-
Surgical Endoscopy Dec 2022The CADISS® system combines the use of a topical formulation of mesna (sodium 2-Mercaptoethane sulfonate) to facilitate selective dissection of pathological and... (Clinical Trial)
Clinical Trial
BACKGROUND
The CADISS® system combines the use of a topical formulation of mesna (sodium 2-Mercaptoethane sulfonate) to facilitate selective dissection of pathological and fibrotic tissues with a non-cutting instrument for a safer dissection. A prospective, multi-site, clinical trial was performed to explore the use of the CADISS® system in laparoscopic cholecystectomy for acute cholecystitis.
METHODS
A total of 15 patients were enrolled at different severity stages of pathology according to Tokyo classification. They were operated on prior to, or after 72 h of, the onset of symptoms. The primary measure was the number of critical dissection steps successfully achieved using the CADISS® system without cutting instruments.
RESULTS
Five patients were operated on before 72 h of symptom onset and ten after. All the dissections were successfully achieved using the CADISS® method. No mortality was recorded. No conversion to open surgery was performed. No bile duct injury was observed. Other endpoints (facilitation of dissection of critical structures, identification of cleavage planes and reduction of risk) had scores of above nine on our Likert scale. Four postoperative serious adverse events including cholangitis, fever, pulmonary embolism and right hepatic artery pseudoaneurysm were reported. However, they seemed to be more related to cholecystitis or local conditions rather than the use of the CADISS® method.
CONCLUSION
This is the first study to investigate the use of the CADISS® System in cholecystectomy. The CADISS® system seemed to facilitate dissection in acute cholecystitis. Encouraging results are reported independently of the severity grade of cholecystitis and the delay in performing the surgery. Even now, laparoscopic cholecystectomy for acute cholecystitis remains a surgical challenge. Techniques that could facilitate this operation and reduce surgical complications may be helpful. Further studies should be conducted to confirm our preliminary results. Trial registration Clinical trials.gov NCT05041686.
Topics: Humans; Acute Disease; Cholecystectomy; Cholecystectomy, Laparoscopic; Cholecystitis; Cholecystitis, Acute; Prospective Studies
PubMed: 36319896
DOI: 10.1007/s00464-022-09616-w -
Life Sciences Jul 2022Cyclophosphamide (CP)-induced cystitis is a challenging clinical problem involving inflammation and dysfunction of bladder. Trimetazidine (TMZ) is an anti-anginal drug...
AIM
Cyclophosphamide (CP)-induced cystitis is a challenging clinical problem involving inflammation and dysfunction of bladder. Trimetazidine (TMZ) is an anti-anginal drug with anti-oxidant and anti-inflammatory properties. We aimed to investigate the protective effects of TMZ in CP-induced cystitis via inhibiting TLR4/NFκB signaling.
MAIN METHODS
Balb/c mice were administrated TMZ (10 or 20 mg/kg/day) intraperitoneally (i.p.) for 5 consecutive days before CP. On day 6, cystitis was induced by a single dose of CP (300 mg/kg, i.p.). Mesna (2-mercaptoethane sulfonate sodium; 30 mg/kg, i.p.) was administered 20 min before and at 4 and 8 h after the CP injection. After 24 h of cystitis induction, the bladders were removed for histopathological evaluation, contractility studies, biochemical analysis and western blotting. MTT assay was performed in a cancer cell line (MDA-MB-231) to evaluate the effect of TMZ on the cytotoxicity of CP.
KEY FINDINGS
CP-induced severe cystitis was confirmed by histological disturbances and the decrease in carbachol-evoked contractions of detrusor strips, which was partially improved by TMZ (20 mg/kg/day). SOD activity and GSH content were decreased whereas TNF-α and IL-1β levels were increased in the bladders of CP-treated mice, which were restored by TMZ or mesna. TMZ reduced the CP-induced increase in the protein expressions of caspase-3, TLR4 and phosphorylated-NFκB in bladder tissues. TMZ alone decreased the cell viability and TMZ also enhanced the cytotoxicity of CP.
SIGNIFICANCE
Our study provides the first preclinical evidence that TMZ attenuates CP-induced urotoxicity by enhancing anti-oxidant capacity and suppressing inflammation possibly via downregulating TLR4-mediated NFκB signaling while augmenting the cytotoxicity of CP.
Topics: Animals; Antioxidants; Cyclophosphamide; Cystitis; Inflammation; Mesna; Mice; Mice, Inbred BALB C; NF-kappa B; Toll-Like Receptor 4; Trimetazidine
PubMed: 35504331
DOI: 10.1016/j.lfs.2022.120590 -
Pharmaceuticals (Basel, Switzerland) Nov 2021One of the major side effects of cyclophosphamide (CPX)-an alkylating anticancer drug that is still clinically used-is urotoxicity with hemorrhagic cystitis. The present...
One of the major side effects of cyclophosphamide (CPX)-an alkylating anticancer drug that is still clinically used-is urotoxicity with hemorrhagic cystitis. The present study was designed to evaluate the ability of carvedilol to protect rats from cyclophosphamide-induced urotoxicity. Rats were injected intraperitoneally () with CPX (200 mg/kg) and administered carvedilol (2 mg/kg) intragastrically a day before, at the day and a day after a single . injection of CPX, with or without mesna (40, 80, and 80 mg/kg 20 min before, 4 h and 8 h after CPX administration, respectively). Pretreatment with carvedilol partly prevented the CPX-induced increase in urinary bladder and kidney index, and completely protects from CPX-evoked alterations in serum potassium and creatinine level, but did not prevent histological alterations in the urinary bladder and hematuria. However, carvedilol administration resulted in significant restoration of kidney glutathione (GSH) level and a decrease in kidney interleukin 1β (IL-1β) and plasma asymmetric dimethylarginine (ADMA) concentrations. Not only did mesna improve kidney function, but it also completely reversed histological abnormalities in bladders and prevented hematuria. In most cases, no significant interaction of carvedilol with mesna was observed, although the effect of both drugs together was better than mesna given alone regarding plasma ADMA level and kidney IL-1β concentration. In conclusion, carvedilol did not counteract the injury caused in the urinary bladders but restored kidney function, presumably via its antioxidant and anti-inflammatory properties.
PubMed: 34959638
DOI: 10.3390/ph14121237 -
Clinical Rheumatology Jan 2021Standard regimens for scleroderma interstitial lung diseases (SSc-ILDs) are pulse intravenous (IV) and oral daily cyclophosphamide (CYC). However, IV CYC has limited...
INTRODUCTION
Standard regimens for scleroderma interstitial lung diseases (SSc-ILDs) are pulse intravenous (IV) and oral daily cyclophosphamide (CYC). However, IV CYC has limited access to diffuse cutaneous SSc, and oral daily CYC is associated with febrile neutropenia and hemorrhagic cystitis. Pulse oral CYC regimen has never been studied.
OBJECTIVE
To determine the effectiveness of pulse oral CYC therapy in SSc-ILDs, predictors of effectiveness, and side-effects.
METHODS
A historical cohort study enrolled SSc-ILDs from the SSc database registry at Srinagarind Hospital, Thailand from 1 January 2012 to 1 October 2018. All patients received monthly oral dosages of CYC 600-750 mg/m, Mesna, and daily prednisolone of 10 mg for 2 years. Changes of FVC, chest radiography, HRCT, 6MWT, and side effects were recorded for the baseline and at the end of the treatment. Response to treatment was defined by (a) stable FVC or a decline ≤ 10% of predicted, (b) unchanged or improved radiographic findings, or (c) a decline 6MWT of ≤ 30 m compared with the baseline.
RESULTS
A total of 76 patients with female 52 patients (68.4%) and with a median age of 54.2 years (IQR 46.6-59.6). The majority was dcSSc subset (59 patients; 78.6%). Fifty-four patients (71%) were defined as responsive to therapy. The mean FVC improvement was 1 ml (SD 9.5). The only factor associated with treatment response was limited cutaneous SSc (OR 7.69, 95% CI (1.01, 339.68), p = 0.029). Hemorrhagic cystitis was found in 1 patient.
CONCLUSIONS
Nearly three-quarters of SSc-ILDs patients had a good response to the pulse oral CYC therapy for 2 years with a few serious side effects. Pulse oral CYC therapy had been effective for SSc-ILDs in case of difficult IV access. Key Point • Pulse oral cyclophosphamide has been used for scleroderma lung disease. It has shown efficacy and safety in scleroderma patients. In patients who have difficulty with intravenous access, pulse oral cyclophosphamide can be an alternative regimen.
Topics: Cohort Studies; Cyclophosphamide; Female; Humans; Immunosuppressive Agents; Lung Diseases, Interstitial; Middle Aged; Respiratory Function Tests; Scleroderma, Systemic; Thailand; Treatment Outcome
PubMed: 32519048
DOI: 10.1007/s10067-020-05217-x -
Rheumatology International Jun 2024There may be some diversity in the practice of co-prescribing 2-mercaptoethane sodium sulfonate (mesna) with cyclophosphamide (CYC) for ANCA-associated vasculitis (AAV).
BACKGROUND
There may be some diversity in the practice of co-prescribing 2-mercaptoethane sodium sulfonate (mesna) with cyclophosphamide (CYC) for ANCA-associated vasculitis (AAV).
OBJECTIVES
To assess the practice of prescribing mesna prophylaxis for CYC-treated patients with AAV.
METHODS
We invited authors of publications on AAV referenced in MEDLINE over the previous 10 years to participate in an anonymous online survey. Respondents were eligible if they were involved in CYC treatments for AAV. The survey asked about the characteristics of the respondents and their practice in using CYC and mesna to treat AAV and the underlying rationale. We compared 18 variables between mesna prescribers and their counterparts to identify factors associated with mesna use.
RESULTS
In total, 139 eligible individuals completed the survey. The participants were from 34 countries and were essentially physicians (98%). Overall, 68%, 19% and 13% of respondents prescribed mesna systematically, never, or on a selective basis. As compared with never/selective-prescribers, systematic-prescribers were more often ≤ 39 years old (P = 0.008), more often used intermittent pulse therapy as the exclusive/predominant CYC administration scheme (P < 0.001), were more frequently based in France/Germany/Italy than in England/United States (P < 0.001), and more often indicated adherence to local standards (P = 0.003) or (inter)national guidelines for AAV (P < 0.001) as a rationale for their mesna practice. Never/selective-prescribers more commonly reported that their mesna prescription pattern had changed as compared with their former practice (P < 0.001).
CONCLUSIONS
Systematic co-prescription of mesna is the prevailing practice for CYC treatments for AAV. The practice seems to involve practicability considerations and differs between generations.
PubMed: 38935122
DOI: 10.1007/s00296-024-05620-6 -
Advances in Rheumatology (London,... May 2024To review current literature to support the use of mesna as a preventive therapy for hemorrhagic cystitis and bladder cancer in patients with systemic autoimmune... (Review)
Review
Position statement of the Brazilian society of Rheumatology on mesna use as a preventive therapy for bladder disease in patients with systemic autoimmune diseases and systemic vasculitis under cyclophosphamide treatment.
OBJECTIVE
To review current literature to support the use of mesna as a preventive therapy for hemorrhagic cystitis and bladder cancer in patients with systemic autoimmune diseases and systemic vasculitis treated with cyclophosphamide.
MATERIALS AND METHODS
The search for articles was conducted systematically through MEDLINE, LILACS, Cochrane Library, and Embase databases. Only articles in English were selected. For available records, titles and abstracts were selected independently by two investigators.
RESULTS
Eighteen studies were selected for analysis. The known adverse effects of cyclophosphamide were hematological toxicity, infections, gonadal toxicity, teratogenicity, increased risk for malignancy and hemorrhagic cystitis. Long-term toxicity was highly dependent on cyclophosphamide cumulative dose. The risk of bladder cancer is especially higher in long-term exposure and with cumulative doses above 36 g. The risk remains high for years after drug discontinuation. Hemorrhagic cystitis is highly correlated with cumulative dose and its incidence ranges between 12 and 41%, but it seems to be lower with new regimens with reduced cyclophosphamide dose. No randomized controlled trials were found to analyze the use of mesna in systemic autoimmune rheumatic diseases and systemic vasculitis. Retrospective studies yielded conflicting results. Uncontrolled prospective studies with positive results were considered at high risk of bias. No evidence was found to support the use of mesna during the treatment with cyclophosphamide for autoimmune diseases or systemic vasculitis to prevent hemorrhagic cystitis and bladder cancer. In the scenarios of high cumulative cyclophosphamide dose (i.e., > 30 g), patients with restricted fluid intake, neurogenic bladder, therapy with oral anticoagulants, and chronic kidney disease, mesna could be considered.
CONCLUSION
The current evidence was found to be insufficient to support the routine use of mesna for the prophylaxis of hemorrhagic cystitis and bladder cancer in patients being treated for systemic autoimmune diseases and systemic vasculitis with cyclophosphamide. The use may be considered for selected cases.
Topics: Humans; Cyclophosphamide; Autoimmune Diseases; Cystitis; Mesna; Urinary Bladder Neoplasms; Systemic Vasculitis; Brazil; Immunosuppressive Agents; Hemorrhage; Societies, Medical; Rheumatology
PubMed: 38773538
DOI: 10.1186/s42358-024-00380-0 -
Current Pharmaceutical Biotechnology 2023Hemorrhagic cystitis is an inflammatory complication that can be caused by the administration of cyclophosphamide, which is widely used as an antineoplastic agent. In...
BACKGROUND
Hemorrhagic cystitis is an inflammatory complication that can be caused by the administration of cyclophosphamide, which is widely used as an antineoplastic agent. In the search for new therapeutic alternatives, probiotics can suppress the inflammatory process and, therefore, can be used to prevent this disease.
OBJECTIVE
Thus, this study aimed to evaluate the effects of using Lactobacillus acidophilus NCFM in the treatment of cyclophosphamide-induced hemorrhagic cystitis in Wistar rats.
METHODS
Lactobacillus acidophilus NCFM (2x10 CFU) was used in the treatment of cyclophosphamide- induced hemorrhagic cystitis (200 mg/kg, intraperitoneal) in 77 female Wistar rats. Rats were distributed into experimental groups (n = 9): control group (GC), zero control group (GCZ), inflammation group (GI), 24-hour acute treatment groups: 24-hour lactobacilli treatment group (GL24H) and mesna group (GM), and 30-day chronic treatment groups: lactobacilli treatment group (GTL) and mesna+lactobacilli group (GM+L). After treatment, animals were euthanized and biological materials were collected for blood count, biochemical analyses, examination of abnormal sediment elements (EAS), and histopathological analysis.
RESULTS
GI results showed development of edema, macroscopic alterations, and signs of bleeding in the bladder; in addition, lesions in the urothelium and hemorrhage were also found. GL24H and GM presented intact urothelium, without inflammatory reaction and hematological or biochemical urine alterations.
CONCLUSION
Therefore, this study demonstrated that L. acidophilus presented uroprotective effect against the action of cyclophosphamide in both the short and long term.
Topics: Female; Rats; Animals; Rats, Wistar; Mesna; Lactobacillus acidophilus; Antineoplastic Agents, Alkylating; Cystitis; Cyclophosphamide; Hemorrhage; Inflammation
PubMed: 35507803
DOI: 10.2174/1389201023666220429121953 -
Acta Scientiarum Polonorum. Technologia... 2020One of the widely used anticancer drugs for the treatment of various neoplasms is cyclophosphamide (CYP). The inactive prodrug CYP is metabolized by cytochrome P450... (Review)
Review
One of the widely used anticancer drugs for the treatment of various neoplasms is cyclophosphamide (CYP). The inactive prodrug CYP is metabolized by cytochrome P450 enzyme into active metabolites, phosphoramide mustard and acrolein. The accumulation of acrolein metabolite inside the urothelium results in hemorrhagic cystitis (HC) which is a urotoxic adverse effect associated with the use of CYP. To counteract the occurrence of HC induced by CYP, Mesna is usually used, with allergic reactions reported in some cases. Therefore, several natural products have drawn much attention as alternative safe therapies to reduce the urotoxicity produced from the use of CYP. This review will focus on certain uroprotective mechanisms related to some medicinal plants that are used to ameliorate the CYP-induced urotoxicity in experimental models. The mechanisms involving oxidative stress, inflammation, immune system, apoptosis, DNA fragmentation, uroplakins, purinergic signaling and muscarinic receptors, and CytoP450 metabolism are discussed.
Topics: Antineoplastic Agents, Alkylating; Apoptosis; Biological Products; Cyclophosphamide; Cytochrome P-450 Enzyme System; DNA Fragmentation; Humans; Immune System; Inflammation; Oxidative Stress; Plant Extracts; Receptors, Muscarinic; Urinary Bladder; Urinary Bladder Diseases; Uroplakins
PubMed: 32978915
DOI: 10.17306/J.AFS.0832 -
Urology Case Reports May 2022Prostate embryonal rhabdomyosarcoma (ERMS) is a common tumour in infants and children, but it is rare in adults. It is characterized by a high degree of malignancy, both...
Prostate embryonal rhabdomyosarcoma (ERMS) is a common tumour in infants and children, but it is rare in adults. It is characterized by a high degree of malignancy, both local rapid growth with formation of large pelvic masses, often leading to renal failure due to bladder outlet obstruction, and systemic spread, commonly to the lungs, liver and bone. We report on a case of a stage III prostate ERMS, approached with combined-modality treatment, with the administration of 5 courses of doxorubicin, ifosfamide and 2-mercaptoethane sulfonate sodium (mesna), with planned subsequent radiotherapy to the prostatic bed (60 Gy/30 fractions).
PubMed: 35530538
DOI: 10.1016/j.eucr.2022.102027 -
Journal of Family Medicine and Primary... Apr 2021Paraquat poisoning is a grave public health problem in the Andaman and Nicobar islands of India. To evaluate various aspects of paraquat poisoning that influence the...
Paraquat poisoning is a grave public health problem in the Andaman and Nicobar islands of India. To evaluate various aspects of paraquat poisoning that influence the outcome, a retrospective study was planned. In this case series study, the information about all cases of acute paraquat poisoning who were admitted to GB Pant Hospital, Port-Blair, in a 12-year period (January 2007-December 2018) were evaluated. A total of 29 referred patients were evaluated with the majority from the early productive age of 16-30 years (68.97%). The case fatality rate was 100%. Most of the incidents took place in South Andaman district (68.97%) and during the rainy season (55.17%). Initially, they presented with local symptoms like mouth and throat pain with ulceration (48.27%), vomiting (44.82%), breathlessness (34.48%), epigastric and abdominal pain (31.03%), hematemesis (27.58%), and oliguria (20.68%). Later on, major organ dysfunctions like a respiratory failure (65.51%), acute kidney injury (62.08%), acute liver failure (55.17%), cardiac dysfunction (31.03%), and multiorgan failure (58.62%) ensued. Patients who were referred early had a significantly longer hospital stay. Few received advanced care, like, methyl prednisolone (24.12%), cyclophosphamide (10.34%), Mesna/NAC (06.89%), charcoal tablets (10.34%), mechanical ventilation (06.89%), and hemodialysis (10.34%). Apart from hemodialysis in acute kidney injury patients and steroid pulse, no other modalities showed improved hospital survival duration. Primary prevention especially government laws, public awareness, and education of health professionals regarding the seriousness of this problem are the keys to get rid of this incurable poisoning in these islands. The government should prioritize preventive works in the south Andaman district and during the rainy season to avoid catastrophe each year and if possible should ban it. Methyl prednisolone therapy and hemodialysis might be advocated to have a better outcome.
PubMed: 34123928
DOI: 10.4103/jfmpc.jfmpc_2020_20