Surgical treatment for neuroendocrine liver metastasis: moving ahead in controversy.
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ABSTRACT:
SUBMITTER: Xiang JX
PROVIDER: S-EPMC8683918 | biostudies-literature | 2021 Dec
REPOSITORIES: biostudies-literature
Publications
Surgical treatment for neuroendocrine liver metastasis: moving ahead in controversy.
Xiang Jun-Xi JX Lv Yi Y Zhang Xu-Feng XF
Hepatobiliary surgery and nutrition 20211201 6
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Project description:Poorly differentiated gastroenteropancreatic neuroendocrine carcinomas are aggressive neoplasms of challenging clinical management. A small proportion of patients with early-stage disease may achieve long-term survival, but the majority of patients present with rapidly lethal metastatic disease. Current standard of care still follows the treatment paradigm of small cell lung cancer, a far more common G3 neuroendocrine neoplasm, although emerging molecular and clinical data increasingly question this approach. In this article, we will briefly summarize epidemiology and prognosis of gastroenteropancreatic neuroendocrine carcinomas to emphasize the very low incidence, aggressive nature, and orphan status of this tumor entity. We will also discuss the current pathological classification and its limitations, as well as recent data on their differential biological background compared with small cell lung cancer, and its potential implications for patients care. Then, we will review the standard of care of systemic therapy, basically focused on platinum-based cytotoxic chemotherapy, including some recent randomized trials providing evidence regarding efficacy of irinotecan vs etoposide platinum doublets. Finally, we will present a comprehensive overview of novel therapeutic strategies in current clinical development, including recently reported data on immunotherapy, tumor-agnostic therapies (microsatellite instability, high tumor mutational burden, NTRK and RET gene fusions, BRAF or KRAS inhibitors), and additional treatment strategies targeting other tumor vulnerabilities (ie, Notch pathway, novel targets for radioligand therapy), and provide some insights regarding unmet needs and future perspectives to improve patient's care and prognosis.
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Project description:Neuroendocrine tumors, or NETs, are cancer originating in neuroendocrine cells. They are mostly found in the gastrointestinal tract or lungs. Functional NETs are characterized by signs and symptoms caused by the oversecretion of hormones and other substances, but most NETs are non-functioning and diagnosis in advanced stages is common. Thus, novel diagnostic and therapeutic strategies are warranted. Epigenetics may contribute to refining the diagnosis, as well as to identify targeted therapy interfering with epigenetic-sensitive pathways. The goal of this review was to discuss the recent advancement in the epigenetic characterization of NETs highlighting their role in clinical findings.
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Project description:Introduction. The role of hepatic resection in patients with liver metastases from gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is still poorly defined. Therefore, we examined the results obtained with surgical resection and other locoregional or systemic therapies by reviewing the recent literature on this topic. We performed the meta-analysis for comparing surgical resection of hepatic metastases with other treatments. Materials and Methods. In this systematic review and meta-analysis of observational studies, the literature search was undertaken between 1990 and 2012 looking for studies evaluating the different survivals between patients treated with surgical resection of hepatic metastases and with other surgical or nonsurgical therapies. The studies were evaluated for quality, publication bias, and heterogeneity. Pooled hazard ratio (HR) estimates and 95% confidence intervals (CI.95) were calculated using fixed-effects model. Results. We selected six studies in the review, five of which were suitable for meta-analysis. We found a significant longer survival in patients treated with hepatic resection than embolisation HR 0.34 (CI.95 0.21-0.55) or all other nonsurgical treatments HR 0.45 (CI.95 0.34-0.60). Only one study compared surgical resection with liver transplantation and meta-analysis was not feasible. Conclusions. Our meta-analysis provides evidence supporting the hypothesis that hepatic resection increases overall survival in patients with liver metastases from GEP-NETs. Further randomized clinical trials are needed to confirm these findings and it would be desirable to identify new markers to properly select patients for surgical treatment.
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Project description:Neuroendocrine neoplasms (NEN) are frequently characterized by a high propensity for metastasis to the liver, which appears to be a dominant site of distant-stage disease, affecting quality of life and overall survival. Liver surgery with the intention to cure is the treatment of choice for resectable neuroendocrine liver metastases (NELM), aiming to potentially prolong survival and ameliorate hormonal symptoms refractory to medical control. Surgical resection is indicated for patients with NELM from well-differentiated NEN, while its feasibility and complexity are largely dictated by the degree of liver involvement. As a result of advances in surgical techniques over the past decades, complex 1- and 2-stage, or repeat liver resections are performed safely and effectively by experienced surgeons. Furthermore, liver transplantation for the treatment of NELM should be anchored in a multimodal and multidisciplinary therapeutic strategy and restricted only to highly selected individual cases. A broad spectrum of interventional radiology treatments for NELM have recently been available, with expanding indications that are more applicable, as they are less limited by patient- and tumor-related parameters, being therefore important adjuncts or alternatives to surgery. Overall, liver-targeted treatment modalities may precede the administration of systemic molecular targeted agents and chemotherapy for patients with liver-dominant metastatic disease; these appear to be a crucial component of multimodal management of patients with NEN. In the present review, we discuss surgical and non-surgical liver-targeted treatment approaches for NELM, each complementing the other, with a view to assisting physicians in optimizing multimodal NEN patient care.
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Project description:Melanoma is a form of skin cancer with an increased ability to metastasis to organs such as the brain and other visceral organs, contributing to its aggressiveness and seriousness. Melanoma's prevalence around the globe rapidly continues to rise. Melanoma development is a complex process often depicted as a step-wise process with the potential to end in metastatic disease. Recent studies suggest that the process could be non-linear. Melanoma has many risk factors including genetics, UV exposure, or exposure to carcinogens. Current treatments for metastatic melanoma include surgery, chemotherapy, and immune checkpoint inhibitors (ICIs); however, each of these treatments comes with limitations, toxicities, and relatively poor outcomes. There are various guidelines set by the American Joint Committee on Cancer guiding surgical treatment options based on the site of metastasis. Surgical treatments cannot fully treat widespread metastatic melanoma but can contribute to better patient outcomes overall. Many chemotherapy options are ineffective against melanoma or come with extreme toxicities; however, alkylating agents, platinum analogs, and microtubular toxins have shown some effectiveness against metastatic melanoma. ICIs are a relatively new treatment option and offer a promising option for patients; however, ICIs are subject to tumor resistance mechanisms and are not effective for every metastatic melanoma patient. Due to the limitations of conventional treatments, there is a need for newer and more effective treatment options for metastatic melanoma. This review aims to highlight the current surgical, chemotherapy, and ICI treatments for metastatic melanoma, as well as current clinical and preclinical investigations to discover revolutionary options for patients.
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Project description:BackgroundRegional lymph node metastasis (LNM) is crucial for planning additional lymphadenectomy, and is directly correlated with poor prognosis in gastroenteropancreatic neuroendocrine tumors (GEP-NETs). However, the patterns of LNM for small (≤20 mm) GEP-NETs remain unclear. This population-based study aimed at evaluating LNM patterns and identifying optimal surgical strategies from the standpoint of lymph node dissemination.MethodsThis retrospective cohort study retrieved data from the Surveillance, Epidemiology, and End Results (SEER) 18 registries database for 17,308 patients diagnosed as having localized well-differentiated GEP-NETs ≤ 20 mm between January 1, 2004, and December 31, 2017. The patterns of LNM were characterized in 6,622 patients who underwent extended resection for adequate lymph node harvest.ResultsOf 6,622 patients with localized small GEP-NETs in the current study, 2,380 (36%) presented with LNM after regional lymphadenectomy. Nodal involvement was observed in approximately 7.4%, 49.1%, 13.6%, 53.7%, 13.8%, 7.8%, and 15.4% of gastric (g-), small intestinal (si-), appendiceal (a-), colonic (c-), rectal (r-), non-functional pancreatic (nfp-), and functional pancreatic (fp-) NETs ≤ 20 mm. Patients with younger age, larger tumor size, and muscularis invasion were more likely to present with LNM. Additional lymphadenectomy conferred a significant survival advantage in NETs (≤10 mm: HR, 0.47; 95% CI, 0.33-0.66; p < 0.001; 11-20 mm: HR, 0.54; 95% CI, 0.34-0.85; p = 0.008) and fp-NETs ≤ 20 mm (HR, 0.08; 95% CI, 0.02-0.36; p = 0.001), as well as g-NETs (HR, 0.39; 95% CI, 0.16-0.96; p = 0.041) and c-NETs of 11-20 mm (HR, 0.07; 95% CI, 0.01-0.48; p = 0.007). Survival benefits of additional lymphadenectomy were not found in a-NETs, r-NETs, and nfp-NETs with a small size.ConclusionsGiven the increased risk for nodal metastasis, primary tumor resection with regional lymphadenectomy is a potential optimal surgical strategy for si-NETs and fp-NETs ≤ 20 mm, as well as g-NETs and c-NETs of 11-20 mm. Local resection is an appropriate and reliable surgical approach for a-NETs, r-NETs, and nfp-NETs ≤ 20 mm.
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