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Archives of Iranian Medicine Jun 2024Macroscopic tumor implants in the hernia sac are a very rare condition. They occur as a result of the implantation of malignant cells in the malignant ascites from the...
Macroscopic tumor implants in the hernia sac are a very rare condition. They occur as a result of the implantation of malignant cells in the malignant ascites from the inguinal canal to the hernia sac. In this case report, we share the clinical and radiological findings of the macroscopic tumoral implants in the hernia sac at the level of the inguinal canal and scrotum in a male patient aged 65 years with a history of total gastrectomy for gastric adenocarcinoma and developing malignant ascites six months after the surgery.
Topics: Humans; Male; Stomach Neoplasms; Hernia, Inguinal; Adenocarcinoma; Aged; Gastrectomy; Tomography, X-Ray Computed; Ascites
PubMed: 38855804
DOI: 10.34172/aim.28951 -
Clinical Case Reports Jun 2024Chronic myelomonocytic leukemia, a rare case of hematological malignancy mainly affects the elderly and may present with life threatening pericardial effusion as an...
KEY CLINICAL MESSAGE
Chronic myelomonocytic leukemia, a rare case of hematological malignancy mainly affects the elderly and may present with life threatening pericardial effusion as an initial manifestation. High index of suspicion is hence key for early management.
ABSTRACT
We present a case of an 81-year-old African male who presented with progressive cough, respiratory distress and bilateral lower limb swelling, and was diagnosed with life-threatening pericardial effusion resulting from chronic myelomonocytic leukemia following complete blood count, peripheral blood film, bone marrow aspirate with trephine biopsy, and flow cytometry studies.
PubMed: 38855083
DOI: 10.1002/ccr3.9048 -
Molecular Cancer Jun 2024Platinum resistance is the primary cause of poor survival in ovarian cancer (OC) patients. Targeted therapies and biomarkers of chemoresistance are critical for the...
BACKGROUND
Platinum resistance is the primary cause of poor survival in ovarian cancer (OC) patients. Targeted therapies and biomarkers of chemoresistance are critical for the treatment of OC patients. Our previous studies identified cell surface CD55, a member of the complement regulatory proteins, drives chemoresistance and maintenance of cancer stem cells (CSCs). CSCs are implicated in tumor recurrence and metastasis in multiple cancers.
METHODS
Protein localization assays including immunofluorescence and subcellular fractionation were used to identify CD55 at the cell surface and nucleus of cancer cells. Protein half-life determinations were used to compare cell surface and nuclear CD55 stability. CD55 deletion mutants were generated and introduced into cancer cells to identify the nuclear trafficking code, cisplatin sensitivity, and stem cell frequency that were assayed using in vitro and in vivo models. Detection of CD55 binding proteins was analyzed by immunoprecipitation followed by mass spectrometry. Target pathways activated by CD55 were identified by RNA sequencing.
RESULTS
CD55 localizes to the nucleus of a subset of OC specimens, ascites from chemoresistant patients, and enriched in chemoresistant OC cells. We determined that nuclear CD55 is glycosylated and derived from the cell surface pool of CD55. Nuclear localization is driven by a trafficking code containing the serine/threonine (S/T) domain of CD55. Nuclear CD55 is necessary for cisplatin resistance, stemness, and cell proliferation in OC cells. CD55 S/T domain is necessary for nuclear entry and inducing chemoresistance to cisplatin in both in vitro and in vivo models. Deletion of the CD55 S/T domain is sufficient to sensitize chemoresistant OC cells to cisplatin. In the nucleus, CD55 binds and attenuates the epigenetic regulator and tumor suppressor ZMYND8 with a parallel increase in H3K27 trimethylation and members of the Polycomb Repressive Complex 2.
CONCLUSIONS
For the first time, we show CD55 localizes to the nucleus in OC and promotes CSC and chemoresistance. Our studies identify a therapeutic mechanism for treating platinum resistant ovarian cancer by blocking CD55 nuclear entry.
Topics: Humans; Ovarian Neoplasms; Female; Cisplatin; Drug Resistance, Neoplasm; Neoplastic Stem Cells; Animals; Mice; CD55 Antigens; Cell Line, Tumor; Histones; Cell Nucleus; Chromatin; Methylation; Xenograft Model Antitumor Assays; Antineoplastic Agents; Protein Transport
PubMed: 38853277
DOI: 10.1186/s12943-024-02028-5 -
Photochemistry and Photobiology Jun 2024Resistance to platinum-based chemotherapies remains a significant challenge in advanced-stage high-grade serous ovarian carcinoma, and patients with malignant ascites...
Resistance to platinum-based chemotherapies remains a significant challenge in advanced-stage high-grade serous ovarian carcinoma, and patients with malignant ascites face the poorest outcomes. It is, therefore, important to understand the effects of ascites, including the associated fluid shear stress (FSS), on phenotypic changes and therapy response, specifically FSS-induced chemotherapy resistance and the underlying mechanisms in ovarian cancer. This study investigated the effects of FSS on response to cisplatin, a platinum-based chemotherapy, and doxorubicin, an anthracycline, both of which are commonly used to manage advanced-stage ovarian cancer. Consistent with prior research, OVCAR-3 and Caov-3 cells cultivated under FSS demonstrated significant resistance to cisplatin. Examination of the role of mitochondria revealed an increase in mitochondrial DNA copy number and intracellular ATP content in cultures grown under FSS, suggesting that changes in mitochondria number and metabolic activity may contribute to platinum resistance. Interestingly, no resistance to doxorubicin was observed under FSS, the first such observation of a lack of resistance under these conditions. Finally, this study demonstrated the potential of photodynamic priming using benzoporphyrin derivative, a clinically approved photosensitizer that localizes in part to mitochondria and endoplasmic reticula, to enhance the efficacy of cisplatin, but not doxorubicin, thereby overcoming FSS-induced platinum resistance.
PubMed: 38849970
DOI: 10.1111/php.13967 -
BMC Cancer Jun 2024Ovarian cancer is the first cause of death from gynecological malignancies mainly due to development of chemoresistance. Despite the emergence of PARP inhibitors, which...
BACKGROUND
Ovarian cancer is the first cause of death from gynecological malignancies mainly due to development of chemoresistance. Despite the emergence of PARP inhibitors, which have revolutionized the therapeutic management of some of these ovarian cancers, the 5-year overall survival rate remains around 45%. Therefore, it is crucial to develop new therapeutic strategies, to identify predictive biomarkers and to predict the response to treatments. In this context, functional assays based on patient-derived tumor models could constitute helpful and relevant tools for identifying efficient therapies or to guide clinical decision making.
METHOD
The OVAREX study is a single-center non-interventional study which aims at investigating the feasibility of establishing in vivo and ex vivo models and testing ex vivo models to predict clinical response of ovarian cancer patients. Patient-Derived Xenografts (PDX) will be established from tumor fragments engrafted subcutaneously into immunocompromised mice. Explants will be generated by slicing tumor tissues and Ascites-Derived Spheroids (ADS) will be isolated following filtration of ascites. Patient-derived tumor organoids (PDTO) will be established after dissociation of tumor tissues or ADS, cell embedding into extracellular matrix and culture in specific medium. Molecular and histological characterizations will be performed to compare tumor of origin and paired models. Response of ex vivo tumor-derived models to conventional chemotherapy and PARP inhibitors will be assessed and compared to results of companion diagnostic test and/or to the patient's response to evaluate their predictive value.
DISCUSSION
This clinical study aims at generating PDX and ex vivo models (PDTO, ADS, and explants) from tumors or ascites of ovarian cancer patients who will undergo surgical procedure or paracentesis. We aim at demonstrating the predictive value of ex vivo models for their potential use in routine clinical practice as part of precision medicine, as well as establishing a collection of relevant ovarian cancer models that will be useful for the evaluation of future innovative therapies.
TRIAL REGISTRATION
The clinical trial has been validated by local research ethic committee on January 25th 2019 and registered at ClinicalTrials.gov with the identifier NCT03831230 on January 28th 2019, last amendment v4 accepted on July 18, 2023.
Topics: Animals; Female; Humans; Mice; Biomarkers, Tumor; Disease Models, Animal; Organoids; Ovarian Neoplasms; Therapies, Investigational; Xenograft Model Antitumor Assays
PubMed: 38849726
DOI: 10.1186/s12885-024-12429-w -
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 -
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 -
Emergency Radiology Jun 2024The goal of our study was to better characterize new CT diagnoses of peritoneal carcinomatosis (PC) in the ED, and to evaluate how to best identify the primary lesion....
PURPOSE
The goal of our study was to better characterize new CT diagnoses of peritoneal carcinomatosis (PC) in the ED, and to evaluate how to best identify the primary lesion. Prompt identification of the source of the carcinomatosis may allow for the patient to receive early initial care from the correct clinical service.
METHODS
All new CT cases of PC-like appearance identified on CT in the ED from January 2017 through July 2020. Each report and corresponding medical record were manually reviewed. Patient demographics, presence/absence of intravenous contrast, source organ predicted by the radiologist in the CT scan report, pathologic diagnosis, and amount of ascites were tabulated. Chi-tests were used to test the statistical significance of differences between groups.
RESULTS
Of the 131 CT cases of new PC-like appearance which received workup, 108 cases had pathologically proven PC and 23 cases had no underlying malignancy yielding a positive predictive value for actual PC of 82%. The most common cause of new PC in women was gynecological (66%), and in men was of GI tract origin (57%). Concordance between radiologist prediction and final pathology was higher with intravenous contrast (58%) compared to without contrast (40%); although this difference was not statistically significant (p = 0.19). A moderate or large amount of ascites was found in more than half of GYN primaries and in adenocarcinoma of unknown primary and there was a statistically significant difference in amount of ascites between cancer primaries (p = 0.01).
CONCLUSION
A PC-like appearance on CT in the ED will likely be in patients with known malignancy, but of the new cases, there is a high PPV for it to represent new peritoneal carcinomatosis. Gynecological and GI malignancies are the most common cause in women and men, respectively, and this may help in focusing the radiologist's search pattern. Usage of intravenous contrast may help in identifying a primary lesion, and the presence of high-volume ascites should suggest a GYN primary or adenocarcinoma of unknown primary when there is no other obvious primary lesion.
PubMed: 38836936
DOI: 10.1007/s10140-024-02238-w