HCV infection background, though the mechanism is not fully understood. Acyclic retinoic acid was shown to decrease multi-centric recurrence after operation, which was reported by only one group. In conclusion, several adjuvant approaches have been studied for their efficacy on recurrence in HCC patients in randomized control trials; however, multi-centric randomized control trial is still needed for further evaluation on their efficacy and systemic or local toxicities;in addition, new adjuvant treatment should be investigated to provide more effective and tolerable methods for the patients with HCC after operation.     

Surgical management of recurrence after resection of colorectal liver metastases

The optimal treatment for recurrent lesions after hepatectomy for colorectal liver metastases is controversial. We report the outcome of aggressive surgery for recurrent disease after the initial hepatectomy and the influence on quality of life of such treatment. Forty-five (70%) of the 64 surviving patients developed recurrence after the initial hepatectomy for liver metastases. The determinants of hepatic recurrence were the distribution and the number of liver metastases. Twenty-eight (62%) of patients with recurrence underwent resection. A second hepatectomy was performed in 20 patients, and a third hepatectomy was done in 5 patients. Ten patients with pulmonary metastasis underwent partial lung resection on 14 occasions, while resection of brain metastases was performed in 3 patients on 5 occasions. There were no operative deaths after resection of recurrent disease. The morbidity rate was 28% after repeat hepatectomy, 21% after pulmonary resection, and 0% after resection of brain metastasis. The Karnofsky performance status (PS) after the last surgery was not significantly different from that after the initial hepatectomy. The 3- and 5-year survival rates after the second hepatectomy were 54% and 14%, respectively. The 3-and 5-year survival rates of the patients undergoing resection of extrahepatic recurrence were both 17%. The survival rate after resection of recurrent disease (n=28) was significantly better than that of patients (n=17) with unresectable recurrence (P < 0.05). For the 66 patients with colorectal liver metastases, the 5-year survival rate after initial hepatectomy was 50%. The distribution and the number of liver metastases and the presence of extrahepatic disease, as single factors, significantly affected prognosis after the initial hepatectomy. Multivariate analysis revealed that only the presence of extrahepatic metastasis and a disease-free interval of less than 6 months were independent predictors of survival after the initial and second hepatectomy, respectively. It is concluded that aggressive surgery is an effective strategy for selected patients with recurrence after initial hepatectomy. Careful selection of candidates for repeat surgery will yield increased clinical benefit, including long-term survival.     

Intraperitoneal chemotherapy and cytoreductive surgery for peritoneal metastases coupled with curative treatment of colorectal liver metastases: an updated systematic review

Introduction: We aimed to assess the efficacy and safety of delivering intraperitoneal chemotherapy and cytoreductive surgery for peritoneal metastases coupled with curative treatment of colorectal liver metastases.

Areas covered: A comprehensive literature search using PubMed was conducted to screen for eligible records. Studies evaluating colorectal surgery and intraperitoneal chemotherapy combined with curative treatment of liver metastases were included. We excluded duplicate publications. Sixty-seven full-text papers were assessed and six papers were finally included. The overall survival in the included studies ranged from 6–49 months. Five-year survival ranged from 18%-28%, three-year survival ranged from 22%-42% and two-year survival ranged from 34%-78%. Survival was lower in patients with liver metastases and peritoneal carcinomatosis (PC) than those with PC alone in the majority of studies.

Expert commentary: This review poses questions rather than presenting answers. The heterogeneity of survival data suggests the possible benefit of this aggressive treatment approach in selected patients. Standardization of the technique used for intraperitoneal chemotherapy instillation, agent used as well as the systemic chemotherapy and targeted therapy type and duration through prospective controlled trials is required to provide an evidence of a higher strength to support or prohibit this treatment strategy.     

Evaluation of prognostic factors on recurrence after curative resections for hepatocellular carcinoma

AIM:To select appropriate patients before surgical resection for hepatocellular carcinoma(HCC),especially those with advanced tumors.METHODS:From January 2000 to December 2012,we retrospectively analyzed the medical records of 298 patients who had undergone surgical resections for HCC with curative intent at our hospital.We evaluated preoperative prognostic factors associated with histologic grade of tumor,recurrence and survival,especially the findings of pre-operative imaging studies such as positron emission tomography-computed tomography(PETCT)and magnetic resonance imaging(MRI).And then,we established a scoring system to predict recurrence and survival after surgery dividing the patients into two groups based on a tumor size of 5 cm.RESULTS:Of the 298 patients,129(43.3%)developed recurrence during the follow-up period.The 5 year disease free survival and overall survival were 47.0%and58.7%respectively.In multivariate analysis,a serum alpha-fetoprotein(AFP)level of>100 ng/m L and a standardized uptake value(SUV)of PET-CT of>3.5 were predictive factors for histologic grade of tumor,recurrence,and survival.Tumor size of>5 cm and a relative enhancement ratio(RER)calculated from preoperative MRI were also significantly associated with prognosis in univariate analysis.We established a scoring system to predict prognosis using AFP,SUV,and RER.In those with tumors of>5 cm,it showed predicted both recurrence(P=0.005)and survival(P=0.001).CONCLUSION:The AFP,tumor size,SUV and RER are useful for prognosis preoperatively.An accurate prediction of prognosis is possible using our scoring system in large size tumors.     

中医药治疗急性胰腺炎临床试验的质量评价

目的评价中医药治疗AP的临床随机对照试验的方法学质量。方法通过计算机检索获得1995年～2004年发表的有关中医药治疗AP的临床随机对照试验文献，按照随机对照试验设计质量评价标准和循证医学原则对文献的方法学质量进行评价。结果中医药治疗AP的临床随机对照试验共94篇，分布在61种杂志上。其中8篇有明确的纳入标准，12篇有明确的排除标准，33篇单组样本量大于50例，4篇对不良反应进行了描述，2篇提及随访。结论中医药治疗AP的临床随机对照试验的方法学质量尚低，还不能为临床应用提供可靠的依据。