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Therapeutic Advances in Medical Oncology 2024Bacterial peritonitis (BP) in patients with gastrointestinal (GI) cancer has been poorly described, and its prevalence is unknown.
BACKGROUND
Bacterial peritonitis (BP) in patients with gastrointestinal (GI) cancer has been poorly described, and its prevalence is unknown.
OBJECTIVES
This study aimed to evaluate in patients with both GI cancer and ascites the prevalence of BP, associated features, mechanisms, prognosis, and the diagnostic performance of neutrophil count in ascites.
DESIGN
A retrospective, multicenter, observational study.
METHODS
All patients with GI cancer and ascites who underwent at least one paracentesis sample analyzed for bacteriology over a 1-year period were included. BP was defined by a positive ascites culture combined with clinical and/or biological signs compatible with infection. Secondary BP was defined as BP related to a direct intra-abdominal infectious source.
RESULTS
Five hundred fifty-seven ascites from 208 patients included were analyzed. Twenty-eight patients had at least one episode of BP and the annual prevalence rate of BP was 14%. Among the 28 patients with BP, 19 (65%) patients had proven secondary BP and 17 (59%) patients had multi-microbial BP, mainly due to . A neutrophil count greater than 110/mm in ascites had negative and positive predictive values of 96% and 39%, respectively, for the diagnosis of BP. The median survival of patients with BP was 10 days (interquartile range 6-40) after the diagnosis.
CONCLUSION
BP is not rare in patients with GI cancer and is associated with a poor short-term prognosis. When a patient with GI cancer is diagnosed with BP, a secondary cause should be sought. Further studies are needed to better define the best management of these patients.
PubMed: 38845791
DOI: 10.1177/17588359241258440 -
Nigerian Journal of Clinical Practice May 2024Imaging is vital for assessing pancreaticobiliary diseases.
BACKGROUND
Imaging is vital for assessing pancreaticobiliary diseases.
AIM
The aim of the study was to investigate the spectrum and pattern of pancreaticobiliary diseases in adult Nigerians using magnetic resonance cholangiopancreatography (MRCP).
METHODS
This was a retrospective, descriptive cross-sectional study. The electronic radiological records of 110 adult Nigerians who had undergone MRCP were reviewed. The MRCP images were evaluated for bile duct dilatation, intraluminal filling defects, strictures, calculi, and other abnormalities.
RESULTS
There were 45 males (40.9%) and 65 females (59.1%) aged 18-83 years, with a mean age of 51.93 ± 15.22 years. Jaundice (59.1%) and right hypochondrial pain (31.8%) were the most common presenting complaints. Gallstones (32.7%), common bile duct strictures (15.5%), choledocholithiasis (11.8%), pancreatic head carcinoma (10.9%), and gallbladder carcinoma (2.7%) were the most frequent abnormalities. There was biliary obstruction in 56.4% of participants, mostly at the distal and proximal common bile duct. Other findings include hepatomegaly (23.6%), hepatic cysts (6.4%), hepatic steatosis (0.9%), duodenal wall thickening (1.8%), and ascites (5.5%). MRCP was normal in 25 (22.7%) participants.
CONCLUSION
Gallstones were the predominant pathology of the various pancreaticobiliary diseases, while Pancreatic head and gallbladder carcinoma were the most common malignant diseases.
Topics: Humans; Male; Female; Middle Aged; Adult; Aged; Cross-Sectional Studies; Retrospective Studies; Cholangiopancreatography, Magnetic Resonance; Nigeria; Aged, 80 and over; Adolescent; Young Adult; Pancreatic Diseases; Biliary Tract Diseases; West African People
PubMed: 38842708
DOI: 10.4103/njcp.njcp_619_23 -
Cureus May 2024A 47-year-old male, a known case of alcoholic chronic liver disease with portal hypertension, presented with complaints of abdominal distension and shortness of breath....
Iatrogenically Acquired Mycobacterium abscessus Infection in an Indwelling Intercostal Drainage In Situ in a Patient With Alcoholic Liver Disease and Bilateral Hepatic Hydrothorax: A Report of a Rare Case.
A 47-year-old male, a known case of alcoholic chronic liver disease with portal hypertension, presented with complaints of abdominal distension and shortness of breath. A provisional diagnosis of ethanol-related compensated chronic liver disease (CLD) with portal hypertension and splenomegaly, gross ascites with bilateral hepatic hydrothorax was made. The left-sided pleural effusion subsided after three pleural taps, but the right-sided effusion kept refilling even after four to five days of repeated therapeutic taps, so a pigtail catheter was left in situ. The pleural fluid was sent for culture which did not grow any pathogenic organisms. Cartridge-based nucleic acid amplification tests where complex (MTBC) was not detected, Ziehl-Neelsen staining was done in which acid-fast bacilli were not seen, and cytology was done where no malignant cells were seen. The patient was discharged with the pigtail in situ on the right side and, after 20 days, the patient again presented with shortness of breath, and imaging revealed moderate right-side pleural effusion. Draining of pleural fluid was done and sent for investigation which again revealed no infective etiology. The patient was admitted to the hospital for one month as the right-sided effusion did not resolve. Suddenly, the patient developed shortness of breath, and a chest X-ray was done, which showed pigtail blockage; pigtail flushing was done, and the bag was drained. The patient was empirically started on IV meropenem 500 mg TID, IV teicoplanin 400 mg BD, and inj polymyxin B 500,000 IU IV BD. The pleural fluid was sent continuously for investigation for the first two months which again did not reveal any infective etiology. After two months of pigtail in situ, the pleural fluid was sent for CBNAAT where MTBC was not detected, and ZN stain showed smooth acid-fast bacilli. The sample was cultured, and it grew acid-fast bacilli in 72 hours on blood agar, MacConkey agar, and Lowenstein-Jensen media. A line probe assay done from the isolate revealed it to be subsp. abscessus which was resistant to macrolides and sensitive to aminoglycosides. subsp. abscessus was isolated from repeated cultures of pleural fluid, and the patient was advised on a combination treatment of amikacin, tigecycline, and imipenem. The patient was discharged with the indwelling pigtail with the advised treatment; unfortunately, we lost patient follow-up as the patient never returned to us.
PubMed: 38832176
DOI: 10.7759/cureus.59626 -
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 -
International Journal of Surgery Case... Jul 2024Ovarian fibromas are benign tumours arising from the connective tissue of the ovarian cortex, classified into three pathological subtypes: fibroma, thecoma, and...
INTRODUCTION AND IMPORTANCE
Ovarian fibromas are benign tumours arising from the connective tissue of the ovarian cortex, classified into three pathological subtypes: fibroma, thecoma, and fibrothecoma. Their diagnosis is complicated by their solid nature and potential association with ascites and pleural effusion, resembling Meigs syndrome. Elevated serum CA125 levels can further complicate differentiation from malignant ovarian epithelial tumours.
CASE PRESENTATION
A 37-year-old female from a rural area presented with a distended abdomen and weight loss lasting 2 months. Clinical examinations revealed a solid pelvic mass and diagnostic tests showed significantly elevated CA125 levels. Imaging suggested a large ovarian mass and surgical intervention confirmed a fibrothecoma of the left ovary. The postoperative course was uneventful, with subsequent resolution of ascites and pleurisy.
CLINICAL DISCUSSION
The diagnosis of ovarian fibromas/fibrothecomas poses challenges due to their asymptomatic nature, solid appearance, and occasional association with the Meigs syndrome. Elevated CA125 levels can mislead the diagnosis of epithelial ovarian carcinoma. The case underscores the importance of considering ovarian fibromas/fibrothecomas in the differential diagnosis of ovarian tumours with elevated CA125 levels, especially in women of reproductive age. The benign nature of these tumours necessitates a conservative surgical approach, emphasizing the importance of intraoperative frozen section analysis.
CONCLUSION
Ovarian fibrothecomas associated with elevated serum CA125 levels are rare. Their presentation can mimic malignant ovarian neoplasms, leading to potential diagnostic confusion. Surgical removal remains the treatment of choice, with a favorable prognosis post-surgery.
PubMed: 38830334
DOI: 10.1016/j.ijscr.2024.109847 -
The Oncologist May 2024Epidermal growth factor receptor kinase domain duplication (EGFR-KDD) is a rare, recurrent oncogenic variant that constitutively activates EGFR in non-small-cell lung...
Epidermal growth factor receptor kinase domain duplication (EGFR-KDD) is a rare, recurrent oncogenic variant that constitutively activates EGFR in non-small-cell lung cancer. Herein, we report the case of a 70-year-old man with resectable colorectal adenocarcinoma who underwent surgery followed by adjuvant therapy. He relapsed with multiple liver metastases and received standard chemotherapy until his disease became refractory. Comprehensive genomic profiling of his postoperative colorectal cancer tissue revealed EGFR-KDD. He was treated with an EGFR tyrosine kinase inhibitor (TKI), afatinib and achieved a partial response (- 55%) after 8 weeks; however, he developed massive malignant ascites after 13 weeks. Osimertinib, another EGFR-TKI, controlled his tumors for 9 months. Patient-derived cancer organoids from his malignant ascites confirmed sensitivity to EGFR-TKIs. The findings suggest that EGFR-TKIs can be a potential treatment option for this molecular subgroup.
PubMed: 38821532
DOI: 10.1093/oncolo/oyae113 -
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 -
Clinical & Translational Immunology 2024Recent studies have identified expression of the non-functional P2X7 (nfP2X7) receptor on various malignant cells including ovarian cancer, but not on normal cells,...
OBJECTIVES
Recent studies have identified expression of the non-functional P2X7 (nfP2X7) receptor on various malignant cells including ovarian cancer, but not on normal cells, which makes it a promising tumour-associated antigen candidate for chimeric antigen receptor (CAR)-T-cell immunotherapies. In this study, we assessed the cytotoxic effects of nfP2X7-CAR-T cells on ovarian cancer using and models.
METHODS
We evaluated the effects of nfP2X7-CAR-T cells on ovarian cancer cell lines (SKOV-3, OVCAR3, OVCAR5), normal peritoneal cells (LP-9) and primary serous ovarian cancer cells derived from patient ascites using monolayer and 3D spheroid assays. We also evaluated the effects of nfP2X7-CAR-T cells on patient-derived tissue explants, which recapitulate an intact tumour microenvironment. In addition, we investigated the effect of nfP2X7-CAR-T cells using the OVCAR-3 xenograft model in NOD-scid IL2Rγnull (NSG) mice.
RESULTS
Our study found that nfP2X7-CAR-T cells were cytotoxic and significantly inhibited survival of OVCAR3, OVCAR5 and primary serous ovarian cancer cells compared with un-transduced CD3 T cells . However, no significant effects of nfP2X7-CAR-T cells were observed for SKOV3 or normal peritoneal cells (LP-9) cells with low P2X7 receptor expression. Treatment with nfP2X7-CAR-T cells increased apoptosis compared with un-transduced T cells in patient-derived explants and correlated with CD3 positivity. Treatment with nfP2X7-CAR-T cells significantly reduced OVCAR3 tumour burden in mice compared with un-transduced CD3 cells for 7-8 weeks.
CONCLUSION
This study demonstrates that nfP2X7-CAR-T cells have great potential to be developed as a novel immunotherapy for ovarian cancer.
PubMed: 38800555
DOI: 10.1002/cti2.1512 -
Cell Death & Disease May 2024Advanced epithelial ovarian cancer (EOC) survival rates are dishearteningly low, with ~25% surviving beyond 5 years. Evidence suggests that cancer stem cells contribute...
Advanced epithelial ovarian cancer (EOC) survival rates are dishearteningly low, with ~25% surviving beyond 5 years. Evidence suggests that cancer stem cells contribute to acquired chemoresistance and tumor recurrence. Here, we show that IRAK1 is upregulated in EOC tissues, and enhanced expression correlates with poorer overall survival. Moreover, low molecular weight hyaluronic acid, which is abundant in malignant ascites from patients with advanced EOC, induced IRAK1 phosphorylation leading to STAT3 activation and enhanced spheroid formation. Knockdown of IRAK1 impaired tumor growth in peritoneal disease models, and impaired HA-induced spheroid growth and STAT3 phosphorylation. Finally, we determined that TCS2210, a known inducer of neuronal differentiation in mesenchymal stem cells, is a selective inhibitor of IRAK1. TCS2210 significantly inhibited EOC growth in vitro and in vivo both as monotherapy, and in combination with cisplatin. Collectively, these data demonstrate IRAK1 as a druggable target for EOC.
Topics: Interleukin-1 Receptor-Associated Kinases; Humans; STAT3 Transcription Factor; Female; Carcinoma, Ovarian Epithelial; Hyaluronic Acid; Animals; Ovarian Neoplasms; Neoplastic Stem Cells; Cell Line, Tumor; Mice; Cisplatin; Mice, Nude; Phosphorylation; Cell Proliferation; Molecular Weight; Xenograft Model Antitumor Assays
PubMed: 38796478
DOI: 10.1038/s41419-024-06717-3 -
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