Ductal Adenocarcinoma Research Articles

Collagen turnover biomarkers to predict outcome of patients with biliary cancer.

The collagen-rich tumor stroma plays a crucial role in biliary tract cancer (BTC). Collagen biomarkers of type I collagen (reC1M), type III collagen (PRO-C3), type IV collagen (C4G), type VIII collagen (PRO-C8), type XI collagen (PRO-C11), type XVII collagen (PRO-C17) and type VIII collagen (TUM) may be used as potential non-invasive biomarkers. We measured the seven biomarkers of collagen turnover in sera of 72 patients with BTC at baseline and after first and second chemotherapy cycle (CTX). Markers were also assessed in sera of 50 healthy controls and compared to levels of patients at baseline. The diagnostic and prognostic value of the markers was evaluated for overall survival (OS) and progression-free survival (PFS). Patients had a median age of 65 years (IQR 57-70), while healthy controls were younger, with a median age of 46 years (IQR 38-54). The majority of patients (62%) were diagnosed with intrahepatic bile duct adenocarcinoma. Except C4G, all collagen turnover markers were significantly (p < 0.001) increased in serum from patients with BTC compared to healthy controls. PRO-C3 was the best marker to discriminate between patients with BTC and controls, reaching an area under a receiver operating characteristic (AUROC) of 0.98 (95% CI 0.95; 0.99) with a sensitivity (92%) and specificity (94%) balanced cutoff of 77.3 ng/ml. Patients with high levels (cohort separated by median split) of PRO-C8 (HR 2.85, 95% CI 1.42; 5.73) followed by C3M (HR 2.33, 95% CI 1.2; 4.5), PRO-C3 (HR 3.09, 95% CI 1.5; 6.36) and CA 19-9 (HR 2.52, 95% CI 1.37; 4.64) as reference biomarker had a shorter OS. Notably, only the novel marker PRO-C8 was also predictive of PFS (HR 3.26, 95% CI 1.53; 6.95). Associations with survival outcomes remained significant after adjusting for relevant risk factors (CA 19-9 and CEA at baseline, age, presence of metastases, weight, height and gender). The collagen turnover markers PRO-C8, C3M, PRO-C3 and the established biomarker CA 19-9 were prognostic for OS in patients with BTC while only PRO-C8 was also predictive for PFS. PRO-C3 showed the best diagnostic performance to discriminate between patients with BTC and controls. Trial registration number and date of registration NCT00661830 (NCT number) 15 April 2008 Trial registry The complete registry can found under: https://clinicaltrials.gov/study/NCT00661830?tab=table#administrative-information (last accessed 01/2025) Principal investigator and study sponsor Markus Moehler, MD Johannes Gutenberg University Mainz.

Treatment with TNFα and lipolysis-stimulated lipoprotein receptor (LSR) antibody in the presence of HDAC inhibitors promotes apoptosis in human salivary duct adenocarcinoma

ABSTRACT Lipolysis-stimulated lipoprotein receptor (LSR), a lipid metabolism-related factor localized in tricellular tight junctions (tTJs), plays an important role in maintaining the epithelial homeostasis. LSR is highly expressed in well-differentiated cancers, and its expression decreases during malignancy. The LSR antibody inhibits cell growth and promotes apoptosis in some cancers. Histone deacetylases (HDACs) are thought to play a crucial role in carcinogenesis, and HDAC inhibitors promote differentiation and prevent cell proliferation and migration in cancers. HDAC inhibitors together with TNFα also induce apoptosis via TNFα-related apoptosis-inducing ligand (TRAIL) in some cancers. In this study, we investigated the apoptosis signaling induced by an anti-LSR antibody in human salivary duct adenocarcinoma (SDC) cell line A253, compared to TRAIL-induced apoptosis. A253 cells were treated with human recombinant TNFα with or without HDAC inhibitor trichostatin A (TSA) and quisinostat (JNJ-26481585). Treatment using TNFα with HDAC inhibitors markedly induced apoptosis in A253 cells and the anti-TNFα antibody prevented the induced apoptosis. A253 cells were treated with an antibody against the extracellular N-terminal domain of human LSR (LSR-N-ab) with or without HDAC inhibitors. Treatment with HDAC inhibitors induced LSR expression in the membranes of A253 cells. Treatment using LSR-N-ab with HDAC inhibitors markedly promoted apoptosis in A253 cells. The tricellular signaling pathway JNK inhibitor SP600125 and Hippo pathway MST1/2 inhibitor XMU-MP-1 prevented the apoptosis induced by treatment using TNFα or LSR-N-ab with HDAC inhibitors. Our findings indicated that treatment with TNFα or LSR-N-ab with HDAC inhibitors might be useful in the therapy for human SDC by enhancing apoptosis.

Prostatic duct adenocarcinoma-A challenging variant of prostate cancer in a low-resource setting.

This case emphasizes the challenges in diagnosing and treating Prostatic Duct Adenocarcinoma, especially in resource-limited settings. Early and accurate diagnosis is crucial for better patient outcomes, but limited access to advanced diagnostics and specialized treatments significantly hinders the effective management of this aggressive form of prostate cancer.

Imaging findings of intrahepatic cholangiocarcinoma for prognosis prediction and treatment decision-making: a narrative review

Intrahepatic cholangiocarcinoma (iCCA) is a heterogeneous bile duct adenocarcinoma with a rising global incidence and a poor prognosis. This review aims to present a comprehensive overview of the most recent radiological research on iCCA, focusing on its histopathologic subclassification and the use of imaging findings to predict prognosis and inform treatment decisions. Histologically, iCCA is subclassified into small duct (SD-iCCA) and large duct (LD-iCCA) types. SD-iCCA typically arises in the peripheral small bile ducts and is often associated with chronic hepatitis or cirrhosis. It presents as a mass-forming lesion with a relatively favorable prognosis. LD-iCCA originates near the hepatic hilum, is linked to chronic bile duct diseases, and exhibits more aggressive behavior and poorer outcomes. Imaging is essential for differentiating these subtypes and assessing prognostic factors like tumor size, multiplicity, vascular invasion, lymph node metastasis, enhancement patterns, and intratumoral fibrosis. Imaging-based prognostic models have demonstrated predictive accuracy comparable to traditional pathological staging systems. Furthermore, imaging findings are instrumental in guiding treatment decisions, including those regarding surgical planning, lymphadenectomy, neoadjuvant therapy, and the selection of targeted therapies based on molecular profiling. Advancements in radiological research have improved our understanding of iCCA heterogeneity, facilitating prognosis prediction and treatment personalization. Imaging findings assist in subclassifying iCCA, predicting outcomes, and informing treatment decisions, thus optimizing patient management. Incorporating imaging-based approaches into clinical practice is crucial for advancing personalized medicine in the treatment of iCCA. However, further high-level evidence from international multicenter prospective studies is required to validate these findings and increase their clinical applicability.

CT and MRI of pancreatic cystic lesions: tricks of the trade

PurposeTo describe CT and MRI findings of pancreatic cystic lesions.BackgroundThe growing use of ultrasound, CT and MRI has led to increasing incidental detection of pancreatic cystic lesions. These lesions range from benign entities (e.g., acute necrotic collection) to potentially malignant neoplasms (e.g., IPMN) and malignant neoplasms (e.g., ductal adenocarcinoma). CT and MRI can help to differentiate pancreatic cystic lesions.FindingsPancreatic cystic lesions neoplasms often have pathognomonic CT and MRI characteristics. It is important to consider size, number of cysts, septa, the relationship with the main pancreatic duct, internal nodules and wall enhancement. Guidelines from different societies have been developed to promote and standardize the management and follow-up of pancreatic cystic lesions.ConclusionCT and MRI play a crucial role in the detection and characterization of pancreatic cystic lesions.

Application of LEF-1 immunohistochemical staining in the diagnosis of solid pseudopapillary neoplasm of the pancreas

IntroductionSolid pseudopapillary neoplasm (SPN) is a tumor of young females with gain-of-function mutation in catenin beta 1 gene involved in Wnt signal transduction pathway. Beta-catenin immunohistochemistry (IHC) is used to diagnose SPN. Lymphoid enhancer-binding factor 1 (LEF-1) has been recognized in the transactivation of Wnt pathway. We aim to study LEF-1 IHC in SPN and other pancreatic tumors and compare it with beta-catenin IHC. MethodsWe retrieved cases of SPN, pancreatic neuroendocrine tumor (PanNET), serous cystadenoma (SCA), ductal adenocarcinoma (PDAC) and acinar cell carcinoma (ACC) from 2011 to 2023. Formalin-fixed, paraffin-embedded blocks with adequate tumor were cut and stained with beta-catenin (B-Catenin-1 clone) and LEF-1 (EP310 clone) IHC. Cases were reviewed by two pathologists independently. Nuclear staining with LEF-1 and beta-catenin was considered as positive. ResultsOur cohort consisted of 111 cases [SPN = 59 (42 resections, 11 FNA, 6 biopsies), PDAC = 24, PanNET = 22, SCA = 5, ACC = 1]. For SPN cases male to female ratio was1:8. Age ranged from 9 to 81 years (average: 32 years). Pancreatic tail was the most common location (47 %) followed by head (28 %), body (19 %) and neck (6 %). Tumor size ranged from 1.0 to 12.2 cm (average: 5 cm). Among the SPN cases 57/59 demonstrated strong nuclear LEF-1 staining. 2/49 cases were negative for LEF-1 (both pathologist in agreement). All SPN tumors demonstrated nuclear staining with beta-catenin. Among the non-SPN tumors, beta-catenin showed nuclear staining in 2/52 cases (2 PDAC). The remaining 50 cases were negative for nuclear beta-catenin and demonstrated variable staining pattern with interpretation variability between the two pathologists. The sensitivity and specificity for LEF-1 were 97 % and 100 %, respectively, while for beta-catenin, they were 100 % and 96 % respectively. ConclusionCrisp nuclear staining of LEF-1 without background staining makes diagnostic interpretation relatively easy and accurate compared to beta-catenin IHC. This is further helpful for small biopsy samples to help differentiate SPN from mimickers such as PanNET. None of the non-SPN cases displayed nuclear LEF-1 rendering it a valuable adjunct to beta-catenin in the diagnostic evaluation of SPN.

Aberrant Expression of Pneumocytic Markers (TTF-1 and Napsin-A) in Biliary Duct and Gallbladder Adenocarcinomas; A Potential Diagnostic Pitfall.

Cholangiocarcinomas and gallbladder carcinomas are epithelial tumours with biliary differentiation. On histology and immunohistochemistry, they resemble adenocarcinomas and possess overlapping immunohistochemical profiles. Diagnosing these tumours is best done using appropriate imaging and clinical features with compatible immunohistochemistry. Immuno-staining for thyroid transcription factor-1 (TTF-1) and novel aspartic proteinase of pepsin A (Napsin-A) is believed to be specific for primary pulmonary adenocarcinomas. We herein report uncommon instances of strong and diffuse expression of these markers in two examples of adenocarcinomas arising from the bile duct and gallbladder. A review of the literature and a summary of similar studies relating to aberrant TTF-1 and Napsin-A expression in biliary tract adenocarcinomas are presented.

Genome-Derived Ampullary Adenocarcinoma Classifier and Postresection Prognostication

Ampullary adenocarcinoma (AA) is characterized by clinical and genomic heterogeneity. A previously developed genomic classifier defined biologically distinct phenotypes with greater accuracy than standard histologic classification. External validation is needed before routine clinical use. To test external validity of the prognostic value of the hidden genome classifier of AA. This retrospective cohort study took place at 6 international academic institutions. Consecutive patients (n = 192) who underwent curative-intent resection of histologically confirmed AA were included. The data were analyzed from January 2005 through July 2020. The multilevel meta-feature regression model previously trained on a prospectively sequenced cohort of 3411 patients (1001 pancreatic adenocarcinoma, 165 distal bile duct adenocarcinoma, and 2245 colorectal adenocarcinoma) was applied to AA sequencing data to quantify the relative proportions of parental cell of origin. Genomic classification was correlated with immunohistologic subtype (intestinal [INT] or pancreatobiliary [PB]) and with overall survival (OS), using the log-rank test and Cox proportional hazard models. Among 192 patients with AA (median age, 69.0 [IQR, 60.0-74.0] years and 134 were male [64%]), concordance between immunohistologic and genomic subtypes was 55%. Most INT subtype tumors were categorized into the colorectal genomic subtype (43 of 57 [72.9%]). Of the 114 PB subtype tumors, 29 had a pancreatic genomic profile (25.4%) and 24 had a distal bile duct genomic profile (21.1%). Whereas the standard immunohistologic subtypes were not associated with survival (log rank P = .26), predicted genomic probabilities were correlated with survival probability. Genomic scores with higher colorectal probability were associated with higher survival probability; higher pancreatic and distal bile duct probabilities were associated with lower survival probability. The AA genomic classifier is reproducible with available molecular testing in a diverse international cohort of patients and improves stratification of the divergent clinical outcomes beyond standard immunohistologic classification. These data provide a molecular classification that may be incorporated into clinical trials for prospective validation.

Unveiling the unexplored secret: Aggressive behavior and poor survival in intrahepatic mucinous adenocarcinoma compared to conventional adenocarcinoma

Intrahepatic bile duct mucinous adenocarcinoma (IHBDMAC) is a rare pathological subtype of intrahepatic cholangiocarcinoma (IHCC), and its tumor biological features and survival outcomes have rarely been explored, especially when compared to the most common subtype, intrahepatic bile duct adenocarcinoma (IHBDAC). Therefore, the aim of this study was to explore the clinical features and survival outcomes of IHBDAC and IHBDMAC using the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2021. A total of 1,126 patients were included, with 1,083 diagnosed with IHBDAC and 43 diagnosed with IHBDMAC. Patients with IHBDMAC presented with a more advanced T stage (55.8% vs. 36.9%, P = 0.012) and higher rate of lymph node metastasis (37.2% vs. 24.9%, P = 0.070). Cox regression identified advanced T stage, lymph node metastasis, and distant metastasis as poor survival predictors, while chemotherapy and surgery were protective factors. Survival analyses revealed significantly worse overall survival (OS) and cancer-specific survival (CSS) for IHBDMAC compared to IHBDAC (P < 0.05). Even after matching, patients with IHBDMAC still had a worse prognosis than those with IHBDAC. These findings highlight the aggressive nature of IHBDMAC and the need for tailored therapeutic strategies. Future research should focus on prospective studies and molecular insights to develop targeted treatments for IHBDMAC.

The significance of neuroendocrine component in cases with intrahepatic cholangiocarcinoma: A SEER-based retrospective cohort study

ObjectiveTo evaluate the significance of neuroendocrine component in cases with intrahepatic cholangiocarcinoma (IHCC). MethodsCases with IHNECA and IHBDAC from the Surveillance, Epidemiology, and End Results (SEER) database were retrospectively reviewed and analyzed. Comparative analyses in terms of clinic-pathological features and long-term survival were performed between cases with intrahepatic neuroendocrine carcinoma (IHNECA) and intrahepatic bile duct adenocarcinoma (IHBDAC). ResultsA total of 5211 cases with IHCC were included (103 with IHNECA and 5108 with IHBDAC). Comparable age status (P=0.168), sex status (P=0.274), and cirrhosis status (P=0.480) were acquired between two groups while inconsistent distributions in races (P=0.027) and marital status (P=0.028) were also acquired. Cases with IHBDAC were generally in a more advanced stage and shared a worse prognosis. A significantly higher incidence of lymph node metastasis was detected among cases with IHBDAC (24.8% vs 15.5%, P=0.031). Although the overall surgery rate was comparable between two groups (P=0.519), chemotherapy (53.0% vs 37.9%, P=0.002) and radiotherapy (6.0% vs 1.0%, P=0.032) were more frequently performed with a much higher cancer-related death (CRD) (79.4% vs 58.3%, P<0.001) acquired in cases with IHBDAC. INHECA served as an independent protective factor for cases with IHCC. Even after matching, cases with IHBDCA still shared a higher incidence with CRD (P=0.010) and a worse prognosis, especially for cases who received surgery. ConclusionIHNECA was associated with less aggressive tumor biological features and worse prognosis. More in-depth research focusing on IHNECA with more detailed clinical and pathological data is required.

(305) MEN WITH PEYRONIE’S DISEASE ARE DIAGNOSED WITH CANCER AT AN EARLIER AGE: GENETICS OR A FOOT IN THE DOOR?

Abstract Introduction Men with Peyronie’s Disease (PD) are theorized to have an increased cancer risk. PD is characterized by infiltrative growth, proliferation, and decreased apoptosis- pathways shared by malignant neoplastic growth. Thus, one can hypothesize a genetic predisposition toward cancer as heralded by PD pathogenesis. Objective To investigate this hypothesis, we identified patients with and without PD over a 28-year period and quantified demographics and cancer incidences. Methods We performed a retrospective review of patients cared for by a single urologic provider in Houston, Texas, from 1995 to 2023 and identified those patients with and without PD. These data were sent to the Texas Cancer Registry who identified those patients with a diagnosis of cancer. They returned data including age at diagnosis, cancer anatomic site, and histologic subtype. Data were then studied in detail, and appropriate statistical analyses performed with GraphPad Prism Software. Results From 1995-2023 we identified 148 patients with PD and a diagnosis of cancer and 707 patients without PD (controls) and a diagnosis of cancer. Overall, patients with PD were diagnosed at an earlier age across all cancers v. controls (median 59 y v 64 y, p = 0.0008, student’s t-test). The relative frequencies of cancer subtypes were then compared between the PD and control group and log transformed. Overall, we found higher relative frequencies (2-fold difference) of nervous system, ill-defined, intrahepatic bile duct, nasal cavity, oropharynx, and thyroid cancers and lower relative frequencies of kidney, large intestine, and renal pelvis/ureter cancers in the PD group. Regarding histologic subtypes in this cohort, we found higher relative frequencies of bile duct adenocarcinoma, follicular lymphoma, intraductal papillary-mucinous carcinoma, Kaposi sarcoma, and melanoma, and lower relative frequencies of carcinoid, clear cell adenocarcinoma, multiple myeloma, and unspecified neoplasms. Conclusions Patients with PD are diagnosed with cancer at an earlier age. Our data aligns with previous work demonstrating higher rates of upper aerodigestive tract and melanoma cancers and lower rates of large intestine and kidney cancers in men with PD. We provide a more detailed and stratified look among histologic cancer subtypes within men with PD. While our data support the genetic similarity hypothesis in which PD and malignant neoplasm share pathologic pathways, it also raises the question of whether PD simply brings patients to the doctor’s office sooner, resulting in increased cancer detection and diagnosis. Disclosure No.

68Ga-PSMA PET/CT and 18F-FDG PET/CT in the diagnosis of prostatic ductal cancer

PurposesTo explore the characteristics of PSMA PET/CT and FDG PET/CT images in prostatic ductal adenocarcinoma (DA) patients. MethodsWe retrospectively enrolled prostatic DA patients with PET/CT scans at Tongji Hospital from 2018 to 2022. Patients with prostatic acinar adenocarcinoma (AA) and benign pathology (BP) were enrolled by 1:1 matching. Differences in the uptake of primary and metastatic foci on PET among the groups were analyzed. ResultsA total of 42 patients were enrolled: 14 in each group. In primary foci, the mean PSMA uptake in the DA group was lower than that in the AA group (14.2 ± 9.6 vs. 27.1 ± 14.3, P = 0.009) and greater than that in the BP group (14.2 ± 9.6 vs. 4.7 ± 1.3, P = 0.003). The AUCs of the DA-AA ROC curve and DA-BP ROC curve were 0.781 and 0.872, respectively. The median PSMA uptake of metastatic lymph nodes in the DA group was lower than that in the AA group (5.6 vs. 14.2, P = 0.033), with no significant difference in metastatic bone lesions (9.5 vs 19.1, P = 0.485). No significant difference was found in the FDG uptake of primary and metastatic foci between the DA and AA groups (P > 0.05). ConclusionProstatic DA has greater PSMA uptake than BP diseases, but lower uptake in both primary foci and metastatic lymph nodes than AA on PSMA PET/CT, aiding in the differential diagnosis of DA, AA and BP diseases. Clinicians should combine traditional imaging with PSMA PET/CT to avoid underestimating the clinical stage of DA patients.

Feasibility study of ADCs targeting TROP-2, HER2, and CD46 in Ductal Adenocarcinoma and Intraductal Carcinoma of the prostate.

Ductal Adenocarcinoma (DAC) and Intraductal Carcinoma of the Prostate (IDC-P) respond poorly to all the currently available conventional therapies. Given their accurate and efficient elimination of cancer cells, Antibody-Drug Conjugates (ADCs) have become one of the most promising anticancer treatments. However, no ADCs have so far been approved for Prostate Cancer (PCa) treatment. This study investigated TROP-2, HER2, and CD46 expression in DAC/IDC-P samples, indirectly analyzing their preliminary feasibility as therapeutic targets for future treatment of the two conditions. We conducted a retrospective study involving 184 participants (87 DAC/IDC-P patients and 97 Prostatic Acinar Adenocarcinoma (PAC) patients with a Gleason score ≥ 8) without prior treatment between August 2017 and August 2022. Immunohistochemical staining was employed to detect the differential protein expressions of TROP-2, HER2, and CD46 in DAC/IDC-P, PAC, and normal prostate tissues. Compared to pure PAC tissues, TROP-2 expression was significantly higher in DAC/IDC-P and DAC/IDC-P-adjacent PAC tissues (H-score 68.8 vs. 43.8, p < 0.001, and 59.8 vs. 43.8, p = 0.022, respectively). No significant differences in HER2 expression were observed across different cancer tissues. Compared to both DAC/IDC-P-adjacent PAC and pure PAC tissues, CD46 expression was significantly higher in DAC/IDC-P tissues (42.3 vs. 28.6, p = 0.041, and 42.3 vs. 24.3, p = 0.0035, respectively). Herein, TROP-2 and CD46 expression was higher in DAC/IDC-P tissues than in pure PAC and normal prostate tissues. This finding implies that ADCs targeting the two proteins hold significant promise as potential future treatments for DAC/IDC-P.

Hsa_circ_0007590/PTBP1 complex reprograms glucose metabolism by reducing the stability of m6A-modified PTEN mRNA in pancreatic ductal adenocarcinoma.

The role of circular RNAs (circRNAs) in glucose metabolism in pancreatic duct adenocarcinoma (PDAC) remains elusive. Through RNA sequencing of cells cultured under conditions of glucose deprivation, we identified hsa_circ_0007590. Sanger sequencing and RNase R and Act D treatments were performed to confirm the circular RNA features of hsa_circ_0007590. RNA in situ hybridization (RNA-ISH) and quantitative reverse transcription PCR (qRT-PCR) were used to estimate hsa_circ_0007590 expression in PDAC clinical specimens and cell lines. hsa_circ_0007590 expression was higher in PDAC patients and closely related to the clinicopathological characteristics of the disease. Cytoplasm‒nuclear fractionation and FISH assays demonstrated that hsa_circ_0007590 was located in the nucleus. Gain-of-function and loss-of-function assays were performed to assess the biological behaviors of PDAC cells. Seahorse XF assays were performed to validate the Warburg effect. hsa_circ_0007590 facilitated the proliferation, migration, and invasion of PDAC cells and promoted the Warburg effect. Mass spectrometry, RNA pulldown, RNA immunoprecipitation (RIP), RNA m6A quantification, m6A dot blot, MeRIP, and Western blotting were conducted to investigate the detailed mechanism through which hsa_circ_0007590 produces these effects. Mechanistically, hsa_circ_0007590 targeted PTBP1 and increased the expression of the m6A reader protein YTHDF2, leading to PTEN mRNA degradation and PI3K/AKT/mTOR pathway activation. Overall, hsa_circ_0007590, which targets PTBP1, reprograms glucose metabolism by attenuating the stability of m6A-modified PTEN mRNA and holds potential promise as a therapeutic target for PDAC.

Implications of unconventional histological subtypes on magnetic resonance imaging and oncological outcomes in patients who have undergone radical prostatectomy

The prognostic significance of unconventional histology (UH) subtypes including intraductal carcinoma of the prostate (IDC-P), ductal adenocarcinoma, and cribriform pattern has been investigated for prostate cancer (PCa). However, little is known about magnetic resonance imaging (MRI) features and the oncological impact of tumor localization in localized PCa with UH. Clinical data of 211 patients with acinar adenocarcinoma (conventional histology [CH]) and 82 patients with UH who underwent robotic-assisted radical prostatectomy (RARP) were reviewed. Patients with UH are more likely to be older and have higher Gleason grade group, higher Prostate Imaging-Reporting and Data System (PI-RADS) v2.1 score, and larger tumor volume (TV) than those with CH. Multivariate analysis identified the presence of UH as an independent prognostic factor for progression-free survival (PFS) (hazard ration (HR) 2.41, 95% confidence interval (CI) 0.22–0.79, P = 0.0073). No significant difference in PFS was seen regarding tumor localization (transition zone [TZ] or peripheral zone [PZ]) in patients with UH (P = 0.8949), whereas PZ cancer showed shorter PFS in patients with CH (P = 0.0174). PCa with UH was associated with higher progression than PCa with CH among resection margin (RM)-negative cases (P < 0.0001). Further, increased PI-RADS v2.1 score did not correlate with larger TV in UH (P = 0.991), whereas a significant difference in TV was observed in CH (P < 0.0001). The prognostic significance of UH tumor was independent of tumor localization, and shorter PFS was observed even in RM-negative cases, indicating an aggressive subtype with micro-metastatic potential. Furthermore, UH tumors are more likely to harbor a large TV despite PI-RADS v2.1 score ≤ 3. These findings will help optimal perioperative management for PCa with UH.

Early detection of pancreatic cancer by liquid biopsy “PANLIPSY”: a french nation-wide study project

BackgroundPancreatic cancer, predominantly characterized by ductal adenocarcinoma (PDAC) accounts for 90% of cases and is the fourth leading cause of cancer-related deaths globally. Its incidence is notably increasing. This poor prognosis is primarily due to late-stage diagnosis (approximately 70% to 80% of patients are diagnosed at an advanced stage), aggressive tumor biology, and low sensitivity to chemotherapy. Consequently, it is crucial to identify and develop a simple, feasible and reproducible blood-based signature (i.e., combination of biomarkers) for early detection of PDAC.MethodsThe PANLIPSY study is a multi-center, non-interventional prospective clinical trial designed to achieve early detection of PDAC with high specificity and sensitivity, using a combinatorial approach in blood samples. These samples are collected from patients with resectable, borderline or locally advanced, and metastatic stage PDAC within the framework of the French Biological and Clinical Database for PDAC cohort (BACAP 2). All partners of the BACAP consortium are eligible to participate. The study will include 215 PDAC patients, plus 25 patients with benign pancreatic conditions from the PAncreatic Disease Cohort of TOuLouse (PACTOL) cohort, and 115 healthy controls, totaling 355 individuals. Circulating biomarkers will be collected in a total volume of 50 mL of blood, divided into one CellSave tube (10 mL), two CELL-FREE DNA BCT® preservative tubes (18 mL), and five EDTA tubes (22 mL in total). Samples preparation will adhere to the guidelines of the European Liquid Biopsy Society (ELBS). A unique feature of the study is the AI-based comparison of these complementary liquid biopsy biomarkers.Main end-points: i) to define a liquid biopsy signature that includes the most relevant circulating biomarkers, ii) to validate the multi-marker panel in an independent cohort of healthy controls and patients, with resectable PDAC, and iii) to establish a unique liquid biopsy biobank for PDAC study.DiscussionThe PANLIPSY study is a unique prospective non-interventional clinical trial that brings together liquid biopsy experts. The aim is to develop a biological signature for the early detection of PDAC based on AI-assisted detection of circulating biomarkers in blood samples (CTCs, ctDNA, EVs, circulating immune system, circulating cell-free nucleosomes, proteins, and microbiota).Trial registrationClinicalTrials.gov Identifier: NCT06128343 / NCT05824403. Registration dates: June 8,2023 and April 21, 2023.

Long-term safety of lanthanum carbonate in the real word: a 19-year disproportionality analysis from the FDA Adverse Event Reporting System

Background Lanthanum carbonate is widely used to manage serum phosphate and calcium levels in end-stage kidney disease (ESKD) patients, yet comprehensive long-term safety data are lacking. This study leverages the FDA Adverse Event Reporting System (FAERS) to assess the extended safety profile of lanthanum carbonate. Research design and methods We analyzed FAERS data (2004-2022) to study the association between lanthanum carbonate and adverse events (AEs). Using MedDRA v25.0, we identified risk signals through System Organ Classes (SOCs) and Preferred Terms (PTs). Disproportionality analyses quantified lanthanum carbonate-associated AE signals. Results Among 3,284 reports, 2,466 were primary suspected AEs linked to lanthanum carbonate. Males reported AEs more frequently than females. Patients aged over 64 represented the majority. Median onset time for lanthanum carbonate-related AEs was 146 days. Gastrointestinal disorders were prevalent. We identified 16 new signals, including stress, abnormal hepatic function, cholelithiasis, bile duct stone, gastric cancer, and adenocarcinoma gastric. Stress was notable, particularly in male patients over 65 and those with lower weight. Conclusions This study affirms lanthanum carbonate’s long-term safety for reducing elevated blood phosphorus levels. While gastrointestinal disorders were common, attention must focus on emerging AEs, particularly stress, especially in elderly patients.

Genomic profile of Japanese patients with rare ductal adenocarcinoma of the prostate has high grade and poor prognostic aspects.

e17046 Background: Ductal adenocarcinoma (DAC) is a rare subtype of prostate cancer with unknown etiology and poor prognosis. Genomic profile analysis using next-generation sequencing has the potential to elucidate the pathogenesis of rare cancers. To date, some studies have investigated the genetic profile of the DAC genotype; however, no definitive findings have been obtained due to the small number of patients and limited geographic coverage. The discovery of novel prognostic biomarkers and identification of new pharmacotherapeutic targets for DAC are currently of research interest. The aim of this study is to analyze the genomic profile of DAC in a Japanese population and to summarize its features. Methods: Clinical and histopathological records from our three hospitals were searched for radical prostatectomy, transurethral resection of the prostate, and prostate needle biopsy specimens containing a DAC component in the past 10 years. Twenty-eight patients diagnosed with DAC of the prostate were identified, of whom 15 were eligible for genomic profile analysis and 10 patients (66.7%) had the pure type. Genomic evaluation was performed using either the FoundationOne CDx or PleSSision testing platform. Results: At least one genomic alteration occurred in 14 patients (93.3%), and the most frequently mutated gene was tumor suppressor protein p53 ( TP53), which was found in seven cases (46.7%). Additionally, five cases (33.3%) had mutations in retinoblastoma transcriptional corepressor 1 ( RB1), and all these patients had the pure type. Four cases had both TP53 and RB1 alterations, and most of these possessed the pure type and had PSA levels of less than 4.0. Compared to previous study results, the frequency of genetic alterations in the phosphoinositide 3-kinase (PI3K) pathway (n = 3; 20.0%) and Wnt-β/catenin pathway (n = 6; 40.0%) was comparable, but alterations in the DNA damage repair (DDR) pathway were few (n=1; 6.7%). None of the patients presented high tumor mutation burden or microsatellite instability. Conclusions: We found that the Japanese cohort with DAC has unique features such as high frequency of alterations in tumor suppressor gene such as TP53 and RB1, and few DDR pathway alterations, suggesting the existence of regional and racial differences in genomic profiles. Genomic analysis using next-generation sequencing is expected to be useful in elucidating the pathogenesis of DAC, and further accumulation of cases is considered important.

Landscape of HER2-low breast cancer: Insights from a six-year study on incidence and clinicopathological characteristics.

e13148 Background: Human epidermal growth factor receptor 2 (HER2)-low breast cancer has emerged as a subtype of breast cancer, defined by HER2 1+ or 2+ in immunohistochemistry (IHC) and the absence of the ERBB2 gene amplification on fluorescence in situ hybridization (FISH). Recent trials showed marked response of HER2 breast cancer to novel anti-HER2 antibody-drug conjugates, rising interest in the HER2-low subtype. To date, data on characteristics of HER2-low breast cancer subtype is limited. Herein, we describe the clinicopathological characteristics of HER2-low breast cancer subtype compared HER2-zero/negative breast cancer. Methods: Real-world data from the Anatomic Pathology Division of Hotel Dieu de France, spanning 2017-2022, was retrospectively collected. Patients with HER2-IHC 3+ and HER2-IHC 2+ with ISH-amplified (HER2-positive) were excluded to compare HER2-low to HER2-zero breast cancer subtypes. Patients were then categorized based on their hormone receptor (HR) status. Clinicopathological characteristics between the groups were compared using a Chi-Square and Mann–Whitney U tests. Results: Out of 1195 patients, we observed 341 (28.5%) HER2-low breast cancers cases. HER2-positive breast cancer cases (n=178; 14.9%) were subsequently excluded. There was no significant difference in age and sex between the HER2-low and the HER2-zero group (p=0.3 and 0.8, respectively). HER2-low breast cancer was associated with positive estrogen receptor (ER) status and positive progesterone receptor (PR) status (p&lt;0.001 and p=0.01, respectively). Ductal adenocarcinomas were more frequently observed in the HER2-low group, whereas lobular and metaplastic adenocarcinomas were especially prevalent in the HER2-zero group (all p&lt;0.001). When stratified by HR status, 87.4% of patients had HR-positive status and 12.6% were HR-negative. Furthermore, the occurrence rate of tumors with a low Ki-67 labeling index was comparable between the two groups (p=0.9). However, among the HR-negative group, HER2-low tumors tended to show lower proliferation index compared to HER2-zero tumors (p = 0.04; Table). Conclusions: In conclusion, this study showed that HER2-low is a distinct from HER2-zero and is frequently present among patients with breast cancer. Clinicopathological features such as histological type differ between HER2-zero and HER2-low breast cancer. Our findings suggest that, within HR-negative breast cancer, breast cancer with low HER2 expression exhibits a less aggressive profile when compared to HER2-zero tumors. [Table: see text]

Caudo-dorsal approach combined with the occlusion of right hepatic vein and Pringle maneuver in laparoscopic anatomical resection of segment 7.

Laparoscopic anatomical resection of segment 7 (LARS7) remains a technically challenging procedure due to the deep anatomical location and the potential risk of injury to the right hepatic vein (RHV). Herein, we initiated an innovative technique of caudo-dorsal approach combined with the occlusion of the RHV and Pringle maneuver for LARS7 and presented the outcomes of our initial series. Since January 2021, the patients who underwent LARS7 by using this novel technique were enrolled in this study. The critical aspect of this technique was the interruption of communication between the RHV and the inferior vena cava. Meanwhile, the Pringle maneuver was adopted to control the hepatic inflow. A total of 11 patients underwent LARS7 by using this novel technique, which included 8 hepatocellular carcinoma, 2 bile duct adenocarcinoma and one focal nodular hyperplasia. The median operative time was 199min (range of 151-318min) and the median blood loss was 150ml (range of 50-200ml). The main trunk of the RHV was fully exposed on the cutting surface in all cases and no patient received perioperative blood transfusion. No procedure was converted to open surgery. Of note, no indications of CO2 gas embolism were observed in these cases after the introduction of double occlusion. Only one patient suffered from postoperative complications and healed after treatment. The median postoperative stay was 5days (range of 4-7days). The 90-day mortality was nil. At a median follow-up period of 19months, all of the patients were alive without any evidence of tumor recurrence. The caudo-dorsal approach combined with the occlusion of RHV and the Pringle maneuver may be a feasible and expected technique for safe exposure of RHV in LARS7. Further validation of the feasibility and efficacy of this technique is needed.