-
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 -
World Journal of Gastrointestinal... Mar 2024Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and the second leading cause of cancer deaths worldwide. It is often diagnosed at an advanced...
BACKGROUND
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and the second leading cause of cancer deaths worldwide. It is often diagnosed at an advanced stage and therefore its prognosis remains poor with a low 5-year survival rate. HCC patients have increasingly complex and constantly changing characteristics, thus up-to-date and comprehensive data are fundamental.
AIM
To analyze the epidemiology and main clinical characteristics of HCC patients in a referral center hospital in the northwest of Italy between 2010 and 2019.
METHODS
In this retrospective study, we analyzed the clinical data of all consecutive patients with a new diagnosis of HCC recorded at "Santa Croce e Carle" Hospital in Cuneo (Italy) between 1 January 2010 and 31 December 2019. To highlight possible changes in HCC patterns over the 10-year period, we split the population into two 5-year groups, according to the diagnosis period (2010-2014 and 2015-2019).
RESULTS
Of the 328 HCC patients who were included (M/F 255/73; mean age 68.9 ± 11.3 years), 154 in the first period, and 174 in the second. Hepatitis C virus infection was the most common HCC risk factor (41%, 135 patients). The alcoholic etiology rate was 18%, the hepatitis B virus infection etiology was 5%, and the non-viral/non-alcoholic etiology rate was 22%. The Child-Pugh score distribution of the patients was: class A 75%, class B 21% and class C 4%. The average Mayo end-stage liver disease score was 10.6 ± 3.7. A total of 55 patients (17%) were affected by portal vein thrombosis and 158 (48%) by portal hypertension. The average nodule size of the HCC was 4.6 ± 3.1 cm. A total of 204 patients (63%) had more than one nodule < 3, and 92% (305 patients) had a non-metastatic stage of the disease. The Barcelona Clinic Liver Cancer (BCLC) staging distribution of all patients was: 4% very early, 32% early, 23% intermediate, 34% advanced, and 7% terminal. Average survival rate was 1.6 ± 0.3 years. Only 20% of the patients underwent treatment. Age, presence of ascites, BCLC stage and therapy were predictors of a better prognosis ( < 0.01). A comparison of the two 5-year groups revealed a statistically significant difference only in global etiology ( < 0.05) and alpha-fetoprotein (AFP) levels ( < 0.01).
CONCLUSION
In this study analyzing patients with a new diagnosis of HCC between 2010-2019, hepatitis C virus infection was the most common etiology. Most patients presented with an advanced stage disease and a poor prognosis. When comparing the two 5-year groups, we observed a statistically significant difference only in global etiology ( < 0.05) and AFP levels ( < 0.01).
PubMed: 38577451
DOI: 10.4251/wjgo.v16.i3.761 -
Scientific Reports Apr 2024The underlying study was carried out aiming at transdermal drug delivery (TDD) of Goniothalamus macrophyllus as sono-photo-sensitizer (SPS) using microneedle (MN) arrays...
Microneedle combined with iontophoresis and electroporation for assisted transdermal delivery of goniothalamus macrophyllus for enhancement sonophotodynamic activated cancer therapy.
The underlying study was carried out aiming at transdermal drug delivery (TDD) of Goniothalamus macrophyllus as sono-photo-sensitizer (SPS) using microneedle (MN) arrays with iontophoresis (MN-IP), electroporation (MN-EP) in conjunction with applying photodynamic therapy (PDT), sonodynamic therapy (SDT) and sono-photodynamic therapy (SPDT) as an up-to-date activated cancer treatment modality. Study was conducted on 120 male Swiss Albino mice, inoculated with Ehrlich ascites carcinoma (EAC) divided into 9 groups. We employed three different arrays of MN electrodes were used (parallel, triangular, and circular), EP, IP with different volts (6, 9, 12 V), an infrared laser and an ultrasound (pulsed and continuous wave) as our two energy sources. Results revealed that parallel 6 V TDD@MN@IP@EP can be used as effective delivery system for G. macrophyllus from skin directly to target EAC cells. In addition MN@IP@EP@TDD G. macrophyllus is a potential SPS for SPDT treatment of EAC. With respect to normal control mice and as opposed to the EAC untreated control mice, MN@EP@IP TDD G. macrophyllus in the laser, ultrasound, and combination activated groups showed a significant increase in the antioxidant markers TAC level and the GST, GR, Catalase, and SOD activities, while decrease in lipid peroxidation oxidative stress parameter MDA levels. In addition significantly increased apoptotic genes expressions (p53, caspase (3, 9), Bax, and TNF alpha) and on the other hand decreased anti- apoptotic (Bcl-2) and angiogenic (VEGF) genes expressions. Moreover significantly ameliorate liver and kidney function decreasing ALT, AST, urea and creatinine respectively. Furthermore MN@IP@EP@TDD G. macrophyllus combined with SPDT was very effective at reducing the growth of tumors and even causing cell death according to microscopic H&E stain results. This process may be related to a sono- and/or photochemical activation mechanism. According to the findings, MN@IP@EP@TDD G. macrophyllus has a lot of potential as a novel, efficient delivery method that in combination with infrared laser and ultrasound activation SPDT demonstrated promising anticancer impact for treating cancer.
Topics: Male; Animals; Mice; Goniothalamus; Iontophoresis; Administration, Cutaneous; Skin; Electroporation; Carcinoma
PubMed: 38575628
DOI: 10.1038/s41598-024-58033-7 -
GE Portuguese Journal of... Apr 2024Nonmalignant portal vein thrombosis (PVT) is a common complication of cirrhosis especially at the stage of decompensations. The diagnosis of PVT in cirrhosis is often... (Review)
Review
Nonmalignant portal vein thrombosis (PVT) is a common complication of cirrhosis especially at the stage of decompensations. The diagnosis of PVT in cirrhosis is often incidental and it may be detected during routine semestral abdominal ultrasound with Doppler during screening for hepatocellular carcinoma or during hospitalization for decompensated cirrhosis. After detection of PVT on abdominal ultrasound, it is important to evaluate patients with cross-sectional imaging to determine the age of thrombus, whether acute or chronic, the extent and degree of luminal occlusion of the portal vein, and to rule out hepatocellular carcinoma or other underlying malignancy. Factors influencing management include the degree and extent of luminal occlusion of PVT, potential listing for liver transplantation, and portal hypertension (PHT) complications such as variceal hemorrhage and refractory ascites, severity of thrombocytopenia, and other comorbidities including chronic kidney disease. Anticoagulation is the most common therapeutic option and it is specially indicated in patients who are candidates for liver transplantation. Interventional procedures including transjugular intrahepatic portosystemic shunt (TIPS) placement and mechanical thrombectomy may be used on a case-by-case basis in patients with contraindications or adverse events related to anticoagulation, who develop worsening PVT while on anticoagulant therapy, or have chronic PVT and PHT complications that are not manageable medically or endoscopically.
PubMed: 38572442
DOI: 10.1159/000533161