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Diagnostic and Interventional Imaging Oct 2023The purpose of this study was to analyze the safety, technical success and clinical outcome of percutaneous intranodal ethiodized oil (Lipiodol®) based lymphangiography...
PURPOSE
The purpose of this study was to analyze the safety, technical success and clinical outcome of percutaneous intranodal ethiodized oil (Lipiodol®) based lymphangiography (L-LAG) for the management of refractory pelvic lymphoceles or chylous ascites using high doses of ethiodized oil.
MATERIALS AND METHODS
Thirty-four patients presenting with symptomatic, refractory postoperative pelvic lymphocele or chylous ascites referred for theranostic, inguinal, intranodal L-LAG treatment between May 2018 and November 2021 were retrospectively included. There were 21 men and 13 women, with a mean age of 62.7 ± 16.2 (standard deviation) years (age range: 9-86 years), who underwent a total of 49 L-LAG for the management of lymphoceles (n = 14), chylous ascites (n = 18) or a combination of lymphocele and chylous ascites (n = 2). Clinical and radiological pre-interventional, procedural and follow-up data up to January 2022 were collected from patients' electronic medical records and imaging files.
RESULTS
Technical success was obtained in 48 out of 49 L-LAG (98%). No complications related to L-LAG were noted. After one or more L-LAG, clinical success was obtained in 30 patients (88%) with a mean of 1.4 interventions per patient and mean intranodal injected volume of 29 mL of ethiodized oil per session. The remaining four patients (12%), with one or more failed L-LAG, underwent additional surgical intervention to definitively treat the postoperative lymphatic leakage.
CONCLUSION
L-LAG using high doses of ethiodized oil is a minimally invasive, safe and effective treatment of postoperative pelvic lymphocele or chylous ascites. Multiple sessions may be needed to obtain a meaningful clinical result.
Topics: Male; Humans; Female; Middle Aged; Aged; Child; Adolescent; Young Adult; Adult; Aged, 80 and over; Ethiodized Oil; Lymphography; Chylous Ascites; Lymphocele; Retrospective Studies; Postoperative Complications
PubMed: 37210283
DOI: 10.1016/j.diii.2023.05.003 -
World Journal of Surgical Oncology Jan 2024Malignant peritoneal mesothelioma (MPM) is a rare and highly aggressive tumor. Its clinical manifestations are diverse, and the symptoms are not specific. Some patients...
BACKGROUND
Malignant peritoneal mesothelioma (MPM) is a rare and highly aggressive tumor. Its clinical manifestations are diverse, and the symptoms are not specific. Some patients will develop paraneoplastic syndrome (PS) during the disease course. This study aims to analyze the risk factors of PS in patients with MPM and their impacts on prognosis.
METHODS
The clinical data of MPM patients who underwent cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) at our center from June 2015 to May 2023 were retrospectively analyzed. MPM patients were divided into PS group and non-PS group according to the diagnostic criteria. Univariate and multivariate analyses were performed to explore the risk factors of PS in MPM patients, and to analyze the impact of PS on prognosis.
RESULTS
There were 146 MPM patients in this study, including 60 patients (41.1%) with PS and 86 patients (58.9%) without PS. The highest incidence of PS was thrombocytosis (33.6%), followed by neoplastic fever (9.6%). Univariate analysis revealed 8 factors (P < 0.05) with statistically significant differences between the two groups: prior surgical scores, targeted therapy history, Karnofsky performance status score, preoperative carbohydrate antigen (CA) 125 level, vascular tumor embolus, peritoneal cancer index, completeness of cytoreduction (CC) score and intraoperative ascites. Multivariate analysis identified 3 independent factors associated with PS: preoperative CA 125 level, vascular tumor embolus, and CC score. Survival analysis demonstrated that MPM patients with PS had worse prognosis, although PS was not an independent prognostic factor.
CONCLUSIONS
PS is not rare in patients with MPM, and is independently associated with preoperative CA 125 level, vascular tumor embolus and CC score. PS often indicates advanced disease and poor prognosis.
Topics: Humans; Retrospective Studies; Vascular Neoplasms; Paraneoplastic Syndromes; Prognosis; Mesothelioma, Malignant; Peritoneal Neoplasms; Risk Factors; CA-125 Antigen; Embolism
PubMed: 38267958
DOI: 10.1186/s12957-024-03312-w -
United European Gastroenterology Journal Dec 2023We studied the impact of Portal hypertension (PHT) on ascites occurrence and on radiotherapy outcome in cirrhotic patients with hepatocellular carcinoma (HCC).
BACKGROUND AND AIMS
We studied the impact of Portal hypertension (PHT) on ascites occurrence and on radiotherapy outcome in cirrhotic patients with hepatocellular carcinoma (HCC).
METHOD
All cirrhotic patients that received radiotherapy for HCC between 2012 and 2022 were included. Portal hypertension-Score was built using univariate analysis with the presence of esophageal varices (EV), platelet count, history of acute variceal bleeding (AVB) and spleen size. Time-to-events data were estimated using Kaplan-Meier method with log-rank and Cox-models.
RESULTS
60 patients were included (female 27%, age 67 years-old, Child-Pugh A 82%, alcoholic/non-alcoholic steatohepatitis/hepatitis C virus 55/40/32%). 38% and 15% presented history of ascites and AVB respectively, 25% had large EV, 53.5% presented PHT score ≥ 5. 92% were BCLC-0/A, median tumor size was 30 mm. At 6 months, ascites incidence was 19% and precluded access to further HCC treatment for all patients with HCC recurrence. All PHT parameters included in the score and PHT score ≥ 5 (hazard ratio (HR) = 14.07, p = 0.01) were associated with ascites occurrence. Transplantation free survival and recurrence free survival at 1 year were 56% and 47% respectively. Albi grade 3 (HR = 3.01; p = 0.04) was independently associated with Transplantation free survival.
CONCLUSION
Radiotherapy should be cautiously performed in patients with PHT score ≥ 5 because of ascites occurrence risk precluding access to further HCC treatments.
Topics: Humans; Female; Aged; Carcinoma, Hepatocellular; Liver Neoplasms; Esophageal and Gastric Varices; Ascites; Treatment Outcome; Gastrointestinal Hemorrhage; Hypertension, Portal; Liver Cirrhosis; Hypertension
PubMed: 38018771
DOI: 10.1002/ueg2.12488 -
Cardiovascular and Interventional... Mar 2024Transarterial radioembolization (TARE) with Yttrium-90 resin microspheres is a treatment option for patients with intrahepatic cholangiocarcinoma (ICC). However,...
Factors Impacting Survival After Transarterial Radioembolization in Patients with Unresectable Intrahepatic Cholangiocarcinoma: A Combined Analysis of the Prospective CIRT Studies.
PURPOSE
Transarterial radioembolization (TARE) with Yttrium-90 resin microspheres is a treatment option for patients with intrahepatic cholangiocarcinoma (ICC). However, optimising the timing of TARE in relation to systemic therapies and patient selection remains challenging. We report here on the effectiveness, safety, and prognostic factors associated with TARE for ICC in a combined analysis of the prospective observational CIRT studies (NCT02305459 and NCT03256994).
METHODS
A combined analysis of 174 unresectable ICC patients enrolled between 2015 and 2020 was performed. Patient characteristics and treatment-related data were collected at baseline; adverse events and time-to-event data (overall survival [OS], progression-free survival [PFS] and hepatic PFS) were collected at every follow-up visit. Log-rank tests and a multivariable Cox proportional hazard model were used to identify prognostic factors.
RESULTS
Patients receiving a first-line strategy of TARE in addition to any systemic treatment had a median OS and PFS of 32.5 months and 11.3 months. Patients selected for first-line TARE alone showed a median OS and PFS of 16.2 months and 7.4 months, whereas TARE as 2nd or further treatment-line resulted in a median OS and PFS of 12 and 9.3 months (p = 0.0028), and 5.1 and 3.5 months (p = 0.0012), respectively. Partition model dosimetry was an independent predictor for better OS (HR 0.59 [95% CI 0.37-0.94], p = 0.0259). No extrahepatic disease, no ascites, and < 6.1 months from diagnosis to treatment were independent predictors for longer PFS.
CONCLUSION
This combined analysis indicates that in unresectable ICC, TARE in combination with any systemic treatment is a promising treatment option.
LEVEL OF EVIDENCE
level 3, Prospective observational.
Topics: Humans; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cholangiocarcinoma; Embolization, Therapeutic; Liver Neoplasms; Prospective Studies; Retrospective Studies; Yttrium Radioisotopes; Observational Studies as Topic
PubMed: 38321223
DOI: 10.1007/s00270-023-03657-x -
World Journal of Gastrointestinal... Dec 2023Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1) and T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) are...
BACKGROUND
Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1) and T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) are beneficial to the resumption of anti-tumor immunity response and hold extreme potential as efficient therapies for certain malignancies. However, ICIs with a single target exhibit poor overall response rate in hepatocellular carcinoma (HCC) patients due to the complex pathological mechanisms of HCC.
AIM
To investigate the effects of combined TIM-3 and PD-1 blockade on tumor development in an HCC mouse model, aiming to identify more effective immunotherapies and provide more treatment options for HCC patients.
METHODS
The levels of PD-1 and TIM-3 on CD4+ and CD8+ T cells from tumor tissues, ascites, and matched adjacent tissues from HCC patients were determined with flow cytometry. An HCC xenograft mouse model was established and treated with anti-TIM-3 monoclonal antibody (mAb) and/or anti-PD-1 mAb. Tumor growth in each group was measured. Hematoxylin and eosin staining and immunohistochemical staining were used to evaluate T cell infiltration in tumors. The percentage of CD4+ and CD8+ T cells in tissue samples from mice was tested with flow cytometry. The percentages of PD-1+CD8+, TIM-3+CD8+, and PD-1+TIM-3+ CD8+ T cells was accessed by flow cytometry. The levels of the cytokines including tumor necrosis factor alpha (TNF-α), interferon-γ (IFN-γ), interleukin (IL)-6, and IL-10 in tumor tissues were gauged with enzyme-linked immunosorbent assay kits.
RESULTS
We confirmed that PD-1 and TIM-3 expression was substantially upregulated in CD4+ and CD8+ T cells isolated from tumor tissues and ascites of HCC patients. TIM-3 mAb and PD-1 mAb treatment both reduced tumor volume and weight, while combined blockade had more substantial anti-tumor effects than individual treatment. Then we showed that combined therapy increased T cell infiltration into tumor tissues, and downregulated PD-1 and TIM-3 expression on CD8+ T cells in tumor tissues. Moreover, combined treatment facilitated the production of T cell effector cytokines TNF-α and IFN-γ, and reduced the production of immunosuppressive cytokines IL-10 and IL-6 in tumor tissues. Thus, we implicated that combined blockade could ameliorate T cell exhaustion in HCC mouse model.
CONCLUSION
Combined TIM-3 and PD-1 blockade restrains HCC development by facilitating CD4+ and CD8+ T cell-mediated antitumor immune responses.
PubMed: 38173440
DOI: 10.4251/wjgo.v15.i12.2138 -
DEN Open Apr 2024Malignant gastric outlet obstruction (GOO) has traditionally been managed with enteral stenting and surgical gastrojejunostomy. Our study aimed to compare outcomes...
OBJECTIVES
Malignant gastric outlet obstruction (GOO) has traditionally been managed with enteral stenting and surgical gastrojejunostomy. Our study aimed to compare outcomes between endoscopic ultrasound-guided gastrojejunostomy (EUS-GJ) using a lumen-apposing metal stent and robotic GJ (R-GJ) for unresectable malignant GOO.
METHODS
Patients undergoing EUS-GJ or R-GJ for unresectable malignant GOO were retrospectively analyzed. The primary outcome was clinical success defined by the ability to tolerate oral intake at the time of discharge. Secondary outcomes included technical success, procedure duration, adverse events, and post-procedure length of stay (LOS).
RESULTS
A total of 44 patients met the inclusion criteria. Of the 44, 29 underwent EUS-GJ and 15 underwent R-GJ. Age, gender, malignant etiology, and presence of ascites were similar between the two groups. Patients treated with EUS-GJ had a higher mean Charlson comorbidity index (10.3 vs. 7.0; 0.0001) and a lower preoperative body mass index (22.3 vs. 27.2; = 0.007). Technical and clinical success was achieved in 100% of patients in both groups ( > 0.99). EUS-GJ was associated with shorter procedure duration (57.5 vs. 146.3 min; < 0.0001), hospital LOS (4.3 vs. 8.2 days, = 0.0009), and time to oral intake (1.0 vs. 5.8 days; < 0.0001) when compared to R-GJ. Adverse events occurred in 5 of the R-GJ patients and none of the EUS-GJ patients ( = 0.003).
CONCLUSIONS
EUS-GJ has similar efficacy and superior clinical outcomes compared to R-GJ in the management of malignant GOO. Prospective studies with longer follow-up duration are needed to validate these findings.
PubMed: 37228709
DOI: 10.1002/deo2.248 -
World Journal of Gastroenterology Aug 2023The albumin-bilirubin (ALBI) score is an index of liver function recently developed to assess prognosis in patients with hepatocellular carcinoma (HCC). It can detect...
BACKGROUND
The albumin-bilirubin (ALBI) score is an index of liver function recently developed to assess prognosis in patients with hepatocellular carcinoma (HCC). It can detect small changes in liver dysfunction and has been successfully applied to the prediction of survival in patients with non-malignant liver diseases of various etiologies.
AIM
To investigate the ALBI score for identifying decompensation risk at the 3-year follow-up in patients with compensated cirrhosis.
METHODS
One-hundred and twenty-three patients with compensated cirrhosis without HCC in King Chulalongkorn Memorial Hospital diagnosed by imaging were retrospectively enrolled from January 2016 to December 2020. A total of 113 patients (91.9%) had Child A cirrhosis with a median model for end-stage liver disease (MELD) score of less than 9. Baseline clinical and laboratory variables and decompensation events were collected. The ALBI score was calculated and validated to classify decompensation risk into low-, middle-, and high-risk groups using three ALBI grade ranges (ALBI grade 1: ≤ -2.60; grade 2: > -2.60 but ≤ -1.39; grade 3: > -1.39). Decompensation events were defined as ascites development, variceal bleeding, or grade 3 or 4 hepatic encephalopathy.
RESULTS
Among 123 cirrhotic patients enrolled, 13.8% ( = 17) developed decompensating events at a median time of 25 [95% confidence interval (CI): 17-31] mo. Median baseline ALBI score in compensated cirrhosis was significantly lower than that of patients who developed decompensation events [-2.768 (-2.956 to -2.453) -2.007 (-2.533 to -1.537); = 0.01]. Analysis of decompensation risk at 3 years showed that ALBI score had a time-dependent area under the curve (tAUC) of 0.86 (95%CI: 0.78-0.92), which was significantly better than that of ALBI-Fibrosis-4 (ALBI-FIB4) score (tAUC = 0.77), MELD score (tAUC = 0.66), Child-Pugh score (tAUC = 0.65), and FIB-4 score (tAUC = 0.48) ( < 0.05 for all). The 3-year cumulative incidence of decompensation was 3.1%, 22.6%, and 50% in the low-, middle-, and high-risk groups, respectively ( < 0.001). The odds ratio for decompensation in patients of the high-risk group was 23.33 (95%CI: 3.88-140.12, = 0.001).
CONCLUSION
The ALBI score accurately identifies decompensation risk at the 3-year follow-up in patients with compensated cirrhosis. Those cirrhotic patients with a high-risk grade of ALBI score showed a 23 times greater odds of decompensation.
Topics: Humans; Bilirubin; Carcinoma, Hepatocellular; End Stage Liver Disease; Esophageal and Gastric Varices; Retrospective Studies; Gastrointestinal Hemorrhage; Liver Neoplasms; Severity of Illness Index; Liver Cirrhosis; Albumins
PubMed: 37701131
DOI: 10.3748/wjg.v29.i32.4873 -
Advanced Science (Weinheim,... Dec 2023Patients with colorectal cancer (CRC) and diffuse peritoneal metastasis (PM) are not eligible for surgical intervention. Thus, palliative treatment remains the standard...
Patients with colorectal cancer (CRC) and diffuse peritoneal metastasis (PM) are not eligible for surgical intervention. Thus, palliative treatment remains the standard of care in clinical practice. Systemic chemotherapy fails to cause drug accumulation at the lesion sites, while intraperitoneal chemotherapy (IPC) is limited by high clearance rates and associated complications. Given the poor prognosis, a customized OxP/R848@PLEL hydrogel delivery system has been devised to improve the clinical benefit of advanced CRC with diffuse PM. This system is distinguished by its simplicity, security, and efficiency. Specifically, the PLEL hydrogel exhibits excellent injectability and thermosensitivity, enabling the formation of drug depots within the abdominal cavity, rendering it an optimal carrier for IPC. Oxaliplatin (OxP), a first-line drug for advanced CRC, is cytotoxic and enhances the immunogenicity of tumors by inducing immunogenic cell death. Furthermore, OxP and resiquimod (R848) synergistically enhance the maturation of dendritic cells, promote the expansion of cytotoxic T lymphocytes, and induce the formation of central memory T cells. Moreover, R848 domesticates macrophages to an anti-tumor phenotype. OxP/R848@PLEL effectively eradicates peritoneal metastases, completely inhibits ascites production, and significantly prolongs mice lifespan. As such, it provides a promising approach to managing diffuse PM in patients with CRC without surgical indications.
Topics: Humans; Animals; Mice; Hydrogels; Peritoneal Neoplasms; Colorectal Neoplasms; Antineoplastic Agents; Oxaliplatin; Immunotherapy
PubMed: 37875399
DOI: 10.1002/advs.202303819 -
Zoological Research May 2024Hepatocellular carcinoma (HCC), a prevalent solid carcinoma of significant concern, is an aggressive and often fatal disease with increasing global incidence rates and...
Hepatocellular carcinoma (HCC), a prevalent solid carcinoma of significant concern, is an aggressive and often fatal disease with increasing global incidence rates and poor therapeutic outcomes. The etiology and pathological progression of non-alcoholic steatohepatitis (NASH)-related HCC is multifactorial and multistage. However, no single animal model can accurately mimic the full NASH-related HCC pathological progression, posing considerable challenges to transition and mechanistic studies. Herein, a novel conditional inducible wild-type human overexpressed mouse model (HRAS-HCC) was established, demonstrating 100% morbidity and mortality within approximately one month under normal dietary and lifestyle conditions. Advanced symptoms of HCC such as ascites, thrombus, internal hemorrhage, jaundice, and lung metastasis were successfully replicated in mice. In-depth pathological features of NASH- related HCC were demonstrated by pathological staining, biochemical analyses, and typical marker gene detections. Combined murine anti-PD-1 and sorafenib treatment effectively prolonged mouse survival, further confirming the accuracy and reliability of the model. Based on protein-protein interaction (PPI) network and RNA sequencing analyses, we speculated that overexpression of HRAS may initiate the THBS1-COL4A3 axis to induce NASH with severe fibrosis, with subsequent progression to HCC. Collectively, our study successfully duplicated natural sequential progression in a single murine model over a very short period, providing an accurate and reliable preclinical tool for therapeutic evaluations targeting the NASH to HCC continuum.
Topics: Animals; Non-alcoholic Fatty Liver Disease; Carcinoma, Hepatocellular; Mice; Liver Neoplasms; Proto-Oncogene Proteins p21(ras); Disease Models, Animal; Mice, Transgenic; Mice, Inbred C57BL; Humans
PubMed: 38757223
DOI: 10.24272/j.issn.2095-8137.2024.002 -
Radiology and Oncology Dec 2023High-grade serous carcinoma (HGSC) is often associated with ascites at presentation. Our objective was to quantify immune cells (ICs) in ascites prior to any treatment...
BACKGROUND
High-grade serous carcinoma (HGSC) is often associated with ascites at presentation. Our objective was to quantify immune cells (ICs) in ascites prior to any treatment was given and evaluate their impact on progression-free survival (PFS) and overall survival (OS).
PATIENTS AND METHODS
Forty-seven patients with primary HGSC and ascites were included. Flow-cytometric analysis was performed to detect percentages of CD3 T cells (CD4, CD8, Tregs, and NKT cells), B cells, NK cells (CD56CD16 and CD56CD16 subsets), macrophages and dendritic cells (DCs). Furthermore, CD103 expression was analyzed on T cells and their subsets, while PD-1 and PD-L1 expression on all ICs. Cut-off of low and high percentages of ICs was determined by the median of variables, and correlation with PFS and OS was calculated.
RESULTS
CD3 cells were the predominant ICs (median 51%), while the presence of other ICs was much lower (median ≤10%). CD103 expression was mostly present on CD8, and not CD4 cells. PD-1 was mainly expressed on CD3 T cells (median 20%), lower expression was observed on other ICs (median ≤10%). PD-L1 expression was not detected. High percentages of CD103CD3 T cells, PD-1 Tregs, CD56CD16 NK cells, and DCs correlated with prolonged PFS and OS, while high percentages of CD8 cells, macrophages, and PD-1CD56CD16 NK cells, along with low percentages of CD4 cells, correlated with better OS only. DCs were the only independent prognostic marker among all ICs.
CONCLUSIONS
Our results highlight the potential of ascites tumor-immune microenvironment to provide additional prognostic information for HGSC patients. However, a larger patient cohort and longer follow-up are needed to confirm our findings.
Topics: Humans; Female; Prognosis; B7-H1 Antigen; Ascites; Programmed Cell Death 1 Receptor; Ovarian Neoplasms; Carcinoma; Tumor Microenvironment
PubMed: 38038414
DOI: 10.2478/raon-2023-0046