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Nature Medicine May 2024Cancer of unknown primary (CUP) site poses diagnostic challenges due to its elusive nature. Many cases of CUP manifest as pleural and peritoneal serous effusions....
Cancer of unknown primary (CUP) site poses diagnostic challenges due to its elusive nature. Many cases of CUP manifest as pleural and peritoneal serous effusions. Leveraging cytological images from 57,220 cases at four tertiary hospitals, we developed a deep-learning method for tumor origin differentiation using cytological histology (TORCH) that can identify malignancy and predict tumor origin in both hydrothorax and ascites. We examined its performance on three internal (n = 12,799) and two external (n = 14,538) testing sets. In both internal and external testing sets, TORCH achieved area under the receiver operating curve values ranging from 0.953 to 0.991 for cancer diagnosis and 0.953 to 0.979 for tumor origin localization. TORCH accurately predicted primary tumor origins, with a top-1 accuracy of 82.6% and top-3 accuracy of 98.9%. Compared with results derived from pathologists, TORCH showed better prediction efficacy (1.677 versus 1.265, P < 0.001), enhancing junior pathologists' diagnostic scores significantly (1.326 versus 1.101, P < 0.001). Patients with CUP whose initial treatment protocol was concordant with TORCH-predicted origins had better overall survival than those who were administrated discordant treatment (27 versus 17 months, P = 0.006). Our study underscores the potential of TORCH as a valuable ancillary tool in clinical practice, although further validation in randomized trials is warranted.
Topics: Humans; Deep Learning; Neoplasms, Unknown Primary; Female; Male; Aged; Middle Aged; ROC Curve; Adult; Cytodiagnosis; Aged, 80 and over; Ascites; Cytology
PubMed: 38627559
DOI: 10.1038/s41591-024-02915-w -
British Journal of Cancer Jun 2024Failure of immunotherapy in high-grade serous ovarian cancer (HGSC) may be due to high levels of transforming growth factor-β (TGF-β) in ascites or tumour immune...
BACKGROUND
Failure of immunotherapy in high-grade serous ovarian cancer (HGSC) may be due to high levels of transforming growth factor-β (TGF-β) in ascites or tumour immune microenvironment (TIME). Here, we test whether coordinated blockade of TGF-β and PD-L1 with bintrafusp alfa (BA) can provoke anti-tumour immune responses in preclinical HGSC models.
METHODS
BA is a first-in-class bifunctional inhibitor of TGF-β and PD-L1, and was tested for effects on overall survival and altered TIME in syngeneic HGSC models.
RESULTS
Using a mouse ID8-derived HGSC syngeneic model with IFNγ-inducible PD-L1 expression, BA treatments significantly reduced ascites development and tumour burden. BA treatments depleted TGF-β and VEGF in ascites, and skewed the TIME towards cytotoxicity compared to control. In the BR5 HGSC syngeneic model, BA treatments increased tumour-infiltrating CD8 T cells with effector memory and cytotoxic markers, as well as cytolytic NK cells. Extended BA treatments in the BR5 model produced ∼50% BA-cured mice that were protected from re-challenge. These BA-cured mice had increased peritoneal T-effector memory and NK cells compared to controls.
CONCLUSIONS
Our preclinical studies of BA in advanced ovarian cancer models support further testing of BA as an improved immunotherapy option for patients with advanced ovarian cancer.
Topics: Female; Animals; Killer Cells, Natural; Ovarian Neoplasms; Mice; Transforming Growth Factor beta; B7-H1 Antigen; Humans; Cell Line, Tumor; Tumor Microenvironment; Disease Models, Animal
PubMed: 38622286
DOI: 10.1038/s41416-024-02677-9 -
Clinical Case Reports Apr 2024Struma ovarii (SO), is a rare and specialized ovarian teratoma. The treatment is controversial depending on the risk of recurrence and metastasis. Here a SO with...
KEY CLINICAL MESSAGE
Struma ovarii (SO), is a rare and specialized ovarian teratoma. The treatment is controversial depending on the risk of recurrence and metastasis. Here a SO with papillary thyroid carcinoma is reported and the approach is thoroughly discussed.
ABSTRACT
Struma ovarii (SO) is a highly specialized ovarian teratoma primarily composed of thyroid tissue. Clinical features associated with SO include lower abdominal discomfort, unusual vaginal bleeding, ascites, and hyperthyroidism. While SO rarely transforms into malignancy, the optimal degree of treatment remains controversial due to the varying risks of recurrence and metastasis. In this report, we present the case of a 64-year-old woman experiencing abdominal pain and diagnosed with SO, accompanied by papillary thyroid carcinoma. We thoroughly discuss the evaluation and management of this rare condition.
PubMed: 38617068
DOI: 10.1002/ccr3.8610 -
Journal of Ovarian Research Apr 2024Our explorative study assessed a panel of molecules for their association with epithelial ovarian carcinomas and their prognostic implications. The panel included tissue...
Pre-operative plasma VEGF-C levels portend recurrence in epithelial ovarian cancer patients and is a bankable prognostic marker even in the initial assessment of a patient.
PURPOSE
Our explorative study assessed a panel of molecules for their association with epithelial ovarian carcinomas and their prognostic implications. The panel included tissue expression of VEGF-C, COX-2, Ki-67 and eNOS alongside plasma levels of VEGF-C and nitric oxide.
METHODS
130 cases were enrolled in the study. Plasma levels were quantified by ELISA and tissue expressions were scored by immunohistochemistry. The Chi square and Fischer's exact test were applied to examine the impact of markers on clinicopathological factors. Non-parametric Spearman's rank correlation test was applied to define the association among test factors.
RESULTS
Plasma VEGF-C levels and COX-2 tissue expression strongly predicted recurrence and poor prognosis (< 0.001). Tissue Ki-67 was strongly indicative of late-stage disease (< 0.001). The aforementioned markers significantly associated with clinicopathological factors. Nuclear staining of VEGF-C was intriguing and was observed to correlate with high grade-stage malignancies, highly elevated plasma VEGF-C, and with recurrence. eNOS tissue expression showed no significant impact while nitric oxide associated positively with ascites levels. Tissue expression of VEGF-C did not associate significantly with poor prognosis although the expression was highly upregulated in most of the cases.
CONCLUSION
Plasma VEGF-C holds immense promise as a prognostic marker and the nuclear staining of VEGF-C seems to have some significant implication in molecular carcinogenesis and is a novel finding that commands further robust scrutiny. We present a first such study that assesses a set of biomarkers for prognostic implications in clinical management of epithelial ovarian carcinomas in a pan-Indian (Asian) population.
Topics: Humans; Female; Carcinoma, Ovarian Epithelial; Prognosis; Ovarian Neoplasms; Cyclooxygenase 2; Vascular Endothelial Growth Factor C; Ki-67 Antigen; Nitric Oxide; Neoplasm Staging; Biomarkers, Tumor
PubMed: 38594780
DOI: 10.1186/s13048-024-01398-0 -
Frontiers in Endocrinology 2024Leukemia patients undergoing cryopreserved ovarian tissue transplantation (OTT) may carry a high risk of disease induction. Measurable residual disease (MRD) in bone...
Evaluating the safety and efficacy of cryopreserved ovarian tissue transplantation in leukemia patients with different bone marrow remission status using xenotransplantation.
BACKGROUND
Leukemia patients undergoing cryopreserved ovarian tissue transplantation (OTT) may carry a high risk of disease induction. Measurable residual disease (MRD) in bone marrow is linked to an elevated risk of relapse. It is controversial whether leukemia patients must be allowed to achieve measurable residual disease negative (MRD-negative) status instead of measurable residual disease positive (MRD-positive) status before ovarian tissue cryopreservation (OTC).
OBJECTIVE
To explore the safety and efficacy of OTT in acute leukemia patients with different MRD status by using xenotransplantation.
METHOD
Cryopreserved ovarian tissue from 19 leukemia patients was thawed and xenotransplanted to ovariectomized BALB/C nude mice (n=36). The mice were divided into 2 groups based on the patient's MRD status before OTC: MRD-negative group (n=18) and MRD-positive group (n=18), additionally, a control group consisted of ovariectomized mice (n=9). Body weight was measured weekly and mortality, emaciation, and other abnormalities were recorded. Twenty-six weeks post-surgery, livers, spleens, uteruses, and ovarian grafts were removed for macroscopic and histological examinations to evaluate the efficacy of xenotransplantation and assess malignant cell contamination in mice.
RESULTS
Follicle growth was visible in the ovarian grafts of the MRD-negative and MRD-positive groups. Compared with the ovariectomized group, a significant decrease in body weight (<0.01) was noted, the uterine volume was notably larger, estradiol (E2) levels were significantly higher (<0.01), and follicle-stimulating hormone (FSH) levels were significantly lower (<0.001) in the other two groups. Mice in the MRD-positive group showed a significantly higher incidence of death (<0.001) and emaciation (<0.01), compared to the MRD-negative group. Histological observation revealed the presence of malignant cells in the grafts, livers, and spleens of 3 mice in the MRD-positive group. No abnormalities were observed in the mice from the MRD-negative group in both macroscopic and histological observations except one mouse was sacrificed for ascites unrelated to leukemia relapse.
CONCLUSION
For leukemia patients having ovarian tissue preserved in the first and only centralized human ovarian tissue cryobank in China, immunodeficient mice xenotransplantation can be a method to evaluate the safety and efficacy of OTT; the risk of malignant cell reimplantation due to OTT is higher in leukemia patients with MRD-positive status than those with MRD-negative status before OTC.
Topics: Female; Humans; Animals; Mice; Transplantation, Heterologous; Bone Marrow; Mice, Nude; Emaciation; Mice, Inbred BALB C; Cryopreservation; Leukemia; Recurrence
PubMed: 38590823
DOI: 10.3389/fendo.2024.1364316 -
Analytical and Bioanalytical Chemistry May 2024Multiplexed lateral flow assays (LFAs) offer efficient on-site testing by simultaneously detecting multiple biomarkers from a single sample, reducing costs. In cancer...
Multiplexed lateral flow assays (LFAs) offer efficient on-site testing by simultaneously detecting multiple biomarkers from a single sample, reducing costs. In cancer diagnostics, where biomarkers can lack specificity, multiparameter detection provides more information at the point-of-care. Our research focuses on epithelial ovarian cancer (EOC), where STn-glycosylated forms of CA125 and CA15-3 antigens can better discriminate cancer from benign conditions. We have developed a dual-label LFA that detects both CA125-STn and CA15-3-STn within a single anti-STn antibody test line. This utilizes spectral separation of green (540 nm) and blue (450 nm) emitting erbium (NaYF:Yb, Er)- and thulium (NaYF: Yb, Tm)-doped upconverting nanoparticle (UCNP) reporters conjugated with antibodies against the protein epitopes in CA125 or CA15-3. This technology allows the simultaneous detection of different antigen variants from a single test line. The developed proof-of-concept dual-label LFA was able to distinguish between the ascites fluid samples from diagnosed ovarian cancer patients (n = 10) and liver cirrhosis ascites fluid samples (n = 3) used as a negative control. The analytical sensitivity of CA125-STn for the dual-label LFA was 1.8 U/ml in buffer and 3.6 U/ml in ascites fluid matrix. Here we demonstrate a novel approach of spectrally separated measurement of STn-glycosylated forms of two different cancer-associated protein biomarkers by using UCNP reporter technology.
Topics: Humans; CA-125 Antigen; Female; Ovarian Neoplasms; Glycosylation; Biomarkers, Tumor; Antigens, Tumor-Associated, Carbohydrate; Luminescent Measurements; Carcinoma, Ovarian Epithelial; Immunoassay; Membrane Proteins; Mucin-1
PubMed: 38584178
DOI: 10.1007/s00216-024-05275-z -
Journal of Gastroenterology Jun 2024During systemic therapy, the management of portal hypertension (PH)-related complications is vital. This study aimed to clarify factors associated with the incidence and...
BACKGROUND
During systemic therapy, the management of portal hypertension (PH)-related complications is vital. This study aimed to clarify factors associated with the incidence and exacerbation of PH-related complications, including the usefulness of contrast-enhanced computed tomography (CECT) in the management of PH-related complications during systemic therapy.
METHODS
A total of 669 patients who received systemic therapy as first-line treatment (443 patients for sorafenib, 131 for lenvatinib, and 90 for atezolizumab/bevacizumab [ATZ/BEV]) were enrolled in this retrospective study. Additionally, the lower esophageal intramural vessel diameters (EIV) on CECT and endoscopic findings in 358 patients were compared.
RESULTS
The cutoff values of the EIV diameter on CECT were 3.1 mm for small, 5.1 mm for medium, and 7.6 mm for large varices, demonstrating high concordance with the endoscopic findings. esophageal varices (EV) bleeding predictors include EIV ≥ 3.1 mm and portal vein tumor thrombosis (PVTT). In patients without EV before systemic therapy, factors associated with EV exacerbation after 3 months were EIV ≥ 1.9 mm and ATZ/BEV use. Predictors of hepatic encephalopathy (HE) include the ammonia level or portosystemic shunt diameter ≥ 6.8 mm. The incidence of HE within 2 weeks was significantly higher (18%) in patients with an ammonia level ≥ 73 μmol/L and a portosystemic shunt ≥ 6.8 mm. The exacerbating factors for ascites after 3 months were PVTT and low albumin levels.
CONCLUSIONS
Careful management is warranted for patients with risk factors for exacerbation of PH-related complications; moreover, the effective use of CECT is clinically important.
Topics: Humans; Hypertension, Portal; Carcinoma, Hepatocellular; Male; Female; Liver Neoplasms; Retrospective Studies; Middle Aged; Aged; Risk Factors; Esophageal and Gastric Varices; Phenylurea Compounds; Sorafenib; Bevacizumab; Tomography, X-Ray Computed; Quinolines; Hepatic Encephalopathy; Antineoplastic Agents; Adult; Aged, 80 and over; Gastrointestinal Hemorrhage; Incidence
PubMed: 38583112
DOI: 10.1007/s00535-024-02097-9 -
Medicine Apr 2024Desmoplastic small round cell tumor (DSRCT) is a rare and rapidly metastasizing soft tissue sarcoma, distinguished by its unique cell morphology and pleomorphic... (Review)
Review
RATIONALE
Desmoplastic small round cell tumor (DSRCT) is a rare and rapidly metastasizing soft tissue sarcoma, distinguished by its unique cell morphology and pleomorphic differentiation.
PATIENT CONCERNS
This report describes the case of an 18-year-old male diagnosed with abdominopelvic DSRCT exhibiting metastases to the peritoneum, liver, pleura, bone, and muscle. The patient primarily presented with symptoms of incomplete intestinal obstruction and an abdominal mass.
DIAGNOSES
Colonoscopy revealed lumen stenosis caused by external compression mass. Contrast-enhanced computed tomography and 18F-fluorodeoxyglucose positron emission tomography/computed tomography revealed multiple lesions in the abdominopelvic cavity. A needle biopsy of an abdominal wall lesion established it as a malignant tumor, origin unknown. Immunohistochemical staining post-surgery showed positive results for Cytokeratin (CK), CK7, Desmin, Vimentin, Caudal type homeobox 2 (CDX2), and Ki-67. Fluorescence in situ hybridization analysis revealed an Ewing sarcoma breakpoint region 1/EWS RNA binding protein 1 (EWSR1) rearrangement, and next-generation sequencing identified an EWSR1-Wilms tumor protein 1 (WT1) gene fusion.
INTERVENTIONS
The patient underwent laparoscopic exploratory surgery, which encompassed biopsy, ascites drainage, adhesion lysis, reinforcement of weakened sections of the small intestinal walls, and repositioning of twisted intestines. Postoperatively, the treatment protocol included fasting, rehydration, gastrointestinal decompression, and parenteral nutrition. However, the patient did not received chemotherapy.
OUTCOMES
The patient declined further treatment and deceased in early November.
LESSONS
This case highlights the nonspecific nature of DSRCT symptoms. In clinical practice, it is crucial to meticulously evaluate unexplained intestinal obstruction in young patients, considering DSRCT as a differential diagnosis to avoid delays in diagnosis.
Topics: Male; Humans; Adolescent; Desmoplastic Small Round Cell Tumor; In Situ Hybridization, Fluorescence; Soft Tissue Neoplasms; Intestinal Obstruction; Oncogene Proteins, Fusion
PubMed: 38579065
DOI: 10.1097/MD.0000000000037664 -
World Journal of Hepatology Mar 2024Long-term abdominal drains (LTAD) are a cost-effective palliative measure to manage malignant ascites in the community, but their use in patients with end-stage chronic...
BACKGROUND
Long-term abdominal drains (LTAD) are a cost-effective palliative measure to manage malignant ascites in the community, but their use in patients with end-stage chronic liver disease and refractory ascites is not routine practice. The safety and cost-effectiveness of LTAD are currently being studied in this setting, with preliminary positive results. We hypothesised that palliative LTAD are as effective and safe as repeat palliative large volume paracentesis (LVP) in patients with cirrhosis and refractory ascites and may offer advantages in patients' quality of life.
AIM
To compare the effectiveness and safety of palliative LTAD and LVP in refractory ascites secondary to end-stage chronic liver disease.
METHODS
A retrospective, observational cohort study comparing the effectiveness and safety outcomes of palliative LTAD and regular palliative LVP as a treatment for refractory ascites in consecutive patients with end-stage chronic liver disease followed-up at our United Kingdom tertiary centre between 2018 and 2022 was conducted. Fisher's exact tests and the Mann-Whitney test were used to compare qualitative and quantitative variables, respectively. Kaplan-Meier survival estimates were generated to stratify time-related outcomes according to the type of drain.
RESULTS
Thirty patients had a total of 35 indwelling abdominal drains and nineteen patients underwent regular LVP. The baseline characteristics were similar between the groups. Prophylactic antibiotics were more frequently prescribed in patients with LTAD ( = 0.012), while the incidence of peritonitis did not differ between the two groups ( = 0.46). The incidence of acute kidney injury ( = 0.014) and ascites/drain-related hospital admissions ( = 0.004) were significantly higher in the LVP group. The overall survival was similar in the two groups (log-rank = 0.26), but the endpoint-free survival was significantly shorter in the LVP group ( = 0.003, < 0.001, = 0.018 for first ascites/drain-related admission, acute kidney injury and drain-related complications, respectively).
CONCLUSION
The use of LTAD in the management of refractory ascites in palliated end-stage liver disease is effective, safe, and may reduce hospital admissions and utilisation of healthcare resources compared to LVP.
PubMed: 38577536
DOI: 10.4254/wjh.v16.i3.428