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Patient Selection and Guidelines for Resection and Liver-Directed Therapies: Non-colorectal, Non-neuroendocrine Liver Metastases: Treatment Strategy and Evolving Therapies
Abstract
Liver resection for colorectal and neuroendocrine hepatic metastases has traditionally been associated with favorable results in well-selected patients. However, the role of hepatic resection and other liver-directed therapies for non-colorectal, non-neuroendocrine liver metastases has been less adequately described. In this chapter, we review the current literature on surgical and other locoregional treatment strategies for non-colorectal, non-neuroendocrine liver metastases, focusing on prognostic factors, survival outcomes, and selection criteria based on the specific histology of the primary tumor, including breast cancer, genitourinary tract cancer, non-colorectal gastrointestinal tract cancer, and melanoma.
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It is widely accepted that the indications for hepatectomy in colorectal cancer liver metastases and liver metastases of neuro-endocrine tumors result in relatively better prognoses, whereas, the indications and prognoses of hepatectomy for non-colorectal non-neuroendocrine liver metastases (NCNNLM) remain controversial owing to the limited number of cases and the heterogeneity of the primary diseases. There have been many publications on NCNNLM; however, its background heterogeneity makes it difficult to reach a specific conclusion. This heterogeneous disease group should be discussed in the order from its general to specific aspect. The present review paper describes the general prognosis and risk factors associated with NCNNLM while specifically focusing on the liver metastases of each primary disease. A multidisciplinary approach that takes into consideration appropriate timing for hepatectomy combined with chemotherapy may prolong survival and/or contribute to the improvement of the quality of life while giving respite from systemic chemotherapy.
Objective:
To evaluate the efficacy of surgical treatment for patients with isolated breast cancer liver metastases (BCLM).
Background:
Single-arm retrospective studies have shown promising results associated with surgery for isolated BCLM; however, this treatment remains controversial and its role is not well-defined.
Methods:
A review of 2150 patients with BCLM who underwent treatment in a single institution was conducted, and 167 (8%) patients with isolated BCLM were identified. A case-control study was conducted to compare outcomes in patients with isolated BCLM who underwent surgery and/or ablation to patients who underwent conventional medical therapy.
Results:
A total of 167 patients were included (surgery/ablation: 69; medical: 98), with a median follow-up for survivors of 73 months. Patients in the surgical cohort more frequently had estrogen receptor-positive tumors and received adjuvant chemotherapy and radiotherapy for their primary breast tumor. The hepatic tumor burden was less and the interval from breast cancer diagnosis to BCLM was significantly longer (53 vs 30 months) in the surgical cohort. Patients undergoing surgical treatment had a median recurrence-free interval of 28.5 months (95% confidence interval (CI): 19-38) with 10 patients (15%) recurrence free after 5 years. There was no significant difference in overall survival (OS) between the surgical and medical cohorts (median OS: 50 vs 45 months; 5-year OS: 38% vs 39%).
Conclusions:
Hepatic resection and/or ablation was not associated with a survival advantage. However, significant recurrence-free intervals can be accomplished with surgical treatment. Surgical intervention might be considered in highly selected patients with the goal of providing time off of systemic chemotherapy.
Purpose:
Defining the benefits of resection of isolated non-colorectal, non-neuroendocrine (NCRNNE) liver metastases is difficult. To better understand the survival benefit in this group of patients, we conducted a systematic review of the previous literature.
Methods:
Medline, Web of Knowledge, and manual searches were performed using search terms, such as "liver resection" and "primary tumor." Inclusion criteria were year>1990, >five patients, and median survival reported or derived. An expected median survival was calculated from weighted averages of median survivals, and differences were assessed using a permutation test.
Results:
A total of 7,857 references were identified. Overall 4,735 abstracts were reviewed; 120 manuscripts evaluated and of these, 73 met the study inclusion criteria. The final population consisted of 3,596 patients with renal (n=234), ovarian (n=119), testicular (n=153), adrenal (n=90), small bowel (n=28), gallbladder (n=21), duodenum (n=38), gastric (n=481), pancreatic (n=55), esophageal (n=23), head and neck (n=15), and lung (n=36) cancers, gastrointestinal stromal tumors (GISTs) (n=106), cholangiocarcinoma (n=13), sarcoma (n=189), and melanoma (n=643). The greatest expected median was 63 months for genitourinary (GU) primaries (n=549; range 5.4-142 months) followed by 44.4 months for breast cancer (n=1,013; range 8-74 months), 22.3 months for gastrointestinal cancer (n=549; range 5-58 months), and 23.7 months for other tumor types (n=1,082; range 10-72 months). Using a permutation test, we observed that survival was best for patients with GU primaries followed by that for breast cancer patients. Additionally, we also observed that survival was similar for those with cancer of the GI tract and other primary sites.
Conclusions:
There appears to be a benefit to resection for patients with NCRNNE liver metastases. The degree of survival advantage is predicated by primary site.
To determine whether, in a highly selected patient population, medical treatment combined with surgical resection of liver metastases from breast cancer is associated with improved survival compared with medical treatment alone.
Between 1988 and 2007, 100 liver resections for metastatic breast cancer were performed at Institut Curie, 51 of which met the criteria for inclusion in this case-control study. With the exception of bone metastases, patients with other distant metastasis sites were excluded. Surgery was only performed in patients with stable disease or disease responding to medical treatment evaluated by imaging evaluation. Surgical cases were individually matched with 51 patients receiving medical treatment only. All patients had 4 or fewer resectable liver metastases. The study group was matched with the control group for age, year of breast cancer diagnosis, time to metastasis, TNM stage, hormone receptor status and breast cancer tumour pathology.
Univariate analysis confirmed a survival advantage for patients lacking bone metastases and axillary lymphadenopathy at the time of breast cancer diagnosis and for surgically treated patients. Multivariate analysis indicated that surgery and the absence of bone metastases were associated with a better prognosis. A multivariate Cox model adapted for paired data showed a RR = 3.04 (CI: 1.87-4.92) (p < 0.0001) in favour of surgical treatment.
Surgical resection of liver metastases from primary breast cancer appears to provide a survival benefit for highly selected patients.
Background: Metastatic renal cell carcinoma (RCC) to the liver portrays a poor prognosis and liver directed therapy remains controversial. We aimed to determine potential selection criteria for patients who might benefit from this strategy.
Materials and Methods: We evaluated 247 consecutive patients with RCC metastatic to the liver from a prospectively maintained database.
Results: Eighteen patients received liver directed therapy (18/247, 7%). Ten patients underwent liver resection (10/247, 4%) and eight patients underwent radiofrequency ablation (RFA, 8/247, 3%). All were rendered free of disease in the liver. Five had synchronous liver disease and underwent synchronous resections with their primary. Mortality was 0%. Fourteen had single (surgery 7, RFA 7) and four (surgery 3, RFA 1) had multiple liver lesions, respectively. Median size of lesions was 5cm (0.5 - 10cm) and 2.5cm (1 - 6cm) in the surgery and RFA groups, respectively. Median DFI was 10 months, and no difference was observed in those with a longer vs. shorter than median DFI (p = 0.95); liver specific progression free survival for the surgery and RFA groups were 4 and 6 months, respectively (p= 0.93). 1, 3 and 5-year actuarial survivals for the whole group were 89%, 40%, 27%. Median survival for the surgery group was 24 (3 to 254+) months, and for the RFA group 15.6 (7-56+) months (p = 0.56). Metachronous liver disease was associated with prolonged survival (p = 0.02).
Conclusions: Liver directed therapy for RCC is safe. For highly selected patients with metachronous liver RCC metastases, liver directed therapy should be considered in a multidisciplinary manner.
The oncologic benefit of resecting liver metastases in patients with breast cancer is unclear. This study was performed to identify predictors of survival after hepatectomy.
Between 1997 and 2010, 86 patients underwent resection of breast cancer liver metastases. Clinicopathologic characteristics of the primary breast neoplasm, timing of metastasis development, and treatment were recorded. Response to prehepatectomy chemotherapy was evaluated according to Response Criteria in Solid Tumors criteria, and the best response to chemotherapy during treatment and the response immediately before hepatectomy were noted. Univariate and multivariate analyses were performed to identify predictors of disease-free survival and overall survival.
Fifty-nine patients (69%) had estrogen receptor- or progesterone receptor- positive primary breast neoplasms. Fifty-three patients (62%) had a solitary breast cancer liver metastasis, and 73 (85%) had breast cancer liver metastases ≤5 cm. Sixty-five patients (76%) received prehepatectomy hormonal and/or chemotherapy. Four patients (6%) had progressive disease as the best response, and 19 patients (30%) had progressive disease before hepatectomy (P < .001). Seventy percent of patients who received preoperative chemotherapy or hormonal therapy had either response or stable disease immediately before hepatectomy. No postoperative deaths were observed. At a 62-month median follow-up, the disease-free survival and overall survival were 14 and 57 months, respectively. On univariate analysis, estrogen receptor/progesterone receptor status of the primary breast neoplasm, best radiographic response, and preoperative radiographic response were associated with overall survival. On multivariate analysis, estrogen receptor-negative primary breast disease (P = .009; hazard ratio, 3.3; 95% confidence interval, 1.4-8.2) and preoperative progressive disease (P = .003; hazard ratio, 3.8; 95% confidence interval, 1.6-9.2) were associated with decreased overall survival.
Resection of breast cancer liver metastases in patients with estrogen receptor-positive disease that is responding to chemotherapy is associated with improved survival. The timing of operative intervention may be critical; resection before progression is associated with a better outcome.
Data are lacking on the efficacy and safety of a combination chemotherapy regimen consisting of oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) as compared with gemcitabine as first-line therapy in patients with metastatic pancreatic cancer.
We randomly assigned 342 patients with an Eastern Cooperative Oncology Group performance status score of 0 or 1 (on a scale of 0 to 5, with higher scores indicating a greater severity of illness) to receive FOLFIRINOX (oxaliplatin, 85 mg per square meter of body-surface area; irinotecan, 180 mg per square meter; leucovorin, 400 mg per square meter; and fluorouracil, 400 mg per square meter given as a bolus followed by 2400 mg per square meter given as a 46-hour continuous infusion, every 2 weeks) or gemcitabine at a dose of 1000 mg per square meter weekly for 7 of 8 weeks and then weekly for 3 of 4 weeks. Six months of chemotherapy were recommended in both groups in patients who had a response. The primary end point was overall survival.
The median overall survival was 11.1 months in the FOLFIRINOX group as compared with 6.8 months in the gemcitabine group (hazard ratio for death, 0.57; 95% confidence interval [CI], 0.45 to 0.73; P<0.001). Median progression-free survival was 6.4 months in the FOLFIRINOX group and 3.3 months in the gemcitabine group (hazard ratio for disease progression, 0.47; 95% CI, 0.37 to 0.59; P<0.001). The objective response rate was 31.6% in the FOLFIRINOX group versus 9.4% in the gemcitabine group (P<0.001). More adverse events were noted in the FOLFIRINOX group; 5.4% of patients in this group had febrile neutropenia. At 6 months, 31% of the patients in the FOLFIRINOX group had a definitive degradation of the quality of life versus 66% in the gemcitabine group (hazard ratio, 0.47; 95% CI, 0.30 to 0.70; P<0.001).
As compared with gemcitabine, FOLFIRINOX was associated with a survival advantage and had increased toxicity. FOLFIRINOX is an option for the treatment of patients with metastatic pancreatic cancer and good performance status. (Funded by the French government and others; ClinicalTrials.gov number, NCT00112658.).
To evaluate outcomes of surgical treatment in patients with hepatic metastases from renal-cell carcinoma in the Netherlands, and to identify prognostic factors for survival after resection. Renal-cell carcinoma has an incidence of 2,000 new patients in the Netherlands each year (12.5/100,000 inhabitants). According to literature, half of these patients ultimately develop distant metastases with 20% involvement of the liver. Resection of renal-cell carcinoma liver metastases (RCCLM) is performed in only a minority of patients. Hence, little is known about outcome of resectable RCCLM.
Patients were retrieved from local databases of the Netherlands Task Force for Liver Surgery (14 centers) and from the Dutch collective pathology database. Survival and prognostic factors were determined by Kaplan-Meier analysis and log rank test.
Thirty-three patients were identified who underwent resection (n = 29) or local ablation (n = 4) of RCCLM in the Netherlands between 1990 and 2008. These patients comprise 0.5% to 1% of the total population of patients diagnosed with RCCLM in that period. There was no operative mortality. The overall survival at 1, 3, and 5 years was 79, 47, and 43%, respectively. Metachronous metastases (n = 23, P = 0.03) and radical resection (n = 19, P < 0.001) were statistically significant prognosticators of overall survival. Size < 50 mm (n = 18, P = 0,54), solitary metastases (n = 19, P = 0.93), and presence of extrahepatic metastases (n = 11, P = 0.28) did not have a statistically significant impact on survival.
The favorable 5-year survival rate of 43% without operative mortality as found in this nationwide study indicates that selected patients with RCCLM can benefit from surgical treatment.
Endometrial cancer is the most common gynecologic malignancy. The majority of patients have disease confined to the uterus and have an excellent overall prognosis. However, subgroups of patients have advanced primary disease or recurrences following primary treatment.
The management of metastatic disease is variable, depending on factors such as comorbidities, tumor grade, performance status, and prior treatments. Management options include hormonal therapy and cytotoxic chemotherapy, as well as targeted therapies that inhibit angiogenesis and the cellular signaling pathways involved in cell growth and proliferation. A comprehensive review of these treatments for metastatic endometrial cancer was conducted and is discussed.
Hormonal therapy and cytotoxic chemotherapy have traditionally been used in the treatment of metastatic endometrial cancer. Advances in molecular biology have led to multiple potential targeted therapies to be used in the treatment of metastatic endometrial cancer.
While several treatment modalities are now available to treat patients who present with metastatic endometrial cancer, overall prognosis remains poor.
Breast cancer liver metastases (BCLM) usually indicate the presence of disseminated cancer with a very poor prognosis. However, systemic treatments now allow control of tumour progression in certain cases. We evaluated, in a group of highly selected patients with stabilization or complete response to systemic therapy, a particular management protocol for medically controlled BCLM: liver surgery.
Fifty-two patients underwent surgery between May 1988 and September 1997. Results of this strategy are reported, together with analysis of prognostic factors for survival and recurrence in the remaining liver (RRL).
The mean number of cycles of chemotherapy, before surgery, was seven (3-24). Resection was considered to be curative in 86% of cases. The median follow-up was 23 months (1-72 months). The survival after surgery, was 86% at 12 months, 79% at 24 months and 49% at 36 months. The 36-month survival rate differed according to the time to onset of BCLM: 45% before versus 82% after 48 months (P=0.023). The RRL rate at 36 months differed according to the lymph node status of the initial breast cancer: 41% for N0-N1 versus 83% for N1b-N2 (P=0.021).
Adjuvant liver surgery allowed discontinuation of chemotherapy in 46% of cases and, in this highly selected patient group, allowed good quality prolonged survival. It could be included in multicentre treatment protocols for controlled BCLM, one arm with prolonged chemotherapy, one with adjuvant liver surgery.
The utility of hepatectomy for patients with metastatic liver tumors from gastrointestinal stromal tumors (GISTs) was evaluated in the present study.
Between 1989 and 2001, ten patients with liver metastases from GIST (four men and six women; age, 34-77 years) underwent hepatectomy at our hospital. All patients underwent complete resection of the primary tumor and hepatectomy with or without microwave coagulation therapy (MCT) for all detectable hepatic tumors.
The median survival time after hepatectomy was 39 months (range, 1 to 96 months). There was one postoperative death. One patient is still alive with relapse of hepatic tumors, and the remaining eight patients died of disease (liver in six, peritoneum in one, and bone in one). Relapse of hepatic tumors occurred in seven patients. The disease-free rate after hepatectomy was 22% at 2 years and 11% at 5 years. The survival times of the four patients who received hepatic arterial chemoembolization for recurrent hepatic metastases were 7 months (still alive), 17, 23, and 28 months (average, 19 months).
Our data suggest that aggressive surgery (hepatectomy and MCT) for all detectable hepatic tumors and hepatic arterial chemoembolization for recurrent hepatic metastases improve survival.
The objective of this study was to identify prognostic factors for survival in patients with advanced oesophageal cancer, who are treated with cisplatin-based combination chemotherapy. We analysed the baseline characteristics of 350 patients who were treated in six consecutive prospective trials with one of the following regimens: cisplatin/etoposide, cisplatin/etoposide/5-fluorouracil, cisplatin/paclitaxel (weekly) and cisplatin/paclitaxel (biweekly). Predictive factors in univariate analyses were further evaluated using multivariate analysis (Cox regression). The median survival of all patients was 9 months. The 1, 2 and 5-year survival rates were 33, 12 and 4%, respectively. The main prognostic factors were found to be WHO performance status (0 or 1 vs 2), lactate dehydrogenase (normal vs elevated), extent of disease (limited disease defined as locoregional irresectable disease or lymph node metastases confined to either the supraclavicular or celiac region vs extensively disseminated disease) in addition to the type of treatment (weekly or biweekly cisplatin/paclitaxel regimen vs 4-weekly cisplatin/etoposide with or without 5-fluorouracil). Although weight loss, liver metastases and alkaline phosphatase were significant prognostic factors in univariate analyses, these factors lost their significance in multivariate analyses. The median survival for patients without any risk factors was 12 months, compared to only 4 months in patients with WHO 2 plus elevated LDH and extensive disease. The performance status, extent of disease, LDH and the addition of paclitaxel to cisplatin are independent prognostic factors in patients with advanced oesophageal cancer, who are treated with cisplatin-based combination chemotherapy.
The usefulness of surgical treatment for hepatic metastases of noncolorectal non-neuroendocrine (NCRNNE) tumors is not yet clear due to the natural history of these tumors, their frequent systemic dissemination and their histological heterogeneity. The aim of this study was to evaluate the long-term outcome of patients who underwent liver resection for NCRNNE metastases. For this purpose we retrospectively analyzed 202 patients who underwent liver resection for metastasis between January 1989 and December 2006 at the Department of Surgery of the University Hospital of Udine. Fifty-six patients underwent liver resection because of NCRNNE metastases. The preoperative assessment was based on hepatic ultrasonography and CT scan; PET was used in a few patients. All patients had intraoperative liver ultrasonography to evaluate the lesions and to define the resection. Gender, age, primary tumor site (gastrointestinal or nongastrointestinal), synchronous or metachronous metastasis, unilobar or bilobar localization, number and diameter of the lesion(s), type of resection, margin status, positive lymph nodes in the hepatoduodenal ligament, and time between surgery and diagnosis of liver metastases were evaluated as possible prognostic factors for survival. Univariate analysis showed that the location of the primary tumor and the disease-free interval since the treatment of the primary tumor were positive predictive factors for longer survival. Multivariate analysis showed that the only independent significant factor was gastrointestinal versus nongastrointestinal origin. Demographic data, the synchronous or metachronous appearance of metastases, their unilobar or bilobar location, number and size, the type of resection, the resection margin status and the involvement of lymph nodes did not prove to be prognostic factors.
Objective:
To estimate the cost-effectiveness of liver resection followed by adjuvant systemic therapy relative to systemic therapy alone for patients with breast cancer liver metastasis.
Background:
Data on cost-effectiveness of liver resection for advanced breast cancer with liver metastasis are lacking.
Methods:
A decision-analytic Markov model was constructed to evaluate the cost-effectiveness of liver resection followed by postoperative conventional systemic therapy (strategy A) versus conventional therapy alone (strategy B) versus newer targeted therapy alone (strategy C). The implications of using different chemotherapeutic regimens based on estrogen receptor and human epidermal growth factor receptor 2 status was also assessed. Outcomes included quality-adjusted life months (QALMs), incremental cost-effectiveness ratio, and net health benefit (NHB).
Results:
NHB of strategy A was 10.9 QALMs compared with strategy B when letrozole was used as systemic therapy, whereas it was only 0.3 QALMs when docetaxel + trastuzumab was used as a systemic therapy. The addition of newer biological agents (strategy C) significantly decreased the cost-effectiveness of strategy B (conventional systemic therapy alone). The NHB of strategy A was 31.6 QALMs versus strategy C when palbociclib was included in strategy C; similarly, strategy A had a NHB of 13.8 QALMs versus strategy C when pertuzumab was included in strategy C. Monte-Carlo simulation demonstrated that the main factor influencing NHB of strategy A over strategy C was the cost of systemic therapy.
Conclusions:
Liver resection in patients with breast cancer liver metastasis proved to be cost-effective when compared with systemic therapy alone, particularly in estrogen receptor-positive tumors or when newer agents were used.
Background and Objectives: Hepatic resection of noncolorectal metastases appears to be performed with increasing frequency. Reported experience is limited and indications are controversial. Methods: Retrospective review of curative hepatic resection in 32 patients (median age 58 years) during 1970- 1995. The primary tumor was a carcinoid in seven patients, other endocrine tumor in five patients, malignant melanoma in three patients, stomach cancer in three patients, exocrine pancreatic cancer in two patients, gynecological cancer in two patients, sarcoma in two patients, and miscellaneous in eight patients. Seven patients (22%) had bilobar disease and 12 patients (38%) had extrahepatic growth. Results: Median survival was 32 months, and 5-year actuarial survival rate was 36% (including operative mortality). Median survival in the endocrine (n = 12) and nonendocrine (n = 20) groups was 72 and 18 months, respectively (corresponding 5-year survival rates were 56 and 25%) (P = 0.16). Prognostic factors could not be established in either group. It is, however, noteworthy that no patient with nonendocrine secondaries and more than one liver tumor or extrahepatic disease survived for 5 years. Major complications were seen in eight patients (25%), including three postoperative deaths (operative mortality 9%) occurring during the first 5 years of the study period. Conclusions: Hepatic resection of metastases from endocrine primary tumors was followed by long-term survival in a substantial proportion of patients. Long-term survival for patients with nonendocrine tumors was observed only when there was a single liver tumor and no extrahepatic growth. Further experience is needed for definition of resection criteria.
Background/aims:
The significance of surgical resection for non-colorectal non-neuroendocrine tumor liver metastasis (NCNNLM) remains controversial. The present study sought to clarify the long-term outcomes of surgical resection for NCNNLM and prognostic factors after hepatectomy in a single institution.
Methodology:
From 1993 to 2009, 145 patients underwent hepatectomy for NCNNLM. The primary sites of the hepatic tumors were gastrointestinal carcinoma in 80 cases, breast in 30, genitourinary in 12, gastrointestinal stromal tumor in 11, and miscellaneous in 12.
Results:
The cumulative 1-, 3-, and 5-year overall survival rates of those who underwent hepatectomy for NCNNLM were 83.9, 55.4, and 41.0%, respectively, with median overall survival times of 41.8 months. Multivariate analysis revealed that postoperative complication was the only independent poor prognostic factor impacting on survival. Postoperative morbidity and mortality rate were 17.9% and 1.4%. There are 38 cases survived more than 5 years including 21 patients without remnant tumors due to the repeat hepatic and/or pulmonary resection for recurrence. A total of 32 patients survived without tumor and without any kinds of chemotherapy in the latest condition.
Conclusions:
Hepatectomy for NCNNLM may be beneficial and might relieve patients from excursive chemotherapy in selected patients. Meticulous surgery avoiding complication may enhance the outcome.
Whereas resection of colorectal liver metastases is gold standard, there is an ongoing debate on benefit of resection of non-colorectal (NCRC) and non-neuroendocrine (NNEC) liver metastases.
The potential survival benefit of patients undergoing resection of NCRC or NNEC liver metastases was investigated. Data from a prospectively maintained database were reviewed over a 7-year period. Kaplan-Meier method was used for the evaluation of outcome following resection.
101 patients underwent 116 surgical procedures for synchronous and metachronous NCRC or NNEC liver metastases with a morbidity of 23% and a mortality of ∼1%. 11 patients underwent repeated liver resection procedures. Overall 5-year survival after liver resection was 30% depending on primary tumour site. Median survival was significantly increased after resection of hepatic metastases from non-gastrointestinal primaries compared to gastrointestinal primaries. Resection of hepatic metastases from non-gastrointestinal primaries resulted in significantly increased median survival compared to exploration only. Patients with hepatic metastases from gastrointestinal primaries did not benefit from hepatic surgery.
Hepatic resection for liver metastases from NCRC or NNEC cancers is a save treatment procedure. However, the decision to perform surgery should depend on the primary cancer. Especially patients with liver metastases from non-gastrointestinal primaries profit from hepatic surgery.
Background:
Very few series have reported indications for and results of hepatectomy for isolated unique or multiple liver metastases (LM) from a noncolorectal primary. We performed a prospective analysis of 147 patients submitted to hepatectomy for LM to evaluate the results and indications for this unusual type of treatment.
Study design:
Of 538 patients submitted to hepatectomy for a malignant tumor between 1984 and 1996, 147 underwent operations for noncolorectal LM. Conventional and unconventional hepatectomy procedures were used with intermittent clamping of the hepatic pedicle, and in some patients with intermittent vascular occlusion of the liver.
Results:
Postoperative hospital mortality was 2%. The crude 5-year survival was 36%, and survival without progressive disease was 28%. No difference was observed in survival when synchronous and metachronous LM were compared, or when patients with more or fewer than three LM were compared. Five-year survival rates were 20% for 35 breast cancers, 74% for 27 neuroendocrine tumors, 46% for 20 testicular tumors, 18% for 13 sarcomas, and slightly less than 20% for 11 gastric carcinomas, 10 melanomas, and 7 tumors of the gallbladder, according to the primary. Survival exceeded 20% for 6 gynecologic tumors but was disappointing for head and neck cancers, when the primary was unknown, or when the tumor was truly undifferentiated.
Conclusions:
Certain guidelines emerge from this series on the indications and uses of adjuvant chemotherapy. Indications for hepatectomy are relatively straightforward for neuroendocrine, testicular, and renal tumors. Hepatectomy for LM from other primaries appears beneficial in certain sarcomas, breast and gynecologic cancers, and perhaps melanoma, for which selection criteria, unfortunately, remain obscure.
To determine the role of liver resection in patients with liver and extrahepatic colorectal cancer metastases and the role of chemotherapy in patients in conjunction with liver resection.
MEDLINE and EMBASE databases were searched for articles published between 1995 and 2010, along with hand searching.
A total of 4875 articles were identified, and 83 were retained for inclusion. Meta-analysis was not performed because of heterogeneity and poor quality of the evidence. Outcomes in patients who had liver and lung metastases, liver and portal node metastases, and liver and other extrahepatic disease were reported in 14, 10, and 14 studies, respectively. The role of perioperative chemotherapy was assessed in 30 studies, including 1 randomized controlled trial and 1 pooled analysis. Ten studies assessed the role of chemotherapy in patients with initially unresectable disease, and 5 studies assessed the need for operation after a radiologic complete response.
The review suggests that: (1) select patients with pulmonary and hepatic CRC metastases may benefit from resection; (2) perioperative chemotherapy may improve outcome in patients undergoing a liver resection; (3) patients whose CRC liver metastases are initially unresectable may benefit from chemotherapy to identify a subgroup who may benefit later from resection; (4) after radiographic complete response (RCR), lesions should be resected if possible.
Due to different biological characteristics of non-colorectal liver metastasizes (NCLM), surgical treatment, especially it´s long term results, is a topic of discussion. The aim of the study was to evaluate the single center experience with surgical treatment of NCLM.
Seventy two patients were prospectively included. The average length of time after the primary surgery was 3.9 years (0-8.5 years). RFA prevailed -50 patients (69.4%), resection presenting 30.6%. Preoperative chemotherapeutical downstaging or portal vein embolization was performed on 12 patients (16.7%). Resectable or radiofrequency ablation (RFA) treatable extrahepatic metastasizes were removed in 26 patients (36.1%).
One, three and five years patient survival after the liver resection or RFA was 88.6, 72.5 and 36.9%. The best survival rate was in patients with carcinoid (5 years-100%), breast cancer (5 years-33.8%), renal carcinoma (3 years-44.4% ) and gynecological tumors metastasizes (2 years-72.9%). With regards to long-term survival of patients, we did not find any statistically significant difference between RFA and resection. Patients with extrahepatic metastasizes had worse prognosis (p<0.01).
Liver resection and RFA in NCLM have an unambiguous place in multi-modal curative strategy. The decision for surgical treatment of patients suffering from NCLM, is strictly individual with the aim of achieving qualitative long-term survival.
Although hepatic metastasectomy is well established for colorectal and neuroendocrine cancer, the approach to hepatic metastases from other sites is not well defined. We sought to examine the management of noncolorectal non-neuroendocrine liver metastases.
A retrospective review from 4 major liver centers identified patients who underwent liver resection for noncolorectal non-neuroendocrine metastases between 1990 and 2009. The Kaplan-Meier method was used to analyze survival, and Cox regression models were used to examine prognostic variables.
There were 420 patients available for analysis. Breast cancer (n = 115; 27%) was the most common primary malignancy, followed by sarcoma (n = 98; 23%), and genitourinary cancers (n = 92; 22%). Crude postoperative morbidity and mortality rates were 20% and 2%, respectively. Overall median survival was 49 months, and 1, 3, and 5-year Kaplan-Meier survival rates were 73%, 50%, and 31%. Survival was not significantly different between the various primary tumor types. Recurrent disease was found after hepatectomy in 66% of patients. In multivariable models, lymphovascular invasion (p = 0.05) and metastases ≥5 cm (p = 0.04) were independent predictors of poorer survival. Median survival was shorter for resections performed between 1990 and 1999 (n = 101, 32 months) when compared with resections between 2000 and 2009 (n = 319, 66 months; p = 0.003).
Hepatic metastasectomy for noncolorectal non-neuroendocrine cancers is safe and feasible in selected patients. Lymphovascular invasion and metastases ≥5 cm were found to be associated with poorer survival. Patients undergoing metastasectomy in more recent years appear to be surviving longer, however, the reasons for this are not conclusively determined.
Aim: To compare the surgical treatment outcomes between patients with colorectal liver metastases (CLM) and non-colorectal liver metastases (NCLM).
Methods: The study population consisted of 132 patients undergoing hepatectomy at Tianjin Medical University Cancer Hospital between January 1996 and December 2008. Survival analyses were used to assess the differences in prognosis and survival between groups.
Results: The primary tumor site was colorectal in 60 (45.5%), breast in 16 (12.1%), lung in 14 (10.6%), non-colorectal gastrointestinal in 12 (9.1%), genitourinary in 10 (7.6%), pancreatobiliary tumor (n = 8, 6.1%) and others in 12 (9.1%). A curative liver resection was performed in all patients by pathological findings. After a median follow-up of 32 months, the overall 3- and 5-year survival rate was 44.7 and 29.5% in all patients, respectively. The 3- and 5-year survival rates were 53.3 and 36.7% for liver metastases from colorectal tumors, 62.5 and 43.8% from breast, 60.0 and 40.0% from genitourinary neoplasm, 41.7 and 25.0% from non-colorectal gastrointestinal cancer, 28.5 and 15.0% from lung, 12.5 and 0% from pancreatobiliary malignancies, and 41.7 and 8.3% from other sites, respectively.
Conclusions: Hepatic resection is an effective and safe treatment for liver metastases mainly depending on primary tumor sites. Hepatic metastases from non-colorectal gastrointestinal cancer, pulmonary and pancreatobiliary malignancies have the worst prognosis; those from breast and genitourinary neoplasm show the best prognosis.
Management of patients with neuroendocrine liver metastasis (NELM) remains controversial. We sought to examine the relative efficacy of surgical management versus intra-arterial therapy (IAT) for NELM and determine factors predictive of survival.
A total of 753 patients who had surgery (n = 339) or IAT (n = 414) for NELM from 1985 to 2010 were identified from nine hepatobiliary centers. Clinicopathologic data were assessed with regression modeling and propensity score matching.
Most patients had a pancreatic (32%) or a small bowel (27%) primary tumor; 47% had a hormonally active tumor. There were statistically significant differences in characteristics between surgery versus IAT groups (hormonally active tumors: 28 vs. 48%; hepatic tumor burden >25%: 52% vs. 76%) (all P < 0.001). Among surgical patients, most underwent hepatic resection alone without ablation (78%). The median number of IAT treatments was 1 (range, 1-4). Median and 5-year survival of patients treated with surgery was 123 months and 74% vs. 34 months and 30% for IAT (P < 0.001). In the propensity-adjusted multivariate Cox model, asymptomatic disease (hazard ratio 2.6) was strongly associated with worse outcome (P = 0.001). Although surgical management provided a survival benefit over IAT among symptomatic patients with >25% hepatic tumor involvement, there was no difference in long-term outcome after surgery versus IAT among asymptomatic patients (P = 0.78).
Asymptomatic patients with a large (>25%) burden of liver disease benefited least from surgical management and IAT may be a more appropriate treatment strategy. Surgical management of NELM should be reserved for patients with low-volume disease or for those patients with symptomatic high-volume disease.
The aim of the present study was to analyse the outcome after hepatic resection for non-colorectal, non-neuroendocrine, non-sarcomatous (NCNNNS) metastatic tumours and to identify the factors predicting survival.
All patients who underwent hepatic resection for NCNNNS metastatic tumours between September 1996 and June 2009 were included. Patients' demographics, clinical and histopathological parameters, overall survival and the factors predicting survival were analysed.
In all, 65 patients underwent hepatic resection for metastasis. The most common site of a primary tumour was the kidney (24 patients). Fifteen patients had synchronous tumours. Fifty patients had major liver resections and 22 patients had bilobar disease. The median number of liver lesions resected was 1 and the median maximum diameter of the metastasis was 6 cm. A R0 resection was performed in 51 patients. The 1-, 3- and 5-year overall survival from the time of metastasectomy was 72.9%, 47.9% and 25.6%, respectively, with a median survival of 19 months. The presence of a tumour of greater than 6 cm (P= 0.048) and a positive resection margin (P= 0.04) were associated with poor survival.
Hepatic resection for metastasis from NCNNNS tumours can offer acceptable long-term survival in selected patients. To offer a chance of a cure a R0 resection must be performed.
The aims of this study were to assess the surgical outcomes and to also determine the prognostic factors in patients with surgically resectable liver metastases for recurrent ovarian cancer.
Between 1991 and 2008, 18 patients with recurrent ovarian cancer who underwent hepatic resection as part of secondary cytoreductive surgery were identified from the tumor registry pathology database. Parameters for safety, efficacy, and survival data were considered as primary endpoints.
Hepatic resections included wedge resection (n = 4), unisegmentectomy (n = 13), and bisegmentectomy (n = 1). There were no surgery-related deaths. Only one patient (5.6%) had postoperative major complications. The median postoperative hospitalization was 15.5 days (range 11-46 days). The prognostic factors associated with improved survival were less abdominal than pelvic disease (38 vs. 11 months, P = 0.032), optimal cytoreduction (40 vs. 9 months, P = 0.0004), and negative margin status of the hepatic resection (40 vs. 9 months, P = 0.0196). The overall median survival after hepatic resection was 38 months (range 3-78 months).
Hepatic resection for recurrent ovarian cancer is safe and is associated with a favorable outcome. Parenchymal liver metastases should not exclude attempts at optimal secondary cytoreductive surgery, and especially, patients with solitary liver metastases should be considered for hepatic resection.
To evaluate the effectiveness of resecting liver metastases of gastrointestinal stromal tumors (GISTs), when performed in conjunction with imatinib treatment.
Forty-one patients with pathologically diagnosed GIST and liver metastases were randomly assigned to an operation group (neoadjuvant therapy + resection + adjuvant therapy with imatinib) or a nonoperation group (imatinib alone). Patients were monitored for up to 36 months, and survival was analyzed.
We monitored 39 patients throughout the 36-month follow-up period, recording 1- and 3-year survival rates of 100% and 89.5% in the operation group and 85% and 60% in the nonoperation group, respectively. There was a significant difference in overall survival between the operation and nonoperation groups (P = 0.03). Furthermore, resection improved the survival of patients who responded poorly to 6 months of preoperative imatinib treatment, compared with that of their counterparts in the nonoperation group (P = 0.04).
These findings suggest that surgical intervention in combination with imatinib treatment is more effective than imatinib alone against GIST liver metastases, with minimal complications and side effects.
The management of patients with peri-ampullary liver metastasis remains controversial. We sought to assess the safety and efficacy of curative intent surgery for peri-ampullary liver metastasis.
Between 1993 and 2009, 40 patients underwent curative intent surgery (resection and/or radiofrequency ablation (RFA)) for peri-ampullary liver metastasis. Clinicopathologic and outcome data were collected and analyzed.
Location of the primary tumor was pancreas head (n = 20), ampulla of Vater (n = 10), distal bile duct (n = 5), or duodenum (n = 5). Most patients (n = 27) presented with synchronous disease, while 13 patients presented with metachronous disease following a median disease-free interval of 22 months. Most patients (n = 25) presented with hepatic metastasis from pancreaticobiliary origin (pancreatic or distal common bile duct) compared with 15 patients who had metastasis from an intestinal-type primary (ampullary or duodenal). There were no differences in metastatic tumor number or size between these groups (P > 0.05). Post-operative morbidity and mortality was 30% and 5% respectively. Overall 1- and 3-year survival was 55% and 18%. Patients who underwent resection of liver metastasis from intestinal-type tumors experienced a longer survival compared with patients who had pancreaticobiliary lesions (median: 13 months vs. 23 months; P = 0.05).
Curative intent surgery for peri-ampullary liver metastasis was associated with post-operative morbidity and a 5% mortality rate. Although the overall survival benefit was modest, patients with liver metastasis from intestinal-type tumors experienced improved survival following resection of liver metastasis compared with pancreaticobiliary lesions.
Management of neuroendocrine tumor liver metastasis (NELM) remains controversial, with some advocating an aggressive surgical approach while others have adopted a more conservative strategy. We sought to define the efficacy of the surgical management of NELM in a large multicenter international cohort of patients.
We identified 339 patients who underwent surgical management for NELM from 1985 to 2009 from an international database of eight major hepatobiliary centers. Relevant clinicopathologic data were assessed using Kaplan-Meier and Cox regression models.
Most patients had a pancreatic (40%) or small bowel (25%) neuroendocrine tumor (NET) primary. The majority of patients (60%) had bilateral liver disease. At surgery, 78% of patients underwent hepatic resection, 3% ablation alone, and 19% resection + ablation. Major hepatectomy was performed in 45% of patients, and 14% underwent a second liver operation. Carcinoid was the most common NET histological subtype (53%). Median survival was 125 months, with overall 5- and 10-year survival of 74%, and 51%, respectively. Disease recurred in 94% of patients at 5 years. Patients with hormonally functional NET who had R0/R1 resection benefited the most from surgery (P = 0.01). On multivariate analyses, synchronous disease [hazard ratio (HR) = 1.9], nonfunctional NET hormonal status (HR = 2.0), and extrahepatic disease (HR = 3.0) remained predictive of worse survival (all P < 0.05).
Liver-directed surgery for NELM is associated with prolonged survival; however, the majority of patients will develop recurrent disease. Patients with hormonally functional hepatic metastasis without prior extrahepatic or synchronous disease derive the greatest survival benefit from surgical management.
The value of surgical resection of renal cell carcinoma (RCC) liver metastases still remains unclear.
Of our study was to evaluate the efficacy of liver resection by comparing patients who could have undergone metastasectomy due to limited disease, but refused surgery.
Eighty-eight patients were identified with liver metastases and indication of surgery between 1995 and 2006. In 68 patients, liver resection was performed, 20 patients denied surgery and served as comparison group. Patients were followed for survival.
Median age was 58. Median amount of liver metastases was 2 (range 1-30). Median follow-up was 26 months (range 1-187). In both groups, 79% received systemic therapy. The 5-year overall survival rate (OSR-5) after metastasectomy was 62.2% +/- 11.4% (SEM) with a median survival (MS) of 142 (95% confidence interval (CI) 115-169) months. OSR-5 in the control group was 29.3% +/- 22.0% (SEM) with a MS of 27 (95% CI 16-38) months (P = 0.003). MS was 155 (95% CI 133-175) months with metachronous metastases compared to 29 (95% CI 25-33) months in the comparison group (P = 0.001). Low-grade primary RCC had a MS of 155 (95% CI 123-187) months compared to 29 (95% CI 8-50) months without resection (P = 0.0036). High-grade RCC as well as patients with synchronous metastases did not benefit from surgery.
Liver metastasectomy is an independent valuable tool in the treatment of metastatic RCC and significantly prolongs patient's survival, even if further systemic treatment is necessary. With the evidence given, patients may benefit from liver metastasis resection if technically feasible.
The aim of this study was to evaluate the role of surgery in the treatment of non-colorectal, non-neuroendocrine (NCRNNE) liver metastases.
One hundred and thirty-four patients undergoing curative liver resection for NCRNNE liver metastases were retrospectively analyzed. Perioperative results (blood transfusion, hospital stay, morbidity and mortality), 3 and 5-year overall and disease-free survival were evaluated. The following prognostic factors were analyzed: age (cut-off 50 year old), single vs. multiple nodules, diameter (cut-off 5 cm), disease-free interval less vs. more than one year, type of primary tumor, blood transfusion, major hepatectomy vs. minor hepatectomy. Survival of patients undergoing liver resection for metastatic colorectal cancer was also analyzed to compare the results with the study population.
Mortality and morbidity rate were 3% and 23.1%, respectively. The 3 and 5-year survival were 56.5% and 40%, respectively. The 3 and 5-year disease-free survival were 44% and 30%, respectively. Diameter, disease-free interval and metastases from gastrointestinal cancers were independently related to the survival at the multivariate analysis. Thirty-nine patients (27%) survived over five years. Patients with liver metastases from gastrointestinal primary tumors were those with a worse survival (25% and 19% at 3 and 5 years, respectively).
Surgery is an effective treatment for patients with NCRNNE liver metastases, providing satisfactory long-term outcomes with acceptable morbidity and mortality, in particular when excluding patients with gastro-intestinal metastases.
Uveal melanoma is characterised by a high prevalence of liver metastases and a poor prognosis.
To review the evolving surgical management of this challenging condition at a single institution over a 16-year period.
Between January 1991 and June 2007, among 3873 patients with uveal melanoma, 798 patients had liver metastases. We undertook a detailed retrospective review of their clinical records and surgical procedures. The data was evaluated with both uni- and multivariate statistical analysis for predictive survival indicators.
255 patients underwent surgical resection. The median interval between ocular tumour diagnosis and liver surgery was 68 months (range 19-81). Liver surgery was either microscopically complete (R0; n = 76), microscopically incomplete (R1; n = 22) or macroscopically incomplete (R2; n = 157). The median overall postoperative survival was 14 months, but increased to 27 months when R0 resection was possible. With multivariate analysis, four variables were found to independently correlate with prolonged survival: an interval from primary tumour diagnosis to liver metastases >24 months, comprehensiveness of surgical resection (R0), number of metastases resected (< or = 4) and absence of miliary disease.
Surgical resection, when possible, is able to almost double the survival and appears at present the optimal way of improving the prognosis in metastatic uveal melanoma. Advances in medical treatments will be required to further improve survival.
Chemotherapy is highly effective for metastatic germ cell tumor (GCT), but experience with resection of hepatic metastases from GCT is limited.
Fifteen patients with GCT metastatic to the liver underwent 16 hepatic operations (1975-2002). Pre-resection therapy, surgical pathology, and operative outcomes were reviewed. All patients were followed to death or last contact for survival and disease status.
Patients underwent biopsy (three), wedge resection (nine), bisegmentectomy (two), and major lobectomy (two). Hepatic histology included: necrosis (33%), viable tumor (27%), mature teratoma (13%), and benign histology (27%). Concomitant resection of extrahepatic disease (14 patients, 93%) found necrosis (53%), mature teratoma (27%), and viable tumor (13%). Operative mortality was 0% and morbidity was 40%. At 8.2 years (mean) from resection, 11 patients (73%) were alive: five with no evidence of disease, two with elevated tumor marker only, and four with gross disease. Four patients (27%) died. The 10-year overall survival was 62% from diagnosis.
Resection of post-chemotherapy hepatic disease is safe, even when combined with resection of extrahepatic residual disease. The varied histologic findings, lack of reliable predictors, and prolonged survival achieved support a multidisciplinary approach which includes surgical resection of hepatic metastases.
Improvements in operative technique and perioperative management have expanded the application of hepatic resection for metastatic cancer. Although a policy of aggressive surgical resection of residual pulmonary and retroperitoneal disease following chemotherapy and normalization of serum tumor markers has been adopted for disseminated germ cell carcinoma, resection of residual hepatic disease in these cases has not been addressed. This report concerns a series of prospectively randomized patients who received systemic cisplatin-based chemotherapy for testis cancer during the past 13 years. Twenty-eight patients underwent resection of residual hepatic disease after serologic remission. Most (23 of 28 patients) of these procedures were performed concomitantly with other cytoreductive procedures. There were no operative deaths, although 28% of the patients developed complications. The 2-year survival rate was 54%, with an average follow-up of 34 months. Patients were stratified into three groups based on the most aggressive histology noted in the resected specimen. Survival is predicted by this histologic classification system. Hepatic resection can be performed safely and is an important component in the treatment of disseminated testicular carcinoma.
The role of liver resection for hepatic metastases from noncolorectal, nonneuroendocrine (NCNN) cancers is unknown. This study examines a large, single institutional experience of hepatic resection for NCNN metastases.
Records of 96 patients who underwent liver resection for metastatic NCNN cancer from 1980 to 1995 at a single institution were reviewed. Survival after liver resection in this cohort of patients is reported, and factors predictive of survival are analyzed.
Resection was performed for liver metastases from genitourinary primary tumors (n = 34), soft tissue primary tumors (n = 41), and metastases from other primary cancers (n = 21). Extent of liver resection included wedge (n = 32), lobectomy (n = 44), and extended hepatic lobectomy (n = 20). No operative deaths occurred. Overall survival rate after resection at 1, 3, and 5 years was 80%, 45% and 37%, respectively (median survival, 32 months), with 12 actual 5-year survivors. There was no difference in survival according to the type of liver resection, bilateral versus unilateral disease, or resection of extrahepatic disease. Disease-free interval of less than 36 months before discovery of liver metastases, curative resection, and primary tumor group (genitourinary was greater than soft tissue, which was greater than gastrointestinal) were predictors of a significantly better survival by multivariate analysis.
Primary tumor type, disease-free interval, and curative resection predict those patients who benefit from hepatic resection. Hepatic resection for patients with NCNN metastasis has value in carefully selected patients.
Advances in the field of liver surgery have lowered its associated mortality and morbidity rates, and hepatic resection for metastatic disease is increasingly performed. There are few well defined guidelines for the heterogeneous group of non-colorectal metastases. This study analysed the risks and benefits of surgical resection for liver metastases from non-colorectal primaries.
A retrospective study was performed of 34 patients who underwent 37 operations over a 10-year period. Compilation of data from 141 patients from eight additional recent series was performed in order to analyse the effect of histological type on survival.
There were no perioperative deaths. Complications occurred after seven of 37 procedures. Actuarial survival rates were 61, 43 and 27 per cent at 1, 2 and 5 years. Survival was significantly improved for curative versus palliative resection (P < 0.05), and for single versus multiple metastases (P < 0.05). A strong correlation was observed between time to presentation with metastasis and length of survival (P< 0.0001). Survival was significantly better for patients with secondaries from neuroendocrine tumours (P < 0.0001), worse for those with intestinal adenocarcinomas (P < 0.0001) and similar for patients with breast carcinoma (P > 0.5) when compared with the whole group.
The low mortality and morbidity rates and the satisfactory survival figures reported justify this type of surgery for selected patients, in the absence of therapeutic alternatives.
To identify prognostic factors and a model predictive for survival in patients with metastatic renal-cell carcinoma (RCC).
The relationship between pretreatment clinical features and survival was studied in 670 patients with advanced RCC treated in 24 Memorial Sloan-Kettering Cancer Center clinical trials between 1975 and 1996. Clinical features were first examined univariately. A stepwise modeling approach based on Cox proportional hazards regression was then used to form a multivariate model. The predictive performance of the model was internally validated through a two-step nonparametric bootstrapping process.
The median survival time was 10 months (95% confidence interval [CI], 9 to 11 months). Fifty-seven of 670 patients remain alive, and the median follow-up time for survivors was 33 months. Pretreatment features associated with a shorter survival in the multivariate analysis were low Karnofsky performance status (<80%), high serum lactate dehydrogenase (> 1.5 times upper limit of normal), low hemoglobin (< lower limit of normal), high "corrected" serum calcium (> 10 mg/dL), and absence of prior nephrectomy. These were used as risk factors to categorize patients into three different groups. The median time to death in the 25% of patients with zero risk factors (favorable-risk) was 20 months. Fifty-three percent of the patients had one or two risk factors (intermediate-risk), and the median survival time in this group was 10 months. Patients with three or more risk factors (poor-risk), who comprised 22% of the patients, had a median survival time of 4 months.
Five prognostic factors for predicting survival were identified and used to categorize patients with metastatic RCC into three risk groups, for which the median survival times were separated by 6 months or more. These risk categories can be used in clinical trial design and interpretation and in patient management. The low long-term survival rate emphasizes the priority of clinical investigation to identify more effective therapy.
The role of liver resection for hepatic metastases from noncolorectal carcinomas has yet to be clarified. The present study examines a single institutional experience of hepatic resection for noncolorectal metastases.
From January 1987 to March 1999, 14 patients underwent curative resection for liver metastases from noncolorectal carcinomas. Records of these patients were reviewed.
Resections were performed for liver metastases from gastric cancers (n = 8), pancreatic cancers (n = 2), and cancers of bile duct, the papilla of Vater, kidney, and breast (n = 1, each). Six patients (5 with gastric cancers and 1 with pancreas cancer) presented with synchronous disease and 8 with metachronous disease. In the gastric cancer patients, there are 2 disease-free survivors (26 and 53 months) in the metachronous group, though all of the 5 patients with synchronous disease died within 29 months. All of the 4 patients with pancreatobiliary carcinomas died within 2 years. One case of breast cancer and another of renal cell cancer are alive without disease at 49 and 9 months, respectively.
For metastases from gastric cancers, better survival after hepatic resection is expected in metachronous cases than in synchronous cases. Hepatic resection may afford little benefit for patients with liver metastases from pancretobiliary cancers.
To evaluate the outcome of patients with liver metastases from sarcoma who underwent hepatic resection at a single institution and were followed up prospectively.
The value of hepatic resection for metastatic sarcoma is unknown.
There were 331 patients with liver metastases from sarcoma who were admitted to Memorial Hospital from 1982 to 2000, and 56 of them underwent resection of all gross hepatic disease. Patient, tumor, and treatment variables were analyzed to assess outcome.
Of the 56 patients who underwent complete resection, 34 (61%) had gastrointestinal stromal tumors or gastrointestinal leiomyosarcomas. Half of the patients required an hepatic lobectomy or extended lobectomy. There were no perioperative deaths in the completely resected group, although 3 of the 75 patients who underwent exploration (4%) died. The postoperative 1-, 3-, and 5-year actuarial survival rates were 88%, 50%, and 30%, respectively, with a median of 39 months. In contrast, the 5-year survival rate of patients who did not undergo complete resection was 4%. On multivariate analysis, a time interval from the primary tumor to the development of liver metastasis greater than 2 years was a significant predictor of survival after hepatectomy.
Complete resection of liver metastases from sarcoma in selected patients is associated with prolonged survival. Hepatectomy should be considered when complete gross resection is possible, especially when the time to the development of liver metastasis exceeds 2 years.
Resection of liver metastases of non-colorectal primary malignancies has been reported to prolong survival. We studied the results in our hospital and compared the survival data with that described in the literature.
Since 1991, a prospective database has been kept at The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital of patients undergoing hepatic surgery (n=180). Between 1991 and 1999, 32 patients underwent laparotomy for hepatic metastases of non-colorectal primaries. This study evaluates the operative technical aspects and determines morbidity, mortality, disease-free and overall survival.
There were 11 males and 21 females with a median age of 52 (25-69) years. Histology of the primary tumour were various carcinomas (n=22), melanomas (n=4) and sarcomas (n=6). Resection was performed in 28 patients; four patients appeared to be irresectable. There was no perioperative mortality. Morbidity was 23%. One re-operation was necessary because of haemorrhage. The median disease-free survival for the 28 patients was 12 months with an actuarial 5-year disease-free survival of 20% (Kaplan-Meier). The 5-year overall survival was 35% with a median survival of 21 months.
Liver metastasectomy for selected types of non-colorectal primary tumours is relatively safe and shows in selected patients long-term survival comparable to that of metastasectomies for colorectal origin.
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.
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.
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.
In carefully selected patients with NCNN liver metastasis, liver resection can prolong survival as well and improve quality of life.
Liver resection for noncolorectal liver metastases has merit for selected primary tumor types. The role of cryosurgical tumor ablation within this cohort of patients has not been evaluated. This is a single institutional review of treatment outcomes using cryosurgical ablation and conventional resection techniques for noncolorectal liver metastases.
The medical records of 42 patients undergoing 48 hepatic tumor ablative procedures from February 1991 through May 2001 at a single institution were retrospectively reviewed. Overall survival and local hepatic tumor recurrence-free survival were analyzed for different surgical procedures and primary tumor types.
Overall survival rates at 1, 3, and 5 years are 82%, 55%, and 39%, respectively (median survival, 45 months). Local hepatic tumor recurrence-free survival rates for resection only (n = 25) and cryosurgery with or without resection (n = 23), at 3 years are 24% and 19%, respectively. The survival rates at 5 years are 40% and 37%, for resection only and cryosurgery with or without resection, respectively.
Cryosurgical hepatic tumor ablation for metastatic noncolorectal primary tumors results in survival and local hepatic tumor recurrence rates similar to resection alone. The combination of cryosurgery and resection extends the cohort of patients with surgically treatable disease.
Hepatic resection for recurrent ovarian carcinoma is controversial because of the paucity of relevant published data. The principles of cytoreduction before chemotherapy suggest that resection of measurable liver lesions in properly selected patients would be beneficial. To determine the effect of resection of metachronous liver metastases on morbidity and survival, we reviewed our experience with this treatment.
Medical records were reviewed retrospectively for all patients who had anatomic hepatic resection for metachronous parenchymal liver metastases from ovarian carcinoma (epithelial or malignant mixed Müllerian tumors) at Mayo Clinic from 1976 to 1999.
We identified 26 patients (median age at hepatic resection, 62 years; range, 39-75 years) who had hepatic resection requiring complete segmentectomies or more extensive hepatic surgery for recurrent ovarian carcinoma. Cytoreduction was optimal (extrahepatic and hepatic residual disease <or=1 cm) in 21 patients and suboptimal in 5. No intraoperative or postoperative deaths occurred. Aside from blood loss requiring transfusion of more than 4 units of erythrocytes in 4 patients, only two complications were noted: one superficial wound infection and one small-bowel perforation that required reoperation. The overall median disease-related survival was 26.3 months after hepatic resection; 18 patients (69%) died of disease at a median of 14.6 months (range, 5.0-41.3 months). However, 8 patients (31%) were alive at median follow-up of 33.2 months (range, 3.6-49.6 months). Factors significantly associated with improved disease-related survival were consistent with known prognostic factors associated with cytoreductive surgery, including more than 12 months since original diagnosis (27.3 vs 5.7 months, P = 0.004) and less than or equal to 1 cm of residual disease after hepatic resection (27.3 vs 8.6 months, P = 0.031).
We present evidence that hepatic resection can be performed with minimal surgical morbidity and mortality by surgical teams trained in the procedures. Because of the disease-related survival advantage afforded women by optimal cytoreductive surgery, parenchymal liver metastases should not preclude secondary cytoreductive surgical efforts.
Liver metastases of malignant renal tumors are regarded as having an ominous prognosis because they are infrequently amenable to radical surgery and respond poorly to chemotherapy. Little is known of the outcome of isolated metastases to the liver for which resection is potentially curative.
Data on 14 patients with liver metastases from renal tumors who underwent a liver resection in a single center between 1982 and 2001 were analyzed retrospectively.
There was no operative or postoperative mortality. The median survival was 26 months, with a survival rate of 69% at 1 year and 26% at 3 years. The curative pattern of hepatectomy (2-year survival, 69% vs. 0%; P =.001), an interval between the nephrectomy and the diagnosis of liver metastases in excess of 24 months (2-year survival, 71% vs. 25%; P =.05), tumor size <50 mm (2-year survival, 83% vs. 17%; P =.006), and the possibility of achieving a repeat hepatectomy in the case of recurrence (2-year survival, 100% vs. 21%; P =.02) were associated with a better outcome after the liver resection. Four patients were alive without evidence of disease at 6, 12, 26, and 96 months after the first hepatic resection, and one was alive with hepatic recurrence 18 months after resection.
In patients with liver metastases of malignant renal tumors, an aggressive policy for achieving tumor eradication seems to offer a chance for long-term survival, especially after a long disease-free interval from the nephrectomy. However, despite an aggressive policy for achieving tumor eradication, recurrence frequently occurs after liver resection.
To define perioperative and long-term outcome and prognostic factors in patients undergoing hepatectomy for liver metastases arising from noncolorectal and nonneuroendocrine (NCNN) carcinoma.
Hepatic resection is a well-established therapy for patients with liver metastases from colorectal or neuroendocrine carcinoma. However, for patients with liver metastases from other carcinomas, the value of resection is incompletely defined and still debated.
Between April 1981 and April 2002, 141 patients underwent hepatic resection for liver metastases from NCNN carcinoma. Patient demographics, tumor characteristics, treatment, and postoperative outcome were analyzed.
Thirty-day postoperative mortality was 0% and 46 of 141 (33%) patients developed postoperative complications. The median follow up was 26 months (interquartile range [IQR]) 10-49 months); the median follow up for survivors was 35 months (IQR 11-68 months). There have been 24 actual 5-year survivors so far. The actuarial 3-year relapse-free survival rate was 30% (95% confidence interval [CI], 21-39%) with a median of 17 months. The actuarial 3-year cancer-specific survival rate was 57% (95% CI, 48-67%) with a median of 42 months. Primary tumor type and length of disease-free interval from the primary tumor were significant independent prognostic factors for relapse-free and cancer-specific survival. Margin status was significant for cancer-specific survival and showed a strong trend for relapse-free survival.
Hepatic resection for metastases from NCNN carcinoma is safe and can offer long-term survival in selected patients. Hepatic resection should be considered if all gross disease can be removed, especially in patients with metastases from reproductive tract tumors or a disease-free interval greater than 2 years.
Uveal melanoma patients with liver metastases have a poor prognosis. The effect of screening and multimodality treatment (including surgery) should be evaluated.
A total of 602 patients treated for uveal melanoma during a 14-year period had abdominal ultrasonography screening every 6 months. Sixty-three developed liver metastases as the first extraocular metastatic site. When possible, liver surgery and intra-arterial catheter implantation were performed. The influence on survival of demographics, uveal tumor characteristics, liver metastasis presentation, and treatment was studied.
The median time to liver metastasis was 29 months. Twenty-eight patients (44%) were operated on: 14 (22%) had R0 liver surgery, and 14 with diffuse liver involvement had R2 liver surgery (there were no significant surgical complications). Thirty-five patients with diffuse liver involvement received systemic chemotherapy or best supportive care only. The median overall survival was 15 months (range, 3-110 months): 25 months for the 14 patients with R0 surgery, 16 months for the 14 with R2 surgery, and 11 months for the 35 with chemotherapy or supportive care. By univariate analysis, age (< or =70 years), number of metastases (< or =10), and quality of operation (R0) were predictive of a better prognosis.
In the case of liver metastases from uveal melanoma, aggressive treatment permitting tumor eradication seems to offer a chance of long-term survival to selected patients. Nevertheless, neither ultrasound screening nor quality of operation had an effect on the outcome of most patients (78%). Better screening tests and more effective multimodality treatments are required to improve survival in uveal melanoma patients with hepatic metastases.
In recent years, imatinib mesylate (STI 571), a tyrosine kinase inhibitor, has shown short-term clinical usefulness for gastrointestinal stromal tumor or gastrointestinal leiomyosarcoma (GIST). The value of surgical resection, including hepatectomy, for metastatic GIST remains unknown. Our aim was to evaluate the outcome of surgical resection, including hepatectomy, for metastatic GIST at a single institute.
Eighteen patients who underwent hepatectomy for metastatic GIST were identified and the clinicopathological data of these patients were analyzed retrospectively.
The primary site of GIST included stomach in 10, duodenum in five, ileum in two and esophagus in one patient. A hemihepatectomy or greater resection was undertaken in eight patients. Six patients underwent simultaneous resection for primary and hepatic disease. There was no in-hospital mortality in this series. The post-hepatectomy 3- and 5-year survival rates were 63.7 and 34.0% respectively, with a median of 36 (17-227) months. Recurrence after the initial hepatectomy was documented in 17 patients (94%), and metastatic mass of the remnant liver developed in 15 of these 17 patients (88%). Three patients survived >5 years after the initial hepatectomy who underwent multiple surgical resections during this period. No clinicopathological characteristic was a significant predictive factor for survival.
Multiple surgical resections, including hepatectomy, may contribute to important palliation in selected patients with metastatic GIST. Surgical cure seems to be difficult due to the high frequency of repeat metastasis to various sites. Therefore, adjuvant therapy must be required in the treatment of metastatic GIST.
The isolated occurrence of noncolorectal liver metastases is rare. The available data are inconsistent in terms of indication for surgery, treatment, and outcome, so a generally applicable therapeutic algorithm is currently lacking.
A total of 162 patients underwent resection for noncolorectal liver metastases between 1978 and 2001. The patients were divided into two groups from different time periods (group 1, 1978-1989; group 2, 1990-2001) that were similar in terms of number of patients, operating surgeons, and surgical techniques used. The groups were compared, and the data were retrospectively analyzed with regard to indication, survival, and factors predictive for survival.
Resection was performed to remove liver metastases from noncolorectal gastrointestinal carcinoma (n = 50), neuroendocrine tumors (n = 12), genitourinary primary tumors (n = 11), breast carcinoma (n = 24), leiomyosarcoma (n = 15), and metastases from other primary cancers (n = 50). Extrahepatic tumor involvement was seen in 38 (23%) of the 162 cases. Sixty-two (38%) major hepatectomies and 100 (62%) minor resections were performed. In 100 (62%) of 162 patients, a curative resection (R0) could be achieved. Overall 2- and 5-year survival rates of 49% and 26%, respectively, were observed, and the median survival was 23 months. Survival was significantly longer in patients who underwent an R0 resection.
In selected patients, resection of noncolorectal liver metastases is associated with a 5-year survival rate of up to 50%. Resection of liver metastases from gastrointestinal adenocarcinomas correlates with a poor prognosis. Extrahepatic metastases may be considered a relative contraindication for liver resection.
Resection of certain hepatic metastases of noncolorectal, nonneuroendocrine (NCNNE) origin provides actual long-term (>5 years) survival. We conducted a retrospective outcome study at a single tertiary referral institution. Between January 1988 and October 1998, 64 consecutive patients underwent resection of hepatic metastases from NCNNE primary tumors. Overall and disease-free survival rates were correlated to clinicopathologic factors and operative morbidity and mortality. Thirteen patients underwent a right hepatectomy, 6 underwent a left hepatectomy, 3 had extended right and 2 extended left hepatectomy, 2 patients had segmentectomy, 24 underwent wedge resections, and 14 underwent a combination of these forms of resection. R0 resection was achieved in 56 patients (87.5%). The operative mortality was 1.5% (1 of 64). Actual 1-, 3-, and 5-year survivals were 81%, 43%, and 30%, respectively. The factor adversely associated with overall and disease-free survival was uniformly related to the interval between primary tumor resection and the development of hepatic metastases. A 1.5% operative mortality and an actual 5-year survival of 30% justifies hepatic resection, including major hepatic resection, for certain NCNNE metastases. The factor affecting prognosis in this highly select group of patients was the biological behavior of the tumor, with tumors that metastasize earlier having poorer survival rates.