Retrospective analysis of interventional treatment of hepatic metastasis from gastroenteropancreatic neuroendocrine tumors

Objective： To analyze the angiography appearance of liver metastases from gastroenteropancreatic neuroendocrine tumors （GEP-NETs）, and evaluate the clinical efficacy and prognostic factors of interventional treatment for hepatic metastases. Methods： Fifty GEP-NETs patients with hepatic metastases were treated from January 2012 to December 2016, and received transarterial embolization （TAE） in the hepatic tumor or hepatic arterial infusion chemotherapy （HAIC）. All patients received 179 times of the intervention therapy in total. Results： Blood supplies were identified in the 50 eases with angiography, which showed that 35 cases had abundant vessels, while 15 eases had poor blood supply. Twenty-two cases were found either collateral blood supply, or portal vein invasion or arterial-portal vein fistula. The best curative efficacy was complete remission （CR） in 4 cases, partial remission （PR） in 28 cases and stable disease （SD） in 18 eases during the process of treatment. The angiography （P=0.047） and the frequency of intervention （P=0.037） showed significantly statistical difference with Kaplan-Meier analysis. The Cox analysis showed that more than 3 times of interventional therapy was an independent prognostic factor. Conclusions： Interventional treatment is safe and effective for GEP-NETs, and is beneficial to patients with main hepatic metastases after endocrine therapy.

Effects of cell membrane phospholipid level and protein kinase C isoenzyme expression on hepatic metastasis of colorectal carcinoma

BACKGROUND: The molecular mechanism of hepaticmetastasis of colorectal cancer is not well understood. Theaim of this study was to assess the relations between phos-pholipid contents of cellular membrane and isoenzyme ex-pression of protein kinase C (PKC) and their effects on he-patic metastasis of colorectal cancer.METHODS: High performance liquid chromatography wasused to detect contents of cell membrane phospholipids:phosphatidylinosital (PI), phosphatidylserine (PS), phos-phatidylethanolamine (PE) and phosphatidylcholine (PC)in primary foci, paratumor mucosa and hepatic metastaticfoci in patients with colorectal carcinoma. The mRNA ex-pression levels of PKC-α, -δ, -ε, -λ, -ξ isoenzymeswere detected with the QRT-PCR technique.RESULTS: The levels of PI, PC and PE in primary foci andhepatic metastatic foci were higher than those in paratumormucosa. The level of PE in hepatic metastatic foci wasmuch higher than that in primary foci (t =98.88, P <0.01);but the levels of PI and PC were not significantly differentbetween primary foci and hepatic metastatic foci (t =1.73 ,1.36, P>0.05). The expression levels of -δ, -ε,-λ, -ξ were enhanced in primary foci and hepatic metasta-tic foci, but the level of PKC-α in primary foci was de-creased as compared with that in paratumor mucosa. Thelevels of PKC-δ, -ε, -λ, -ξ in hepatic metastatic foci werehigher than those in primary foci. A positive correlationwas observed between the expression levels of PI, PC andand also between those of PE and PKC-δ, -ε, -λ,-ξ. However, there was a close negative correlation be-tween PE and PKC-α.CONCLUSION: Increased levels of PI and PC and de-creased ratio of PKC-α to are related to colorectalcancer genesis. Increased levels of PE, increased expressionof PKC-δ, -ε, -λ, -ξ isoenzymes and decreased level ofPKC-α are related to hepatic metastasis in colorectal carci-noma.

Effects of Down-regulation of Integrin-β_1 Expression on Migration and Hepatic Metastasis of Human Colon Carcinoma

Organ-specific tumor cell adhesion to extracellular matrix (ECM) components and cell migration into host organs often involve integrin-mediated cellular processes. Direct integrin-mediated cell adhesion to ECM components in the space of Disse appears to be required for the successful liver metastatic formation of colon cancer. In the present study, human colon cancer HT-29 cells were transfected by liposome with integrin-β1 antisense oligodeoxynucleotide (ASODN). The integrin-β1 gene expression in HT-29 cel...

Surgery for oligometastasis of pancreatic cancer

The incidence of pancreatic adenocarcinoma（PDAC） has steadily increased over the past several decades. The majority of PDAC patients will present with distant metastases, limiting surgical management in this population. Hepatectomy and pulmonary metastasectomy（PM） has been well established for colorectal cancer patients with isolated, resectable hepatic or pulmonary metastatic disease. Recent advancements in effective systemic therapy for PDAC have led to the selection of certain patients where metastectomy may be potentially indicated. However, the indication for resection of oligometastases in PDAC is not well defined. This review will discuss the current literature on the surgical management of metastatic disease for PDAC with a specific focus on surgical resection for isolated hepatic and pulmonary metastases.

Application of Computed Tomography Virtual Noncontrast Spectral Imaging in Evaluation of Hepatic Metastases： A Preliminary Study

Objective：The objective was to qualitatively and quantitatively evaluate hepatic metastases using computed tomography （CT） virtual noncontrast （VNC） spectral imaging in a retrospective analysis.Methods：Forty hepatic metastases patients underwent CT scans including the conventional true noncontrast （TNC） and the tri-phasic contrast-enhanced dual energy spectral scans in the hepatic arterial,portal venous,and equilibrium phases.The tri-phasic spectral CT images were used to obtain three groups of VNC images including in the arterial （VNCa）,venous （VNCv）,and equilibrium （VNCe） phase by the material decomposition process using water and iodine as a base material pair.The image quality and the contrast-to-noise ratio （CNR） of metastasis of the four groups were compared with ANOVA analysis.The metastasis detection rates with the four nonenhanced image groups were calculated and compared using the Chisquare test.Results：There were no significant differences in image quality among TNC,VNCa and VNCv images （P 〉 0.05）.The quality of VNCe images was significantly worse than that of other three groups （P 〈 0.05）.The mean CNR of metastasis in the TNC and VNCs images was 1.86,2.42,1.92,and 1.94,respectively; the mean CNR of metastasis in VNCa images was significantly higher than that in other three groups （P 〈 0.05）,while no statistically significant difference was observed among VNCv,VNCe and TNC images （P 〉 0.05）.The metastasis detection rate of the four nonenhanced groups with no statistically significant difference （P 〉 0.05）.Conclusions：The quality of VNCa and VNCv images is identical to that of TNC images,and the metastasis detection rate in VNC images is similar to that in TNC images.VNC images obtained from arterial phase show metastases more clearly.Thus,VNCa imaging may be a surrogate to TNC imaging in hepatic metastasis diagnosis.

Vimentin significantly promoted gallbladder carcinoma metastasis

Background The precise molecular mechanisms underlying the gallbladder carcinoma （GBC） metastasis has not been fully elucidated. Methods In the present study, metastasis-associated proteins were identified by comparative proteomic analysis. The functional study of the candidate protein vimentin was further investigated. First, a pair of higher and lower metastatic sublines （termed GBC-SD/M3 and GBC-SD, respectively）, originated from the same parental cell line, was screened by spontaneous tumorigenicity and metastasis in vivo in animal study and further characterized by metastatic phenotypes analysis in vitro. Subsequently, a proteomic approach comprised two-dimensional gel electrophoresis analysis and mass spectroscopy was used to identify and compare the protein expression patterns between higher metastatic GBC-SD/M3 and lower metastatic GBC-SD cell lines. Then twenty-six proteins were identified. Results Among the 26 proteins identified, fourteen proteins were up-regulated and 12 proteins were down-regulated in GBC-SD/M3. Vimentin was identified and found to be overexpressed in GBC-SD/M3 as compared with GBC-SD. This result was further confirmed by quantitative PCR and Western blotting analysis. Furthermore, the cell migration and invasion potency of GBC-SD/M3 in vitro was remarkably suppressed after small interference RNA-mediated knockdown of vimentin. Moreover, immunoblot and immunohistochemical analysis on 12 human GBC specimens showed consistently increased vimentin expression in metastases compared with primary tumors. Conclusion Tumor vimentin level may reflect the pathological progression in some GBC and may be a useful marker for predicting tumor metastasis and a therapeutic target for the treatment of GBC patients with metastases.

Surgery for metastatic pancreatic neuroendocrine tumors: a narrative review

Background and Objective:Pancreatic neuroendocrine tumors(PanNETs)are derived from the islet cells of the pancreas and have been increasing in incidence.Most of these tumors are nonfunctional although some can secrete hormones and lead to hormone-specific clinical syndromes.Surgery is the mainstay of treatment for localized tumors,however,surgical resection is controversial in metastatic PanNETs.This narrative review seeks to summarize the current literature surrounding surgery,specifically in the controversial area of metastatic PanNETs,review current treatment paradigms,and understand the benefits of surgery in this group of patients.Methods:Authors searched PubMed using the terms“surgery pancreatic neuroendocrine tumor”,“metastatic neuroendocrine tumor”,and“liver debulking neuroendocrine tumor”from January 1990 to June 2022.Only English language publications were considered.Key Content and Findings:There is no consensus among the leading specialty organizations regarding surgery for metastatic PanNETs.When considering surgery for metastatic PanNETs,tumor grade and morphology,location of the primary tumor,extra-hepatic or extra-abdominal disease,as well as liver tumor burden and metastatic distribution should be considered.Because the liver is the most common site of metastasis and liver failure is the most common cause of death in patients with hepatic metastases,attention is centered here on debulking and other ablative techniques.Liver transplantation is rarely used for hepatic metastases but could be beneficial in a small subset of patients.Retrospective studies have demonstrated improvement in survival and symptoms after surgery for metastatic disease,but the lack of prospective randomized control trials significantly limits analysis of surgical benefits in patients with metastatic PanNETs.Conclusions:Surgery is the standard of care for localized PanNETs,while it remains controversial in metastatic disease.Many studies have shown a survival and symptomatic benefit to surgery and liver debulking in select groups of patients.However,most of the studies on which recommendations are based in this population are retrospective in nature and are subject to selection bias.This presents an opportunity for future investigation.