Non-neuroendocrine Metastases Research Articles

Surgery for Liver Metastasis of Non-Colorectal and Non-Neuroendocrine Tumors.

Surgery has become well established for patients with colorectal and neuroendocrine liver metastases. However, the value of this procedure in non-colorectal and non-neuroendocrine metastases (NCRNNELMs) remains unclear. We analyzed the outcomes of patients that underwent liver surgery for NCRNNELMs and for colorectal liver metastases (CRLMs) between 2012 and 2017 at our institution. Prognostic factors of overall and recurrence-free survival were analyzed, and a comparison of survival between two groups was performed. Seventy-three patients (30 NCRNNELM and 43 CRLM) were included in this study. Although the mean age, extrahepatic metastases, and rate of reoperation were significantly different between the groups, recurrence-free survival was comparable. The 5-year overall survival rates were 38% for NCRNNELM and 55% for CRLM. In univariate analysis, a patient age of ≥60 years, endodermal origin of the primary tumor, and major complications were negative prognostic factors. Resection for NCRNNELM showed comparable results to resection for CRLM. Age, the embryological origin of the primary tumor, and the number of metastases might be the criteria for patient selection.

Noncolorectal, Nonneuroendocrine Liver Metastasis

Noncolorectal, nonneuroendocrine metastases represent a heterogeneous group with variable tumor biology. Successes in the use of hepatectomy for colorectal liver metastases has increased interest in resection of noncolorectal, nonneuroendocrine metastases. Cure rates equivalent to those of colorectal liver metastases have not been achieved, but resection of noncolorectal, nonneuroendocrine metastases can often provide improved overall survival compared with systemic therapy alone or exclusively palliative care. Overall survival outcomes can be achieved with acceptable perioperative morbidity and mortality relative to rates for hepatectomies in general. Prospective data regarding the utilization of resection for noncolorectal, nonneuroendocrine metastases are lacking, but retrospective data are encouraging. In appropriately selected patients with favorable tumor biology and excellent performance status, resection of noncolorectal, nonneuroendocrine may offer a survival benefit. This review contains 1 figure, 2 tables, and 31 references. Key Words: breast cancer, cytoreduction, gastric cancer, GIST, hepatectomy, melanoma, metastasis, ovarian cancer, pancreatic cancer, renal cell carcinoma

Noncolorectal, Nonneuroendocrine Liver Metastasis

Noncolorectal, nonneuroendocrine metastases represent a heterogeneous group with variable tumor biology. Successes in the use of hepatectomy for colorectal liver metastases has increased interest in resection of noncolorectal, nonneuroendocrine metastases. Cure rates equivalent to those of colorectal liver metastases have not been achieved, but resection of noncolorectal, nonneuroendocrine metastases can often provide improved overall survival compared with systemic therapy alone or exclusively palliative care. Overall survival outcomes can be achieved with acceptable perioperative morbidity and mortality relative to rates for hepatectomies in general. Prospective data regarding the utilization of resection for noncolorectal, nonneuroendocrine metastases are lacking, but retrospective data are encouraging. In appropriately selected patients with favorable tumor biology and excellent performance status, resection of noncolorectal, nonneuroendocrine may offer a survival benefit. This review contains 1 figure, 2 tables, and 31 references. Key Words: breast cancer, cytoreduction, gastric cancer, GIST, hepatectomy, melanoma, metastasis, ovarian cancer, pancreatic cancer, renal cell carcinoma

Outcome of liver resection for non-colorectal, non-neuroendocrine metastases - a single-center experience

Background: Evidence is increasing that subgroups of non-colorectal (NCRC), non-neuroendocrine (NNE) liver metastases (LM) benefit from liver surgery. Methods: Patients who underwent curative surgery for NCRC/NNE-LM were recorded in a prospective institutional data base. Patient age, tumor entity, histology, type of resection, R-status, extrahepatic disease, overall (OS) and disease-free survival (DFS) were assessed. Re-resections were excluded. Results: Of 129 patients who underwent liver resection for NCRC/NNE LM, 83 patients with a median age of 61.2 years were included. Liver surgery was performed for metastases from periampullary (n=14), urogenital (UGT, n=13), upper gastrointestinal (UGI, n=13), breast (BC, n=9) and renal cancer (n=6), as well as for gastrointestinal stromal tumors (GIST, n=11) and others (n=17). Twenty-nine major resections were performed, while the remaining 54 were resections of less than 3 segments. R0 resection was achieved in 76 cases (91.6%). Median OS and DFS for the entire cohort were 46.1 and 16.4 months, respectively. Patients with metastases from GIST and BC revealed the best median OS (92.5 months). Patients with renal cancer, urogenital tumors, and others revealed a median survival of 57.3 months while the remaining entities achieved a median OS of 29.6 months. Conclusion: Patients with NCRC/NNE LM benefit from liver resection with curative intent. Breast cancer and GIST liver metastases have benefited the most from liver surgery in our cohort of patients.

Outcome of liver resection for non-colorectal, non-neuroendocrine metastases - a single-center experience

Outcome of liver resection for non-colorectal, non-neuroendocrine metastases - a single-center experience

Evolving Role of Hepatic Resection for Metastatic Urologic Malignancies

Liver resection for noncolorectal, nonneuroendocrine metastases remains controversial. Here, we evaluate a single institutional experience with hepatic resection for metastatic urologic malignancies. A single-institution review of patients who underwent hepatic resection for metastatic urologic tumors between the years of 2000 and 2013 was performed. Patient charts were analyzed for pathologic data and perioperative outcomes including short- and long-term morbidity, mortality, and overall and disease-free survival. Eleven patients were identified who underwent hepatic resection for metastatic urologic malignancy. The mean age was 63.5 years. All patients had an R0 resection. There were three major complications. Mean length of stay was 6.5 days and there was no 90-day mortality. Three patients have died of recurrent disease at an average of 11.2 months from resection to death. The remaining patients are still alive during a mean follow-up of 31.5 months. Five-year overall and disease-free survival was 50 and 21 months, respectively. Hepatic resection for metastatic urologic tumors is safe with low morbidity and mortality and durable long-term survival can be achieved. Liver resection for isolated hepatic disease should be considered for this rare metastatic disease to the liver.

Liver resection for noncolorectal and nonneuroendocrine metastases: results of a study on 56 patients at a single institution.

The usefulness of surgical treatment for hepatic metastases of noncolorectal nonneuroendocrine (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.

Is Hepatic Resection for Non-colorectal, Non-neuroendocrine Liver Metastases Justified?

Discussions about the benefit of liver resection (LRx) for non-colorectal, non-neuroendocrine metastases are controversial. This study aimed to analyze the outcome of LRx for these patients and validate a previously published prognostic risk model. The study analyzed 150 patients who underwent LRx for non-colorectal non-neuroendocrine (NCNN) metastases. Patients' demographics, tumor characteristics, treatment options, and postoperative outcome were investigated. The Kaplan-Meier method and Cox regression models were used to assess survival and prognostic variables. After a median follow-up period of 61 months, 39 % of the patients were alive. The 30-day mortality rate was 0.7 %. The overall, disease-free, and intrahepatic recurrence-free survival rates were respectively 42, 29, and 51 % at 5 years and 28, 23, and 47 % at 10 years. The negative prognostic factors identified in the multivariate analysis were melanoma (p = 0.04), squamous tumors (p = 0.01), and a primary tumor liver metastasis, with an interval shorter than 2 years (p = 0.02), whereas the predictive prognostic factors identified were breast cancer (p = 0.04), stromal tumors (p = 0.03), and major LRx (p = 0.04). The prognostic risk score stratified patients into low risk (0-3 points: n = 50; 5-year overall survival [OS] 58 %), medium risk (4-6 points: n = 91; 5-year OS 35 %), and high risk (≥7 points: n = 9; 5-year OS, 33 %) groups (p = 0.01). Liver resection for patients with NCNN metastases is a safe treatment option. More than 25 % of patients can achieve a long-term survival of 10 years when the histology of the primary tumor and the surrogates for the individual biologic tumor behavior are taken into account. Exclusion of patients with NCNN liver metastases from surgical therapy is no longer justified.

Tumors of the Liver and Biliary Tract

This review discusses several different types of tumors that affect the liver, biliary tree, and gallbladder. Primary and secondary liver cancers are discussed, including hepatocellular carcinoma, intrahepatic cholangiocarcinoma, colorectal metastases, neuroendocrine metastases, and noncolorectal, nonneuroendocrine metastases. Clinical evaluation, investigative studies, tumor staging, and treatment options are presented for each. Benign or premalignant hepatic lesions are also discussed, including the appropriate workup and surgical options for hemangioma, hepatic adenoma, focal nodular hyperplasia, and nonparasitic cystic tumors. Cancers of the biliary tract (cholangiocarcinomas) are subdivided into intrahepatic and extrahepatic cholangiocarcinomas. The latter are subdivided into hilar and distal cholangiocarcinoma; their clinical evaluation, investigative studies, staging, and management are discussed. The clinical evaluation, investigative studies, testing, imaging, staging, and management are presented for gallbladder cancer, including incidentally discovered gallbladder cancer and gallbladder polyps. Figures include the anatomic divisions of the liver and Brisbane terminology for resections, CT and MR images showing characteristic features of the liver and biliary tract tumors, Bismuth-Corlette classification of hilar cholangiocarcinoma, and algorithms for the management of hepatocellular carcinoma and neuroendocrine metastases. Tables include the American Joint Committee on Cancer’s classification and staging systems for hepatocellular carcinoma, cholangiocarcinoma, and gallbladder cancer; Brisbane terminology for liver resections; and neuroendocrine tumors with their corresponding biochemical markers. This review contains 14 figures, 7 tables, and 83 references.

Surgical management of non‐colorectal hepatic metastasis

Isolated hepatic metastases from non-colorectal primary tumors are rare. Patients with neuroendocrine tumors have an indolent biology compared with other non-colorectal histologies. This article discusses the surgical management options for patients with neuroendocrine liver metastases and, separately, for those with non-colorectal, non-neuroendocrine metastases. Emphasis is placed on the importance of patient selection, understanding the tumor biology and response to systemic therapy.

Liver Resection for Noncolorectal, Nonneuroendocrine Metastases: A Single-center Experience

Liver Resection for Noncolorectal, Nonneuroendocrine Metastases: A Single-center Experience

Liver resection post-selective internal radiation therapy – an overview

Surgical resection of primary and secondary liver tumours or liver transplantation are the only potentially curative options. However, only a minority of patients (15−25%) with primary hepatocellular carcinoma, intrahepatic cholangiocarcinoma, colorectal liver metastases, neuroendocrine metastases and non-colorectal and nonneuroendocrine metastases are suitable for surgical resection. There remains debate about the definition of resectability, but this is broadly acknowledged to be complete removal of all tumour (R0 resection) whilst leaving sufficient functioning liver remnant (approximately 25% of the liver) for post-operative survival. The balance of tumour clearance and residual liver parenchyma is dictated by the anatomical distribution of the tumours and the function of the underlying liver parenchyma. The value of liver resection for colorectal metastases is reported by the Liver Met Survey database (www.livermetssurvey.com). There is however, wide

Liver resection for noncolorectal and nonneuroendocrine metastases: Results of a study on 56 patients at a single institution

The usefulness of surgical treatment for hepatic metastases of noncolorectal nonneuroendocrine (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.

Local Recurrence After Laparoscopic Radiofrequency Ablation of Liver Tumors: An Analysis of 1032 Tumors

The best measure of the technical success of radiofrequency ablation (RFA) is local recurrence (LR). The aim of this prospective study is to identify factors that predict LR. Three hundred thirty-five patients with 1032 unresectable liver tumors underwent laparoscopic RFA between November 1999 and August 2005. All lesions were assessed prospectively regarding tumor type, size, liver segment, blood vessel proximity, and central or peripheral location in the operating room and size of ablation zone at 1-week computed tomographic (CT) scans. Lesions that recurred in follow-up CT scans were identified prospectively. LR was categorized as contiguous or adjacent. Univariate Kaplan-Meier and Cox proportional hazard models were used for statistical analysis. LR was identified 21.7% of tumors on CT scans with a mean follow-up of 17 months (median, 12 months; range, 3-68 months). This was contiguous in 70% and adjacent in 30%. LR rate per tumor was highest for colorectal metastasis (34%), followed by noncolorectal, nonneuroendocrine metastasis (22%), hepatocellular carcinoma (18%), and neuroendocrine metastasis (6%). By univariate analysis, tumor type and size, ablation margin, liver segmental location, blood vessel proximity, and type of ablation (first time vs. repeat) were found to affect LR. The Cox proportional hazard model identified tumor type, tumor size, ablation margin, and blood vessel proximity to be independent predictors of LR. LR after RFA is predicted by certain tumor characteristics and technical factors. This information can be used intraoperatively to identify those tumors at a higher risk for failure.

Liver resection for non-colorectal, non-neuroendocrine metastases: analysis of a multicenter study from Argentina

Background and aim: Resection of colorectal liver metastases has become a standard of care, although the value of this procedure in non-colorectal non-neuroendocrine (NCRNNE) metastases remains controversial and is still a matter of debate. The aim of the study was to determine the utility of liver resection in the long-term outcome of patients with NCRNNE metastases. Material and methods: The records of 106 patients who underwent liver resection for NCRNNE metastases in the period 1989 to 2006 at 5 HPB Centers in Argentina were analyzed. Patient demographics, tumor characteristics, type of resection, long-term outcome and prognostic factors were analyzed. Depending on primary tumor sites, a comparative analysis of survival was performed. Results: Mean age was 54 (17–76). Hepatic metastases were solitary in 62.3% and unilateral in 85.6%. Primary tumor sites: Urogenital (37.7%), sarcomas (21.7%), breast (17.9%), gastrointestinal (6.6%), melanoma (5.7%), and others (10.4%). Fifty-one major hepatectomies and 55 minor resections were performed. Twenty patients underwent synchronous resections. An R0 resection could be achieved in 89.6%. Perioperative mortality was 1.8%. Overall, 1-year, 3-year, and 5-year survival rates were 67%, 34%, and 19%, respectively. Survival was significantly longer for metastases of urogenital (p=0.0001) and breast (p=0.003) origin. Curative resections (p=0.04) and metachronous disease (p=0.0001) were predictors of better survival. Conclusions: Liver resection is an effective treatment for NCRNNE liver metastases; it gives satisfactory long-term survival especially in metachronous disease, in patients with metastases from urogenital and breast tumors and when R0 procedures can be performed.

Long-Term Results of Liver Resection for Non-colorectal, Non-neuroendocrine Metastases

The safety and efficacy of liver resection for colorectal and neuroendocrine liver metastases is well established. However, there is lack of consensus regarding long-term effectiveness of hepatic resection for non-colorectal, non-neuroendocrine (NCNN) liver metastases. A review of prospectively collected data of patients undergoing hepatic resection for NCNN liver metastases at two tertiary referral centres in the UK and Australia was undertaken. Survival analysis was used to evaluate the clinical, demographic and operative factors associated with long-term survival. A total of 114 hepatic resections in 102 patients were performed between 1986 and 2006. Postoperative mortality and morbidity was 0.8% and 21.1%, respectively. At 3 and 5 years overall survival was 56.1% and 38.5%, whereas disease-free survival was 37.2% and 26.5%, respectively. On multivariate analysis, factors associated with poor overall survival were diameter of liver metastasis [<5 cm versus >5 cm: hazard ratio (HR) = 2.83, p = 0.001] and the presence of extrahepatic nodal disease (HR = 3.58, p = 0.001). The type of tumor, the presence of distant extra-hepatic metastases, tumor-free interval, number and distribution of metastases did not effect long-term survival. These results of the present study suggest that liver resection is an effective management option in selected patients with NCNN metastases confined to the liver.

Diagnostic des tumeurs du sein : cytoponction ou microbiopsie ?

Isolated liver metastases occur rarely in patients with metastatic breast cancer. The success of liver resection (LR) for other metastatic disease has led centres to explore the option of LR for patients with isolated breast cancer liver metastases (BCLM). A number of small series have been published in the literature, however the evidence is conflicting. This study aimed to systematically review the literature to determine the perioperative outcome and survival of patients undergoing LR for BCLM.An electronic search of Medline and Embase databases was performed to identify all published series. Patient demographics, management, peri-operative outcome and overall survival (OS) were obtained.A total of 1705 articles were identified of which 531 included patients with non-colorectal and non-neuroendocrine metastases. 43 articles including 1686 patients, met all the inclusion and exclusion criteria. R0 resection was achieved in 83% (683/825). Morbidity and 30-day mortality rates were 20% (174/852) and 0.7% (6/918), respectively. The median OS was 36 months (12–58 months). The median 1-, 3-and 5-year OS were 90%, 56% and 37%, respectively.LR for BCLM can be carried out with acceptable peri-operative risks in selected patients with survival outcomes that appear to be superior to chemotherapy alone.

The Role of Liver Resections for Noncolorectal, Nonneuroendocrine Metastases: Experience With 142 Observed Cases

To evaluate the role of liver resection for noncolorectal, nonneuroendocrine metastases, indications and results were retrospectively reviewed in 142 observed patients. A curative liver resection was performed in 83 cases (58.5%), and the remaining 59 patients received palliative treatments. The primary tumor site was gastrointestinal in 18, breast in 21, genitourinary in 15, leiomyosarcoma in 10, and other in 19. The mean number of metastases was 1.4. The mean diameter of the nodules was 5.7 cm. Liver metastases were synchronous in 11 (13.3%) cases and metachronous in the remaining 72 (86.7%). There was no operative mortality. Postoperative morbidity was 20.5%. The median postoperative stay was 9.5 days. The 3- and 5-year actuarial survival rate was 49.5% and 34.3% in resected cases, respectively, whereas there were almost no survivors 3 years after diagnosis in unresected cases (P < .05). The 3- and 5-year disease-free survival was 41.4% and 23.8%, respectively. Among the 83 resected cases, the 3- and 5-year actuarial survival was 17.3% and 8.6% for metastases from gastrointestinal tumors, 53.9% and 24.6% from breast cancer, 63.7% and 36.4% from leiomyosarcoma, 50.4% and 37.8% from genitourinary neoplasms, and 55.6% and 42.4% from other sites, respectively. Fifteen patients (18.1%) survived longer than 5 years. Liver resection is an effective treatment for noncolorectal, nonneuroendocrine metastases; it allows satisfactory long-term survival with an acceptable operative risk in selected patients. Hepatic metastases from gastrointestinal carcinoma have the worst prognosis; those from genitourinary tumors show a better outcome. Patient selection is the key to achieving encouraging results.

Liver ablation therapy.

The first description of percutaneous ethanol injection (PEI) was published in 1986, a small series of just 14 patients with small, non-resectable hepatocellular carcinoma (HCC) [1]. Thermal techniques were first performed in the liver at our institution in 1989, initially using single bare tip neodymium yttrium aluminium garnet (NdYAG l 1064 nm) laser fibres placed under ultrasound guidance [2]. 15 years on there are hundreds of centres performing thousands of ablations mostly using radiofrequency (RF). The most common site for treatment remains the liver but ablation has been performed in many other sites including lung, renal, adrenal, pleura, bone, pelvic tumours and nodal masses. Two particularly promising areas of development are RF ablation for inoperable lung cancer and as a minimally invasive, nephron sparing technique in renal cell carcinoma. This article looks at liver ablation; the different technologies available, the clinical results and current status of ablation in patients with colorectal liver metastases, neuroendocrine metastases and non-colorectal, non-neuroendocrine metastases, e.g. breast, and HCC.

Liver Resection for Noncolorectal, Nonneuroendocrine Metastases

In noncolorectal, nonendocrine liver metastases, the role of surgery is less define than in colorectal or neuroendocrine cancer. This role is marginal as liver is not the primary site of metastases of these cancers. Less than 2 to 5% of the patients with these malignancies might be one day considered as potential candidates for liver resection, as most patients suffer from extra hepatic tumour spread at the time they develop liver involvement. However, in these few cases with liver metastases only, as no other therapeutic option may provide mid-or long-term tumour-free survival, liver resection is indicated in resectable liver metastases. Some prognostic factors have been established in the literature from the few published series: unique versus multiple hepatic metastases, unilobar vs bilobar, metachronous vs synchronous, R0 vs R1 or R2 liver resections. The type of primary tumour is also of great importance, as cutaneous melanoma, pancreatic and gastric adenocarcinoma have a very bad prognosis for liver resection of metastases, even after R0 resection. In these cases, percutaneous or laparoscopic radiofrequency ablation may find its place. In sarcoma, breast carcinoma, uveal melanoma, and genitourinary cancers, liver resection may provide satisfactory long-term results in selected cases, and is the standard of care for isolated, resectable metastasis. However, due to the scarcity of indication of liver resection for noncolorectal, nonneuroendocrine metastases, the decision should be multidisciplinary, and the patients should be informed of the advantages and pitfalls of the surgical procedure.