Diagnosis Of PC Research Articles

The value of 68Ga-PSMA PET/CT in the diagnosis of intracapsular prostate cancer with a poor prognosis

ObjectiveTo evaluate the diagnostic value of 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) for intracapsular prostate cancer with a poor prognosis (PPC) and no extracapsular invasion or distant metastasis.MethodsThe PET/CT images and clinical data of 221 patients were retrospectively analyzed. These patients all had clear pathological results. The maximum standard uptake value (SUVmax) of the main lesions was measured at the postprocessing workstation and was tested for correlation with the pathological score. The diagnostic accuracy was calculated using the receiver operating characteristic (ROC) curve, and the best diagnostic threshold was calculated. The correlation between SUVmax and the International Society of Urological Pathology Grade Group (GG) was also analyzed.ResultsThe pathological results of the 221 patients were 48 benign lesions and 173 malignant lesions, including 81 PPC. Low-, intermediate-, and high-risk prostate cancers made up 21.97% (38/173), 54.33% (94/173), and 23.70% (41/173) of the malignant lesions, respectively. SUVmax and GG were positively correlated (r = 0.54, P < 0.01). The best SUVmax thresholds for 68Ga-PSMA PET/CT for the diagnosis of intracapsular PC and PPC were 7.95 and 13.94, respectively; the specificities were 0.83 and 0.85, the negative predictive values were 0.55 and 0.87, and the areas under the ROC curves were 0.88 and 0.88, respectively.Conclusion68Ga-PSMA PET/CT has high specificity and NPV in the diagnosis of intracapsular PPC, but the sensitivity for the diagnosis of intracapsular low-risk PC is low, which may cause some cases to be undetected.

Long non-coding RNA MIR600HG as a ceRNA inhibits the pancreatic cancer progression through regulating the miR-1197/PITPNM3 axis

ObjectivePancreatic cancer (PC) is considered to be a highly malignant cancer with poor prognosis. Long non-coding RNAs (lncRNAs) is the potential factor to predict cancer prognosis. The effect of MIR600HG in PC needs to be further studied. Our work mainly focused on the importance of MIR600HG for PC prognosis and its underlying molecular mechanism of regulating PC progression. MethodsData set was acquired from TCGA database to find differentially expressed genes and prognostic significance of MIR600HG in PC, and to construct the MIR600HG competitive endogenous RNA (ceRNA). Clinical specimens were collected to prove the analysis results. Vector over-expressed MIR600HG was transfected to study the roles of MIR600HG in proliferation, apoptosis, invasion and migration. The methods of CCK-8, flow cytometry, Transwell and scratch assays were all used in order to explore the apoptosis, migration and invasion. We evaluated the proliferation-related genes (PCNA, CyclinD1 and P27), as well as invasion and migration-related genes such as MMP-9, MMP-7 and ICAM-1. The transcriptional regulation between MIR600HG and miR-1197/PITPNM3 axis was determined with luciferase reporter assays. ResultsIn present study, MIR600HG was dropped in both PC tissues and cells, and the down-regulated MIR600HG was closely related to the poor clinical outcomes in PC patients. MIR600HG could inhibit proliferation, migration and invasion in PC cells. We also investigated whether MIR600HG acting as a sponge of microRNA-1197 (miR-1197) and miR-1197 acting on PITPNM3. We found the positive association between MIR600HG and PITPNM3, as well as the negative association of miR-1197 and MIR600HG (or PITPNM3). Moreover, PITPNM3 mRNA and protein expression saw a simultaneous increase after the MIR600HG-overexpression (MIR600HG-OE), but this result partially diminished in MIR600HG-OE cells and miR-1197 mimics. ConclusionsOur study explored the anticancer action of MIR600HG in PC by regulating miR-1197 to increase the expression of PITPNM3, which might help the diagnosis and therapy of PC.

The role of immunohistochemical examination in the differential diagnosis of atypical tumors and carcinomas of parathyroid glands

Studying the role of IHC analysis in the differential diagnosis of APT and PC. The study included 44 patients with morphologic diagnosis of the APT established after surgical treatment for primary hyperparathyroidism on the basis of Endocrinology Research Centre during 2018-2023. All cases underwent IHC examination with evaluation of CD31/CD34 and parathormone (PTH) expression for identification of vascular invasion, Ki-67, parafibromin. According to the results of IHC analysis in 8/44 patients (18.2%) the diagnosis of APT was revised in favor of the PC: in 7 of them vascular invasion was detected; in 1 patient the additional series of slices in the surrounding fatty tissue revealed foci of tumor growth, confirmed by positive reaction with antibodies to PTH. According to IHC results, the material was divided into 2 groups: APT and PC. There were no differences in clinical and morphological characteristics, Ki-67% level and parafibromin expression between the groups. Assessment of clinical and laboratory-instrumental data at the preoperative stage does not allow differentiating APT from PC. In case of APT diagnosis and detection of suspicious morphological features, it is necessary to perform IHC examination to exclude PC.

Bibliometric analysis of global research trends between gut microbiota and pancreatic cancer: from 2004 to 2023

BackgroundPancreatic cancer (PC) is one of the most lethal malignancies of the digestive system and is expected to be the second leading cause of cancer-related death in the United States by 2030. A growing body of evidence suggests that the gut microbiota (GM) is intimately involved in the clinical diagnosis, oncogenic mechanism and treatment of PC. However, no bibliometric analysis of PC and GM has been reported.MethodsThe literature on PC and GM was retrieved from the Web of Science Core Collection (WoSCC) database for the period from January 1, 2004 to April 25, 2023. Microsoft Excel 2021, CiteSpace, VOSviewer, Scimago Graphica, Graphpad Prism, Origin, the R package “bibliometrics” and the bibliometric online analysis program were used to visualize the publishing trends and hot spots in this field.ResultsA total of 1,449 articles were included, including 918 articles and 531 reviews. Publishing had grown rapidly since 2017, with the 2023 expected to publish 268 articles. Unsurprisingly, the United States ranked highest in terms of number of literatures, H index and average citations. The University of California System was the most active institution, but Harvard University tended to be cited the most on average. The three most influential researchers were Robert M. Hoffman, Zhao Minglei, and Zhang Yong. Cancers had published the most papers, while Nature was the most cited journal. Keyword analysis and theme analysis indicated that “tumor microenvironment,” “gemcitabine-resistance,” “ductal adenocarcinoma,” “gut microbiota” and “diagnosis” will be the hotspots and frontiers of research in the future.ConclusionIn summary, the field is receiving increasing attention. We found that future hotspots of PC/GM research may focus on the mechanism of oncogenesis, flora combination therapy and the exploitation of new predictive biomarkers, which provides effective suggestions and new insights for scholars.

A US real-world study of treatment patterns and outcomes in localized or locally advanced prostate cancer patients

PurposeMen with localized or locally advanced prostate cancer (LPC/LAPC) are at risk of progression after radiotherapy (RT) or radical prostatectomy (RP). Using real-world data, we evaluated patient characteristics, treatment patterns, and outcomes in LPC/LAPC.MethodsOptum claims and electronic health records (EHR) data from January 2010 to December 2021 were queried for men with LPC/LAPC who received primary RT, RP, or androgen deprivation therapy alone within 180 days after diagnosis. Survival outcomes were analyzed using descriptive statistics and Kaplan–Meier curves. Real-world overall survival (rwOS) was compared in patients with and without evidence of disease (i.e., disease recurrence, metastasis, diagnosis of castration-resistant PC) at defined time points.Results61,772 and 62,361 men in claims and EHR cohorts met the inclusion criteria. Median follow-up was 719 and 901 days, respectively. Most men received primary RT (51.0% claims, 35.0% EHR) or RP (39.4% claims, 53.8% EHR). Survival was greatest among men treated with RP, followed by RT. Adjusted for age and comorbidity, rwOS was shorter among men with evidence of disease within 1, 3, 4, and 5 years after primary treatment than those without at the same time points.ConclusionReal-world claims and EHR data show that survival among men with LPC/LAPC differs by primary treatment and time point of disease recurrence thereafter. Poor outcomes in men with LPC/LAPC who progress early indicate an unmet medical need for more effective primary treatment. If validated for surrogacy, no evidence of disease at specific time points could represent an intermediate efficacy endpoint in future trials.

Intermittent Versus Continuous Androgen Deprivation Therapy for Biochemical Progression After Primary Therapy in Hormone-Sensitive Nonmetastatic Prostate Cancer: Comparative Analysis in Terms of CRPC-M0 Progression

IntroductionTo analyze whether the use of an intermittent (IAD) versus continuous (CAD) androgen deprivation therapy for the treatment of biochemical progression after primary treatments in prostate cancer can influence the development of nonmetastatic castration resistant prostate cancer (CRPC-M0). Patients170 male patients with an histologically confirmed diagnosis of PC, presenting a biochemical progression after primary treatments (82 after radical prostatectomy and 88 after external radiation therapy), nonmetastatic at imaging were considered for continuous (85 cases) or intermittent (85 cases) administration of androgen deprivation therapy. Methodswe retrospectively collect all data regarding histological diagnosis, primary treatment, imaging for M0-M1 staging, PSA at progression, time to biochemical progression from primary therapy, ADT used, IAD cycles, so to compare in 2 groups (IAD vs. CAD) time for progression from the beginning of ADT treatment and type of progression in terms of CRPC-M0 versus CRPC-M1 cases. Resultsno significant (P= .4955) difference in the whole CRPC progression was found between IAD (25.8%) and CAD (30.5%) treatment at a mean of 32.7 ± 7.02 months and 35.6 ± 13.1 months respectively (P= .0738). Mean PSA at CRPC development was significantly higher in the IAD group (5.16 ± 0.68 ng/mL) than in the CAD group (3.1 ± 0.7 ng/mL) (P < .001). In all cases, imaging to detect M status at CRPC development was PET TC scan. At univariate analysis CAD administration significantly increases the RR for CRPC-M0 progression (RR 3.48; 95%CI 1.66-7.29; P = .01) when compared to the IAD administration, and this effect at multivariate analysis remained significant and independent to the other variables (RR 2.34, 95%CI 1.52-5.33; P = .03). Conclusionsin our population with biochemical progression after primary treatment for PC, the intermittent administration of ADT significantly reduces the risk to develop CRPC-M0 disease when compared to a continuous administration of ADT, whereas no difference between the 2 strategies in terms of CRPC-M1 progression exists.

Role of 68Ga-Labelled PSMA PET/CT in Assessment and Staging of Prostate Cancer

Background Prostate cancer (PCa) is the most common worldwide tumor in men with increasing incidence. Aim of the Work The purpose of our study is to evaluate the potential role of 68Ga-labelled PSMA PET/CT in assessment and staging of prostate cancer and correlate those positive findings with biopsy. Patients and Methods Thirty patients with pathologically confirmed prostate cancer who underwent PET/CT study. They were selected from Department of Radiology at Ain Shams University Hospital from November 2020 to May 2021. The patients’ ages ranged between 53 and 89 years old (mean age 66.43 ± 8.9 years). All patients underwent a 68Ga-PSMA PET/CT examination. For each patient, we determined the disease stage, the Gleason score, and the maximum standardized uptake value (SUVmax) for primary prostatic tumor and extraprostatic metastases. The diagnostic sensitivity and specificity of 68Ga-PSMA PET/CT for diagnosis and staging of PC were established by histopathology as the reference standard. Results Median SUVmax for the primary tumor was 12.88 (range, 6.7–25). Nineteen patients had associated PSMAavid lymph nodes, median SUVmax for those was 11 (range, 3.7–29). 68Ga-PSMA PET/CT detected extraprostatic metastases in 19 (63.3%) patients. The most common site of extraprostatic metastases was the bone (17 patients). The sensitivity of 68Ga-PSMA PET/CT examination in the diagnosis of PC was 90.9% and specificity was 68.4%. Conclusion 68Ga-PSMA PET/CT is a valuable tool with high diagnostic sensitivity and good specificity for diagnosis and staging of patients with newly diagnosed PC.

Mediastinal parathyroid carcinoma: a case report and review of the literature

BackgroundParathyroid carcinoma (PC) is an uncommon cause of primary hyperparathyroidism (PHPT) and particularly rare in the mediastinum. Herein, we present a case of mediastinal PC and conduct a related literature review.Case presentationWe described a case of a 50-year-old female patient with PHPT due to mediastinal PC. She was initially admitted to a local hospital in her hometown with hypercalcemia and high blood concentrations of PTH (parathyroid hormone). The patient underwent neck parathyroidectomy and pathological examination suggested parathyroid adenoma. Although the overproduction of serum calcium and PTH declined after the surgery, calcium and PTH increased again one month later, so the patient was transferred to our hospital. A 99mTc-sestamibi scan revealed an ectopic finding in the mediastinum, which was also indicated on the CT image. After removing the mediastinal mass, the metabolism of calcium and PTH quickly reverted to normal and the pathologic features of the mass were consistent with PC. By reviewing the related literature, we noticed that only scattered reports were published before 1982, and those were not included in the present review due to their differences with current radiological examination and treatment methods. After excluding outdated studies, we summarized and analyzed 20 reports of isolated mediastinal PC and concluded that. Parathyroidectomy remains the only curative treatment for the disease. Furthermore, the success of treatment directly depends on accurate preoperative localization.ConclusionWith this study, we emphasize the importance of accurate preoperative diagnosis of mediastinal PC and improve clinicians’ understanding of the disease.

Predicting the risk of pancreatic cancer in patients with new-onset diabetes based on CT image.

e16320 Background: While long-standing diabetes mellitus (LsDM) is an etiologic factor for PC, new-onset diabetes (NoDM) has been considered as a manifestation and harbinger of this cancer as well. Current evidence support that the PC-associated NoDM was mainly caused by disease of the exocrine pancreas, which was different from the typical type 2 DM. Therefore, we hypothesize that, in the NoDM patients, CT image features of “normal” pancreas from PC-associated NoDM patients might be different from that of the new-onset type 2 DM. We sought to develop and validate a risk prediction model to facilitate the distinction between NoDM vs potential early PC-associated NoDM on pancreatic CT imaging. Methods: We retrospectively collected CT imaging from three types of patients at Guangdong Provincial People's Hospital between January 2015 and December 2022: PC patients with pathological diagnosis of pancreatic ductal adenocarcinoma (n=249: 139 patients without DM, 63 patients with NoDM, 47 patients with LsDM), NoDM patients diagnosed with PC within 3 years (n=12), NoDM patients without development of cancer within the next 5 years (n=151). We used four different machine learning algorithms, including support vector machine (SVM), random forest (RF), eXtreme Gradient Boosting (XGB), and generalized linear model (GLM), and gradient boost methods, to build prediction models based on PC pateints and cancer-free NoDM patients. The algorithm with best ROC was used to build a final model, which was validated in the “normal” CT images of NoDM patients prior to their diagnosis of PC within 3 years. Results: In PC cases, the radiomics features exclusive to NoDM-PC cases were selected using a non-parametric test, and 134 radiomics features were retained (86 from arterial and 48 from venous phases, respectively). The RF algorithm showed best prediction skill (AUC of ROC: 0.952). Based on the variable importance measures in the RF algorithm, a risk-scoring model was generated for NoDM patients as a tool to differentiate between PC patients and cancer-free DM patients. As a result of validation, the scores calculated based on the “normal” CT images of NoDM patients prior to their diagnosis of PC within 3 years, were significantly higher than the scores from CT images of NoDM patients who were cancer-free within the next 5 years (P &lt; 0.01). Conclusions: In NoDM patients, even the PC lesion was nonvisible on CT, the radiomics features of “normal” pancreas of PC patients were different from that of the real DM patients. Our model has the potential for identifying individuals with PC in the whole NoDM population.

Epidemiological and clinicopathological features of patients (pts) with early- (EOPC) and late-onset pancreatic cancer (LOPC): A mono-institutional retrospective analysis.

10533 Background: PC is mostly diagnosed in the 7th decade of life. Recent evidence suggests a rising incidence of both EOPC and LOPC. However, there are few data about their specific characteristics. The aim of our study is to determine the incidence of EOPC and LOPC and their correlation with epidemiological and clinicopathological features. Methods: Real world data were extracted and analyzed by the Gemelli GENERATOR within the Gemelli Science and Technology Park (G-STeP). Study population was identified from health records matching main inclusion criteria: hospitalized pts with a diagnosis of PC (International Classification of Disease 9, ICD-9 codes captured from structured data source) or pts with at least one anatomic pathology report including PC evidence (selected using clinically validated text mining techniques from unstructured data source). Two subgroups were defined: EOPC ( &lt; 50 years old) and LOPC ( &gt; 75 years old) pts. Epidemiological and clinicopathological variables (gender; age, BMI, diabetes, history of pancreatitis, histology, primary tumor site, primary tumor surgery) were extracted using SAS (SAS(R) Institute suite for ETL). Statistical analyses were conducted using R (v4.2.1). Results: From January 2018 to December 2020, a total of 1606 PC pts treated at our Institution were included in the analysis. The median age was 69 years, 51% were male and the median BMI was 25. Regarding comorbidities, only 4% and 3% of pts had diabetes and history of pancreatitis, respectively. Adenocarcinoma (1120/1126; 99%) was the most common histotype and pancreatic head (576/901, 64%) was the most frequent primary tumor site. Two hundred and ninety-three pts (18%) underwent primary tumor surgery. Concerning the two subgroups, 92 (6%) pts had EOPC and 510 (32%) had LOPC. The median age was 43 years in EOPC group and 81 years in LOPC group. No difference between the two groups was found in gender (p 0.83), BMI (p 1) and tumor histology (p 1). Diabetes was present in 1% and 7% of EOPC and LOPC pts (p 0.07) and pancreatitis history in 3% and 2% (p 0.79), respectively. The primary tumor site was pancreatic head in 78% and 65% (p 0.06) of LOPC and EOPC, respectively. Regarding primary tumor surgery, a significant difference was observed between the two groups (27% in EOPC pts vs 11% LOPC pts; p &lt; 0.001). Conclusions: In our study, we did not observe a different epidemiology or a distinctive clinicopathological profile between EOPC and LOPC pts. Despite the retrospective nature of our analysis and single-institution evaluation, our findings showed that EOPC pts more frequently underwent primary tumor surgery, probably related to better clinical conditions. Additional analyses on survival outcomes, molecular and genetic features may help to clarify differences between the two groups.

Metagenomic next-generation sequencing contributes to the diagnosis of mixed pulmonary infection: a case report

BackgroundPulmonary cryptococcosis (PC) and mixed pulmonary infection are difficult to be diagnosed due to the non-specificity and their overlapping clinical manifestations. In terms of the clinical diagnosis of PC and mixed pulmonary infection, conventional tests have limitations such as a long detection period, a limited range of pathogens, and low sensitivity. Metagenomics next-generation sequencing (mNGS) is a nascent and powerful method that can detect pathogens without culture, to diagnose known and unexplained infections in reduced time.Case presentationA 43-year-old female was admitted to the hospital after suffering from a cough for one month. At the time of admission, a contrast-enhanced chest CT revealed multiple nodules and plaques in her right lung, as well as the formation of cavities. The blood routine assays showed evidently increased white blood cell count (mainly neutrophils), CRP, and ESR, which suggested she was in the infection phase. The serum CrAg-LFA test showed a positive result. Initially, she was diagnosed with an unexplained pulmonary infection. Bronchoalveolar lavage fluid (BALF) samples were collected for microbial culture, immunological tests and the mNGS. Microbial culture and immunological tests were all negative, while mNGS detected Corynebacterium striatum, Pseudomonas aeruginosa, Streptococcus pneumoniae, and Cryptococcus neoformans. The diagnosis was revised to PC and bacterial pneumonia. Lung infection lesions were healed after she received targeted anti-infection therapy with mezlocillin and fluconazole. In a follow-up after 2 months, the patient’s symptoms vanished.ConclusionsHere, we demonstrated that mNGS was capable of accurately distinguishing Cryptococcus from M. tuberculosis in pulmonary infection, and notably mNGS was capable of swiftly and precisely detecting pathogens in mixed bacterial and fungal pulmonary infection. Furthermore, the results of mNGS also have the potential to adjust anti-infective therapies.

PSAT015 A Rare Case of Incidental Massive Pheochromocytoma with Ectopic Parathyroid Hormone Secretion

Abstract Background Pheochromocytoma (PC) is a rare neuroendocrine tumor with an annual incidence of 2 to 8 cases per million that can secrete excess catecholamines precipitating hyper-adrenergic symptoms. In rarer instances, PCs can also secrete substances other than catecholamines. Case A 51-year-old female underwent MRI lumbar spine that demonstrated an incidental 13 cm right adrenal mass. History was significant for newly diagnosed hypertension and a five-year history of episodic headaches, diaphoresis, palpitations and anxiety. A previous cardiac evaluation including Holter monitor, echocardiogram, and stress test was unrevealing. Physical exam was significant only for chronic back pain and BMI 20.4. Labs revealed elevated serum catecholamines with metanephrines and normetanephrines &amp;gt;40x and &amp;gt;65x the upper limit of normal respectively, elevated urine catecholamines and elevated chromogranin A suggestive of PC. Labs also demonstrated mild hypercalcemia &amp;gt;10.3 mg/dL (8.6-10.4 mg/dL) with elevated PTH 78 pg/mL (14-64 pg/mL) and low vitamin D 25-OH 25 ng/mL (30-100 ng/mL). Calcitonin, albumin and phosphorus were normal. She was treated with non-competitive alpha and beta-blockade and metyrosine before undergoing successful right adrenalectomy. Post-operative labs demonstrated normalization of catecholamines, PTH and calcium. Surgical pathology confirmed the diagnosis of PC and demonstrated tumor cells which stained for PTH confirming ectopic PTH secretion, a rare phenomenon. The PC was very large with an elevated PASS (Pheochromocytoma of the Adrenal Gland Scaled Score) indicating increased risk for malignancy/recurrence; however, there was low Ki-67 activity and no capsular involvement, which suggested benign behavior. Furthermore, an MIBG scan was negative for metastatic disease, and an extensive genetic workup for familial PC/PGL (including MEN, RET, SDHx) was negative. Conclusion PC is a rare neuroendocrine tumor that can secrete excess catecholamines precipitating hyper-adrenergic symptoms and potentially fatal complications including hypertensive crises, cardiovascular disease, ischemia and multi-organ failure if untreated. Consequently, early recognition of PCs is imperative. The patient in this case had a five-year history of symptoms seen with PC and newly diagnosed hypertension despite normal BMI and negative cardiac workup. However, she had no evaluation for secondary causes of hypertension. Despite the large tumor size and significantly elevated catecholamines, she functioned without significant morbidity potentially due to adrenergic receptor desensitization. This case also highlights the rare phenomenon of ectopic secretion in PCs, specifically ectopic PTH secretion. A 2019 systemic review identified only 150 cases of pheochromocytomas/paragangliomas with ectopic hormone secretion – of those, only 17 secreted PTH or PTH-related peptide [1]. It is important to consider ectopic secretion in patients with PCs as they may have additional clinical manifestations associated with the hormone or substance secreted. Fortunately, this patient had no overt manifestations of hyperparathyroidism or hypercalcemia.

P11.31.B Pseudotumor Cerebri - a rare paraneoplastic manifestation

Abstract Background Pseudotumor Cerebri (PC) is defined by an elevated intracranial pressure of unidentified cause, associated with normal cerebrospinal fluid (CSF) composition and no cause for hypertension on the neuroimaging evaluations. The symptoms described in association are headache, papilledema, changes in vision, and sometimes tinnitus. Its pathophysiology is far from being elucidated and the mechanisms proposed are multiple. There are some cases described in the literature in which PC is the first manifestation of a systemic neoplasm, most probably due to an abnormal response of the immune system to cancerous growth. We aim to emphasize a possible connection between adenocarcinoma of the lung and PC as the first paraneoplastic manifestation. Material and Methods We present the case of a 59-year-old patient, female, non-obese, who presented to the hospital for severe headache, blurred vision, tinnitus, and paresthesia on both her upper limbs. On the first evaluation, the usual blood tests showed an increased creatinine level, and the subsequent abdominal echography and CT scan revealed bilateral ureter hydronephrosis, without an obvious obstacle, for which nephrostomies were implanted. On the ophthalmological evaluation bilateral papillary edema was described, although the cerebral CT with angiography and MRI showed no pathological modifications. A lumbar puncture with manometry was performed, that showed a CSF pressure of approximately 500 mmH2O. Results Following the clinical, imagistic, and biological manifestations, the diagnosis of PC was established. The decision to start the corticotherapy was made, followed by the addition of acetazolamide. Although the treatment tented was not efficient, the neurosurgery team decided that she is not a suitable candidate for a CSF shunting procedure and the ophthalmologist advised against an optic nerve sheath fenestration. The evolution was unfavorable, with the persistence of the symptoms. She underwent extensive investigations, the second cerebral MRI showing a slight dilation of the ventricles. On the thoracic-abdominal-pelvic CT, a pulmonary nodule with a malignant aspect was described, the histopathological results pleading for adenocarcinoma. The decision to excise the lesion was made, but after the surgery, the patient developed a cardiorespiratory arrest, without response to resuscitation. Conclusion Although there is scarce evidence of PC as a paraneoplastic syndrome, the evolution and investigations results support the possibility of a causal relationship. This is, to our knowledge, the second case of adenocarcinoma of the lung that primarily presents with PC. Further studies must be conducted to understand the underlying pathophysiology of this condition and to develop new treatment possibilities.

Diagnostic evaluation and incorporation of PSA density and the prostate imaging and data reporting system (PIRADS) version 2 classification in risk-nomograms for prostate cancer.

The diagnostic approach for prostate cancer still depends on PSA and DRE. to evaluate the diagnostic validity of PSA-Density and PIRADSv2 as diagnostic tests regarding biopsy results, and to design nomograms that include all diagnostic variables for malignancy, significant tumor (ST) and high-grade tumor. Cross-sectional study which included men with PSA ≥ 4ng/ml and/or suspicious DRE, PIRADSv2 ≥ 3 lesions on multiparametric MRI and prostate biopsy. The gold standard test was the maximum ISUP of the targeted biopsy per patient (malignancy: ISUP ≥ 1, ST: ISUP ≥ 2, high-grade tumor: ISUP ≥ 4). Association and logistic regression tests were used and diagnostic validity parameters using PSA-Density and PIRADSv2 classification was analyzed. Nomograms were designed for malignancy, ST, and high-grade tumor using the best model selection procedure from all possible equations. 336 men with median age, PSA and PSA-Density of 67.7years (IQR:12.6), 6.3ng/ml(IQR:3.3) and 0.12ng/ml/cc(IQR:0.10), respectively; 63 index lesions were PIRADS3, 204 PIRADS4, and 69 PIRADS5. 65.8% and 37.8% were malignant and ST, respectively. The significant positive association highlighted between malignancy and ST with age, DRE, PSA-Density and PIRADSv2. PSA-Density and PIRADSv2 ≥ 3 presented the highest sensitivity to detect malignancy, and their combination showed sensitivity nearly 95% (AUC:0.803). Nomograms for malignancy and ST included the variables age, DRE, PSA-Density, and PIRADSv2 with a sensitivity closely 91% (AUC:0.833), and a specificity of almost 85% for ST, exposing risk < 5% for ST when PSA-Density is < 0.15, not suspicious DRE and PIRADS3. PSA-Density and PIRADSv2 classification in risk nomograms can provide highly relevant information to increase the accuracy in the diagnosis of PC and ST.

Abstract 5107: Development of modified telomerase-specific adenovirus-based identification for viable-peritoneal tumor cells in peritoneal lavage fluid in resectable pancreatic cancer

Abstract Pancreatic cancer (PC) is a highly aggressive disease with dismal prognosis. Although only a surgical resection can offer the chance of a cure, the 5-year survival rate after a potentially curative resection have been reported to be a low as 10-30%. Peritoneal recurrence is a major recurrence pattern after surgery for PC. Peritoneal lavage cytology (CY) is employed widely in the diagnosis and staging of PC to rule out patients with occult peritoneal metastasis. However, the prognostic significance of CY+ in potentially resectable PC is still controversial. We rise the question of whether CY+ status in PC has predictive value for survival and early peritoneal recurrence. We conducted this study to evaluate use of a new genetically modified telomerase-specific replication-selective adenovirus, expressing GFP (TelomeScan F35) in rapid detection of viable peritoneal tumor cell (v-PTC) dissemination of PC. This human clinical trial sought to determine if the presence of virally-detected, rare v-PTC predict peritoneal recurrence and patient outcome. This study was approved by the IRB in Osaka Police Hospital and Rinku General Medical Center. Patients with resectable cytologically or histologically proven ductal adenocarcinoma of the pancreas were enrolled. 100ml of saline as peritoneal lavage fluid was harvested just after a laparotomy in 53 patients with PC. Half of the fluid was examined by cytology with papanicolau staining and MOC-31 immunostaining and the remaining half was analyzed to detect v-PTC with TelomeScan F35. To distinguish between leucocyte and cells with epithelial origin, cells were stained with anti-CD45 Ab. To further distinguish cells with primary tumor origin, cells were labeled with anti-CEA, anti-CA19-9 and EpCAM Abs. GFP-positive and CD45-negative, and either CEA-, CA19-9- or EpCAM-positive cells were counted as v-PTC by automatic detection system using NIS Elements imaging software. Patients were followed after surgery to evaluate its clinical significance. Among 53 patients aged 53-87 years (30 males and 23 females), 6 were cytologically positive (CY+), other 12 were virally positive by TelomeScan F35 (v-PTC+). All 53 patients underwent a surgical resection (PD/DP/TP=32/14/7). 2 patients were double positive (CY+/v-PTC+), and peritoneal recurrence early occurred at 7 month after surgery despite adjuvant chemotherapy. 4 were CY+, but v-PTC-, and no peritoneal recurrence were observed (0%). On the other hand, other 10 were CY-, but v-PTC+, and 4 of these 10 patients occurred peritoneal recurrence (40%). Remaining 37 patients were double negative (CY-/v-PTC-), peritoneal recurrence were observed in only 4 patients. In conclusion, the TelomeScan F35-based v-PTC detection may be an independent prognostic factor in patients with resectable PC and had close association with peritoneal recurrence. Citation Format: Masahiro Tanemura, Kenta Furukawa, Manabu Mikamori, Tadafumi Asaoka, Yasuo Urata, Kentaro Kishi, Daisaku Yamada, Shogo Kobayashi, Hidetoshi Eguchi. Development of modified telomerase-specific adenovirus-based identification for viable-peritoneal tumor cells in peritoneal lavage fluid in resectable pancreatic cancer [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 5107.

Association of RB1 mutational status with overall genomic landscape in neuroendocrine prostate cancer (NEPC).

5063 Background: NEPC is a high-grade aggressive form of prostate cancer. We queried whether RB1 mutation status would impact the genomic features of NEPC in RB1 mutated vs non-mutated cases. Methods: From a series of 13,496 cases of clinically advanced PC, we identified 415 cases (3.1%) with a diagnosis of small cell PC or NEPC as determined by the submitting physician. They were sequenced using a hybrid capture-based FDA-approved clinical genomic profiling (CGP) assay to detect all classes of genomic alterations (GA). Tumor mutational burden (TMB) was determined on 0.8 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 95 loci. PD-L1 expression was determined by IHC (Dako 22C3) with low tumor cell positive staining 1-49% and high staining ≥50% expression. Results: 253 (61%) of NEPC feature GA in RB1 (RB1 mut+). This contrasts with a 5.8% frequency of RB1 GA in the non-NEPC (P &lt;.0001). The RB1 mut+ NEPC featured a slightly greater number of pathogenic GA/tumor than the RB1 mut- NEPC (5.1 vs 4.2). Age and TMPRSS2-ERG fusion frequency were similar between the groups. RB1 Mut- NEPC was associated with significantly higher amplifications (amp) and total GA in AR compared to RB1 mut+ NEPC. RB1 mut+ NEPC featured significantly greater frequency of PTEN GA. GA frequencies in targetable kinases and DNA repair GA including BRCA1/2 and ATM linked to PARP inhibitor (PARPi) response were similar in both groups. For potential immune-oncology (IO) biomarkers, RB1 Mut+ NEPC featured significantly greater frequency of positive PD-L1 expression and lower frequencies of MDM2 and CDK12 GA. CD274 ( PD-L1) amplification, MSI-high status and cases with TMB ≥10 mut/Mb were uncommon in both groups. gLOH was higher in RB1 mut+ than RB1 mut- (P =.005). There were more cases of non-European ancestry in the RB1 mut- group. APC I1307K mut were found in 3/162 (1.9%) RB1 mut- NEPC only. Conclusions: In NEPC, the presence of RB1 mutation is associated with various GA that may have clinical relevance. Further study of RB1 status as a guide in trial designs on therapy selection for men with NEPC appears warranted. [Table: see text]

Association of social determinants of health with late diagnosis and survival of patients with pancreatic cancer.

Pancreatic cancer disparities have been described. However, it is unknown if they contribute to a late diagnosis and survival of patients with metastatic disease. Identifying their role is important as it will open the door for interventions. We hypothesize that social determinants of health (SDH) such as income, education, race, and insurance status impact (I) stage of diagnosis of PC (Stage IV vs. other stages), and (II) overall survival (OS) in Stage IV patients. Using the National Cancer Database, we evaluated a primary outcome of diagnosis of Stage IV PC and a secondary outcome of OS. Primary predictors included race, income, education, and insurance. Covariates included age, sex and Charlson-Deyo comorbidity score. Univariate, multivariable logistic regression models evaluated risk of a late diagnosis. Univariate, multivariable Cox proportional hazards model examined OS. 95% confidence intervals were used. 230,877 patients were included, median age of 68 years (SD 12.1). In univariate analysis, a better education, higher income, and insurance decreased the odds of Stage IV PC, while Black race increased it. In multivariable analysis, education [>93% high-school completion (HSC) vs. <82.4%, OR 0.96 (0.93-0.99)] and insurance [private vs. no, OR 0.72 (0.67-0.74)] significantly decreased the risk of a late diagnosis, whereas Black race increased the odds [vs. White, OR 1.09 (1.07-1.12)]. In univariate Cox analysis, having a higher income, insurance and better education improved OS, while Black race worsened it. In multivariable Cox, higher income [>$63,333 (vs. <$40,277), HR 0.87 (0.85-0.89)] and insurance [private vs. no, HR 0.77 (0.74-0.79)] improved OS. SDH impacted the continuum of care for patients with advanced pancreatic cancer, including stage at diagnosis and overall survival.

Hereditary-Genealogical features of Parkinson's disease and their early detection of the disease

In recent years, various levels of scientific research have been conducted on the early detection of Parkinson’s disease. Neurotrophic factors in the nervous system injury today, especially in the study of degeneration of dopaminergic neurons. In particular, there is a growing interest in the gall neurotrophic factor. rather, they can be used as a predictor of early detection of diseases, as well as to draw conclusions about their consequences. The practical significance of the results of the study is the introduction of tests using IFA method of glial neurotrophic factor in the serum of patients, special attention as a predictor for Parkinson's disease, early detection and comparative diagnosis of PC using specially developed criteria, as well as optimization of differential treatment measures.

Real-world treatment patterns among patients with metastatic castration-resistant prostate cancer (mCRPC) in the US.

49 Background: mCRPC is an incurable disease with poor prognosis. Though multiple treatments such as novel hormonal therapies (NHT: abiraterone [abi], enzalutamide [enza], docetaxel [doce], cabazitaxel [caba], sipuleucel-T [Sip-T] etc.) are approved, real-world data regarding treatment sequencing are lacking. This study assesses the real-world treatment patterns within the context of FDA-approved life-prolonging treatments for mCRPC. Methods: The IBM MarketScan database was used to identify newly diagnosed (incident) mCRPC patients from 1/1/2014-5/31/2020. Adult males were required to have a diagnosis of PC, and subsequently evidence of metastasis and castration (medical or surgical). Incident mCRPC status (index) was determined 3 ways: 1) treatment with an NHT within 3 months after castration and an FDA-approved mCRPC treatment ≥3 months after NHT; 2) first FDA-approved treatment ≥6 months after castration; 3) first FDA-approved treatment 3-6 months after castration and a second FDA-approved treatment ≥3 months after treatment. Lines of therapy (LOT) were measured in the variable-length follow-up of ≥1 month and consisted of all drugs observed within 28 days of first observed treatment. Duration of therapy was measured as start of line to start of next line or end of enrollment. Results: A total of 2,912 mCRPC patients met all study criteria and received ≥1 LOT. Among those, 48.7% had ≥2 LOT, and 21.8% had ≥3 LOT. Patients were an average age of 71 years at index and used leuprolide (87%), abi (10%), doce (9%) and enza (8%) prior to index. In mCRPC the most common observed first line (1L) monotherapy regimens were abi (35%), enza (34%), and doce (14%). The most common observed second-line (2L) treatments were enza (36%), abi (27%), and doce (14%). Mean duration of 1L was 292 days compared to 245 days in 2L. The most frequently observed treatment sequences (1L to 2L) are reported in the table. Opioids (62%) and denosumab (47%) use was common in mCRPC patients. Conclusions: Among mCRPC patients, NHTs were the most common 1st and 2nd LOTs and alternate NHT after a first NHT was the most common sequence. With rapidly evolving treatment options in metastatic prostate cancer, these data can help guide estimation of eligible patients for different clinical trials. Further studies are needed to understand the high attrition from 1L to subsequent lines of therapy, the reasons for treatment preference and impact on clinical outcomes with different treatment sequencings.[Table: see text]

Impact of U.S. Preventative Services Task Force grade D recommendation against prostate-specific antigen screening on prostate cancer mortality.

51 Background: The U. S. Preventative Services Task Force (USPSTF) recommendation regarding prostate-specific antigen (PSA) transitioned to a grade D recommendation against PSA screening for adult males in 2012. The impact of this recommendation against PSA screening on prostate cancer-specific mortality (PCSM) in contemporary cohorts is unknown. Our study evaluated PCSM between 1999-2019, comparing mortality rates before and after this change to screening guidelines. Methods: Age-adjusted PCSM rates per 100,000 men were obtained from the National Center for Health Statistics from 1999 – 2019. Trends in PCSM rates from 1999 – 2012 and 2014 – 2019 were estimated using linear regression with year and binary indicator of pre-2013/post-2013 status as interaction terms. Age-adjusted rates of PCSM were calculated for men ≥50 years and by race, ethnicity, urbanization and census region. Similarly, age-adjusted rates of overall cancer mortality (exclusive of PCSM) were calculated. Behavioral Risk Factor Surveillance System was used to establish trends in PSA screening from 2001 – 2018. North American Association of Central Cancer Registries was used to determine age-adjusted incidence of localized and metastatic PC at the time of diagnosis from 1999 – 2017. Results: The age-adjusted PCSM rate in the U.S. decreased linearly at a rate of (-)0.28 per 100,000/year from 1999 – 2012 and subsequently stalled at a rate of no change from 2014 – 2019 (p &lt; 0.001). This effect was particularly striking for men aged 60 – 69, men &gt; 80 years, and Black men. Men aged 60 – 64 had a decreasing rate of (-)0.009 per 100,000/year prior to 2013, followed by a rise of (+)0.001 per 100,000/year (p &lt; 0.001). Among Black men, PCSM rate was decreasing linearly at (-)0.700/100,000/year from 1999-2012 and flattened at a rate of (-)0.091/100,000/year from 2014-2019 (p &lt; 0.001). These changes were seen across races, urbanization and census regions (p &lt; 0.001) and were accompanied by decreases in PSA screening (p = 0.02) together with increases in diagnosis of metastatic disease. These trends were inconsistent with mortality trends observed across all malignancies. Conclusions: Using comprehensive data on PCSM through 2019, this study illustrates decreasing PCSM over time which flattened or increased following the 2012 change in USPSTF guideline, along with a decrease in PSA screening. The change in PCSM was seen in all ages, races, ethnicities, urbanization and census regions, but particularly in men from 60 – 69 and &gt; 80 years old, and Black men. These changes were accompanied by increased diagnosis of metastatic PC and are discordant from trends across other malignancies. These findings suggest that the change in PSA screening guideline may have contributed to the stagnancy of PCSM rates in recent years. The updated 2018 USPSTF guideline supporting shared-decision making may reverse these trends over time.