Biomarkers Predict Outcomes Following Cytoreductive Surgery for Hepatic Metastases from Functional Carcinoid Tumors

BACKGROUND: Cytoreductive therapy for metastatic carcinoid provides symptomatic relief and improvement in overall survival. We evaluated whether CgA and 5HIAA could predict symptomatic relief and control of disease progression after cytoreductive surgery. METHODS: We retrospectively reviewed 70 patients who underwent cytoreductive surgery for neuroendocrine hepatic metastases between 1996 and 2005. Twenty-two patients had pre and post-operative CgA and/or 5HIAA levels measured. Reduction of biomarkers following cytoreduction was correlated with patient symptoms and progression of disease following surgery. RESULTS: Our study consisted of 14 males and 8 females with a mean age of 55 (+/-12 years). Median follow-up was 18 months (range 5-64 months). Six patients (26.1%) had complete (R0) cytoreduction, while 4 (17.4%) and 13 (56.5%) had microscopic (R1) and gross (R2) disease remaining. All patients reported improvements in their symptoms, with 12 (54.5%) reporting complete resolution (CR) and 10 (45.5%) reporting partial resolution (PR). Reduction of CgA of >or= 80% was highly predictive of complete resolution of symptoms (P = 0.007) and stabilization of disease (P = 0.034). Reduction of 5HIAA levels of >or= 80% (or normalization) was predictive of symptomatic relief, but not progression of disease (P = 0.026 and P = 0.725). Five of six patients who had R0 resections had CR and were free of disease at last follow-up (median 24.5 months, range: 11-48, P = 0.002). CONCLUSIONS: We conclude that >or= 80% reduction in CgA level following cytoreductive surgery for carcinoid tumors is predictive of subsequent symptom relief and disease control. Substantial reduction in CgA is associated with improved patient outcomes, even after incomplete cytoreduction.     

Results of Preoperative Hepatic Arterial Infusion Chemotherapy in Patients Undergoing Liver Resection for Colorectal Liver Metastases

Background Although hepatic artery infusion chemotherapy (HAIC) of floxuridine (FUDR) for colorectal liver metastases (CLM) can produce high response rates, data concerning preoperative HAIC are scarce. The aim of this study was to assess the feasibility and results of liver resection after preoperative HAIC with FUDR. Methods Between 1995 and 2004, 239 patients with isolated CLM received HAIC in our institution. Fifty of these patients underwent subsequent curative liver resection (HAIC group). Short- and long-term results of the HAIC group were compared with the outcomes of 50 patients who underwent liver resection for CLM without preoperative chemotherapy. Results Postoperative morbidity rate were comparable between the two groups. Overall disease-free survival at 1 and 3 years after hepatectomy were 77.5% and 57.5% in the HAIC group and 62.9% and 37% in the control group (P = .036). Overall survival from diagnosis of CLM at 1, 3, and 5 years were 97%, 59%, and 49% in the HAIC group versus 94%, 48%, and 35% in the control group (P = .097). When patients were stratified according to clinical-risk scoring (CRS) system, patients with more advanced disease at the time of liver resection (CRS ≥3) had a median survival of 41 months in the HAIC group (n = 37) and 35 months in the control group (n = 34) (P = .031). Conclusions HAIC of FUDR does not negatively affect the outcome of subsequent liver resection. Preoperative HAIC of FUDR may reduce liver recurrence rate and improve long-term survival in patients with more advanced liver disease. Part of this article was presented at the International Hepato-Pancreato-Biliary Association, 7th World Congress in Edinburgh, Scotland, September 3–7, 2006.     

Transarterial Chemoembolization vs Radioembolization for Neuroendocrine Liver Metastases: A Multi-Institutional Analysis

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Transarterial chemoembolization (TACE) in the management of hepatocellular carcinoma: Results of a French national survey on current practices

Purpose

To report current practices of transarterial chemoembolization (TACE) by interventional radiologists (IR) for hepatocellular carcinoma (HCC) through a French national survey.

Long-Term Results of Hepatectomy After Hepatic Arterial Infusion Chemotherapy for Initially Unresectable Hepatic Colorectal Metastases

Background  The prognosis of unresectable hepatic colorectal metastases is poor even if chemotherapy is administered. The purpose of this study was to evaluate the long-term efficacy of hepatic arterial infusion (HAI) chemotherapy and hepatectomy following HAI for such condition. Methods  Seventy-two patients with unresectable hepatic colorectal metastases received continuous HAI of 5-fluorouracil. Results  The overall response rate was 38%. The median survival of all patients was 18 months. The overall 3-year survival rate was 18%. Seven patients (10%) survived more than 58 months. Of the eight patients with a complete response, seven developed liver and/or lung metastases, and of these, one patient undergoing additional hepatectomy has been disease-free and the other six receiving chemotherapy died of disease. Another complete-response case died of liver abscess. Of the 19 patients with a partial response, six could undergo hepatectomy after HAI. The overall 5-year survival rate of seven patients undergoing hepatectomy was 71%, whereas for patients without hepatectomy, the rate was 0%. Conclusions  Most patients showing response after HAI for unresectable hepatic colorectal metastases had relapses. The long-term prognosis of patients undergoing hepatectomy after HAI was favorable. Therefore, when HAI makes liver metastases resectable, they should be resected.     

Treatment of Unresectable Cholangiocarcinoma with Gemcitabine-Based Transcatheter Arterial Chemoembolization (TACE): A Single-Institution Experience

Background Survival for patients with unresectable cholangiocarcinoma is reported to range from only 5–8 months without treatment. Systemic chemotherapy has not been shown to significantly improve survival, but newer regimens involving gemcitabine have shown increased response rates. Transcatheter arterial chemoembolization (TACE) has been shown to prolong survival in hepatocellular carcinoma patients, but experience using TACE in the treatment of cholangiocarcinoma is limited. We report our experience treating cholangiocarcinoma with TACE using chemotherapeutic regimens based on the well-tolerated drug gemcitabine. Methods Forty-two patients with unresectable cholangiocarcinoma were treated with one or more cycles of gemcitabine-based TACE at our institution. Chemotherapy regimens used for TACE included: gemcitabine only (n = 18), gemcitabine followed by cisplatin (n = 2), gemcitabine followed by oxaliplatin (n = 4), gemcitabine and cisplatin in combination (n = 14), and gemcitabine and cisplatin followed by oxaliplatin (n = 4). Results Patients were 59 years of age (range 36–86) and received a median of 3.5 TACE treatments (range 1–16). Thirty-seven patients (88%) had central cholangiocarcinoma, and five (12%) had peripheral tumors. Nineteen patients (45%) had extrahepatic disease. Grade 3 adverse events (AEs) after TACE treatments were seen in five patients, whereas grade 4 AEs occurred in two patients. No patients died within 30 days of TACE. Median survival from time of first treatment was 9.1 months overall. Results did not vary by patient age, sex, size of largest initial tumor, or by the presence of extra-hepatic disease. Treatment with gemcitabine–cisplatin combination TACE resulted in significantly longer survival (13.8 months) compared to TACE with gemcitabine alone (6.3 months). Conclusions Our report represents the largest series to date regarding hepatic-artery-directed therapy for unresectable cholangiocarcinoma and provides evidence in favor of TACE as a promising treatment modality in unresectable cholangiocarcinoma. Our results suggest that gemcitabine-based TACE is well tolerated and confers better survival when given in combination therapy (with cisplatin or oxaliplatin) for patients with unresectable cholangiocarcinoma. Presented at the 2007 American Hepato-Pancreato-Biliary Association, Las Vegas, Nevada, April 19–22, 2007 (President’s Plenary Oral Presentation).     

Recurrence and Survival Outcomes after Hepatic Resection with or without Cryotherapy for Liver Metastases from Colorectal Carcinoma

Background Some reports support resection combined with cryotherapy for patients with multiple bilobar colorectal liver metastases (CRLM) that would otherwise be ineligible for curative treatments. This series demonstrates long-term results of 415 patients with CRLM who underwent resection with or without cryotherapy. Methods Between April 1990 and January 2006, 291 patients were treated with resection only and 124 patients with combined resection and cryotherapy. Recurrence and survival outcomes were compared. Kaplan-Meier and Cox-regression analyses were used to identify significant prognostic indicators for survival. Results Median length of follow-up was 25 months (range 1–124 months). The 30-day perioperative mortality rate was 3.1%. Overall median survival was 32 months (range 1–124 months), with 1-, 3- and 5-year survival values of 85%, 45% and 29%, respectively. The overall recurrence rates were 66% and 78% for resection and resection/cryotherapy groups, respectively. For the resection group, the median survival was 34 months, with 1-, 3- and 5- year survival values of 88%, 47% and 32%, respectively. The median survival for the resection/cryotherapy group was 29 months, with 1-, 3- and 5-year survival values of 84%, 43% and 24%, respectively (P = 0.206). Five factors were independently associated with an improved survival: absence of extrahepatic disease at diagnosis, well- or moderately-differentiated colorectal cancer, largest lesion size being 4 cm or less, a postoperative CEA of 5 ng/ml or less and absence of liver recurrence. Conclusions Long-term survival results of resection combined with cryotherapy for multiple bilobar CRLM are comparable to that of resection alone in selected patients.     

Repeat Pulmonary Resection for Isolated Recurrent Lung Metastases Yields Results Comparable to Those after First Pulmonary Resection in Colorectal Cancer

Pulmonary resection for colorectal metastases is well accepted. However, the main cause of death after pulmonary resection is recurrence in the lung. The aim of this study was to clarify whether a repeat pulmonary resection was warranted in patients with recurrent lung metastases. The records of 76 patients undergoing initial pulmonary resection, including 14 patients undergoing a repeat operation for lung metastases, were reviewed for survival, operative morbidity, and mortality. Overall, pulmonary resection was performed 96 times in this group of patients. The operative mortality was 0%, morbidity involved only one case of major postoperative hemorrhage associated with the first operation. The cumulative 5-year survival rate for the 76 patients was 32%. After the second pulmonary operation, recurrence was identified in 79% (11 of 14) of the patients. In 10 patients with isolated lung recurrence after a first pulmonary resection, who showed no extrapulmonary disease before or at the time of first thoracotomy, the 3-year, and 5-year-survival rate after the second pulmonary resection was 67%, and 33%, respectively, comparing favorably with the survival rate in those who underwent primary pulmonary resection. In contrast, all 4 patients with extrapulmonary disease before or at the time of thoracotomy had poor prognosis. Repeat pulmonary operation for isolated recurrent colorectal metastases to the lung yielded results comparable to those after the first pulmonary resection in terms of operative mortality and survival in the absence of hilar/mediastinal lymph node or extrathoracic involvement.     

Evaluation of Treatment for Synchronous Hepatic Metastases from Gastric Cancer with Special Reference to Long-Term Survivors

Abstract. Purpose: The purpose of this study was to determine the most effective means of treating liver metastases from gastric cancer. Methods: We retrospectively examined 43 patients with liver metastases, but without peritoneal dissemination, who had received different forms of treatment. Results: The crude 5-year survival rates of patients who underwent gastrectomy with complete hepatectomy (curative gastrectomy), noncurative gastrectomy, and no gastrectomy were 33.3%, 3.7%, and 0%, respectively. The curative gastrectomy group showed the highest survival rate (not significant). The median survival of patients given hepatic artery infusion (HAI), systemic chemotherapy, and no chemotherapy were 353, 189, and 61 days, respectively. The patients given chemotherapy survived significantly longer than those not given chemotherapy. Three patients survived for more than 5 years without any signs of recurrence. The long-term survivors all had primary lesions without serosal invasion (T2) and no other noncurative factors. Two patients underwent curative gastrectomy and one underwent noncurative gastrectomy. All were given postoperative chemotherapy; as HAI in two cases, and as systemic chemotherapy in one case. Conclusion: These findings suggest that curative gastrectomy combined with HAI or systemic chemotherapy should be attempted for patients with primary tumors without serosal invasion or any other noncurative factors. Received: July 13, 2001 / Accepted: January 8, 2002     

Carcinoid of the Rectum Risk Stratification (CaRRs): A Strategy for Preoperative Outcome Assessment

Background Predicting rectal carcinoid behavior based exclusively on tumor size is imprecise. We sought to identify factors associated with outcome and incorporate them into a pre-operative risk stratification scheme. Methods Seventy rectal carcinoid patients evaluated at our institution were identified. Demographic, clinical, and histopathologic data were collected and correlated with recurrence and survival. Results The mean age of our cohort was 53.6 years. Fifty-seven percent of patients were female. The mean tumor size was 1.3 cm (range: 0.1–5 cm). Twenty-five percent of patients had deeply invasive tumors (into the muscularis propria or deeper); an equal percentage had tumors with lymphovascular invasion (LVI) or an elevated mitotic rate (≥2/50 HPF). Eleven patients (17%) had distant metastases at presentation. Sixty-one patients were followed for a median of 22 months (2–308 months), during which seven patients developed recurrence and seven died of disease (2/7 who developed recurrence). Poor outcome was associated with large tumor size, deep invasion, presence of LVI, and elevated mitotic rate. These factors were incorporated into a carcinoid of the rectum risk stratification (CaRRS) score. CaRRS predicted recurrence-free and disease-specific survival better than any single factor alone. Conclusions Poor prognostic features of rectal carcinoids include: large size, deep invasion, LVI, and elevated mitotic rate. The CaRRS score incorporates these features and accurately predicts outcome. Because the CaRRS score is based upon values available on pre-operative biopsy, it can identify patients with very favorable prognosis as well as those with poor prognosis that may benefit from additional staging or surveillance.     

Carcinoid of the Rectum Risk Stratification (CaRRS): A Strategy for Preoperative Outcome Assessment

Background Predicting rectal carcinoid behavior exclusively on the basis of tumor size is imprecise. We sought to identify factors associated with outcome and incorporate them into a preoperative risk stratification scheme. Methods Seventy patients with rectal carcinoid evaluated at our institution were identified. Demographic, clinical, and histopathologic data were collected and correlated with recurrence and survival. Results The mean age of our cohort was 53.6 years. Fifty-seven percent of patients were women. The mean tumor size was 1.3 cm (range, .1–5 cm). Twenty-five percent of patients had deeply invasive tumors (into the muscularis propria or deeper); an equal percentage had tumors with lymphovascular invasion (LVI) or an increased mitotic rate (two or more mitoses per 50 high-power fields). Eleven patients (17%) had distant metastases at presentation. Sixty-one patients were followed for a median of 22 months (range, 2–308 months), during which seven patients developed recurrence and seven died of disease (including two of seven whose disease recurred). Poor outcome was associated with large tumor size, deep invasion, presence of LVI, and increased mitotic rate. These factors were incorporated into a Carcinoid of the Rectum Risk Stratification (CaRRS) score. CaRRS predicted recurrence-free and disease-specific survival better than any single factor alone. Conclusions Poor prognostic features of rectal carcinoids include large size, deep invasion, LVI, and increased mitotic rate. The CaRRS score incorporates these features and accurately predicts outcome. Because the CaRRS score is based on values available by preoperative biopsy, it can identify patients with favorable prognosis and those with poor prognosis who may benefit from additional staging or surveillance.     

A Decision Analysis Model Identifies the Interval of Efficacy for Transarterial Chemoembolization (TACE) in Cirrhotic Patients with Hepatocellular Carcinoma Awaiting Liver Transplantation

Introduction For liver transplant candidates with hepatocellular carcinoma (HCC), the ability of neoadjuvant transarterial chemoembolization (TACE) to improve outcomes remains unproven. The objective of our study was to determine if there was a specific time interval where neoadjuvant TACE would decrease the number of HCC patients removed from the pretransplant waitlist. Materials and Methods A decision model was developed to simulate a randomized trial of neoadjuvant treatment with TACE vs. no TACE in 600 virtual patients with HCC and cirrhosis. Transition probabilities for TACE morbidity (1 ± 1%), TACE response rates (30 ± 20%), and disease progression (7 ± 7% per month) were assigned by systematic review of the literature (18 reports). Sensitivity analyses were performed to determine time thresholds where TACE would decrease the number of delisted patients. Results TACE treatment had statistical benefit at waitlist time breakpoints of 4 and 9 months (P < 0.05). When waitlist times were less than 4 months, waitlist attrition was similar (20% vs. 34%, P = 0.08). When waitlist times exceed 9 months, waitlist dropout rates re-equilibrated (33% vs. 46%, P = 0.06). Review of the current literature determined that only those studies reporting on patients with waitlist times between 4 and 9 months found a benefit to neoadjuvant TACE. Conclusions This analysis indicates that the benefit of neoadjuvant TACE may be limited to those patients transplanted from 4 to 9 months from first TACE. These data may help transplant programs to tailor TACE treatments based on predicted waitlist times to achieve optimal resource utilization and improved organ allocation efficiency. Presented at the 7th World Congress of the International Hepato Pancreato Biliary Association Meeting, September 6, 2006, Edinburgh, Scotland.     

中国结直肠癌肝转移诊断和综合治疗指南（2020版）

第一部分诊疗指南肝脏是结直肠癌血行转移最主要的靶器官,结直肠癌肝转移是结直肠癌治疗的重点和难点之一。15%~25%结直肠癌病人在确诊时即合并有肝转移,而另有15%~25%的病人在结直肠癌原发灶根治术后发生肝转移,其中绝大多数(80%~90%)的肝转移灶初始无法获得根治性切除。肝转移也是结直肠癌病人最主要的死亡原因,未经治疗的肝转移病人的中位生存期仅6.9个月,无法切除病人的5年生存率<5%,而肝转移灶能完全切除[或可以达到无疾病证据(no evidence of disease,NED)状态]病人的中位生存期为35个月,5年生存率可达30%~57%。     

Outcome After Hepatectomy for Multiple (Four or More) Colorectal Metastases in the Era of Effective Chemotherapy

Background Hepatic resection is generally accepted as the only potential for long-term survival in patients with colorectal metastases confined to the liver. Despite an unknown benefit, hepatic resection is playing an increasing role in patients with extensive disease. Methods A retrospective review of a prospectively maintained hepatobiliary surgical database was carried out. Outcome after hepatectomy for four or more colorectal hepatic metastases was reviewed. Results Between 1998 and 2002, out of a total of 584 patients, 98 (17%) with four or more colorectal hepatic metastases were resected. Actuarial 5-year survival was 33% for the entire group, with seven actual 5-year survivors. There were no perioperative deaths, and the perioperative morbidity was 28%. Positive margins and extrahepatic disease resection were independently associated with poor outcome. The median disease-free survival was 12 months, with no actuarial disease-free survivors at 5 years. Recurrence pattern, response to neoadjuvant chemotherapy, time to recurrence, and resection of recurrent disease were also associated with outcome. Conclusions Long-term survival can be achieved after resection of multiple colorectal metastases; however, because most patients will experience recurrence of disease, effective adjuvant therapy and close follow-up is necessary.     

合并肝硬化中晚期肝癌TACE治疗后血清AFP检测的意义

目的 探讨合并肝硬化的中晚期肝癌患者血清AFP水平对经肝动脉化疗栓塞术（TACE）治疗预后的意义.方法 收集250例TACE术后的中晚期肝癌合并肝硬化患者的血清,采用放射免疫法测定患者血清AFP的水平.将测定的结果分成AFP升高组（＞20 μg/L,n＝165）例和正常组（＜20 μg/L,n＝85）,并对肝癌患者进行随访（1周～65个月,中位时间21.5个月）.用Kaplan-Meier生存曲线分析患者生存率,评估AFP水平及相关因素对中晚期肝癌患者预后的意义.结果 AFP升高组的1、2、5年生存率为57%、48%、5.1%,AFP正常组为37%、46%、12%.AFP升高组的1年生存率明显高于AFP正常组（P＜0.05）,AFP升高组5年生存率明显低于AFP正常组（P＜0.05）.结论 对于中晚期肝癌的患者,血清AFP水平高者较血清AFP水平低者短期预后好,但远期预后差.     

Hepatic Intra-Arterial Injection of Drug-Eluting Bead, Irinotecan (DEBIRI) in Unresectable Colorectal Liver Metastases Refractory to Systemic Chemotherapy: Results of Multi-Institutional Study

Introduction

Response rates and overall outcome for patients who have failed first-line and in some cases second-line chemotherapy are as low as 12% and 7 months, respectively. The aim of this study is to evaluate the efficacy of hepatic arterial sulfonate hydrogel microsphere (drug-eluting beads), irinotecan preloaded therapy (DEBIRI) in metastatic colorectal cancer refractory to systemic chemotherapy.

Methods

This was a multicenter multinational single-arm study of metastatic colorectal cancer patients who received DEBIRI after failing systemic chemotherapy from 10/2006 to 8/2008. Primary endpoints were safety, tolerance, tumor response rates, and overall survival.

Results

Fifty-five patients who had received prior systemic chemotherapy and who underwent a total of 99 DEBIRI treatments were reviewed. The median number of DEBIRI treatments was 2 (range 1–5), median treatment dose was 100 mg (range 100–200 mg), with total hepatic treatment of 200 mg (range 200–650 mg), with 86% of treatments performed as lobar infusion and 30% of patients treated with concurrent simultaneous chemotherapy. Adverse events occurred in 28% of patients with median grade of 2 (range 1–3) with no deaths at 30 days post procedure. Response rates were 66% at 6 months and 75% at 12 months. Overall survival in these patients was 19 months, with progression-free survival of 11 months.

Conclusions

Hepatic arterial drug-eluting bead, irinotecan (DEBIRI) was safe and effective in treatment of metastatic colorectal cancer (MCC) refractory to multiple lines of systemic chemotherapy. DEBIRI is an acceptable therapy for treatment of metastatic colorectal cancer to the liver.     

Photodynamic Therapy With 5,10,15,20-Tetrakis(<Emphasis Type="Italic">m</Emphasis>-Hydroxyphenyl) Bacteriochlorin for Colorectal Liver Metastases Is Safe and Feasible: Results From a Phase I Study

Background

The prognosis for patients with liver metastases from colorectal carcinoma is limited because of the low number of patients who are eligible for curative hepatic resection. In this phase I study, 31 liver metastases in 24 patients with nonresectable metastases from colorectal carcinoma were treated with photodynamic therapy (PDT).

Methods

The photosensitizer 5,10,15,20-tetrakis(m-hydroxyphenyl)bacteriochlorin (mTHPBC) was intravenously administered in a dose of .6 mg/kg (n = 12) or .3 mg/kg (n = 12). After 120 hours (n = 18) or 48 hours (n = 6), tumors were illuminated for 300 to 600 seconds through percutaneously inserted optical fibers with a light dose of 60 J/cm of diffuser (740 nm).

Results

Tumor necrosis at 1 month after PDT was achieved in all treated lesions. Laser treatment was associated with mild pain (n = 8) and transient subclinical hepatotoxicity (n = 21). In one patient, PDT damage to the pancreas was inflicted, and in another patient, PDT damage of the skin occurred, but no serious clinical complications from PDT were reported. Administration of .6 mg/kg of mTHPBC led to transient phlebitis in 10 patients, and 3 patients experienced mild skin phototoxicity after excess light exposure.

Conclusions

Colorectal liver metastases that are ineligible for resection can be safely and effectively treated with interstitial mTHPBC-based PDT.

     

Human telomerase reverse transcriptase (hTERT) and Ki-67 are better predictors of survival than established clinical indicators in patients undergoing curative hepatic resection for colorectal metastases

BACKGROUND: We evaluated hTERT and Ki-67 expression in patients who underwent curative resection of hepatic colorectal metastases to determine if these markers of cell proliferation correlated better with survival than an established scoring system that is based on clinical predictors. METHODS: Patients operated on between 1993 and 1997 whose survival time was known were analyzed. For each patient, the clinical prognostic score was derived on the basis of primary node status, disease-free interval, number of hepatic tumors, largest tumor, and carcinoembryonic antigen level, and tumor specimens were analyzed for Ki-67 and hTERT with use of standard immunohistochemical techniques. The immunohistochemical analysis was blinded to all patient characteristics. RESULTS: The study included 66 patients. Twenty-six survived less than 2 years after surgery, 19 survived 2-5 years, and 21 survived more than 5 years. Ki-67 positivity and hTERT positivity (labeling indexes greater than or equal to 50%) were observed in 24 patients and 23 patients, respectively. The clinical score did not predict survival, although there was a weak trend toward a lower score in patients with better survival. Both Ki-67 (P =.04) and hTERT (P =.0001) correlated better with survival than did the clinical score. CONCLUSIONS: In patients undergoing curative resection of hepatic colorectal metastases, hTERT and Ki-67 are better predictors of survival than is a score based on clinical features.