Use Of Mesna Research Articles

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

ObjectiveTo 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 methodsThe 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.ResultsEighteen 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.ConclusionThe 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.

Vocal Fold Submucosal Mesna Injection and Microflap Elevation in a Rabbit Model.

Mesna triggers chemical dissection in tissues by breaking down disulfide bonds and is used during surgical dissections in several areas. In this study, we aimed to investigate the effect of submucosal mesna infiltration on microflap elevation and the histopathological findings of its effects on the vocal fold lamina propria in a rabbit model. Eight adult male New Zealand white rabbits were used in the study. Each vocal fold was randomized, and 0.1 mL of mesna was injected into one-fold and 0.1 mL of saline to the contralateral fold. An incision was made on the epithelium and elevation was performed. The animals were sacrificed after two weeks, and the vocal folds were excised. Inflammatory response, fibrosis, and epithelial thickness were evaluated with hematoxylin eosin and Masson's Trichrome staining. Elevation time and histopathological features were compared between the two groups. The elevation time (20.9 ± 1.6 second) in the saline group was significantly higher (P < 0.05) than in the mesna group (15.0 ± 3.4 second). The inflammation (1.3 ± 0.5 vs. 1.1 ± 1.0, respectively) and fibrosis scores (1.0 ± 0.8 vs. 0.8 ± 0.7, respectively) did not differ significantly (P > 0.05 in both). Epithelial thickness (12.5 ± 4.7 vs. 10.3 ± 5.3, respectively) did not differ significantly (P ˃ 0.05) in the mesna and saline groups either. We determined that mesna facilitates the microflap elevation of the vocal folds in rabbits and does not damage the histological structure of vocal folds. This study encourages future studies to evaluate the use of mesna, now actively used across disciplines, in phonosurgery as well.

The assesment of intraoperative use of mesna in canal wall-up cholesteatoma surgery - preliminary report.

&lt;b&gt;Introduction:&lt;/b&gt; Surgery is still the method of choice in chronic otitis media with cholesteatoma. Except for some specific clinical situations, classic canal wall up technique (CWU), remains a gold standard as a primary treatment in most departments. Unfortunately, the risk of recurrence in such an approach is estimated at 9 to even 70%. This fact prompts researchers to look for ways to reduce those unfavourable statistics. One of the recognized methods supporting the removal of cholesteatoma is the intraoperative use of mesna (sodium 2-mercaptoethanesulfonate). This synthetic sulphur compound disrupts disulfide bridges in polypeptide chains, thanks to which it facilitates matrix preparation.&lt;/br&gt;&lt;/br&gt; &lt;b&gt;Aim:&lt;/b&gt; To evaluate the effect of intraoperative use of mesna on the treatment outcomes in patients with chronic otitis media with cholesteatoma operated on by means of the canal wall up technique (CWU).&lt;/br&gt;&lt;/br&gt; &lt;b&gt;Material and methods:&lt;/b&gt; 459 surgical reports of patients with middle ear cholesteatoma were analyzed. In total, 52 adult patients with no history of previous ear surgery operated on by means of the CWU technique by the same experienced otosurgeon with all follow-up data available were included in the study. Twenty-six were operated on with the use of mesna (mesna group) and 26 by means of the classic CWU technique (control / no-mesna group). There were 28 women and 24 men with a mean age of 41 years.&lt;/br&gt;&lt;/br&gt; &lt;b&gt;Main Outcome Measure(s):&lt;/b&gt; Postoperative hearing results and cholesteatoma recidivism rate.&lt;/br&gt;&lt;/br&gt; &lt;b&gt;Results:&lt;/b&gt; Overall recidivism rate was 21.15 %. It was higher in the no-mesna (26.9%) than in the mesna group (15.4%) - although the outcomes were better in the mesna group, the difference was not statistically significant (P = 0.49715). Hearing gain was better in the mesna than in the no-mesna group (10 dB vs 7 dB), but the difference was not statistically significant (P = 0.20089).&lt;/br&gt;&lt;/br&gt; &lt;b&gt;Conclusions:&lt;/b&gt; Our preliminary results show that mesna reduces recidivism rates in patients with cholesteatoma. Further study with the analysis of a larger group of patients is needed to prove it statistically.

Fabrication of impedimetric sensor based on metallic nanoparticle for the determination of mesna anticancer drug

Electrochemical impedance spectroscopy (EIS) is a highly effective technique for studying the surface of electrodes in great detail. EIS-based electrochemical sensors have been widely reported, which measure the charge transfer resistance (Rct) of redox probes on electrode surfaces to monitor the binding of target molecules. One of the protective drugs against hemorrhagic cystitis caused by oxazaphosphorine chemotherapy drugs such as ifosfamide, cyclophosphamide and trophosphamide is Mesna (sodium salt of 2-mercaptoethanesulfonate). The increase in the use of Mesna due to the high consumption of anti-cancer drugs, the determination of this drug in biological samples is of particular importance. So far, no electrochemical method has been reported to measure Mesna. In this research, a novel impedimetric sensor based on a glassy carbon electrode (GCE) modified with oxidized multiwalled carbon nanotubes (MWCNTs)/gold nanoparticle (AuNPs) (denoted as Au NPs/MWCNTs/GCE) for impedimetric determination of Mesna anticancer drug was developed. The modified electrode materials were characterized by field emission scanning electron microscopy (FESEM), energy dispersive X-ray (EDX), and EIS. The electrochemical behavior of Mesna at the surface of Au NPs/MWCNTs/GCE was studied by an impedimetric method. The detection mechanism of Mesna using the proposed impedimetric sensor relied on the increase in the Rct value of [Fe (CN)6]3−/4− as an electrochemical probe in the presence of Mesna compared to the absence of Mesna as the analyte. Under the optimum condition, which covered two linear dynamic ranges from 0.06 nmol L−1 to 1.0 nmol L−1 and 1.0 nmol L−1 to 130.0 µmol L−1, respectively. The detection limit was 0.02 nmol L−1. Finally, the performance of the proposed sensor was investigated for Mesna electrochemical detection in biological samples.

Use of Mesna in the treatment of ossicular chain fixation related to tympanosclerosis; prospective, clinical study.

Mesna is a thiol compound effective in the connective tissue, which is used for its chemical dissector, mucolytic, mucosal damage preventive and antioxidant effects. The aim of this study was to investigate Mesna's effects in easy dissection in type 4 tympanosclerosis cases and in the prevention of formation of new sclerotic plaques. 11 patients were included in the study. All patients were in the Wielinga Kerr type 4 class of tympanosclerosis. All patients were administered a 100% concentration of Mesna in the middle ear during tympanosclerosis surgery. All patients underwent audiological evaluation before and 20months after the operation. Air-conduction thresholds, bone-conduction thresholds and air-bone difference were statistically compared. The patients were followed-up for a mean 20.48±2.37months. The mean preoperative air-conduction threshold of the patients was 58.09±9.73dB and the mean postoperative air-conduction threshold was 34.63±15.46dB and there was a significant difference. The mean preoperative bone-conduction threshold of the patients was 16.27±5.47dB and the mean postoperative bone-conduction threshold was 14.72±6.11dB and there was a significant difference. The mean preoperative air-bone gap of the patients was 41.81±10.51, and the mean postoperative air-bone gap was 19.90±12.48, and the difference was statistically significant. Mesna prevented hearing loss related to type 4 tympanosclerosis and prevented the formation of new sclerotic structures in our follow-up period. We believe that this effect is due to the chemical dissector and antioxidant effects of Mesna.

Incidence of hemorrhagic cystitis after cyclophosphamide therapy with or without mesna: A cohort study and comprehensive literature review.

Cyclophosphamide is an alkylating agent associated with significant toxicities, most importantly hemorrhagic cystitis. Many approaches including mesna use were established to reduce this toxicity. However, data on mesna efficacy are conflicting. To investigate the incidence of hemorrhagic cystitis in patients receiving cyclophosphamide therapy with or without mesna. A retrospective chart review was done on all adult patients receiving cyclophosphamide therapy with or without mesna at the King Saud University Medical City. The incidence of hemorrhagic cystitis was recorded. Patients receiving mesna were compared with those not receiving mesna. Data were reported as numbers and percentages, and appropriate statistical tests of association were used. This step was followed by a comprehensive literature review using appropriate keywords in PubMed from the inception of the database until August 2019. All studies of interest were reported. A total of 718 patients' medical records were reviewed. The majority of the patients received mesna (n = 433, 60%). The mesna group had a greater incidence of hemorrhagic cystitis (3.5% vs. 0.4%, p < 0.004) and received a significantly larger cumulative dose (3103 ± 1696 vs. 2465 ± 1528, p < 0.001) mg of cyclophosphamide therapy. Our literature review revealed large differences in the conclusions of published trials with highly diverse study designs and populations, emphasizing on the need of large prospective trials to address this topic.Conclusion and relevance: Our study results do not support the use of mesna in preventing hemorrhagic cystitis. We found that the only influential factor in the development of hemorrhagic cystitis was the dose of cyclophosphamide therapy.

Cyclophosphamide‐induced hemorrhagic cystitis in young patients with solid tumors: A single institution study

Although hemorrhagic cystitis (HC) is a significant complication in young patients who undergo chemotherapy with cyclophosphamide (CPA), risk factors and supportive care to prevent HC are unclear. This study attempted to identify optimal supportive care to prevent CPA-induced HC. Patients (<30-year-old) with malignant solid tumors who had been treated with CPA-containing chemotherapy in inpatient treatment were eligible. Vigorous hydration to increase urine output and intravenous 2-mercaptethane sulfonate (mesna) were used for prophylaxis of CPA-induced HC. We retrospectively analyzed 81 patients who had been treated with CPA-containing chemotherapy over (collectively) 486 cycles, and examined relationships between HC and various factors, especially CPA dosage, use of mesna, and fluid infusion volume/rate. HC occurred in four patients (4.9%) and five cycles (1%). When stratifying by doses and methods of administration of CPA, HC occurred in 3/323 low- and intermediate-dose (<1500mg/m2 /day) cycles and mesna was used in all three cycles with HC. Patients who were given mesna had a lower flow rate than those given hydration alone in the low- and intermediate-dose CPA (126 ± 25 vs 106 ± 16mL/m2 /h; P<0.01). All patients who received high-dose CPA (≥1500mg/m2 /day) were also given mesna and vigorous hydration (115 ± 16mL/m2 /h). Our supportive care measures may be effective in preventing CPA-induced HC. Patients who receive CPA doses<1500mg/m2 /day should get ≥125mL/m2 /h of infused fluid, regardless of mesna usage; those who receive of CPA ≥1500mg/m2 /day should also receive mesna and vigorous hydration.

Different concentrations of mesna application have an effect on the internal ear?

ObjectiveThe use of Mesna as a chemical dissector in higher concentrations may reduce the length of time of operation by providing more effective dissection as well as being used in otologic pathologies such as tympanosclerosis. In this study, it was aimed to assess the effect of Mesna on the internal ear, which was applied intra-tympanically in higher concentrations than the conventional use. MethodsTwenty-four female rats were included in our study. The rats were randomly divided into three groups (Group 1: Mesna 50%, Group 2: Mesna 100%, Group 3: Saline). At the beginning of the study, DPOAE and ABR measurements were carried out on every rat on days 7 and 14. At the end of the study, cochleas of the rats were excised and histopathological assessments were carried out. ResultsBasal values and DPOAE and ABR values on day 7 and 14 of Group 1, Group 2, and Group 3 were similar to each other. No significant difference was detected among the three groups in the histopathological assessment carried out at the end of the study. ConclusionIt was revealed by audiological and histopathological parameters that the use of Mesna at 50% and 100% concentrations did not create toxicity effects on the internal ear. Mesna would be more effective by being used in higher concentrations in audiological surgeries, that its duration of operation world reduce and could being used in different indications including tympanosclerosis.

Research progress of hemorrhagic cystitis after hematopoietic stem cell transplantation

Hemorrhagic cystitis (HC) is one of the common complications of hematopoietic stem cell transplantation (HSCT). And its clinical features are hematuria, accompanied by urinary frequency, urgency, urine pain and other bladder irritation symptoms. Early onset hemorrhagic cystitis (EOHC) mainly results from uroepithelial injury induced by irradiation/chemotherapy during conditioning regimen particularly high-dose cyclophosphamide. With the use of mesna, the incidence decreased significantly. Late onset hemorrhagic cystitis (LOHC) is usually associated with viral infection and immune dysfunction, but the treatment of LOHC remains a challenge. As the HSCT is extensively used, the researches on diagnosis and treatment of HC are increasing. This article reviews literatures on the etiology, pathogenesis, diagnosis and treatment of HC. Key words: Cystitis; Hematopoietic stem cell transplantation; Etiology

Chemically assisted dissection by means of mesna in cholesteatoma surgery.

To investigate whether the use of mesna (sodium 2-mercaptoethanesulfonate), a mucolytic agent capable of breaking disulfur bonds, reduces the frequency of residual cholesteatoma in canal wall up tympanomastoidectomy. Retrospective study. Tertiary care otology and skull base centers. Two hundred fourteen patients operated on by means of canal wall up tympanomastoidectomy for a middle ear cholesteatoma. Planned staged canal wall up tympanomastoidectomy. In the study group, the cholesteatoma removal was performed with the support of chemically assisted dissection by using mesna. In the control group, the dissection of the disease was performed by means of a traditional mechanical technique alone. Prevalence of residual cholesteatoma at the second-stage operation in the 2 groups of study. One hundred eight patients were treated with the ancillary use of mesna and one hundred six without chemically assisted dissection. A residual cholesteatoma was found in 12 (11.1%) of the 108 patients treated with chemically assisted dissection and in 26 (24.5%) of the 106 patients treated with mechanical dissection. After adjusting for potential confounders, CADISS procedure was associated with a significantly lower risk of having residual cholesteatoma (OR, 0.39; 95% CI, 0.18-0.84, p = 0.02). This study showed that chemically assisted dissection by using mesna represents a valid support in reducing the frequency of residual disease in cholesteatoma surgery.

BK virus-associated hemorrhagic cystitis after pediatric stem cell transplantation.

Hemorrhagic cystitis is a common stem cell transplantation-related complication. The incidence of early-onset hemorrhagic cystitis, which is related to the pretransplant conditioning regimen, has decreased with the concomitant use of mesna and hyperhydration. However, late-onset hemorrhagic cystitis, which is usually caused by the BK virus, continues to develop. Although the BK virus is the most common pathogenic microorganism of poststem cell transplantation late-onset hemorrhagic cystitis, pediatricians outside the hemato-oncology and nephrology specialties tend to be unfamiliar with hemorrhagic cystitis and the BK virus. Moreover, no standard guidelines for the early diagnosis and treatment of BK virus-associated hemorrhagic cystitis after stem cell transplantation have been established. Here, we briefly introduce poststem cell transplantation BK virus-associated hemorrhagic cystitis.

A double-blind, block-randomized, placebo-controlled trial to identify the chemical assistance effect of mesna submucosal injection for gastric endoscopic submucosal dissection

Previous animal studies and a pilot clinical trial demonstrated that submucosal injection of a thiol compound called mesna could chemically soften connective tissues and thus facilitate endoscopic submucosal dissection (ESD). To evaluate whether mesna injection could reduce procedural times for gastric ESD. Double-blind, block-randomized, controlled trial. University hospital. A total of 101 patients with superficial gastric cancer indicated for ESD were enrolled and randomly assigned to either the mesna or control (saline solution) group. Traditional ESD was performed with a single bolus injection of mesna or saline solution. Time for submucosal dissection (TSD). En bloc resection was achieved for all lesions in the mesna group (53/53) and 51 of 52 lesions (98.08%) in the control group. TSD was not statistically different between the groups (18.62 ± 13.9 [mean ± SD] minutes for the mesna group and 24.58 ± 24.55 [mean ± SD] minutes for the control group; P = .128), and there were fewer time-consuming cases (times over 30 minutes) in the mesna group compared with controls (7/53 vs 15/52; P = .049). Multivariate regression analysis demonstrated that use of mesna, specimen size, and the presence of fibrous scars were significantly correlated with TSD (P < .05). Single-center study. TSD was not significantly different between the mesna and control injection groups, but multivariate analysis indicated that mesna injection reduced procedural challenges associated with the submucosal dissection. ( UMIN000003786.).

Extended Use of Ciprofloxacin Markedly Decreases the Incidence of Severe BK Virus-Associated Hemorrhagic Cystitis In Allogeneic HSCT Recipients

AbstractAbstract 2317 Introduction:The polyoma virus BK is present in the urothelial tract of the majority of patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Urothelial damage by the conditioning regimen triggers early viral replication and subsequent immune mediated damage to the urothelium. Clinical manifestations of BK virus-associated hemorrhagic cystitis (BKHC), with typical onset in the first 100 days after HSCT, range from asymptomatic microscopic hematuria to massive life threatening blood loss and urinary obstruction. There is no standard prophylaxis or treatment for BKHC. The antibacterial fluoroquinolones have been shown in vitro to inhibit BK viral replication by direct inhibition of the BK encoded DNA gyrase. Therefore, we hypothesized that extended prophylaxis with the fluoroquinolone ciprofloxacin might decrease the incidence of severe BKHC after HSCT. Methods:In March 2009 we began prescribing prophylaxis for BKHC with ciprofloxacin 500 mg orally twice daily from day 0 until day 60 after transplantation in all allograft recipients (except patients allergic to ciprofloxacin). Patient and transplant variables, as well as incidence of severe BKHC, were collected retrospectively for all consecutive patients undergoing allogeneic HSCT between June 2006 and July 2010. Severe BKHC was defined as grades 3 or 4 hemorrhagic cystitis with evidence of urinary excretion of BK virus by polymerase chain reaction. We estimated the incidence of severe BKHC and the survival free of severe BKHC for patients receiving (ciprofloxacin group) or not (control group) prophylaxis. Additionally, we performed a multivariate analysis to assess the independent role of ciprofloxacin prophylaxis in preventing episodes of severe BKHC. Results:Eighty-one consecutive patients were included in the analysis, of which 33 received ciprofloxacin prophylaxis. Median age of patients was 50 years (range 19–70) and 37% were female. Overall 47% of patients received a myeloablative conditioning regimen and 60% had an alternative (not HLA-matched sibling) donor. Median follow up for patients in the ciprofloxacin and control groups were respectively 180 (range 33–504) and 515 days (range of 29–1645). There was no difference in overall survival between ciprofloxacin and control groups. Episodes of severe BKHC occurred after a median of 60 days (range 27–118) after transplantation and were less frequent in the ciprofloxacin than in the control group (2.9% vs. 22.9%, chi-square test P= 0.01). Survival free of severe BKHC was also significantly superior in the ciprofloxacin group (Log-rank test P=0.04; Figure). In a multivariate Cox-regression analysis including age, gender, intensity of the conditioning regimen, use of mesna during conditioning and alternative donor, only the use of ciprofloxacin prophylaxis was significantly associated with the endpoint survival free of severe BKHC (P=0.01). There were no complications associated with prolonged use of ciprofloxacin, in particular no increase in Clostridium difficile associated diarrhea. Conclusion:Ciprofloxacin prophylaxis appears safe and effective in reducing the incidence of severe BKHC after allogeneic HSCT. This finding requires confirmation with a prospective randomized trial. [Display omitted] Disclosures:Off Label Use: Ciprofloxacin- prevention of BK associated hemorragic cystitis.

MESNA for chemically assisted tissue dissection

Importance of the field: To date, surgical dissection is based only on mechanical forces. The use of a chemical product that is able to ease tissue dissection represents an important advance. MESNA (sodium-2-mercaptoethanesulfonate) has recently been validated for chemically assisted tissue dissection during surgery or invasive procedures. No other drugs are available for this.Areas covered in this review: An extensive literature search was conducted that included published articles and abstracts on the use of MESNA during surgery or invasive procedures in the experimental and clinical setting, since 1997. Clinically validated settings are ear, nose and throat (ENT), gynecological and orthopedic fields.What the reader will gain: A state-of-the-art overview of intraoperative applications of MESNA, and a consideration of the possible mechanisms underlying chemically assisted tissue dissection.Take home message: MESNA has been successfully used to ease abdominal myomectomies and excision of endometrial cysts; in ENT surgery, topical MESNA could be widely used, from ear and skull base to head and neck diseases, in both outpatient and operating-room settings. In revision lumbar spine surgery, its use resulted in significantly easier surgery and reduction of postoperative complications. Given the high efficacy and favorable complications rate, future applications in the surgical field are expected to increase.

Effectiveness of a mucolythic agent as a local adjuvant in revision lumbar spine surgery

Aim of this prospective randomized trial was to analyze the effectiveness of MESNA in chemical dissection of peridural fibrosis in patients who underwent revision lumbar spine surgery. Between January 2003 and October 2006, 30 patients who underwent revision lumbar spine surgery were enrolled in the study. Patients were randomly assigned to one of two groups: a study group (A) and a control group (B). Once peridural fibrosis was exposed, MESNA (Uromixetan MESNA, 50 mg/ml) was intraoperatively applied on the fibrous tissue (Group A) to ease tissue dissection and enter the canal. In patients of Group B, saline solution was used. Surgical time, preoperative and 1 week postoperative hemoglobin (Hb), length of hospitalization (days), and incidence of perioperative complications were evaluated. The blinded surgeon assigned the surgeries to one of four categories as none, minimal, moderate, and severe basing on intraoperative difficulty in dissecting the fibrous tissue and intraoperative bleeding. Statistical analysis used chi-square analysis to evaluate the difference in surgery difficulty and the incidence of intraoperative complications between the two groups. The analysis of surgical time and hemoglobin levels was performed using a one-sample Wilcoxon test and Mann-Whitney U test. Patients in whom MESNA was used intraoperatively (Group A) presented better intraoperative and perioperative parameters with respect to the control group. Average surgical time and decrease in Hb postoperatively were more in the saline group (B) respect to MESNA (A) (P = 0.004 and P = 0.001, respectively), while no difference in average hospital stay was reported between the two groups. Surgeon-blinded intraoperative report on surgical difficulty showed a significant difference between the two groups (P < 0.05). Postoperatively, no complications directly attributable to the use of MESNA were experienced. The incidence of dural tears and intraoperative bleeding from epidural veins were significantly less in Group A with respect to the control group. MESNA contributed significantly to reduce the operative complications, with a diminution of the surgical time and the grade of difficult for the surgeon, confirming its ability as chemical dissector also for epidural fibrosis in revision lumbar spine surgery.

Chemically assisted endoscopic mechanical submucosal dissection by using mesna

A class of thiol compounds, mesna (sodium-2-mercaptoethanesulfonate), has been used to facilitate tissue dissection in surgical fields. To evaluate the technical feasibility and efficacy of chemically assisted endoscopic mechanical submucosal dissection (CAEMSD) by using mesna. An in vivo controlled blind trial by using porcine models. Nonsurvival study in an animal laboratory. Six pigs were studied. Mucosal targets of about 2 cm (estimated) for treatment were created with a circle of cauterized spots along the greater curvature of the gastric body and the antrum. A mesna solution or the control hydroxypropyl methylcellulose solution was submucosally injected. The target mucosa was mechanically isolated with balloon dissection and removed by circumferential incision with a hook-knife inserted into the submucosal space. Necropsy and mucosal specimens from both groups were examined by histology. En bloc resection of the target was achieved in all 8 attempts of the mesna group and in 7 of 8 attempts of the control group. Use of mesna significantly reduced tissue resistance to the initial balloon-catheter insertion into the submucosa and the technical difficulty of subsequent submucosal balloon dissection by using a subjective grading system (P < .05). There was no difference in histology between both groups. CAEMSD is a unique methodology to facilitate mucosal resection.

Practical Use of MESNA in Atelectatic Ears and Adhesive Otitis Media

Objective: MESNA is a synthetic sulfur compound that produces mucolysis by disrupting disulfide bonds. This study aimed to address indications and technique of MESNA application in otologic surgery, especially in retraction pockets and adhesive otitis media. Methods: MESNA application was performed in 42 ears of 39 patients. The diagnoses were retraction pockets fixed to incudostapedial joint, stapes or promontorium, and adhesive otitis media in 24 and 17 ears, respectively. Calculations were performed according to 24 ears of 23 patients with follow-up data. Results: One or more of the following surgical interventions were performed: MESNA application alone and ventilation tube insertion, reinforcement or mastoidectomy in addition to MESNA application. Sensorineural hearing loss was not encountered after MESNA application. The operation was successful in 79.2%. Overall revision surgery was needed in 20.8% of the ears. In 71.4% of the ears treated with MESNA alone, revision surgery was needed. Conclusion: In the light of our experience, we advocate the use of MESNA in atelectatic ears, because it makes the operation easy and safe by allowing elevation of the tympanic membrane by its mechanical and chemical actions.

Amifostine and glutathione prevent ifosfamide- and acrolein-induced hemorrhagic cystitis

Ifosfamide (IFS) is an antineoplastic alkylating agent whose major side effect is hemorrhagic cystitis (HC). This toxicity is attributed to the renal excretion of acrolein (ACR), a highly urotoxic IFS metabolite. Despite the clinical use of mesna to prevent HC, a significant percent ( approximately 33%) of patients present with at last one feature of HC, mainly hematuria. To investigate the use of two antioxidants-amifostine and glutathione-for the prevention of experimental IFS- and ACR-induced HC. Male Swiss mice were treated intraperitoneal (i.p.) with saline (control), glutathione (125, 250 or 500 mg/kg) or amifostine (25, 50 or 100 mg/kg), and 30 min later they received a single i.p. injection of IFS at a dose of 400 mg/kg. To investigate the systemic effects of the antioxidants on ACR-induced HC, the animals were treated with saline, amifostine (50 mg/kg, i.p.) or glutathione (500 mg/kg, i.p.), and 30 min afterward with 75 mug ACR intravesically (i.ve.). In another set of experiments, the antioxidants were injected directly into the bladder, where the mice received a single i.ve injection of ACR (75 mug) plus amifostine (1.5 mg/kg) or glutathione (2 mg/kg). HC was measured 3 h after IFS or ACR injection according to bladder wet weight, macroscopic (edema and hemorrhage) and microscopic changes, i.e., edema, hemorrhage, cellular infiltration, fibrin deposition and urothelial desquamation. Pretreatments with amifostine or glutathione prevented IFS-induced HC in a dose-dependent manner. Furthermore, ACR-induced HC was also prevented by systemic (i.p.) or local (i.ve.) pretreatment with glutathione or amifostine. The greatest protective effect was seen with local amifostine treatment (2 mg/kg i.ve.) (P < 0.05). Glutathione and amifostine show a beneficial effect in experimental IFS- and ACR-induced HC. Thus, they should be investigated as an alternative treatment to prevent HC observed in patients undergoing IFS treatment.

Cyclophosphamide or ifosfamide in patients with advanced and/or recurrent endometrial carcinoma: a randomized phase II study of the EORTC Gynecological Cancer Cooperative Group

Currently, available chemotherapy regimens for patients with advanced or recurrent endometrial cancer are generally not curative. Thus, there is a need to identify more active single agents in this disease. In this study patients pre-treated and not pre-treated with first line combination chemotherapy were entered into a randomized phase II study of either cyclophosphamide (CYCLO) or Ifosfamide (IFOS). Patients and method: Sixty one eligible patients with recurrent or metastatic histologically proven, adenocarcinoma of the uterine corpus entered the study. The median age at entry was 62 (range 40–74) years. Twenty patients (33%) had prior hormonal treatment and 31 (51%) prior chemotherapy. CYCLO was given at a dose of 1200 mg/m2 and IFOS at a dose of 5 g/m2. Both drugs were administered i.v. over 24 hours on day one every three weeks. Adequate pre- and post hydration as well as use of Mesna in the Ifosfamide arm were mandatory. Results: A median of two treatment cycles (range 1–12) per patient were given. In the chemotherapy-naive patients, in the CYCLO arm two PRs (RR 14%, C.I. 2–43%) were seen and in the IFOS arm two CRs, two PRs, (RR 25%, C.I. 7–52%) were observed. No responses were seen in pre-treated patients. The duration of responses were: 15+, 7+ months for the CRs, 15+ and 5 months for PRs in IFOS arm and 67+, 4 months in CYCLO arm. The hematological toxicity was dose-limiting and similar in both treatment arms. No serious non hematological toxicities were reported, but a transient increase of the creatinine blood level was seen in two IFOS patients (6%). Conclusion: Ifosfamide is an active drug in the treatment of chemotherapy-naive patients with advanced endometrial cancer and its application in currently used (combination) regimens should be considered.

Use of mesna to prevent ifosfamide-induced urotoxicity.

The purpose of this study was to make evidence-based recommendations regarding the mode, dosage and schedule of delivery of concomitant mesna (sodium-2-mercaptoethanesulfonate) to protect against ifosfamide-induced uroepithelial toxicity. A critical review of the literature from 1966 to 1996 was undertaken on mesna administration via the intravenous, oral, or combined modality routes. Outcome measures of urinary symptoms and macrohematuria were emphasized, since these endpoints of urotoxicity are most clinically relevant. The quality of evidence obtained from published clinical research was evaluated based on guidelines developed by the Canadian Task Force on the Periodic Health Examination. Recommendations are now made according to the strength of available evidence on the proper usage of mesna as a protective agent against ifosfamide-induced urotoxicity. There is good evidence that the use of mesna significantly reduces urinary symptoms of dysuria and frequency, as well as the incidences of macrohematuria and microhematuria, when administered concurrently with any dosage of ifosfamide regardless of tumor site. Mesna, given intravenously or orally, is superior to standard prophylaxis with vigorous hydration and alkalinization of urine. A commonly used schedule of intravenous mesna involves a dose equal to 60% of the total ifosfamide dose, divided into three aliquots and administered at 0 h, 4 h and 8 h after ifosfamide. Combined oral and intravenous mesna delivered in some tested schedules is equivalent to intravenous mesna alone, but the optimal schedule and dosage of combined formulation have not yet been established. There is fair indirect but no direct evidence that oral mesna alone is equivalent to intravenous mesna or combined modality use. Further research issues, such as patient compliance with oral mesna and other routes of mesna delivery, are discussed. Ongoing study in the appropriate use of mesna is needed to maximize its value as a uroprotective agent in the clinical setting.