Liver Resection for Non-Colorectal,Non-Carcinoid,Non-Sarcoma Metastases: A Multicenter Study

Background

The role of liver resection for non-colorectal, non-neuroendocrine, non-sarcoma (NCNNNS) metastases is ill-defined. This study aimed to examine the oncologic outcomes of liver resection in such patients.

Methods

A retrospective analysis of liver resection for NCNNNS metastases was performed at two large centers. Liver resection was offered selectively in patients with stable disease. Oncologic outcomes were examined using the Kaplan-Meier method.

Results

Fifty-two patients underwent liver resection for NCNNNS metastases. Overall 5-year survival was 58%. Five-year survival was 85% for breast metastases, 66% for ocular melanoma, 83% for other melanomas, 50% for gastro-esophageal metastases, and 0% for renal cell carcinoma metastases. A contemporary colorectal liver metastasis cohort had a survival of 63% (p=0.89).

Conclusions

Liver resection is an effective option in the management of selected patients with NCNNNS metastases which have been deemed stable. Five-year survival rates were comparable to that of a contemporary cohort of patients with colorectal liver metastases in carefully selected patients. Further, larger studies are required to help identify potential prognostic variables and aid in decision-making in this heterogeneous population.     

吉西他滨联合奥沙利铂经肝动脉化疗栓塞对肝癌术后复发的预防作用探究

目的：探讨吉西他滨联合奥沙利铂经肝动脉化疗栓塞对肝癌术后复发的预防作用及其疗效分析。方法：回顾性分析2006年1月～2011年10月我院收治入院的97例晚期原发性肝癌患者的临床资料,将患者随机分为观察组（48例）和对照组（49例）,观察组采用吉西他滨联合奥沙利铂,对照组采用阿霉素灌注进行肝动脉化疗栓塞治疗,观察两组不同患者对肝癌术后复发的预防作用及其临床疗效。结果：两组患者疾病控制率及1年、2年的生存率比较上差异有统计学意义（P〈0.05）。结论：在肝癌治疗中给予吉西他滨联合奥沙利铂经肝动脉化疗栓塞治疗,疗效确切,不良反应较轻,耐受性好,帮助患者改善生活质量,是晚期原发性肝癌的有效治疗方案。     

Safety of simultaneous resections of colorectal cancer and liver metastases

Liver resection is the only potentially curative method for patients with colorectal cancer metastases and 5-year survival rates are 20%-40%. Simultaneous resection of colorectal cancer and synchronous liver metastases has been recommended if minor hepatectomy is indicated. The purpose of this paper is to analyze the treatment of hepatic colorectal secondaries and to assess the safety of simultaneous and delayed liver resections and relations of morbidity to the extensiveness of hepatectomy and perioperative factors. Analyzed were 21 patients with liver metastases from colorectal cancer operated between 1997 and 1999 in the Clinical Hospital "Sestre milosrdnice". Operating time for simultaneous colorectal and liver resections was not significantly longer compared to liver resections alone. No significant difference in complication rate was found after simultaneous procedures and liver resection alone (38% vs. 31%). Complication rate after major liver resections was not significantly greater than after minor resections (38% vs. 31%). No statistically significant differences were found in operation time and blood replacement between patients who developed postoperative complications and those who did not. In conclusion, simultaneous resections of primary colorectal cancer and liver metastases may be considered safe. Morbidity rates are not significantly different from those after liver resections alone, nor depend significantly upon the extensiveness of liver resection, providing that the operation time and blood loss are within the range observed in this study.     

Radiofrequency ablation as locoregional therapy for unresectable hepatic malignancies: initial results in 24 patients with 5-years follow-up

Radiofrequency ablation (RFA) is one treatment modality for unresectable liver metastases. Patients with hepatic malignancies (n = 24) underwent elective RFA. All tumors were ablated with a curative intent, with a margin of 1 cm, in a single session of RFA. The median diameter of tumor was 3.1 cm (range 1.7-6.9 cm). Studied patients were not candidates for resection due to multifocal hepatic disease, extrahepatic disease, proximity to major vascular structures or presence of cirrhosis with functional hepatic reserve inadequate to tolerate major hepatic resection. Complete tumor necrosis was achieved in 87.5% and tumor recurred in 3 patients (12.5%) with lesions larger than 5 cm. Distant intrahepatic recurrence was diagnosed in another 4 (16.7%). Distant metastases were found in 7 (29.2%) patients. Four of these 7 patients had also distant intrahepatic recurrence of disease. Two and 5-years survival rates were 41.7% (10 patients) and 8.3% (2 patients) respectively. RFA is safe and effective option for patients with unresectable hepatic malignancies smaller than 5 cm without distant metastatic disease. RF ablation resulted in complete tumor necrosis in 87.5% with 2 and 5-years survival rates much higher than with chemotherapy alone or only supportive therapy, when survival is measured in weeks or months. If RFA is unavailable, percutaneous ethanol injection therapy can be done but with inferior survival rates.     

Primary hepatic carcinoid tumor

Primary hepatic carcinoid tumor is rare and poses a challenge for diagnosis and management. We presented a case of primary hepatic carcinoid tumor in a 53-year-old female with a complaint of right upper abdominal pain. Computer tomography scans revealed a hypervascular mass in segment 4 of the liver. An ultrasonography-guided biopsy showed a carcinoid tumor. No other lesions were found by the radiological investigations. Surgery resection was performed and histopathological examination revealed a primary hepatic carcinoid tumor. Three years later, recurrence was found and transcatheter arterial chemoembolization was performed. After transcatheter arterial chemoembolization, the patient has been free of symptom and had no radiological disease progression for over 6 months. Surgical resection combination with transcatheter arterial chemoembolization is effective to offer excellent palliation.     

Oncolytic viral therapy for human colorectal cancer and liver metastases using a multi-mutated herpes simplex virus type-1 (G207).

G207 is a multi-mutated, replication-competent type-1 herpes simplex virus designed to target, infect, and lyse neurological tumors. This study examines the feasibility of using G207 in the treatment of human colorectal cancer and defines the biological determinants of its antitumor efficacy. This virus was tested on five human colorectal cancer cell lines in vitro to determine efficacy of infection and tumor cell kill. These results were correlated to measures of tumor cell proliferation. In vivo testing was performed through direct injections of G207 into xenografts of human colorectal cancer tumors grown in flanks of athymic rats. To evaluate an alternate method of administration, hepatic portal vein infusion of G207 was performed in a syngeneic model of liver metastases in Buffalo rats. Among the five cell lines tested, infection rates ranged between 10% and 90%, which correlated directly with S-phase fraction (8.6%-36.6%) and was proportional to response to G207 therapy in vitro (1%-93%). Direct injection of G207 into nude rat flank tumors suppressed tumor growth significantly vs. control (0.58 +/- 0.60 cm(3) vs. 9.16 +/- 3.70 cm(3), P<0. 0001). In vivo tumor suppression correlated with in vitro effect. In the syngeneic liver tumor model, portal infusion resulted in significant reduction in number of liver nodules (13 +/- 10 nodules in G207-treated livers vs. 80 +/- 30 nodules in control livers, P<0.05). G207 infects and kills human colorectal cancer cells efficiently. In vitro cytotoxicity assay and tumor S-phase fraction can be used to predict response to treatment in vivo. This antineoplastic agent can be delivered effectively by both direct tumor injection and regional vascular infusion. G207 should be investigated further as therapy for colorectal cancer and liver metastases.     

三氧化二砷栓塞联合肝动脉介入治疗转移性肝癌的疗效并33例临床观察

目的：观察并探讨三氧化二砷碘油栓塞联合置管介入化疗治疗转移性肝癌的临床效果。方法：选取辽宁省肿瘤医院介入治疗科2008-2010年收治的转移性肝癌患者33例,进行肝动脉造影及间接门脉造影,根据肝动脉造影或门脉造影结果,根据肝动脉供血情况分别采取肝动脉化疗栓塞及肝动脉灌注化疗方法治疗,3．4周为1治疗周期,共完成4个治疗周期,治疗结束后评价患者,陆床有效率,随访半年、1年、2年患者生存率。结果：①介入治疗后,患者,临床症状均改善,KPS得分明显高于化疗前（P〈0．05）,临床总有效率81．82％。②随访半年、1年、2年生存率分别为90．9l％、66．67％、33.33％,肝动脉化疗栓塞组患者中远期生存率明显高于肝动脉灌注化疗的患者。结论：三氧化二砷可从多角度抑制癌细胞,临床应用安全有效;对于不能手术和不适宜手术的转移性肝癌患者,根据肝动脉供血情况和特点选择合适的介入治疗,可获得满意疗效。     

Retrospective Analysis of 234 Nasopharyngeal Carcinoma Patients with Distant Metastasis at Initial Diagnosis: Therapeutic Approaches and Prognostic Factors

Purpose

The purpose of this retrospective study was to identify the independent prognostic factors and optimize the treatment for nasopharyngeal carcinoma (NPC) patients with distant metastasis at initial diagnosis.

Methods

A total of 234 patients referred between January 2001 and December 2010 were retrospectively analyzed. Among the 234 patients, 94 patients received chemotherapy alone (CT), and 140 patients received chemoradiotherapy (CRT). Clinical features, laboratory parameters and treatment modality were examined with univariate and multivariate analyses.

Results

The median overall survival (OS) time was 22 months (range, 2-125 months), and the 1-year, 2-year, 3-year overall survival rates were 82.2%, 51.3% and 34.1%. The overall response and disease control rates of metastatic lesions after chemotherapy were 56.0% and 89.8%. The factors associated with poor response were karnofsky performance score (KPS) <80, liver metastasis, lactate dehydrogenase (LDH)>245 IU/L, and number of chemotherapy cycles <4. The 3-year OS of patients receiving CRT was higher than those receiving CT alone (48.2% vs. 12.4%, p<0.001). Subgroup analysis showed that significantly improved survival was also achieved by radiotherapy of the primary tumor in patients who achieved complete remission (CR)/partial remission (PR) or stable disease (SD) of metastatic lesions after chemotherapy. Significant independent prognostic factors of OS were KPS, liver metastasis, levels of LDH, and multiple metastases. Treatment modality, response to chemotherapy and chemotherapy cycles were also associated with OS.

Conclusion

A combination of radiotherapy and chemotherapy seems to have survival benefits for selected patients with distant metastases at initial diagnosis. Clinical and laboratory characteristics can help to guide treatment selection. Prospective randomized studies are needed to confirm the result.     

伽玛刀联合肝动脉栓塞化疗治疗原发性肝癌的临床疗效观察

目的:研究伽玛刀联合肝动脉栓塞化疗治疗临床疗效,探索治疗原发性肝癌的最优方案。方法:选择2005年10月~2013年10月在我院伽玛刀室实施伽玛刀治疗的肝癌病例183例,随机分为对照组(n=88)和试验组(n=95),对照组患者采取单纯伽马刀治疗,试验组采用伽马刀联合肝动脉栓塞化疗。治疗后对全部患者进行随访3~24个月,复查肝功能、甲胎蛋白(AFP)等,追踪有无不良反应及并发症的出现,了解其近期与远期疗效。结果:治疗后3个月复查,对照组和试验组的总体有效率分别为60.5%和76.84%,两组近期疗效比较,差异具有统计学意义(P0.05)。两组治疗后肝功能及AFP改善情况,差异均具有统计学意义(P0.05)。两组患者在治疗期间及后均出现不同程度的不良反应,对照组放射诱导的肝病5例,试验组3例,经内科对症处理后,患者情况均好转。试验组在治疗后6、12、18、24个月的生存率均高于对照组,差异均存在统计学意义(P0.05)。结论:伽玛刀联合肝动脉栓塞化疗治疗原发性肝癌的临床疗效优于单纯伽马刀治疗,可进一步研究,进行临床推广。     

Long-term results of endovascular treatment of metastatic renal cell cancer

The authors analyse the long-term results of treatment of 106 patients with advanced renal cell carcinoma. The patients were divided in two groups. Group 1 (42 patients) included cases with single metastatic lesion. Patients of group 2 (n = 64) had more than one site of metastases. All patients were treated by nephrectomy, embolization with chemotherapeutic agent or arterial occlusion without cytostatic drug except nine patient of group 2, who has undergone chemo and hormonal therapy. The survival according to method at treatment was studies. After occlusion satisfactory results were obtained in cases with single metastasis lesion and also in cases with many sites of metastases. Oily chemoembolization in renal cell carcinoma with distant metastases has given better results as compared with the embolization without chemodrugs. We conclude that endovascular method of treatment is an alternative to the traditional nephrectomy in palliation of renal cell carcinoma.     

Role of liver scanning in the preoperative evaluation of patients with cancer

Liver scan characteristics and liver function tests of 72 patients with proved hepatic malignancy (54 metastatic, 18 primary) were evaluated. Well-defined focal defects were observed in 83% of patients with metastatic and 77% of patients with primary liver carcinoma. In 10% of the patients with metastatic liver disease the distribution of radioactivity was normal. Four or more biochemical liver function tests were normal in 33% of metastatic and 29% of primary liver cancer patients. Hepatic enlargement was present in the scan in 94% of the patients with liver metastases; however, data obtained from 104 necropsies of patients with hepatic metastases showed that only 46% had hepatomegaly. We recommend, therefore, that a liver scan should be performed before major tumour surgery in every patient with known malignancy regardless of normal liver size or normal liver function tests.     

肝动脉化疗栓塞联合索拉菲尼治疗中晚期肝细胞癌的临床疗效评估

目的:探讨中晚期肝细胞癌(HCC)采用肝动脉化疗栓塞联合索拉菲尼治疗的临床疗效。方法:按照随机数字表法将2012年3月-2014年3月我院收治的中晚期HCC患者分为两组,对照组行肝动脉化疗栓塞术治疗,观察组在对照组基础上联合索拉菲尼治疗。比较两组的疗效,毒副反应及远期生存率。结果:观察组患者治疗后6个月的临床疗效优于对照组,差异有统计学意义(Z=-2.316,P=0.021),观察组有效率52.50%,高于对照组的28.21%,差异有统计学意义(x2=4.837,P=0.028)。治疗后观察组手足皮肤反应和口腔黏膜炎症的发生率为22.50%、25.00%,分别高于对照组的5.13%、5.13%,差异有统计学意义(P0.05)。观察组6、12个月的生存率为95.00%、85.00%,分别高于对照组的79.49%、64.10%,差异有统计学意义(P0.05)。结论:肝动脉化疗栓塞联合索拉菲尼治疗HCC具有疗效好、明显延长患者生存时间的特点,临床有重要的参考价值。     

Conclusive diagnosis of hepatic and pancreatic malignancies by fine needle aspiration

A study of the diagnosis of hepatic and pancreatic malignancies by fine needle aspiration (FNA) was made, based on 221 aspirates obtained from 209 patients with histologic or clinical confirmation: 159 with hepatic and 50 with pancreatic lesions. The values of sensitivity, specificity and predictivity for positive FNA results were, respectively, 0.84, 0.96 and 1.0 for the liver and 0.76, 1.0 and 1.0 for the pancreas. The composition of the case material showed an incidence of malignant tumors of the liver and pancreas of 84% and 60%, respectively (among which the primary malignancies were 39% and 48%), while nonneoplastic lesions had incidences of 14% and 40%. However, conclusive FNA diagnoses of the histologic type of the primary and the site of origin of metastatic tumors were made in 60% of the hepatic lesions but in only 9% of the pancreatic lesions. Primary hepatocellular carcinoma was diagnosed by FNA of the liver in 95% of the cases; FNA specifically diagnosed 42% of intrahepatic bile duct carcinomas and 40% of hepatic metastases. These findings correlate with the unique cytologic features of primary hepatocellular carcinoma of intrahepatic rather nonspecific morphology of carcinoma of intrahepatic and extrahepatic origin, as well as of pancreatic ductal origin.     

Monitoring liver alterations during hepatic tumorigenesis by NMR profiling and pattern recognition

Human hepatocellular carcinoma (HCC) is the most recurrent malignancy of the liver and represents one of the main causes of cancer death worldwide. Furthermore, the liver is the most frequent site of metastatic colonization, and hepatic metastases are far more common than primary cancers in Western countries. A possible way of investigating liver diseases is to study the tissue metabolic profiles. High-resolution nuclear magnetic resonance (NMR) spectroscopy of hepatic tissue extracts was combined with pattern-recognition and visualization techniques to uncover metabolic differences among analyzed tissue types. Extracts were from primary HCC, chronic hepatitis-C-virus related cirrhotic tissues, hepatic metastases from colorectal carcinomas, and non-cirrhotic normal liver tissues adjacent to metastases as controls. We identified all metabolites present in the NMR spectra, and after statistical evaluation of all spectral classes, we were able to define the metabolic changes underlying the different liver conditions and diseases. In particular, the lactate and the glucose tissue signals were found to primarily discriminate the different histological samples. We followed the biochemical changes of human hepatic lesions through primary (HCC) and secondary (metastases from colorectal carcinoma) liver tumors, cirrhotic tissues, and non-cirrhotic histologically-confirmed normal liver tissues adjacent to metastases, achieving a metabolic differentiation of the various pathological states based upon the variation of the intracellular lactate/glucose ratio. It is suggested that such a signal pattern may act as a potential marker for assessing pathological hepatic lesions.     

CT-guided percutaneous cryoablation combined with systemic chemotherapy for liver metastases from esophageal carcinoma: Initial experience

ObjectiveTo explore the feasibility, safety and effectiveness of percutaneous cryoablation combined with systemic chemotherapy in the treatment of liver metastases from esophageal carcinoma (ECLM).Materials and methodsWe retrospectively collected data of 16 patients who received CT-guided percutaneous cryoablation concurrent systemic chemotherapy for liver metastases after primary esophageal carcinoma resection. Functional Assessment of Cancer Therapy-General (FACT-G) was used for the assessment of quality of life (QOL), and overall survival (OS), progression-free survival (PFS) and complications were also evaluated.ResultsThe technical success rate was 96%, and no major complications related to cryoablation procedure were detected. Median OS and PFS after cryoablation were 14.5 months (range, 4–51 months) and 7.5 months (range, 1–31 months), respectively. The 1-year, 2-year, and 3-year survival rates were 56.3%, 31.3%, and 18.8%, respectively. The PFS rate at 6-month, 1-year, and 2-year after procedure were 68.8%, 31.3% and 18.8%, respectively. Furthermore, the QOL of patients was improved after cryoablation therapy compared with preoperative scores (P < 0.05).ConclusionsPercutaneous cryoablation combined with systemic chemotherapy is a safe, feasible and effective method to treat liver metastases from esophageal carcinoma. And to a certain extent, this approach is very efficacious in improving the QOL of patients with ECLM.     

Cryoablation for liver tumors - is there clinical utility?

The large majority of liver tumors are metastatic, of which colorectal deposits are the most common. Resection is the preferable mode of treatment because it offers the possibility of prolonged survival, but this strategy is only viable in about 25% of patients. This is due to either the proximity of the disease to the portal structures or to the number of metastases. Other treatment options are therefore required for liver tumors, such as chemotherapy, radiofrequency ablation, laser photocoagulation, chemoembolization, and cryotherapy. This article focuses on cryotherapy as a method of treating unresectable hepatic tumors.     

Stereotactic body radiation therapy for liver metastases: Clinical outcomes and literature review

Background and aimThe role of stereotactic body radiation therapy (SBRT) in the management of liver metastasis is increasing, using ablative doses with the goal of local control and ultimately improving survival. The aim of this study is to evaluate our initial results regarding local control, overall survival and toxicity in patients with liver metastases treated with this technique, due to the lack of evidence reported in Latin America.Materials/methodsWe performed a retrospective chart review from November 2012 to June 2018 of 24 patients with 32 liver metastases. Kaplan–Meier curves were constructed for local control and overall survival. Clinical and prognostic factors were further analyzed by independent analysis. Median follow-up period was 22 months (range, 1–65 months).ResultsMedian age was 62 years (range, 40–84 years). Colorectal carcinoma was the most common primary cancer. Overall 1-year and 2-years local control rates were 82% (95% Confidence Interval [CI], 70–98%) and 76.2% (95% CI, 45–90%), respectively. Median overall survival rate was 35 months (95%, CI 20.5–48 months). Overall 1-year and 2-year survival rates were 85.83% (95% CI, 64–99%) and 68% (95% CI, 45–84%), respectively. No acute or late grade 3 or 4 toxicity was observed during the follow-up period.ConclusionsSBRT achieves excellent local control and overall survival rates with low toxicity in patients with liver metastases. Based on our literature review, our results are consistent with larger reports. Further randomized trials are required to compare with other local therapies.     

Carcinoembryonic antigen gene and carcinoembryonic antigen expression in the liver metastasis of colorectal carcinoma.

The presence of the carcinoembryonic antigen (CEA) gene and CEA expression in the liver was tested to identify their possible roles in the liver metastasis of colorectal carcinoma. The CEA gene in the liver was identified by amplifying the CEA-specific N-terminal domain exon with digoxigenin-dUTP labeling in 16 colorectal carcinomas with liver metastases. Next, CEA expression was tested by immunostaining using the anti-CEA monoclonal antibody (T84.66, ATCC). Liver tissues from 13 stomach cancer patients and 12 colorectal cancer patients without liver metastasis were also tested as control groups. Three grades (<25%, 25-50%, and 50%< or =) were given according to the proportion of positive cells. The CEA gene was amplified in the metastatic tumor cells of the liver (2.6 +/- 0.2, mean grade +/- SEM) and their surrounding hepatocytes (1.5 +/- 0.2) in all cases. CEA expression was found in all metastatic tumor cells and 14 cases of the surrounding hepatocytes. Among the control groups, the CEA gene of the hepatocytes was found in 9 cases each of the colorectal and the stomach cancers that did not exhibit CEA expression. The level of serum CEA was related with the numbers and volume of liver metastases, but not with CEA expression in tumor cells and surrounding hepatocytes. The CEA gene in the metastatic tumor cells, not in the hepatocytes, was closely associated with CEA expression in the surrounding hepatocytes (p<0.01). Although the precise mechanism of CEA gene regulation in hepatocytes remains to be proven, the CEA gene in the metastatic tumor of the liver seems to affect CEA expression in the surrounding hepatocytes facilitating liver metastasis in colorectal carcinoma.     

Retrospective review of pelvic malignancies undergoing total pelvic exenteration

ABSTRACT: BACKGROUND: In patients with locally advanced or recurrent pelvic malignancies, total pelvic exenteration (TPE) may be necessary for curative treatment. Despite improvements in mortality rates since TPE was first described, morbidity rates remain high due to the extensive resection and the aggressiveness of these tumors. We have studied the outcomes of TPE surgery performed at our institution. METHODS: Fifty-three patients with various pelvic pathologies underwent TPE between 2004 and 2010. Patients were divided into two groups based on pathology: colorectal (n =36) versus noncolorectal (n =17) malignancies. Demographics, operative reports, pathology reports, periprocedural events, and outcomes were analyzed. Comparison of the two groups was performed using student'st-test and Fisher's exact test. Survival curves were constructed using the Kaplan-Meier method and compared using the log rank test. RESULTS: The colorectal and non-colorectal groups were similar in demographics, operative times, length of stay, estimated blood loss, and rates of preoperative and intraoperative radiation use. Chemotherapy use was increased in the colorectal group compared with the noncolorectal group (55.6% vs. 23.5%, P =0.04). Complication rates were similar: 86% in the colorectal group and 76% in the non-colorectal group. In the colorectal group, 27.8% of patients developed perineal abscesses, whereas no patients developed these complications in the non-colorectal group (P =0.02). No survival difference was seen in primary versus recurrent colorectal tumors; however, within the colorectal group there was a survival advantage when comparing R0 resection to R1 and R2 resection combined. Median survival rates were 27.3 months for R0 resection and 10.7 months for R1 and R2 resection combined. The median survival was 21.4 months for the colorectal group and 6.9 months for the noncolorectal group (P =0.002). CONCLUSIONS: Patients undergoing TPE for colorectal tumors have improved survival when compared with patients undergoing exenteration for pelvic malignancies of other origins. Within the colorectal group, the extent of resection demonstrated a significant survival benefit of an R0 resection compared with R1 and R2 resections. Despite TPE carrying a high morbidity rate, mortality rates have improved and careful patient selection can optimize outcomes.