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International Journal of Surgery Case... Jun 2024Disseminated Peritoneal Leiomyomatosis (DPL) is a rare benign proliferation of solid peritoneal lesions along the abdominopelvic cavity comprised of smooth muscle and...
INTRODUCTION AND IMPORTANCE
Disseminated Peritoneal Leiomyomatosis (DPL) is a rare benign proliferation of solid peritoneal lesions along the abdominopelvic cavity comprised of smooth muscle and connective tissue. Though hormonal and iatrogenic causes have been theorized, the exact etiology remains unknown. Most patients with DPL are frequently premenopausal with a history of myomectomy or prior hysterectomy. These patients can present asymptomatically or with abnormal uterine bleeding and abdominal discomfort. DPL is a rare entity with less than 150 cases reported in the literature, showcasing the need of awareness of this poorly understood neoplasm. Imaging, if performed, is helpful as positron emission tomography (PET) can differentiate DPL from malignant peritoneal disease. Treatment involves medical and surgical options based on patient's clinical presentation, with medical treatment with gonadotropin-releasing hormone agonist being first line.
CASE PRESENTATION
We report a case of a previously healthy female presenting for desired laparoscopic tubal ligation with incidental countless peritoneal nodules suspicious for carcinomatosis found during the operative event but proven leiomyomas after histologic examination.
CLINICAL DISCUSSION
Differentiating DPL from mimickers such as leiomyosarcoma, endometriosis, and carcinomatosis remains a challenge as macroscopic appearances are similar ultimately requiring histology evaluation.
CONCLUSION
Awareness of the entity is crucial to avoid misdiagnosis and unnecessary anxiety associated with a presumptive diagnosis of malignancy for a largely benign entity.
PubMed: 38878730
DOI: 10.1016/j.ijscr.2024.109908 -
Clinical and Translational Medicine Jun 2024
Topics: Humans; Stomach Neoplasms; Claudins; Antibodies, Monoclonal; Receptor, Fibroblast Growth Factor, Type 2; Protein Isoforms; Neoplasms
PubMed: 38877656
DOI: 10.1002/ctm2.1736 -
JAMA Network Open Jun 2024The European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO) have recently proposed a consensus...
IMPORTANCE
The European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO) have recently proposed a consensus definition and diagnostic criteria for sarcopenic obesity (SO).
OBJECTIVE
To implement the ESPEN-EASO diagnostic algorithm to investigate the prevalence of SO and its association with outcomes in patients with solid tumor cancers, with particular regard to associations among SO, overall survival (OS), and patient quality of life (QoL).
DESIGN, SETTING, AND PARTICIPANTS
This prospective cohort study included patients diagnosed with solid tumor starting in May 7, 2013, with the last follow-up on June 30, 2022. Patients with solid tumors were categorized into SO and non-SO groups according to ESPEN-EASO criteria. The primary outcome was OS and the secondary outcomes included patient QoL and risk of intensive care unit (ICU) admission. Data were analyzed from June to December 2023.
RESULTS
A total of 6790 patients were included in the study (mean [SD] age, 59.64 [10.77] years; 3489 were female [51.4%]). The prevalence of SO was 4.36% (296 of 6790) in the whole cohort and 14.98% (296 of 1976) in the subgroup with obesity. SO prevalence increased with age. During a median (IQR) follow-up period of 6.83 (5.67-7.04) years, 2103 patients died. Cox regression analysis indicated that SO was independently associated with lower OS (hazard ratio [HR], 1.54; 95% CI, 1.23-1.92), which was observed in both men (HR, 1.51; 95% CI, 1.09-2.10) and women (HR, 1.53; 95% CI, 1.12-2.07). SO was also associated with poorer QoL and higher risk of ICU admission (odds ratio, 2.39; 95% CI, 1.06-5.29). Among the diagnostic components of SO, low hand grip strength (HGS) was the only SO component associated with poor OS (HR, 1.15; 95% CI, 1.04-1.28).
CONCLUSIONS AND RELEVANCE
This cohort study of SO found that SO was significantly associated with lower OS, poorer QoL, and higher risk of ICU admission. Weak HGS, 1 of the diagnostic conditions, was the only component of SO associated with OS. The ESPEN-EASO algorithm appears to be an applicable tool to identify cancer-associated SO, which represents a major clinical complication and factor associated with risk for poor outcomes in these patients.
Topics: Humans; Male; Female; Neoplasms; Middle Aged; Obesity; Sarcopenia; Quality of Life; Prospective Studies; Aged; Prevalence
PubMed: 38874924
DOI: 10.1001/jamanetworkopen.2024.17115 -
Frontiers in Immunology 2024The five-year survival rates for pancreatic ductal adenocarcinoma (PDAC) have scarcely improved over the last half-century. It is inherently resistant to FDA-approved...
The five-year survival rates for pancreatic ductal adenocarcinoma (PDAC) have scarcely improved over the last half-century. It is inherently resistant to FDA-approved immunotherapies, which have transformed the outlook for patients with other advanced solid tumours. Accumulating evidence relates this resistance to its hallmark immunosuppressive milieu, which instils progressive dysfunction among tumour-infiltrating effector T cells. This milieu is established at the inception of neoplasia by immunosuppressive cellular populations, including regulatory T cells (T), which accumulate in parallel with the progression to malignant PDAC. Thus, the therapeutic manipulation of T has captured significant scientific and commercial attention, bolstered by the discovery that an abundance of tumour-infiltrating T correlates with a poor prognosis in PDAC patients. Herein, we propose a mechanism for the resistance of PDAC to anti-PD-1 and CTLA-4 immunotherapies and re-assess the rationale for pursuing T-targeted therapies in light of recent studies that profiled the immune landscape of patient-derived tumour samples. We evaluate strategies that are emerging to limit T-mediated immunosuppression for the treatment of PDAC, and signpost early-stage trials that provide preliminary evidence of clinical activity. In this context, we find a compelling argument for investment in the ongoing development of T-targeted immunotherapies for PDAC.
Topics: Animals; Humans; Carcinoma, Pancreatic Ductal; Immune Checkpoint Inhibitors; Immunotherapy; Lymphocytes, Tumor-Infiltrating; Pancreatic Neoplasms; T-Lymphocytes, Regulatory; Tumor Microenvironment
PubMed: 38873607
DOI: 10.3389/fimmu.2024.1406250 -
Cureus May 2024Renal cell carcinoma (RCC) is the predominant solid lesion found in the kidney. Extra-renal RCC is a rare entity. We present the case of a 75-year-old male with an...
Renal cell carcinoma (RCC) is the predominant solid lesion found in the kidney. Extra-renal RCC is a rare entity. We present the case of a 75-year-old male with an incidentally discovered mass in the right iliac fossa. The patient underwent active surveillance because a percutaneous biopsy revealed a mesenchymal neoplastic lesion of benign biological behavior. As the mass had high growth rates, a decision for open surgical exploration and excision was made. The pathology results indicated clear cell renal carcinoma, and negative results on F-FDG whole-body positron emission tomography-computed tomography (PET/CT) established the diagnosis of extra-renal clear cell RCC. Similar types of neoplasms are extremely rare and are estimated to have developed primarily in mesodermal embryonic remnants. Clinicians should be aware of this rare entity as its diagnosis is challenging and is based on pathology.
PubMed: 38872671
DOI: 10.7759/cureus.60246 -
Cancer Medicine Jun 2024Secreted Frizzled-Related Protein 5 (SFRP5) modulates Wnt signalling pathways, affecting diverse biological processes. We assessed the diagnostic and prognostic value of...
BACKGROUND
Secreted Frizzled-Related Protein 5 (SFRP5) modulates Wnt signalling pathways, affecting diverse biological processes. We assessed the diagnostic and prognostic value of circulating SFRP5 (cSFRP5) in colorectal cancer (CRC) METHODS: Plasma cSFRP5 concentrations were measured using enzyme-linked immunosorbent assay (ELISA) in healthy donors (n = 133), individuals diagnosed with CRC (n = 449), colorectal polyps (n = 85), and medical conditions in other organs including cancer, inflammation, and benign states (n = 64).
RESULTS
Patients with CRC, polyps, and other conditions showed higher cSFRP5 levels than healthy individuals (p < 0.0001). Receiver operating characteristic curves comparing healthy donors with medical conditions, polyps and CRC were 0.814 (p < 0.0001), 0.763 (p < 0.0001) and 0.762 (p < 0.0001), respectively. In CRC, cSFRP5 correlated with patient age (p < 0.0001), tumour stage (p < 0.0001), and histological differentiation (p = 0.0273). Levels, adjusted for patient age, sex, plasma age and collection institution, peaked in stage II versus I (p < 0.0001), III (p = 0.0002) and IV (p < 0.0001), were lowest in stage I versus III (p = 0.0002) and IV (p = 0.0413), with no difference between stage III and IV. Elevated cSFRP5 levels predicted longer overall survival in stages II-III CRC (univariate: HR 1.82, 95% CI: 1.02-3.26, p = 0.024; multivariable: HR 2.34, 95% CI: 1.12-4.88, p = 0.015).
CONCLUSION
This study confirms cSFRP5 levels are elevated in CRC compared to healthy control and reveals a correlation between elevated cSFRP5 and overall survival in stages II-III disease.
Topics: Humans; Colorectal Neoplasms; Male; Female; Prognosis; Middle Aged; Aged; Biomarkers, Tumor; Adaptor Proteins, Signal Transducing; Adult; Neoplasm Staging; ROC Curve; Aged, 80 and over; Case-Control Studies
PubMed: 38872420
DOI: 10.1002/cam4.7352 -
Cancer Medicine Jun 2024Patients with metastatic cancer experience high healthcare use and costs, most of which are unplanned. We aimed to assess whether patients with more competent informal...
BACKGROUND
Patients with metastatic cancer experience high healthcare use and costs, most of which are unplanned. We aimed to assess whether patients with more competent informal caregivers have lower unplanned healthcare use and costs.
METHODS
This study used data from a prospective cohort of patients with solid metastatic cancer. Patients and their informal family caregivers were surveyed every 3 months until patients' death. Patients' unplanned healthcare use/costs were examined through hospital records. Caregivers responded to the 4-item Caregiver Competence Scale. First, in a deceased subsample of patients and their caregivers, we used patients' last 2 years of data (226 dyads) to assess the association between caregivers' competency (independent variable) and patients' unplanned healthcare use/costs (outcomes). Next, in a prospective sample of patient-caregiver dyads (up to 15 surveys), we assessed whether patients' functional well-being and psychological distress moderated the association between caregivers' competency and unplanned healthcare use/costs (311 dyads).
RESULTS
In the deceased subsample, during last 2 years of patients' life, caregivers' higher competency lowered the odds of patients' unplanned healthcare use [OR (CI) = 0.86 (0.75, 0.98), p = 0.03], and was associated with a significant reduction in unplanned healthcare costs [Coeff (CI) = -0.19 (-0.36, -0.01), p = 0.03]. In the prospective sample, patients' functional well-being and psychological distress moderated the association between caregivers' competency and patients' unplanned healthcare use/costs.
CONCLUSION
With deterioration in patients' condition and an increase in caregiving demands, improving caregivers' competency can reduce patients' unplanned healthcare use and costs. This should be further tested in future trials.
Topics: Humans; Caregivers; Female; Male; Neoplasms; Middle Aged; Prospective Studies; Aged; Health Care Costs; Patient Acceptance of Health Care; Surveys and Questionnaires; Adult
PubMed: 38872395
DOI: 10.1002/cam4.7366 -
European Radiology Experimental Jun 2024New immunotherapies activate tumor-associated macrophages (TAMs) in the osteosarcoma microenvironment. Iron oxide nanoparticles (IONPs) are phagocytosed by TAMs and,...
BACKGROUND
New immunotherapies activate tumor-associated macrophages (TAMs) in the osteosarcoma microenvironment. Iron oxide nanoparticles (IONPs) are phagocytosed by TAMs and, therefore, enable TAM detection on T2*- and T2-weighted magnetic resonance images. We assessed the repeatability and reproducibility of T2*- and T2-mapping of osteosarcomas in a mouse model.
METHODS
Fifteen BALB/c mice bearing-murine osteosarcomas underwent magnetic resonance imaging (MRI) on 3-T and 7-T scanners before and after intravenous IONP infusion, using T2*-weighted multi-gradient-echo, T2-weighted fast spin-echo, and T2-weighted multi-echo sequences. Each sequence was repeated twice. Tumor T2 and T2* relaxation times were measured twice by two independent investigators. Repeatability and reproducibility of measurements were assessed.
RESULTS
We found excellent agreement between duplicate acquisitions for both T2* and T2 measurements at either magnetic field strength, by the same individual (repeatability), and between individuals (reproducibility). The repeatability concordance correlation coefficient (CCC) for T2* values were 0.99 (coefficients of variation (CoV) 4.43%) for reader 1 and 0.98 (CoV 5.82%) for reader 2. The reproducibility of T2* values between the two readers was 0.99 (CoV 3.32%) for the first acquisitions and 0.99 (CoV 6.30%) for the second acquisitions. Regarding T2 values, the repeatability of CCC was similar for both readers, 0.98 (CoV 3.64% for reader 1 and 4.45% for reader 2). The CCC of the reproducibility of T2 was 0.99 (CoV 3.1%) for the first acquisition and 0.98 (CoV 4.38%) for the second acquisition.
CONCLUSIONS
Our results demonstrated high repeatability and reproducibility of quantitative T2* and T2 mapping for monitoring the presence of TAMs in osteosarcomas.
RELEVANCE STATEMENT
T2* and T2 measurements of osteosarcomas on IONP-enhanced MRI could allow identifying patients who may benefit from TAM-modulating immunotherapies and for monitoring treatment response. The technique described here could be also applied across a wide range of other solid tumors.
KEY POINTS
• Optimal integration of TAM-modulating immunotherapies with conventional chemotherapy remains poorly elucidated. • We found high repeatability of T2* and T2 measurements of osteosarcomas in a mouse model, both with and without IONPs contrast, at 3-T and 7-T MRI field strengths. • T2 and T2* mapping may be used to determine response to macrophage-modulating cancer immunotherapies.
Topics: Animals; Osteosarcoma; Mice; Magnetic Resonance Imaging; Reproducibility of Results; Mice, Inbred BALB C; Disease Models, Animal; Bone Neoplasms; Female
PubMed: 38872042
DOI: 10.1186/s41747-024-00467-9 -
International Journal of Surgery Case... Jun 2024Solid pseudopapillary neoplasms (SPNs) of the pancreas are rare neoplasms, accounting for only 1 %-2 % of all pancreatic tumors, and predominantly affect female patients.
INTRODUCTION
Solid pseudopapillary neoplasms (SPNs) of the pancreas are rare neoplasms, accounting for only 1 %-2 % of all pancreatic tumors, and predominantly affect female patients.
CASE PRESENTATION
The present case report details a patient presenting to the emergency department with abdominal pain for 3 days who ultimately received a diagnosis of SPNs in the pancreatic body and tail. A contrast-enhanced computed tomography (CT) scan revealed a sizable mass arising from the pancreas, featuring an enhancing cystic component with involvement of the liver and spleen. The patient underwent subsequent exploratory laparotomy, a distal pancreatectomy, splenectomy, and partial hepatectomy. SPN diagnosis was confirmed by histopathology and immunohistochemistry with negative resection margins.
CLINICAL DISCUSSION
Approximately 70 % of SPN cases are asymptomatic and are incidentally discovered. Despite advances in diagnostic modalities, preoperative diagnosis of SPNs remains a clinical challenge. Surgical management with negative resection margins remains the primary treatment approach. The recurrence rate after surgical resection has been reported to be 3 %-9 %. The prognosis for SPNs limited to the pancreas is generally favorable, with a cure rate exceeding 95 % after complete surgical resection.
CONCLUSION
An SPN of the pancreas is a rare tumor observed in young female patients. Although it is classified as a malignant tumor, SPN has low malignant potential. Aggressive surgical resection, however, has proven effective in curing SPN for the majority of patients.
PubMed: 38870658
DOI: 10.1016/j.ijscr.2024.109867 -
Journal of Cancer Research and Clinical... Jun 2024With the development of immunotherapy research, the role of immune checkpoint blockade (ICB) in the treatment of cervical cancer has been emphasized, but many patients...
PURPOSE
With the development of immunotherapy research, the role of immune checkpoint blockade (ICB) in the treatment of cervical cancer has been emphasized, but many patients still can't receive long-term benefits from ICB. Poly ADP ribose polymerase inhibitor (PARPi) has been proved to exert significant antitumor effects in multiple solid tumors. Whether cervical cancer patients obtain better benefits from the treatment regimen of PARPi combined with ICB remains unclear.
METHODS
The alteration of PD-L1 expression induced by niraparib in cervical cancer cells and its underlying mechanism were assessed by western blot and immunofluorescence and quantitative real-time polymerase chain reaction (qRT-PCR).The regulation of PTEN by KDM5A was confirmed using Chromatin immunoprecipitation (ChIP) assay and RNA interference. Analyzing the relationship between PD-L1 and immune effector molecules through searching online databases. Therapeutic efficacy of niraparib, PD-L1 blockade or combination was assessed in syngeneic tumor model. The changes of immune cells and cytokines in vivo was detected by immunohistochemistry (IHC) and qRT-PCR.
RESULTS
We found that niraparib upregulated PD-L1 expression and potentiated the antitumor effects of PD-L1 blockade in a murine cervical cancer model. Niraparib inhibited the Pten expression by increasing the abundance of KDM5A, which expanded PD-L1 abundance through activating the PI3K-AKT-S6K1 pathway. PD-L1 was positively correlated with immune effector molecules including TNF-α, IFN-γ, granzyme A and granzyme B based on biological information analysis. Niraparib increased the infiltration of CD8 T cells and the level of IFN-γ, granzyme B in vivo.
CONCLUSION
Our findings demonstrates the regulation of niraparib on local immune microenvironment of cervical cancer, and provides theoretical basis for supporting the combination of PARPi and PD-L1 blockade as a potential treatment for cervical cancer.
Topics: Uterine Cervical Neoplasms; Female; Humans; Animals; Piperidines; B7-H1 Antigen; Indazoles; Mice; Immune Checkpoint Inhibitors; Poly(ADP-ribose) Polymerase Inhibitors; Cell Line, Tumor
PubMed: 38869633
DOI: 10.1007/s00432-024-05819-x