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Hepatectomy is an established treatment for colorectal liver metastasis (CLM) or neuroendocrine liver metastasis. However, its role in non-colorectal non-neuroendocrine liver metastasis (NCNNLM) is controversial. This study aims to compare long-term survival outcomes after hepatectomy between NCNNLM and CLM in a population-based cohort. From 2009 to 2018, curative hepatectomy were performed in 964 patients with NCNNLM (n ​= ​133) or CLM (n ​= ​831). Propensity score (PS) matching was performed. Short-term and long-term outcomes were compared between PS-matched groups. Univariate and multivariate analyses were performed to identify prognostic factors affecting survival. There were 133 patients in the NCNNLM group and 266 patients in the CLM group. The mortality (1.5 ​% vs 1.5 ​%) and morbidity (19.5 ​% vs 20.3 ​%) rates were comparable between the two groups. There was no statistically significant difference in 5-year overall (48.9 ​% vs 39.8 ​%) and recurrence-free (25.1 ​% vs 23.4 ​%) survival rates between NCNNLM and CLM groups. A high pre-operative serum bilirubin level, severe postoperative complications and multiple tumors were independent prognostic factors for poor survival. Hepatectomy for selected patients with NCNNLM can achieve similar long-term oncological outcomes as those with CLM. High serum bilirubin, severe postoperative complication and multiple tumors are poor prognostic factors for survival. • Mortality and morbidity rates were comparable between NCNNLM and CLM groups. • No difference in 5-year overall and recurrence-free survival rates between groups. • High bilirubin and severe postoperative complications were poor prognostic factors. [ABSTRACT FROM AUTHOR]

Hepatic resection (HR) is effective for colorectal or neuroendocrine liver metastases. However, the role of HR for non-colorectal non-neuroendocrine liver metastases (NCNNLM) is unknown. This study aims to perform a systematic review and meta-analysis on long-term clinical outcomes after HR for NCNNLM. electronic search was performed to identify relevant publications using PRISMA and MOOSE guidelines. Primary outcomes were 3- and 5-year overall survival (OS) and disease-free survival (DFS). Secondary outcomes were post-operative morbidity and 30-day mortality. There were 40 selected studies involving 5696 patients with NCNNLM undergone HR. Pooled data analyses showed that the 3- and 5-year OS were 40% (95% CI 0.35–0.46) and 32% (95% CI 0.29–0.36), whereas the 3- and 5-year DFS were 28% (95% CI 0.21–0.36) and 24% (95% CI 0.20–0.30), respectively. The postoperative morbidity rate was 28%, while the 30-day mortality was 2%. Subgroup analysis on HR for gastric cancer liver metastasis revealed the 3-year and 5-year OS of 39% and 25%, respectively. HR for NCNNLM may achieve satisfactory survival outcome in selected patients with low morbidities and mortalities. However, more concrete evidence from prospective study is warrant in future. • Pooled data analyses of high quality studies on NCNNLM • Three-year overall survival (OS): 40%; 5-year OS: 32% • Three-year disease-free survival (DFS): 28%; 5-year DFS: 24% • Postoperative morbidity: 28%; 30-day mortality: 2%. • Hepatic resection for NCNNLM may result in satisfactory survival outcome. [ABSTRACT FROM AUTHOR]

Abstract Background The 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. Methods Data 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. Results The 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

Abstract Background The indication for hepatic resection (HR) in patients suffering from liver metastases (LM) other than colorectal and neuroendocrine tumors is one focus of current multidisciplinary, oncologic considerations. This study retrospectively analyzes outcome after HR for non-colorectal, non-neuroendocrine (NCNNE) LM in the absence of distant or extrahepatic metastases. Methods We included 100 consecutive patients undergoing HR for isolated NCNNE LM from a prospective database in our institution, including postoperative follow-up. Primary tumors were of mesodermal origin in 44%, of ectodermal origin in 29% and of entodermal origin in 27%. Survival analysis was performed by univariate and multivariable methods. Mean follow-up after hepatic surgery was 3.6 years (0.25–16). Results Median age at the time of HR was 59.5 years. Kaplan-Meier-estimated survival after liver resection was 56.8%, 34.3% and 24.5% after 5, 10 and 15 years, respectively. Univariate analysis after HR revealed residual disease (hepatic or primary; p = 0.02), female gender (p = 0.013), entodermal origin (p = 0.009) and early onset of metastatic disease (≤24 months, p = 0.002), as negative prognostic factors. Multivariable survival analysis confirmed residual disease, female gender, entodermal embryologic origin and early onset of metastatic disease (≤24 months) as independent negative prognostic factors. Conclusion Overall outcome after HR of NCNNE LM results in acceptable long-term outcome. Although individual decision-making today mostly relies on clinical experience for this type of disease, risk factors derived from the embryologic origin of the tumor might help in patient selection.

Background: The 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. Methods: Data 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. Results: The 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. Conclusion: In 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. [ABSTRACT FROM AUTHOR]

Objective: 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. Method: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Hepatic resection of liver metastases of non-colorectal, non-neuroendocrine, and non-sarcoma (NCNNNS) primary malignancies seems to improve survival in selected patients. The aims of the current review were to describe long-term results of surgery and to evaluate prognostic factors for survival in patients who underwent resection of NCNNNS liver metastases. Methods: We identified 30 full texts (25 single-center and 5 multicenter studies) published after year 1995 and published in English with a total of 3849 patients. For NCNNNS liver metastases, 83.4 % of these subjects were resected. Results: No prior systematic reviews or meta-analyses on this topic were identified. All studies were case series without matching control groups. The most common primary sites were breast (23.8 %), genito-urinary (21.8 %), and gastrointestinal tract (19.8 %). The median 5- and 10-year overall survival were 32.3 % (range 19-42 %) and 24 % (indicated only in two studies, range 23-25 %), respectively, with 71 % of R0 resections. Conclusions: There is evidence suggesting that surgery of NCNNNS metastases is safe, feasible, and effective if treatment is part of a multidisciplinary approach and if indication is based on the prognostic factors underlined in literature analysis. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: 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. Methods: 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. Results: 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. Conclusion: 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. [Copyright &y& Elsevier]

Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) are rare mixed tumors containing both neuroendocrine (NE) and non-NE components. Each component must occupy at least 30% of the tumor volume by definition. Recent molecular evidence suggests MiNENs are clonal neoplasms and potentially harbor targetable mutations similar to conventional carcinomas. There have been multiple changes in the nomenclature and classification of MiNENs which has created some confusion among pathologists on how to integrate the contributions of each component in a MiNEN, an issue which in turn has resulted in confusion in communication with front-line treating oncologists. This mini review summarizes our current understanding of MiNENs and outline diagnosis, prognosis, and management of these neoplasms. The authors emphasize the importance of treating the most aggressive component of the tumor regardless of its percentage volume., Competing Interests: Conflict-of-interest statement: JL has received consulting fees from Taiho, Ipsen, Novartis, Amgen, Eisai, and Bayer; research funding from Ipsen Biopharmaceuticals, Amgen, and Foundation Medicine., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The role of metastectomy for colorectal and neuroendocrine liver secondaries is well established. Significant palliation and survival have been reported after aggressive surgical resection. However, the role of liver resection for secondaries from other primary tumours is less well defined. In this study, we aim to describe our experience, including indications and selection criteria, operative strategy and clinical outcome of liver resection, for non-colorectal, non-neuroendocrine liver metastases. Methods: A review of prospectively collected operative database was conducted and patients who underwent liver resection of secondaries from non-colorectal, non-neuroendocrine primary tumours were studied. Eighteen patients were included in the study. There were 4 men and 14 women with a median age of 48 years (range, 37–78 years). Liver resection was carried out either for cure or for palliation of debilitating symptoms. Selection criteria included: (i) absence of extrahepatic disease and (ii) functional status of the liver and volume of remnant liver after hepatectomy. The median follow up was 24 months (range, 7–81 months) for 17 patients, excluding the one who defaulted after surgery. Cancer-specific survival and recurrence-free interval was calculated from the date of hepatectomy. Results: Liver resection was considered curative in 13 patients. There was no 30-day mortality in this cohort of patients. The median recurrence-free survival time was 13 months (95% confidence interval (CI), 8–18 months). The median follow-up time for the 12 patients was 23.5 months (range, 7–35 months). Only five patients died due to cancer-specific causes and one died from acute myocardial infarction. The median cancer-specific survival time was 30 months (95% CI, 25–35 months). The 2-year survival rate was 77.1% (95% CI, 48.9–100%). Conclusion: The results are encouraging and suggest that with appropriate selection criteria, there is a role for metastectomy of non-colorectal, non-neuroendocrine liver secondaries. [ABSTRACT FROM AUTHOR]

Background: Liver resection is a well-established treatment for colorectal, neuroendocrine and sarcomatous metastases but remains ill-defined for metastases from other primary sites. This study aimed to analyze the outcomes of hepatic resection for metastases not of colorectal, neuroendocrine, sarcomatous, or ovarian (NCNSO) origin and to identify predictors of outcome., Methods: Retrospective analysis of patients undergoing resection for NCNSO metastases in three western centers. Patients were analyzed according to the primary cancer. Outcomes were recurrence and survival., Results: We analyzed 188 patients, divided in: gastrointestinal (59), breast (59) and "others" (70). Median time to recurrence was 15.3 months, while median survival was 52 months. Survival at 1, 3, and 5 years was 78%, 60.4% and 47.8%, respectively. In term of prognostic factors, metastases >35 mm from gastrointestinal tumors were associated with lower survival (p = 0.029) and age>60 years was associated with better survival in breast metastases (p = 0.018)., Conclusions: Liver resection for NCNSO metastases is feasible and results in long-term survival are similar to colorectal metastases. In gastrointestinal metastases, size (<35 mm) could be used to select patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)