Absence Of Extrahepatic Disease Research Articles

Current status of liver surgery for non-colorectal non-neuroendocrine liver metastases: the NON.LI.MET. Italian Society for Endoscopic Surgery and New Technologies (SICE) and Association of Italian Surgeons in Europe (ACIE) collaborative international survey.

Despite the increasing trend in liver resections for non-colorectal non-neuroendocrine liver metastases (NCNNLM), the role of surgery for these liver malignancies is still debated. Registries are an essential, reliable tool for assessing epidemiology, diagnosis, and therapeutic approach in a single hub, especially when data are dispersive and inconclusive, as in our case. The dissemination of this preliminary survey would allow us to understand if the creation of an International Registry is a viable option, while still offering a snapshot on this issue, investigating clinical practices worldwide. The steering committee designed an online questionnaire with Google Forms, which consisted of 37 questions, and was open from October 5th, 2022, to November 30th, 2022. It was disseminated using social media and mailing lists of the Italian Society of Endoscopic Surgery and New Technologies (SICE), the Association of Italian Surgeons in Europe (ACIE), and the Spanish Chapter of the American College of Surgeons (ACS). Overall, 141 surgeons (approximately 18% of the total invitations sent) from 27 countries on four continents participated in the survey. Most respondents worked in general surgery units (62%), performing less than 50 liver resections/year (57%). A multidisciplinary discussion was currently performed to validate surgical indications for NCNNLM in 96% of respondents. The most commonly adopted selection criteria were liver resectability, RECIST criteria, and absence of extrahepatic disease. Primary tumors were generally of gastrointestinal (42%), breast (31%), and pancreaticobiliary origin (13%). The most common interventions were parenchymal-sparing resections (51% of respondents) of metachronous metastases with an open approach. Major post-operative complications (Clavien-Dindo > 2) occurred in up to 20% of the procedures, according to 44% of respondents. A subset analysis of data from high-volume centers (> 100 cases/year) showed lower post-operative complications and better survival. The present survey shows that NCNNLM patients are frequently treated by surgeons in low-volume hospitals for liver surgery. Selection criteria are usually based on common sense. Liver resections are performed mainly with an open approach, possibly carrying a high burden of major post-operative complications. International guidelines and a specific consensus on this field are desirable, as well as strategies for collaboration between high-volume and low-volume centers. The present study can guide the elaboration of a multi-institutional document on the optimal pathway in the management of patients with NCNNLM.

Prognostic Factors for Effectiveness Outcomes After Transarterial Radioembolization in Metastatic Colorectal Cancer: Results From the Multicentre Observational Study CIRT

BackgroundTransarterial radioembolisation (TARE) with Yttrium-90 resin microspheres is a treatment option for patients with metastatic colorectal cancer in the liver (mCRC). A better understanding of the prognostic factors and treatment application can improve survival outcomes. MethodsWe analysed the safety and effectiveness of 237 mCRC patients included in the prospective observational study CIRSE Registry for SIR-Spheres Therapy (CIRT) for independent prognostic factors for overall survival (OS), progression-free survival (PFS) and hepatic progression-free survival (hPFS) using the Cox proportional-hazard model. ResultsThe median OS was 9.8 months, median PFS was 3.4 months and median hPFS was 4.2 months. Independent prognostic factors for an improved overall survival were the absence of extra-hepatic disease (P= .0391), prior locoregional procedures (P= .0037), an Aspartate transaminase to Platelet Ratio Index (APRI) value of ≤0.40 (P< .0001) and International Normalized Ratio (INR) ≤1 (P= .0078). Partition model dosimetry resulted in improved OS outcomes compared to the body surface area model (P = .0120). Independent predictors for PFS were APRI >0.40 (P = .0416) and prior ablation (P = .0323), and for hPFS these were 2 to 5 tumor nodules (P = .0148), Albumin-bilirubin (ALBI) grade 3 (P = .0075) and APRI >0.40 (P = .0207). During the study, 95 of 237 (40.1%) patients experienced 197 adverse events, with 28 of 237 (11.8%) patients having a grade 3 or higher adverse events. ConclusionIncluding easy-to-acquire laboratory markers INR, APRI, ALBI and using partition model dosimetry can identify mCRC patients that may benefit from TARE.

Trends in long-term survival after liver resection for gastric cancer liver metastasis: Analysis of a single-center experience over 28 years.

290 Background: While systemic chemotherapy for gastric cancer has evolved significantly in the last decade, the role of surgery for liver metastasis remained controversial. The aims of this study were to examine the trend in outcomes of patients with gastric cancer liver metastasis (GCLM) undergoing resection at our center, and to define the optimal selection criteria for resection. Methods: One hundred and twenty-two consecutive patients who underwent liver resection for GCLMs with curative intent at our institution from 1993 through 2021 were included. The patients were grouped into 2 eras: era I, 1993 to 2010; era II, 2011 to 2021. Our criteria for liver resection included absence of extrahepatic disease, and the limited number of liver metastasis (often 3 or less). Median follow-up was 34 months for all and 71 months for the survivors. Results: There were 63 patients in era I and 59 in era II. The patients in era II received chemotherapy prior to liver resection more often (68% vs 41%, p = 0.004), and their primary tumor was less advanced (T3/4; 66% vs 85%, p = 0.021) with less regional lymph node metastasis (median No. of positive nodes; 4 vs 1, p = 0.034) compared to those in ear I. Median and 5-year disease-specific survival (DSS) were better in era II (not reached, 55%) than in era I (35 months, 35%, p = 0.025). In the multivariate analysis for the entire cohort, elevated CEA (&gt; 50 ng/ml), primary T4, and primary at the proximal stomach emerged as independent factors associated with shorter DSS. Number of these risk factors are highly predictive for long-term survival; among the patients without or with a single factor alone, 5-year DSS was 50%, whereas none of those with multiple risk factors survived beyond 5 years ( p&lt; 0.0001). Conclusions: Long-term outcomes for patients with oligo-GCLM has improved in the modern chemotherapy era. Liver resection should be considered unless they carry multiple risk factors.

Laparoscopic vs open liver resection for metastatic colorectal cancer: analysis of surgical margin status and survival.

Liver resection represents the curative treatment of choice for patients with colorectal liver metastases (CRLM). Laparoscopic hepatectomy in CRLM is considered a safe approach. However, the information on their oncological results in the different series is deficient. This study aimed to compare the surgical margin, overall survival (OS), and disease-free survival (DFS) in patients with oncological resections of CRLM according to the type of surgical approach performed. Between April 2007 and June 2017, 263 patients with CRLM underwent hepatic resection. Inclusion criteria were initial resectability, tumor size ≤ 50mm, 3 or less metastases, no bilobar involvement, and absence of extrahepatic disease. A propensity score was performed to adjust the indication bias. Eighty-two patients were included (56 open and 26 laparoscopic). Twenty-eight (50%) patients had synchronous presentation in the open approach and 6 (23%) in the laparoscopic approach (p = 0.021), with more frequent simultaneous open resections (p = 0.037). The resection margin was positive (R1) in 5 patients with an open approach and 2 with a laparoscopic approach (8.9% and 7.6% respectively; p = 0.852). Nine patients (16%) with conventional approach and 2 (7.7%) with laparoscopic approach had local complications (p = 0.3). There was one death in the open group and none in the laparoscopic. There were no significant differences in OS and DFS rate between both groups (1-3years, OS: 92-77% and 96-75% respectively; 1-3years, DFS: 63-20% and 73-36% respectively). There were no significant differences in terms of surgical margin, OS rate, and DFS rate between the laparoscopic and open approach in patients with CRLM.

Proposal of a New Definition of "Very Early" Intrahepatic Cholangiocarcinoma-A Retrospective Single-Center Analysis.

Intrahepatic cholangiocarcinoma (ICC) is a rare disease with poor outcome, despite advances in surgical and non-surgical treatment. Recently, studies have reported a favorable long-term outcome of “very early” ICC (based on tumor size and absence of extrahepatic disease) after hepatic resection and liver transplantation, respectively. However, the prognostic value of tumor size and a reliable definition of early disease remain a matter of debate. Patients undergoing resection of histologically confirmed ICC between February 1996 and January 2021 at our institution were reviewed for postoperative morbidity, mortality, and long-term outcome after being retrospectively assigned to two groups: “very early” (single tumor ≤ 3 cm) and “advanced” ICC (size > 3 cm, multifocality or extrahepatic disease). A total of 297 patients were included, with a median follow-up of 22.8 (0.1–301.7) months. Twenty-one (7.1%) patients underwent resection of “very early” ICC. Despite the small tumor size, major hepatectomies (defined as resection of ≥3 segments) were performed in 14 (66.7%) cases. Histopathological analyses revealed lymph node metastases in 5 (23.8%) patients. Patients displayed excellent postoperative outcome compared to patients with “advanced” disease: intrahospital mortality was not observed, and patients displayed superior long-term survival, with a 5-year survival rate of 58.2% (versus 24.3%) and a median postoperative survival of 62.1 months (versus 25.3 months; p = 0.013). In conclusion, although the concept of a “very early” ICC based solely on tumor size is vague as it does not necessarily reflect an aggressive tumor biology, our proposed definition could serve as a basis for further studies evaluating the efficiency of either surgical resection or liver transplantation for this malignant disease.

Surgical Resection of Huge Hepatocellular Carcinoma. Prognostic Factors and Outcomes in a Mexican Cohort Study

Surgery is the best choice for curative treatment for hepatocellular carcinoma (HCC), that includes liver resection (LR) or liver transplantation (LT). Tumors larger than 10 cm are considered huge HCC. Huge HCC doesn't fit any criteria for LT. Although surgical resection may be associated with higher morbidity it's still the best chance of survival in this subgroup of patients. The purpose of our study is to analyze prognostic factors and outcomes in a Mexican population. We analyzed patients who underwent LR for huge HCC between January 2015 to January 2021. Prognostic factors included in the study were age, HCC size, serum alpha fetoprotein (AFP) and vascular invasion. Only patients with Child-Pugh grade A in absence of extrahepatic disease was offered major LR. The future liver remnant volume was calculated by CT scan volumetry. Morbidity, disease free-survival and overall survival was evaluated. Fifty two patients underwent major LR: male 30 (57.6%) and female 22 (42.3%). The median age was 65 years (range, 25-76 years), median HCC size was 16 cm (range, 14-45 cm), median AFP was 85 ng/mL (range, 18-19,500 ng/mL). Lymphovascular invasion was found in 58% of liver specimens. The overall morbidity was 12% and perioperative mortality was seen in 1 (1.95%) due to heart failure. The overall 1-year and 3-year survival were 88.4% and 51.9% respectively. Factors of adverse outcome after major LR in patients with huge HCC were the presence of lymphovascular invasion, AFP > 1,000 ng/mL, and age > 65 years.

Neuroendocrine liver metastases: a contemporary review of treatment strategies.

Well-differentiated neuroendocrine tumors (NETs) are globally increasing in prevalence and the liver is the most common site of metastasis. Neuroendocrine liver metastases (NELM) are heterogeneous in clinical presentation and prognosis. Fortunately, recent advances in diagnostic techniques and therapeutic strategies have improved the multidisciplinary management of this challenging condition. When feasible, surgical resection of NELM offers the best long-term outcomes. General indications for hepatic resection include performance status acceptable for major liver surgery, grade 1 or 2 tumors, absence of extrahepatic disease, adequate size and function of future liver remnant, and feasibility of resecting >90% of metastases. Adjunct therapies including concomitant liver ablation are generally safe when used appropriately and may expand the number of patients eligible for surgery. Among patients with synchronous resectable NELM, resection of the primary either in a staged or combined fashion is recommended. For patients who are not surgical candidates, liver-directed therapies such as transarterial embolization, chemoembolization, and radioembolization can provide locoregional control and improve symptoms of carcinoid syndrome. Multiple systemic therapy options also exist for patients with advanced or progressive disease. Ongoing research efforts are needed to identify novel biomarkers that will define the optimal indications for and sequencing of treatments to be delivered in a personalized fashion.

Primary Tumor Location Is a Prognostic Factor for Intrahepatic Progression-Free Survival in Patients with Colorectal Liver Metastases Undergoing Portal Vein Embolization as Preparation for Major Hepatic Surgery.

The aim of this study was to identify prognostic factors affecting intrahepatic progression-free survival (ihPFS) and overall survival (OS) in patients with colorectal cancer liver metastases (CRCLM) undergoing portal vein embolization (PVE) and subsequent (extended) right hemihepatectomy. A total of 59 patients (mean age: 60.8 ± 9.3 years) with CRCLM who underwent PVE in preparation for right hemihepatectomy were included. IhPFS and OS after PVE were calculated using the Kaplan–Meier method. Cox regression analyses were conducted to investigate the association between the following factors and survival: patient age, laterality of the colorectal cancer (right- versus left-sided), tumor location (colon versus rectal cancer), time of occurrence of hepatic metastases (synchronous versus metachronous), baseline number and size of hepatic metastases, presence or absence of metastases in the future liver remnant (FLR) before PVE, preoperative carcinoembryogenic antigen (CEA) levels, time between PVE and surgery, history of neoadjuvant or adjuvant chemotherapy, and the presence or absence of extrahepatic disease before PVE. Median follow up was 18 months. The median ihPFS was 8.2 months (95% confidence interval: 6.2–10.2 months), and median OS was 34.1 months (95% confidence interval: 27.3–40.9 months). Laterality of the primary colorectal cancer was the only statistically significant predictor of ihPFS after PVE (hazard ratio (HR) = 2.242; 95% confidence interval: 1.125, 4.465; p = 0.022), with patients with right-sided colorectal cancer having significantly shorter median ihPFS than patients with left-sided cancer (4.0 ± 1.9 months versus 10.2 ± 1.5 months; log rank test: p = 0.018). Other factors, in particular also the presence or absence of additional metastases in the FLR, were not associated with intrahepatic progression-free survival. The presence of extrahepatic disease was associated with worse OS (HR = 3.050, 95% confidence interval: 1.247, 7.459; p = 0.015).

Liver Metastases-directed Therapy in the Management of Oligometastatic Breast Cancer

IntroductionIn the context of metastatic breast cancer, dissemination to the liver is a frequent occurrence. We aimed to evaluate the outcome and toxicity of metastatic breast cancer with liver oligometastases treated with metastases-directed therapies (MDTs), including surgery, stereotactic body radiation therapy, or thermal ablation (radiofrequency or microwaves). Patients and MethodsWe included patients with diagnosis of 1 to 5 liver metastases. Selection criteria included also age > 18 years; Eastern Cooperative Oncology Group performance status 0 to 2; absence of extra-hepatic disease or other controlled metastatic sites. Endpoints were liver progression-free survival (LPFS), progression-free survival (PFS), and overall survival. ResultsA total of 72 patients were included. Previous local treatments were performed in 13 (18.1%) patients, whereas systemic therapy was used in 81.9% of cases. Treatment of choice was stereotactic body radiation therapy in 54 (75%) patients followed by surgery (13 patients; 18%) and thermal ablation (5 patients; 7%). With a median follow-up of 26.2 months, LPFS at 1 and 2 years was 52.4% and 38.8%, respectively. The number of metastases predicted LPFS (hazard ratio [HR], 1.70; P = .004). Rates of PFS were 38.7% and 22% at 1 and 2 years, respectively. Systemic therapy before MDT (HR, 2.89; P = .016) was correlated with PFS. Overall survival at 1 and 2 years was 95.5% and 76.9%, respectively. Human epidermal growth factor receptor 2 status correlated with survival (HR, 1.82; P = .010). ConclusionCombination of systemic therapy with liver MDT in oligometastatic breast cancer results in durable disease control in a significant proportion of patients. Tumor biology, prior treatment, and extent of disease may be useful to guide the decision to add MDT to standard therapy.

Prognostički parametri kod bolesnika operisanih od metastaza kolorektalnog karcinoma u jetri nakon biološke terapije i hemioterapije

The aim of the research was to investigate prognostic factors in patients with resected colorectal liver metastases (CLMs) after biological and chemotherapy, which made initially unresectable disease suitable for resection. Sixty-six patients with resected CLMs, operated after induction bio-chemotherapy with bevacizumab + FOLFOX4, treated at the Clinic of Oncology, Clinical Center Niš from 2010 - 2017 were included. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared using the log-rank test according to demographic characteristics, characteristics of the disease and the treatment. A univariate COX regression analysis was performed. In patients with up to 4 CLMs, DFS was significantly longer than in patients with five or more metastases (18,384 v.s. 6,85 months; p &lt; 0,001). Significantly longer OS was present in patients with up to four CLMs than in those with five or more CLMs (44,687 v.s. 29,723 months; p=0,006) and in patients without extrahepatic disease (41,71 v.s. 23,283 months; p=0,012). In the univariate analysis, five or more CLMs were predictors of poorer DFS (HR 3,989; 95% CI 1,055 - 15,087; p = 0,042), whereas the absence of extrahepatic disease was a predictor of better OS (HR 0,122; 95% CI 0,017 - 0,869; p = 0,036). Results of this research are in concordance with previous larger studies in patients with resected CLMs. The number of hepatic and the presence of extrahepatic metastases are prognostic parameters in patients with resected CLM after conversion bio-chemotherapy.

Outcomes following liver SBRT for metastatic pancreatic cancer.

418 Background: Traditionally, the role of localized therapy for metastatic pancreatic cancer (MPC) has been limited. However, with more effective systemic therapies, recent studies have explored a potential role for local therapies. We aimed to report outcomes following SBRT (stereotactic body radiation therapy) for liver metastases (LM) in setting of MPC and to identify predictors of response. Methods: 41 patients who underwent ablative RT to LM for MPC (2005-17) were retrospectively identified. Median RT dose was 50 Gy (range: 8-60 Gy), delivered in 5-6 fractions. Kaplan Meier method was used to calculate local control (LC), progression-free survival (PFS) and overall survival (OS). Univariate (UVA) and multivariate (MVA) Cox proportional hazards models were used to identify predictors of clinical outcomes. Results: Median follow up was 14.6 months. This cohort included 19 men and 22 women. 61% of pts had metachronous LM, 39% had synchronous LM. At time of RT, the treated lesion was stable /responding to chemotherapy (CTX) in 36.6% of pts; 46.3% were progressing with mixed response; 17% were off/refused CTX. Median number of prior CTX regimens was 2 (range: 0-5). Median number of LM was 1 (range: 1-4). Median pre-RT CEA was 7 ng/mL, median pre-RT CA19-9 was 354 U/ml. The 12-month outcomes were 75.8% LC, 16.5% PFS, and 36.3% OS. 8/41 (20%) patients were off CTX for ≥ 4 months. On UVA for LC, pre-RT CA19-9 (log10 scale) was associated with LC (HR 2.28, p = 0.03). Timing of LM, CTX response of LM, number of lesions, RT dose and CEA did not predict LC. On UVA for PFS, extrahepatic disease at time of RT was associated with worse PFS (HR: 2.47, p = 0.04), and response to CTX (progressive vs. stable/responding) approached significance (HR 1.83, p = 0.10). On UVA for OS, lower pre-RT CEA (HR 1.009, p = 0.03), lower pre-RT CA19-9 (HR 1.67, p = 0.01), and response to CTX (HR 6.42, p &lt; 0.001) were associated with improved OS. On MVA for OS, response to CTX at time of liver RT remained significant for OS. Conclusions: SBRT of LM for MPC offers high rate of LC. In a small subset of patients, SBRT to LM may offer prolonged duration off systemic therapy. Lower pre-RT CA 19-9 and CEA, absence of extrahepatic disease, and stability/response of CTX at time of liver RT may select for patients most likely to benefit.

Gastric cancer liver metastasis: Optimal management for oligo-metastatic disease.

136 Background: The role of surgery for gastric cancer liver metastasis (GCLM) has not been established and particularly, the optimal management for liver-isolated, oligo-GCLMs remains controversial. The aims of this study were to review the outcomes for our patients with GCLM who underwent liver resection and to define the optimal selection criteria for resection. Methods: The medical records of patients who underwent liver resection for GCLMs with curative intent at our institution from 1993 through 2018 were reviewed. Our criteria for liver resection included absence of extrahepatic disease, and the limited number of liver metastasis (often 3 or less). Results: Total 101 patients with GCLM (77 men [76%], median age 66 years) were included. Forty-seven patients (46%) had synchronous metastasis and all underwent simultaneous resection with the primary disease. Those with synchronous disease received neoadjuvant therapy more often than those with metachronous disease (63% vs 37%, p = 0.021). Median RFS and OS for the entire cohort were 11 months and 39 months, respectively, and 5-year-OS rate was 41%. Of note, 25 patients achieved survival longer than 5 years without any recurrence thereafter with median follow-up of 137 months. In the multivariate analyses, elevated CEA 50 ng/ml or greater and nodal status of the primary were associated with shorter RFS, while primary T4 disease, liver tumor 5cm or great and elevated CEA were associated with shorter OS (Table 1). Conclusions: For well selected patients with GCLM, liver resection is an effective therapy not only to prolong disease-free time, but also to achieve cure. CEA is useful to select patients with GCLM who unlikely benefit from aggressive surgery. [Table: see text]

Predictors of Survival after Yttrium-90 Radioembolization for Colorectal Cancer Liver Metastases

PurposeTo identify clinical parameters that are prognostic for improved overall survival (OS) after yttrium-90 radioembolization (RE) in patients with liver metastases from colorectal cancer (CRC). Materials and MethodsA total of 131 patients who underwent RE for liver metastases from CRC, treated at 2 academic centers, were reviewed. Twenty-one baseline pretreatment clinical factors were analyzed in relation to OS by the Kaplan-Meier method along with log-rank tests and univariate and multivariate Cox regression analyses. ResultsThe median OS from first RE procedure was 10.7 months (95% confidence interval [CI], 9.4–12.7 months). Several pretreatment factors, including lower carcinoembryonic antigen (CEA; ≤20 ng/mL), lower aspartate transaminase (AST; ≤40 IU/L), neutrophil-lymphocyte ratio (NLR) <5, and absence of extrahepatic disease at baseline were associated with significantly improved OS after RE, compared with high CEA (>20 ng/mL), high AST (>40 IU/L), NLR ≥5, and extrahepatic metastases (P values of <.001, <.001, .0001, and .04, respectively). On multivariate analysis, higher CEA, higher AST, NLR ≥5, extrahepatic disease, and larger volume of liver metastases remained independently associated with risk of death (hazard ratios of 1.63, 2.06, 2.22, 1.48, and 1.02, respectively). ConclusionsThe prognosis of patients with metastases from CRC is impacted by a complex set of clinical parameters. This analysis of pretreatment factors identified lower AST, lower CEA, lower NLR, and lower tumor burden (intra- or extrahepatic) to be independently associated with higher survival after hepatic RE. Optimal selection of patients with CRC liver metastases may improve survival rates after administration of yttrium-90.

Radioembolization for Unresectable Intrahepatic Cholangiocarcinoma: Review of Safety, Response Evaluation Criteria in Solid Tumors 1.1 Imaging Response and Survival.

The optimal palliative treatment for unresectable intrahepatic cholangiocarcinoma (ICC) remains controversial. While selective internal radiation therapy (SIRT) using yttrium-90 microspheres is a well-accepted treatment for hepatocellular carcinoma, data related to its use for locally advanced ICC remain relatively scarce. Twenty-nine patients (mean age 66 ± 11 years; 15 female) with unresectable biopsy-proven ICC treated with SIRT between June 2008 and April 2015 were retrospectively evaluated for post-treatment toxicity, overall survival, and imaging response using response evaluation criteria in solid tumors (RECIST) 1.1 criteria. RECIST 1.1 response was evaluable following 26 treatments [complete response (CR):0, partial response (PR):3; stable disease (SD):16, progression of disease (PD):7]. Objective response rate (CR+PR) was 12%. Disease control rate (CR+PR+SD) was 73%. Median time to progression was 5.6 [95% confidence interval (CI): 0-12.0] months. Median survival following SIRT was 9.1 (95% CI: 1.7-16.4) months. Post-treatment survival was prolonged in patients with absence of extrahepatic disease (p = 0.03) and correlated with RECIST 1.1 response (p = 0.02). Toxicities were limited to grade I severity and occurred following 27% of treatments. These findings support the safe, effective use of SIRT for unresectable ICC. Post-treatment survival is prolonged in patients with absence of extrahepatic disease at baseline. RECIST 1.1 response following SIRT for ICC is predictive of survival.

Long-Term Outcomes of Phase 1 and 2 Studies of SBRT for Hepatic Colorectal Metastases

To report mature outcomes of prospective phase 1 and 2 studies of stereotactic body radiation therapy (SBRT) for the treatment of colorectal liver metastases (CLMs). Patients with histologically confirmed CLMs unsuitable for resection or standard therapies were eligible for sequential phase 1 and 2 studies conducted from 2003 to2012. Of 60 patients treated, 82% had received previous chemotherapy, 23% had undergone previous focal liver treatment, and 38% had extrahepatic disease at the time of SBRT. The median number of gross tumor volume (GTV) targets per patient was 1 (range, 1-6), with a median total target volume of 117.7cm3 (range, 6.7-3115.4cm3). The median minimum dose to the GTV was 37.6Gy (range, 22.7-62.1Gy) in 6 fractions over a period of 2weeks. Other than 1 case of grade 3 nausea, there were no acute toxicities greater than grade 2. With a median follow-up period of 28.1months for survivors, no gastrointestinal bleed or biliary or liver toxicity was seen.The local control rate per lesion at 1 and 4years was 49.8% and 26.2%, respectively. Increasing minimum dose to the GTV was associated with improved local control (P=.003).Median overall survival was 16.0months (95% confidence interval, 11.9-20.5months). On multivariate analysis, improved survival was associated with smaller total GTV (P=.017), performance status of 0 or 1 (P=.007), no extrahepatic disease at the time of treatment (P=.005), and local control of targeted liver disease (P=.001). Two long-term survivors remain disease free at 49 and 125months. Six-fraction SBRT for CLM is safe and may be associated with long-term cure. Local control was significantly associated with delivered dose and was lower than seen in other studies using a higher SBRT dose. Survival was associated with smaller tumor volume, absence of extrahepatic disease, performance status of 0 or 1, and local control of treated liver lesions.

Selective portal vein injection for the design of syngeneic models of liver malignancy

Liver metastases are the most frequent cause of death due to colorectal cancer (CRC). Syngeneic orthotopic animal models, based on the grafting of cancer cells or tissue in host liver, are efficient systems for studying liver tumors and their (patho)physiological environment. Here we describe selective portal vein injection as a novel tool to generate syngeneic orthotopic models of liver tumors that avoid most of the weaknesses of existing syngeneic models. By combining portal vein injection of cancer cells with the selective clamping of distal liver lobes, tumor growth is limited to specific lobes. When applied on MC-38 CRC cells and their mouse host C57BL6, selective portal vein injection leads with 100% penetrance to MRI-detectable tumors within 1 wk, followed by a steady growth until the time of death (survival ∼7 wk) in the absence of extrahepatic disease. Similar results were obtained using CT-26 cells and their syngeneic Balb/c hosts. As a proof of principle, lobe-restricted liver tumors were also generated using Hepa1-6 (C57BL6-syngeneic) and TIB-75 (Balb/c-syngeneic) hepatocellular cancer cells, demonstrating the general applicability of selective portal vein injection for the induction of malignant liver tumors. Selective portal vein injection is technically straightforward, enables liver invasion via anatomical routes, preserves liver function, and provides unaffected liver tissue. The tumor models are reproducible and highly penetrant, with survival mainly dependent on the growth of lobe-restricted liver malignancy. These models enable biological studies and preclinical testing within short periods of time.

Net health benefit of hepatic resection versus intraarterial therapies for neuroendocrine liver metastases: A Markov decision model

Management of patients with neuroendocrine liver metastasis (NELM) remains controversial. We sought to compare the net health benefit (NHB) of hepatic resection (HR) versus intraarterial therapy (IAT) among patients with NELM. A decision analytic Markov model was created to estimate and compare the cost effectiveness associated with different management strategies (HR vs IAT) for a simulated cohort of patients with NELM. The primary (base case) analysis was calculated based on a 57-year-old male patient with metachronous, symptomatic NELM that involved <25% of the liver in the absence of extrahepatic disease. The endpoints were quality-adjusted life-months (QALMs), quality-adjusted life-year (QALY), incremental cost-effectiveness ratio (ICER), and NHB. In the base case analysis, HR was strongly favored over IAT providing NHB of 20.0 QALMs and an ICER of $8,427 per QALY. In the Monte Carlo simulation, the greatest NHB for HR was among patients with functioning/symptomatic NELM, regardless of liver tumor burden. In the symptomatic group, IAT was favored only in a minority of old patients (>60 years) with extrahepatic disease and synchronous NELM. In contrast, in patients with nonfunctioning/asymptomatic NELM, hepatic tumor burden was the most important variable and HR was always cost ineffective in large tumors, independent of patient age and extrahepatic disease characteristics. A Markov decision model demonstrated that HR was the preferred strategy among patients with symptomatic NELM, regardless of hepatic disease burden. In contrast, IAT should be preferred for patients with large volume nonfunctioning/asymptomatic NELM.

Percutaneous microwave ablation vs radiofrequency ablation in the treatment of hepatocellular carcinoma.

Hepatocellular cancer ranks fifth among cancers and is related to chronic viral hepatitis, alcohol abuse, steatohepatitis and liver autoimmunity. Surgical resection and orthotopic liver transplantation have curative potential, but fewer than 20% of patients are suitable candidates. Interventional treatments are offered to the vast majority of patients. Radiofrequency (RFA) and microwave ablation (MWA) are among the therapeutic modalities, with similar indications which include the presence of up to three lesions, smaller than 3 cm in size, and the absence of extrahepatic disease. The therapeutic effect of both methods relies on thermal injury, but MWA uses an electromagnetic field as opposed to electrical current used in RFA. Unlike MWA, the effect of RFA is partially limited by the heat-sink effect and increased impedance of the ablated tissue. Compared with RFA, MWA attains a more predictable ablation zone, permits simultaneous treatment of multiple lesions, and achieves larger coagulation volumes in a shorter procedural time. Major complications of both methods are comparable and infrequent (approximately 2%-3%), and they include haemorrhage, infection/abscess, visceral organ injury, liver failure, and pneumothorax. RFA may incur the additional complication of skin burns. Nevertheless, there is no compelling evidence for differences in clinical outcomes, including local recurrence rates and survival.

Liver Transplantation for Unresectable Neuroendocrine Tumor Liver Metastases

Liver transplantation (LT) is performed in selected patients with neuroendocrine hepatic metastases. Survival benefit and the risk of tumor recurrence after LT, also exacerbated by immunosuppressive therapy, remain important clinical issues. Whether patients with particular types of neuroendocrine tumors (NET) benefit more than others is unclear. Bibliographical searches were performed in PubMed for the terms "liver transplantation and neuroendocrine tumors," "liver transplant and neuroendocrine tumors," "liver transplantation and immunosuppressive therapy," "tumor recurrence." Promising results have been reported for LT for NET metastases with 5-year survival of up to 90 % in patients with well-differentiated gastroenteropancreatic NETs, but only few patients are free of tumor 5 years after LT. Better outcomes have been reported for gastrointestinal tumors than for pancreatic NETs for both survival and risk or recurrence after LT. Selection criteria for LT are limited and include the 2007 Milan Criteria and the 2012 European Neuroendocrine Tumor Society guidelines, including: well-differentiated NET (Ki-67 <10 %), age <55 years, absence of extrahepatic disease, primary tumor removed before transplantation, stable disease for at least 6 months before LT, and <50 % liver involvement. LT might be considered in carefully selected patients. The risk of tumor recurrence remains a significant clinical problem after LT, but data focused on immunosuppression issue are lacking, and there are no currently approved strategies for prevention of recurrence or follow-up protocols. Further studies are needed to define universally accepted inclusion criteria, reliable predictors of better outcome, and optimal timing for LT.

Indication for Liver Transplantation in Young Patients with Small Intestinal NETs Is Rare?

A majority of patients with small intestinal neuroendocrine tumors (SI-NETs) present with or develop liver metastases (LM). A number of treatments for LM are used clinically, including liver transplantation (LTx). Indications for LTx are under debate; young age(<65 years), absence of extrahepatic disease, resected primary tumor and limited extent of LM have been suggested as inclusion criteria for LTx with the aim to optimize outcome. From our series of 672 patients with SI-NET treated at the University Hospital in Uppsala between 1985 and 2012, we identified 78 patients according to the following criteria: <65 years of age, locoregional surgery (LRS) of the primary tumor and mesenteric metastases successfully performed, LM present but no extrahepatic disease. Baseline was chosen as the first date the following points were met: First visit to our center,LRS performed, LM present. The patients underwent treatment according to the standard clinical protocols at our center, and during this time period we did not perform or refer any SI-NET patients for LTx. Kaplan-Meier survival analyses were performed in three different groups based on hypothetical criteria for LTx. Five-year overall survival rates for patients <65 years (n = 78) and <55 years (n = 36) of age were 84 ± 8 and 92 ± 9 %, respectively. For patients fulfilling the Milan criteria (n = 33) the 5-year survival was 97 ± 6 %. Most young patients (<65 years) with SINET and LM have a favorable survival with standardized multimodality treatment. Indeed, most survival figures reported after LTx of NET do not surpass these figures.