Search Results (319)

Objective: Tumor progression is regulated by systemic immune status, nutritional metabolism, and the inflammatory microenvironment. This study aims to investigate inflammatory–nutritional biomarkers associated with metachronous liver metastasis (MLM) in colorectal cancer (CRC) and develop a machine learning model for accurate prediction. Methods: This study enrolled 680 patients with CRC who underwent curative resection, randomly allocated into a training set (n = 477) and a validation set (n = 203) in a 7:3 ratio. Feature selection was performed using Boruta and Lasso algorithms, identifying nine core prognostic factors through variable intersection. Seven machine learning (ML) models were constructed using the training set, with the optimal predictive model selected based on comprehensive evaluation metrics. An interactive visualization tool was developed to interpret the dynamic impact of key features on individual predictions. The partial dependence plots (PDPs) revealed a potential dose–response relationship between inflammatory–nutritional markers and MLM risk. Results: Among 680 patients with CRC, the cumulative incidence of MLM at 6 months postoperatively was 39.1%. Multimodal feature selection identified nine key predictors, including the N stage, vascular invasion, carcinoembryonic antigen (CEA), systemic immune–inflammation index (SII), albumin–bilirubin index (ALBI), differentiation grade, prognostic nutritional index (PNI), fatty liver, and T stage. The gradient boosting machine (GBM) demonstrated the best overall performance (AUROC: 0.916, sensitivity: 0.772, specificity: 0.871). The generalized additive model (GAM)-fitted SHAP analysis established, for the first time, risk thresholds for four continuous variables (CEA > 8.14 μg/L, PNI < 44.46, SII > 856.36, ALBI > −2.67), confirming their significant association with MLM development. Conclusions: This study developed a GBM model incorporating inflammatory-nutritional biomarkers and clinical features to accurately predict MLM in colorectal cancer. Integrated with dynamic visualization tools, the model enables real-time risk stratification via a freely accessible web calculator, guiding individualized surveillance planning and optimizing clinical decision-making for precision postoperative care. Full article

Background: Liver cancer is a major health concern worldwide. Radiofrequency ablation is a safe treatment option that can be guided by either ultrasound, computer tomography (CT), or fluoroscopy. Although ultrasound-guided radiofrequency ablation is commonly used in clinical practice, radiofrequency ablation guided by CT is more precise but requires more time and does not offer real-time monitoring, which may result in complications such as pneumothorax or organ damage. Objectives: In this study, we investigated the effect of ultrasound, CT, and combined ultrasound/CT guidance on patient survival and complication development. Methods: A total of 982 radiofrequency ablation sessions conducted on 553 patients were analyzed. Clinical outcomes were assessed during follow-up to determine the survival and recurrence rates of malignant tumors. Results: Overall, the three guidance approaches exhibited significant differences in terms of tumor size, number, complication development, and treatment duration. However, no significant differences were observed in survival rate. A comparison of the effect of CT guidance and ultrasound guidance on complication development revealed a higher odds ratio for CT guidance in some cases. A comparison of combined ultrasound/CT guidance and ultrasound guidance revealed nonsignificant differences in complication development. A comparison of CT guidance and combined ultrasound/CT guidance revealed a higher odds ratio for CT guidance in some cases. Radiofrequency ablation is a safe and effective treatment for liver tumors. However, CT has an increased incidence of complications. Conclusions: Combined ultrasound/computer tomography guidance is recommended for patients with multiple or large tumors or tumors near the hepatic dome or diaphragm. Full article

This study aimed to compare the contents of copper (Cu), zinc (Zn), magnesium (Mg), and iron (Fe) in healthy liver tissue from deceased liver donors (DGs), in cirrhotic tissue from patients without (CIR) or with hepatocellular carcinoma (CIR-HCC) and in HCC tissue from the latter patients. Liver tissue samples were obtained from cirrhotic liver transplant recipients, with (n = 14) and without HCC (n = 14), and from DGs (n = 18). In patients with HCC, both cirrhotic and tumor tissue was collected. The tissue metal content was measured using atomic absorption spectrometry. The Cu content of DG tissue was significantly lower than that of CIR-HCC and HCC tissue but not CIR tissue. The tissue Zn and Mg contents were significantly higher in DG tissue than in CIR, CIR-HCC, and HCC tissues. No difference was observed for Fe. The Cu/Zn ratio progressively increased in DG, CIR, CIR-HCC, and HCC tissues. The increased Cu content in cirrhotic and tumor tissue of HCC patients and the fact that the latter had the highest value for the Cu/Zn ratio indirectly suggest the potential role of these metals in hepatocarcinogenesis. These findings support a pathophysiological basis for further experimental studies to investigate the potential therapeutic implications of pharmacological agents targeting metal homeostasis in this malignancy. Full article

Background/Objectives: Gypenosides (Gps) are the main active compounds of Gynostemma and show promise in managing diabetes; nevertheless, the mechanism by which Gps exert anti-diabetic effects is still not fully understood. The aim of this study is to clarify the molecular mechanisms of Gps in ameliorating glucose dysregulation. Methods: Qualitative and quantitative analyses on the chemical components of Gps were performed, respectively. Type 2 diabetes mellitus mouse models were established, and the mice were subsequently treated with Gps at doses of 200, 100, or 50 mg/kg for 4 weeks. Biochemical markers were measured. Histopathological assessments of hepatic and colonic tissues were conducted. The compositions of the intestinal microbiota, short-chain fatty acids (SCFAs), and bile acids (BAs) in fecal samples were analyzed. Western blotting was applied to examine the activation of relevant signaling pathways. Results: Gps have potent regulatory effects on metabolic homeostasis by improving glucose and lipid profiles and alleviating hepatic tissue damage. Treatment with Gps significantly reduced serum levels of lipopolysaccharides and key pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α). Moreover, Gps enhanced the integrity of the gut barrier by upregulating the level of tight junction proteins (ZO-1 and occludin). Microbiota profiling revealed that Gps markedly increased microbial diversity and richness, decreased the ratio of Firmicutes/Bacteroidetes, and elevated Bacteroidia abundance from the phylum to the genus level. Targeted metabolomics further demonstrated that Gps modulated gut microbial metabolites by promoting SCFA production and reshaping BA profiles. Specifically, Gps elevated the primary-to-secondary BA ratio while reducing the 12α-hydroxylated to non-12α-hydroxylated BA ratio. Mechanistically, Western blotting demonstrated that Gps triggered the hepatic PI3K/AKT pathway and the intestinal BA/FXR/FGF15 axis, suggesting the coordinated regulation of metabolic and gut–liver axis signaling pathways. Conclusions: Gps significantly ameliorate hyperglycemia and hyperlipidemia through a multifaceted mechanism involving gut microbiota modulation, the restoration of intestinal barrier function, and the regulation of microbial metabolites such as SCFAs and BAs. These findings offer novel insights into their mechanism of action via the gut–liver axis. Full article

Background: The use of photon-counting detector computed tomography (PCD-CT) has improved image quality in cardiac, pulmonary, and musculoskeletal imaging. Abdominal imaging research, especially about the use of PCD-CT in hepatocellular carcinoma (HCC), is sparse. Objectives: We aimed to compare the image quality of tumors, the liver parenchyma, and the vasculature in patients with HCC using PCD-CT reconstructions at different slice thicknesses and kernels to identify the most appropriate settings for the clinical routine. Methods: CT exams from twenty adult patients with HCC performed with a clinically approved, first-generation PCD-CT scanner (Naeotom Alpha^®, Siemens Healthineers), were retrospectively reviewed. For each patient, images were reconstructed at four different sharp kernels, designed for abdominal imaging (Br40; Br44; Br48; Br56) and at three slice thicknesses (0.4 mm; 1 mm; 3 mm). The reconstruction with the Br40 kernel at 3 mm (Br40_{3 mm}) was used as a clinical reference. Three readers independently assessed the image quality of different anatomical abdominal structures and hypervascular HCC lesions using a five-point Likert scale. In addition, image sharpness was assessed using line-density profiles. Results: Compared with the clinical reference, the Br44_{1 mm} and Br48_{1 mm} reconstructions were rated superior for the assessment of the hepatic vasculature (median difference +0.67 [+0.33 to +1.33], p < 0.001 and +1.00 [+0.67 to +1.67], p < 0.001). Reconstructions for Br40_{1 mm} (+0.33 [−0.67 to +1.00], p < 0.001), and Br44_{3 mm} (+0.0 [0.0 to +1.00], p = 0.030) were scored superior for overall image quality. The noise demonstrated a continuous increase when using sharper kernels and thinner slices than Br40_{3 mm} (p < 0.001), leading to a decrease in contrast-to-noise ratio. Although there was a trend toward increased image sharpness using the slope analysis with higher kernels, this was not significantly different compared with the reference standard. Conclusion: PCD-CT reconstruction Br40_{1 mm} was the most suitable setting for overall image quality, while reconstructions with sharper kernels (Br44_{1 mm} and Br48_{1 mm}) can be considered for the assessment of the hepatic vasculature in patients with HCC. Full article

This study aimed to design dual-responsive chitosan–polylactic acid nanosystems (PLA@CS NPs) for controlled and targeted ledipasvir (LED) delivery to HepG2 liver cancer cells, thereby reducing the systemic toxicity and improving the therapeutic selectivity. Two formulations were developed utilizing ionotropic gelation and w/o/w emulsion techniques: LED@CS NPs with a size of 143 nm, a zeta potential of +43.5 mV, and a loading capacity of 44.1%, and LED-PLA@CS NPs measuring 394 nm, with a zeta potential of +33.3 mV and a loading capacity of 89.3%, with the latter demonstrating significant drug payload capacity. Since most drugs work through interaction with DNA, the in vitro affinity of DNA to LED and its encapsulated forms was assessed using stopped-flow and other approaches. They bind through multi-modal electrostatic and intercalative modes via two reversible processes: a fast complexation followed by a slow isomerization. The overall binding activation parameters for LED (cordination affinity, K_a = 128.4 M⁻¹, K_d = 7.8 × 10⁻³ M, ΔG = −12.02 kJ mol⁻¹), LED@CS NPs (K_a = 2131 M⁻¹, K_d = 0.47 × 10⁻³ M, ΔG = −18.98 kJ mol⁻¹) and LED-PLA@CS NPs (K_a = 22026 M⁻¹, K_d = 0.045 × 10⁻³ M, ΔG = −24.79 kJ mol⁻¹) were obtained with a reactivity ratio of 1/16/170 (LED/LED@CS NPs/LED-PLA@CS NPs). This indicates that encapsulation enhanced the interaction between the DNA and the LED-loaded nanoparticle systems, without changing the mechanism, and formed thermodynamically stable complexes. The drug release kinetics were assessed under tumor-mimetic conditions (pH 5.5, 10 mM GSH) and physiological settings (pH 7.4, 2 μM GSH). The LED@CS NPs and LED-PLA@CS NPs exhibited drug release rates of 88.0% and 73%, respectively, under dual stimuli over 50 h, exceeding the release rates observed under physiological conditions, which were 58% and 54%, thereby indicating that the LED@CS NPs and LED-PLA@CS NPs systems specifically target malignant tissue. Release regulated by Fickian diffusion facilitates tumor-specific payload delivery. Although encapsulation did not enhance the immediate cytotoxicity compared to free LED, as demonstrated by an in vitro cytotoxicity in HepG2 cancer cell lines, it significantly enhanced the therapeutic index (2.1-fold for LED-PLA@CS NPs) by protecting non-cancerous cells. Additionally, the nanoparticles demonstrated broad-spectrum antibacterial effects, suggesting efficacy in the prevention of chemotherapy-related infections. The dual-responsive LED-PLA@CS NPs allowed controlled tumor-targeted LED delivery with better selectivity and lower off-target toxicity, making LED-PLA@CS NPs interesting candidates for repurposing HCV treatments into safer cancer nanomedicines. Furthermore, this thorough analysis offers useful reference information for comprehending the interaction between drugs and DNA. Full article

Background/Objectives: Pancreatic cancer is the fourth leading cause of deaths related to cancer. It is a highly aggressive malignancy and often metastasizes quickly to other parts of the body and organs. The most effective cure is surgical resection, which also is limited by tumor identification and clear tumor margin visualization. Previously, we used MUC4 antibodies labeled with IRDye800CW (anti-MUC4-IR800) to target primary human pancreatic cancer in orthotopic cell line mouse models. Methods: In the present study, we established a pancreatic cancer liver metastasis mouse model by implanting a tumor fragment in the liver and a peritoneal carcinomatosis mouse model by injecting pancreatic cancer cells interperitoneally. Once the tumors were established, anti-MUC4-IR800 was administered to the mice by tail vein injection. Laparotomy was performed and tumors were imaged under white-light and near-infrared (NIR) fluorescence with the Pearl Small Animal Imaging System. Results: NIR imaging after 72 h shows the bright targeting of pancreatic cancer metastasis in both mouse models with high tumor-to-background ratios. Conclusions: Anti-MUC4-IR800 was able to successfully target and brightly label metastatic pancreatic cancer as small as 1 mm. Future clinical applications of the results of the present study are discussed. Full article

Backgrounds: Direct-acting antiviral (DAA) therapy, which achieves a high sustained virological response (SVR) rate, has been established as a standard treatment for patients with hepatitis C virus (HCV) infection. However, the risk factors for postoperative recurrence in patients with HCV-related hepatocellular carcinoma (HCC) detected after the achievement of an SVR by DAAs are unknown. Methods: The clinical records of 95 patients with initial HCV-related HCC detected after DAA-SVR achievement, who underwent liver resection between September 2014 and December 2020, were retrospectively reviewed. Patients with major vascular invasion and/or SVR achievement induced by interferon-based therapy were excluded. In this study, the patients were divided into two groups according to their alcohol intake status: without alcohol abuse (<80 g of ethanol each day for at least 5 years, n = 85) and with (continuous) alcohol abuse (n = 10). The risk factors for recurrence after liver resection were investigated, with special reference to the alcohol intake status. Results: The 3- and 5-year disease-free survival (DFS) rates after liver resection were 68.7% and 55.3%, respectively. Univariate and multivariate analyses identified alcohol abuse [hazard ratio (HR) 3.36, p = 0.004] and tumor size (HR 2.53, p = 0.010) as independent risk factors for postoperative recurrence. The 3- and 5-year postoperative DFS rates were 72.2% and 61.5% for patients without alcohol abuse and 40.0% and 13.3% for those with alcohol abuse (p = 0.001). Conclusions: Continuous alcohol abuse is a risk factor for recurrence after surgery of HCC detected after the achievement of DAA-SVR. Full article

Background/Objectives: Neurotensin receptors (NTSRs), members of the G protein-coupled receptor (GPCR) family, have been found to be overexpressed in several types of human cancers, including breast, colon, lung, liver, prostate, and pancreatic cancer. In particular, NTSR1 is overexpressed in at least 75% of pancreatic ductal adenocarcinomas. The aim of the present study was the development and evaluation of new ^99mTc-labeled nonpeptide NTSR1-antagonists for SPECT imaging of NTSR-positive tumors. Methods: Multistep syntheses of NTSR1 antagonist derivatives were performed following our previously described procedure. Two different chelating strategies were applied for ^99mTc radiolabeling to provide the [^99mTc]Tc-HYNIC complex [^99mTc]1 and the [^99mTc]Tc-tricarbonyl complex [^99mTc]2. Receptor binding assays were performed using hNTSR1-expressing CHO cells. Radiochemical yields (RCYs) were determined by radio-HPLC. For [^99mTc]1 and [^99mTc]2, log D_7.4, plasma protein binding, stability in human plasma and serum, and cellular uptake in HT-29 cells were determined. Biodistribution studies and small animal SPECT studies were performed in HT-29 tumor-bearing nude mice. Results: The radiosynthesis of [^99mTc]1 (log D_7.4 = −0.27) and [^99mTc]2 (log D_7.4 = 1.00) was successfully performed with RCYs of 94–96% (decay-corrected). Both radioligands were stable in human serum and plasma, showed plasma protein binding of 72% ([^99mTc]1) and 82% ([^99mTc]2), and exhibited high and specific uptake in HT-29 cells. Biodistribution studies in HT-29 tumor-bearing mice showed a higher tumor accumulation of [^99mTc]1 compared to [^99mTc]2 (8.8 ± 3.4 %ID/g vs. 2.7 ± 0.2 %ID/g at 2 h p.i.). [^99mTc]2 showed exceptionally high intestinal accumulation (49 ± 22 %ID/g at 1 h p.i.) and was therefore considered unfavorable. In the SPECT/CT imaging of HT-29 tumor xenografts, [^99mTc]1 showed a higher NTSR1-specific tumor uptake than [^99mTc]2 at all time points after tracer injection, with 12 ± 2.8 %ID/g for [^99mTc]1 vs. 3.1 ± 1.1 %ID/g for [^99mTc]2 at 4 h p.i. and adequate tumor-to-background ratios. Conclusions: In particular, the [^99mTc]Tc-HYNIC ligand ([^99mTc]1) showed promising preclinical results, being a potential candidate for SPECT imaging and, therefore, appropriate for translation into the clinic. Full article

Background/Objectives: MVI is a relevant prognostic factor among patients with hepatocellular carcinoma (HCC) receiving liver transplantation (LT). The preoperative assessment of the risk for MVI is relevant to pre-LT patient management and selection. The objective of this study was to create and validate a model to predict microvascular invasion (MVI) based on preoperative variables in the LT setting. Methods: A total of 2170 patients from 11 collaborative centers in Europe, Asia, and the US, who received transplants between 1 January 2000 and 31 December 2017, were enrolled in the study. The entire cohort was split into a training and a validation set (70/30% of the initial cohort, respectively) using random selection. Results: MVI was reported in 586 (27.0%) explanted specimens. Using the training set data, multivariable logistic regression identified three preoperative parameters associated with MVI: α-fetoprotein (lnAFP; odds ratio [OR] = 1.19; 95% confidence interval [CI] = 1.13–1.27), imaging tumor burden score (lnTBS; OR = 1.66; 95%CI = 1.39–1.99), and a fast-track approach before LT due to the availability of a live donation (OR = 1.99; 95%CI = 1.56–2.53). In the validation set, the LT-MVI c-index was 0.74, versus 0.69 for the MVI score proposed by Endo et al. (Brier Skill Score +75%). The new score had a relevant net reclassification index (overall value = 0.61). Stratifying the validation set into three risk categories (0–50th, 51st–75th, and >75th score percentiles), a very good stratification was observed in terms of disease-free (5-year: 89.3, 75.5, and 50.7%, respectively) and overall survival (5-year: 79.5, 72.6, and 53.7%, respectively). Conclusions: The preoperative assessment of MVI using the proposed score demonstrated very good accuracy in predicting MVI after LT. Full article

Background: Hepatocellular carcinoma (HCC), a primary liver cancer, continues to pose a significant challenge to the healthcare system because of its elevated incidence and fatality rates. This study aims to assess new biomarkers for early diagnosis and prognosis, comparing them to the established gold standard alpha-fetoprotein (AFP) and liver ultrasonography. Methods: A literature review was conducted in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guideline. A total of 670 papers were identified using internet databases. After applying the exclusion criteria, eight studies were included in this literature review. Results: It was identified that certain analyzed biomarkers, or the combinations thereof, exhibited superior sensitivity compared to the existing gold standard. The circulating cell-free DNA (cfDNA) and microRNAs (miRNAs), proved to have encouraging outcomes, particularly for the early identification of HCC. Additional indicators, such as circulating tumor cells (CTCs) and the alkaline phosphatase plus gamma-glutamyl transpeptidase to lymphocyte ratio (AGLR), may forecast disease progression, particularly regarding vascular invasion. Conclusions: These biomarkers may assist clinicians in making better therapeutical choices in order to provide personalized treatment and optimal follow-up for HCC patients. Full article

Background: Liver cancer, especially hepatocellular carcinoma, a prevalent malignant tumor of the digestive system, poses significant therapeutic challenges. While traditional chemotherapy can inhibit tumor progression, its clinical application is limited by insufficient efficacy. Hydrophobic therapeutic agents further encounter challenges including low tumor specificity, poor bioavailability, and severe systemic toxicity. This study aimed to develop a liver-targeted, glutathione (GSH)-responsive micellar system to synergistically enhance drug delivery and antitumor efficacy. Methods: A GSH-responsive disulfide bond was chemically synthesized to conjugate glycyrrhetinic acid (GA) with curcumin (Cur) at a molar ratio of 1:1, forming a prodrug Cur-GA (CGA). This prodrug was co-assembled with glycyrrhizic acid (GL) at a 300% w/w loading ratio into micelles. The system was characterized for physicochemical properties, in vitro drug release in PBS (7.4) without GSH and in PBS (5.0) with 0, 5, or 10 mM GSH, cellular uptake in HepG2 cells, and in vivo efficacy in H22 hepatoma-bearing BALB/c mice. Results: The optimized micelles exhibited a hydrodynamic diameter of 157.67 ± 2.14 nm (PDI: 0.20 ± 0.02) and spherical morphology under TEM. The concentration of CUR in micelles can reach 1.04 mg/mL. In vitro release profiles confirmed GSH-dependent drug release, with 67.5% vs. <40% cumulative Cur release observed at 24 h with/without 10 mM GSH. Flow cytometry and high-content imaging revealed 1.8-fold higher cellular uptake of CGA-GL micelles compared to free drug (p < 0.001). In vivo, CGA-GL micelles achieving 3.6-fold higher tumor accumulation than non-targeted controls (p < 0.001), leading to 58.7% tumor volume reduction (p < 0.001). Conclusions: The GA/GL-based micellar system synergistically enhanced efficacy through active targeting and stimuli-responsive release, providing a promising approach to overcome current limitations in hydrophobic drug delivery for hepatocellular carcinoma therapy. Full article

Background/Objectives: Antibody–drug conjugates (ADCs) show significant promise in oncology but often suffer from a narrow therapeutic window. Introducing a positive charge on the antibody is one proposed strategy to enhance tumor distribution and efficacy of ADC. Accordingly, this study evaluates the pharmacokinetics (PK) and pharmacology of an ADC developed using a positively charged (+5) version of anti-HER2 antibody trastuzumab conjugated with vc-MMAE linker-payload. Methods: A positively charged variant of trastuzumab was generated and conjugated to vc-MMAE. In vitro cytotoxicity assays were performed in cell lines with varying HER2 expression levels: N87 (high), MCF-7 (low), and MDA-MB-468 (non-expressing). In vivo biodistribution of wild-type (WT) and positively charged (+5) ADC was investigated in plasma, tumors, liver, and spleen. A pilot efficacy and toxicity study was also conducted in N87 tumor-bearing mice. Results: The charged ADC showed differential potency and PK behavior compared to the WT ADC. The charged ADC had similar potency in N87 cells but demonstrated ~20-fold and ~60-fold higher potency in MCF-7 and MDA-MB-468 cells. Plasma exposures of all the analytes were found to be reduced following the administration of charged ADC. However, total antibody exposure was found to increase in liver, spleen, and low antigen-expressing MCF-7 tumors. Tumor payload exposures were found to be significantly reduced for the charged ADCs, but liver and spleen displayed higher peak concentrations and increased tissue-to-plasma exposure ratios for the payload, suggesting preferential distribution of ADC with high drug–antibody ratio (DAR) to liver and spleen. Consistent with reduced tumor exposures, charged ADC showed lower efficacy in N87 tumor-bearing mice. No overt toxicity was observed for the charged ADC. Conclusions: Our findings suggest that while positively charged ADCs may be more potent in vitro, their efficacy in vivo may be compromised due to altered PK behavior. Thus, introducing a positive charge into the antibody framework may not be a viable strategy for improving the therapeutic potential of ADCs. Full article

Background/Objectives: There is increasing evidence that a subset of patients with stage IV pancreatic ductal adenocarcinoma (PDAC) and liver-only metastasis may benefit from surgical resection of both the primary tumor and metastatic lesions. Methods: A meta-analysis and systematic review were conducted in patients with stage IV PDAC and hepatic-only metastasis. A comprehensive literature search (January 2015–June 2023) was performed using PubMed with keywords including “pancreatic cancer”, “oligometastatic”, and “surgery”. Results: Sixteen articles were included in the final review and characterized based on patient selection factors and prognostic indicators. Seven studies reported hazard ratios (HRs) or Kaplan–Meier curves for survival in synchronous resected cohorts versus chemotherapy/palliation alone, which indicated a statistically significant survival benefit in the resection cohorts (pooled HR: 0.41, 95% CI: 0.31–0.53, p < 0.01). Prognostic indicators for synchronous and metachronous resection included lower pre-operative CA19-9, negative margin status of the primary tumor, moderate-to-well-differentiated tumors (grades I–II), and receiving pre-operative chemotherapy. Conclusions: Surgical/ablation selection factors are evolving, with priorities on (1) response to induction chemotherapy, (2) ability to achieve R0 resection, and (3) minimally invasive approaches remaining critical to optimal patient selection. Standardized radiologic and tumor marker evaluation and response to neoadjuvant therapy and optimizing performance status are critical to improved outcomes. Full article

Post-transplant lymphoproliferative disorder (PTLD) is the most common malignancy in adults who receive solid organ transplantation (SOT), apart from skin cancer. It is a serious and potentially fatal complication of chronic immunosuppression (ISI) in SOT recipients. This report describes a 20-year (2001–2021) clinicopathological experience with 59 PTLD patients at an urban center. The median time from transplant to PTLD was 8.5 years and the most common types of transplants were kidney (41%) and liver (31%). Epstein–Barr encoding region (EBER) was positive in 51% tumors, and 50% patients had Epstein–Barr virus (EBV) viremia at diagnosis. Overall survival (OS) at 1 year and 5 years was 78% and 64%, respectively. OS was significantly (p < 0.05) shorter in males (hazard ratio [HR] 3.7), certain organ transplants (lung HR 10.4; liver HR 3.9 relative to kidney), PTLD diagnosed within 12 months of transplant (HR 4.1), multi-organ involvement at diagnosis (HR 7.1), vitamin D deficiency at diagnosis (HR 4.5), and low serum albumin level at diagnosis (HR 3.6). Our study highlights the prognostic factors of PTLD and corroborates improved PTLD outcomes in the past 20 years. Full article