Metastatic Liver Lesions Research Articles

Delineating the molecular landscape of different histopathological growth patterns in colorectal cancer liver metastases.

Histopathological growth patterns (HGPs) have shown important prognostic values for patients with colorectal cancer liver metastases, but the potential molecular mechanisms remain largely unknown. We performed an exploratory analysis by conducting the RNA sequencing of primary colorectal lesions, colorectal liver metastatic lesions and normal liver tissues. We found that desmoplastic HGPs of the metastatic lesions were significantly enriched in EMT, angiogenesis, stroma, and immune signaling pathways, while replacement HGPs were enriched in metabolism, cell cycle, and DNA damage repair pathways. With the exception of immune-related genes, the differentially expressed genes of the two HGPs from colorectal liver metastases were mostly inherited from the primary tumor. Moreover, normal liver tissue in the desmoplastic HGP subgroup was markedly enriched in the fibrinous inflammation pathway. We surmised that HGPs are observable morphological changes resulting from the regulation of molecular expressions, which is the combined effect of the heterogeneity and remodeling of primary tumors seeds and liver soils.

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

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

Comparison of laparoscopic and open simultaneous surgeries for synchronous metastases of colorectal cancer in the liver: meta-analysis

Aim. To analyze studies focused on comparing laparoscopic and open simultaneous surgeries for synchronous metastases of colorectal cancer in the liver.Materials and methods. The electronic databases PubMed, Web of Science, Scopus, Embase, Cochrane Library were searched for the studies focused on the comparison of open and laparoscopic simultaneous surgeries for synchronous metastatic liver lesions, dated till October 20, 2020. Keywords: simultaneous resections, colorectal cancer, liver metastases, simultaneous laparoscopic.Results. Meta-analysis contains the results of 1211 simultaneous surgeries for simultaneous metastases of colorectal cancer in the liver: 450 laparoscopic and 761 open surgeries. Laparoscopic surgery was characterized with lower blood loss [weighted mean difference (WMD) = -131.77, 95% CI: -232.54 to -31.00, p = 0.01], a shorter postoperative hospitalization [WMD = -2.87, 95% CI: -3.41 to -2. 33, p < 0.00001], early first bowel movement [WMD = -0.99, 95% CI: -1.40 to -0.58, p < 0.0001], early initiation of enteral feeding [WMD = -1.20, 95% CI: -2.06 to -0.33, p = 0.007]), lower incidence of postoperative complications [OR = 0.60, 95% CI: 0.46–0.80, p = 0.0004]. A statistically significant advantage of laparoscopic access was established in overall [OR = 0.80, 95% CI: 0.64–0.99, p = 0.04] and recurrence-free survival [OR = 0.73, 95% CI: 0.60–0.89, p = 0.002].Conclusion. Perioperative and distant oncologic outcomes demonstrate safety and efficacy of laparoscopic simultaneous interventions for synchronous metastases of colorectal cancer in comparison with open interventions.

Anti-Programmed Cell Death-1 Antibody and Dasatinib Combination Therapy Exhibits Efficacy in Metastatic Colorectal Cancer Mouse Models.

In this study, we investigated the in vivo metastasis suppression effects of the platelet-derived growth factor receptor inhibitor dasatinib, which targets cancer-associated fibroblasts (CAFs), in combination with an anti-programmed cell death-1 (PD-1) antibody. We classified clinical CRC cases as inflamed, excluded, or desert using immunohistochemical analysis and evaluated the tumor stroma. The excluded type was the most common, and cases with high-volume stroma in the primary lesions also had a high stromal volume in the liver metastatic lesions. Liver-metastasis mouse models with different stromal volumes were established and treatment-induced changes in the tumor immune microenvironment were evaluated. The anti-PD-1 antibody alone exhibited a therapeutic effect for the liver metastases with low stromal volumes but not for the liver metastases with high stromal volumes. In contrast, antitumor effects were observed with anti-PD-1 antibody/dasatinib combination therapy even in the liver metastases with high stromal volumes. Combination therapy reduced the stromal volume, promoted immune cell infiltration, induced antitumor cytotoxic T-cell responses, activated antitumor immunity, and promoted tumor regression. These results suggest that CAFs play an important role in the immune evasion of CRC and that anti-PD-1 antibody/dasatinib combination therapy has potential as a treatment option for patients with metastatic CRC for whom immunotherapy alone is ineffective.

Evaluation of segmental distribution of liver metastases in colorectal carcinomas by computed tomography

Objective: We aimed to investigate the relationship between the localization of colorectal carcinomas and the topographic distribution of metastatic liver lesions. Material and Methods: Patients diagnosed with colorectal cancer and metastatic liver lesions constituted the target population of this study. Demographic data, primary tumor localization, and data regarding liver metastases were retrieved and retrospectively reviewed. Patient files, including endoscopy and computerized tomography reports, were the primary data source. In addition, data concerning segmental localization of the metastatic liver lesions based on the Couinaud classification were collected. Results: Ninety-six patients were diagnosed with colorectal cancer with liver metastases during the study period. A total of 251 metastases were detected. The number of metastases was 169 (67.3%) in the right and 80 (31.9%) in the left lobe (p0.05). Conclusion: Liver metastases of colorectal cancer are significantly more common in the right lobe than the left lobe, irrespective of the location of the colorectal tumor. Segment VIII of the right lobe is the main target of the metastases.

Integrated Multi-Omics Landscape of Liver Metastases

Lack of thorough knowledge about the complicated immune microenvironment (IM) within a variety of liver metastases (LMs) leads to inappropriate treatment and unsatisfactory prognosis. We aimed to characterize IM subtypes and investigate potential mechanisms in LMs. Mass cytometry was applied to characterize immune landscape of a primary liver cancers and liver metastases cohort. Transcriptomic and whole-exome sequencing were used to explore potential mechanisms across distinct IM subtypes. Single-cell transcriptomic sequencing, multiplex fluorescent immunohistochemistry, cell culture, mouse model, Western blot, quantitative polymerase chain reaction, and immunohistochemistry were used for validation. Five IM subtypes were revealed in 100 LMs and 50 primary liver cancers. Patients featured terminally exhausted (IM1) or rare T-cell-inflamed (IM2 and IM3) immune characteristics showed worse outcome. Increased intratumor heterogeneity, enriched somatic TP53, KRAS, APC, and PIK3CA mutations and hyperactivated hypoxia signaling accounted for the formation of vicious subtypes. SLC2A1 promoted immune suppression and desert via increasing proportion of Spp1+ macrophages and their inhibitory interactions with T cells in liver metastatic lesions. Furthermore, SLC2A1 promoted immune escape and LM through inducing regulatory T cells, including regulatory T cells and LAG3+CD4+ T cells in primary colorectal cancer. The study provided integrated multi-omics landscape of LM, uncovering potential mechanisms for vicious IM subtypes and confirming the roles of SLC2A1 in regulating tumor microenvironment remodeling in both primary tumor and LM lesions.

A rare case of pulmonary adenoid cystic carcinoma with liver metastases treated effectively with stereotactic body radiation therapy

AbstractPulmonary adenoid cystic carcinoma (PACC) is an extremely rare neoplasm. Adenoid cystic carcinoma (ACC) usually occurs in the salivary glands of the head and neck. Given its rare occurrence, there are no established guidelines for the treatment of progressive and/or relapsed disease. We herein report a case of a 57‐year‐old female who was incidentally found to have biopsy confirmed PACC following trauma diagnostic workup. She underwent pneumonectomy and adjuvant radiation therapy with an initial good response. On follow‐up a year later, she was noted to have two metastatic liver lesions treated with stereotactic body radiation therapy (SBRT) and lenvatinib. This case report adds to the growing area of research on PACC, especially among patients requiring SBRT for oligometastatic disease.

Complete response in patient with liver metastasis of HER2-positive breast cancer following therapy with margetuximab: a case report.

Metastatic human epidermal growth factor receptor 2 (HER2) positive breast cancer has a poor prognosis and few effective targeted therapies. However, several anti-HER2 agents are emerging in conjunction with chemotherapy, which may lead to increased rates of pathological complete response in patients with HER2-positive metastatic breast cancer. Among them, margetuximab demonstrated a significant improvement in progression-free survival compared with trastuzumab, when combined with chemotherapy in pretreated patients. Here we present a case of a 67-year-old female patient who was diagnosed with HER2-positive, histological grade III and invasive ductal carcinoma of the left breast in September 2018. She received postoperative adjuvant therapy with EC-TH plus radiotherapy, followed by therapy with HER2-targeted trastuzumab for 1 year (till December 2019). In May 2020, routine reexamination showed a supraclavicular lymph node and bone metastasis. Patient was then treated with pyrotinib, capecitabine and bisphosphonate for a period of 3 months. In December 2020, liver MRI revealed multiple liver metastases. The patient received eight cycles of second-line therapy (vinorelbine plus margetuximab) from January 2021. Since the ninth cycle, the patient was continued with only margetuximab. In March 2021, MRI showed a 70% decrease in the liver metastasis lesions. By June 2021, liver lesions were totally disappeared. During therapy, patient experienced only grade-1 anemia. This case demonstrates that margetuximab plus chemotherapy is safe and might bring clinical benefits for patients with HER2-positive breast cancer with liver metastasis. Further studies evaluating the efficacy and safety of margetuximab in Chinese HER2-positive breast cancer patients are needed.

MACC1 promotes pancreatic cancer metastasis by interacting with the EMT regulator SNAI1

Metastasis is the dominant cause of cancer-related mortality. Metastasis-associated with colon cancer protein 1 (MACC1) has been proven to play a critical role in cancer metastasis. However, the prometastatic role of MACC1 in regulating the pancreatic cancer (PC) metastatic phenotype remains elusive. Here, we report that MACC1 is highly expressed in The Cancer Genome Atlas (TCGA) and tissue microarray (TMA) and identified as a good indicator for poor prognosis. Overexpression or knockdown of MACC1 in PC cells correspondingly promoted or inhibited pancreatic cancer cell migration and invasion in a MET proto-oncogene receptor tyrosine kinase (MET)-independent manner. Notably, knockdown of MACC1 in PC cells markedly decreased the liver metastatic lesions in a liver metastasis model. Mechanistically, MACC1 binds to the epithelial-mesenchymal transition (EMT) regulator snail family transcriptional repressor 1 (SNAI1) to drive EMT via upregulating the transcriptional activity of SNAI1, leading to the transactivation of fibronectin 1 (FN1) and the trans-repression of cadherin 1 (CDH1). Collectively, our results unveil a new mechanism by which MACC1 drives pancreatic cancer cell metastasis and suggest that the MACC1-SNAI1 complex-mediated mesenchymal transition may be a therapeutic target in pancreatic cancer.

Clinicopathological Significance of Poorly Differentiated Clusters in Liver Metastatic Lesions of Colorectal Carcinoma

Clinicopathological Significance of Poorly Differentiated Clusters in Liver Metastatic Lesions of Colorectal Carcinoma

The Effectiveness of Proton Beam Therapy for Liver Metastatic Lesions in Colorectal Cancer Patients

<h3>Purpose/Objective(s)</h3> The purpose of this study was to evaluate the efficacy and safety of proton beam therapy (PBT) for liver metastatic (LM) lesion in colorectal cancer (CRC) patients. <h3>Materials/Methods</h3> Consecutive CRC patients who underwent PBT for ≤3 LM lesions from 2009 to 2018 were isolated from our institutional database. Patients with extrahepatic metastatic lesions were excluded. The effectiveness was assessed based on the local control (LC), overall survival (OS) and progression-free survival (PFS) rates. The LC, OS and PFS rates were calculated using the Kaplan–Meier method and log-rank test. Factors that may be related to LC, such as tumor size, fraction size, BED₁₀ and the distance from the lesion to the most recently involved intestinal tract were investigated. The cut-off values were estimated using the ROC curve and AUC. P-values below 0.05 were consider significant. Adverse events were described according to CTCAE ver 5.0. <h3>Results</h3> This study included 23 men and 18 women whose median age was 66 years (24 - 87 years). Sixty-three lesions were enrolled. The most frequent dosage was 72.6 Gy (RBE) /22fr. The median lesion size, fraction size, BED₁₀, the distance between LM lesion and adjacent were 30 mm (9-103 mm), 3.3 Gy(RBE)/fr (2-8 Gy(RBE)/fr),105.6 Gy(RBE) (72-154.7 Gy(RBE)), 42.4mm (0-147mm), respectively. The median follow-up period was 27.6 months (5.2-84.7 months). As of November 2020, 20 patients died (including one of intercurrent disease death). The 3-year LC, OS and PFS rates were 54.9%, 61.6%, and 16.7%, respectively. Twenty-three lesions were local recurrence which of five lesions were surgically removed and one lesion was re-irradiated with PBT. Both re-treatments after PBT were performed safely and without complications. Distant metastasis occurred in 24 patients. The most common site of distant metastasis was the lung with 11 patients. Any statistically significant LC related factors were not found. However, the P-value for tumor size was the smallest, P=0.0665. The 2-year LC rates in the group with less than 14.1 mm and the larger group were 100% and 50%, respectively. and 50%, respectively. No grade ≥3 adverse events were observed. No patients experienced liver failure in the acute or late phase. The only acute adverse event was one cases of G2 dermatitis radiation. The only late adverse effect was three cases of G1 radiation-induced rib fracture. <h3>Conclusion</h3> PBT might be a treatment option for patients with liver metastasis of CRC. Tumor size tended to be associated with local control rates.

Development of a Support Vector Machine-Based Tool for Survival Prediction after Stereotactic Body Radiotherapy for Liver Metastases Using Multi-Institutional Data

<h3>Purpose/Objective(s)</h3> Stereotactic body radiotherapy (SBRT) has been increasingly used as well-tolerated, effective treatment for metastatic liver lesions. Machine learning can predict outcomes and aid in developing treatment regimens; however, few studies have attempted to predict liver SBRT outcomes and most have been limited to a single institution. Support vector machine (SVM) algorithms can address complex classification by mapping data into multi-dimensional space. This study aims to develop an SVM-based model to predict survival after SBRT for liver metastases using multi-institutional data. <h3>Materials/Methods</h3> The Comprehensive Liver Pooled SBRT Outcomes (CaLiPSO) is an international consortium of four high-volume SBRT academic centers. Patients who received SBRT for liver metastases were identified from the CaLiPSO database; baseline demographic, clinical, and dosimetric data were collected. Outcomes of interest were overall survival at 12, 18, and 24 months (12mo-OS, 18mo-OS, and 24mo-OS). We investigated a SVM algorithm using a Gaussian kernel and 10-fold cross-validation schema. Performance was measured by accuracy defined as the ratio of correct classifications to samples and by computing the area under the receiving operator characteristic curve (AUC of ROC). Training was performed using a programming environment. <h3>Results</h3> A total of 132 patients with metastatic liver lesions treated with SBRT were included in this study, 77 females (58.3%) and 55 males (41.7%) with median age of 65 years (range 27-88). The median 2-Gy Equivalent Dose (EQD2) was 60 Gy. At the time of SBRT, 62 patients (47.0%) had extrahepatic disease and 70 (53.0%) did not. The number of patients alive at 12, 18, and 24 months were 64 (48.5%), 52 (39.4%), and 41 (31.1%), respectively. Patients were randomly divided into training (n=92) and testing (n=40) sets. Predictive factors included in the SVM were age, EQD2, planning target volume (PTV), and percentage of normal liver volume. Training set AUCs were above 0.95; results for the testing set are listed in Table 1. Performance at 18 and 24 months had AUC of 0.74 and 0.68, respectively, and was improved compared to at 12 months. <h3>Conclusion</h3> Using clinical and dosimetric variables, promising results were obtained for accurate prediction of liver SBRT outcomes. To our knowledge, this is the first SVM-based tool for SBRT outcome prediction in liver metastases validated using international, multi-institutional data for over 100 patients. This tool can help improve care and facilitate appropriate treatment escalation; it can be implemented online for the radiation oncology community as it uses commonly collected data and is easy to compute. The tool can be further refined and validated with larger cohorts in prospective trials.

Efficacy of SBRT in High Volume Metastatic Carcinoma Breast – A Berry Picking Approach in the Era of High Precision Radiotherapy

<h3>Purpose/Objective(s)</h3> Treatment of metastatic breast cancer is always challenging. Management mainly involves chemotherapy, targeted therapy and immunotherapy. Though novel conformal techniques have evolved in the field of radiotherapy, the same has not been optimally tried in metastatic carcinoma breast patients except for low burden oligometastatic disease. Systemic therapy has been the cornerstone of management till date. In the present study we evaluate the role of SABR in high volume metastatic breast carcinoma in regards with efficacy and feasibility. <h3>Materials/Methods</h3> 47 patients with biopsy proven carcinoma breast were prospectively analyzed (age > 18 years, ECOG ≤2). SBRT was delivered to metastatic lesions in brain, liver, lung, bone and adrenal. Median dose of 30 Gy (25 to 35) in 3 to 5 sessions. PETCT based planning was done in all patients. Robotic assisted SABR was done using real time tumor tracking during treatment. All patients were continued on systemic therapy. Clinical outcomes were studied in regards with local control, overall and progression free survival. Survival analysis was performed using Kaplan-Meier method. <h3>Results</h3> 47 patients with metastatic carcinoma breast (median age: 51 years, range: 29 to 70 years) ER positive 60%, PR positive in 45%, HER2 over expression was seen in 25%, Triple negative (34%) were included in our study. All patients were treated with SBRT to a total of 103 metastatic sites, including brain (27%); bone (20.3%); lung (17.4%); lymph node (17.4%); liver (12.6%); and adrenal (4%) from the years 2009 - 2021. OS at the end of 1, 3 and 5 years was 78.37, 43.24 and 21.62 respectively. Local control (LC) - sitewise has been mentioned below. <h3>Conclusion</h3> SABR is feasible option in high volume metastatic carcinoma breast with good local control, improved survival and well tolerable approach and can be considered as an adjunct to systemic therapy. Further randomized trials are needed to validate the same.

Multi-perspective comparison of the immune microenvironment of primary colorectal cancer and liver metastases

BackgroundLiver metastases are a major contributor to the poor immunotherapy response in colorectal cancer patients. However, the distinctions in the immune microenvironment between primary tumors and liver metastases are poorly characterized. The goal of this study was to compare the expression profile of multiple immune cells to further analyze the similarities and differences between the microenvironments of liver metastases and the primary tumor.MethodsTissues from 17 patients with colorectal cancer who underwent resection of primary and liver metastases was analyzed using multispectral immunofluorescence. The expression of multiple immune cells (CD8, Foxp3, CD68, CD163, CD20, CD11c, CD66b, CD56, PD-L1, INF-γ, Ki67 and VEGFR-2) in the tumor center (TC), tumor invasive front (< 150 µm from the tumor center, TF) and peritumoral region (≥ 150 µm from the tumor center, PT) was evaluated via comparison. The expression of CD68 and CD163 in different regions was further analyzed based on the cell colocalization method. In addition, different immune phenotypes were studied and compared according to the degree of CD8 infiltration.ResultsThe expression trends of 12 markers in the TF and TC regions were basically the same in the primary tumor and liver metastasis lesions. However, in comparison of the TF and PT regions, the expression trends were not identical between primary and liver metastases, especially CD163, which was more highly expressed in the PT region relative to the TF region. In the contrast of different space distribution, the expression of CD163 was higher in liver metastases than in the primary foci. Further analysis of CD68 and CD163 via colocalization revealed that the distribution of macrophages in liver metastases was significantly different from that in the primary foci, with CD68−CD163+ macrophages predominating in liver metastases. In addition, among the three immunophenotypes, CD163 expression was highest in the immune rejection phenotype.ConclusionsThe immune cells found in the primary tumors of colorectal cancer differed from those in liver metastases in terms of their spatial distribution. More immunosuppressive cells were present in the liver metastases, with the most pronounced differential distribution found for macrophages. CD68−CD163+ macrophages may be associated with intrahepatic immunosuppression and weak immunotherapeutic effects.

Ablative therapies in primary and metastatic liver tumours: An early experience

Background: Hepatic resection and hepatic transplantation are considered the only definitive treatment modalities capable of achieving cure for primary and metastatic liver tumours. As few patients qualify to receive these treatments, local ablative therapies are increasingly being used as treatment for primary and metastatic tumours of the liver. Methods: During the period January 2018 to January 2022 we prospectively studied the utility of chemical and thermal ablation ablative therapy in 22 patients with primary and metastatic liver disease. All patients were followed at 1, 3 and 6 months. Results: Percutaneous ethanol injection (PEI) was done in 2 patients. Radiofrequency ablation (RFA) was done in 13 patients [hepatocellular carcinoma (HCC) 8, metastases 5]. With RFA, out of eight HCC patients, complete ablation was seen in 4; 2 patients underwent partial hepatectomy; 2 patients died within a month of ablation due to associated co-morbidities. In 5 patients with metastases, 3 achieved complete ablation; partial hepatectomy and systemic chemotherapy was needed in 1 patient each. With microwave ablation (MA) (n=6; HCC 3, metastases 3), complete ablation was achieved in 3 HCC patients. In patients with metastases, complete ablation was seen in 2 and one patient in addition, underwent transarterial chemoembolization. One patient with metastasis underwent both RFA and MA; complete ablation was achieved; MA was repeated a few months after RFA as new lesion developed. Conclusions: Our study results suggest that chemical and thermal ablation ablative therapies are effective both as palliative and curative in the management of primary and metastatic liver lesions.

S1932 Acute Pancreatitis After Liver Biopsy: Clots or Stones?

Introduction: Percutaneous liver biopsy is a frequently utilized tool in the diagnosis of many liver diseases including metastatic liver lesions. Bleeding complications occur in 1% of cases and hemobilia is rare. Hemobilia causing acute pancreatitis after percutaneous liver biopsy is extremely rare with approximately 20 reported cases in literature. Symptoms include right upper quadrant pain, nausea, jaundice, hematemesis, hematochezia or melena. We present an interesting case of a woman who developed acute pancreatitis secondary to hemobilia after liver biopsy. Case Description/Methods: A 60-year-old female with recurrent high-grade serious peritoneal cancer and recent metastases to liver was admitted for acute pancreatitis. Patient presented with nausea and right upper quadrant pain that started after percutaneous liver biopsy one day prior. Labs notable for Hgb 10.4, lipase > 3000, amylase 3349, total bilirubin 3.6, direct 3.3, AST 631, ALT 482, alkaline phosphatase 240. CT A/P showed diffuse swelling of pancreas with fluid and mesenteric fat stranding suspicious for acute pancreatitis. Given liver enzyme elevation with mixed hepatocellular and cholestasis pattern, abdominal MRI was obtained to evaluate any biliary obstruction. MRI showed mildly prominent CBD at 0.8 cm with debris in distal CBD, cystic duct, and gallbladder indicative of hemorrhagic products. No hematoma noted in the liver parenchyma. Patient underwent ERCP with sphincterotomy and clots were cleared from the duct with balloon sweep (Figure). Discussion: Hemobilia, described as upper GI bleeding within the biliary tree has a reported incidence of less than 0.059% after percutaneous liver biopsy. It can occur within a few hours or several days later, with an average interval of five days. Although rare, hemobilia can lead to acute pancreatitis in a mechanism similar to gallstone pancreatitis. Excessive bleeding and increased clot formation cause obstruction in the biliary tree and impedes drainage from the ampulla which in turn triggers pancreatitis. Diagnosis can be made by ultrasound, angiography, ERCP, or MRCP. Treatment depends on the extent of bleeding and includes conservative management to advanced interventions-hepatic angiography with arterial embolization, ERCP with sphincterotomy or stent placement. Thus, our case highlights importance of recognizing hemobilia as an etiology for acute pancreatitis after percutaneous liver biopsy.Figure 1.: Removal of blood clots from bile duct by balloon sweep via ERCP

S1676 Things Are Not Always What They Seem: A Rare Case of Pancreatic Carcinoma Manifesting Through Cutaneous Metastasis

Introduction: Pancreatic cancer is an aggressive disease that commonly metastasizes to the liver, lung, and peritoneum. Cutaneous metastasis is a rare occurrence with an incidence of only 2.0%. We present a case of metastatic pancreatic adenocarcinoma primarily presenting as a cutaneous nodule. Case Description/Methods: A 50-year-old male was undergoing outpatient evaluation for a raised, left scalp lesion along with neck nodules. Associated symptoms included an unintentional 30lb weight loss. Outpatient CT soft tissue neck revealed numerous necrotic lateral neck lymph nodes, lytic lesion with epidural soft tissue extension at C2-4, and occlusion/thrombosis of the left subclavian, brachiocephalic, and left internal jugular veins (Figure). Given these findings, the patient was referred to the Emergency Department (ED). At time of ED arrival, vital signs were stable along with initial laboratory values. CTA PE study showed no pulmonary embolism but revealed numerous pulmonary and bilateral adrenal nodules, multifocal liver and osseous lesions, and widespread lymphadenopathy. Additionally, CT head demonstrated a left scalp soft tissue lesion. Follow up CT abdomen/pelvis revealed a 2.8 x 2.2 x 1.8 cm ill-defined pancreatic lesion and confirmed widespread metastasis including to the muscles. Additional testing revealed elevated cancer markers with Cancer antigen 19-9 (CA 19-9) of 5418 U/mL and carcinoembryonic antigen (CEA) of 63.8 ng/mL. Pathology from initial scalp lesion biopsy showed fragments of necrotic dermis with small foci of poorly differentiated carcinoma. Biopsies of the right and left neck masses revealed poorly differentiated adenocarcinoma of uncertain primary. Therefore, liver biopsy was performed and confirmed non-small cell carcinoma of pancreatobiliary origin. Further imaging to determine treatment course discovered intracranial metastasis and cervical spine disease resulting in cord compression. Ultimately, the patient underwent 4 out of 10 fractions of palliative radiation to the cervical spine but passed away after transitioning to comfort care one month after diagnosis. Discussion: There are less than 25 documented cases of pancreatic cancer with cutaneous involvement; however, it is even more rare that cutaneous involvement prompts initial diagnosis. The umbilicus is the most common site of cutaneous involvement and is referred to as the Sister Mary Joseph Nodule. Involvement of the soft tissue of the scalp and neck is much less common and poorly documented making this case extremely unique.Figure 1.: Axial contrast enhanced CT of the abdomen shows a 2.8 cm ill-defined hypoattenuating mass in the pancreatic tail (A) with multifocal metastatic liver lesions and bilateral adrenal metastasis (B). Axial CT image of the pelvis shows a metastatic lesion in the right rectus femoris muscle (C). On liver biopsy, H&E, 40X,(S21-41666) revealed high grade carcinoma with vesiculated nuclei, prominent nucleoli (D), CA 19-9 IHC 20X diffuse positivity in tumor cells (E) and CK AE1/3 IHC, 20X, diffusely positivee for pancytokeratin in tumor cells confirming carcinoma (F). Axial CT of the head shows a 2.4 cm nodular left parietal scalp soft tissue lesion (G) which was also seen on clinical examination (H). Biopsy of the scalp lesion (H&E, 40X) demonstrated high grade carcinoma with vesiculated nuclei, prominent nucleoli and mitoses (I), histologically similar to liver biopsy findings.

Patient-Derived Organoids from Colorectal Cancer with Paired Liver Metastasis Reveal Tumor Heterogeneity and Predict Response to Chemotherapy.

There is no effective method to predict chemotherapy response and postoperative prognosis of colorectal cancer liver metastasis (CRLM) patients. Patient-derived organoid (PDO) has become an important preclinical model. Herein, a living biobank with 50 CRLM organoids derived from primary tumors and paired liver metastatic lesions is successfully constructed. CRLM PDOs from the multiomics levels (histopathology, genome, transcriptome and single-cell sequencing) are comprehensively analyzed and confirmed that this organoid platform for CRLM could capture intra- and interpatient heterogeneity. The chemosensitivity data in vitro reveal the potential value of clinical application for PDOs to predict chemotherapy response (FOLFOX or FOLFIRI) and clinical prognosis of CRLM patients. Taken together, CRLM PDOs can be utilized to deliver a potential application for personalized medicine.

Pathological complete response with immunotherapy and brachytherapy to 15 metastatic liver lesions in a single patient.

Materials & methods:High dose rate interstitial brachytherapy (HDR-IBT) treatment plan for 15 metastatic liver lesions in a patient with pancreatic cancer was retrieved and analyzed for liver dose parameters and diaphragm dose. Serial 18F-FDG PET-CT scans were reviewed for disease response assessment and left liver lobe volume. Serial laboratory records were analyzed for liver parameters.Results:Left liver lobe volume increased from 241 cm3 pre-HDR-IBT to estimated 600 cm3 after seven sessions of HDR-IBT. Metabolic complete response (CR) and subsequently pathological CR was confirmed in the right hepatotectomy specimen for all the 15 PET-CT avid lesions treated with HDR-IBT. Maximum diaphragm dose in a single fraction was 82 Gy. The liver parameters were stable and patient did not develop radiation induced liver disease.Discussion:This is the largest reported series of HDR-IBT to liver lesions in a single patient. This first ever reported combined treatment of immunotherapy (IT) and HDR-IBT had likely rendered this patient disease free both at local the liver and systemically. Metabolic CR by PET-CT can be seen as early as 46 days after HDR-IBT. Diaphragm can tolerate very high doses of radiation and repeated treatment.Conclusion:In this patient HDR-IBT for multiple liver lesions with IT is well tolerated. PET-CT can be used for response assessment of HDR-IBT liver. Synergistic effect of IT with HDR-IBT and it’s role as bridging for liver resection has clinical potential and should be further studied in prospective trials.

Is liver resection justified for ovarian sarcoma liver metastases?

Ovarian sarcoma represents an aggressive subtype of ovarian malignancies which is characterized by poor outcomes. However, it seems that applying the principles of radical surgery might increase the long-term outcomes especially if no residual disease is achievable. Even though, most cases will experience a recurrent disease. As expected a significant number of cases will present disseminated lesions and will be therefore submitted to palliative treatment. The aim of the current paper is to present two such cases, the first one being diagnosed with a metachronous metastatic liver lesion while the second one being diagnosed with synchronous liver metastases.