Liver Lymphoma Research Articles

Primary hepatic diffuse large B- cell lymphoma mimicking cholangiocarcinoma

Primary lymphoma of liver is a rare malignancy with non-specific clinical features and tumor markers. The presentation and imaging features may be indistinguishable from other hepatic malignant lesions. Pathological diagnosis is the gold standard, and early detection is essential to choose the treatment modality. Here, we share an interesting case of Primary Diffuse Large B cell lymphoma of liver and its imaging findings on Computed tomography (CT), Magnetic Resonance Imaging (MRI) and F-18 FDG PET/CT.

The contribution of second primary cancers to the mortality of patients with a first primary breast cancer

PurposeSecond primary cancers (SPCs) are estimated to affect nearly 5% of patients with breast cancer within 10 years of their diagnosis. This study aimed to estimate the contribution of SPCs to the mortality of patients with a breast first primary cancer (FPC).MethodsA population-based cohort of 17,210 patients with a breast FPC diagnosed between 2000 and 2010 was followed for SPCs (31/12/2015) and vital status (30/06/2021). Patients diagnosed with an SPC (265 synchronous and 897 metachronous, ≤ 1 and > 1 year after the FPC, respectively) were matched (1:3, by five-year age group and year of breast FPC diagnosis) to those without an SPC and alive when the corresponding SPC was diagnosed.ResultsSignificantly higher hazards of death were found among patients with an SPC [hazard ratio of 1.56, 95% confidence interval (CI) 1.29–1.89 for synchronous SPCs; and 2.85, 95%CI 2.56–3.17 for metachronous SPCs] compared to patients with a breast FPC only. Estimates were higher for synchronous lung, stomach, non-Hodgkin lymphoma and breast SPCs, and metachronous liver, stomach, ovary, lung, rectum, corpus uteri, colon, breast, and non-Hodgkin lymphoma SPCs. The 15-year cumulative mortality was 59.5% for synchronous SPCs and 68.7% for metachronous SPCs, which was higher than in patients with a breast FPC only (43.6% and 44.8%, respectively).ConclusionsIn Northern Portugal, patients with an SPC following a breast FPC have a higher mortality compared with patients with a breast FPC only.

A multi-instance tumor subtype classification method for small PET datasets using RA-DL attention module guided deep feature extraction with radiomics features

Background:Positron emission tomography (PET) is extensively employed for diagnosing and staging various tumors, including liver cancer, lung cancer, and lymphoma. Accurate subtype classification of tumors plays a crucial role in formulating effective treatment plans for patients. Notably, lymphoma comprises subtypes like diffuse large B-cell lymphoma and Hodgkin’s lymphoma, while lung cancer encompasses adenocarcinoma, small cell carcinoma, and squamous cell carcinoma. Similarly, liver cancer consists of subtypes such as cholangiocarcinoma and hepatocellular carcinoma. Consequently, the subtype classification of tumors based on PET images holds immense clinical significance. However, in clinical practice, the number of cases available for each subtype is often limited and imbalanced. Therefore, the primary challenge lies in achieving precise subtype classification using a small dataset. Method:This paper presents a novel approach for tumor subtype classification in small datasets using RA-DL (Radiomics-DeepLearning) attention. To address the limited sample size, Support Vector Machines (SVM) is employed as the classifier for tumor subtypes instead of deep learning methods. Emphasizing the importance of texture information in tumor subtype recognition, radiomics features are extracted from the tumor regions during the feature extraction stage. These features are compressed using an autoencoder to reduce redundancy. In addition to radiomics features, deep features are also extracted from the tumors to leverage the feature extraction capabilities of deep learning. In contrast to existing methods, our proposed approach utilizes the RA-DL-Attention mechanism to guide the deep network in extracting complementary deep features that enhance the expressive capacity of the final features while minimizing redundancy. To address the challenges of limited and imbalanced data, our method avoids using classification labels during deep feature extraction and instead incorporates 2D Region of Interest (ROI) segmentation and image reconstruction as auxiliary tasks. Subsequently, all lesion features of a single patient are aggregated into a feature vector using a multi-instance aggregation layer. Result:Validation experiments were conducted on three PET datasets, specifically the liver cancer dataset, lung cancer dataset, and lymphoma dataset. In the context of lung cancer, our proposed method achieved impressive performance with Area Under Curve (AUC) values of 0.82, 0.84, and 0.83 for the three-classification task. For the binary classification task of lymphoma, our method demonstrated notable results with AUC values of 0.95 and 0.75. Moreover, in the binary classification task of liver tumor, our method exhibited promising performance with AUC values of 0.84 and 0.86. Conclusion:The experimental results clearly indicate that our proposed method outperforms alternative approaches significantly. Through the extraction of complementary radiomics features and deep features, our method achieves a substantial improvement in tumor subtype classification performance using small PET datasets.

Comments and illustrations of the WFUMB CEUS liver guidelines: Rare malignant hematological liver lesions.

Diagnosing rare hematological malignancies in the liver is often challenging owing to their infrequency, and confirmation generally necessitates histological examination. Due to the rarity of these lesions, there are limited data concerning theirappearance on ultrasound and, specifically, contrast-enhanced ultrasound. In this review, we describe the pathological andultrasound features of several hematological malignant liver lesions, including lymphoma of the liver and chloroma. Furthermore, two specific forms of liver lymphoma are described: mucosa-associated lymphoid tissue (MALT) lymphoma andplasmacytoma of the liver.

Suppression of Innate Immunity by the Hepatitis C Virus (HCV): Revisiting the Specificity of Host-Virus Interactive Pathways.

The hepatitis C virus (HCV) is a major causative agent of hepatitis that may also lead to liver cancer and lymphomas. Chronic hepatitis C affects an estimated 2.4 million people in the USA alone. As the sole member of the genus Hepacivirus within the Flaviviridae family, HCV encodes a single-stranded positive-sense RNA genome that is translated into a single large polypeptide, which is then proteolytically processed to yield the individual viral proteins, all of which are necessary for optimal viral infection. However, cellular innate immunity, such as type-I interferon (IFN), promptly thwarts the replication of viruses and other pathogens, which forms the basis of the use of conjugated IFN-alpha in chronic hepatitis C management. As a countermeasure, HCV suppresses this form of immunity by enlisting diverse gene products, such as HCV protease(s), whose primary role is to process the large viral polyprotein into individual proteins of specific function. The exact number of HCV immune suppressors and the specificity and molecular mechanism of their action have remained unclear. Nonetheless, the evasion of host immunity promotes HCV pathogenesis, chronic infection, and carcinogenesis. Here, the known and putative HCV-encoded suppressors of innate immunity have been reviewed and analyzed, with a predominant emphasis on the molecular mechanisms. Clinically, the knowledge should aid in rational interventions and the management of HCV infection, particularly in chronic hepatitis.

Sex differences in cancer incidence among solid organ transplant recipients.

Males have 2-3-fold greater risk of cancer than females at most shared anatomic sites, possibly reflecting enhanced immune surveillance against cancer in females. We examined whether these sex differences remained among immunocompromised adults. Using the Transplant Cancer Match (TCM) study, we estimated the male-to-female incidence rate ratio in TCM (M:F IRRTransplant) for 15 cancer sites diagnosed between 1995 and 2017 using Poisson regression. Male to female IRRs in the general population (M:F IRRGP) were calculated using expected cancer counts from the Surveillance, Epidemiology, and End Results Program, standardized to the transplant population on age, race and ethnicity, and diagnosis year. Male to female IRRs were compared using a chi-square test. Among 343 802 solid organ transplants, 211 206 (61.4%) were among men and 132 596 (38.6%) among women. An excess cancer incidence in males was seen in transplant recipients, but the sex difference was attenuated for cancers of the lip (M:F IRRTransplant: 1.81 vs M:F IRRGP: 3.96; P < .0001), stomach (1.51 vs 2.09; P = .002), colorectum (0.98 vs 1.43; P < .0001), liver (2.39 vs 3.44; P = .002), kidney (1.67 vs 2.24; P < .0001), bladder (2.02 vs 4.19; P < .0001), Kaposi sarcoma (1.79 vs 3.26; P = .0009), and non-Hodgkin lymphoma (1.34 vs 1.64; P < .0001). The M:F IRRTransplant was not statistically different from the M:F IRRGP for other cancer sites. Although male solid organ transplant recipients have higher cancer incidence than female recipients, the attenuation in the male to female ratio for many cancers studied relative to the general population might suggest the importance of immunosurveillance, with some loss of advantage in female recipients due to immunosuppression after transplantation.

Evolving Changes in the Characteristics of Death in Transfusion Dependent Thalassemia in Greece

Introduction: During the last decades, improvements in the treatment of transfusion-dependent thalassemia (TDT) with safer transfusion schemas, improved management of iron overload and of comorbidities, have resulted in significantly increased life expectancy. With increased survival, the pattern of characteristics of death is changing. Aim: The aim of our study was to analyze the causes and other characteristics of death in transfusion-dependent thalassemia patients in Greece during the last 45 years. Patients and Methods: A retrospective cohort study was conducted in our Unit, which is the largest one in country, where around 15-20% of Greek patients (pts) are followed. The study included all deaths in TDT pts occuring between 1979 and 2023. The observation period was analyzed in 5 years' segments. For each patient, data on the age of death, cause of death, age of splenectomy, age at first chelation treatment and mean ferritin values for the last two years before death, were captured. Patients were classified into two groups: (1) mild (ferritin &amp;lt; 2500 μg/L) and (2) moderate-severe (ferritin: &amp;lt;2.500g/L). Statistical analysis performed with RStudio v.3.6.2. Results: A total of 172 deaths (male/female: 107/65) were recorded during this observation period. Pts' characteristics are summarized in table1. The overall incidences of the main causes of death are heart disease (57%), malignancy (12%), infections (included HIV and sepsis) (12%), liver failure (4.6%) and accidental events (4.6%). Distribution of causes of death during the different intervals are shown in figure 1. Malignancies (20 pts) are the most prevalent cause of death for the last observation period 2019-2023 and include liver cancer (11pts), renal cancer (2 pts), colorectal cancer (2 pts), lymphoma (2 pts), lung cancer (1 pt), pancreatic cancer (1 pt) and cholangiocarcinoma (1 pt). Malignancy has gradually replaced cardiac disease as the leading cause of death over the last years. Infections increased as a cause of death in the last 5 years and reached similar levels to the initial observation time segment. A gradual increase in the age of pts at the time of death was noted, starting from a mean (±SD) of 15.7±.3.6 years at the period of 1979-1983 to 46.6±.6.0 years for 2019-2023. The percentage of splenectomized pts varies significantly throughout the observation period. There is a positive correlation between ferritin levels and causes of death due to cardiovascular disease. The percentage of deceased pts on chelation therapy gradually increased while the age of starting chelation therapy gradually decreased during the observation period. Conclusions: The present study shows that there is a shift in the main cause of death in transfusion-dependent thalassemia patients the last 45 years, from cardiovascular to malignancies, while there is variability in the distribution of all causes of death during the different 5-year intervals. This reflects the overall changes in the treatment of TDT, which has transformed TDT from a pediatric disease of guarded prognosis to a chronic disease of adulthood.

Disease Quantification of Liver Lymphoma in CT Images without Lesion Segmentation.

This study aimed to automatically implement liver disease quantification (DQ) in lymphoma using CT images without lesion segmentation. Computed Tomography (CT) imaging manifestations of liver lymphoma include diffuse infiltration, blurred boundaries, vascular drift signs, and multiple lesions, making liver lymphoma segmentation extremely challenging. The method includes two steps: liver recognition and liver disease quantification. We use the transfer learning technique to recognize the diseased livers automatically and delineate the livers manually using the CAVASS software. When the liver is recognized, liver disease quantification is performed using the disease map model. We test our method in 10 patients with liver lymphoma. A random grouping cross-validation strategy is used to evaluate the quantification accuracy of the manual and automatic methods, with reference to the ground truth. We split the 10 subjects into two groups based on lesion size. The average accuracy for the total lesion burden (TLB) quantification is 91.76%±0.093 for the group with large lesions and 95.57%±0.032 for the group with small lesions using the manual organ (MO) method. An accuracy of 85.44%±0.146 for the group with larger lesions and 81.94%±0.206 for the small lesion group is obtained using the automatic organ (AO) method, with reference to the ground truth. Our DQ-MO and DQ-AO methods show good performance for varied lymphoma morphologies, from homogeneous to heterogeneous, and from single to multiple lesions in one subject. Our method can also be extended to CT images of other organs in the abdomen for disease quantification, such as Kidney, Spleen and Gallbladder.

Cancer incidence and mortality in Brunei Darussalam, 2011 to 2020

This study presents the trends of age-standardised incidence and mortality rates of common cancers in Brunei Darussalam from 2011 to 2020. All cancer cases diagnosed among Brunei Darussalam citizens and permanent residents in the period 2011 to 2020 were included in the study. De-identified data were provided by the CanReg5 based BDCR, Ministry of Health Brunei Darussalam. The annual age-standardised incidence and mortality rates per 100,000 persons were standardised by the direct method using the World Health Organization (WHO) world standard population distribution. Joinpoint regression analyses were used to study the incidence and mortality trends of cancer in Brunei Darussalam over the 2011–2020 period. Trends were expressed as average annual percent change (AAPC) over 2011 to 2020, or annual percent change (APC) for a given time period. There were a total of 6,495 new cancer cases diagnosed and 3,359 death cases recorded from 2011 to 2020, in Brunei Darussalam. The five common cancers for males were colorectal, lung and bronchus, prostate, liver, and non-Hodgkin lymphoma. Among females, the five most common cancers were breast, colorectal, lung and bronchus, corpus uteri and cervix uteri. The five leading cancer deaths for males were lung and bronchus, colorectal, liver, prostate, and stomach, while for females, the five leading cancer deaths were breast, lung and bronchus, colorectal, ovary, and cervix uteri. There was a significant increase in the incidence trend of corpus uteri (AAPC:13.3) and a significant decline in the incidence trend for cervical cancer (AAPC:-4.5) from 2011 to 2020. There was a significant increase in the mortality trend of female breast cancer from 2011 to 2015 (APC:16.3), but the trend significantly declined from 2015 to 2020 (APC:-12.5). We also found a significant decrease in mortality trends for stomach cancer (AAPC:-4.7) from 2011 to 2020 for both genders combined. The burden of common cancers is expected to continue to grow with ageing population, effective public health interventions targeting high burden cancers and high-risk groups, and control of modifiable risk factors will continue to be the essential approaches in reducing cancer burden.

CLINICAL AND PATHOLOGICAL CHARACTERIZATION OF HEPATIC LYMPHOMAS: A RETROSPECTIVE SINGLE-CENTER STUDY.

The incidence of hepatic lymphoma has been increasing recently and diagnosis can be challenging as clinical presentation and radiological findings are usually variable and non-specific. The aims of this study were to describe their main clinical, pathological and imaging characteristics and identify poor prognostic factors. A retrospective study that included all patients with histological diagnosis of liver lymphoma over a 10-year period at our center was performed. A total of 36 patients were identified, with mean age of 56.6 years and male predominance (58%). There were three patients with primary liver lymphoma (8.3%) and 33 with secondary liver lymphoma (91.7%). The most common histological type was diffuse large B-cell lymphoma (33.3%). The most common clinical manifestations included fever, lymphadenopathy, weight loss, night sweats and abdominal discomfort; three patients (11.1%) were asymptomatic. Computed tomography scan revealed heterogenous radiological patterns including a single nodule (26.5%), multiple nodules (41.2%) or diffuse infiltration (32.4%). The mortality rate during follow-up was 55.6%. Higher levels of C-reactive protein (P=0.031) and absence of treatment response (P<0.001) were significantly associated with higher mortality. Hepatic lymphoma is a rare disease that may involve liver as part of a systemic disease or, less commonly, be confined to this organ. Clinical presentation and radiological findings are often variable and non-specific. It is associated with high mortality and poor prognostic factors include higher levels of C-reactive protein and absence of response to treatment.

Effect of Peripheral Blood Lymphocytes on Prognosis of Multiple Cancers.

In the era of immunotherapy, the immune function of patients with cancer has attracted increasingly more attention. The immune scoring system is an important supplement to the classical tumor staging and classification process. The immune system plays a controversial role in the development of cancer. Meanwhile, the prognostic significance of peripheral blood lymphocytes is still controversial. The present study aimed to assess the prognostic significance of peripheral blood lymphocytes in eight types of cancers. We performed a retrospective analysis of 32731 patients with cancer hospitalized in Shanxi Cancer Hospital from January 2012 to December 2016. The percentages of CD3+, CD4+, CD8+, CD19+, CD56+, and CD127+ lymphocytes in the peripheral blood of all patients were examined using flow cytometry. The immune cell subsets of patients with cancer were classified into three groups using the K-means clustering method via the R language software. Differences in the overall survival rate were analyzed using the Kaplan-Meier method. The Cox regression model was utilized for univariate and multivariate analysis. The mean survival time of patients with liver cancer, rectal cancer, gastric cancer, breast cancer, esophageal cancer, colon cancer, ovarian cancer, and lymphoma was 30.25, 21.74, 37.67, 16.28, 21.62, 30.25, 31.43, and 34.27 months, respectively. The survival curves showed that the most prognostically beneficial immune state of the patients was when the expression of the immune cells in the peripheral blood was in equilibrium. Moreover, Cox proportional hazards regression model analysis revealed that the factors affecting the overall survival (OS) of patients with eight different kinds of cancer were not identical. However, CD19+ lymphocytes had the most significant impact on the prognosis of these patients. Cancer occurrence and development were associated with the density of lymphocyte infiltration. Thus, immune homeostasis could be an effective indicator to evaluate prognosis and judge cancer treatment.

Primary Hepatic Lymphoma: Role of Low-Dose Radiotherapy at a Single Institution with Genetic Characterization and Paired Literature Review

Purpose/Objective: Primary hepatic lymphomas (PHL) are an extremely rare form of non-Hodgkin Lymphoma (NHL) for which there are no established treatment guidelines, with available literature largely comprised of small case reports. Therefore, we evaluate our institutional experience treating PHL within the context of existing literature to better understand treatment modalities, role of radiotherapy (RT), and outcomes. Traditionally, radiotherapy for indolent lymphomas has involved treatment of up to 2400cGy in 12 fractions, however the use of low-dose radiotherapy of 400cGy in 1-2 fractions has been increasingly utilized. However to our knowledge, use of low-dose RT for liver lymphomas has not previously been reported in the literature. Materials/Methods: We conducted a single institutional retrospective analysis of all PHL patients (pts) diagnosed from 2000-2021 with a biopsy-proven liver lesion without other lymphomatous solid organ involvement, except for concurrently diagnosed splenic lymphomas. Subgroup analysis was performed for diffuse large B-cell lymphoma (DLBCL) and indolent lymphomas, which included marginal zone (MZL), follicular (FL), and low-grade B-cell lymphoma (BCL), NOS. Univariable (UVA) and multivariable analysis (MVA) for overall survival (OS) was performed using the Cox proportional hazards model. A literature review was also conducted using key words "liver", "lymphoma", and "treatment" to identify all available reported cases of PHL. An institutional targeted sequencing database was queried to identify patients with PHL of DLBCL histology. Results: We identified 30 PHL pts within the institutional cohort and 192 pts from comprehensive literature review. Sixteen patients were male (53%), and 25 (83%) were ECOG 0. Twenty five (83%) were Lugano Stage I, 3 (10%) were Stage III, and 2 (7%) were Stage IV. Six (20%) patients had bulky disease and 3 (10%) had nodal involvement. Systemic therapy was the most common treatment modality with 20 patients (67%), and 4 patients (13%) each received surgery, radiation and observation in our institutional cohort. In the paired literature review, 96 patients (50%) received systemic therapy, 69 (36%) underwent surgery, 10 (5%) received radiation and 11 (6%) underwent observation. Seventeen (57%) of patients were alive and 5 (17%) lost to follow-up within our institutional cohort, compared with 97 patients (51%) alive and 3 (2%) lost to follow-up. Median survival in our cohort was 6 years, compared with 2 years among the literature review cohort. Subgroup analysis of DLBCL included 15 pts (Table 1). On MVA for OS, only ECOG score (p=0.02) and Lugano stage (p=0.04) remained significant. Subgroup analysis of the indolent lymphoma group included 9 pts (Figure 1). On MVA for OS, only age remained significant. Six DLBCL patients with available targeted sequencing data were identified, with 4 mutations mutated more than once: TP53 (50%), MEF2B (33%), P2RY8 (33%), and IRF8 (33%). Pathway mapping of genetic mutations was notable for alterations in cell cycle pathway genes TP53 and ATM (17%). No other pathways had greater than one genetic alteration. Conclusion: PHLs are a rare subtype of NHL without clear treatment consensus. Primary hepatic DLBCL is predominantly treated with chemotherapy in both our institutional experience and as reported in the literature, with reasonable disease control. Importantly, indolent PHL patients in the institutional cohort have been treated with various modalities including low-dose radiotherapy, which appears to achieve comparable disease control. However radiotherapy was not utilized as a modality for indolent PHL within the literature review. Therefore, this is the first report of the use of low-dose radiotherapy for treatment of indolent liver lymphomas. Our RT data is limited by short follow-up duration of RT pts compared to pts who received chemotherapy, surgery or observation. However, our results are encouraging for the consideration of low-dose radiotherapy as a management option for appropriate patients with indolent PHL. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Refractory hepatosplenic T-cell lymphoma was successfully treated with salvage allogeneic hematopoietic stem cell transplantation combined with enhanced myeloablative preconditioning.

This study aimsto evaluate the clinical benefit of salvage allogeneic hematopoietic stem cell transplantation (allo-HSCT) in combination with enhanced myeloablative preconditioning in the treatment of refractory liver and spleen T-cell lymphomas. A retrospective analysis was performed on three patients (with refractory liver and spleen T-cell lymphomas) who have been treated with salvage allo-HSCT combined with enhanced myeloablative preconditioning. One of three patients had a liver biopsy; the other two underwent bone marrow analysis using morphology, immunology, cytogenetics, and molecular biology. All three patients were resistant to chemotherapy and with a high tumor load, so a new total body irradiation/splenic region irradiation/GEM/CLAG/ATG preconditioning regimen was conducted and followed with salvage HSCT. Two patients received haploidentical-donor hematopoietic stem cell transplants, and one received an unrelated full-donor hematopoietic stem cell transplant. The three patients survived disease-free until May 2021. Clinically, hepatosplenic T-cell lymphoma (HSTCL) is rare, with a poor prognosis and chemotherapy response. Based on the present study's encouraging clinical results, salvage allo-HSCT in conjunction with an enhanced myeloablative preconditioning regiment may be an effective and safe treatment for HSTCL.

Milk consumption and risk of twelve cancers: A large-scale observational and Mendelian randomisation study

Milk consumption is a modifiable lifestyle factor that has been associated with several cancer types in observational studies. Limited evidence exists regarding the causality of these relationships. Using a genetic variant (rs4988235) near the lactase gene (LCT) locus that proxies milk consumption, we conducted a comprehensive survey to assess potential causal relationships between milk consumption and 12 types of cancer. Our analyses were conducted using white British participants of the UK Biobank (n=up to 255,196), the FinnGen cohort (up to 260,405), and available cancer consortia. We included cancers with previous evidence of an association with milk consumption in observational studies, as well as cancers common in both UK Biobank and FinnGen populations (>1000 cases). We evaluated phenotypic associations of milk intake and cancer incidence in the UK Biobank, and then used a Mendelian randomisation (MR) approach to assess causality in the UK Biobank, FinnGen consortium, and combined analyses incorporating additional consortia data for five cancers. In MR meta-analyses, case numbers for cancers of breast, ovary, uterus, cervix, prostate, bladder and urinary tract, colorectum, and lung ranged between 6000 and 148,000 cases, and between 780 and 1342 cases for cancers of the liver, mouth, stomach and diffuse large B-cell lymphoma. In observational analyses, milk consumption was associated with higher risk of bladder and urinary tract cancer (OR 1.23, 95% CI 1.03-1.47), but not with any other cancer. This association was not confirmed in the MR analysis, and genetically predicted milk consumption showed a significant association only with lower risk of colorectal cancer (0.89, 0.81-0.98 per additional 50g/day). In the MR analyses conducted among individual cohorts, genetically predicted milk consumption provided evidence for an association with lower colorectal cancer in the FinnGen cohort (0.85, 0.74-0.97), and in the UK Biobank greater risk of female breast cancer (1.12, 1.03-1.23), and uterine cancer in pre-menopausal females (3.98, 1.48-10.7). In a comprehensive survey of milk-cancer associations, we confirm of a protective role of milk consumption for colorectal cancer. Our analyses also provide some suggestion for higher risks of breast cancer and premenopausal uterine cancer, warranting further investigation.

C-reactive protein and cancer risk: a pan-cancer study of prospective cohort and Mendelian randomization analysis

BackgroundAlthough observational studies have reported associations between serum C-reactive protein (CRP) concentration and risks of lung, breast, and colorectal cancer, inconsistent or absent evidences were showed for other cancers. We conducted a pan-cancer analysis to comprehensively assess the role of CRP, including linearity and non-linearity associations.MethodsWe analyzed 420,964 cancer-free participants from UK Biobank cohort. Multivariable-adjusted Cox proportional hazards model was conducted to evaluate the observed correlation of CRP with overall cancer and 21 site-specific cancer risks. Furthermore, we performed linear and non-linear Mendelian randomization analyses to explore the potential causal relation between them.ResultsDuring a median follow-up period of 7.1 years (interquartile range: 6.3, 7.7), 34,979 incident cancer cases were observed. Observational analyses showed higher CRP concentration was associated with increased risk of overall cancer (hazard ratio (HR) = 1.02, 95% CI: 1.01, 1.02 per 1mg/L increase, P < 0.001). There was a non-linear association between CRP and overall cancer risk with inflection point at 3mg/L (false-discovery rate adjust (FDR-adjusted) Poverall < 0.001 and FDR-adjusted Pnon-linear < 0.001). For site-specific cancer, we observed positive linear associations for cancers of esophagus and stomach (FDR-adjusted Poverall < 0.050 and FDR-adjusted Pnon-linear > 0.050). In addition, we also observed three different patterns of non-linear associations, including “fast-to-low increase” (head and neck, colorectal, liver, lung, kidney cancer, and non-Hodgkin lymphoma), “increase-to-decrease” (breast cancer), and “decrease-to-platform” (chronic lymphocytic leukemia). Furthermore, the inflection points of non-linear association patterns were consistently at around 3mg/L. By contrast, there was no evidence for linear or non-linear associations between genetically predicted CRP and risks of overall cancer or site-specific cancers.ConclusionsOur results indicated that CRP was a potential biomarker to assess risks of overall cancer and 12 site-specific cancers, while no association were observed for genetically-predicted CRP and cancer risks.

Abstract 5934: Weight loss and subsequent cancer diagnosis: A prospective cohort study

Abstract Background: Weight loss is a common symptom in patients with cancer. However, little is known about how much weight loss and over what time period weight loss precedes cancer diagnosis. Herein, we evaluate the association between weight loss and subsequent 2-year cancer diagnosis using repeatedly measured weight data in two large prospective cohorts. Methods: The analysis included 111,891 US women from the Nurses’ Health Study and 45,498 US men from the Health Professional Follow-up Study, who were enrolled in 1978 and 1988, respectively, and followed through 2012, and who were cancer-free and ≥40 years old at study entry. Current weight and lifestyle information were assessed every 2 years by questionnaire, and weight change in the previous 2 years was calculated by comparing two consecutive questionnaires. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for subsequent risk of cancer diagnosis according to weight change percentage. We also examined 20-year trajectories of body mass index (BMI) before cancer diagnosis. Results: During 4.1 million person-years of follow-up, we documented 30,441 incident cancers. Participants with recent weight loss were at increased risk for cancer diagnosis in the subsequent 2 years (Ptrend &amp;lt;0.0001). Compared with participants without weight loss, those who had a weight loss of 5-10% or &amp;gt;10% had a multivariable-adjusted HR for total cancer of 1.09 (95% CI, 1.04-1.13) and 1.17 (95% CI, 1.10-1.24), respectively. For individual cancer types, increased weight loss was associated with a subsequent cancer diagnosis of esophagus, liver, pancreas, leukemia, stomach, myeloma, lung, colorectal, and non-Hodgkin lymphoma (all Ptrend &amp;lt;0.005). Comparing participants with weight loss of &amp;gt;10% to those without weight loss, multivariable-adjusted HRs were 4.22 (95% CI, 2.50-7.13) for esophageal cancer, 3.30 (95% CI, 1.65-6.61) for liver cancer, 2.46 (95% CI, 1.84-3.30) for pancreatic cancer, 2.40 (95% CI, 1.59-3.61) for leukemia, 2.26 (95% CI, 1.32-3.87) for stomach cancer, 1.80 (95% CI, 1.14-2.83) for myeloma, 1.45 (95% CI, 1.22-1.73) for lung cancer, 1.38 (95% CI, 1.14-1.66) for colorectal cancer, and 1.35 (95% CI, 1.06-1.72) for non-Hodgkin lymphoma. The 20-year trajectory of BMI indicated that most weight loss occurred in the 2 years before cancer diagnosis, with the magnitude of weight loss increasing closer to the time of subsequent cancer diagnosis. Conclusion: Recent weight loss of &amp;gt;10% predicts elevated risk of cancer diagnosis in the forthcoming 2 years, particularly for cancers of the upper gastrointestinal tract, hematological system, colorectum, and lung. Citation Format: Qiao-Li Wang, Ana Babic, Michael H. Rosenthal, Alice A. Lee, Yin Zhang, Xuehong Zhang, Mingyang Song, Leandro F. Rezende, Dong Hoon Lee, Leah Biller, Kimmie Ng, Andrew T. Chan, Meir J. Stampfer, Edward L. Giovannucci, Peter Kraft, Chen Yuan, Brian M. Wolpin. Weight loss and subsequent cancer diagnosis: A prospective cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5934.

A Review on the Marek's Disease Outbreak and Its Virulence-Related meq Genovariation in Asia between 2011 and 2021.

Simple SummaryMarek’s disease is continuously causing an economic loss in Asia, despite the wide use of vaccines in the last decade. This review aims at summarizing the outbreak, the virulence-related meq gene variation, and the pathological information of Marek’s disease in the last decade in Asia. We found that a total of 132 viral strains emerged in 12 countries with different meq sequences. Among the evidence we have collected, 12 strains found in China were vaccine-resistant, reaching a mortality rate of 30% and above. This evidence requires the related region in China to consider the renewal of its vaccination type; however, more studies regarding the vaccination efficiency in other Asian countries are recommended, as the current information is not enough. The visceral tumor is the most common pathological type (13 in 16 studies) in Asia, while it is possible that a neural type may exist. We suggest that farmers monitor the behavioral changes of chickens to identify this harmful disease at the early stage. The phylogenetic analysis shows interconnection between Middle Eastern, South Asian, and East Asian countries that are geologically connected—poultry trading managers should consider the potential of viral transmitting.Marek’s disease is an infectious disease in poultry that usually appears in neural and visceral tumors. This disease is caused by Gallid alphaherpesvirus 2 infection in lymphocytes, and its meq gene is commonly used in virulent studies for coding the key protein functional in oncogenic transformation of the lymphocytes. Although vaccines have been introduced in many countries to control its spread and are proven to be efficient, recent records show a decline of such efficiency due to viral evolution. In this study, we reviewed the outbreak of Marek’s disease in Asia for the last 10 years, together with associated meq sequences, finding a total of 36 studies recording outbreaks with 132 viral strains in 12 countries. The visceral type is the most common (13 in 16 studies) form of Marek’s disease, but additional unobserved neural changes may exist. MD induces liver lymphoma most frequently (11 in 14 studies), and tumors were also found in spleen, kidney, heart, gizzard, skin, intestine, lung, and sciatic nerve. Twelve viral strains distributed in China have been reported to escape the CVI988 vaccine, reaching a mortality rate of more than 30%. Phylogenetic analyses show the internal connection between the Middle East (Turkey, Iraq, Iran, Saudi Arabia), South Asia (India, Indonesia), and East Asia (China and Japan), while external viral communications might occasionally occur. In 18 strains with both sequential and mortality data, amino acid alignment showed several point substitutions that may be related to its virulence. We suggest more behavioral monitoring in Marek’s disease-endemic regions and further studies on strain virulence, together with its Meq protein structural changes.

Imaging Spectrum of Intrahepatic Mass-Forming Cholangiocarcinoma and Its Mimickers: How to Differentiate Them Using MRI.

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malignancy, with mass-forming growth pattern being the most common. The typical imaging appearance of mass-forming ICC (mICC) consists of irregular ring enhancement in the arterial phase followed by the progressive central enhancement on portal venous and delayed phases. However, atypical imaging presentation in the form of hypervascular mICC might also be seen, which can be attributed to distinct pathological characteristics. Ancillary imaging features such as lobular shape, capsular retraction, segmental biliary dilatation, and vascular encasement favor the diagnosis of mICC. Nevertheless, these radiological findings may also be present in certain benign conditions such as focal confluent fibrosis, sclerosing hemangioma, organizing hepatic abscess, or the pseudosolid form of hydatid disease. In addition, a few malignant lesions including primary liver lymphoma, hemangioendothelioma, solitary hypovascular liver metastases, and atypical forms of hepatocellular carcinoma (HCC), such as scirrhous HCC, infiltrative HCC, and poorly differentiated HCC, may also pose a diagnostic dilemma by simulating mICC in imaging studies. Diffusion-weighted imaging and the use of hepatobiliary contrast agents might be helpful for differential diagnosis in certain cases. The aim of this manuscript is to provide a comprehensive overview of mICC imaging features and to describe useful tips for differential diagnosis with its potential mimickers.

Risk of second primary malignancies associated with radiotherapy in prostate cancer patients: competing risk analysis.

Background: The effect of radiotherapy (RT) for second primary malignancies (SPMs) among prostate cancer survivors iscontroversial. Methods: Applying logistic regression, competing risk analysis and propensity score matching method, this study analyzed clinical data from the Surveillance, Epidemiology, and End Results program to compare the risk for SPMs between patients receiving RT and non-RT. Results: In this study, prostate cancer patients treated with RT developed more SPMs in the anus, bladder, rectum, liver, lung and bronchus and lymphoma than non-RT groups. Conclusion: More intensive surveillance should be adopted for these cancers among prostate cancer survivors.

Primary liver lymphoma and systemic sclerosis.

Primary liver lymphoma and systemic sclerosis.