Presence Of Hepatic Metastases Research Articles

Immunotherapy and PD-L1 Tumor Expression in Moroccan Non-Small Cell Lung Cancer Patients with Various Metastasis.

The question of whether tumor expression of PD-L1 and the presence of distant metastasis could influence the efficacy of immunotherapy represents a major challenge and needs to be further elucidated. The aim of this study is to evaluate the predictive significance of tumor expression of PD-L1 as well as the number and site of metastasis in non-small cell lung cancer (NSCLC) among Moroccan patients treated with immunotherapy. Between January 2019 and February 2023, we recruited Moroccan patients with metastatic NSCLC. All were treated with immunotherapy, either as monotherapy or in combination with chemotherapy. Immunohistochemistry was used to assess PD-L1 (clone 22C3) and ALK (clone D5F3) status. EGFR status was established by qPCR. Tumor PD-L1 expression was classified into 2 levels: TPS <1% (negative expression) and TPS ≥1% (positive expression). Statistical analysis was performed using SPSS Statistics V.21 software. The median age of patients (N=40) was 67 years (39- 92 years) and the sex ratio was 9. Disease dissemination revealed that 22.5% (N=9) of patients had a metastatic burden ≥ 3 (MB≥3). As for the sites of metastasis, the results showed that 20% (N=8), 10% (N=4), 42.5% (N=17), 22.5% (N=9), 27.5% (N=11), 45% (N=18) and 27.5% (N=11) of patients had developed lymph node, liver, bone, brain, pleural, contralateral lung and adrenal metastasis respectively. Positive PD-L1 expression was significantly associated with shorter overall survival (OS = 17.19 vs. 28.85 months, p=0.01). High metastatic burden (MB ≥ 3) was associated with lower objective response rate (ORR), shorter progression-free survival (PFS), and reduced OS, respectively (ORR = 0 vs. 58.06%, p=0.002; PFS = 10.23 vs. 25.27 months, p=0.001; and OS = 11.60 vs. 27.91 months, p=0.003). Only the presence of osseous metastasis was significantly associated with lower ORR, shorter PFS, and OS compared to other metastatic locations (ORR = 5.88 vs. 73.9%, p=0.000; PFS = 10.72 vs. 31.33 months, p=0.000; and OS = 11.39 vs. 36.17 months, p=0.000). Finally, the presence of hepatic metastasis was significantly associated with shorter PFS (10.75 months) compared to those without hepatic metastasis (22.53 months) (p=0.046). Finally, the results of the multivariate analysis revealed that the presence of bone metastasis was strongly correlated with a significant decrease in progression-free survival (p=0.001) as well as overall survival (p=0.002). Our results suggest that tumor expression of PD-L1 and metastatic burden should play a significant role in predicting the response to immunotherapy. Furthermore, it is important to note that the presence of osseous and hepatic metastasis could negatively influence the clinical outcomes of immunotherapy.

Influence of Biomarkers on Mortality among Patients with Hepatic Metastasis of Colorectal Cancer Treated with FOLFOX/CAPOX and FOLFIRI/CAPIRI, Including Anti-EGFR and Anti-VEGF Therapies.

Background and objectives: Colorectal cancer is a major global health concern, with a significant increase in morbidity and mortality rates associated with metastatic stages. This study investigates the prognostic significance of various clinical and laboratory parameters in patients with metastatic CRC. Materials and Methods: A retrospective cohort of 188 CRC patients with hepatic metastasis from the OncoHelp Association in Timisoara was analyzed from January 2016 to March 2023. Data on demographics, clinical characteristics, and biomarkers, such as lymphocyte counts, as well as various inflammation indices, were examined. Statistical analyses included univariate and multivariate logistic regression, Kaplan-Meier survival analysis, and ROC curve assessments. Results: Our findings indicate significant associations between survival outcomes and several biomarkers. Higher BMI and lymphocyte counts were linked with better survival rates, while higher values of Neutrophil-Hemoglobin-Lymphocyte (NHL) score, Neutrophil-Lymphocyte Ratio (NLR), Platelet-Lymphocyte Ratio (PLR), and Systemic Immune-Inflammation Index (SII) were predictors of poorer outcomes. Notably, the presence of hepatic metastasis at diagnosis was a critical factor, significantly reducing overall survival. Conclusions: The study has expanded the current understanding of prognostic factors in CRC, advocating for a multi-dimensional approach to prognostic evaluations. This approach should consider not only the traditional metrics such as tumor stage and histological grading but also incorporate a broader spectrum of biomarkers. Future studies should aim to validate these findings and explore the integration of these biomarkers into routine clinical practice, enhancing the precision of prognostic assessments and ultimately guiding more personalized treatment strategies for CRC patients.

Diagnostic and prognostic role of long non-coding RNAs (lncRNAs) in metastatic melanoma patients with BRAF gene mutation receiving BRAF and MEK inhibitors

Melanoma is a cancer with a high incidence rate that, despite the significant development of therapeutic options, still remains a major problem. The identification of biomarkers to select the right therapy for the right patient is one of the possibilities to improve the prognosis of patients. Potentially, the function of biomarkers could be played long non-coding RNAs (lncRNAs). The expression of selected 90 lncRNAs in serum from 30 metastatic melanoma patients with confirmed mutations in the BRAF V600 E or K gene was studied. Serum was collected prior to BRAF and MEK inhibitor therapy. The control group consisted of 16 healthy volunteers. A total of 41 lncRNAs were identified the expression of which differed statistically significantly between the patient group and the healthy volunteers. In addition, it was shown that the expression of HOXA3as (p = 0.033), PRINS (p = 0.036) and RNCR3 (p = 0.045) is higher in patients with the presence of CNS metastases, PFS inhibiting RNA (p = 0.048) is higher among patients with the presence of hepatic metastases, UCA1 (p = 0.008) expression is lower in patients with increased lactate dehydrogenase levels, while HOTAIRM1 (p = 0.044) and E2F4 antisense (p = 0.040) expression is lower in patients over 60 years of age. In addition, patients with high lincRNASFMBT2 expression showed longer median PFS (8.75 vs. 17.5 months, p = 0.0319) and OS (9.75 vs. 38 months (open observation, p = 0.0253). The obtained results require validation on a larger group of patients. If the results are confirmed, the indicated lncRNAs may play an important role as diagnostic and prognostic markers.

Subclinical Echocardiographic Parameters and Biomarker Approach to Characterize the Pathophysiology of Carcinoid Syndrome

Introduction: Carcinoid heart disease is a rare cause of right-sided valvular dysfunction, an important complication in patients with carcinoid syndrome. Objectives: We aim to present our own experience regarding early myocardial dysfunction in patients with carcinoid syndrome. Methods: 64 patients (35-90 year old, 62,5% female, 37,5% male patients) with carcinoid syndrome were evaluated between October 2017 and June 2021. All patients underwent two-dimensional echocardiography with additional tissue Doppler and speckle-tracking techniques. For all patients there were measured urinary level of 5- hydroxyindolacetic acid, serotonin and NT-proBNP values. Results: The following echocardiographic features: global longitudinal strain of both ventricles, mean systolic velocity of the left ventricle, systolic velocity of the free wall of right ventricle, correlated with high values of specific biomarkers: serotonin, and urinary 5-hydroxyindolacetic acid, and also with the presence of hepatic metastases and poorly differentiated tumors. Discussion: In this study we identified several patients with early myocardial dysfunction due to carcinoid syndrome, representing a predictive model of poor prognosis, requiring further investigations. Conclusion: Echocardiographic assessment based on the measurement of systolic velocities, as well as the global longitudinal strain of both ventricles, together with specific biomarkers may contribute to better recognition of carcinoid heart disease in clinical practice, but this needs validation through further studies enrolling larger number of patients.

Molecular and Clinical Determinants of Acquired Resistance and Treatment Duration for Targeted Therapies in Colorectal Cancer.

Targeted therapies have improved outcomes for patients with metastatic colorectal cancer, but their impact is limited by rapid emergence of resistance. We hypothesized that an understanding of the underlying genetic mechanisms and intrinsic tumor features that mediate resistance to therapy will guide new therapeutic strategies and ultimately allow the prevention of resistance. We assembled a series of 52 patients with paired pretreatment and progression samples who received therapy targeting EGFR (n = 17), BRAF V600E (n = 17), KRAS G12C (n = 15), or amplified HER2 (n = 3) to identify molecular and clinical factors associated with time on treatment (TOT). All patients stopped treatment for progression and TOT did not vary by oncogenic driver (P = 0.5). Baseline disease burden (≥3 vs. <3 sites, P = 0.02), the presence of hepatic metastases (P = 0.02), and gene amplification on baseline tissue (P = 0.03) were each associated with shorter TOT. We found evidence of chromosomal instability (CIN) at progression in patients with baseline MAPK pathway amplifications and those with acquired gene amplifications. At resistance, copy-number changes (P = 0.008) and high number (≥5) of acquired alterations (P = 0.04) were associated with shorter TOT. Patients with hepatic metastases demonstrated both higher number of emergent alterations at resistance and enrichment of mutations involving receptor tyrosine kinases. Our genomic analysis suggests that high baseline CIN or effective induction of enhanced mutagenesis on targeted therapy underlies rapid progression. Longer response appears to result from a progressive acquisition of genomic or chromosomal instability in the underlying cancer or from the chance event of a new resistance alteration.

An Analysis of Clinical and Systemic Factors Associated with Palliative Radiotherapy Delivery and Completion at the End of Life in Alberta, Canada.

Radiotherapy (RT) is often utilized for symptom control at the end of life. Palliative RT (pRT) may not be taken to completion by patients, thus decreasing clinical benefits and adversely impacting resource allocation. We determined rates of incomplete pRT and examined predictors of non-completion using an electronic questionnaire. Methods: A questionnaire was embedded within the RT electronic prescribing system for all five cancer centers of Alberta, Canada, between 2017 and 2020. Prescribing radiation oncologists (ROs) were tasked with completing the questionnaire. Treatment variables were collected for 2040 patients prescribed pRT. Details on pRT courses delivered and completed were used to determine rates of incomplete RT. Electronic medical records of a subset of 367 patients randomly selected from the 2040 patients were then analyzed to examine for association of non-completion of RT with patient, disease, and therapy-related factors. Results: Overall, 10% of patients did not complete pRT. The rate of single fractions prescribed as a proportion of all RT fractions increased from 18% (pre-2017: pre-study era) to 29% (2017-2020: study era) (p < 0.0001). After conducting multivariate analysis on the overall group, multiple lifetime malignancies (OR:0.64) or increasing the number of pRT fractions (OR:0.08-0.17) were associated with non-completion. Being selected for stereotactic RT (OR:3.75) or survival > 30 days post-RT prescription (OR:2.20-5.02) were associated with greater rates of RT completion. The ROs' estimates of life expectancy at the time of RT prescription were not predictive of RT completion. In the multivariate analysis of the 367-patient subset, the presence of hepatic metastases (OR 2.59), survival 30-59 days (OR 6.61) and survival 90+ days (OR 8.18) post-RT prescription were associated with pRT completion. Only increasing pRT fractionation (OR:0.05-0.2) was associated with non-completion. Conclusion: One in ten patients prescribed pRT did not complete their treatment course. Decreasing pRT fractionation and improving prognostication in patients near the end of life may decrease rates of incomplete RT courses.

Percutaneous image-guided ablation for hepatic metastases.

The presence of hepatic metastases indicates advanced disease and is associated with significant morbidity and mortality, especially when the hepatic disease is not amenable to locoregional treatments. The primary tumour of origin, the distribution and extent of metastatic disease, the underlying liver reserve, the patient performance status and the presence of comorbidities are factors that determine whether a patient will benefit from hepatectomy or local curative-intent treatments. For patients with metastatic colorectal cancer, the most common primary cancer that spreads to the liver, several studies have demonstrated a survival benefit for patients who can be treated with hepatectomy and/or percutaneous ablation, compared to those treated with chemotherapy alone. Despite advances in surgical techniques increasing the percentage of patients eligible for surgery, most patients have unresectable disease or are poor surgical candidates. Percutaneous ablation can be used to provide local disease control and prolong survival for both surgical and non-surgical candidates. This is typically offered to patients with small hepatic metastases that can be ablated with optimal (≥10 mm) or at least adequate minimum ablation margins (≥5 mm), as high local tumour control rates can be achieved for these patients which are comparable to surgical resection. This review summarizes available evidence and outcomes following percutaneous ablation of the most frequently encountered types of hepatic metastases in the clinical practice of interventional oncology. Patient selection, technical considerations, follow-up protocols and oncologic outcomes are presented and discussed.

Liver resection modulates hepatic chemokine levels in breast cancer

BackgroundResection of metastatic hepatic tumors of breast cancer may result in the acceleration of hepatic and extrahepatic tumor progression due to the microenvironmental circulation of chemokines. This study aimed to investigate the effect of hepatectomy on a large panel of chemokines, liver regeneration, and myeloid cell levels in an experimental breast cancer model. MethodsThe 4T1 breast cancer cells were inoculated, and 30% to 40% hepatectomy was performed. Mice without tumors or only laparotomy (no hepatectomy) served as control groups. After 14 days (short-term) and 21 days (long-term), tissue samples were obtained from the regions near and distant from the resection site. Chemokine levels were evaluated by enzyme-linked immunosorbent assay arrays. Myeloid infiltration in the liver and the primary tumor and hepatic regeneration status were also histopathologically evaluated. ResultsThe levels of pro-tumorigenic chemokines such as CCL2, CCL3, CCL4, and CCL5 were elevated in hepatectomized tumor-bearing animals. This observation was consistent with the presence of hepatic metastases. Liver regeneration and myeloid cell infiltration showed significant differences between the tumor-bearing hepatectomized groups followed in the short and long term. ConclusionOur study showed elevation and variations in chemokines after hepatectomy, with a prominent increase in pro-tumorigenic chemokines. These results can be associated with the acceleration of metastasis after liver resection. However, further prospective studies are required to better define the impact of resection, which may transform the liver into a favorable site for metastasis.

A Transcriptomic-Based Tool to Predict Gemcitabine Sensitivity in Advanced Pancreatic Adenocarcinoma

A Transcriptomic-Based Tool to Predict Gemcitabine Sensitivity in Advanced Pancreatic Adenocarcinoma

CDK4/6 Inhibitors in Advanced HR+/HER2 – Breast Cancer: A Multicenter Real-World Data Analysis

Purpose: CDK4/6 inhibitors (CDK4/6i) combined with endocrine therapy are considered standard-of-care for first-line therapy of patients with hormone receptor positive, HER2 negative, advanced breast cancer (HR+/HER2- ABC). Superiority of combination therapy over endocrine monotherapy has been demonstrated in a multitude of randomized controlled trials (RCTs) in phase III and IV. However, RCTs reflect clinical reality only to a limited extent, as narrow inclusion criteria lead to a selected patient collective. Here, we present real-world data (RWD) on CDK4/6i treatment in patients with HR+/HER2- ABC at four certified German university breast cancer centers. Methods: Patients diagnosed with HR+/HER2- ABC who were treated in clinical routine with CDK4/6i between November 2016 and December 2020 at four certified German university breast cancer centers (Saarland University Medical Center, University Medical Center Charité Berlin, University Medical Center Bonn, and University Medical Center Hospital Schleswig-Holstein, Campus Kiel) were identified and enrolled in this retrospective study. Clinicopathological characteristics and clinical outcomes were recorded with particular emphasis on CDK4/6i therapy course [progression-free survival (PFS) following treatment initiation, toxicity, dose reduction, therapy discontinuation, prior and subsequent therapy line]. Results: Data from n = 448 patients were evaluated. The mean patient age was 63 (±12) years. Of these patients, n = 165 (36.8%) were primarily metastasized, and n = 283 (63.2%) had secondary metastatic disease. N = 319 patients (71.3%) received palbociclib, n = 114 patients (25.4%) received ribociclib, and n = 15 patients (3.3%) received abemaciclib, respectively. Dose reduction was performed in n = 132 cases (29.5%). N = 57 patients (12.7%) discontinued the treatment with CDK4/6i due to side effects. N = 196 patients (43.8%) experienced disease progression under CDK4/6i treatment. The median PFS was 17 months. Presence of hepatic metastases and prior therapy lines were associated with shorter PFS, whereas estrogen positivity and dose reduction due to toxicity were positively associated with PFS. Presence of bone and lung metastases, progesterone positivity, Ki67 index, grading, BRCA1/2 and PIK3CA mutation status, adjuvant endocrine resistance, and age did not significantly impact on PFS. Conclusion: Our RWD analysis on CDK4/6i treatment in Germany supports data from RCTs regarding both treatment efficacy and safety of CDK4/6i for treatment of patients with HR+/HER2- ABC. In comparison to data from the pivotal RCTs, median PFS was lower but within the expected range for RWD, which could result from inclusion of patients with more advanced diseases (i.e., higher therapy lines) to our dataset.

Pre- and intratherapeutic predictors of overall survival in patients with advanced metastasized castration-resistant prostate cancer receiving Lu-177-PSMA-617 radioligand therapy

BackgroundSystemic Lutetium-177 prostate-specific membrane antigen-617 radioligand therapy (Lu-177-PSMA-617-RLT) is a novel treatment approach in patients suffering from metastasized castration-resistant prostate cancer. Nonetheless, a therapeutic response may fail to appear in a proportion of patients. This study aims to identify routinely obtainable pre- and intratherapeutic parameters to allow a prediction of overall survival in patients receiving Lu-177-PSMA-617 radioligand therapy.MethodsBetween January 2015 and December 2020 52 patients treated with a total of 146 cycles Lu-177-PSMA-617-RLT were retrospectively analysed in a single-center trial. The median overall survival time (OS) was compared to pre-therapeutic serological parameters, the extend of metastatic spread and previously performed therapies using Kaplan–Meier estimators and multivariate Cox-regression. Bonferroni-Holm correction was performed on all statistical tests.ResultsThe median OS of all patients was 55.6 weeks. Multivariate Cox-regression revealed significant lower survival for decreased pretherapeutic hemoglobin levels (HR 0.698 per g/dl; 95%-CI 0.560–0.872; p = 0.001), increased lactate dehydrogenase (LDH) levels (HR 1.073 per 25 U/l; 95%-CI 1.024–1.125; p = 0.003) and the presence of hepatic metastasis (HR 6.981; 95%-CI 2.583–18.863; p < 0.001). Increased pretherapeutic c-reactive protein (CRP), alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT) levels were also associated with a shorter survival. A prostate-specific antigen decline after one therapy cycle did not significantly correlate with an increased survival. No significant relations were observed between overall survival time and other serological parameters or previously performed therapies.ConclusionPre-therapeutic hemoglobin and LDH levels, as well as the presence of hepatic metastasis are independent predictors of overall survival in patients receiving Lu-177-PSMA-617-RLT. CRP, ALP and GGT levels cloud be utilized as additional decision aids when a Lu-177-PSMA-617-RLT is intended.Trial Registration Not applicable (retrospective observational study).

Amlodipine improves the outcomes of regorafenib in metastatic colorectal cancer.

Regorafenib is a multikinase inhibitor. It is used for metastatic colorectal cancer (mCRC) treatment. It has a mild effect. Regorafenib outcomes, and side effects may vary across patients. This study was aimed to evaluate the factors that affect regorafenib outcomes in mCRC patients. We conducted a single-center and retrospective study. Fifty-six patients were included. All patients had received regorafenib for mCRC. Some clinical and pathological factors and the effects of these factors on overall survival (OS), progression-free survival (PFS), and disease control rates (DCR) were analyzed. Concomitant amlodipine intake with regorafenib improved OS [14.26 vs. 6.97 months; 95% confidence interval, 4.04-20.84; P = 0.031] and DCR at 12th week (90% vs. 46%; P = 0.012). Hepatic metastasis was found as the poorest prognostic factor in both univariate and multivariate analyses. Patients who received chemotherapy after regorafenib had better OS. Good performance status was the strongest indicator of better OS. Patients taking amlodipine for arterial hypertension at the same time with regorafenib had numerically better OS and PFS and statistically better DCR. Amlodipine itself already has anticancer effects, and it has additive anticancer effects with regorafenib. The presence of hepatic metastases was found to be the most important prognostic factor for OS. There were not any predictive factors of side effects to regorafenib.

The role of hepatic surgery as treatment for sarcoma liver metastasis. a restrospective survival analysis

Background: The presence of hepatic metastases (HM) in sarcomatous tumours is associated with poor prognosis, surgical resection of HM has been suggested as a tool to improve survival rates in selected patients. However, there is inadequate literature reporting the role of hepatic surgery as treatment for sarcoma liver metastasis. The aim of this study is to describe the survival after hepatic resection in patients afected of sarcoma liver metastasis in our cohort.

External validation of life expectancy prognostic models in patients evaluated for palliative radiotherapy at the end-of-life.

BackgroundThe TEACHH and Chow models were developed to predict life expectancy (LE) in patients evaluated for palliative radiotherapy (PRT). We sought to validate the TEACHH and Chow models in patients who died within 90 days of PRT consultation.MethodsA retrospective review was conducted on patients evaluated for PRT from 2017 to 2019 who died within 90 days of consultation. Data were collected for the TEACHH and Chow models; one point was assigned for each adverse factor. TEACHH model included: primary site of disease, ECOG performance status, age, prior palliative chemotherapy courses, hospitalization within the last 3 months, and presence of hepatic metastases; patients with 0‐1, 2‐4, and 5‐6 adverse factors were categorized into groups (A, B, and C). The Chow model included non‐breast primary, site of metastases other than bone only, and KPS; patients with 0‐1, 2, or 3 adverse factors were categorized into groups (I, II, and III).ResultsA total of 505 patients with a median overall survival of 2.1 months (IQR: 0.7‐2.6) were identified. Based on the TEACHH model, 10 (2.0%), 387 (76.6%), and 108 (21.4%) patients were predicted to live >1 year, >3 months to ≤1 year, and ≤3 months, respectively. Utilizing the Chow model, 108 (21.4%), 250 (49.5%), and 147 (29.1%) patients were expected to live 15.0, 6.5, and 2.3 months, respectively.ConclusionNeither the TEACHH nor Chow model correctly predict prognosis in a patient population with a survival <3 months. A better predictive tool is required to identify patients with short LE.

Intestinal and diffuse gastric cancer: a retrospective study comparing primary sites

ObjectiveWe assessed differences in primary sites and spread patterns of the intestinal and diffuse subtypes of gastric carcinoma. We also compared survival outcomes based on spread patterns. Materials and methodsFor this retrospective IRB-approved study, our institutional imaging database was mined for patients with gastric cancer. We included 99 treatment-naïve patients. Patient demographics, pathologic data, tumor classification, primary tumor site, and metastasis sites were recorded. Pearson's chi-squared test was used to correlate tumor pathology with metastatic sites. Kaplan–Meier survival curves were compared between baseline metastatic types. A heat map was created based on the relative frequencies of metastatic sites for each primary tumor site. ResultsOf the 99 patients, 66 patients had intestinal and 33 had diffuse gastric carcinoma. The intestinal subtype was significantly associated with hepatic metastases (p < 0.001). Diffuse subtype was associated with peritoneal metastases, including omental metastases (p < 0.006), gastrosplenic ligament involvement (p < 0.004), and mesocolonic implants (p < 0.008). Patients with primary gastric tumors occurring at the greater curvature had longer overall survival than those with primary sites at the antrum, GE junction and lesser curvature (p = 0.0015). Patients with peritoneal metastases had a significantly shorter overall survival than patients without peritoneal metastases (p < 0.001). Patients without mesocolon, gastrohepatic ligament, and gastrosplenic ligament involvement had a better survival (p = 0.005, p = 0.0002, and p = 0.0005, respectively). Presence of hepatic metastases had no effect on survival (p = 0.16). ConclusionRecognizing distinctive spread patterns for intestinal versus diffuse gastric carcinoma can aid radiologists in diagnosis and guide clinical management.

Predicting prognosis of short survival time after palliative whole-brain radiotherapy.

Using existing prognostic models, including the Graded Prognostic Assessment (GPA), it is difficult to identify patients with brain metastases (BMs) who are not likely to survive 2 months after whole-brain radiotherapy (WBRT). The purpose of this study was to identify a subgroup of patients who would not benefit clinically from WBRT. We retrospectively reviewed the records of 111 patients with BMs who were ineligible for surgery or stereotactic irradiation and who underwent WBRT between March 2013 and April 2016. Most patients were scheduled to receive a total dose of 30 Gy in 10 fractions. Non–small cell lung cancer represented the most common primary cancer type (67%), followed by breast cancer (12%). Median survival time (MST) was 109 days (range, 4–883). Univariate analysis identified five factors significantly associated with poor prognosis: performance status (PS) 2–4, perilesional edema, elevated serum lactate dehydrogenase (LDH), using steroids during WBRT, and presence of hepatic metastases. Multivariate analysis confirmed elevated LDH (>300 IU/l) as an independent predictor. MST for LDH >300 IU/l (n = 30) and LDH ≤300 IU/L (n = 87) cohorts were 47 days and 148 days, respectively (P < 0.001). MSTs for GPA 0–1 patients (n = 85) with and without elevated LDH were 37 days and 123 days, respectively (P < 0.001). More than half of the patients with GPA 0–1 and elevated LDH died within two months. Adding elevated LDH to the GPA will permit identification of patients with BMs who have extremely unfavorable prognoses.

Mesenteric Fibrosis in Midgut Neuroendocrine Tumors: Functionality and Radiological Features

Background: Mesenteric fibrosis (MF) surrounding a lymph node metastasis is a known phenomenon in midgut neuroendocrine tumors (NETs) with characteristic radiological appearance. Its etiology is poorly understood as it affects some but not all midgut NET patients with lymphatic involvement. This study assessed a potential relationship of MF with carcinoid syndrome, urinary 5-hydroxyindoleacetic acid (5-HIAA), and carcinoid heart disease (CHD). Methods: A cohort of 81 patients with pathologically proven NETs with the primary site in the midgut and mesenteric lymphatic metastases on imaging were retrospectively included. Imaging characteristics of lymphatic and hepatic metastases at diagnosis (size, number, burden, and morphologic features, including presence of MF), Ki67 grading, 5-HIAA, functionality, and development of CHD were analyzed. Results: Overall, 54% of patients had MF. The presence of MF was more frequently associated with mesenteric vessel encasement (100 vs. 46% without MF; p < 0.001), presence of hepatic metastases (91 vs. 62%; p = 0.002), larger hepatic tumor burden (15 vs. 5%; p = 0.001), and functionality (86 vs. 43%; p < 0.001). Multivariate analysis revealed 5-HIAA ≥395 µmol/day (p = 0.020), age (p = 0.013), and largest lymphatic metastasis ≥24 mm (p = 0.009) as independent predictors of MF, while functionality (p = 0.098) and CHD (p = 0.070) showed a tendency towards significance. MF was associated with decreased time to development of CHD in functional midgut NETs (p = 0.043). Conclusions: We found a significant association of MF with metastatic patterns and with criteria of functionality. The association of MF with elevated 5-HIAA, and consecutively with carcinoid syndrome and potential development of CHD, suggests a linked pathophysiological mechanism, which might be similar to that of endocardial fibrosis.

Continuous infusion of octreotide combined with perioperative octreotide bolus does not prevent intraoperative carcinoid crisis

Operations and anesthesia in carcinoid patients can provoke carcinoid crises, which can have serious sequelae, including death. Prophylactic octreotide is recommended to prevent crises. Recommended prophylaxis regimens vary from octreotide long-acting repeatable to preoperative bolus to continuous octreotide infusion; however, efficacy data are lacking. We have shown previously that crises correlated with major complications and that octreotide long-acting repeatable and preoperative bolus failed to prevent crises. This study examines the impact of continuous octreotide infusion. A total of 127 patients (71% with liver metastases, 74% with carcinoid syndrome) who underwent 150 operations with continuous octreotide infusions were enrolled in this prospective case series. Our main outcome measures were the occurrence of intraoperative carcinoid crises and post-operative complications. Crises occurred at a rate of 30% as compared with 24% in our previous series, which examined the impact of preoperative octreotide bolus. Crises were significantly associated with the presence of hepatic metastases (P = .02) or history of carcinoid syndrome (P = .006), although neither was required for crises. Prompt vasopressor treatment shortened the mean duration of hypotension to 8.7 minutes, compared with 19 minutes in our prior series. Crises no longer correlated with major complications (P = .481) unless instability persisted for greater than 10 minutes (P = .011). Octreotide infusions do not prevent intraoperative crises. Patients without liver metastases or carcinoid syndrome can have intraoperative crises. Postoperative complications can be decreased by reducing the duration of crises. Further study is needed to determine how best to shorten hemodynamic instability during crises.

Assessing the value of hepatic arterial phase CT imaging in patients with breast cancer.

5 Background: Hypervascular liver metastases, classically seen in melanoma and other cancers, may be best seen on a hepatic arterial phase (HAP) CT and possibly missed on the standard portal venous phase (PVP). Breast cancer sometimes produces hypervascular liver metastases, but the incidence of this is not well established. Hence, some centers perform biphasic liver CT (HAP + PVP) as standard protocol in breast cancer patients, while others do not. Our center does not include HAP in this patient population; although, it is sometimes protocolled with HAP as per radiologist preference. We sought to determine if the detection for presence or absence of liver metastases is significantly affected by the addition of HAP in breast cancer. Methods: This retrospective study was conducted using a custom search on our Picture Archiving and Communication System for all female patients who received a biphasic liver CT (HAP + PVP) from Mar 2013 - Mar 2015. Inclusion criteria included known breast cancer, liver metastases described on CT report, and follow-up imaging to confirm the finding. A total of 25 CT studies met inclusion criteria. Results: 14/25 (56%) studies demonstrated typical non-hypervascular hepatic metastases. 11/25 (44%) demonstrated hypervascular hepatic lesions. Of these latter, 4/25 (16%) represented hypervascular metastases, while 7/25 (28%) pertained to indeterminate arterial-enhancing lesions called suspicious by the reporting radiologist. Further imaging including MRI, ultrasound, and follow-up CT were recommended in these indeterminate suspicious lesions, all of which confirmed benign entities. Of the 18 studies with true hepatic metastases, the presence of metastatic disease was detectable on the PVP in 18/18 (100%, P&lt; .0001) regardless of the metastases’ hypervascular status. Conclusions: We found hypervascular metastases to be present in 22% (4/18; CI95 [3-41%]) of breast cancer patients with true liver metastases. However, the detection for the presence of hepatic metastases was not improved with the addition of HAP. The HAP instead led to detection of more indeterminate but ultimately benign entities of no clinical significance, thus resulting in unnecessary imaging and arguably greater patient anxiety.

Characterization of patients with advanced pancreatic cancer and high serum interleukin-6 levels.

High serum level of interleukin 6 (IL-6) is associated with high degree of tumor progression and systemic weakness. Anti-IL-6 therapy possibly improves the deterioration of clinical characteristics in patients with high IL-6 level. However, IL-6-related factors in patients with treatment-naive advanced pancreatic cancer (PC) have not been established. The goal of this study was to identify IL-6-related factors in patients with advanced PC who were scheduled to undergo first-line chemotherapy. Patients with treatment-naive advanced PC were eligible for inclusion in this study. Patients who did not receive first-line chemotherapy were excluded. Serum IL-6 levels and clinical parameters were prospectively recorded. Analyses were performed to identify risk factors for high IL-6 levels. Eighty patients were analyzed. IL-6-related factors were advanced age (P < 0.01), the presence of liver metastasis (P < 0.01), the large volume of liver metastasis (P < 0.01), severe fatigue (P = 0.02), high carcinoembryonic antigen levels (P = 0.02), anemia (P < 0.01), and high C-reactive protein levels (P = 0.02) in multivariate analyses. Decreased skeletal muscle mass tended to be associated with high IL-6 levels. High serum IL-6 was related to advanced age, the presence of hepatic metastasis, large tumor burden in liver, severe fatigue, high carcinoembryonic antigen, high C-reactive protein, and anemia in patients with treatment-naive advanced PC.