Diagnosis Of Liver Metastases Research Articles

A multidimensional recommendation framework for identifying biological targets to aid the diagnosis and treatment of liver metastasis in patients with colorectal cancer

The quest to understand the molecular mechanisms of tumour metastasis and identify pivotal biomarkers for cancer therapy is increasing in importance. Single-omics analyses, constrained by their focus on a single biological layer, cannot fully elucidate the complexities of tumour molecular profiles and can thus overlook crucial molecular targets. In response to this limitation, we developed a multiobjective recommendation system (RJH-Metastasis 1.0) anchored in a multiomics knowledge graph to integrate genome, transcriptome, and proteome data and corroborative literature evidence and then conducted comprehensive analyses of colorectal cancer with liver metastasis (CRCLM). A total of 25 key genes significantly associated with CRCLM were recommended by our system, and GNB1, GATAD2A, GBP2, MACROD1, and EIF5B were further highlighted. Specifically, GNB1 presented fewer mutations but elevated RNA transcription and protein expression in CRCLM patients. The role of GNB1 in promoting the malignant behaviours of colon cancer cells was demonstrated via in vitro and in vivo studies. Aberrant expression of GNB1 could be regulated by METTL1-driven m7G modification. METTL1 knockdown decreased m7G modification in the 3’ UTR of GNB1, increasing its mRNA transcription and translation during liver metastasis. Furthermore, GNB1 induced the formation of an immunosuppressive microenvironment by promoting the CLEC2C-KLRB1 interaction between memory B cells and KLRB1+PD-1+CD8+ cells. GNB1 expression and the efficacy of PD-1 antibody-based treatment in CRCLM patients were significantly correlated. In summary, our recommendation system can be used for effective exploration of key molecules in colorectal cancer, among which GNB1 was identified as a critical CRCLM promoter and immunotherapy biomarker in colorectal cancer patients.

Initial Assessment of Resectability of Colorectal Cancer Liver Metastases Versus Clinical Outcome

BackgroundSurgery improves long-term survival for resectable, liver-only metastatic colorectal cancer (mCRC). With no consensus definition of “resectable” disease, decisions regarding resectability are reliant on the expertise and judgement of the treating clinician working in consultation with a multidisciplinary team (MDT). This study examines the clinical outcome versus initial assessment of resectability in an Australian population with mCRC. Patients and MethodsPatients with liver-only mCRC diagnosed January 2009 to December 2022 were identified from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry. Patients were classified based on prospectively documented treatment assessment as “resectable,” “potentially resectable,” or “unresectable.” The correlation between initial assessment of resectability and clinical outcome, and any impact of clinicopathologic factors were examined. Kaplan-Meier analysis assessed overall survival based on initial resectability assessment and resection status. Results: Of 4437 patients with mCRC identified through TRACC, 1250 (28%) had liver-only disease at presentation, with 497 (43%), 277 (24%), and 374 (33%) classified as “unresectable,” “potentially resectable,” and “resectable,” respectively. In total, 516 (41%) ultimately underwent surgical resection, including 30 (6%) of the “initially unresectable,” 148 (53%) of the “potentially resectable,” and 338 (90%) of the “resectable” at a median of 9.5, 5.9, and 2.4 months from the diagnosis of liver metastases, respectively. Resection in the “unresectable” patient population was associated with younger age (mean age 63 vs. 69, P = .0006), better performance status (ECOG 0-1 100% vs. 74%, P = .0017), and fewer comorbidities (Charlson index 0-3 in 73% vs. 53%, P = .0296) compared with no resection. Median overall survival was longer for resected versus nonresected patients across all categories: “unresectable” (59.2 vs. 17.6 months, P < .0001), “potentially resectable” (57.2 vs. 22.8 months, P < .0001), and “resectable” (108 vs. 55 months, P < .0001). ConclusionsThis real-world study demonstrates the potential for “initially unresectable” patients to become surgical candidates following systemic therapy, more likely in younger and fitter patients, with overall excellent survival outcomes in resected patients. This highlights the value of routine, repeated MDT assessments for patients with liver-only disease who are continuing to respond to systemic therapy, even for those initially considered never to be surgical candidates.

99mTc-FAPI-04 SPECT/CT outperforms contrast-enhanced CT in detecting metastasis in postoperative patients with colorectal cancer.

To compare the performance of 99mTc-FAPI-04 SPECT/CT and contrast-enhanced CT (CECT) in the detection of postoperative metastasis in patients with colorectal cancer (CRC). The postoperative patients with CRC were consecutively recruited from January 2023 to June 2023, and the enrolled patients completed 99mTc-FAPI-04 SPECT/CT imaging and CECT examination within two weeks. Histopathological analysis and the follow-up results were used as the reference criteria. The location and number of metastatic sites and the detection accuracy between the two imaging methods were compared. The tumor-to-background ratio (TBR) of liver metastasis and lymph node metastasis in 99mTc-FAPI-04 SPECT/CT imaging were also calculated for comparison. In total, 19 postoperative CRC patients, including 15 patients with metastasis, were included in this study. In the patient-based analysis, 99mTc-FAPI-04 SPECT/CT showed a significantly higher sensitivity for the detection of metastasis than CECT (93.3% vs. 80.0%, p = 0.038), but both techniques had the same specificity (100%, 4/4). For the lesion-based analysis, the detection rates of metastatic sites were 92.2% (47/51) and 72.5% (37/51) for 99mTc-FAPI-04 SPECT/CT and CECT, respectively, and the difference between them was statistically significant. In the diagnosis of liver metastasis and lymph node metastasis, 99mTc-FAPI-04 SPECT/CT both exceeded CECT. Additionally, the TBR in lymph node metastasis was higher than that in liver metastasis. The findings suggested that 99mTc-FAPI-04 SPECT/CT could detect metastasis more effectively than CECT, especially liver and lymph node metastases, in postoperative CRC patients.

The Clinical Features and Outcomes of Pseudocirrhosis in Breast Cancer.

Pseudocirrhosis is a diffuse nodularity of the liver that radiologically mimics cirrhosis but is a distinct pathological process. It is seen almost exclusively in patients with liver metastases and may represent a response to systemic treatment. Data on the risk factors for pseudocirrhosis and outcomes are limited. In total, 170 patients with a diagnosis of breast cancer and pseudocirrhosis in a 10-year period were identified and retrospectively analysed. Data were collected on baseline patient characteristics, treatments received, and outcomes. Median time between diagnosis of liver metastases and diagnosis of pseudocirrhosis was 17.1 months (range, 0-149 months). In total, 89.4% of patients received chemotherapy between their diagnosis of breast cancer liver metastases and their diagnosis of pseudocirrhosis, most commonly a taxane (74.7%) or capecitabine (67.1%), and the median treatment lines received was 3. Median OS from first diagnosis of pseudocirrhosis was 7.6 months (95% CI: 6.1-9.6 months) and was longer in patients with HER2+ disease at 16.7 months (95% CI: 6.4-32.9 months), which was statistically significant. In our study, pseudocirrhosis occurred in the presence of liver metastases and was associated with a poor prognosis. HER2+ patients with pseudocirrhosis had a better prognosis than other subtypes, but we did not identify other significant predictors of survival. Chemotherapy was not a prerequisite for pseudocirrhosis development, although the majority of patients had received at least one line of chemotherapy before pseudocirrhosis was diagnosed.

Tuning Tumor Targeting and Ratiometric Photoacoustic Imaging by Fine-Tuning Torsion Angle for Colorectal Liver Metastasis Diagnosis.

Photoacoustic (PA) tomography is an emerging biomedical imaging technology for precision cancer medicine. Conventional small-molecule PA probes usually exhibit a single PA signal and poor tumor targeting that lack the imaging reliability. Here, we introduce a series of cyanine/hemicyanine interconversion dyes (denoted Cy-HCy) for PA/fluorescent dual-mode probe development that features optimized ratiometric PA imaging and tunable tumor-targeting ability for precise diagnosis and resection of colorectal cancer (CRC). Importantly, Cy-HCy can be presented in cyanine (inherent tumor targeting and long NIR PA wavelength) and hemicyanine (poor tumor targeting and short NIR PA wavelength) by fine-tuning torsion angle and the ingenious transformation between cyanine and hemicyanine through regulation optically tunable group endows the NIR ratiometric PA and tunable tumor-targeting properties. To demonstrate the applicability of Cy-HCy dyes, we designed the first small-molecule tumor-targeting and NIR ratiometric PA probe Cy-HCy-H2S for precise CRC liver metastasis diagnosis, activated by H2S (a CRC biomarker). Using this probe, we not only visualized the subcutaneous tumor and liver metastatic cancers in CRC mouse models but also realized PA and fluorescence image-guided tumor excision. We expect that Cy-HCy will be generalized for creating a wide variety of inherently tumor-targeting NIR ratiometric PA probes in oncological research and practice.

Transcriptomic analysis of the tumor immune microenvironment (TIME) in patients with breast cancer with liver metastasis (BCLM).

e13045 Background: Breast cancer with liver metastasis (BCLM) is a significant predictor of worse prognosis and poor overall survival. Liver specific homing of breast cancer is not well understood, and the tumor immune microenvironment (TIME) likely plays a critical role in the process of forming BCLM. This retrospective study was conducted to determine the clinical risk factors and transcriptomic biomarkers associated with BCLM. Methods: A retrospective single institute chart review was conducted. Patient, disease characteristics and treatment variables were reviewed. Liver metastasis specific survival (defined by overall survival time from the diagnosis of liver metastasis) were compared across three breast subtypes (i.e., ER+/HER2-, HER2+, and triple-negative (TN) breast cancer) using Kaplan-Meier curves. Next generation sequencing (NGS) via commercial platforms were then used to obtain transcriptomic data. Transcriptomic analysis including differential gene expression analysis, gene set enrichment analysis (GSEA), as well as gene deconvolution analysis with TIMER2.0 were conducted for comparison of transcriptomic profiles and immune compositions across the three breast cancer subtypes. Results: 176 patients with BCLM and available liver metastasis biopsy were identified through retrospective chart review. Liver metastasis specific survival was compared, HER2+ BCLM patients (n = 17) had the best outcome and TN BCLM patients (n = 46) had the worst outcome with ER+ BCLM patients (n = 112) in the middle (p &lt; 0.0001, ER+ vs TNBC p &lt; 0.0001, ER+ vs HER2+ p = 0.038, HER2+ vs TNBC p = 0.00011). Principle component analysis on the transcriptomic data of 30 liver metastatic samples revealed different expression profiles between ER+ (n = 20) and TN (n = 7) BCLM, while HER2+ (n = 3) BCLM did not shown statistical differences with either group. B cell mediated immunity was upregulated in TN BCLM compared to ER+HER2- BCLM by GSEA (normalized enrichment score = 2.35, adjusted P-value = 0.19). Consistently, plasma cells were relatively enriched in TN BCLM compared to ER+ and HER2+ BCLM (p = 0.037) based on CIBERSORT estimation. In contrast, monocytes and neutrophils were enriched in ER+ BCLM (p = 0.0093 &amp; 0.018) based on TIMER2.0 estimation. Additional NGS analysis is currently underway for increased sample size. Conclusions: BCLM in TNBC was associated with significantly worse overall survival. TIME in TN BCLM enriched for genes associated with B cell mediated immunity while ER+ BCLM had more monocyte/neutrophil mediated immunity.

Size selection of intrahepatic lesions for cryoablation contributes to abscopal effect and long-term survival in patients with liver metastatic melanoma receiving PD-1 blockade therapy

ObjectivesIn this study, we aimed to examine parameters of cryoablation, tumor characteristics, and their correlations with distant tumor response and survival of liver metastatic melanoma patients receiving cryoablation and PD-1 blockade (cryo-PD-1) combination treatment.Materials and methodsA retrospective study was conducted among 45 melanoma patients who received combined PD-1 blockade therapy and cryoablation for liver metastasis from 2018 to 2022. Cox regression was utilized to determine the associations between factors and overall survival (OS). Changes in cytokines and immune cell compositions in peripheral blood samples following the combined treatment were investigated, along with their correlations with treatment response.ResultsThe mean cycle of cryo-PD-1 combination treatment was 2.2 (range, 1–6), and the 3-month overall response rate (RECIST 1.1 criteria) was 26.7%. Of the 21 patients who failed previous PD-1 blockade therapy after diagnosis of liver metastasis, 4 (19.0%) achieved response within 3 months since combination treatment. The diameter of ablated lesion ≤ 30 mm, metastatic organs ≤ 2, and pre-treatment LDH level ≤ 300 U/L were independent prognostic factors for favorable OS. Further analysis showed patients with intrahepatic tumor size of 15–45 mm, and ablated lesion size of ≤ 30 mm had significantly higher 3-month response rate (42.9% vs 12.5%; P = 0.022) and survival time (30.5 vs 14.2 months; P = 0.045) than their counterparts. The average increase in NLR among patients with ablated tumor size of ≤ 3 cm and > 3 cm were 3.59 ± 5.01 and 7.21 ± 12.57, respectively. The average increase in serum IL-6 levels among patients with ablated tumor size of ≤ 3 cm and > 3 cm were 8.62 ± 7.95 pg/ml and 15.40 ± 11.43 pg/ml, respectively.ConclusionSize selection of intrahepatic lesions for cryoablation is important in order to achieve abscopal effect and long-term survival among patients with liver metastatic melanoma receiving PD-1 blockade therapy.

Radiological complete response with regorafenib for multiple lung metastases of ascending colon cancer: a case report

BackgroundRegorafenib is an oral diphenylurea multikinase inhibitor and currently approved for use following third-line therapy for metastatic colorectal cancer (CRC) patients. Only one case has previously been reported of metastatic CRC showing a complete response (CR) to regorafenib.Case presentationA 68-year-old Japanese man underwent laparoscopy-assisted ileocecal resection and D3 lymphadenectomy due to his ascending colon cancer. Eighteen months after surgery, a laparoscopic hepatic left lateral segmentectomy was performed due to a liver tumor, and a pathological diagnosis of colorectal liver metastasis was made. Three months after the second surgery, contrast-enhanced computed tomography (CT) revealed multiple lung metastases. The patient had undergone 18 courses of the FOLFOX + bevacizumab chemotherapy regimen as their first-line therapy and 11 courses of the FOLFIRI + ramucirumab chemotherapy regimen as their second-line therapy. As their third-line therapy, the patient was administered the regorafenib chemotherapy regimen. We evaluated the chemotherapy treatment’s effect on the lung tumors by CT after 3, 7, 11, and 17 courses of the regorafenib chemotherapy regimen, finding that the lung tumors had shrunk with time; thus, each tumor was considered a partial response (PR) based on the RECIST guidelines. After 21 courses of the regorafenib chemotherapy regimen, the chemotherapy was discontinued in response to the patient’s wishes. Even at 1 and 3 months after the discontinuation of the chemotherapy, CT revealed that the lung tumors had shrunk, with each considered a PR. Furthermore, 9 months after the discontinuation of the chemotherapy, CT revealed scarring of the lung tumors. This was considered a CR, rather than a PR. The patient remains disease-free 18 months after the discontinuation of chemotherapy.ConclusionsIn this paper, we present the second case of radiological CR with regorafenib for multiple lung metastases of ascending colon cancer. Currently, there is no consensus on a treatment strategy for patients with radiological CR.

The Correlation Between Serum Tumor Markers and Liver Metastasis of Lung Cancer

Purpose: To investigate the relationship between the changes of lactate dehydrogenase (LDH), neuron‐specific enolase (NSE), keratin‐19 fragment antigen 21‐1 (cyfra21‐1), and liver metastases of lung cancer.Methods: Eighty patients who had lung cancer that had spread to their liver diagnosed in our hospital from October 2021 to October 2023 (Group A), 80 individuals with advanced lung cancer who have metastasized to other sites (Group B), and 80 individuals with lung cancer who have not spread (control group) were selected as the study objects. LDH, NSE, and serum cyfra21‐1 levels of patients in the three groups were detected, and pathological results were used as the diagnostic gold standard. ROC curves were drawn to examine the clinical value of NSE, cyfra21‐1, and LDH levels in the distinct types of lung cancer identification of liver metastases.Results: There was no remarkable variation in pathological types among the three groups (p &gt; 0.05), but there were remarkable variations in TNM stage and lymph node metastasis among the three groups (p &lt; 0.05). The levels of cyfra21‐1, NSE, and LDH in Group A and Group B were greater compared to those in the control group (p &lt; 0.05), and the levels of cyfra21‐1, NSE, and LDH in Group A were greater compared to those in Group B (p &lt; 0.05). The critical value, sensitivity, specificity, and area under the curve (AUC) of serum cyfra21‐1 in the distinct identification of liver metastasis of lung cancer were 8.22 ng/mL, 37.42%, 65.18%, and 0.508, respectively. The critical value, sensitivity, specificity, and AUC of NSE for distinct types of lung cancer identification of liver metastases were 23.96 ng/mL, 64.56%, 81.23%, and 0.723, respectively. The critical value, sensitivity, specificity, and AUC of LDH for differential diagnosis of liver metastasis of lung cancer were 304.78 U/L, 75.65%, 85.73%, and 0.821.Conclusion: The serum levels of NSE, cyfra21‐1, and LDH in patients with liver metastasis of lung cancer were remarkably greater compared to patients without liver metastasis, which can be useful as a clinical auxiliary in determining lung cancer metastasis.

Trends in Selective Internal Radiation Therapy (SIRT) for Treating Hepatocellular Carcinoma, Cholangiocarcinoma, and Liver Metastasis: A Total Population Analysis from 2006 to 2021 in Germany.

The aim of this study was to investigate trends in selective internal radiation therapy (SIRT) for hepatocellular carcinoma (HCC), cholangiocarcinoma (CCC), and liver metastasis in Germany. We analyzed the nationwide German hospital billing database from 2006 to 2019 for the diagnosis of HCC, CCC or liver metastasis in combination with SIRT. For analyses of SIRT on the hospital level, we used the reimbursement.INFO tool based on German hospitals' quality reports from 2008 to 2021. Linear regression analysis was performed to detect changes over time. We included a total of 14,165 SIRT procedures. The annual numbers increased from 99 in 2006 to 1605 in 2015 (p < 0.001; increase by 1521%), decreasing to 1175 cases in 2019 (p < 0.001). In 2008, 6 of 21 hospitals (28.6%) performed more than 20 SIRTs per year, which increased to 19 of 53 (35.8%) in 2021. The share of SIRT for HCC increased from 29.8% in 2006 to 44.7% in 2019 (p < 0.001) and for CCC from 0% in 2006 to 9.5% in 2019 (p < 0.001), while the share of SIRT for liver metastasis decreased from 70.2% in 2006 to 45.7% in 2019 (p < 0.001). In-hospital mortality was 0.2% after the SIRT procedure. Gastritis (2.7%), liver failure (0.4%), and sepsis (0.3%) were the most common in-hospital complications reported. We observed an increase in SIRT procedures in Germany, with the number of hospitals offering the procedure going up from 21 in 2008 to 53 in 2021. While the treatment of liver metastasis remains the most common indication, SIRT for HCC and CCC increased significantly over the last few years. The mortality and complication rates show that SIRT is a relatively safe procedure.

Whole Liver Radiotherapy for Multiple Liver Metastases in Thoracic Malignancies

Liver metastases (LM) are common in advanced thoracic cancer patients with dismal oncological outcomes. Even in the modern era of novel systemic therapy, LM led to a 21% increased mortality risk compared with those without. Options for progressive multiple LM after systemic therapy are limited. Therefore, a different treatment modality is urgently needed to overcome such a predicament. Herein, we renovate the classical whole liver radiotherapy (WLRT) and evaluate its efficacy and safety in treating thoracic cancer patients with progressive multiple LM. Patients with lung or thymic cancer who had multiple LM treated by WLRT between 2018 and 2022 were enrolled. Radiotherapy (RT) was delivered with a median dose of 24 Gy (range 8-25 Gy) in 8 fractions (range 1-16) at the discretion of treating physicians. Overall survival (OS) and cumulative incidence of intrahepatic progression were calculated from the completion of WLRT till death or progression by Kaplan-Meier and competing risk analyses, respectively. Twenty-four patients were enrolled in this retrospective study. Eleven patients (46%) had lung adenocarcinoma, of which nine patients had oncogenic mutations. Six patients (25%) had small cell lung cancer (SCLC), four patients (17%) had thymic squamous cell carcinoma (SqCC), two patients (8%) had lung SqCC, and one patient (4%) had mixed histology. Eighteen patients (75%) were under systemic therapy treatment before the diagnosis of LM, and fifteen (63%) received LM biopsy. The median time from the diagnosis of LM to WLRT was 7.5 months (range, 0.5-33.9 months). Eleven patients (46%) had concurrent RT and systemic therapy. With a median follow-up of 3.1 months, the 3-, 6- and 12-month OS were 57%, 38%, and 15%, respectively. After adjusting death as a competing risk, the cumulative incidence of LM progression at 3, 6, and 12 months were 10%, 19%, and 44%, respectively. Within three months after the completion of RT, one patient (4%) had grade 5 radiation-induced liver disease (RILD), one patient (4%) had grade 4 abnormal liver function test (LFT), three patients (13%) had grade 3 abnormal LFT, and twelve patients (50%) had ≤ grade 2 abnormal LFT. The patient who had Gr.5 RILD expired 51 days after the completion of RT with 24 Gy in 8 fractions concurrently with topotecan. He had primary SCLC with viral hepatitis B. His LFT was around the normal upper limit before WLRT. WLRT provided favorable intrahepatic control with acceptable radiation-related toxicities and could be considered a treatment option for patients with progressive LM under systemic therapy. Further investigation with a larger cohort is warranted to identify patients at a high risk of developing severe RILD.

Phase 1 Trial of SPECT-Guided Liver-Directed Ablative Radiotherapy for Patients with Low Functional Liver Volume

Traditional liver dose constraints specify that a critical volume of 700 cc of non-tumor liver should be spared from receiving a hepatotoxic dose. We evaluated the safety of liver-directed ablative radiotherapy for patients with hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), or liver metastases (LM) with Child-Pugh (CP) A5 liver function at baseline and with low functional liver volume as estimated by Tc-99m sulfur colloid single photon emission computed tomography (SPECT). We hypothesized that functional liver image guidance with SPECT would allow safe delivery of ablative radiotherapy in patients with limited liver volume. A phase 1 trial with a 3+3 design was conducted to evaluate the safety of comprehensive ablative radiotherapy to the liver disease using escalating functional non-target liver radiation dose constraints. Eligibility criteria included (1) a diagnosis of HCC, iCCA, or LM, (2) prior treatment with irinotecan or oxaliplatin chemotherapy or liver resection, and (3) a minimum functional liver volume of 400 cc as estimated by SPECT using a threshold of 40% maximum intensity. Patients with CP >A5 liver function, prior liver-directed radiotherapy, or prior Yttrium-90 therapy were excluded. The prescription dose was 67.5-75 Gy in 15 fractions or 75-100 Gy in 25 fractions. The volumetric dose constraint for functional non-target liver receiving <24 Gy for 15 fractions or <27 Gy for 25 fractions was determined by the dose level of trial enrollment: level 0 was ≥400 cc and level +1 was ≥300 cc. A level -1 was included if needed. We used standard 15 and 25 fraction dose constraints for other organs at risk. The following dose limiting toxicities (DLTs) were assessed within 6-8 weeks of completing radiotherapy: Grade 3 hypoalbuminemia, increase in INR, increase in bilirubin, or ascites, or Grade 4 hepatic failure or any radiation-related toxicity. Twelve patients enrolled between February 2016 and June 2022. The median (range) GTV was 36 (2-651) cc. The median CT anatomical non-tumor liver volume was 1584 (764-2699) cc, and the median SPECT functional liver volume was 1117 (570-1928) cc, with a Pearson correlation coefficient of 0.98 (p<0.001). The median non-target SPECT functional liver volume below the volumetric dose constraint was 684 (429-1244) cc. None of the 3 patients treated in dose level 0, and none of the 9 patients treated in dose level +1 experienced any DLTs. The 1-year in-treatment-field control rate was 55%, and 1-year overall survival was 71%. Ablative radiotherapy can be safely delivered using functional SPECT image guidance, which enables sparing lower volumes of functional liver than traditionally accepted in patients with CP A5 liver function. Further evaluation with a phase 2 study is warranted.

Probe-based confocal laser endomicroscopy for real-time evaluation of colorectal liver metastasis in resected surgical specimens

Probe-based confocal laser endomicroscopy (pCLE) enables real-time examination of tissue structure. This study investigated pCLE with or without fluorescein sodium for the intraoperative diagnosis of colorectal liver metastasis (CLM) and detection of surgical margins. Thirty-four specimens of CLM and adjacent noncancerous tissue were obtained from 21 patients and examined by pCLE between May 2017 and March 2018. Images were obtained both without and with fluorescein sodium applied to the cut surface and compared with hematoxylin and eosin-stained tissue. Fluorescence intensity (FI) was measured by luminance-analysis software. Without external fluorophores, pCLE visualized 91.2% of CLM tissues as an irregular structure with low autofluorescence and 90.5% of noncancerous liver tissues as a regular structure with high autofluorescence. The median FI was significantly lower in cancer than in benign tissue in patients without chemotherapy [70.4 (51.6–110) vs. 48.3 (39.0–59.4), p = 0.002] and with chemotherapy [67.9 (54.6–89.2) vs. 48.6 (28.8–82.1), p < 0.001]. The border was clearly visible; pCLE with fluorescein sodium clearly showed their morphologies. In summary, our study demonstrated real-time pCLE distinguished CLM and noncancerous tissue by differences in structure and FI regardless of prehepatectomy chemotherapy. Fluorescein spray facilitated clear visualization of differences in the morphology.

A case in which ultrasound-guided fine needle aspiration was useful in the diagnosis of liver metastasis of gallbladder cancer

A case in which ultrasound-guided fine needle aspiration was useful in the diagnosis of liver metastasis of gallbladder cancer

Two machine learning-based nomogram to predict risk and prognostic factors for liver metastasis from pancreatic neuroendocrine tumors: a multicenter study

BackgroundPancreatic neuroendocrine tumors (PNETs) are one of the most common endocrine tumors, and liver metastasis (LMs) are the most common location of metastasis from PNETS; However, there is no valid nomogram to predict the diagnosis and prognosis of liver metastasis (LMs) from PNETs. Therefore, we aimed to develop a valid predictive model to aid physicians in making better clinical decisions.MethodsWe screened patients in the Surveillance, Epidemiology, and End Results (SEER) database from 2010–2016. Feature selection was performed by machine learning algorithms and then models were constructed. Two nomograms were constructed based on the feature selection algorithm to predict the prognosis and risk of LMs from PNETs. We then used the area under the curve (AUC), receiver operating characteristic (ROC) curve, calibration plot and consistency index (C-index) to evaluate the discrimination and accuracy of the nomograms. Kaplan-Meier (K-M) survival curves and decision curve analysis (DCA) were also used further to validate the clinical efficacy of the nomograms. In the external validation set, the same validation is performed.ResultsOf the 1998 patients screened from the SEER database with a pathological diagnosis of PNET, 343 (17.2%) had LMs at the time of diagnosis. The independent risk factors for the occurrence of LMs in PNET patients included histological grade, N stage, surgery, chemotherapy, tumor size and bone metastasis. According to Cox regression analysis, we found that histological subtype, histological grade, surgery, age, and brain metastasis were independent prognostic factors for PNET patients with LMs. Based on these factors, the two nomograms demonstrated good performance in model evaluation.ConclusionWe developed two clinically significant predictive models to aid physicians in personalized clinical decision-makings.

Hepatectomy Before Primary Tumor Resection as Preferred Approach for Synchronous Liver Metastases from Rectal Cancer.

For patients with synchronous liver metastases (LM) from rectal cancer, a consensus on surgical sequencing is lacking. We compared outcomes between the reverse (hepatectomy first), classic (primary tumor resection first), and combined (simultaneous hepatectomy and primary tumor resection) approaches. A prospectively maintained database was queried for patients with rectal cancer LM diagnosed before primary tumor resection who underwent hepatectomy for LM from January 2004 to April 2021. Clinicopathological factors and survival were compared between the three approaches. Among 274 patients, 141 (51%) underwent the reverse approach; 73 (27%), the classic approach; and 60 (22%), the combined approach. Higher carcinoembryonic antigen level at LM diagnosis and higher number of LM were associated with the reverse approach. Combined approach patients had smaller tumors and underwent less complex hepatectomies. More than eight cycles of pre-hepatectomy chemotherapy and maximum diameter of LM > 5 cm were independently associated with worse overall survival (OS) (p = 0.002 and 0.027, respectively). Although 35% of reverse-approach patients did not undergo primary tumor resection, OS did not differ between groups. Additionally, 82% of incomplete reverse-approach patients ultimately did not require diversion during follow-up. RAS/TP53 co-mutation was independently associated with lack of primary resection with the reverse approach (odds ratio: 0.16, 95% CI 0.038-0.64, p = 0.010). The reverse approach results in survival similar to that of combined and classic approaches and may obviate primary rectal tumor resections and diversions. RAS/TP53 co-mutation is associated with a lower rate of completion of the reverse approach.

Platinum-based chemotherapy in patients with castration-resistant prostate cancer and hepatic metastases.

e17063 Background: Patients with metastatic castration-resistant prostate cancer (mCRPC) and hepatic metastases face a dismal prognosis. In fact, the majority of phase 3 trials show no benefit of novel treatment modalities including Lutetium PSMA radioligand therapy (LuPSMA-RLT) in comparison with standard therapies for the subgroup of visceral metastases. In aggressive variant prostate cancer, the addition of platinum resulted in a clinically relevant improvement of progression free survival (PFS) and overall survival (OS). Whether adding platinum is also beneficial in unselected mCRPC patients with hepatic metastasis is unclear. Methods: We retrospectively analyzed mCRPC patients diagnosed with hepatic metastasis and treated with platinum-based chemotherapy or LuPSMA-RLT in three German centers (Hamburg, Essen, Munich). Patients with pure neuroendocrine prostate cancer were excluded. Survival rates and 95% confidence intervals (CI) were compared using the Kaplan Meier method and the logRank test. Results: A total of 84 mCRPC patients with hepatic metastasis who had received at least one platinum-based therapy and 32 patients treated with LuPSMA-RLT were evaluated. Median age at treatment initiation was 67 and 73 years. Patients had undergone a median of three treatment lines (83% ≥ 1 new hormonal agent (NHA); 87% ≥ 1 taxane based chemotherapy) before initiation of platinum based chemotherapy and a median of 4 treatment lines before LuPSMA-RLT. Median time to initiation of 1st platinum-based chemotherapy after diagnosis of liver metastases was 55 days. In total, 37% received carboplatin/cabazitaxel, 26% cisplatin or carboplatin/ etoposide, 11% carboplatin/docetaxel, and 26% other platinum-based combination therapies. In the platinum-treated group, 52.6% and 27% of the patients did not show progression at 3 and 6 months after treatment initiation as compared to 44.1% and 19.3% of the patients who received LuPSMA-RLT with a median PFS of 3.1 and 2.4 months, respectively. At 6 months 71.3% of the platinum-treated patients and 56.6% of the LuPSMA-RLT were alive. Overall, BRCA1/2 status was available for 53 of the platinum-treated patients, 15% of whom had a pathogenic alteration in either gene. This small subgroup was found to have a similar OS compared to the overall cohort. Conclusions: Platinum-based chemotherapy showed promising activity in mCRPC patients with hepatic metastasis. Given the high unmet medical need, platinum-based combination therapies should be further evaluated prospectively. [Table: see text]

Identifying liver metastasis-related hub genes in breast cancer and characterizing SPARCL1 as a potential prognostic biomarker.

The liver is the third most common metastatic site for advanced breast cancer (BC), and liver metastases predict poor prognoses. However, the characteristic biomarkers of BC liver metastases and the biological role of secreted protein acidic and rich in cysteine-like 1 (SPARCL1) in BC remain unclear. The present study aimed to identify potential biomarkers for liver metastasis of BC and to investigate the effect of SPARCL1 on BC. The publicly available GSE124648 dataset was used to identify differentially expressed genes (DEGs) between BC and liver metastases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to annotate these DEGs and understand the biological functions in which they are involved. A protein-protein interaction (PPI) network was constructed to identify metastasis-related hub genes and further validated in a second independent dataset (GSE58708). Clinicopathological correlation of hub gene expression in patients with BC was determined. Gene set enrichment analysis (GSEA) was performed to explore DEG-related signaling pathways. SPARCL1 expression in BC tissues and cell lines was verified by RT-qPCR. Further in vitro experiments were performed to investigate the biological functions of SPARCL1 in BC cells. We identified 332 liver metastasis-related DEGs from GSE124648 and 30 hub genes, including SPARCL1, from the PPI network. GO and KEGG enrichment analyses of liver-metastasis-related DEGs revealed several enriched terms associated with the extracellular matrix and pathways in cancer. Clinicopathological correlation analysis of SPARCL1 revealed that its expression in BC was associated with age, TNM stage, estrogen receptor status, progesterone receptor status, histological type, molecular type, and living status of patients. GSEA results suggested that low SPARCL1 expression in BC was related to the cell cycle, DNA replication, oxidative phosphorylation, and homologous recombination. Lower expression levels of SPARCL1 were detected in BC tissues compared to adjacent tissues. The in vitro experiments showed that SPARCL1 knockdown significantly increased the proliferation and migration of BC cells, whereas the proliferation and migration were suppressed after elevating the expression of SPARCL1. We identified SPARCL1 as a tumor suppressor in BC, which shows potential as a target for BC and liver metastasis therapy and diagnosis.

Artificial intelligence-powered software detected more than half of the liver metastases overlooked by radiologists on contrast-enhanced CT

PurposeTo evaluate the sensitivity of artificial intelligence (AI)-powered software in detecting liver metastases, especially those overlooked by radiologists. MethodsRecords of 746 patients diagnosed with liver metastases (November 2010–September 2017) were reviewed. Images from when radiologists first diagnosed liver metastases were reviewed, and prior contrast-enhanced CT (CECT) images were checked for availability. Two abdominal radiologists classified the lesions into overlooked lesions (all metastases missed by radiologists on prior CECT) and detected lesions (all metastases if any of them were correctly identified and invisible on prior CECT or those with no prior CECT). Finally, images from 137 patients were identified, 68 of which were classified as “overlooked cases.” The same radiologists created the ground truth for these lesions and compared them with the software’s output at 2-month intervals. The primary endpoint was the sensitivity in detecting all liver lesion types, liver metastases, and liver metastases overlooked by radiologists. ResultsThe software successfully processed images from 135 patients. The per-lesion sensitivity for all liver lesion types, liver metastases, and liver metastases overlooked by radiologists was 70.1%, 70.8%, and 55.0%, respectively. The software detected liver metastases in 92.7% and 53.7% of patients in detected and overlooked cases, respectively. The average number of false positives was 0.48 per patient. ConclusionThe AI-powered software detected more than half of liver metastases overlooked by radiologists while maintaining a relatively low number of false positives. Our results suggest the potential of AI-powered software in reducing the frequency of overlooked liver metastases when used in conjunction with the radiologists’ clinical interpretation.

Tumour-derived exosomes in liver metastasis: A Pandora's box.

The liver is a common secondary metastasis site of many malignant tumours, such as the colorectum, pancreas, stomach, breast, prostate, and lung cancer. The clinical management of liver metastases is challenging because of their strong heterogeneity, rapid progression, and poor prognosis. Now, exosomes, small membrane vesicles that are 40-160 nm in size, are released by tumour cells, namely, tumour-derived exosomes (TDEs), and are being increasingly studied because they can retain the original characteristics of tumour cells. Cell-cell communication via TDEs is pivotal for liver pre-metastatic niche (PMN) formation and liver metastasis; thus, TDEs can provide a theoretical basis to intensively study the potential mechanisms of liver metastasis and new insights into the diagnosis and treatment of liver metastasis. Here, we systematically review current research progress about the roles and possible regulatory mechanisms of TDE cargos in liver metastasis, focusing on the functions of TDEs in liver PMN formation. In addition, we discuss the clinical utility of TDEs in liver metastasis, including TDEs as potential biomarkers, and therapeutic approaches for future research reference in this field.