Administration Of 5-fluorouracil Research Articles

Effect of growth hormone on colonic anastomosis after intraperitoneal administration of 5-fluorouracil, bleomycin and cisplatin: An experimental study.

Growth hormone (GH) plays a crucial role in wound healing and tissue repair in postoperative patients. In particular, colonic anastomosis healing following colorectal surgery is impaired by numerous chemotherapy agents. To investigate whether GH can improve the healing of a colonic anastomosis following the adverse effects of intraperitoneal administration of 5-fluorouracil (5-FU), bleomycin and cisplatin. Eighty Wistar rats underwent laparotomy and a 1 cm-resection of the transverse colon, followed by an end-to-end anastomosis under general anesthesia. The rats were blindly allocated into four equal groups and administered a different daily intraperitoneal therapeutic regimen for 6 days. The control group (A) received normal saline. Group B received chemotherapy with 5-FU (20 mg/kg), bleomycin (4 mg/kg) and cisplatin (0.7 mg/kg). Group C received GH (2 mg/kg), and group D received the aforementioned combination chemotherapy and GH, as described. The rats were sacrificed on the 7th postoperative day and the anastomoses were macroscopically and microscopically examined. Body weight, bursting pressure, hydroxyproline levels and inflammation markers were measured. All rats survived until the day of sacrifice, with no infections or other complications. A decrease in the body weight of group D rats was observed, not statistically significant compared to group A (P = 1), but significantly different to groups C (P = 0.001) and B (P < 0.01). Anastomotic dehiscence rate was not statistically different between the groups. Bursting pressure was not significantly different between groups A and D (P = 1.0), whereas group B had a significantly lower bursting pressure compared to group D (P < 0.001). All groups had significantly more adhesions than group A. Hydroxyproline, as a measurement of collagen deposition, was significantly higher in group D compared to group B (P < 0.05), and higher, but not statistically significant, compared to group A. Significant changes in group D were recorded, compared to group A regarding inflammation (3.450 vs 2.900, P = 0.016) and fibroblast activity (2.75 vs 3.25, P = 0.021). Neoangiogenesis and collagen deposition were not significantly different between groups A and D. Collagen deposition was significantly increased in group D compared to group B (P < 0.001). Intraperitoneal administration of chemotherapy has an adverse effect on the healing process of colonic anastomosis. However, GH can inhibit the deleterious effect of administered chemotherapy agents and induce colonic healing in rats.

OXIDATIVE MODIFICATION OF PROTEINS IN COLORECTAL CANCER UNDER THE INFLUENCE OF 5-FLUOROURACIL AND MOLECULAR HYDROGEN

The aim of the study – to investigate the effect of water saturated with molecular hydrogenand 5-fluorouracil on the content of carbonyl groups of oxidatively modified proteins inthe blood serum of white rats with colorectal cancer.Material and Methods. The experiments were conducted on 50 male Wistar rats. Theanimals were modeled with colorectal cancer (CRC) by subcutaneous injection of1,2-dimethylhydrazine (DMH) at a dose of 7.2 mg/kg body weight once a week for 30weeks. 5-Fluorouracil was administered intraperitoneally for 4 days at 12 mg/kg andfor another 4 days every other day at 6 mg/kg. Animals consumed water enriched withmolecular hydrogen at a concentration of 0.6 ppm ad libitum. Rats were euthanizedunder thiopental anesthesia. Blood serum was used for the study, in which the content ofcarbonyl groups was determined by the colorimetric method. Statistical data processingwas performed using the SPSS-22 software package.Results. It was found that the modeling of colorectal cancer led to a 1.77-fold increase inthe content of carbonyl groups in the blood serum of rats compared to intact animals. Thecontent of carbonyl groups in the blood serum of rats with CRC treated with chemotherapyby administration of 5-fluorouracil increased 1.93 times compared to the intact groupand 1.1 times compared to animals with CRC. Consumption of water saturated withmolecular hydrogen 30 days after modeling CRC and administration of 5-fluorouracilto white rats led to a 1.18-fold decrease in the content of carbonyl groups in their bloodserum compared to animals with CRC who were administered 5-fluorouracil but did notconsume water saturated with molecular hydrogen.Conclusions. The use of molecular hydrogen saturated water is an effective methodof reducing oxidative modification of proteins in rats with colorectal cancer under5-fluorouracil chemotherapy.

Effect of Hydration with Bicarbonate Ringer's Solution on Cisplatin-induced Acute Kidney Injury in Patients with Esophageal Cancer: A Retrospective Cohort Study.

Cisplatin (CDDP) often causes acute kidney injury (AKI), and magnesium supplementation has been suggested to be important in preventing CDDP-induced AKI. Sodium bicarbonate Ringer's solution (BRS) is a crystalloid solution composed of various electrolytes, including Mg2+, and can be generally used to supplement missing extracellular fluid and correct metabolic acidosis; however, the clinical outcomes of hydration with BRS for CDDP-induced AKI remain unclear. In this study, we retrospectively compared the effects of BRS and normal saline for hydration in patients undergoing CDDP treatment. We analyzed the incidence rate of AKI (grade ≥ 1), the severity of AKI, the serum magnesium level, and the incidence rate of grade ≥ 3 hematological toxicities (leukopenia, neutropenia, anemia, or thrombocytopenia) following CDDP and fluorouracil (5-FU) administration in 131 in-patients who received CDDP and 5-FU for the first time to treat esophageal cancer. Fifty-six patients (43%) received saline alone, while 75 patients (57%) received BRS for hydration. The incidence rate of AKI (grade ≥ 1) was significantly lower in the BRS group (11%) than that in the saline group (39%, p &lt; 0.001). Moreover, severe AKI (grade ≥ 2) was significantly less common in the BRS group than in the saline group. Although the serum magnesium levels before CDDP administration were not significantly different between the two groups (p = 0.939), the serum magnesium levels on days 2-3 after CDDP administration in the BRS group were significantly higher than those in the saline group (p &lt; 0.001). In contrast, there were no significant differences in the incidence rates of hematological toxicity between the two groups. Multivariate analysis revealed that BRS use was an independent factor that significantly contributed to AKI prevention (odds ratio = 0.061, p &lt; 0.001). Hydration with BRS could prevent CDDP-induced AKI in patients with esophageal cancer.

Effect of electroacupuncture of "Zusanli" (ST36) combined with capeOX on apoptosis and ferroptosis in nude mice with colorectal cancer.

To investigate the impact of combined treatment of colorectal cancer (CRC) with electroacupuncture (EA) and capeOX (combined administration of fluorouracil, oxaliplatin and capecitabine) on the tumor volume, weight, spleen coefficient, apoptosis and ferroptosis of tumor tissue, and liver and kidney functions in nude mice with CRC, so as to explore its mechanisms underlying inhibiting CRC and alleviating toxic reactions of capeOX. Female Balb/c nude mice were randomly assigned to 3 groups：model, capeOX, and EA+capeOX, with 8 nude mice in each group. The CRC model was established by subcutaneous injection of colon cancer cells at the right inguinal region. Nude mice of the capeOX group received intraperitoneal injection of oxaliplatin for 1 day and gavage of capecitabine from day 2 to day 7. EA (1 mA, 2 Hz/100 Hz) was applied to bilateral "Zusanli" (ST36) for 20 min, once daily for 7 days. During the interven-tion, the tumor volume and weight were measured every day, and at the end of intervention, the weight of the tumor tissue and spleen were measured, with tumor volume difference and spleen coefficient calculated. The proportion of apoptotic cells was measured by flow cytometry, and the contents of serum malondialdehyde (MDA), alanine aninotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine (Cr) were detected using ELISA. The expression level of glutathione peroxidase 4 (GPX4, a key regulator for ferroptosis) protein of the tumor tissue was determined using Western blot. Compared to the model group, both the capeOX group and EA+capeOX group showed a decrease in the tumor volume (on day 3 and 4 in the capeOX group, and from day 2 to 7 in the EA+capeOX group) and body weight (P<0.05, on day 3 to 7 in the EA+capeOX group and on day 2 to 7 in the capeOX group), being evidently lower in the tumor volume on day 7 in the EA+capeOX than in the capeOX group (P<0.05), and evidently higher in the body weight on day 6 and 7 in the EA+capeOX group than in the capeOX group (P<0.05). In comparison with the model group, the tumor volume difference, tumor weight and spleen coefficient in both capeOX and EA+capeOX groups were significantly decreased (P<0.05), and MDA content in EA+capeOX group was significantly decreased (P<0.05), while the contents of ALT, BUN and Cr in the capeOX group, the proportion of apoptotic cells in both capeOX and EA+capeOX groups, and the GPX4 expression level in the EA+capeOX group were all significantly increased (P<0.05). The tumor volume difference, tumor weight, and contents of MDA, ALT, AST, BUN and Cr in the EA+capeOX group were markedly lower than in the capeOX group (P<0.05), while the spleen coefficient, proportion of apoptotic cells and GPX4 expression level in the EA+capeOX group were markedly higher than those in the capeOX group (P<0.05). EA of ST36 can enhance the effect of capeOX in inhibiting colorectal cancer growth in nude mice with CRC, which may be related with its functions in promoting tumor cell apoptosis, inhibiting ferroptosis, and modulating immune tolerance. In addition, EA can lower the side effects of capeOX in hematopoietic and immune, liver, and kidney functions.

Rapid determination of uracil in biological fluids at mercury thin film electrode for early detection of potential 5-fluorouracil toxicity due to dihydropyrimidine dehydrogenase deficiency

Determination of plasma uracil was reported as a method for evaluation of Dihydropyrimidine dehydrogenase (DPD) activity that is highly demanded to ensure the safe administration of 5-fluorouracil (5-FU)-based therapies to cancer patients. This work reports the development of a simple electroanalytical method based on adsorptive stripping square wave voltammetry (AdSWV) at mercury film-coated glassy carbon electrode (MF/GCE) for the highly sensitive determination of uracil in biological fluids that can be used for diagnosis of decreased DPD activity. Due to the formation of the HgII–Uracil complex at the electrode surface, the accuracy of the measurement was not affected by the complicated matrices in biological fluids including human serum, plasma, and urine. The high sensitivity of the developed method results in a low limit of detection (≈1.3 nM) in human plasma samples, falling below the practical cut-off level of 15 ng mL−1 (≈0.14 μM). This threshold concentration is crucial for predicting 5-FU toxicity, as reported in buffer, and ≤1.15% in biological samples), and accuracy (recovery percentage close to 100%).

MiR-146a reduces fibrosis after glaucoma filtration surgery in rats

PurposeTo explore the impact of microRNA 146a (miR-146a) and the underlying mechanisms in profibrotic changes following glaucoma filtering surgery (GFS) in rats and stimulation by transforming growth factor (TGF)-β1 in rat Tenon’s capsule fibroblasts.MethodsCultured rat Tenon’s capsule fibroblasts were treated with TGF-β1 and analyzed with microarrays for mRNA profiling to validate miR-146a as the target. The Tenon’s capsule fibroblasts were then respectively treated with lentivirus-mediated transfection of miR-146a mimic or inhibitor following TGF-β1 stimulation in vitro, while GFS was performed in rat eyes with respective intraoperative administration of miR-146a, mitomycin C (MMC), or 5-fluorouracil (5-FU) in vivo. Profibrotic genes expression levels (fibronectin, collagen Iα, NF-KB, IL-1β, TNF-α, SMAD4, and α-smooth muscle actin) were determined through qPCR, Western blotting, immunofluorescence staining and/or histochemical analysis in vitro and in vivo. SMAD4 targeting siRNA was further used to treat the fibroblasts in combination with miR-146a intervention to confirm its role in underlying mechanisms.ResultsUpregulation of miR-146a reduced the proliferation rate and profibrotic changes of rat Tenon’s capsule fibroblasts induced by TGF-β1 in vitro, and mitigated subconjunctival fibrosis to extend filtering blebs survival after GFS in vivo, where miR-146a decreased expression levels of NF-KB-SMAD4-related genes, such as fibronectin, collagen Iα, NF-KB, IL-1β, TNF-α, SMAD4, and α-smooth muscle actin(α-SMA). Additionally, SMAD4 is a key target gene in the process of miR-146a inhibiting fibrosis.ConclusionsMiR-146a effectively reduced TGF-β1-induced fibrosis in rat Tenon’s capsule fibroblasts in vitro and in vivo, potentially through the NF-KB-SMAD4 signaling pathway. MiR-146a shows promise as a novel therapeutic target for preventing fibrosis and improving the success rate of GFS.

CLINICAL CASE OF KERATOACANTHOMA

Keratoacanthoma is a common, rapidly growing skin tumour that has long been considered benign due to its staged course and ability to spontaneously regress. However, according to the latest World Health Organization classification, keratoacanthoma is classified as a well-differentiated form of squamous cell carcinoma.&#x0D; Despite its long history keratoacanthoma remains a subject of controversy with regard to epidemiology, diagnosis, prognosis, and treatment.&#x0D; The etiology and pathogenesis of keratoacanthoma are also not clearly defined. However, a number of factors have been identified that are highly likely to lead to the development of a tumour. In particular, these are ultraviolet and X-ray radiation, thermal and traumatic injuries, chemical carcinogens, genetic and immunological predictors, human papillomaviruses and certain drugs (sorafenib, infliximab, etc.).&#x0D; Clinically, keratoacanthoma appears on the skin as a single or multiple crater-like nodule. Dermoscopy can be used for early diagnosis and differentiation from other tumour formations. The choice of therapy varies widely and depends on the location, stage of development, and size of the tumour.&#x0D; The publication presents a number of cases which demonstrate the clinical, dermoscopic, and histological picture of keratoacanthomas.&#x0D; Case presentation. Patient A, 44 years old, skin with signs of photodamage. A single dense nodule, up to 0.5 cm in diameter, on the anterior surface of the right lower leg. It appeared and grew rapidly over the past month.&#x0D; Dermoscopy with photographic fixation was performed. A non-pigmented dome-shaped lesion with central yellow-brown keratinous masses, sporadic haemorrhages, and white structureless areas was observed. The vascular pattern was represented by looped, glomerular and helical vessels in a radial arrangement. The lesion was surgically excised. A pathohistological study was carried out. The conclusion was a well-differentiated squamous cell carcinoma of the skin.&#x0D; In typical cases, the diagnosis of keratoacanthoma is not difficult. However, the combination with other skin lesions can distort the clinical picture. For example, in Patient B, keratoacanthoma developed against the background of seborrheic keratosis. In such cases, the use of dermoscopy can provide additional clues to the diagnosis and, accordingly, influence treatment methods.&#x0D; Considering keratoacanthoma as a well-differentiated squamous cell carcinoma, surgical excision is preferred. The metastatic potential of this tumour is not significant, but in high-risk areas such as the lip or ear, it can reach 30%. At the same time, surgery reduces the risk of local recurrence. Other approaches include electrodissection and curettage, cryodestruction, intratumoural administration of methotrexate, 5-fluorouracil, bleomycin, and photodynamic therapy. These methods are appropriate in cases where the size or location of the tumour do not allow achieving the desired aesthetic effect.&#x0D; Conclusions: 1. Keratoacanthoma is a well-differentiated squamous cell carcinoma with a low potential for metastasis. 2. Central yellow-brown keratinous masses, sporadic haemorrhages, white structureless areas, in combination with looped and glomerular vessels in radial disposition seen during dermoscopy of a nodule, may be a sign of keratoacanthoma. 3. The choice of treatment method for keratoacanthoma depends on its location and size; surgical excision of the tumour should be preferred.

RE-TRABECULECTOMY + 5-FLUOROURACIL IN PRIMARY ANGLE CLOSURE GLAUCOMA PATIENTS AGGRAVATED BY CONSUMPTION OF SCHIZOAFFECTIVE DRUG

Introduction : PACG occurs when the anterior chamber angle is occluded by the iris thus reducing aqueous humor outflow. Most schizoaffective patients use anticholinergic drugs which may result in iridocorneal angle closure through deposition. This article reported a Re-Trabeculectomy + 5 FU surgery in PACG which was aggravated by the use of schizoaffective drugs&#x0D; Case Illustration : A 43 year old woman, underwent Re-Trabeculectomy + 5 FU on LE after increasing IOP and regularly took schizoaffective drugs. Tapering of schizoaffective therapy was done 1 month preoperatively. Patient presented with LE UCVA of 3/60 and LE IOP is 30.9 mmHg with three anti- glaucoma medications. LE examinations revealed VH1 AC, bayonet sign and cupping on funduscope, closed angle on gonioscope, nasal step defect on humphrey and diffuse RNFL thinning on OCT. On the first postoperative day LE IOP is 18.5 mmHg. The schizoaffective therapy was re-initiated from psychiatric and evaluation was done weekly&#x0D; Discussion : Re-trabeculectomy surgery have been done considering the failure of the first trabeculectomy and administration of 5-Fluorouracil as an anti-fibrosis. The benefits of reducing preoperative dose of schizoaffective drugs for a month due to having an anticholinergic effect and reduces IOP by 5 mmHg. Psychiatrists and ophthalmologists work together to try to administer basic schizoaffective drug doses and evaluate IOP to keep it under control.&#x0D; Conclusion : The re-operative action was carried out by adding anti-fibrosis and cooperating with psychiatry for postoperative tapering of schizoaffective drugs. Long-term use of antidepressant drugs and benzodiazepines increases PACG.

Two Cases of Hyperammonemia After Administration of 5-Fluorouracil for Head and Neck Cancer

Two Cases of Hyperammonemia After Administration of 5-Fluorouracil for Head and Neck Cancer

Pharmacogenomics of 5-Fluorouracil in Oesophageal Carcinoma Association of Single Nucleotide Polymorphisms with Efficacy and Adverse Effects

Esophageal carcinoma (EC) is a highly fatal cancer. The usual therapy for localized squamous cell carcinoma has traditionally been surgically removing the tumor from its main location. However, recent clinical advancements have led to the development of new therapeutic options. The available choices encompass chemotherapy which involves continuous administration of 5-fluorouracil (5-FU), cisplatin, and simultaneous radiation treatment. To enhance clinical outcomes, future advancements would have to improve the integration of new anticancer medications, the administration of cisplatin, or 5-FU, guided by pharmacokinetics, and the identification of potential responders through genetic profiling of patients before treatment initiation. This review provides a comprehensive summary of the information about the genetic variation in ABCB1, ERCC!, TYMS, XPD, and DYPD genes that most likely contribute to the pharmacokinetic or genotype-guided administration of 5-FUfor the treatment of oesophageal cancer. The review aims to facilitate personalized treatment strategies for this condition in the future.

Ganoderma lucidum polysaccharides associated with 5-Fluorouracil impair OSCC tumorigenesis in vitro

BackgroundsGanoderma lucidum polysaccharides have been shown several anti-cancer, anti-inflammatory, and immunomodulatory properties among studies with different tumor models and its use with advanced and conventional combination therapies is a world trend. The administration of 5-Fluorouracil is already used as chemotherapy for many tumors and works on tumor remission; however, its adverse effects are still severe, impoverishing treatment and quality of life for patients. Cancer stem cells represent a subpopulation of cells with defense mechanisms against chemotherapy agents and are the main cause of relapses and metastases in cancer treatments. Also, the Epithelial-Mesenchymal Transition program increases properties related to tumor malignancy and mortality. In this scenario, the aim of the study is to evaluate the effects of Ganoderma lucidum polysaccharides in combination with 5-Fluorouracil on the subpopulation of cancer stem cells present in the human oral squamous carcinoma cell line SCC-9. MethodsSCC-9 cells were treated in vitro for 72 h with different 5-Fluorouracil low doses, associated or not with Ganoderma lucidum polysaccharides. Cells maintained with culture media or cisplatin were used as control. All the cells were evaluated for cytotoxicity, cancer stem cells, and Epithelial-Mesenchymal Transition properties. ResultsThe associated treatment avoided proliferation, delayed migration, slightly modified morphology of cells, increased apoptosis, decreased colony and blocked spheres formation, and downregulated cancer stem cells, Epithelial-Mesenchymal Transition, and ABC drug transporters expression. In addition, Ganoderma lucidum polysaccharides + 5-Fluorouracil changed the treated cells into a non-cancer stem cell phenotype, a characteristically not resistant and less proliferative population. The 5-Fluorouracil treatment alone showed remarkable modification in cellular morphology, apoptosis, and absence of holoclones; however, it upregulated the molecular expression of cancer stem cells' hallmarks. ConclusionsThese findings demonstrate that combining Ganoderma lucidum polysaccharides with a low dose of 5-Fluorouracil is effective against oral squamous cell carcinoma in vitro by enhancing the cells' sensitivity to drugs and reducing the characteristics associated with cancer stem cells (CSCs). This suggests the possibility of reducing conventional chemotherapy doses and improving oral squamous cell carcinoma treatment. It also highlights the potential for this combination to be used as an adjunct in Complementary Alternative Medicine (CAM).

Impact of neoadjuvant FLOT treatment of advanced gastric and gastroesophageal junction cancer following surgical therapy.

Therapeutic treatment for advanced-stage (T2-T4) gastroesophageal junction (GEJ) and gastric cancer involves neoadjuvant chemotherapy with subsequent surgical intervention. Neoadjuvant oncological treatment for GEJ and gastric cancer previously consisted of the intravenous administration of epirubicin, cisplatin and fluorouracil (ECF) or epirubicin, cisplatin and capecitabine (ECX) combination (Group 1). The new protocol (FLOT, F: 5-FU, L: leucovorin, O: oxaliplatin, T: docetaxel), included patients with resectable GEJ and gastric cancer who had a clinical stage cT2 or higher nodal positive cN+ disease (Group 2). Between 31 December 2008 and 31 October 2022, the effect of different oncological protocols in terms of surgical outcomes in cases of T2-T4 tumours were retrospectively evaluated. Results of randomly assigned patients from the earlier ECF/ECX protocol (n = 36) (Group 1) and the new FLOT protocol (n = 52) (Group 2) were compared. Effect of different neoadjuvant therapies on tumour regression, types of possible side effects, type of surgery, and oncological radicality of surgical procedures were analysed. When comparing the two groups, we found that in case of the FLOT neoadjuvant chemotherapy (Group 2, n = 52), complete regression was achieved in 13.95% of patients, whereas in the case of ECF/ECX (Group 1, n = 36), complete regression occurred in only 9.10% of patients. Furthermore, in the FLOT group, the mean number of lymph nodes removed was slightly higher (24.69 vs. 20.13 in the ECF/ECX group). In terms of the safety resection margin (proximal), no significant difference was found between the two treatment groups. Nausea and vomiting were the most common side effects. The occurrence of diarrhea was significantly higher in the FLOT group (p = 0.006). Leukopenia and nausea occurred more commonly with the old protocol (Group 1). The rate of neutropenia was lower following FLOT treatment (p = 0.294), with the lack of grade II and III cases. Anaemia occured at a significantly higher rate (p = 0.036) after the ECF/ECX protocol. As a result of the FLOT neoadjuvant oncological protocol for advanced gastro-esophageal junction and gastric cancer, the rate of complete tumour regression increased significantly. The rate of side effects was also appreciably lower following the FLOT protocol. These results strongly suggest a significant advantage of the FLOT neoadjuvant treatment used before surgery.

Bioluminescence Imaging and ICP-MS Associated with SPION as a Tool for Hematopoietic Stem and Progenitor Cells Homing and Engraftment Evaluation.

Bone marrow transplantation is a treatment for a variety of hematological and non-hematological diseases. For the transplant success, it is mandatory to have a thriving engraftment of transplanted cells, which directly depends on their homing. The present study proposes an alternative method to evaluate the homing and engraftment of hematopoietic stem cells using bioluminescence imaging and inductively coupled plasma mass spectrometry (ICP-MS) associated with superparamagnetic iron oxide nanoparticles. We have identified an enriched population of hematopoietic stem cells in the bone marrow following the administration of Fluorouracil (5-FU). Lately, the cell labeling with nanoparticles displayed the greatest internalization status when treated with 30 µg Fe/mL. The quantification by ICP-MS evaluate the stem cells homing by identifying 3.95 ± 0.37 µg Fe/mL in the control and 6.61 ± 0.84 µg Fe/mL in the bone marrow of transplanted animals. In addition, 2.14 ± 0.66 mg Fe/g in the spleen of the control group and 2.17 ± 0.59 mg Fe/g in the spleen of the experimental group was also measured. Moreover, the bioluminescence imaging provided the follow up on the hematopoietic stem cells behavior by monitoring their distribution by the bioluminescence signal. Lastly, the blood count enabled the monitoring of animal hematopoietic reconstitution and ensured the transplantation effectiveness.

ANTI-TUMORAL EFFECT OF 5-FLUOROURACIL AND OXALIPLATIN IN A LIVER REGENERATION MODEL

Abstract Introduction Colorectal cancer liver metastases (CRCLM) continue to be a therapeutic challenge, since their resectability is usually limited by the functionality of the liver remnant. In this context, it is necessary to study the regenerative response of the liver in a selective portal vein ligation (PVL) model, after the administration of 5-fluorouracil and oxaliplatin, and to assess the effect of compensatory hypertrophy on tumor progression. Methods Twenty-eight WAG/RijHsd rats carrying CRCLM were divided into four groups: control, PVL, 5FU (50mg/kg) and 5FU+Oxaliplatin (50mg/kg+10mg/kg). After 18 days of tumor development, a dose of the corresponding treatment was administered, performing a PVL of 50% 72h later. Seven days later, tumor size was quantified and a biochemical profile was performed. Results The 5FU+Oxaliplatin and 5FU alone treatment decreased tumor growth by 6 and 3 times compared to the PVL and control groups, respectively (p&amp;lt;0.001). At a biochemical level, the combination of drugs resulted in a decrease in albumin levels (3.3 ± 0.39 mg/dl; p&amp;lt;0.02) and a significant weight loss of 10%; however, glucose (152±6.6 mg/dl), AST (161±27.1 IU/L), and ALT (46.7±9.4 IU/L) were not significantly altered. Seven days after PVL, the liver remnant did not change in either group (5FU+Oxaliplatin: 8±1; 5FU: 9.7±1.2; control 9.4±1.9 g; p&amp;gt;0.05). Conclusion In our model, the combined therapy of 5-Fluorouracil and oxaliplatin, prior to PVL, does not affect the necessary hepatic regeneration; while the volume of tumor implants decreases, no significant alteration of the biochemical parameters is detected.

A Rat Model for Oral Mucositis Induced by a Single Administration of 5-Fluorouracil.

This study aimed to develop a reliable chemotherapy-induced oral mucositis (CIOM) rat model by intraperitoneally administering a single dosage of 5-fluorouracil (5-FU) combined with a chemical stimulus. The 5-FU dosage for CIOM development was determined by the survival rate of rats administrated 160 mg/kg, 200 mg/kg, and 240 mg/kg of 5-FU. Thirty rats were assigned to normal control (NC) and three experimental groups: i) ulcer formation without 5-FU administration (PBS/U+), ii) 5-FU administration without ulcer formation (5-FU/U-), and iii) ulcer formation after 5-FU administration (5-FU/U+). White blood cell count and weight were measured at the day of 5-FU administration (D0), ulcer formation (D2), and two days after ulcer formation (D4). The oral mucosa for histologic evaluations was obtained two (D4) and five days (D7) after ulcer formation. The 5-FU dosage for CIOM development was 200 mg/kg. White blood cell count (WBC) counts and weight of rats were significantly lower in 5-FU/U- (WBC, p<0.001; weight, p=0.002) and 5-FU/U+ (WBC, p<0.001; weight, p<0.001) groups compared to those in the NC group at D4. The number of Ki-67 positive cells in the oral epithelium was lower in 5-FU/U+ group compared to that in NC (p<0.001) and PBS/U+ (p=0.047) groups at D7. Single administration of 200 mg/kg of 5-FU combined with a chemical stimulus can lead to an immune-suppressive status, failure of weight gain, and impairment of epithelium regeneration as observed in a CIOM rat model.

Current trends in the treatment of hypertrophic scars

BACKGROUND: The therapeutic arsenal for the treatment of hypertrophic scars and keloids has expanded significantly in recent years. Traditional methods of treatment, such as intraocular injection of corticosteroids, pressure therapy and cryotherapy, are increasingly supplemented with new methods. The level of evidence for treatment approaches has increased due to the development of systematic reviews and national and international recommendations.&#x0D; AIM: To study the effectiveness of pneumokinetic micro-jet "needle-free" delivery of corticosteroid drug and fluorouracil in hypertrophic scars.&#x0D; MATERIAL AND METHODS: We observed 23 patients (with hypertrophic scars. The average age was 31.34.3 years. The duration of the existence of hypertrophic scars in the average group was 7.82.3 months. Previously, patients did not receive therapy for the correction of scars. All patients were treated with intra-cicatricial administration of durant corticosteroid and fluorouracil. The technology of pneumokinetic micro-jet "needle-free" was used.&#x0D; RESULTS: A high effect was achieved in all patients. Thus, the total Dermatological symptom scale index decreased with localization of the process on the face by 79.1% (p 0.01), with localization on the neck by 81.2% (p 0.01), with localization on the abdomen by 73.4% (p 0.01).&#x0D; CONCLUSION: The technology of pneumokinetic micro-jet "needle-free" delivery of corticosteroid drug and fluorouracil subdermally can be considered as the method of choice in this category of patients.

Final Analysis of Diagnostic Endoscopic Resection Followed by Selective Chemoradiotherapy for Stage I Esophageal Cancer: JCOG0508

Final Analysis of Diagnostic Endoscopic Resection Followed by Selective Chemoradiotherapy for Stage I Esophageal Cancer: JCOG0508

Short term results of the FLOT neoadjuvant therapy on the surgical management of advanced gastro-oesophageal junction adenocarcinoma

Introduction. Recently the therapeutic treatment for advanced, stage T2-T4 gastro-oesophageal junction cancer and those adjacent to the regional lymph nodes involves neoadjuvant chemotherapy with subsequent surgical intervention. Method. Neoadjuvant oncological treatment for gastro-oesophageal junction cancer previously consisted of the intravenous administration of epirubicin, cisplatin and fluorouracil (ECF) or epirubicin, cisplatin and capecitabine (ECX) combination (Group I). In the course of the new protocol (FLOT-, F: 5-FU, L: leucovorin, O: oxaliplatin, T: docetaxel), patients were included with resectable gastro-oesophageal junction cancer who had a clinical-stage cT2 or higher nodal positive cN+ disease (Group II). Between 31st of December 2013 and 1st of June 2021 we retrospectively analyzed the effect of these FLOT oncological protocols in terms of surgical outcomes in cases of T2-T4 tumors (n= 9). We compared the results of the randomly assigned nine patients from earlier ECF/ECX protocol (Group I). We analyzed the effect of the different neoadjuvant therapy on tumor regression, and evaluated the types of possible side effects, type of surgery, and the oncological radicality of surgical procedures (number of removed regional lymph nodes, resection margins). Results. Comparing the two groups we found that in cases of FLOT neoadjuvant chemotherapy complete regression was achieved significantly a higher number like in earlier ECX/ECF therapy. Furthermore, the average number of removed lymph nodes, and the safety resection margins (distal, circumferential) no significant difference was found between the two groups. Neutropenia was the most frequently encountered side effect. Leukopenia, neutropenia and nausea occurred more frequently in cases of the old protocol (Group I). Conclusions. As a result of the FLOT neoadjuvant oncological protocol for advanced gastro-oesophageal junction cancer, the number of cases with complete tumor regression has significantly increased. The present results strongly suggest a significant advantage in favor of FLOT neoadjuvant treatment following surgery. The prevalence of side effects was also appreciably lower in cases of the FLOT protocol.

Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer

BackgroundThe incidence of anal cancer is substantially higher among persons living with the human immunodeficiency virus (HIV) than in the general population. Similar to cervical cancer, anal cancer is preceded by high-grade squamous intraepithelial lesions (HSILs). Treatment for cervical HSIL reduces progression to cervical cancer; however, data from prospective studies of treatment for anal HSIL to prevent anal cancer are lacking.MethodsWe conducted a phase 3 trial at 25 U.S. sites. Persons living with HIV who were 35 years of age or older and who had biopsy-proven anal HSIL were randomly assigned, in a 1:1 ratio, to receive either HSIL treatment or active monitoring without treatment. Treatment included office-based ablative procedures, ablation or excision under anesthesia, or the administration of topical fluorouracil or imiquimod. The primary outcome was progression to anal cancer in a time-to-event analysis. Participants in the treatment group were treated until HSIL was completely resolved. All the participants underwent high-resolution anoscopy at least every 6 months; biopsy was also performed for suspected ongoing HSIL in the treatment group, annually in the active-monitoring group, or any time there was concern for cancer.ResultsOf 4459 participants who underwent randomization, 4446 (99.7%) were included in the analysis of the time to progression to cancer. With a median follow-up of 25.8 months, 9 cases were diagnosed in the treatment group (173 per 100,000 person-years; 95% confidence interval [CI], 90 to 332) and 21 cases in the active-monitoring group (402 per 100,000 person-years; 95% CI, 262 to 616). The rate of progression to anal cancer was lower in the treatment group than in the active-monitoring group by 57% (95% CI, 6 to 80; P=0.03 by log-rank test).ConclusionsAmong participants with biopsy-proven anal HSIL, the risk of anal cancer was significantly lower with treatment for anal HSIL than with active monitoring. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02135419.)

Diagnosis and management of 5-fluorouracil (5-FU)-induced acute leukoencephalopathy: lessons learnt from a single-Centre case series

BackgroundThe administration of 5-fluorouracil (5FU) in the treatment of gastrointestinal (GI) malignancies is associated with common side effects such as mucositis, diarrhoea, and myelosuppression, which are easily managed with supportive measures and dose adjustments. Cardiotoxicity and neurotoxicity are rare but reversible side effects of 5-FU and are treated with withdrawal of the drug and conservative measures. The presenting symptoms of 5-FU-induced leukoencephalopathy are often confusing and pose a diagnostic dilemma in routine clinical practice.MethodsWe report a series of five patients with GI malignancies who developed 5-FU-induced leukoencephalopathy.ResultsAll (n = 5) had Naranjo scores of 6–7, predictive of 5-FU-related adverse effects, with clinical and radiological findings suggestive of 5-FU-induced encephalopathy as described in prior literature. The median time to onset of symptoms from initiation of 5FU was 3 days (range: 2–4 days). All patients improved after conservative management with complete neurological recovery.ConclusionPrompt recognition of this rare yet severe adverse effect of 5-FU-based chemotherapy aids early withdrawal of the offending agent (5-FU) and timely initiation of supportive measures and helps plan alternative oncological interventions.