Neuroendocrine Tumor Liver Metastases Research Articles

Ablative Dose Y90 Radiation Segmentectomy for Treatment of Neuroendocrine Liver Metastases

PurposeTo assess the safety and efficacy of Y90 radiation segmentectomy (RS) for neuroendocrine tumor liver metastases (NELMs). Materials and MethodsThis single-institution retrospective study included 18 patients with 23 liver tumors not amenable to resection or ablation, who underwent RS between 2009 and 2021. Tumor grades by Ki-67/mitotic indices were Grade I (n=9/23, 39%), Grade II (n=10/23, 45%) and Grade III (n=4/23, 17%). Eleven patients (61%) were previously treated with somatostatin analogs, five (28%) with chemotherapy, and two (11%) with peptide receptor radionuclide therapy. Safety was assessed with pre/post liver chemistries, blood counts and clinical adverse events (AEs) using National Cancer Institute Common Terminology Criteria for AEs v5.0. Tumor response was assessed per Response Evaluation Criteria in Solid Tumors 1.1 and modified RECIST criteria. Kaplan-Meier analysis was used to estimate median overall survival (OS), progression-free survival (PFS), and time to progression (TTP) from the date of Y90. ResultsMedian follow-up was 31.9 months. Grade 1 fatigue was observed in 13/18 patients (72%), with 1/18 patient (6%) experiencing grade 3 fatigue. Three patients (17%) exhibited grade 3 lymphopenia. No other grade 3 or any grade 4 AE was observed. Tumor objective response was achieved in 83% of patients by RECIST size criteria and 100% by mRECIST enhancement criteria. Median OS was 69.4 months (95% CI, 23.1-99.4) and median PFS was 12.2 months (95% CI, 4.6-28.8). Median overall TTP was 13.0 months (95% CI, 4.6-45.1), with median treated tumor TTP not reached. ConclusionY90 RS demonstrates high rates of antitumor response with a favorable toxicity profile and durable OS in the treatment of NELMs.

Head-to-head comparison of contrast-enhanced CT, dual-layer spectral-detector CT, and Gd-EOB-DTPA-enhanced MR in detecting neuroendocrine tumor liver metastases

PurposeTo explore the optimal of kiloelectron voltage (keV) of virtual monoenergetic imaging (VMI) of dual-layer spectral-detector CT (DLCT) in detecting neuroendocrine tumor liver metastases (NETLM) and to investigate diagnostic performance of polyenergetic images (PEI), DLCT, and Gd-EOB-DTPA-enhanced MR. MethodsSeventy-two patients with suspected NETLM who underwent DLCT and Gd-EOB-DTPA-enhanced MR were retrospectively enrolled. Tumor signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were compared between PEI and VMI at 40–140 keV. Two radiologists read the CT examinations with and without VMI separately in consensus. Two other radiologists read the Gd-EOB-DTPA-enhanced MR in consensus. The diagnostic performance was evaluated. Reference standard was histopathology, follow-up, and interpretation of all available imaging. ResultsThe highest SNR and CNR were observed at VMI40keV, significantly higher than PEI in the arterial and venous phases (all P<0.01). A total of 477 lesions were identified (396 metastases, 81 benign lesions). Per-lesion AUC was 0.86, 0.91, and 0.97 (PEI, DLCT, and Gd-EOB-DTPA-enhanced MR, respectively). Sensitivity of PEI, DLCT, and Gd-EOB-DTPA-enhanced MRI were 0.76, 0.86, and 0.95, respectively. DLCT significantly improved sensitivity compared to PEI. MR had significantly higher sensitivity than DLCT and PEI. Subgroup analysis demonstrated that the difference in diagnostic performance was concentrated on lesions < 10 mm. ConclusionThe image quality of VMI40keV is higher than that of PEI. DLCT with VMI40keV provides better diagnostic sensitivity for NETLM detection than PEI. Gd-EOB-DTPA-enhanced MR yielded the best diagnostic performance for NETLM detection.

Development of 3D-iNET ORION: a novel, pre-clinical, three-dimensional in vitro cell model for modeling human metastatic neuroendocrine tumor of the pancreas

Neuroendocrine tumors (NETs) of the pancreas are rare neoplasms that present complex challenges to diagnosis and treatment due to their indolent course. The incidence of pancreatic neuroendocrine tumors has increased significantly over the past two decades. A limited number of pancreatic neuroendocrine cell lines are currently available for the research. Here, we present 3D-iNET ORION, a novel 3-dimensional (spheroid) cell line, isolated from human pancreatic neuroendocrine tumor liver metastasis. Three-dimensionally grown (3D) cancer cell lines have gained interest over the past years as 3D cancer cell lines better recapitulate the in vivo structure of tumors, and are more suitable for in vitro and in vivo experiments. 3D-iNET ORION cancer cell line showed high potential to form tumorspheres when embedded in Matrigel matrix and expresses synaptophysin and EpCAM. Electron microscopy analysis of cancer cell line proved the presence of dense neurosecretory granules. When xenografted into athymic mice, 3D-iNET ORION cells produce slow-growing tumors, positive for chromogranin and synaptophysin. Human Core Exome Panel Analysis has shown that 3DiNET ORION cell line retains the genetic aberration profile detected in the original tumor. In conclusion, our newly developed neuroendocrine cancer cell line can be considered as a new research tool for in vitro and in vivo experiments.

Neuroendocrine Tumors of Unknown Primary in the Setting of Cytoreductive Hepatectomy.

Surgical cytoreduction for neuroendocrine tumor liver metastasis (NETLM) consistently shows positive long-term outcomes. Despite reservations in guidelines for surgery when the primary tumor is unidentified (UP-NET), this study compared the surgical and oncologic long-term outcomes between patients with these rare cases undergoing cytoreductive surgery and patients who had liver resection for known primaries. The study identified 32 unknown primary liver metastases (UP-NETLM) in 522 retrospectively evaluated patients who underwent resection of well-differentiated NETLM between January 2000 and December 2020. Tumor and patient characteristics were compared with those in 490 cases of liver metastasis from small intestinal (SI-NETLM) or pancreatic (pNETLM) primaries. Survival analysis was performed to highlight long-term outcome differences. Surgical outcomes were compared between liver resections alone and simultaneous primary resections to assess surgical risk distinctions. The UP-NET patients had fewer NETLMs (p = 0.004), which on the average were largerthan SI-NETLMs or pNETLMs (p = 0.002). Expression of Ki-67 was balanced among the groups. Major hepatectomy was performed more often in the UP-NETLM group (p = 0.017). The 10-year survival rate of 53% for UP-NETLM was comparable with that for SI-NETML (58%; p = 0.463) and pNETLMs (47%; p = 0.497). The median hepatic progression-free survival was 26 months for the UP-NETLM patients and 25 months for the SI-NETLM patients compared to 12 months for the pNETLM patients (p < 0.001). Perioperative mortality was lower than 2%, and severe postoperative morbidity occurred in 21%, similarly distributed among all the groups. The surgical risk and long-term outcomes for the UP-NETLM patients were comparable with those for other NETLM cases, affirming the validity of equally aggressive surgical cytoreduction as a therapeutic option in carefully selected cases.

Utility of clinical and MR imaging parameters for prediction and monitoring of response to capecitabine and temozolomide (CAPTEM) therapy in patients with liver metastases of neuroendocrine tumors.

This study explores the predictive and monitoring capabilities of clinical and multiparametric MR parameters in assessing capecitabine and temozolomide (CAPTEM) therapy response in patients with neuroendocrine tumors (NET). This retrospective study (n = 44) assessed CAPTEM therapy response in neuroendocrine liver metastases (NELM) patients. Among 33 monitored patients, as a subgroup of the overall study cohort, pretherapeutic and follow-up MRI data (size, apparent diffusion coefficient [ADC] values, and signal intensities), along with clinical parameters (chromogranin A [CgA] and Ki-67%), were analyzed. Progression-free survival (PFS) served as the reference. Responders were defined as those with PFS ≥ 6 months. Most patients were male (75%) and had G2 tumors (76%) with a pancreatic origin (84%). Median PFS was 5.7 months; Overall Survival (OS) was 25 months. Non-responders (NR) had higher Ki-67 in primary tumors (16.5 vs. 10%, p = 0.01) and increased hepatic burden (20% vs. 5%, p = 0.007). NR showed elevated CgA post-treatment, while responders (R) exhibited a mild decrease. ADC changes differed significantly between groups, with NR having decreased ADCmin (-23%) and liver-adjusted ADCmean/ADCmean liver (-16%), compared to R's increases of ADCmin (50%) and ADCmean/ADCmean liver (30%). Receiver operating characteristic (ROC) analysis identified the highest area under the curve (AUC) (0.76) for a single parameter for ∆ ADC mean/liver ADCmean, with a cut-off of < 6.9 (76% sensitivity, 75% specificity). Combining ∆ Size NELM and ∆ ADCmin achieved the best balance (88% sensitivity, 60% specificity) outperforming ∆ Size NELM alone (69% sensitivity, 65% specificity). Kaplan-Meier analysis indicated significantly longer PFS for ∆ ADCmean/ADCmean liver < 6.9 (p = 0.024) and ∆ Size NELM > 0% + ∆ ADCmin < -2.9% (p = 0.021). Survival analysis emphasizes the need for adapted response criteria, involving combined evaluation of CgA, ADC values, and tumor size for monitoring CAPTEM response in hepatic metastasized NETs.

Dose–effect relationships in neuroendocrine tumour liver metastases treated with [166Ho]-radioembolization

PurposeAim of this study was to investigate a dose-response relationship, dose-toxicity relationship, progression free survival (PFS) and overall survival (OS) in neuroendocrine tumour liver metastases (NELM) treated with holmium-166-microspheres radioembolization ([166Ho]-radioembolization).Materials and methodsSingle center, retrospective study included patients with NELM that received [166Ho]-radioembolization with post-treatment SPECT/CT and CECT or MRI imaging for 3 months follow-up. Post-treatment SPECT/CT was used to calculate tumour (Dt) and whole liver healthy tissue (Dh) absorbed dose. Clinical and laboratory toxicity was graded by Common Terminology Criteria for Adverse Events (CTCAE), version 5 at baseline and three-months follow-up. Response was determined according to RECIST 1.1. The tumour and healthy doses was correlated to lesion-based objective response and patient-based toxicity. Kaplan Meier analyses were performed for progression free survival (PFS) and overall survival (OS).ResultsTwenty-seven treatments in 25 patients were included, with a total of 114 tumours. Median follow-up was 14 months (3 – 82 months). Mean Dt in non-responders was 68 Gy versus 118 Gy in responders, p = 0.01. ROC analysis determined 86 Gy to have the highest sensitivity and specificity, resp. 83% and 81%. Achieving a Dt of ≥ 120 Gy provided the highest likelihood of response (90%) for obtaining response. Sixteen patients had grade 1–2 clinical toxicity and only one patient grade 3. No clear healthy liver dose-toxicity relationship was found. The median PFS was 15 months (95% CI [10.2;19.8]) and median OS was not reached.ConclusionThis study confirms the safety and efficacy of [166Ho]-radioembolization in NELM in a real-world setting. A clear dose–response relationship was demonstrated and future studies should aim at a Dt of ≥ 120 Gy, being predictive of response. No dose-toxicity relationship could be established.

Intra-arterial Peptide Receptor Radionuclide Therapy for the Treatment of Hepatic Neuroendocrine Tumor Metastases: Hope or Hype?

Peptide receptor radionuclide therapy (PRRT) confers significant progression-free survival advantage for patients with small bowel grade 1 and 2 well-differentiated neuroendocrine tumors (WD NET). PRRT may also be clinically beneficial for patients with NET of pancreatic, bronchial, and other sites of origin; patients with paragangliomas; as well as for patients with well-differentiated grade 3 NET. Direct intra-arterial (IA) administration of PRRT into the hepatic artery for patients with NET liver metastases may result in higher radiopharmaceutical dose and longer dwell time in the liver tumors while relatively sparing non-tumor liver tissue and other organs such as the kidneys and bone marrow when compared with intravenous (IV) administration. This review summarizes currently available data on IA and IV PRRT dose distribution, reports safety and efficacy of IA PRRT, and proposes future research questions.

Comparison of 68Ga-DOTATATE Positron Emmited Tomography/Computed Tomography and Gadoxetic Acid-Enhanced Magnetic Resonance Imaging for the Detection of Liver Metastases from Well-Differentiated Neuroendocrine Tumors.

This study aimed to compare the detection of neuroendocrine tumor liver metastases (NLMs) in hepatobiliary-specific contrast-enhanced MRI (pMR) versus 68Ga-DOTATATE PET/CT (DT-PET). This retrospective study cohort included 30 patients with well-differentiated neuroendocrine tumors who underwent both DT-PET and pMR. Two readers independently assessed NLMs count, SUVmax on DT-PET, and signal characteristics on pMR. A consensus review by two additional readers resolved discrepancies between the modalities. Results showed concordance between DT-PET and pMR NLM count in 14/30 patients (47%). pMR identified more NLMs in 12/30 patients (40%), of which 4 patients showed multiple deposits on pMR but only 0-1 lesions on DT-PET. DT-PET detected more in 4/30 patients (13%). Overall, pMR detected more metastases than DT-PET (p = 0.01). Excluding the four outliers, there was excellent agreement between the two methods (ICC: 0.945, 95%CI: 0.930, 0.958). Notably, pMR had a higher NLM detection rate than DT-PET, with correlations found between lesion size on pMR and DT-PET detectability, as well as diffusion restriction on pMR and SUVmax on DT-PET. In conclusion, in consecutive patients with well-differentiated NETs, the detection rate of NLM is higher with pMR than with DT-PET. However, when excluding patients whose tumors do not overexpress somatostatin receptors (13% of the cohort), high concordance in the detection of NLM is observed between DT PET and pMR.

Diagnostic accuracy of SSR-PET/CT compared to histopathology in the identification of liver metastases from well-differentiated neuroendocrine tumors

BackgroundHistopathology is the reference standard for diagnosing liver metastases of neuroendocrine tumors (NETs). Somatostatin receptor-positron emission tomography / computed tomography (SSR-PET/CT) has emerged as a promising non-invasive imaging modality for staging NETs. We aimed to assess the diagnostic accuracy of SSR-PET/CT in the identification of liver metastases in patients with proven NETs compared to histopathology.MethodsHistopathologic reports of 139 resected or biopsied liver lesions of patients with known NET were correlated with matching SSR-PET/CTs and the positive/negative predictive value (PPV/NPV), sensitivity, specificity, and diagnostic accuracy of SSR-PET/CT were evaluated. PET/CT reading was performed by one expert reader blinded to histopathology and clinical data.Results133 of 139 (95.7%) liver lesions showed malignant SSR-uptake in PET/CT while initial histopathology reported on ‘liver metastases of NET´ in 127 (91.4%) cases, giving a PPV of 91.0%. Re-biopsy of the initially histopathologically negative lesions (reference standard) nevertheless diagnosed ‘liver metastases of NET’ in 6 cases, improving the PPV of PET/CT to 95.5%. Reasons for initial false-negative histopathology were inadequate sampling in the sense of non-target biopsies. The 6 (4.3%) SSR-negative lesions were all G2 NETs with a Ki-67 between 2–15%.ConclusionSSR-PET/CT is a highly accurate imaging modality for the diagnosis of liver metastases in patients with proven NETs. However, we found that due to the well-known tumor heterogeneity of NETs, specifically in G2 NETs approximately 4–5% are SSR-negative and may require additional imaging with [18F]FDG PET/CT.

Single center outcomes from parenchymal-sparing resections and microwave ablations for neuroendocrine tumor liver metastases

BackgroundReported outcomes after surgical debulking in patients with advanced neuroendocrine tumor liver metastases (NETLM) are sparse. MethodsNETLM patients that underwent surgical debulking from 2019 to 2021 were reviewed. Trends in perioperative liver function, complications, symptom response, and progression-free survival were examined. Results1069 liver lesions were debulked from 53 patients using a combination of parenchymal-sparing resections (PSR) and ultrasound-guided microwave ablations (MWA). Post-operative transaminitis and thrombocytopenia were common, and severity correlated with increasing number of lesions. Laboratory markers for synthetic liver function did not differ according to the number of lesions debulked. 13% of patients sustained a Clavien-Dindo grade 3 or 4 complication which was not associated with the number of lesions targeted. All patients with preoperative symptoms had improvement after surgery. Median time to progression was 10.9 months. ConclusionsPSR with MWA for large numbers of NETLM is safe and effective for symptom control and does not affect synthetic liver function.

Local Treatment of Neuroendocrine Liver Metastases: How Effective and Safe is Stereotactic Microwave Ablation?

Abstract Background The less invasiveness of local ablation techniques such as stereotactic microwave ablation (SMWA) for the treatment of malignant hepatic lesions has made it an attractive alternative to conventional surgical resection. Aims The aim of this retrospective study was to assess the successful ablation rate of neuroendocrine tumor liver metastases (NETLM) 3 months after SMWA, the recurrence-free survival time, as well as the rate of peri- and early post interventional complications. Methods Retrospective analysis including all patients treated with SMWA for NETLM in our institution between 03/2015 and 07/2022. SMWA was performed as per the decision of the interdisciplinary tumorboard. Patients were included independent of location of primary tumors, disease stage, prior treatments. Patients underwent follow-up imaging (FU) every 1-6 months. Results 41 metastases were ablated in 21 interventions in 17 patients with a mean age of 63.6±9.7 years. A median of two lesions (range 1-4) were ablated per intervention. Mean time until first FU was 2.8±1.5 months. 39 of 41 (95.1%) lesions were fully ablated at the first FU. The two incompletely ablated lesions were treated using re-ablation and systemic treatment, respectively. A local recurrence occurred in further two ablation zones (4.9%) after 3.6 years in a patient with a progressive disease. Remaining 37 (90.2%) patients had no tumor recurrence in the ablation zone at the latest available FU (mean 24.3±17.3 months). Postinterventional length of hospital stay was a median of 1 [IQR 1;1.5]. No complications higher than Clavien Dindo Grade II occurred. Conclusions SMWA is a good minimal invasive intervention for the treatment of NETLM with low morbidity and high local efficacy.

Histopathological growth patterns of neuroendocrine tumor liver metastases

Histopathological growth patterns (HGPs) of liver metastases represent a potential biomarker for prognosis after resection. They have never been studied in neuroendocrine tumor liver metastases (NETLM). This study evaluated if distinct HGPs can be observed in resected NETLM and if they have prognostic value. Sixty-three patients who underwent resection of NETLM between 01–01-2001 and 31–12-2021 were retrospectively included. HGPs were scored on Haematoxylin&Eosin slides using light microscopy, distinguishing desmoplastic- (dHGP), pushing- (pHGP) and replacement HGP (rHGP). Average HGP scores were calculated per patient. Each patient was classified according to predominant HGP. Overall and Disease-Free Survival (OS and DFS) were evaluated through Kaplan–Meier analysis and Cox regression. Eighteen patients had predominant dHGP (29%), 33 had predominant pHGP (52%) and 11 had predominant rHGP (17%). One patient had mixed HGP (2%). Five-year OS was 76% (95%CI: 66–87%) for the overall cohort. Five-year OS was 92% (95%CI: 77–100%) for dHGP, was 73% (95%CI: 59–91%) for pHGP, 50% (95%CI: 25–100%) for rHGP. Five-year DFS was 39% (95%CI: 19–83%) for dHGP, 44% (95%CI: 27–71%) for rHGP and 50% (95%CI: 23–100%) for pHGP. There was no significant association between HGP and OS or DFS in multivariable analysis. Distinct HGPs could be identified in NETLM. In patients who underwent resection of NETLM, no association was found between HGPs and postoperative survival. Half of the patients with NETLM have a predominant pushing growth pattern, which is a rare growth pattern in liver metastases from breast and colorectal cancer.

The possibilities of intra-arterial chemioembolization in the treatment of patients with unresectable liver metastases of neuroendocrine tumors

Введение. Печень является основным органом метастазирования нейроэндокринных опухолей. Количество, размеры и распространение метастазов в печени считаются важными факторами, определяющими прогноз заболевания и качество жизни пациента. Относительно недавно резекция была единственным предпочтительным методом лечения. Однако, учитывая мультифокальный, преимущественно билобарный, характер поражения печени, пациенты с метастазами нейроэндокринных опухолей не подходят для оперативного вмешательства. Цель. Анализ результатов применения внутриартериальной химиоэмболизации в лечении пациентов с нерезектабельными метастазами нейроэндокринных опухолей в печень. Материалы и методы. Проведена ретроспективная оценка результатов лечения методами интервенционной радиологии 142 пациентов с метастатическим поражением печени при нейроэндокринных опухолях за период с 2006 по 2021 гг. Результаты. После 2-х циклов регионарной химиотерапии полный ответ достигнут у 13 % пациентов, частичный — у 20 %, стабилизация — у 53 %, прогрессирование — у 14 %. Снижение проявлений карциноидного синдрома отмечено у 65 % пациентов. У пациентов с первично нерезектабельными метастазами нейроэндокринных опухолей в печень после регионарной химиотерапии удалось провести в 5 % случаев радикальные и в 8 % случаев циторедуктивные операции. Заключение. Количество, размеры и расположение метастазов в печени считаются важными факторами, определяющими прогноз заболевания и качество жизни пациента. Учитывая мультифокальный, преимущественно билобарный, характер поражения печени, большинство пациентов с метастазами нейроэндокринных опухолей не подходят для оперативного вмешательства. Методы интервенционной радиологии являются эффективным альтернативным лечением, которое может уменьшить опухолевую нагрузку, облегчить симптоматическое проявление карциноидного синдрома, подготовить пациента к дальнейшему циторедуктивному вмешательству.

Number of Hepatic Resections and Association with Complication after Metastatic Neuroendocrine Tumor Debulking: An American College of Surgeons NSQIP Database Study.

Neuroendocrine tumor liver metastases (NELM) are a major source of morbidity and mortality in neuroendocrine tumor patients and can be treated with hepatic debulking surgery (HDS). This study aims to identify variables associated with postoperative morbidity in NELM HDS. This analysis uses the American College of Surgeons NSQIP targeted hepatectomy-specific Participant User File from 2014 to 2020. Surgeries were grouped by number of hepatic resections performed (1 to 5, 6 to 10, greater than 10). Multivariable logistic regression and matching were used to identify prognostic factors of morbidity. A total of 1,163 patients were included. A total of 1,011 (87%) had 1 to 5 hepatic resections, 101 (8.7%) had 6 to 10 resections, and 51 (4.4%) had greater than 10 resections. The overall complication rate was 35%, and surgical and medical complications reached 30% and 13%, respectively. Mortality occurred in 11 patients (0.9%). Significantly higher rates of any (34% vs 35% vs 53%, p = 0.021) and surgical complications (29% vs 28% vs 49%, p = 0.007) were noted for those undergoing greater than 10 resections (1 to 5 resections, 6 to 10, greater than 10). "Bleeding requiring transfusion" (p < 0.0001) occurred more frequently in the greater than 10 resection group. On multivariable logistic regression, greater than 10 resections were an independent risk factor for any (odds ratio [OR] 2.53, p = 0.002; OR 2.52, p =. 0013) and surgical (OR 2.53, p = 0.003; OR 2.88, p = 0.005) complications compared with 1 to 5 resections and 6 to 10 resections, respectively. Medical complications (OR 2.34, p = 0.020) and length of stay greater than 5 days (OR 1.98, p = 0.032) were also increased with greater than 10 vs 1 to 5 resections. As reported by NSQIP, NELM HDS were performed safely with low mortality. However, more hepatic resections, especially greater than 10, were associated with increased postoperative morbidity and length of stay.

Defining a New Classification System for the Surgical Management of Neuroendocrine Tumor Liver Metastases.

Although rarely curative, hepatic cytoreduction of neuroendocrine tumor liver metastases (NETLM) is associated with improved symptom control and prolonged survival. Preoperative 68Ga DOTATATE and gadoxetic acid-enhanced liver MRI can improve characterization of hepatic disease extent to improve surgical clearance, and resection of the primary tumor is associated with improved survival regardless of whether the liver metastases are treated. As parenchymal-sparing surgical techniques and the lowering of the debulking threshold have expanded the numbers of eligible NETLM patients for hepatic cytoreduction, we propose a new classification system to help guide surgical management. A multimodal approach that includes surgery, liver-directed therapies, and systemic therapies has improved outcomes and increased longevity for patients with well-differentiated metastatic NET.

Results of Application of Saturable Microspheres of Domestic Production in Locoregional Endovascular Treatment of Inoperable Patients with Malignant Liver Tumors

The incidence of malignant liver tumors is steadily increasing. Most patients are considered inoperable at the time of detection of a malignant liver lesion. In general, unsatisfactory liver function, comorbidities, bilobar lesion, extrahepatic metastasis allow performing radical treatment in not more than 20 % of cases. Thus, the majority of patients are indicated for other types of treatment, including endovascular locoregional techniques. Taking into account the implementation of the federal program for state support of import substitution in Russia, the creation and production of competitive products in the field of medicine, including for endovascular surgery, becomes relevant. The aim of this article was to study the properties, tolerability and safety of domestically produced saturable microspheres and evaluate the immediate results of transarterial chemoembolization in the treatment of inoperable patients with primary and metastatic liver cancer. Within the framework of the State Scientific Program, clinical studies on the use of saturable microspheres produced in Russia were conducted. The results of treatment of 32 patients who underwent transarterial chemoembolization (TACE) with the use of domestic microspheres “Sphere-Spectrum” at the N.N. Blokhin Research Institute of Oncology from January 2020 to October 2022 were analyzed. Of these, TACE was performed in 24 patients diagnosed with HCC, 5 patients with liver metastases of neuroendocrine tumors, and 3 patients with melanoma metastases. TACE was performed using microspheres with sizes 35–40 in dry (210–240 μm in saturated) 50–60 μm in dry (300–360 μm in saturated), 25 mg or 50 mg in one vial. A total of 40 endovascular procedures were performed in all 32 patients with malignant liver tumor lesions. In 11 of them (34.3 %) a single TACE session was sufficient to achieve an objective response. Partial response was observed in 21 (65.7 %) patients, including those with bilobar metastatic liver lesion. All patients tolerated treatment satisfactorily, the desired therapeutic effect was achieved in 26 (81.2 %) cases (taking into account repeated interventions). One patient (3.1 %) diagnosed with HCC had a complication in the form of liver abscess formation.

Laparoscopic-assisted liver transplantation: A realistic perspective

Laparoscopic approach was rarely described in recipients for liver transplantation (LT). We report the feasibility and safety of laparoscopic-assisted LT (LA-LT) in patients with unresectable liver metastases of neuroendocrine tumors. Total hepatectomy was performed laparoscopically with graft implantation through an upper midline incision. Liver grafts were retrieved from deceased donors. From July 2019 to July 2021, six patients (4 women, 2 men) underwent LA-LT. Median age and BMI were 46 (29-54) and 24 (19-35) kg/m2 , respectively. Implanted grafts were reduced (n= 3), full (n= 2), and a right split liver (n= 1). Median surgical time was 405 min (390-450) and median blood loss was 425 ml (250-600). Median cold and warm ischemia times were 438 min (360-575) and 35 min (30-40), respectively. Median anhepatic phase was 51 min (40-67) and midline incision was 14 cm (13-20) long. On postoperative day 5, median prothrombin index and serum bilirubin levels were 95% (70-117) and 11 (10-37) μmol/L, respectively. No Clavien-Dindo > III complications were encountered. Median hospital stay was 12 days (10-14). After a median follow-up of 8 (8-32) months, all patients were alive without tumor recurrence or adverse event. This preliminary series suggests that in selected patients, LA-LT is a safe and effective option.

Analysis of Tumor Burden as a Biomarker for Patient Survival with Neuroendocrine Tumor Liver Metastases Undergoing Intra-Arterial Therapies: A Single-Center Retrospective Analysis.

To assess the value of quantitative analysis of tumor burden on baseline MRI for prediction of survival in patients with neuroendocrine tumor liver metastases (NELM) undergoing intra-arterial therapies. This retrospective single-center analysis included 122 patients with NELM who received conventional (n = 74) or drug-eluting beads, (n = 20) chemoembolization and radioembolization (n = 28) from 2000 to 2014. Overall tumor diameter (1D) and area (2D) of up to 3 largest liver lesions were measured on baseline arterially contrast enhanced MR images. Three-dimensional quantitative analysis was performed using the qEASL tool (IntelliSpace Portal Version 8, Philips) to calculate enhancing tumor burden (the ratio between enhancing tumor volume and total liver volume). Based on Q-statistics, patients were stratified into low tumor burden (TB) or high TB. The survival curves were significantly separated between low TB and high TB groups for 1D (p < 0.001), 2D (p < 0.001) and enhancing TB (p = 0.008) measurements, with, respectively, 2.7, 2.6 and 2.2 times longer median overall survival (MOS) in the low TB group (p < 0.001, p < 0.001 and p = 0.008). Multivariate analysis showed that 1D, 2D, and enhancing TB were independent prognostic factors for MOS, with respective hazard ratios of 0.4 (95%CI: 0.2-0.6, p < 0.001), 0.4 (95%CI: 0.3-0.7, p < 0.001) and 0.5 (95%CI: 0.3-0.8, p = 0.003). The overall tumor diameter, overall tumor area, and enhancing tumor burden are strong prognostic factors of overall survival in patients withneuroendocrine tumor liver metastases undergoing intra-arterial therapies.

Abstract No. 251 Bland embolization of neuroendocrine tumor liver metastases: rates of periprocedural hemodynamic instability

Transarterial bland embolization (TAE) is commonly used for treatment of neuroendocrine tumor liver metastases (NETLMs). Hormonal release causing hemodynamic instability and carcinoid symptoms is frequently observed during bland embolization of NETLMs. Data are lacking about the hemodynamic changes that can occur following TAE of NETLMs. The purpose of our study was to investigate the rate of periprocedural hemodynamic instability (PPHDI) associated with TAE for NETLMs.

Abstract No. 563 Yttrium-90 radiation segmentectomy for neuroendocrine tumor liver metastases

Yttrium-90 (Y-90) radioembolization is a liver-directed treatment option for patients with neuroendocrine tumor liver metastases (NELMs), but there are concerns of long-term hepatotoxicity. Radiation segmentectomy (RS) has been described in hepatocellular carcinoma, selectively delivering tumor-ablative radiation doses in a parenchymal-sparing approach. We hypothesize that RS of NELMs can achieve considerable locoregional disease control with a positive safety profile.