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SAGE Open Medical Case Reports 2024Retroperitoneal cysts, a rare surgical phenomenon, present diagnostic challenges due to their typically asymptomatic nature. A 62-year-old male presented with a 4-month...
Retroperitoneal cysts, a rare surgical phenomenon, present diagnostic challenges due to their typically asymptomatic nature. A 62-year-old male presented with a 4-month history of abdominal distension and increased burping. Upon clinical examination, a soft, distended, nontender abdomen with a palpable mass extending from the epigastric region to 3 cm below the umbilicus was revealed. Imaging revealed a 14.6 cm × 15.8 cm × 16.4 cm nonenhancing retroperitoneal lesion, compressing the right ureter and causing mild right hydronephrosis. Multiple gall bladder calculi, an umbilical hernia, and lipomatous lesions associated with adrenal glands were also discovered. Laparoscopic retroperitoneal cystectomy, cholecystectomy, and umbilical hernia repair were performed. Intraoperatively, 150 ml ascitic fluid and 1200 ml cystic fluid were found. This case highlights the intricate clinical presentation of a retroperitoneal cyst, emphasizing the need for surgical exploration. Successful laparoscopic management contributes to the evolving understanding of optimal treatment strategies.
PubMed: 38911179
DOI: 10.1177/2050313X241263773 -
Cancers May 2024Bromodomain and extra-terminal (BET) domain proteins that bind to acetylated lysine residues of histones serve as the "readers" of DNA acetylation. BRD4 is the most...
BACKGROUND
Bromodomain and extra-terminal (BET) domain proteins that bind to acetylated lysine residues of histones serve as the "readers" of DNA acetylation. BRD4 is the most thoroughly studied member of the BET family and regulates the expression of key oncogenes. BRD4 gene amplification has been identified in ovarian cancer (~18-19%) according to (TCGA) analysis. BET inhibitors are novel small molecules that displace BET proteins from acetylated histones and are currently tested in Phase I/II trials. We here aim to explore the prognostic role of the BRD4 gene and protein expression in the ascitic fluid of patients with advanced FIGO III/IV high-grade serous ovarian carcinoma (HGSC).
METHODS
Ascitic fluid was obtained from 28 patients with advanced stage (FIGO III/IV) HGSC through diagnostic/therapeutic paracentesis or laparoscopy before the initiation of chemotherapy. An amount of ~200 mL of ascitic fluid was collected from each patient and peripheral blood mononuclear cells () were isolated. Each sample was evaluated for BRD4 and GAPDH gene expression through RT-qPCR and BRD4 protein levels through enzyme-linked immunosorbent assay (ELISA). The study protocol was approved by the Institutional Review Board of Alexandra University Hospital and the Committee on Ethics and Good Practice (CEGP) of the National and Kapodistrian University of Athens (NKUA).
RESULTS
Low BRD4 gene expression was associated with worse prognosis at 12 months compared to intermediate/high expression (95% CI; 1.75-30.49; = 0.008). The same association was observed at 24 months although this association was not statistically significant (95% CI; 0.96-9.2; = 0.065). Progression-free survival was shorter in patients with low BRD4 gene expression at 12 months (5.6 months; 95% CI; 2.6-8.6) compared to intermediate/high expression (9.8 months; 95% CI; 8.3-11.3) (95% CI; 1.2-16.5; = 0.03). The same association was confirmed at 24 months (6.9 months vs. 13.1 months) (95% CI; 1.1-8.6; = 0.048). There was a trend for worse prognosis in patients with high BRD4 protein levels versus intermediate/low BRD4 protein expression both at 12 months (9.8 months vs. 7.6 months; = 0.3) and at 24 months (14.2 months vs. 16.6 months; = 0.56) although not statistically significant. Again, there was a trend for shorter PFS in patients with high BRD4 protein expression although not statistically significant both at 12 months ( = 0.29) and at 24 months ( = 0.47).
CONCLUSIONS
There are contradictory data in the literature over the prognostic role of BRD4 gene expression in solid tumors. In our study, intermediate/high BRD4 gene expression was associated with a favorable prognosis in terms of overall survival and progression-free survival compared to low BRD4 gene expression.
PubMed: 38893083
DOI: 10.3390/cancers16111962 -
Frontiers in Immunology 2024Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer and peritoneal dissemination is one major cause for this poor prognosis. Exosomes have...
BACKGROUND
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer and peritoneal dissemination is one major cause for this poor prognosis. Exosomes have emerged as promising biomarkers for gastrointestinal cancers and can be found in all kinds of bodily fluids, also in peritoneal fluid (PF). This is a unique sample due to its closeness to gastrointestinal malignancies. The receptor tyrosine kinase-like orphan receptor 1 (ROR1) has been identified as a potential biomarker in human cancers and represents a promising target for an immunotherapy approach, which could be considered for future treatment strategies. Here we prospectively analyzed the exosomal surface protein ROR1 (exo-ROR1) in PF in localized PDAC patients (PER-) on the one hand and peritoneal disseminated tumor stages (PER+) on the other hand followed by the correlation of exo-ROR1 with clinical-pathological parameters.
METHODS
Exosomes were isolated from PF and plasma samples of non-cancerous (NC) (n = 15), chronic pancreatitis (CP) (n = 4), localized PDAC (PER-) (n = 18) and peritoneal disseminated PDAC (PER+) (n = 9) patients and the surface protein ROR1 was detected via FACS analysis. Additionally, soluble ROR1 in PF was analyzed. ROR1 expression in tissue was investigated using western blots (WB), qPCR, and immunohistochemistry (IHC). Exosome isolation was proven by Nano Tracking Analysis (NTA), WB, Transmission electron microscopy (TEM), and BCA protein assay. The results were correlated with clinical data and survival analysis was performed.
RESULTS
PDAC (PER+) patients have the highest exo-ROR1 values in PF and can be discriminated from NC (p <0.0001), PDAC (PER-) (p <0.0001), and CP (p = 0.0112). PDAC (PER-) can be discriminated from NC (p = 0.0003). In plasma, exo-ROR1 is not able to distinguish between the groups. While there is no expression of ROR1 in the exocrine pancreatic tissue, PDAC and peritoneal metastasis show expression of ROR1. High exo-ROR1 expression in PF is associated with lower overall survival (p = 0.0482).
CONCLUSION
With exo-ROR1 in PF we found a promising diagnostic and prognostic biomarker possibly discriminating between NC, PDAC (PER-) and PDAC (PER+) and might shed light on future diagnostic and therapeutic concepts in PDAC.
Topics: Humans; Receptor Tyrosine Kinase-like Orphan Receptors; Exosomes; Male; Ascitic Fluid; Pancreatic Neoplasms; Female; Carcinoma, Pancreatic Ductal; Middle Aged; Biomarkers, Tumor; Prognosis; Aged; Peritoneal Neoplasms; Adult; Prospective Studies
PubMed: 38846943
DOI: 10.3389/fimmu.2024.1253072 -
Cureus May 2024Ascites can manifest as a result of many conditions, with cirrhosis being the most common cause in the United States. Here, we present a case of lymphocytic ascites, a...
Ascites can manifest as a result of many conditions, with cirrhosis being the most common cause in the United States. Here, we present a case of lymphocytic ascites, a less common variant that occurred due to infection with Chlamydia trachomatis. This was a 37-year-old female with a history of substance and sexual abuse who presented with the chief complaints of abdominal pain, abdominal distension, and weight gain. She was febrile on admission with a distended, tender abdomen. The more common cardiac, renal, and hepatic causes were ruled out with extensive workup. Diagnosis and therapeutic paracentesis were done with fluid analysis significant for lymphocyte predominance and absence of malignant cells. Multi-modal imaging had ruled out suspicious malignant masses but CT abdomen/pelvis did show complex large volume ascites. Urine chlamydia and gonorrhea polymerase chain reaction (PCR) had resulted positive for chlamydia, leading us to start Doxycycline. Other infectious workups were negative, but ascitic fluid chlamydia NAAT was positive. Though initially worsening, the patient started showing significant clinical improvement after starting doxycycline, with the resolution of ascites and associated symptoms. This case report intends to bring to attention the importance of testing for chlamydia infection in cases of lymphocytic ascites, especially in sexually active females.
PubMed: 38846180
DOI: 10.7759/cureus.59760 -
Journal of Surgical Case Reports Jun 2024Neuroendocrine carcinomas (NECs) of the gallbladder are very rare and aggressive tumors with poor prognosis. Most of them are poorly differentiated and belong to the...
Neuroendocrine carcinomas (NECs) of the gallbladder are very rare and aggressive tumors with poor prognosis. Most of them are poorly differentiated and belong to the small cell type. We report a case of a 59-year-old woman who presented with abdominal pain and distension. Contrast-enhanced computed tomography revealed a large heterogeneous mass in the liver, adjacent to the gallbladder, and omental nodules. CA 19-9 level was elevated and ascitic fluid cytology was suspicious for malignancy. Percutaneous biopsy of the liver mass confirmed the diagnosis of small cell NEC of the gallbladder. The patient was considered inoperable and planned for chemotherapy, but she died 20 days after admission. This case illustrates the diagnostic challenges and the dismal outcome of small cell NEC of the gallbladder. Early detection and multimodal treatment are essential for improving the survival of these patients.
PubMed: 38832057
DOI: 10.1093/jscr/rjae386 -
Journal of Family Medicine and Primary... Apr 2024Portal hypertension commonly occurs due to liver cirrhosis, and esophageal varices (EV) is one of the major complications associated with it. The most common cause of...
BACKGROUND
Portal hypertension commonly occurs due to liver cirrhosis, and esophageal varices (EV) is one of the major complications associated with it. The most common cause of death in liver cirrhosis is EV bleeding. Hence, GE screening for EV is required, which is an invasive procedure. Regular use of endoscopy results in low compliance due to cost and discomfort for patients. Hence, identifying non-invasive markers that could grade EV provides a useful screening tool for family physicians and primary health centers (PHCs) by referring the patient to higher centers for definitive treatment, which could reduce mortality due to variceal bleeding in cirrhotic patients.
AIMS
To assess non-invasive predictors of grade EV in patients diagnosed with liver cirrhosis.
SETTINGS AND DESIGN
Cross-sectional study.
METHODS AND MATERIAL
A total of 109 patients with liver cirrhosis underwent clinical and biochemical evaluation, USG abdomen with spleen bipolar diameter, ascitic fluid analysis, and upper GE with a grade of EV are recorded.
STATISTICAL ANALYSIS USED
SPSS software with Student -test, Chi-square -test, analysis of variance, receiver operator characteristic (ROC) curves, and Spearman correlation with 95% CI is used. <0.05 is considered significant.
RESULTS
Aminotransferase to Platelet count Ratio Index (APRI) score >1.815, PC/SD ≤909, and SAAG >1.1g/dl showed EV in liver cirrhosis ( < 0.05). The order of prediction with ROC curves shows APRI score > PC/SD > SAAG. In grading EV, APRI scores of 1.9-2.5 and >2.5 showed small and large EV, respectively ( < 0.05).
CONCLUSIONS
APRI score may be used in PHC as an early intervention to grade EV and refer the patient to higher centers for definitive treatment. This would prevent the progression of varices to rupture and reduce mortality due to variceal bleeds in liver cirrhosis patients.
PubMed: 38827661
DOI: 10.4103/jfmpc.jfmpc_792_23 -
Biomedicine & Pharmacotherapy =... Jul 2024Peritoneal metastases (PM) commonly occur in colorectal cancer patients. Systemic chemotherapy yields poor outcomes for these patients. It is hypothesised that...
BACKGROUND
Peritoneal metastases (PM) commonly occur in colorectal cancer patients. Systemic chemotherapy yields poor outcomes for these patients. It is hypothesised that traditional systemic chemotherapy is not very effective for this patient population. This study investigates to what extent systemic anti-cancer therapy crosses the peritoneal barrier.
METHODS
In a Phase I study, eighteen patients received systemic oxaliplatin, 5-FU, and bevacizumab. Plasma and peritoneal fluid samples were collected to measure drug concentrations. A non-compartmental analysis determined the Area Under the Curve (AUC) for oxaliplatin and 5-FU in both matrices. Intraperitoneal (IP) and intravenous (IV) exposure ratios were calculated, along with the bevacizumab concentration IP/IV ratio. The relationship between tumour load and IP/IV ratios and the correlation between the IP/IV ratios of different treatments were assessed statistically.
RESULTS
A total of 438 5-FU samples and 578 oxaliplatin samples were analysed in plasma and peritoneal fluid. Bevacizumab was quantified with 17 measurements in plasma and 15 measurements IP. Median IP/IV ratios were 0.143, 0.352 and 0.085 for 5-FU, oxaliplatin and bevacizumab, respectively. Oxaliplatin exhibited a longer IP half-life than 5-FU. A correlation was found between oxaliplatin and bevacizumab IP/IV ratios (R=0.69, p=0.01). No statistical correlations were found between the other investigated drugs.
CONCLUSIONS
Our findings indicate that only a small percentage of systemically administered anti-cancer treatment reaches the IP cavity, questioning their efficacy against PM. This strengthens the hypothesis for repeated intraperitoneal chemotherapy to reach adequate anti-cancer drug levels.
Topics: Humans; Bevacizumab; Colorectal Neoplasms; Peritoneal Neoplasms; Fluorouracil; Oxaliplatin; Male; Middle Aged; Female; Aged; Antineoplastic Combined Chemotherapy Protocols; Adult; Ascitic Fluid; Area Under Curve; Injections, Intraperitoneal
PubMed: 38810398
DOI: 10.1016/j.biopha.2024.116820 -
International Journal of Molecular... May 2024Primary cancer cells reflect the genetic background and phenotype of a tumor. Immortalized cells with higher proliferation activity have an advantage over primary cells.... (Comparative Study)
Comparative Study
Primary cancer cells reflect the genetic background and phenotype of a tumor. Immortalized cells with higher proliferation activity have an advantage over primary cells. The aim of the study was to immortalize the primary ovarian cancer (OvCa) cells using the plasmid-carrying human telomerase reverse transcriptase (hTERT) gene and compare their phenotype and biological activity with the primary cells. The primary OvCa3 A and OvCa7 A cells were isolated from the ascitic fluid of two high-grade serous ovarian cancer patients and were characterized using immunocytochemical methods, flow cytometry, real-time RT-PCR, Western blot, metabolic activity, and migratory potential. Both immortalized ovarian cancer cell lines mirrored the phenotype of primary cancer cells, albeit with modifications. The OvCa3 A hTERT cells kept the mesenchymal stem cell phenotype of CD73/CD90/CD105-positivity and were CD133-negative, whereas the cell population of OvCa7 A hTERT lost CD73 expression, but almost 90% of cells expressed the CD133 characteristic for the CSCs phenotype. Immortalized OvCa cells differed in gene expression level with respect to and , which was associated with stemness properties. The OvCa7 A hTERT cells showed higher metabolic and migratory activity and ALDH1 expression than the corresponding primary OvCa cells. Both primary and immortalized cell lines were able to form spheroids. The newly established unique immortalized cell line OvCa7 A hTERT, with the characteristic of a serous ovarian cancer malignancy feature, and with the accumulation of the p53, Pax8, and overexpression of the CD133 and CD44 molecules, may be a useful tool for research on therapeutic approaches, especially those targeting CSCs in ovarian cancer and in preclinical 2D and 3D models.
Topics: Humans; Female; Ovarian Neoplasms; Telomerase; Cell Line, Tumor; Neoplastic Stem Cells; Cell Movement; Gene Expression Regulation, Neoplastic
PubMed: 38791431
DOI: 10.3390/ijms25105384 -
Sheng Wu Gong Cheng Xue Bao = Chinese... May 2024The antibodies to the microtubule-associated protein tau play a role in basic and clinical studies of Alzheimer's disease (AD) and other tauopathies. With the...
The antibodies to the microtubule-associated protein tau play a role in basic and clinical studies of Alzheimer's disease (AD) and other tauopathies. With the recombinant human tau441 as the immunogen, the hybridoma cell strains secreting the anti-human tau N-terminal domain (NTD-tau) monoclonal antibodies were generated by cell fusion and screened by limiting dilution. The purified monoclonal antibodies were obtained by inducing the mouse ascites and affinity chromatography. The sensitivity and specificity of the monoclonal antibodies were examined by indirect ELISA and Western blotting, respectively. A double antibody sandwich ELISA method for detecting human tau protein was established and optimized. The results showed that the positive cloning rate of hybridoma cells was 83.6%. A stable cell line producing ZD8F7 antibodies was established, and the antibody titer in the supernatant of the cell line was 1:16 000. The antibody titer in the ascitic fluid was higher than 1:256 000; and the titer of purified ZD8F7 monoclonal antibodies was higher than 1:128 000. The epitope analysis showed that the ZD8F7 antibody recognized tau21-37 amino acid in the N-terminal domain. The Western blotting results showed that the ZD8F7 antibody recognized the recombinant human tau protein of 50-70 kDa and the human tau protein of 50 kDa in the brain tissue of transgenic AD model mice (APP/PS1/tau). With ZD8F7 as a capture antibody, a quantitative detection method for human tau protein was established, which showed a linear range of 7.8-500.0 pg/mL and could identify human tau protein in the brain tissue of AD transgenic mice and human plasma but not recognize the mouse tau protein. In conclusion, the human NTD-tau-specific monoclonal antibody and the double antibody sandwich ELISA method established in this study are highly sensitive and can serve as a powerful tool for the detection of tau protein in neurodegenerative diseases.
Topics: tau Proteins; Animals; Antibodies, Monoclonal; Humans; Mice; Alzheimer Disease; Enzyme-Linked Immunosorbent Assay; Recombinant Proteins; Hybridomas; Mice, Inbred BALB C; Antibody Specificity; Protein Domains; Epitopes
PubMed: 38783817
DOI: 10.13345/j.cjb.230655 -
Journal of Cytology 2024The "International System of Reporting Serous Fluid Cytology (TIS)" together with cytomorphology promotes the use of ancillary techniques to resolve difficulties in...
BACKGROUND
The "International System of Reporting Serous Fluid Cytology (TIS)" together with cytomorphology promotes the use of ancillary techniques to resolve difficulties in reporting serous fluid cytology.
OBJECTIVE
To classify serous effusion fluid samples received at our department in line with "TIS", indicating the risk of malignancy (ROM), and directing appropriate usage of ancillary testing.
MATERIALS AND METHODS
Prospective study carried out from October 2021 to September 2022. The study included all pleural, ascitic, and pericardial fluid samples, reported according to 'TIS'. Flow cytometry and immunocytochemistry were ancillary methods utilized to assist in reporting. Cases with available history and convincing correlations didn't require further assessment.
RESULTS
A total of 1200 serous effusion samples were evaluated including 604 pleural, 591 ascitic, and 5 pericardial fluid samples. After categorization, there were 23 samples in non-diagnostic (ND, 1.9%), 575 in negative for malignancy (NFM, 47.91%), 44 in atypia of undetermined significance (AUS, 3.66%), 64 in suspicious for malignancy (SFM, 5.33%), and 494 in malignant category (MAL, 41.16%). Ancillary studies were beneficial in the recategorization of 26% (11/44) AUS cases, 29.6% (19/64) SFM cases, and it helped refine tumor characteristics in 35.42% (175/494) cases categorized as malignant. Final ROM calculated for each category: ND 25%, NFM 18.6%, AUS 66.6%, SFM 88%, and MAL 100%.
CONCLUSION
Serous fluid is an easily obtainable sample that can provide opportunities for ancillary testing with clinical implications. In AUS and suspicious category although, diagnostic yield is increased however, a larger number of cases are required to obtain definite results.
PubMed: 38779601
DOI: 10.4103/joc.joc_114_23