Search Results (29)

Introduction: Peritoneal metastasis (PM) is the most common site of recurrence following curative resection for advanced gastric cancer (GC). Along with disease progression, it can lead to complications such as intestinal obstruction, hydronephrosis, obstructive jaundice, and ascites, significantly impairing the patient’s quality of life. Therefore, peritoneal metastasis is considered a critical target for treatment. In general, these patients are treated with systemic chemotherapy; however, the therapeutic effect is often limited due to the anticancer agents’ poor penetration into the peritoneal cavity. We aim to identify factors associated with the best overall survival (OS) in GC patients with peritoneal metastasis. Methods: Patients with advanced GC who were diagnosed as having macroscopic PM or positive peritoneal cytology by staging laparoscopy were enrolled. We introduced intraperitoneal Paclitaxel (IP-PTX) combined with S-1 plus oxaliplatin (SOX). Gastrectomy with lymph node dissection was performed as conversion surgery when the PM showed an excellent response. Results: Ninety-six patients received IP-PTX + SOX, with a median of 16 courses. The 1- and 5-year OS rates were 70.2% and 24.5%, respectively, with a mean survival time (MST) of 20.0 months. No chemotherapy-related mortality was observed. Conversion surgery was performed in 44 patients (45.8%), with a 1-year OS rate of 100%. Conclusions: Combination chemotherapy using the IP-PTX + SOX regimen is highly effective and is recommended as induction chemotherapy for patients with PM from GC. Conversion gastrectomy should be considered following an excellent response, particularly in patients with peritoneal cancer index (PCI) scores below 20. Full article

Background/objectives: Despite the incremental improvement of survival with systemic therapy in metastatic gastric cancer (GC), the outcomes of patients with peritoneal carcinomatosis (PC) remain poor. The limited effectiveness of systemic therapy is attributed to the blood–peritoneal barrier and anarchic intra-tumoral circulation, which reduce the penetration of systemic therapy. Approaches that incorporate intraperitoneal (IP) chemotherapy, in addition to systemic therapies, may be a viable alternate strategy. Therefore, we provide a review of biology of gastric cancer peritoneal metastasis and evidence for bidirectional iterative IP chemotherapy in GCPC. Methods: A comprehensive search in PubMed, Scopus, Embase, Web of Science, Google Scholar, and ClinicalTrials.gov was performed to find the relevant articles and ongoing phase II/III clinical trials in iterative IP chemotherapy in GCPC. Results: Intraperitoneal (IP) chemotherapy leverages the blood–peritoneal barrier to allow for the administration of high concentrations of chemotherapy directly to the peritoneal metastases, with a significant reduction in the systemic toxicity and enhanced drug efficacy against peritoneal metastasis. This pharmacokinetic advantage of IP chemotherapy can be further enhanced by additional measures such as heat or aerosolization. There are three IP chemotherapy approaches, namely, heated intraperitoneal chemotherapy (HIPEC), pressurized intraperitoneal aerosolized chemotherapy (PIPAC), and normothermic intraperitoneal chemotherapy (NIPEC). Recent evidence suggests that iterative IP chemotherapy combined with systemic therapy may offer significant survival benefits for patients with peritoneal metastasis. Furthermore, bidirectional treatment approaches may also increase the chances of surgical resection and survival. Conclusions: IP chemotherapy plays a pivotal role in the management of gastric carcinomatosis, particularly in combination with cytoreduction in highly selected patients. The combination of systemic and regional control may increase the chances of surgical resection and may ultimately lead to significant survival benefits. Full article

Despite therapeutic treatments and the growing utilization of multimodal therapies, gastric cancer (GC) remains a highly aggressive malignancy with high mortality worldwide. Much of the complexity in treating GC is due to the high incidence of peritoneal metastasis (PM), with mean overall survival typically ranging from 4 to 10 months. With current systemic therapy, targeted therapies, and immunotherapies continuing to remain ineffective for GC/PM, there has been a significant growing interest in intraperitoneal (IP) therapies for the treatment of GC/PM. In this review, we summarize the development of PM and evolving treatment strategies for GC/PM. Furthermore, we explore the various advancements and outcomes of IP therapies, including heated intraperitoneal chemotherapy (HIPEC), neoadjuvant HIPEC, and pressurized intraperitoneal aerosolized chemotherapy (PIPAC). Full article

Objectives: To compare the clinical outcomes of intravenous carboplatin/paclitaxel chemotherapy plus bevacizumab versus intraperitoneal cisplatin/paclitaxel chemotherapy without bevacizumab as the frontline treatment in women with advanced ovarian, fallopian tube and primary peritoneal cancer. Methods: Between November 2012 and January 2024, medical records of all consecutive women with stage II~IV cancer treated with either frontline adjuvant intraperitoneal cisplatin/paclitaxel without bevacizumab (IP group), intravenous carboplatin/paclitaxel without bevacizumab (IV group) or intravenous carboplatin/paclitaxel with bevacizumab (IVB group) at a tertiary referral center were reviewed. Results: A total of 143 women (IP group, n = 57; IVB group, n = 23; IV group, n = 63) were reviewed. The IP group had greater progression-free survival compared to the IVB group (49.1 months, 95% confidence interval [CI] = 27.8 months to infinity, versus 11.9 months, 95% CI = 11.2 to 16.2 months; adjusted hazard ratio [HR] = 0.45, 95% CI = 0.24 to 0.87, p = 0.017). Additionally, the IP group also had a higher overall survival compared to the IVB group (not reached, 95% CI = 55.6 months to infinity, versus 38.9 months, 95% CI = 21.9 months to infinity; adjusted HR = 0.34, 95% CI = 0.15 to 0.79, p = 0.012). Conclusions: Intraperitoneal cisplatin/paclitaxel chemotherapy without bevacizumab seems to offer a survival advantage when compared with intravenous carboplatin/paclitaxel with bevacizumab in the frontline treatment of women with advanced ovarian cancer. Full article

Despite advances in systemic chemotherapy, patients with gastric cancer (GC) and peritoneal metastases (PMs) continue to have poor prognoses. Intraperitoneal (IP) administration of Paclitaxel (PTX) combined with systemic chemotherapy shows promise in treating PMs from GC. However, methods of drug administration need to be optimized to maximize efficacy. In this study, we utilized a mouse model with PMs derived from a human GC cell line, administering PTX either IP or intravenously (IV), and Carboplatin (CBDCA) IV 0, 1, and 4 days after PTX administration. The PMs were resected 30 min later, and concentrations of PTX and CBDCA in resected tumors were measured using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Results indicated that PTX concentrations were higher with IP administration than with IV administration, with significant differences observed on days 0 and 1. CBDCA concentrations 4 days post-IP PTX administration were higher than with simultaneous IV PTX administration. These findings suggest that IP PTX administration enhances CBDCA concentration in peritoneal tumors. Therefore, sequential IV administration of anti-cancer drugs appears more effective than simultaneous administration with IP PTX, a strategy that may improve prognoses for patients with PMs. Full article

Cyclophosphamide, an alkylating agent integral to specific cancer chemotherapy protocols, is often curtailed in application owing to its significant hepatotoxic side effects. Therefore, this study was conducted to assess the hepatoprotective potential of sesamin, a plant-originated antioxidant, using rat models. The rats were divided into five groups: a control group received only the vehicle for six days; a cyclophosphamide group received an intraperitoneal (i.p.) single injection of cyclophosphamide (150 mg/kg) on day four; a sesamin group received a daily high oral dose (20 mg/kg) of sesamin for six days; and two groups were pretreated with oral sesamin (10 and 20 mg/kg daily from day one to day six) followed by an i.p. injection of cyclophosphamide on day four. The final and last sesamin dose was administered 24 h before euthanasia. At the end of the experiment, blood and liver tissue were collected for biochemical and histopathological assessments. The results indicated significantly increased liver markers (AST, ALT, ALP, and BIL), cytokines (TNFα and IL-1β), caspase-3, and malondialdehyde (MDA) in the cyclophosphamide group as compared to the normal control. Additionally, there was a significant decline in antioxidants (GSH) and antioxidant enzymes (CAT and SOD), but the sesamin treatment reduced liver marker enzymes, cytokines, and caspase-3 and improved antioxidants and antioxidant enzymes. Thus, sesamin effectively countered these alterations and helped to normalize the histopathological alterations. In conclusion, sesamin demonstrated the potential for attenuating cyclophosphamide-induced hepatotoxicity by modulating cytokine networks, apoptotic pathways, and oxidative stress, suggesting its potential role as an adjunct in chemotherapy to reduce hepatotoxicity. Full article

Paclitaxel-induced neuropathic pain (PINP) is a serious adverse effect of chemotherapy. Dendrobii caulis (D. caulis) is a new food source used as herbal medicine in east Asia. We examined the antinociceptive effects of D. caulis extract on PINP and clarified the mechanism of action of transient receptor potential vanilloid 1 receptor (TRPV1) in the spinal cord. PINP was induced in male mice using multiple intraperitoneal injections of paclitaxel (total dose, 8 mg/kg). PINP was maintained from D10 to D21 when assessed for cold and mechanical allodynia. Oral administration of 300 and 500 mg/kg D. caulis relieved cold and mechanical allodynia. In addition, TRPV1 in the paclitaxel group showed increased gene and protein expression, whereas the D. caulis 300 and 500 mg/kg groups showed a significant decrease. Among various substances in D. caulis, vicenin-2 was quantified by high-performance liquid chromatography, and its administration (10 mg/kg, i.p.) showed antinociceptive effects similar to those of D. caulis 500 mg/kg. Administration of the TRPV1 antagonist capsazepine also showed antinociceptive effects similar to those of D. caulis, and D. caulis is thought to exhibit antinociceptive effects on PINP by modulating the spinal TRPV1. Full article

Intraperitoneal (IP) chemotherapy is a promising treatment approach for patients diagnosed with peritoneal carcinomatosis, allowing the direct delivery of therapeutic agents to the tumor site within the abdominal cavity. Nevertheless, limited drug penetration into the tumor remains a primary drawback of this method. The process of delivering drugs to the tumor entails numerous complications, primarily stemming from the specific pathophysiology of the tumor. Investigating drug delivery during IP chemotherapy and studying the parameters affecting it are challenging due to the limitations of experimental studies. In contrast, mathematical modeling, with its capabilities such as enabling single-parameter studies, and cost and time efficiency, emerges as a potent tool for this purpose. In this study, we developed a numerical model to investigate IP chemotherapy by incorporating an actual image of a tumor with heterogeneous vasculature. The tumor’s geometry is reconstructed using image processing techniques. The model also incorporates drug binding and uptake by cancer cells. After 60 min of IP treatment with Doxorubicin, the area under the curve (AUC) of the average free drug concentration versus time curve, serving as an indicator of drug availability to the tumor, reached 295.18 mol·m⁻³·s⁻¹. Additionally, the half-width parameter W_1/2, which reflects drug penetration into the tumor, ranged from 0.11 to 0.14 mm. Furthermore, the treatment resulted in a fraction of killed cells reaching 20.4% by the end of the procedure. Analyzing the spatial distribution of interstitial fluid velocity, pressure, and drug concentration in the tumor revealed that the heterogeneous distribution of tumor vasculature influences the drug delivery process. Our findings underscore the significance of considering the specific vascular network of a tumor when modeling intraperitoneal chemotherapy. The proposed methodology holds promise for application in patient-specific studies. Full article

Peritoneal metastasis, also known as peritoneal carcinomatosis (PC), is a refractory cancer that is typically resistant to conventional therapies. The typical treatment for PC is a combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Recently, research in this area has seen significant advances, particularly in immunotherapy as an alternative therapy for PC, which is very encouraging. Catumaxomab is a trifunctional antibody intraperitoneal (IP) immunotherapy authorized in Europe that can be used to diminish malignant ascites by targeting EpCAM. Intraperitoneal (IP) immunotherapy breaks immunological tolerance to treat peritoneal illness. Increasing T-cell responses and vaccination against tumor-associated antigens are two methods of treatment. CAR-T cells, vaccine-based therapeutics, dendritic cells (DCs) in combination with pro-inflammatory cytokines and NKs, adoptive cell transfer, and immune checkpoint inhibitors are promising treatments for PC. Carcinoembryonic antigen-expressing tumors are suppressed by IP administration of CAR-T cells. This reaction was strengthened by anti-PD-L1 or anti-Gr1. When paired with CD137 co-stimulatory signaling, CAR-T cells for folate receptor cancers made it easier for T-cell tumors to find their way to and stay alive in the body. Full article

(1) Background: Doxorubicin (DOX) is extensively used for cancer treatments; however, its clinical application is limited because of its cardiotoxic adverse effects. A combination of DOX and agents with cardioprotective properties is an effective strategy to ameliorate DOX-related cardiotoxicity. Polyphenolic compounds are ideal for the investigation of novel cardioprotective agents. Chlorogenic acid (CGA), an essential dietary polyphenol found in plants, has been previously reported to exert antioxidant, cardioprotective, and antiapoptotic properties. The current research evaluated CGA’s in vivo cardioprotective properties in DOX-induced cardiotoxicity and the probable mechanisms underlying this protection. (2) Methods: CGA’s cardioprotective properties were investigated in rats that were treated with CGA (100 mg/kg, p.o.) for fourteen days. The experimental model of cardiotoxicity was induced with a single intraperitoneal (15 mg/kg i.p.) injection of DOX on the 10th day. (3) Results: Treatment with CGA significantly improved the DOX-caused altered cardiac damage markers (LDH, CK-MB, and cTn-T), and a marked improvement in cardiac histopathological features accompanied this. DOX downregulated the expression of Nrf2/HO-1 signaling pathways, and the CGA reversed this effect. Consistently, caspase-3, an apoptotic-related marker, and dityrosine expression were suppressed, while Nrf2 and HO-1 expressions were elevated in the cardiac tissues of DOX-treated rats after treatment with the CGA. Furthermore, the recovery was confirmed by the downregulation of 8-OHdG and dityrosine (DT) expressions in immunohistochemical findings. (4) Conclusions: CGA demonstrated a considerable cardioprotective effect against DOX-induced cardiotoxicity. One of the possible mechanisms for these protective properties was the upregulation of the Nrf2/HO-1-dependent pathway and the downregulation of DT, which may ameliorate oxidative stress and cardiomyocyte apoptosis. These findings suggest that CGA may be cardioprotective, particularly in patients receiving DOX-based chemotherapy. Full article

Objective: We aimed to compare the survival outcomes and adverse events of hyperthermic intraperitoneal chemotherapy (HIPEC), intraperitoneal chemotherapy (IP)and intravenous chemotherapy (IP)for primary advanced ovarian cancer. Methods: PubMed, CENTRAL (Cochrane Central Registry of Controlled Trials), Embase, Web of Science and Scopus were searched using multiple terms for primary advanced ovarian cancer, including randomized controlled trials and comparative studies in both Chinese and English (up to date 15 August 2022). Outcomes include overall survival, progression-free survival and adverse events. The data were pooled and reported as hazard ratio (HRs) with 95% confidence intervals. The Newcastle–Ottawa Scales were used to assess the risk of bias in the included comparative study. The Cochrane Collaboration’s Risk of Bias Tool was used for randomized controlled trials. Results: In total, 32 studies, including 6347 patients and 8 different platinum-based chemotherapy regimens, were included in this network meta-analysis. Our analysis results showed that HIPEC2 (carboplatin with area under the curve 10) exhibited a statistically significant OS benefit compared to IV, weekly dose-dense chemotherapy and HIPEC1 (cisplatin with 75/100 mg/m²). Intraperitoneal plus intravenous chemotherapy was associated with a statistically significantly better likelihood of overall survival compared to IV. For progression-free survival, our statistical results only suggest a better progression-free survival in ovarian cancer patients treated with HIPEC1 compared with weekly dose-dense chemotherapy. No evidence of difference was observed between the other comparison groups. Compared with the non-HIPEC group, HIPEC may had a higher incidence of electrolyte disturbances (≥grade 3). Conclusion: Our statistical analysis suggests that the groups receiving HIPEC2 had a better OS than the groups receiving IV, weekly dose-dense chemotherapy and HIPEC1. For PFS, our analysis only showed HIPEC1 is better than IV. Moreover, HIPEC may lead to a higher incidence of electrolyte disturbances (≥grade 3). HIPEC therapy for advanced ovarian cancer is currently controversial. Full article

The immune tumor microenvironment (TME) of epithelial ovarian cancer (EOC) carries both effector and suppressive functions. To define immune correlates of chemotherapy-induced tumor involution, we performed longitudinal evaluation of biomarker expression on serial biological specimens collected during intraperitoneal (IP) platinum-based chemotherapy. Serial biological samples were collected at several time points during IP chemotherapy. RNA from IP fluid cells and tumor tissue was analyzed via NanoString. Meso Scale Discovery (MSD) multiplex assay and ELISA for MUC1 antibodies were performed on plasma and IP fluid. Differentially expressed genes in IP fluid demonstrate an upregulation of B cell function and activation of Th2 immune response along with dampening of Th1 immunity during chemotherapy. MSD analysis of IP fluid and gene expression analysis of tumor tissue revealed activation of Th2 immunity and the complement system. Anti-MUC1 antibodies were detected in IP fluid samples. IP fluid analysis in a secondary cohort also identified chemotherapy-induced B cell function genes. This study shows that serial IP fluid sampling is an effective method to capture changes in the immune TME during chemotherapy and reveals treatment induced changes in B cell function and Th2 immunity. Full article

Doxorubicin (DOX) is a well-known and effective antineoplastic agent of the anthracycline family. But, multiple organ toxicities compromise its invaluable therapeutic usage. Among many toxicity types, nephrotoxicity is one of the major concerns. In recent years many approaches, including bioactive agents of natural origin, have been explored to provide protective effects against chemotherapy-related complications. α-Bisabolol is a naturally occurring monocyclic sesquiterpene alcohol identified in the essential oils of various aromatic plants and possesses a wide range of pharmacological properties such as antioxidant, anti-inflammatory, analgesic, cardioprotective, antibiotic, anti-irritant, and anticancer activities. The present study aimed to evaluate the effects of α-Bisabolol on DOX-induced nephrotoxicity in Wistar male albino rats. Nephrotoxicity was induced in rats by injecting a single dose of DOX (12.5 mg/kg, i.p.), and the test compound, α-Bisabolol (25 mg/kg) was administered intraperitoneally along with DOX as a co-treatment daily for 5 days. DOX-injected rats showed reduction in body weight along with a concomitant fall in antioxidants and increased lipid peroxidation in the kidney. DOX-injection also increased levels/expressions of proinflammatory cytokines namely tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) and inflammatory mediators like inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and activated nuclear factor kappa-B (NF-κB)/mitogen-activated protein kinases (MAPK) signaling in the kidney tissues. DOX also triggered apoptotic cell death, evidenced by the increased expression of pro-apoptotic markers like BCL2-Associated X Protein (Bax), cleaved caspase-3, caspase- 9, and cytochrome-C) and a decrease in the expressions of anti-apoptotic markers namely B-cell lymphoma 2 (Bcl2) and B-cell lymphoma-extra large (Bcl-xL) in the kidney. These biochemical alterations were additionally supported by light microscopic findings, which revealed structural alterations in the kidney. However, treatment with α-Bisabolol prevented body weight loss, restored antioxidants, mitigated lipid peroxidation, and inhibited the rise in proinflammatory cytokines, as well as favorably modulated the expressions of NF-κB/MAPK signaling and apoptosis markers in DOX-induced nephrotoxicity. Based on the results observed, it can be concluded that α-Bisabolol has potential to attenuate DOX-induced nephrotoxicity by inhibiting oxidative stress and inflammation mediated activation of NF-κB/MAPK signaling alongwith intrinsic pathway of apoptosis in rats. The study findings are suggestive of protective potential of α-Bisabolol in DOX associated nephrotoxicity and this could be potentially useful in minimizing the adverse effects of DOX and may be a potential agent or adjuvant for renal protection. Full article

Background: Peritoneal carcinomatosis (PC) is the most common form of metastasis in gastric cancer (GC) and is related with a poor prognosis. Several treatment modalities including systemic chemotherapy and intraperitoneal chemotherapy have been studied and adopted in treatment of GC patients with PC. Nevertheless, few studies have reported the comparison of the oncologic outcomes between minimally invasive surgery (MIS) with intraperitoneal (IP) chemotherapy and conventional chemotherapy for GC with PC. Methods: We retrospectively reviewed the clinical records of 74 patients who had been diagnosed as GC with PC via either intra-abdominal exploration or abdominopelvic computed tomography between January 2011 and April 2021. After performing propensity score-matching for this retrospective data, we compared the outcomes of 26 patients who underwent MIS followed by IP combined systemic chemotherapy (MIS-IP group) and 26 patients who underwent systemic chemotherapy only (SC-only group). Results: The 2-year progression free survival rate of the MIS-IP group was significantly higher than the SC-only groups (36.4% and 10.5%, respectively; p = 0.010). In multivariate analysis to detect relevant factors on PFS, IP chemotherapy (HR 0.213; p < 0.001), Eastern Cooperative Oncology Group performance status (HR 3.689; p = 0.002), and the amount of ascites (p = 0.011) were significant prognostic factors. Conclusions: This study demonstrated the therapeutic potential of MIS conjoined IP plus systemic chemotherapy for GC patients with PC. MIS conjoined by IP plus systemic chemotherapy can be adopted as a treatment option to reboot the role of IP chemotherapy in GC patients with PC. Full article

Novel treatment strategies are needed to provide a better prognosis for ovarian cancer. For this purpose, the current study was designed to evaluate the effects of different types of particle drug carriers on tumor response and on the tumor immune microenvironment (TME) after intraperitoneal (IP) administration in a murine tumor model. Mice with ID8-fLuc ovarian cancer were injected IP with pegylated liposomes, hydroxyapatite, polystyrene, poly(lactic-co-glycolic acid) (PLGA) and calcium carbonate (CaCO₃) microparticles to evaluate the effect of the candidate carriers without drugs. Our results show that several types of microparticle drug carriers caused hyperproliferation of the tumor when injected IP, as reflected in a reduced survival or an accelerated onset of ascites. Alterations of the product formulation of CaCO₃ microparticles could result in less hyperproliferation. The hyperproliferation caused by CaCO₃ and PLGA was largely driven by a strong innate immune suppression. A combination with chemotherapy was not able to sufficiently counteract the tumor progression caused by the drug carriers. This research points towards the importance of evaluating a drug carrier before using it in a therapeutic setting, since drug carriers themselves can detrimentally influence tumor progression and immune status of the TME. However, it remains to be determined whether the hyperproliferation in this model will be of relevance in other cancer models or in humans. Full article