Surgical therapy of liver metastases

The liver is the most common site of metastatic disease from both gastrointestinal and extra-intestinal malignancies. Historically, only a minority of patients with colorectal liver metastases were candidates for resection. However, over the past several decades, liver resection has evolved as a safe and potentially curative treatment for hepatic colorectal metastases. The development of active chemotherapy and molecular targeted therapies, together with newer modalities like radiofrequency ablation, have expanded the indications for hepatic resection and improved survival. Selected patients with isolated liver metastases from neuroendocrine tumors, germ cell cancers, ocular melanoma, gastrointestinal stromal tumors (GIST), and breast cancer also may be considered for hepatic surgery.     

Radiofrequency ablation of hepatic metastases

The liver is one of the most common sites for cancer metastases that result in significant morbidity and mortality. Although surgical resection is associated with improvements in local control and survival, only a minority of patients are candidates for this approach. Radiofrequency ablation (RFA) is an important alternative/complementary tool in the treatment of metastatic disease to the liver and can lead to palliation as well as increased survival in selected patients. RFA has been shown to be safer and better tolerated than other ablative techniques and has been associated with a low rate of local recurrence when performed properly. RFA also has shown some promise in combination with surgical resection and other therapies. Patients who undergo RFA still suffer from progressive metastatic disease, reinforcing the premise that local therapies have little impact on the natural history of aggressive cancers. Trials combining RFA with surgical resection and regional and systemic chemotherapy are ongoing and it is the hope that RFA combined with multimodality adjuvant therapy will reduce the development of both local disease and progressive metastatic disease, leading to improved overall survival.     

Surgical treatment of hepatic metastases from colorectal cancer

Colorectal carcinoma is one of the most frequent cancers in Western societies with an incidence of around 700 per million people.About half of the patients develop metastases from the primary tumor and liver is the primary metastatic site.Improved survival rates after hepatectomy for metastatic colorectal cancer have been reported in the last few years and these may be the result of a variety of factors,such as advances in systemic chemotherapy,radiographic imaging techniques that permit more accurate determination of the extent and location of the metastatic burden,local ablation methods,and in surgical techniques of hepatic resection.These have led to a more aggressive approach towards liver metastatic disease,resulting in longer survival.The goal of this paper is to review the role of various forms of surgery in the treatment of hepatic metastases from colorectal cancer.     

Treatment options for limited or symptomatic metastatic melanoma

BACKGROUND: Patients who develop metastatic melanoma often have limited effective treatment options. However, a select group of patients will benefit from aggressive surgery or a multidisciplinary approach, depending on the site of metastasis. METHODS: The current literature was reviewed and summarized regarding the collective recommendations for staging and treating patients with metastatic melanoma. RESULTS: A thorough preoperative staging includes positron-emission tomography, MRI of the brain, and CT of the chest, abdomen, and pelvis. Tumor biology ultimately determines the success of intervention. A long disease-free interval is a good indicator of potential benefit from resection of metastatic disease. If surgery is performed, no less than a complete resection will affect the overall survival of the patient. Surgery and other multimodality treatment options can be used for symptomatic palliation but will not affect survival. Chemotherapy and radiation are often used to control the symptoms of brain and bony metastases but have limited if any impact on survival. CONCLUSIONS: A select group of patients with metastatic melanoma will benefit from aggressive surgery. Identifying which patients will benefit from treatment requires good clinical judgment and a thorough radiologic evaluation to identify the true extent of disease.     

Liver fatty acid-binding protein is a new prognostic factor for hepatic resection of colorectal cancer metastases.

BACKGROUND AND OBJECTIVES: Liver fatty acid-binding protein (L-FABP) is reported as a biological marker for enterocytic differentiation. We evaluated the prognostic value of L-FABP expression for patients undergoing hepatic resection of colorectal cancer metastases. METHODS: The study group comprised 68 patients who underwent hepatic resection for colorectal cancer metastases between 1982 and 1996 at Niigata University Medical Hospital, Niigata, Japan. L-FABP expression was immunohistochemically studied in metastatic liver tumors and their primary colorectal cancers. The relationship between L-FABP expression and patient prognoses was statistically analyzed. RESULTS: L-FABP was positively stained in 56% (38/68) of liver metastases from colorectal cancers and in 56% (38/68) of their primary tumors. Of 68 cases, 54 (79%) showed similar immunohistochemical findings between primary and metastatic tumors. Patients with L-FABP-positive liver metastases showed better prognosis than patients with L-FABP-negative metastases (P = 0.046). L-FABP expression in primary colorectal cancers more significantly (P = 0.009) affected long-term survival after hepatic surgery. Multivariate analysis revealed that the prognostic effect of L-FABP expression in primary colorectal cancers was exerted independently and that its impact was larger than conventional pathological prognosticators. CONCLUSIONS: L-FABP expression is suitable for use as a new presurgical prognostic factor for patients undergoing hepatic surgery for colorectal cancer metastases.     

Metastases of colorectal cancer to the liver and peritoneum: comparison of surgical paradigms

The treatment of metastatic colorectal cancer is evolving. Although the advent of new chemotherapeutic and biologic agents has certainly improved the outlook for many patients, surgical resection in certain subsets of patients with advanced colorectal cancer is the only chance for long-term survival. Traditionally, patients with limited hepatic or pulmonary metastases were the only candidates for metastasectomy. Since hepatic metastases are the most common, there is a tremendous amount of data on the efficacy of this approach and the clinical outcomes. However, more recently, another metastatic site in colorectal cancer has received attention as a potential organ system that can be completely extirpated with improved clinical outcomes. This is the peritoneum, and tumor lesions at this site are referred to as peritoneal surface disease. Macroscopically complete cytoreductive surgery in combination with intraperitoneal hyperthermic chemotherapy for peritoneal surface disease has been demonstrated to produce survival outcomes equal to liver resection for hepatic metastases. This review will examine recent evidence regarding these two surgical oncology paradigms and compare patient populations, clinical outcomes and future challenges.     

Metastases of colorectal cancer to the liver and peritoneum: comparison of surgical paradigms

The treatment of metastatic colorectal cancer is evolving. Although the advent of new chemotherapeutic and biologic agents has certainly improved the outlook for many patients, surgical resection in certain subsets of patients with advanced colorectal cancer is the only chance for long-term survival. Traditionally, patients with limited hepatic or pulmonary metastases were the only candidates for metastasectomy. Since hepatic metastases are the most common, there is a tremendous amount of data on the efficacy of this approach and the clinical outcomes. However, more recently, another metastatic site in colorectal cancer has received attention as a potential organ system that can be completely extirpated with improved clinical outcomes. This is the peritoneum, and tumor lesions at this site are referred to as peritoneal surface disease. Macroscopically complete cytoreductive surgery in combination with intraperitoneal hyperthermic chemotherapy for peritoneal surface disease has been demonstrated to produce survival outcomes equal to liver resection for hepatic metastases. This review will examine recent evidence regarding these two surgical oncology paradigms and compare patient populations, clinical outcomes and future challenges.     

Transarterial perfusion of liver metastases

Progressive growth of unresectable metastatic or primary malignancies confined to the liver is a significant clinical problem. Approximately 25% of patients with colorectal cancer will develop metastatic disease exclusively or largely confined to liver, the vast majority of which are not amenable to surgical resection. Despite aggressive systemic or regional chemotherapy, survival is only 12 to 18 months. More than 80% of patients with ocular melanoma develop liver metastases as the first site of recurrent disease, and death from hepatic disease progression typically occurs 2 to 7 months after diagnosis. In addition, the liver is also the preferred site of metastatic disease for gastrointestinal or pancreatic neuroendocrine tumors. A number of physiological and anatomic features of the liver make it an ideal organ for regionally directed therapy to allow dose intensification to the cancer-burdened area while reducing or eliminating unnecessary systemic toxicity. To that end, complete vascular isolation and perfusion of the liver using a recirculating extracorporeal circuit, also called isolated hepatic perfusion (IHP), has been under clinical evaluation at our institution and others. In this article, we review the current results with IHP and its potential utility in the treatment of patients with unresectable hepatic malignancies.     

Histologic grade is correlated with outcome after resection of hepatic neuroendocrine neoplasms

BACKGROUND: The behavior of neuroendocrine neoplasms is poorly defined, and predictors of outcome after surgical resection have yet to be identified. Consequently, guidelines for treatment remain unclear. Current pathologic classification systems do not permit meaningful discrimination of hepatic neuroendocrine neoplasms. METHODS: The authors reviewed prospectively maintained databases from 2 institutions of patients who underwent hepatic resection for neuroendocrine neoplasms between 1990 and 2006. Patient, tumor, and operative characteristics were analyzed to identify factors associated with overall survival, progression-free survival, and symptom control. Hepatic neoplasms were stratified by using a 3-tier pathologic classification system based on the number of mitotic figures and the presence of tumor necrosis that was recently validated for pancreatic neuroendocrine neoplasms. RESULTS: Seventy patients were identified from the databases. Low-grade, intermediate-grade, and high-grade neoplasms were identified in 53%, 37%, and 10% of patients, respectively. After a median follow-up of 51 months, the median overall survival for all patients was 91 months, and it was 108 months when 7 patients with high-grade neuroendocrine carcinomas were excluded. Progressive disease was eventually observed in 81% of patients, and the median progression-free survival was 17 months. The median time to the onset of symptoms was 39 months for patients who presented with hormonal symptoms and 80 months for all patients. Histologic grade was associated with poorer overall and progression-free survival. CONCLUSIONS: When performed in a context of aggressive multimodality therapy, long-term outcomes after partial hepatectomy for hepatic neuroendocrine neoplasms were favorable; however, disease progression was eventually observed in the majority of patients. Several oncologic variables were associated with significant differences in survival after resection. A novel pathologic classification system appears to enhance prognostic stratification of patients with hepatic neuroendocrine neoplasms.     

Current concepts and controversies in the treatment of parenchymal brain metastases: improved outcomes with aggressive management

The multimodality management of brain metastases has undergone significant refinement in the last decade. Although brain metastases remain a significant source of morbidity and mortality for many cancer patients, aggresive management has led to pronounced gains in neurological functioning, disease free survival and overall survival compared to standard treatment regimens consisting of only whole brain radiation therapy. Representative studies reviewing the role of aggressive management approaches including surgical resection with or without whole brain radiation therapy or non-surgical approaches employing stereotactic radiosurgery alone or in combination with whole brain radiation therapy are highlighted. Additionally, the emerging role of systemic agents showing distinct clinical activity in patients with brain metastases are also discussed. As we continue to gain advances in systemic therapies for metastatic disease, local control of brain metastases in these patients is likely to become more critical in improving survival and quality of life, thereby calling for a more aggressive multi-modal approach to this population of patients.     

Palliation of hepatic tumors

Palliation is treatment aimed at alleviating the symptomatic effects of a disease rather than at curing the disease. The four most common types of liver tumors that often require palliative treatment include hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), metastatic colorectal carcinoma (mCRC), and metastatic neuroendocrine tumors (mNET). Modalities employed in the palliative treatment of these tumors most often include resection, stenting, chemotherapy, radiation, ablation, and the general treatment of liver failure symptoms. Many of these modalities can be applied to the palliative care of all hepatic tumor types, regardless of the specific tumor histology--as incurable cancers often converge along a final common pathway. We herein provide a review of the therapeutic approaches to palliate hepatic tumors, as well as how such therapies are designed to alleviate the symptoms of patients with end-stage liver tumors.     

Peritoneal carcinomatosis of colorectal origin

Peritoneal carcinomatosis is, after liver metastases, the second most frequent cause of death in colorectal cancer patients and at the present time, is commonly inserted and treated as a stage IV tumour. Because there is no published data that outlines the impact of new therapeutic regimens on survival of patients with peritoneal surface diffusion, the story of carcinomatosis can be rewritten in light of a new aggressive approach based on the combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Also if these treatment perhaps allow to obtain better results than standard therapies, we suggest, that a large prospective randomised control trial is needed to compare long-term and progression-free survival under the best available systemic therapy with or without cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.     

Hepatic arterial infusion chemotherapy in gastric cancer: a report of four cases and analysis of the literature

AIMS AND BACKGROUND: Gastric cancer is associated with high mortality. Although the liver is a common site of metastases in this tumor, the experience with liver-directed therapies is limited. METHODS: We report a single-center experience involving four patients with liver metastases from gastric cancer treated by hepatic arterial infusion (HAI). In addition, we performed a search for reports on HAI in gastric cancer metastatic to the liver and used the studies with data on survival of individual patients for a pooled analysis. RESULTS: Among three valuable patients, one had a complete response, one had stable disease and one had progressive disease. The patient with complete response is still alive 41 months after the diagnosis of liver metastases, while the other patients died 6, 22 and 31 months after the diagnosis. Objective responses were observed in 48% of the 25 patients in the pooled analysis. Objective response and limited hepatic involvement were independent predictors of survival in these patients. CONCLUSIONS: Although isolated liver involvement in metastatic gastric cancer is rare, HAI seems to be similarly effective in these patients as in patients with liver metastases from colorectal cancer. The prognosis is significantly better in gastric cancer patients who have limited hepatic involvement and attain an objective response after HAI.     

Surgical treatment of combined hepatic and pulmonary colorectal cancer metastases

Aims

Surgical resection of combined hepatic and pulmonary metastases remains controversial in light of limited supportive evidence. This study aimed to audit our initial experience with this aggressive surgical strategy.

Methods

Between 1997 and 2006 we assessed 19 patients with colorectal cancer metastases for combined liver and lung metastasectomy, of whom 16 patients underwent surgery. We retrospectively reviewed perioperative and survival data.

Results

Synchronous liver metastases were present in three out of 16 patients at time of diagnosis of the primary tumour, and one out of 16 patients had synchronous lung and liver metastases with the primary tumour. Of those 12 patients who developed metachronous metastases five patients developed liver metastases first, one patient developed pulmonary metastases first, and six patients developed synchronous liver and lung metastases. Thirty nine operations were performed on 16 patients. The median hospital stay was 5.5 (2–10) days for the pulmonary and 7 (1–23) days for the hepatic resections. There were no in-hospital deaths. Chemotherapy was given to five patients prior to metastasectomy and nine received adjuvant chemotherapy following metastasectomy. Median survival from diagnosis of metastatic disease was 44 months (8–87 months). Estimated 1-year survival from diagnosis of metastatic disease was 94%, estimated 5-year survival was 20%.

Conclusion

We believe an aggressive but selective surgical approach to combined hepatic and pulmonary colorectal metastases is justified by limited resource requirements and encouraging survival.     

Treatment resistant small cell carcinoma of the cervix

Background: Small cell undifferentiated carcinoma of the cervix is an uncommon malignancy with a poor prognosis. Treatment of localized disease has an approximate 40% 5-year survival with multimodality therapies. Case Report: We describe the case of a 24-year-old woman with small cell carcinoma of the cervix that recurred locally despite intensive chemotherapy and radiotherapy. Hysterectomy was performed and the patient is now 18 months disease free. Following treatment, the pathological appearance of the tumor had changed from a typical small cell neuroendocrine malignancy to a more intermediate neuroendocrine cell type. Conclusion: Small cell carcinoma of the cervix is a rare aggressive malignancy that may require cytostatic multimodality therapy including chemotherapy, radiotherapy and surgery, even in early stage disease. Copyright Copyright 1999 S. Karger AG, Basel     

Liver resection for metastatic non-colorectal non-neuroendocrine hepatic neoplasms.

AIMS: Major liver surgery can be performed safely and hepatic resection for metastatic disease is increasingly carried out. However, the role of liver resection for hepatic metastases from non-colorectal, non-neuroendocrine (NCNN) cancers is unknown. Our aim was to evaluate our experience from hepatectomies for NCNN metastases. A retrospective study of 170 patients with liver resection performed the last 8 years was performed in two liver units in affiliated university hospitals. METHODS: Eighteen patients underwent liver resection for NCNN tumours. Origins included kidney (n=6), breast (n=4), gastric tumours (n=4), intestinal leiomyosarcoma (n=2) and malignant melanoma and in one patient a metastatic papillary of unknown origin was found. Eleven patients underwent a hepatic lobectomy and seven had local resections. Ten hepatectomies were performed at the same time with the primary tumour resection (synchronous resections) with five of those in an en bloc fashion with the primary tumour. RESULTS: There were no post-operative deaths and the peri-operative morbidity was minimal. During a median follow-up time of 3.2 years, 14 patients are alive with one of them having developed pulmonary metastases. CONCLUSION: In carefully selected patients with NCNN liver metastasis, liver resection can prolong survival as well and improve quality of life. Copyright Harcourt Publishers Limited.     

Result of liver resection as treatment for metastases from noncolorectal cancer

BACKGROUND AND OBJECTIVES: While liver resection for metastatic disease from colorectal cancer extends survival in selected patients, the efficacy of hepatectomy for metastases from other malignancies has not been defined. METHODS: Between 1988 and 1998, 20 hepatic resections were performed in 18 patients (2 underwent a double resection due to recurrence) as treatment of noncolorectal metastases. One-, 2-, and 5-year overall and disease-related actuarial survival rates were calculated. RESULTS: No intraoperative or early postoperative deaths were reported. Seven minor (30%) and 1 major (5%) postoperative complications occurred; mean blood loss was 401 +/- 324 ml. In 25% of patients, intra- or postoperative blood transfusion was needed. The mean postoperative hospital stay was 13. 2 days (range 9-23). The overall actuarial survival rate was 54% at 1 year, 42% at 2 years, and 21% at 5 years (mean 38 +/- 11 months). Survival is related to the primary tumor nature. CONCLUSIONS: Hepatic resection for metastases from noncolorectal carcinoma is safe and feasible, with a relatively low incidence of intra- or postoperative complications and a short hospital stay. Although it achieves good results in terms of survival in patients suffering from neuroendocrine metastases, it could also have a cytoreductive effect for other tumors.     

Preoperative and intraoperative approaches to improve resectability of hepatic colorectal metastases

Given recent improvements in surgical technique and the development of more effective systemic therapies, the indications for surgical resection of colorectal liver metastases are expanding. The major limitation to the complete resection of colorectal liver metastases in the majority of patients, who present with bilobar or bulky disease, is the need to preserve a sufficient functional liver remnant. Strategies to increase the proportion of patients who are candidates for curative resection have emerged over the past several years, including neoadjuvant chemotherapy, portal vein embolization, staged and repeat hepatectomies, minimal-margin resections, ablative techniques, and the systematic resection of extrahepatic disease. The goal of all of these strategies is to permit a complete resection of all metastatic disease while preserving sufficient functional hepatic parenchyma. In this article, we review these novel strategies and discuss their impact on the increasingly complex and evolving multimodality treatment of patients with colorectal liver metastases.     

肝脏部分切除术在复发性上皮性卵巢癌肝实质转移治疗中的价值

目的 探讨复发性上皮性卵巢癌肝实质转移患者行肝脏部分切除术的临床价值.方法 回顾性分析39例复发性上皮性卵巢癌肝实质转移患者的临床病理资料.结果 39例患者中,10例进行了肝脏部分切除术,29例仅行挽救性化疗.手术组患者的病变均为单叶,且病灶＜3个,与化疗组比较,差异有统计学意义(P＜0.05),在年龄、初次手术病理类型及病理分级、初次减瘤手术结果、初次治疗后的无瘤生存时间、肝转移瘤大小及肝转移时CA125水平等方面,差异均无统计学意义(P＞0.05).10例手术患者中,单纯行肝脏手术6例,同时行其他部位肿瘤细胞减灭术4例,其中7例减瘤手术满意.3例发生手术并发症,无手术死亡病例.8例肝脏病理切缘为阴性的患者中,局部复发6例,中位复发时间为术后12个月.减瘤手术满意的患者与行挽救性化疗的患者,肝转移后的中位总生存时间分别为26个月和9个月,肝转移后3年累积生存率分别为60.0%和16.8%,两组比较,差异有统计学意义(P＜0.05).结论 对存在肝实质转移的复发性上皮性卵巢癌患者施行包括肝脏部分切除术在内的满意肿瘤细胞减灭术,术后辅以化疗,有可能改善患者的预后.

Abstract：

Objective To investigate the validity of hepatic resection as a treatment option for hepatic parenchymal metastasis in patients with recurrent epithelial ovarian cancer. Methods A retrospective review of the clinicopathological and follow up data of 39 patients treated in our hospital from 1996 to 2008was conducted. Results Ten patients underwent partial hepatic resection for metastatic ovarian cancer.All the 10 patients underwent surgery were with unilobar metastasis and the number of tumors was lower than 3 (P ＜0.05).No significant difference existed in patient age,the primary pathology type and tumor grade,the rate of optimal primary cytoreductive surgery,the disease free survival after the primary therapy and the serum CA125 level at the liver metastasis when compared with the 29 patients accepted salvage chemotherapy(P ＞0.05).There were 7 patients who achieved optional surgery.The operation complication was 3/10 andthere was no perioperative mortality.There were 2 patients without postoperative chemotherapy in the 8 recurrent patients with microscopic negative margins.The median recurrence time was 12(5-24) months after the hepatic resection.The overall median survival periods after hepatic metastasis were 26 and 9 months and the 3-years cumulative survival rates were 60.0% and 16.8% for the optimal surgery patients including hepatic surgery and the salvage chemotherapy patients,respectively(P ＜0.05).Conclusion Hepatic resection for liver metastatic epithelial ovarian cancer is safe and may achieve long-term survival in patients after optimal second cytoreductive surgery.     

Neuroendocrine tumors of the pancreas, excluding gastrinoma

In summary, neuroendocrine tumors of the pancreas comprise a unique and relatively rare group of tumors, of which gastrinoma and insulinoma are the most common types. Insulinomas tend to be small, solitary and benign, with surgical resection curable in most cases. The remainder of the neuroendocrine tumors are usually large, and unlikely to be cured with surgery; their slow-growing nature, however, mandates aggressive surgical therapy; even in cases where metastatic disease is present. Somatostatin analogs such as octreotide, are used to control the symptoms of hormone secretion; they are generally less effective in patients with insulinoma than in those with the other neuroendocrine tumors. Streptozocin, 5-fluorouracil, and doxorubicin are the most widely used chemotherapeutic agents in metastatic neuroendocrine tumors; their efficacy is limited, and significant side effects limit their use. Finally, liver transplantation in very select patients may prolong survival and alleviate debilitating symptoms.