Resection and thermal hepatic ablation of pancreatic neuroendocrine tumor liver metastases for prolonged survival.
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ABSTRACT:
SUBMITTER: Ke X
PROVIDER: S-EPMC9660050 | biostudies-literature | 2022 Oct
REPOSITORIES: biostudies-literature
Publications
Resection and thermal hepatic ablation of pancreatic neuroendocrine tumor liver metastases for prolonged survival.
Journal of gastrointestinal oncology 20221001 5
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Project description:This study investigates survival of patients diagnosed with pancreatic neuroendocrine tumor with liver metastases based on local treatment on the primary tumor. Patients diagnosed with stage IV PNET between 2010 and 2014 were identified from the Surveillance Epidemiology and End Results database. Cancer-Specific Survival and Overall Survival were examined. A total of 191 patients with pancreatic neuroendocrine tumor with liver metastases were included in this analysis. There were 47 patients (24.6%) who received surgical resection and 144 (75.4%) who did not. Patients with N1 stage was more likely to be treated with surgical resection. The results showed that surgical resection of primary tumor was associated with Cancer-Specific Survival (p = 0.028) and Overall Survival (p = 0.025) benefit. Not receiving surgery, being unmarried and N1 stage are factors associated with poor survival. This study reveals that local treatment on the primary benefits both Cancer-Specific Survival and Overall Survival in PNET patients with LM. This may be suggestive for the management on this patient population.
| S-EPMC5668092 | biostudies-other
Project description:BackgroundThe aim of this study was to investigate the effectiveness of adjuvant hepatic arterial infusion pump (HAIP) chemotherapy after complete resection or ablation of recurrent colorectal liver metastases (CRLM).MethodsA retrospective cohort study was conducted of patients from two centers who were treated with resection and/or ablation of recurrent CRLM only between 1992 and 2018. Overall survival (OS) and hepatic disease-free survival (hDFS) were estimated using the Kaplan-Meier method. The Cox regression method was used to calculate hazard ratios (HRs) with corresponding 95% confidence intervals (CI).ResultsOf 374 eligible patients, 81 (22%) were treated with adjuvant HAIP chemotherapy. The median follow-up for survivors was 65 months (IQR 32-118 months). Patients receiving adjuvant HAIP were more likely to have multifocal disease and receive perioperative systemic chemotherapy at time of resection for recurrence. A median hDFS of 46 months (95% CI 29-81 months) was found in patients treated with adjuvant HAIP compared with 18 months (95% CI 15-26 months) in patients treated with resection and/or ablation alone (p = 0.001). The median OS and 5-year OS were 89 months (95% CI 52-126 months) and 66%, respectively, in patients treated with adjuvant HAIP compared with 57 months (95% CI 47-67 months) and 47%, respectively, in patients treated with resection and/or ablation only (p = 0.002). Adjuvant HAIP was associated with superior hDFS (adjusted HR 0.599, 95% CI 0.38-0.93, p = 0.02) and OS (adjusted HR 0.59, 95% CI 0.38-0.92, p = 0.02) in multivariable analysis.ConclusionAdjuvant HAIP chemotherapy after resection and/or ablation of recurrent CRLM is associated with superior hDFS and OS.
| S-EPMC7801355 | biostudies-literature
Project description:BackgroundPalliative resection of the primary tumor for metastatic pancreatic neuroendocrine carcinoma (pNEC) patients is not recommended because of the poor prognosis compared to that of patients with well-differentiated, lower grade tumors. However, the published data supporting this recommendation regarding pNEC are limited. In the present study, we assessed whether palliative primary tumor resection in stage IV pNEC patients affects survival and identified other factors that affect survival in these patients.MethodsWe collected data from stage IV pNEC patients registered in the Surveillance, Epidemiology, and End Results (SEER) database between 1988 and 2014. Univariate and multivariate Cox regression analysis were used to compare overall survival (OS) and cancer-specific survival (CSS) of patients who did or did not undergo primary tumor resection.ResultsWe identified 350 patients with metastatic, poorly differentiated, and undifferentiated pNEC. A total of 14.3% (50/350) of patients underwent primary tumor resection. Multivariate Cox regression analysis showed that primary tumor resection provided a significant benefit for both OS and CSS in stage IV pNEC patients. Additionally, chemotherapy and the presence of the primary tumor in the pancreatic tail were independent positive prognostic factors for metastatic pNEC patients in the multivariate Cox regression analysis.ConclusionsThe present study suggests that chemotherapy, location of the primary tumor in the pancreatic tail, and, most importantly, surgical removal of the primary tumor are associated with prolonged survival in stage IV pNEC patients.
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Project description:BackgroundAlthough surgical resection has been considered the only curative option for colorectal liver metastases (CLM), thermal ablation has recently been suggested as an alternative curative treatment. A prospective randomised trial is required to define the efficacy of resection vs ablation for the treatment of colorectal liver metastases.MethodsDesign and setting: This is a multicentre, open, randomised controlled non-inferiority trial design with internal pilot and will be performed in tertiary liver centres in UK and The Netherlands.ParticipantsEligible patients will be those with colorectal liver metastases at high surgical risk because of their age, co-morbidities or tumour burden and who would be suitable for liver resection or thermal ablation.InterventionThermal ablation as per local policy.ControlSurgical liver resection performed as per centre protocol. Co-interventions: Further chemotherapy will be offered to patients as per current practice. Outcomes Pilot study: Same as main study and in addition patients and clinicians' acceptability of the trial to assist in optimisation of recruitment.Primary outcomeDisease-free survival (DFS) at two years post randomisation.Secondary outcomesOverall survival, timing and site of recurrence, additional therapy after treatment failure, quality of life, complications, length of hospital stay, costs, trial acceptability, DFS measured from end of intervention.Follow-up24 months from randomisation; five-year follow-up for overall survival.Sample size330 patients to demonstrate non-inferiority of thermal ablation.DiscussionThis trial will determine the effectiveness and cost-effectiveness of thermal ablation vs surgical resection for high-risk people with colorectal liver metastases, and guide the optimal treatment for these patients.Trial registrationISRCTN Registry, ISRCTN52040363 . Registered on 9 March 2016.
| S-EPMC5811975 | biostudies-literature
Project description:BackgroundHepatic steatosis and chemotherapy in the treatment of colorectal liver metastases (CLM) are often linked to increased mortality and morbidity after liver resection. This study evaluates the influence of macrovesicular hepatic steatosis and chemotherapeutic regimes on graded morbidity and mortality after liver resection for CLM.MethodsA total of 323 cases of liver resection for CLM were retrospectively analysed using univariable and multivariable linear, ordinal and Cox regression analyses. The resected liver tissue was re-evaluated by a single observer to determine the grade and type of hepatic steatosis.ResultsMacrovesicular steatosis did not influence postoperative morbidity and survival, as evidenced by risk-adjusted multivariable Cox regression analysis (p = 0.521). Conversion chemotherapy containing oxaliplatin was an independent and significant risk factor for mortality in risk-adjusted multivariable Cox regression analysis (p = 0.005). Identified independently, significant risk factors for postoperative morbidity were neoadjuvant treatment of metastases of the primary tumour with irinotecan (p = 0.003), the duration of surgery in minutes (p = 0.001) and the number of intraoperatively transfused packed red blood cells (p ≤ 0.001). Surprisingly, macrovesicular hepatic steatosis was not a risk factor for postoperative morbidity and was even associated with lower rates of complications (p = 0.006).ConclusionThe results emphasize the multifactorial influence of preoperative liver damage and chemotherapy on the severity of postoperative morbidity, as well as the significant impact of conversion chemotherapy containing oxaliplatin on survival.
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Project description: Not available
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Project description:Most patients with pancreatic ductal adenocarcinoma (PDAC) undergoing curative resection relapse within months, often with liver metastases. The hepatic microenvironment determines induction and reversal of dormancy during metastasis. Both tumor growth and metastasis depend on the Tumor necrosis factor (TNF)-related apoptosis-inducing ligand-receptor 2 (TRAIL-R2). This study investigated the interplay of TRAIL-R2 and the hepatic microenvironment in liver metastases formation and the impact of surgical resection. Although TRAIL-R2-knockdown (PancTu-I shTR2) decreased local relapses and number of macroscopic liver metastases after primary tumor resection in an orthotopic PDAC model, the number of micrometastases was increased. Moreover, abdominal surgery induced liver inflammation involving activation of hepatic stellate cells (HSCs) into hepatic myofibroblasts (HMFs). In coculture with HSCs, proliferation of PancTu-I shTR2 cells was significantly lower compared to PancTu-I shCtrl cells, an effect still observed after switching coculture from HSC to HMF, mimicking surgery-mediated liver inflammation and enhancing cell proliferation. CXCL-8/IL-8 blockade diminished HSC-mediated growth inhibition in PancTu-I shTR2 cells, while Vascular Endothelial Growth Factor (VEGF) neutralization decreased HMF-mediated proliferation. Overall, this study points to an important role of TRAIL-R2 in PDAC cells in the interplay with the hepatic microenvironment during metastasis. Resection of primary PDAC seems to induce liver inflammation, which might contribute to outgrowth of liver metastases.
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Project description:The role of perioperative chemotherapy in the management of initially resectable colorectal liver metastases (CRLM) is still unclear. The EPOC trial [the European Organization for Research and Treatment of Cancer (EORTC) 40983] is an important study that declares perioperative chemotherapy as the standard of care for patients with resectable CRLM, and the strategy is widely accepted in western countries. Compared with surgery alone, perioperative FOLFOX therapy significantly increased progression-free survival (PFS) in eligible patients or those with resected CRLM. Overall survival (OS) data from the EPOC trial were recently published in The Lancet Oncology, 2013. Here, we discussed the findings and recommendations from the EORTC 40983 trial.
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Project description:The objectives of this systematic review and pooled analysis were to examine long-term survival, morbidity, and mortality following thermal ablation of gastric cancer hepatic metastases and to identify prognostic factors that improve survival.Patients with hepatic metastases from gastric cancer are traditionally treated with palliative chemotherapy. Surgical resection is an alternative treatment of hepatic metastases. Whether patients can obtain benefit from thermal ablation of hepatic metastases is still controversial.A systematic literature search was undertaken (1990-2018). Publications were included if they studied more than 7 patients undergoing thermal ablation for hepatic metastasis from gastric cancer in the absence of peritoneal disease or other distant organ involvement. The primary outcome was the hazard ratio (HR) for overall survival. Comparison between thermal ablation and systematic chemotherapy or hepatic resection had been carried out. The influence of liver metastasis-related factors, such as <3 cm versus >3 cm, single versus multiple and metachronous versus synchronous upon survival was also assessed.The median survival of thermal ablation for the 12 studies included was 22.93[20.45-25.41] months. Procedures were associated with a median 30-day morbidity of 6% (0%-23%) and with no mortality. The median 1-year, 2-year, 3-year, and 5-year survival were 79.14%, 39.79%, 28.45%, and 19.46%, respectively. Thermal ablation of hepatic metastasis was associated with improved overall survival compared with systematic chemotherapy (HR = 2.12; 95% CI 0.77-3.47; P=.000). Meta-analysis confirmed the additional survival benefit of size <3 cm (HR = 1.46; 95% CI 1.03-1.88; P = .002) and receiving chemotherapy after thermal ablation (HR = 2.14; 95% CI 1.05-3.23; P = .000).A use of RFA/ microwave ablation (MWA) as a liver-directed treatment may provide greater survival benefit than chemotherapy and is an alternative option for the treatment of liver-only metastases from gastric cancer. With the appropriate selection of patients, such as tumors <3 cm in diameter, thermal ablation may provide better prognosis than hepatic resection of hepatic metastasis with lower morbidity and mortality. Postoperation chemotherapy should be provided to patients with GLM who received thermal ablation.
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Project description:In patients with neuroendocrine tumors with liver metastases (NETLMs), complete resection of both the primary and liver metastases is a potentially curative option. When complete resection is not possible, debulking of the tumour burden has been proposed to prolong survival. The objective of this systematic review was to evaluate the effect of curative surgery (R0-R1) and debulking surgery (R2) on overall survival (OS) in NETLMs. For the subgroup of R2 resections, outcomes were compared by the degree of hepatic debulking (≥ 90% or ≥ 70%). A systematic review of the literature was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines using PubMed, Medline, CINAHL, Cochrane, and Embase databases. Hazard ratios (HRs) were estimated for each study and pooled using a random-effects inverse-variance meta-analysis model. Of 538 articles retrieved, 11 studies (1,729 patients) reported comparisons between curative and debulking surgeries. After pooling these studies, OS was found to be significantly shorter in debulking resections, with an HR of 3.49 (95% confidence interval, 2.70-4.51; p < 0.001). Five studies (654 patients) compared outcomes between ≥ 90% and ≥ 70% hepatic debulking approaches. Whilst these studies reported a tendency for OS and progression-free survival to be shorter in those with a lower degree of debulking, they did not report sufficient data for this to be assessed in a formal meta-analysis. In patients with NETLM, OS following surgical resection is the best to achieve R0-R1 resection. There is also evidence for a progressive reduction in survival benefit with lesser debulking of tumour load.
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