Optimal therapeutic strategies for hepatic metachronous oligometastatic nasopharyngeal carcinoma: Insights from a retrospective study.

Hepatic metachronous oligometastatic nasopharyngeal carcinoma (hmoNPC) exhibits distinct clinical characteristics compared to other types of metastatic NPC. We investigated the optimal therapy for hmoNPC. 160 patients with hmoNPC treated in Sun Yat-sen University Cancer Center between 2010 and 2021 were retrospectively recruited. A total of 56 patients were classified into the local therapy (LT) cohort, 23 into the systemic therapy (ST) cohort and 81 into the combination therapy (LT + ST) cohort. The median PFS was 7.9 months (95% confidence interval [CI]: 4.1-11.9 months) in the LT cohort, 15.5 months (95% CI: 10.5-32.3 months) in the ST cohort, and 31.3 months (95% CI: 20.3 to NA months) in the LT + ST cohort. The median OS was 41.1 months (95% CI: 30.0-54.0 months) in the LT cohort, 50.4 months (95% CI: 41.5 to NA months) in the ST cohort and not reached (NR) (95% CI: 77.3 to NA months) in the LT + ST cohort. Cox analysis was used to construct nomograms to predict patient outcomes. Among patients with no evidence of disease status after LT, the prognosis was significantly better in the LT + ST cohort than LT cohort (median PFS: NR [95% CI: 29.0 to NA months] vs. 20.0 months [95% CI: 10.4 to NA months]). More survival benefits were achieved with platinum-based chemotherapy than oral monotherapy (median PFS: NR [95% CI: 21.7 to NA months] vs. 17.2 months [95% CI: 10.2 to NA months]). Fewer postoperative early progression events were observed in neoadjuvant chemotherapy cohort than in adjuvant chemotherapy cohort (2.78% vs. 18.81%, P = .013). In conclusion, combining neoadjuvant platinum-based chemotherapy and local therapy was the best strategy for patients with hmoNPC.

LINC00858 facilitates formation of hepatic metastases from colorectal cancer via regulating the miR-132-3p/IGF2BP1 axis.

Hepatic metastasis is a major cause of colorectal cancer (CRC)-related deaths. Presently, the role of long non-coding RNAs (lncRNAs) in hepatic metastases from CRC is elusive. We dissected possible interplay between LINC00858/miR-132-3p/IGF2BP1 via bioinformatics approaches. Subsequently we analyzed mRNA expression of LINC00858, miR-132-3p and IGF2BP1 through qRT-PCR. Western blot was used to detect protein expression of IGF2BP1. RNA immunoprecipitation chip and dual-luciferase assay validated interaction between LINC00858 and miR-132-3p, as well as miR-132-3p and IGF2BP1. Cell viability, invasion, and migration were examined via CCK-8, colony formation, transwell and wound healing assays. Effect of LINC00858 on CRC hepatic metastases was validated via in vivo assay. Upregulated LINC00858 and IGF2BP1, and downregulated miR-132-3p were predicted in tumor tissues of patients with hepatic metastases from CRC. There were targeting relationships between LINC00858 and miR-132-3p, as well as miR-132-3p and IGF2BP1. Besides, LINC00858 facilitated progression of CRC cells. Rescue assay suggested that silencing LINC00858 suppressed CRC cell progression, while further silencing miR-132-3p or overexpressing IGF2BP1 reversed such effects. LINC00858 could facilitate CRC tumor growth and hepatic metastases. LINC00858 induced CRC hepatic metastases via regulating miR-132-3p/ IGF2BP1, and this study may deliver a new diagnostic marker for the disease.

Prognostic value of creatine kinase (CK)-MB to total-CK ratio in colorectal cancer patients after curative resection.

OBJECTIVES: This study aimed to evaluate the prognostic significance of postoperative Creatine Kinase type M and B (CK-MB) to total Creatine Kinase (CK) ratio (CK-MB/CK) in colorectal cancer (CRC) patients after radical resection. METHODS: This was a single-center retrospective cohort analysis. Subjects were stage I-III CRC patients hospitalized in Sichuan Cancer Hospital from January 2017 to May 2021. Patients were divided into abnormal group and normal group according to whether the CK-MB/CK ratio was abnormal after surgery. Through a comparative analysis of clinical data, laboratory test results, and prognosis differences between the two groups, we aimed to uncover the potential relationship between abnormal CK-MB > CK results and CRC patients. To gauge the impact of CK-MB/CK on overall survival (OS) and disease-free survival (DFS), we employed the multivariable COX regression and LASSO regression analysis. Additionally, Spearman correlation analysis, logistic regression, and receiver-operating characteristic (ROC) curve analysis were conducted to assess the predictive value of the CK-MB/CK ratio for postoperative liver metastasis. RESULTS: Cox regression analysis revealed that the CK-MB/CK ratio was a stable risk factors for OS (HR = 3.82, p < 0.001) and DFS (HR = 2.31, p < 0.001). To distinguish hepatic metastases after surgery, the ROC area under the curve of CK-MB/CK was 0.697 (p < 0.001), and the optimal cut-off value determined by the Youden index was 0.347. CONCLUSIONS: Postoperative abnormal CK-MB/CK ratio predicts worse prognosis in CRC patients after radical resection and serves as a useful biomarker for detecting postoperative liver metastasis.

Thrombus formation in the suprahepatic inferior vena cava after microwave ablation in patients with hepatic metastasis: a case report.

BACKGROUND: Microwave ablation (MWA) via ultrasound guidance is an important tool in the treatment of liver metastases. The most common postoperative complications are abdominal hemorrhage and bile leakage, whereas thrombosis in the suprahepatic inferior vena cava (IVC) is very rare, and clinical management is very difficult when the head end of the thrombus reaches the right atrium. CASE PRESENTATION: This is a case report of a 52-year-old man with hepatic metastasis 21 months after radical resection of rectal cancer. After chemotherapy combined with targeted therapy, metastasis in segment IV (S4) of the liver was treated with microwave ablation. Two months after treatment, the hepatic metastasis in S4 showed a microwave ablation zone on MRI.Enhanced MRI showed venous thrombosis located in the left hepatic vein and IVC, and the head of the thrombus reached the right atrium. After two weeks of anticoagulation and thrombolytic treatment, the follow-up MRI showed that the venous thrombus had nearly disappeared. CONCLUSION: When liver metastases are close to the hepatic vein, clinicians should pay attention to the occurrence of hepatic vein and IVC thrombosis following MWA; through early diagnosis and anticoagulation, pulmonary thromboembolism (PTE) can be minimized.

CT-based radiomics to distinguish progressive from stable neuroendocrine liver metastases treated with somatostatin analogues: an explorative study.

BACKGROUND: Accurate response evaluation in patients with neuroendocrine liver metastases (NELM) remains a challenge. Radiomics has shown promising results regarding response assessment. PURPOSE: To differentiate progressive (PD) from stable disease (SD) with radiomics in patients with NELM undergoing somatostatin analogue (SSA) treatment. MATERIAL AND METHODS: A total of 46 patients with histologically confirmed gastroenteropancreatic neuroendocrine tumors (GEP-NET) with ≥1 NELM and ≥2 computed tomography (CT) scans were included. Response was assessed with Response Evaluation Criteria in Solid Tumors (RECIST1.1). Hepatic target lesions were manually delineated and analyzed with radiomics. Radiomics features were extracted from each NELM on both arterial-phase (AP) and portal-venous-phase (PVP) CT. Multiple instance learning with regularized logistic regression via LASSO penalization (with threefold cross-validation) was used to classify response. Three models were computed: (i) AP model; (ii) PVP model; and (iii) AP + PVP model for a lesion-based and patient-based outcome. Next, clinical features were added to each model. RESULTS: In total, 19 (40%) patients had PD. Median follow-up was 13 months (range 1-50 months). Radiomics models could not accurately classify response (area under the curve 0.44-0.60). Adding clinical variables to the radiomics models did not significantly improve the performance of any model. CONCLUSION: Radiomics features were not able to accurately classify response of NELM on surveillance CT scans during SSA treatment.

Tumor attachment to Major intrahepatic vascular for Colorectal liver metastases.

BACKGROUND: Colorectal liver metastases attached major intrahepatic vessels has been considered to be a risk factor for survival outcome after liver resection. The present study aimed to clarify the outcomes of R1 surgery (margin < 1 mm) in CRLM patients, distinguishing parenchymal margin R1 and attached to major intrahepatic vessels R1. METHODS: In present study, 283 CRLM patients who were evaluated to be attached to major intrahepatic vessels initially and underwent liver resection following preoperative chemotherapy. They were assigned to two following groups: R0 (n = 167), R1 parenchymal (n = 58) and R1 vascular (n = 58). The survival outcomes and local recurrence rates were analyzed in each group. RESULTS: Overall, 3- and 5-year overall survival rates after liver resection were 53.0% and 38.2% (median overall survival 37 months). Five-year overall survival was higher in patients with R0 than parenchymal R1 (44.9%% vs. 26.3%, p = 0.009), whereas there was no significant difference from patients with vascular R1 (34.3%, p = 0.752). In the multivariable analysis, preoperative chemotherapy > 4 cycles, clinical risk score 3-5, RAS mutation, parenchymal R1 and CA199 > 100 IU/ml were identified as independent predictive factors of overall survival (p < 0.05). There was no significant difference for local recurrence among three groups. CONCLUSION: Parenchymal R1 resection was independent risk factor for CRLM. Vascular R1 surgery achieved survival outcomes equivalent to R0 resection. Non-anatomic liver resection for CRLM attached to intrahepatic vessels might be pursued to increase patient resectability by preoperative chemotherapy.

The impact of AMIGO2 on prognosis and hepatic metastasis in gastric cancer patients.

BACKGROUND: Gastric cancer (GC) is one of the most common malignancies, and the liver is the most common site of hematogenous metastasis of GC. AMIGO2 is a type I transmembrane protein that has been implicated in tumour cell adhesion in adenocarcinomas; however, its importance in GC remains undetermined. METHODS: We analyzed AMIGO2 expression by immunohistochemistry using the specific monoclonal antibody for human AMIGO2 in 128 patients who underwent GC surgery to evaluate its relationship between various metastatic and clinical outcomes in GC. RESULTS: Immunohistochemistry revealed that AMIGO2 expression was an independent prognostic factor for overall survival, disease-specific survival, and liver metastasis in GC patients. CONCLUSIONS: This study showed that AMIGO2 is induced in GC tissues and can mediate hepatic metastasis. Determining AMIGO2 expression in GC will help predict patient prognosis and the incidence of liver metastasis.

The role of liver resection in metastatic nephroblastoma: a systematic review and Meta-regression analysis.

BACKGROUND: The impact of hepatic resection for liver metastases (LM) on the survival of pediatric patients with Wilms' tumor (WT) is unclear. So far, there is a lack of studies investigating the best suited treatment for patients with WTLM, and the role of liver resection has rarely been investigated. Thus, the development of evidence-based guidelines concerning indications of liver resection for WTLM remains difficult. AIM: To investigate the role of surgery in the therapy of WTLM. All available data on liver resections and subgroup outcomes of patients with WTLM are analyzed. Main research question is whether liver resection improves survival rates of patients with WTLM compared to non-surgical treatment. METHODS: A systematic literature search of MEDLINE, Web of Science, and Central provided the basis for this PRISMA-compliant systematic review. For the main analysis (I), all studies reporting on surgical treatment of pediatric WTLM were included. To provide a representative overview of the general outcome of WTLM patients, in analysis II all studies with cohorts of at least five WTLM patients, regardless of the kind of treatment, were reviewed and analyzed. A Multiple meta-regression model was applied to investigate the impact liver resection on overall survival. RESULTS: 14 studies with reports of liver resection for WTLM were found (Analysis I). They included a total of 212 patients with WTLM, of which 93 underwent a liver resection. Most studies had a high risk of bias, and the quality was heterogenous. For the analysis II, eight studies with subgroups of at least five WTLM patients were found. The weighted mean overall survival (OS) of WTLM patients across the studies was 55% (SD 29). A higher rate of liver resection was a significant predictor of better OS in a multiple meta-regression model with 4 covariates (I2 29.43, coefficient 0.819, p = 0.038). CONCLUSIONS: This is the first systematic review on WTLM. Given a lack of suited studies that specifically investigated WTLM, ecological bias was high in our analyses. Generating evidence is complicated in rare pediatric conditions and this study must be viewed in this context. Meta-regression analyses suggest that liver resection may improve survival of patients with WTLM compared to non-surgical treatment. Especially patients with persisting disease after neoadjuvant chemotherapy but also patients with metachronous LM seem to benefit from resection. Complete resection of LM is vital to achieve higher OS. Studies that prospectively investigate the impact of surgery on survival compared to non-surgical treatment for WTLM are highly needed to further close the current evidence gap. STUDY REGISTRATION: PROSPERO 2021 CRD42021249763  https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=249763 .

Clinical outcomes following colorectal resection of colorectal cancer with simultaneous hepatic and pulmonary metastases at the time of diagnosis.

PURPOSE: There are no established treatment strategies for patients with hepatic and pulmonary metastases at the time of primary colorectal cancer (CRC) diagnosis. This study assessed patients undergoing complete resection of primary CRC and hepatic and pulmonary metastases, to evaluate long-term outcomes and clarify clinicopathological factors associated with failure of complete resection. METHODS: This retrospective analysis enrolled patients at Shizuoka Cancer Center between 2002 and 2018 who underwent colorectal resection with curative intent for primary CRC with hepatic and pulmonary metastases. The curative resection (CR) group comprised patients who underwent complete resection of the primary tumor and metastatic lesions, and the non-curative resection (Non-CR) group consisted of those in whom resection of the metastatic lesions was not performed. Univariate and multivariate analyses were conducted to determine clinicopathological factors associated with non-curative resection. RESULTS: Of 26 total patients, the CR and Non-CR groups consisted of 14 (54%) and 12 patients (46%), respectively. In the CR group, the 3-year overall and relapse-free survival rates were 92.9% and 28.6%, respectively. Multivariate analysis showed that pathological stage T4 (odds ratio 8.58, 95% confidence interval 1.13-65.20, p = 0.04) was independently associated with non-curative resection. CONCLUSION: The percentage of patients undergoing complete resection of primary CRC and metastatic lesions was 56%, and the 3-year OS rate was 92.9%. Resection of primary CRC and metastatic lesions was considered to be appropriate in this population, and pathological stage T4 tumor was associated with incomplete resection of metastatic tumors.

Role of Fibroblast Growth Factors in the Crosstalk of Hepatic Stellate Cells and Uveal Melanoma Cells in the Liver Metastatic Niche.

Hepatic metastasis is the critical factor determining tumor-associated mortality in different types of cancer. This is particularly true for uveal melanoma (UM), which almost exclusively metastasizes to the liver. Hepatic stellate cells (HSCs) are the precursors of tumor-associated fibroblasts and support the growth of metastases. However, the underlying mechanisms are widely unknown. Fibroblast growth factor (FGF) signaling is dysregulated in many types of cancer. The aim of this study was to analyze the pro-tumorigenic effects of HSCs on UM cells and the role of FGFs in this crosstalk. Conditioned medium (CM) from activated human HSCs significantly induced proliferation together with enhanced ERK and JNK activation in UM cells. An in silico database analysis revealed that there are almost no mutations of FGF receptors (FGFR) in UM. However, a high FGFR expression was found to be associated with poor survival for UM patients. In vitro, the pro-tumorigenic effects of HSC-CM on UM cells were abrogated by a pharmacological inhibitor (BGJ398) of FGFR1/2/3. The expression analysis revealed that the majority of paracrine FGFs are expressed by HSCs, but not by UM cells, including FGF9. Furthermore, the immunofluorescence analysis indicated HSCs as a cellular source of FGF9 in hepatic metastases of UM patients. Treatment with recombinant FGF9 significantly enhanced the proliferation of UM cells, and this effect was efficiently blocked by the FGFR1/2/3 inhibitor BGJ398. Our study indicates that FGF9 released by HSCs promotes the tumorigenicity of UM cells, and thus suggests FGF9 as a promising therapeutic target in hepatic metastasis.

Comparison of Diagnostic Performance and Confidence between Contrast-Enhanced Computed Tomography Scan and Non-Contrast-Enhanced Computed Tomography Plus Abdomen Ultrasound for Hepatic Metastasis in Patients with Breast Cancer.

Background: The purpose of this study was to compare the performance between noncontrast-enhanced computed tomography (NECT) plus abdominal ultrasound (US) (NECT + US) with contrast-enhanced computed tomography (CECT) for the detection of hepatic metastasis in breast cancer patient with postsurgical follow-up. Methods: A total of 1470 patients without already diagnosed hepatic metastasis were included. All patients underwent US and multiphase CECT including the NECT. Independent reviewers analyzed images obtained in four settings, namely, abdominal US, NECT, NECT + US, and CECT and recorded liver metastases using a 5-grade scale of diagnostic confidence. Sensitivity, specificity (diagnostic performance), and area under the receiver operating characteristic curve (AUC, diagnostic confidence) were calculated. Interoperator agreement was calculated using the kappa test. Results: Reference standards revealed no metastases in 1108/1470 patients, and metastasis was detected in 362/1470 patients. Abdominal US (P < 0.01) and NECT (P = 0.01) significantly differed from CECT, but NECT + US did not significantly differ from CECT in terms of sensitivity (P = 0.09), specificity (P = 0.5), and AUC (P = 0.43). After an additional review of abdominal US, readers changed the diagnostic confidence scores of 106 metastatic lesions diagnosed using NECT. Interobserver agreements were good or very good in all four settings. Additional review of abdominal US with NECT allowed a change in the therapeutic plan of 108 patients. Conclusion: Abdominal US + NECT showed better diagnostic performance for the detection of hepatic metastases than did NECT alone; its diagnostic performance and confidence were similar to those of CECT.

Clinical features and imaging manifestations of retinoblastoma with hepatic metastasis.

Clinical data of five patients with hepatic metastases of retinoblastoma were analyzed retrospectively (two had bilateral tumors three had unilateral intraocular tumors). On computed tomography, multiple and single low-density foci were observed. Four patients had tumor remission, and one showed no response after chemotherapy. Three patients who underwent enucleation were at high risk for extensive choroidal invasion. Central nervous system and bone metastases occurred in all five patients. Neuron-specific enolase and lactate dehydrogenase levels were significantly elevated in all patients. Two patients died (not from hepatic metastasis). Three patients (one with tumor progression and two with shorter courses) are continuing treatment.

Hepatic metastasis from perianal Paget's disease without identified underlying carcinoma: a case report.

BACKGROUND: Perianal Paget's disease (PPD) is a rare malignancy, often associated with an underlying adenocarcinoma and a poor prognosis. CASE PRESENTATION: A 69-year-old female was presented with a history of perianal pruritus for 6 months and enlarged inguinal lymph nodes in the left side. Paget cells were confirmed by pathology after a wide excision of perianal skin. Radiotherapy was performed covering the bilateral inguinal lymphatic drainage area. Hepatic metastasis was found 8 months after surgery. Hepatic artery embolization (HAE) and high-intensity focused ultrasound therapy (HIFU) were performed successively. However, hepatic metastasis happened again 3 months later. Ultrasound-guided percutaneous radiofrequency ablation (PRFA) was carried out and various means of inspection could not identify the primary tumor. In the case of rapid progression of the tumor, we gave the patient chemotherapy regimens of XELOX. After 4 cycles of chemotherapy, the tumor marker went down continuously and the hepatic metastasis stayed stable. CONCLUSIONS: Hepatic metastasis from perianal Paget's disease without identified underlying carcinoma may benefit from XELOX on the basis of adenocarcinoma.

[Application of MRI-based Radiomics Models in the Assessment of Hepatic Metastasis of Rectal Cancer].

OBEJECTIVE: To explore the clinical value of using radiomics models based on different MRI sequences in the assessment of hepatic metastasis of rectal cancer. METHODS: 140 patients with pathologically confirm edrectal cancer were included in the study. They underwent baseline magnetic resonance imaging (MRI) between April 2015 and May 2018 before receiving any treatment. According to the results of liver biopsy, surgical pathology, and imaging, patients were put into two groups, the patients with hepatic metastasis and those without. T2 weighted images (T2WI), diffusion weighted images (DWI) and apparent diffusion coefficient (ADC) images were used to draw the region of interest (ROI) of primary lesions on consecutive slices on ITK-SNAP. 3-D ROIs were generated and loaded into Artificial Intelligent Kit for extraction of radiomics features and 396 features were extracted for each sequence. The feature data were preprocessed on Python and the samples were oversampled, using Support Vector Machine-Synthetic Minority Over-Sampling Technique (SVM-SMOTE) to balance the number of samples in the group with liver metastasis and the group with no liver metastasis at the end of the follow-up. Then, the samples were divided into the training cohort and the test cohort at a ratio of 2∶1. The logistic regression models were developed with selected radionomic features on R software. The receiver operating characteristics (ROC) curves and calibration curves were used to evaluate the performance of the models. RESULTS: In total, 52 patients with liver metastasis and 88 patients without liver metastasis at the end of follow-up were enrolled. Carcinoembryonic antigen (CEA) and T stage and N stage evaluated on the MRI images showed statistically significant difference between the two groups ( P<0.05). After data preprocessing and selecting, except for 17 non-radiomic features, the model combining T2WI, DWI and ADC features, the model of T2WI features alone, the model of DWI features alone and the model of ADC features alone were developed with 32 features, 10 features, 30 features and 15 features, respectively. The combined model (T2WI+DWI+ADC), the T2WI model, and the ADC model can assess hepatic metastasis accurately, with the area under curve ( AUC) on the train set reaching 93.5%, 89.2%, 90.6% and that of the test set reaching 80.8%, 80.5%, 81.4%, respectively. The combined model did not show a higher AUC than those of the T2WI and ADC alone models. Model based on DWI features has a slightly insufficient AUC of 90.3% in the train set and 75.1% in the test set. The calibration curve showed the smallest fluctuation in the combined model, which is closest fit to the diagonal reference line. The fluctuation in the three independent data set models were similar. The calibration curves of all the four models showed that as the risk increased, the prediction of the models turned from an underestimation to an overestimating the risk. In brief, the combined model showed the best performance, with the best fit to the diagonal reference line in calibration curve and high AUC comparable to the AUC of the T2WI model and ADC model. The performance of T2WI and ADC alone models were second to that of the combined model, while the DWI alone model showed relatively poor performance. CONCLUSION: Radiomics models based on MRI could be effectively used in assessing liver metastasis in rectal cancer, which may help determine clinical staging and treatment.

Verification of EZH2 as a druggable target in metastatic uveal melanoma.

BACKGROUND: Hepatic metastasis develops in ~ 50% of uveal melanoma (UM) patients with no effective treatments. Although GNAQ/GNA11 mutations are believed to confer pathogenesis of UM, the underlying mechanism of liver metastasis remains poorly understood. Given that profound epigenetic evolution may occur in the long journey of circulating tumor cells (CTCs) to distant organs, we hypothesized that EZH2 endowed tumor cells with enhanced malignant features (e.g., stemness and motility) during hepatic metastasis in UM. We aimed to test this hypothesis and explore whether EZH2 was a therapeutic target for hepatic metastatic UM patients. METHODS: Expression of EZH2 in UM was detected by qRT-PCR, Western blotting and immunohistochemistry staining. Proliferation, apoptosis, cancer stem-like cells (CSCs) properties, migration and invasion were evaluated under circumstances of treatment with either EZH2 shRNA or EZH2 inhibitor GSK126. Antitumor activity and frequency of CSCs were determined by xenografted and PDX models with NOD/SCID mice. Hepatic metastasis was evaluated with NOG mice. RESULTS: We found that EZH2 overexpressed in UM promoted the growth of UM; EZH2 increased the percentage and self-renewal of CSCs by miR-29c-DVL2-ß-catenin signaling; EZH2 facilitates migration and invasion of UM cells via RhoGDIγ-Rac1 axis. Targeting EZH2 either by genetics or small molecule inhibitor GSK126 decreased CSCs and motility and abrogated the liver metastasis of UM. CONCLUSIONS: These findings validate EZH2 as a druggable target in metastatic UM patients, and may shed light on the understanding and interfering the complicated metastatic process.

Incidental hepatic tuberculosis during planned resection of locally advanced ampullary carcinoma: a case report.

BACKGROUND: Tuberculosis (TB) is classified according to the site of disease as pulmonary or extrapulmonary. Extrapulmonary TB is less common than its counterpart in which it can be found anywhere in the body including the liver. Similar to ampullary carcinoma, TB liver can manifest with jaundice and deranged liver function tests, particularly in the obstructed biliary systems. CASE PRESENTATION: A 43-year-old gentleman with locally advanced ampullary carcinoma was noticed to have multiple suspicious liver nodules intraoperatively during curative ampulla resection. The surgery was then abandoned after a biopsy. The histology was consistent with chronic granulomatous inflammation. He was then subjected to a Whipple pancreaticoduodenectomy procedure after initiation of anti-tubercular treatment. He recovered well with no evidence of tumour recurrence and worsening TB. CONCLUSIONS: A high index of suspicion and quick decision making can help to diagnose a possible extrapulmonary TB masquerading as a malignant disease in a patient with curative intention of ampullary carcinoma.

A phenotypical map of disseminated hepatocellular carcinoma suggests clonal constraints in metastatic sites.

AIMS: Access to tissue in patients with hepatocellular carcinoma (HCC) is limited compared to other malignancies, particularly at advanced stages. This has precluded a thorough characterisation of molecular drivers of HCC dissemination, particularly in relation to distant metastases. Biomarker assessment is restricted to early stages, and paired primary-metastatic comparisons between samples from the same patient are difficult. METHODS AND RESULTS: We report the evaluation of 88 patients with HCC who underwent autopsy, including multiregional sampling of primary and metastatic sites totalling 230 nodules analysed. The study included morphological assessment, immunohistochemistry and mutation status of the TERT promoter, the most frequently mutated gene in HCC. We confirm a strong predilection of HCC for lung dissemination, including subclinical micrometastases (unrecognised during imaging and macroscopic examinations) in 30% of patients with disseminated disease. Size of dominant tumour nodule; multinodularity; macrovascular invasion; high histological, nuclear and architectural grades; and cellular crowding were associated with the presence of extrahepatic metastasis. Among the immunohistochemistry markers tested, metastatic nodules had significantly higher K19 and EpCAM expression than primary liver tumours. Morphological and immunohistochemical features showed that metastatic HCC could be traced back to the primary tumour, sometimes to a specific hepatic nodule. CONCLUSIONS: This study suggests limited heterogeneity in metastatic sites compared to primary tumour sites.

Trends and Outcomes of Synchronous Resection of Colorectal Metastasis in the Modern Era-Analysis of Targeted Hepatic NSQIP Database.

BACKGROUND: Previous studies using the NSQIP database to study hepatectomies lacked hepatic specific variables and outcomes. We used the targeted NSQIP hepatectomy database to examine the nationwide trend and the safety profile of synchronous liver and colorectal resection compared with hepatectomy alone for colorectal liver metastasis. METHODS: The targeted NSQIP hepatectomy database from 2014 was used to study patients who underwent hepatectomy for diagnosis of adenocarcinoma of the colon and rectum. RESULTS: Of the 3064 hepatic resections in the database, 1138 cases were performed for colorectal metastasis. Of these, 1040 were liver-alone surgery and 98 were synchronous liver and colorectal resection. Most (58.7%) patients received neoadjuvant therapy. The rate of neoadjuvant therapy, intraoperative ablation, biliary reconstruction, and the use of minimally invasive technique were similar between the two groups. The overall 30-d mortality in this cohort was low (1.1%). While the mortality rate in the synchronous group was similar to liver-only group (3.1% versus 0.9%, P = 0.077). The rate of liver failure (3.3% versus 4.1%, P = 0.722) and biliary leak (5.3% versus 9.6%, P = 0.084) were similar between the two groups. However, the rate of major complications was higher on multivariable analyses (25.5% versus 12.1%, OR 2.5, 95% CI 1.5-4.1, P < 0.001) for the synchronous group. CONCLUSIONS: Hepatic resection for colorectal metastasis in the modern era has low short-term mortality. While synchronous resection was associated with a higher incidence of major complications, liver-specific complications did not increase with synchronous resection.

Focal Liver Uptake on FDG PET/CT Without CT Correlate: Utility of MRI in the Evaluation of Patients With Known Malignancy.

OBJECTIVE. The purpose of this study was to determine the significance and utility of MRI in evaluation of focal hepatic uptake on FDG PET/CT without a CT correlate in patients with known malignancy. MATERIALS AND METHODS. In this retrospective study, we identified 36 of 1851 patients between 2005 and 2012 with known malignancy (19 women, 17 men; mean age, 56.1 years old) who had focal hepatic uptake on FDG PET/CT without a CT correlate and follow-up MRI within 100 days for assessment of uptake. Two radiologists reviewed the FDG PET/CT images together, reached consensus about presence of focal hepatic uptake, and measured maximum standardized uptake value (SUVmax) of the focal uptake and background liver. MR images were then reviewed to identify any correlate. Follow-up imaging and histopathologic data were reviewed to confirm or refute metastasis. Statistical correlation between intensity of FDG uptake and presence of focal lesions on MRI was performed. RESULTS. Fifty sites of focal hepatic uptake without CT correlate were identified. The median SUVmax was 4.1 (range, 2.1-10.1), whereas the ratio of median SUVmax of the hepatic lesion to that of normal parenchyma was 1.3 (range, 0.98-2.6). MRI confirmed focal lesions in 26 of 50 sites (52%). Seventy-seven percent of cases of hepatic uptake with an MRI correlate (20/26) were confirmed as metastatic disease (six cases at histopathology). Therefore, 40% of cases of hepatic uptake without a CT correlate (20/50) were metastases. We found no statistically significant difference in the SUVmax of hepatic lesions and SUVmax ratio between the groups with and without an MRI correlate (median SUVmax = 3.85 vs 4.2, p = 0.5; SUVmax ratio = 1.32 vs 1.31, p = 0.97) as well as between the groups with the final diagnosis of benign lesions and metastasis (SUVmax = 4.05 vs 3.95, p = 0.64; SUVmax ratio = 1.31 vs 1.32, p = 0.91). CONCLUSION. More than half of the cases of focal hepatic uptake on PET/CT without a CT correlate had an MRI correlate in our study, and more than 75% of these lesions were metastases, regardless of SUVmax.

Retinoblastoma binding protein 4 up-regulation is correlated with hepatic metastasis and poor prognosis in colon cancer patients.

BACKGROUND: Retinoblastoma binding protein 4 (RBBP4) plays an essential role in the development of multiple cancers. However, its relationship with prognosis in colon cancer and colon cancer hepatic metastasis has not been elucidated. The aim of this study was to explore the relationship between RBBP4 expression and prognosis of colon cancer patients and to evaluate RBBP4 as a new prognostic marker in these patients. METHODS: Eighty colon cancer patients underwent surgical resection of the colon were enrolled. Among them, forty colon cancer patients suffered with hepatic metastasis. The colon cancer tissues, para-colon cancer tissues, and hepatic metastatic cancer tissues were collected from the pathological department for further analysis. The expression of RBBP4 proteins was examined by immunohistochemistry and correlated with clinicopathological parameters. The Cancer Genome Atlas (TCGA) database was used to validate the expression and explore its relationship with clinical characteristics. RESULTS: RBBP4 was up-regulated in the colon cancer tissues compared with the para-colon cancer tissues. The analysis of TCGA database verified the upregulation of RBBP4 in the colon cancer tissues and RBBP4 overexpression was correlated with nerve invasion and poor outcomes of chemotherapy. Moreover, the positive rate of RBBP4 expression in 40 colon cancer patients with hepatic metastasis was higher in the hepatic metastatic cancer tissues (39/40, 97.5%) than in the colon cancer tissues (26/40, 65.0%). Our clinicopathological analysis showed that RBBP4 expression was significantly correlated with vascular invasion, hepatic metastasis, and lymph node involvement (all P < 0.05). Additionally, the survival analysis demonstrated that RBBP4 over-expression was correlated with poor prognosis. CONCLUSIONS: RBBP4 was upregulated in the colon cancer. RBBP4 may be a novel predictor for poor prognosis of colon cancer and colon cancer hepatic metastasis.