Non-colorectal Non-neuroendocrine Liver Metastases Research Articles

Current status of liver surgery for non-colorectal non-neuroendocrine liver metastases: the NON.LI.MET. Italian Society for Endoscopic Surgery and New Technologies (SICE) and Association of Italian Surgeons in Europe (ACIE) collaborative international survey.

Despite the increasing trend in liver resections for non-colorectal non-neuroendocrine liver metastases (NCNNLM), the role of surgery for these liver malignancies is still debated. Registries are an essential, reliable tool for assessing epidemiology, diagnosis, and therapeutic approach in a single hub, especially when data are dispersive and inconclusive, as in our case. The dissemination of this preliminary survey would allow us to understand if the creation of an International Registry is a viable option, while still offering a snapshot on this issue, investigating clinical practices worldwide. The steering committee designed an online questionnaire with Google Forms, which consisted of 37 questions, and was open from October 5th, 2022, to November 30th, 2022. It was disseminated using social media and mailing lists of the Italian Society of Endoscopic Surgery and New Technologies (SICE), the Association of Italian Surgeons in Europe (ACIE), and the Spanish Chapter of the American College of Surgeons (ACS). Overall, 141 surgeons (approximately 18% of the total invitations sent) from 27 countries on four continents participated in the survey. Most respondents worked in general surgery units (62%), performing less than 50 liver resections/year (57%). A multidisciplinary discussion was currently performed to validate surgical indications for NCNNLM in 96% of respondents. The most commonly adopted selection criteria were liver resectability, RECIST criteria, and absence of extrahepatic disease. Primary tumors were generally of gastrointestinal (42%), breast (31%), and pancreaticobiliary origin (13%). The most common interventions were parenchymal-sparing resections (51% of respondents) of metachronous metastases with an open approach. Major post-operative complications (Clavien-Dindo > 2) occurred in up to 20% of the procedures, according to 44% of respondents. A subset analysis of data from high-volume centers (> 100 cases/year) showed lower post-operative complications and better survival. The present survey shows that NCNNLM patients are frequently treated by surgeons in low-volume hospitals for liver surgery. Selection criteria are usually based on common sense. Liver resections are performed mainly with an open approach, possibly carrying a high burden of major post-operative complications. International guidelines and a specific consensus on this field are desirable, as well as strategies for collaboration between high-volume and low-volume centers. The present study can guide the elaboration of a multi-institutional document on the optimal pathway in the management of patients with NCNNLM.

Influence of the tumor site and histopathology after resection for non-colorectal non-neuroendocrine liver metastases. A single center experience

IntroductionIt remains unclear whether liver resection is justified in patients with non-colorectal non-neuroendocrine liver metastases (NCNNLM). A single-center study was conducted to analyse overall survival (OS), disease-free survival (DFS), and potential prognostic factors in patients with different types of NCNNLM. MethodA retrospective analysis of all patients who underwent liver resection of NCNNLM from January 2006 to July 2019 was performed. ResultsA total of 62 patients were analyzed. 82.3% presented metachronous metastases and 74.2% were unilobar. The most frequent primary tumor site (PTS) were breast (24.2%), urinary tract (19.4%), melanoma (12.9%), and pancreas (9.7%). The most frequent primary tumor pathologies were breast carcinoma (24.2%), non-breast adenocarcinoma (21%), melanoma (12.9%) and sarcoma (12.9%). The most frequent surgical procedure performed was minor hepatectomy (72.6%). R0 resection was achieved in 79.5% of cases. The major complications’ rate was 9.7% with a 90-day mortality rate of 1.6%. The 1, 3 and 5-year OS/DFS rate were 65%/28%, 45%/36% and 46%/28%, respectively. We identified the response to neoadjuvant therapy and PTS as possible prognostic factors for OS (P =0.06) and DFS (P =0.06) respectively. ConclusionBased on the results of our series, NCNNLM resection produces beneficial outcomes in terms of OS and DFS. PTS and the response to neoadjuvant therapy could be the main prognostic factors after resection.

Therapie von Lebermetastasen

BackgroundThe liver is the main destination for distant metastases of gastrointestinal as well as other malignancies. Consequently, the therapy of liver metastases plays a key role in oncological treatment strategies.ObjectivesIn this review, the current treatment options and multimodal therapy strategies for liver metastases are presented.Materials and methodsCurrent literature and national/international consensus guidelines are reviewed and general treatment options for liver metastases are summarized and then presented for the respective malignancies.ResultsAccording to treatment strategy and prognosis, liver metastases are divided into three categories: colorectal liver metastases (CRLM), neuroendocrine liver metastases, and non-colorectal non-neuroendocrine liver metastases which include liver metastases of all other malignancies. Due to their highest incidence, CRLM are of major interest. The individual treatment is chosen according to patient’s oncological situation, liver function, and comorbidities.ConclusionsSurgery is the best curative treatment option. Thus, all patients should be evaluated for surgery in specialized oncological boards. Despite higher local recurrence, local ablation methods are good alternative options for small and limited metastases. Systemic treatments and radiation are implemented in palliative settings as well as multimodal treatment strategies with the goal of cure.

Influence of the tumor site and histopathology after resection for non-colorectal non-neuroendocrine liver metastases. A single center experience

IntroductionIt remains unclear whether liver resection is justified in patients with non-colorectal non-neuroendocrine liver metastases (NCNNLM). A single-center study was conducted to analyse overall survival (OS), disease-free survival (DFS), and potential prognostic factors in patients with different types of NCNNLM. MethodA retrospective analysis of all patients who underwent liver resection of NCNNLM from January 2006 to July 2019 was performed. ResultsA total of 62 patients were analyzed. 82.3% presented metachronous metastases and 74.2% were unilobar. The most frequent primary tumor site (PTS) were breast (24.2%), urinary tract (19.4%), melanoma (12.9%), and pancreas (9.7%). The most frequent primary tumor pathologies were breast carcinoma (24.2%), non-breast adenocarcinoma (21%), melanoma (12.9%) and sarcoma (12.9%). The most frequent surgical procedure performed was minor hepatectomy (72.6%). R0 resection was achieved in 79.5% of cases. The major complications’ rate was 9.7% with a 90-day mortality rate of 1.6%. The 1, 3 and 5-year OS/DFS rate were 65%/28%, 45%/36% and 46%/28%, respectively. We identified the response to neoadjuvant therapy and PTS as possible prognostic factors for OS (P =0.06) and DFS (P =0.06) respectively. ConclusionBased on the results of our series, NCNNLM resection produces beneficial outcomes in terms of OS and DFS. PTS and the response to neoadjuvant therapy could be the main prognostic factors after resection.

Histopathological growth patterns of resected non-colorectal, non-neuroendocrine liver metastases: a retrospective multicenter study.

Distinct Histopathological Growth Patterns can be identified in liver metastases from melanoma, breast and colorectal cancers. For each of these distinct liver metastasis types the HGP has proven a biomarker for survival after partial hepatectomy, with the desmoplastic type marking favourable prognosis. Whether HGPs can be considered a pan-cancer phenomenon remains unknown. This study therefore evaluates the presence of HGPs and their prognostic value across non-colorectal non-neuroendocrine liver metastases. A retrospective multicentre cohort study was performed in patients who underwent curative intent resection of non-colorectal non-neuroendocrine liver metastasis. HGPs were assessed on Haematoxylin and Eosin slides according to consensus guidelines and classified as desmoplastic or non-desmoplastic. Overall- and recurrence-free survival were evaluated using Kaplan-Meier and multivariable Cox regression analysis. In total, 132 patients with liver metastasis from 25 different tumour types were eligible for analysis, of which 26 (20%) had a desmoplastic HGP. Five-year OS and RFS (95%CI) were 53% (36-78%) versus 40% (30-53%), and 33% (19-61%) versus 15% (9-27%) for patients with desmoplastic compared to non-desmoplastic metastases, respectively (p = 0.031 & p = 0.004). On multivariable analysis (adjusted HR [95%CI]) a desmoplastic HGP was prognostic for both OS (0.46 [0.25-0.86]) and RFS (0.38 [0.21-0.69]). This study demonstrates that HGPs apply to liver metastases across a wide variety of primary tumour origins. They hold a prognostic value in these cases, suggesting that HGPs could represent a pan-cancer biomarker for survival after surgical resection of liver metastases.

Laparoscopic liver resection for non-colorectal non-neuroendocrine liver metastases: narrative review of literature

: Liver resection for resectable colorectal and neuroendocrine liver metastases is the treatment of choice, and laparoscopic approach is considered safe and viable in these patients, with less postoperative complications compared to open surgery. Liver surgery for non-colorectal non-neuroendocrine liver metastases (NCNNLM) is a controversial issue as well as the role of minimally invasive surgery for this heterogeneous groups of malignancies. Patients with NCNNLM in fact are frequently referred to palliation due to the presence of extra-hepatic disease, and even in case of surgery, they usually undergo laparotomic approach. This article aims to examine and consider some of the most relevant contribution to this issue published in literature, trying to take stock of this still unsolved topic of oncologic surgery. Several studies have stated that liver resection can improve outcome in patients with NCNNLM, after careful selection based on different aspects and characteristics. Several criteria of selection have been identified, trying to select patients who could benefit more of surgery, and they include primary tumor histology, age, type of hepatectomy, presence of extra hepatic disease (EHD), length of disease-free interval. Recent reports not only confirm the pivotal role of selection of patient but also specify the technique of liver surgery (open vs. laparoscopic technique), confirming that laparoscopy has better short-term outcomes such as acceptable operative times, blood losses and conversion rate, whereas long-term survival is comparable to those of open liver resection. In conclusion, careful patient selection is the mainstay of treatment of NCNNLM, based on tumor biology and characteristics, and laparoscopic surgery seems to be an adequate approach. Unfortunately, evidence in literature remain scarse or even contradictory, lacking a sufficient number of patients for each tumor. Not rarely studies take into considerations different criteria of selection, which results in additional variability of cohort of populations among studies, and difficult in comparing them.

Surgical treatment of liver metastases from non-colorectal non-neuroendocrine carcinomas

IntroductionIn the literature, results after surgical treatment of non-colorectal non-neuroendocrine liver metastases (NCNNLM) are reported that are often inferior to those from colorectal liver metastases. The selection of patients with favorable tumor biology is currently still a matter of discussion.Materials/methodsThe retrospective data analysis was based on data that were collected for the multicenter study “Role of surgical treatment for non-colorectal liver metastases” in county Thuringia.ResultsFor the study, 637 patients were included from 1995 to 2018. 5 and 10-year survival of R0 resected patients were 33% and 19%, respectively. In the multi-variate analysis of the entire group, sex, timing, disease-free interval, number of metastases, R-classification as well as lymph node status of the primary lesion showed an independent statistical influence on the 5-year survival. In the group of R0 resected patients, disease-free interval, number of metastases and lymph node status of the primary lesion influenced the 5-year survival in the multi-variate analysis. In kidney malignancies, R-classification, timing and number of liver metastases were statistically significant in the multi-variate analysis of the 5-year survival, in mamma carcinomas only the R-classification.ConclusionThe Adam score identifies some risk factors which influence prognosis in most but not in all tumor entities. For kidney cancer and breast cancer it can be simplified.

The lack of selection criteria for surgery in patients with non-colorectal non-neuroendocrine liver metastases

BackgroundThe benefit of surgery in patients with non-colorectal non-neuroendocrine liver metastases (NCRNNELM) remains controversial. At the population level, several statistical prognostic factors and scores have been proposed but inconsistently verified. At the patient level, no selection criteria have been demonstrated to guide individual therapeutic decision making. We aimed to evaluate potential individual selection criteria to predict the benefit of surgery in patients undergoing treatment for NCRNNELM.MethodsData for 114 patients undergoing surgery for NCRNNELM were reviewed. In this population, we identified an early relapse group (ER), defined as patients with unresectable recurrence < 1 year postoperatively who did not benefit from surgery (N = 28), and a long-term survival group (LTS), defined as patients who were recurrence-free ≥ 5 years postoperatively and benefited from surgery (N = 20). Clinicopathologic parameters, the Association Française de Chirurgie (AFC) score, and a modified 4-point Clinical Risk Score (mCRS) (excluding CEA level) were analyzed and compared between LTS and ER groups.ResultsThe majority of patients were female and a majority had an ASA score ≤ 2 at the time of liver surgery. The median age was 55 years. Almost half of the patients (46%) presented with a single-liver metastasis. Intermediate- and low-risk AFC scores represented 40% and 60% of the population, respectively. Five- and 10-year overall survival (OS) and disease-free survival (DFS) rates were 56% and 27%, and 30% and 12%, respectively. Negative prognostic factors were the size of liver metastases > 50 mm and delay between primary and NCRNNELM <24 months for OS and DFS, respectively. AFC score was not prognostic while high-risk mCRS (scores 3–4) was predictive for the poorer OS. The clinicopathologic parameters were similar in the ER and LTS groups, except the presence of N+ primary tumor, and the size of liver metastases was significantly higher in the ER group.ConclusionIn patients with resectable NCRNNELM, no predictive factors or scores were found to accurately preoperatively differentiate individual cases in whom surgery would be futile from those in whom surgery could be associated with a significant oncological benefit.

Laparoscopic liver resection for non-colorectal non-neuroendocrine metastases: perioperative and oncologic outcomes

BackgroundLiver resection is a treatment of choice for colorectal and neuroendocrine liver metastases, and laparoscopy is an accepted approach for surgical treatment of these patients. The role of liver resection for patients with non-colorectal non-neuroendocrine liver metastases (NCNNLM), however, is still disputable. Outcomes of laparoscopic liver resection for this group of patients have not been analyzed.Material and methodsIn this retrospective study, patients who underwent laparoscopic liver resection for NCNNLM at Oslo University Hospital between April 2000 and January 2018 were analyzed. Perioperative and oncologic data of these patients were examined. Postoperative morbidity was classified using the Accordion classification. Kaplan–Meier method was used for survival analysis. Median follow-up was 26 (IQR, 12–41) months.ResultsFifty-one patients were identified from a prospectively collected database. The histology of primary tumors was classified as adenocarcinoma (n = 16), sarcoma (n = 4), squamous cell carcinoma (n = 4), melanoma (n = 16), gastrointestinal stromal tumor (n = 9), and adrenocortical carcinoma (n = 2). The median operative time was 147 (IQR, 95–225) min, while the median blood loss was 200 (IQR, 50–500) ml. Nine (18%) patients experienced postoperative complications. There was no 90-day mortality in this study. Thirty-five (68%) patients developed disease recurrence or progression. Seven (14%) patients underwent repeat surgical procedure for recurrent liver metastases. One-, three-, and five-year overall survival rates were 85%, 52%, and 38%, respectively. The median overall survival was 37 (95%CI, 25 to 49) months.ConclusionLaparoscopic liver resection for NCNNLM results in good outcomes and should be considered in patients selected for surgical treatment.

Role of surgical resection for non-colorectal non-neuroendocrine liver metastases.

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.

Liver resection for non-colorectal non-neuroendocrine metastases.

Liver resections for non-colorectal non-neuroendocrine liver metastases (NCNELM) are gaining popularity. This study examines the outcomes of liver resections in patients with NCNELM in an Australian hospital. A database search identified 21 attempted liver resections on 20 patients (12 men, eight women, mean age: 63.1) from 1998 to 2013. A retrospective analysis considered patient demographics and primary malignancy details. Complication rates were compared to those for colorectal metastases at the same institution. Kaplan-Meier curves were used to plot overall survival. Complete resection was achieved in 16 of the 21 operations with 13 cases having proven metastases (three cases were benign lesions on final histology). Primary cancers were gastric (n = 4), gall bladder/bile duct (n = 3), renal (n = 3), soft tissue sarcoma (n = 3), melanoma (n = 2), pancreatic (n = 2), anal (n = 2), breast (n = 1) and unknown (n = 1). Primary histology types were adenocarcinoma (n = 10), sarcoma (n = 3), renal cell (n = 3), squamous cell (n = 2), melanoma (n = 2) and gastrointestinal stromal tumour (n = 1). There was no peri-operative mortality. Significant post-operative complications (Clavien-Dindo Grade III or more) occurred in six patients (28.5%). Overall survival at 2 and 5 years was 46.2% and 30.8%, respectively, for all 21 cases of attempted resection, and 51.9% and 34.6%, respectively, for the 13 cases of complete resection of malignant metastases. This study produced comparable 5-year survival rates to those reported after liver resection for colorectal metastases and in other studies on NCNELM. Complication rates were comparable to those for colorectal liver metastasis resection at the same institution.

Margin status is a predictor of long-term survival following resection of non-colorectal, non-net liver metastases

Aims: The role of resectional surgery for colorectal liver metastases is well defined with improved 5-year survival rates. Non-colorectal, non-neuroendocrine liver metastases (NCNNLM) are not uncommonly encountered but the role of surgery is not yet clearly defined. This study is aimed to assess the immediate and long-term outcomes following liver resection for NCNNLM. Methods: Patients who underwent liver resection for NCNNLM between 2004 and 2014 were included from a prospectively maintained database at a tertiary referral centre. 90-day mortality, post-operative morbidity, disease-free (DFS) and overall survival (OS) were assessed. Univariable analyses were performed to identify predictors of survival. All analyses were performed using IBM SPSS 19 (IBM Corp. Armonk, NY), with p < 0.05 being statistically significant. Results: A total of 44 patients underwent 54 liver resections. Median age group was 54 years (range, 32–77 years). Metastases from breast (25%) and renal (15%) primaries were most commonly encountered. 19.3% were synchronous metastases. 90-day mortality and post-operative morbidity were 2% and 11% respectively. OS and DFS for NCNNLM at 1- year were 90% and 60% and at 5-years were 57% and 25% respectively. OS for breast and renal cancer at 1 year were 93% and 67% and at 5-years were 49% and 51% respectively. Positive resection margin has a significant influence on the OS (p = 0.018) on univariate analysis. Conclusions: Resection of liver metastases should be considered for NCNNLM as the survival rates are satisfactory. R0 resection remains an important determinant of overall survival.

Liver Resection for Non-colorectal Non-neuroendocrine Metastases: Where Do We Stand Today Compared to Colorectal Cancer?

The continuing controversy about surgery for non-colorectal non-neuroendocrine liver metastases (NCRNNE) necessitates identifying risk factors of worsened outcomes to improve patient selection and survival. Prospectively collected data of 167 patients undergoing hepatectomy for NCRNNE were analyzed, and a comparison to a matched population of colorectal liver metastases (CLM) was performed. Overall survival (OS) (35 vs. 54 months; P = 0.008) and recurrence-free survival (RFS) (15 vs. 29 months; P = 0.004) of NCRNNE patients were significantly shorter compared to those with CLM. The best survival was found in the genitourinary (GU; OS, 45 months; RFS, 21 months) NCRNNE subgroup, whereas survival for gastrointestinal (GI) metastases was low (OS, 8 months; RFS, 7 months). Patients with renal cell carcinoma (RCC) showed excellent outcomes when compared to CLM (OS, 50 vs. 51 months; P = 0.901). Extrahepatic disease (EHD) was identified as independent prognostic factor for reducing both RFS (P = 0.040) and OS (P = 0.046). The number of liver lesions (P = 0.024), residual tumor (P = 0.025), and major complications (P = 0.048) independently diminished OS. The degree of survival advantage by surgery is determined by the primary tumor site, EHD, the number of metastases, and residual tumor. Thus—even more than in CLM—these oncological selection criteria must prevail. GU metastases, especially RCC, represent a favorable subgroup.

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.

Surgical Approach of Cervical Cancer Liver Metastases: Case Report

Cervical cancer is an aggressive malignancy with a high tendency of invasion of the surrounding organs and also with capacity to give birth to metastases on both lymphatic and hematogenous routes. Cases who present distant metastases at the moment of diagnosis are generally referred to the medical oncologist than to the surgeon; however increasing reports on the benefit of liver surgery in non-colorectal non-neuroendocrine liver metastases have decreased the general reluctance to perform radical visa surgery on such cases. We present the case of a 53 years old female diagnosed with cervical cancer and liver metastases in which a radical resection was performed with good oncologic outcomes.