Impact of extended infusional mesna prophylaxis on the incidence of BK viruria and hemorrhagic cystitis following post-transplantation cyclophosphamide and CTLA4Ig-based haploidentical transplantation.

Hemorrhagic cystitis (HC) has been reported with increased frequency following post-transplantation cyclophosphamide (PTCy)-based haploidentical hematopoietic cell transplantation (HCT) along with a strong association with BK viruria. We prospectively evaluated the incidence of BK viruria and HC in 115 patients (median age 20 years, 2-65) undergoing PTCy-based haploidentical HCT with (n = 71) or without (n = 44) CTLA4Ig. HC prophylaxis consisted of a continuous infusion of mesna 30 min prior and 48 h post-PTCy. The overall incidence of BK viruria was 65.7%. None with BK viruria < 104 copies/ml developed clinical symptoms (n = 65). The incidence of BK viruria ≥ 104 copies/ml was 7.1% (n = 8) and 75% developed HC. The incidence of HC was 5.4% at a median of 30 days. Both BK viruria ≥ 104 copies/ml and HC were strongly associated with acute GVHD (p < 0.001). A higher NRM was observed in those with BK viruria ≥ 104 copies/ml, related to GVHD and its complications (41.7% vs 12.6%, p = 0.04). The incidences of acute GVHD, vis-à-vis, overall BK viruria, BK viruria ≥ 104 copies/ml, and HC, tended to be lower in patients receiving CTLA4Ig. Thus, extended infusional mesna, coupled with significant reduction in alloreactivity along with possible preservation of antiviral immunity associated with the use of CTLA4Ig, was probably responsible for a much lower incidence of BK viruria and resultant HC than reported previously following PTCy-based haploidentical HCT.

Topical Application of High-Dose Mesna Prevents Adhesion Formation: An Experimental Animal Study.

BACKGROUND: Adhesion formation is a common complication of abdominal surgeries. Mesna is a drug with fibrinolytic properties which has been used in surgical field to facilitate tissue dissection. The aim of this experimental animal study was to investigate the effect of mesna on prevention of intra-abdominal adhesion in rats. MATERIALS AND METHODS: Twenty-eight Wistar albino rats were used in the study. To create abdominal adhesion, cecum was abraded in all rats. No additional surgical procedure was performed other than adhesion in group 1 (only adhesion). In the other groups, rats were treated topically by administering 0.9% saline (group 2), 40 mg/kg mesna (group 3), and 400 mg/kg mesna (group 4). All rats were sacrificed on postoperative 21st day. Histopathological and macroscopic evaluations of adhesion formation were performed. RESULTS: Quantity of adhesion scores (P = 0.022), severity of adhesion scores (P = 0.041), total adhesion scores (P = 0.023), and histopathological adhesion grading scores (P < 0.001) were reduced by 400 mg/kg mesna. CONCLUSIONS: This is the first study for mesna on prevention of abdominal adhesion formation in rats. We concluded that dose-dependent reduction of adhesion was achieved by mesna. With future studies, topical administration of mesna during open abdominal surgeries may be used to prevent adhesion formation.

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

OBJECTIVE: 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. METHODS: 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 20 months after the operation. Air-conduction thresholds, bone-conduction thresholds and air-bone difference were statistically compared. RESULTS: The patients were followed-up for a mean 20.48 ± 2.37 months. The mean preoperative air-conduction threshold of the patients was 58.09 ± 9.73 dB and the mean postoperative air-conduction threshold was 34.63 ± 15.46 dB and there was a significant difference. The mean preoperative bone-conduction threshold of the patients was 16.27 ± 5.47 dB and the mean postoperative bone-conduction threshold was 14.72 ± 6.11 dB 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. CONCLUSION: 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.

Clinical Outcome of Neoadjuvant Radiochemotherapy in Locally Advanced Cervical Cancer: Results of an Open Prospective, Multicenter Phase 2 Study of the North-Eastern German Society of Gynecological Oncology.

OBJECTIVE: The aim of this study was to determine the response rate, toxicity, operability, and surgical complication rate of neoadjuvant concomitant radiochemotherapy (cRCH) (ifosfamide + carboplatin) followed by radical hysterectomy plus external-beam radiotherapy with curative intention in locally advanced primary inoperable stages IIB and IIIB squamous cell cervical cancer. METHODS: Patients with cervical cancer from 8 departments were enrolled. Patients received 3 cycles of ifosfamide 1.2 mg/m (+mesna 20%) plus carboplatin (area under the curve = 4), every 21 days, and concomitant external-beam radiotherapy (50.4 Gy [1.8 Gy/d]). Operability and remission were evaluated by clinical gynecological examination in general anesthesia (magnetic resonance imaging was optional), 4 weeks after the third cycle of cRCH. In case of achieved operability, a radical hysterectomy with pelvic lymphadenectomy was performed within 6 weeks after cRCH. If surgery was not performed because of incomplete remission or patient preferences, vaginal brachytherapy (15 Gy [5 Gy/d]) was given additionally. RESULTS: Forty-four patients were enrolled. Distribution of FIGO (International Federation of Gynecology and Obstetrics) tumor stage was as follows: IIB (19 patients) and IIIB (25 patients). All patients completed cRCH. Grade 3/4 hematologic toxicities (% of all cycles) were moderate: leukopenia, 7.3; thrombocytopenia, 2.4; and anemia, 3.2. In 13.8%, treatment cycles were delayed because of hematologic toxicity. Blood transfusions were given in 17.7% and granulocyte colony-stimulating factor in 39.5%. Overall, grade 3/4 nonhematologic toxicities were seldom (6.5%). Clinical overall response rate was 95.2%. Operability was achieved in 85.7%. Surgery was performed in 83.3%. Pathological response rates were as follows: pathological complete remission, 33.3%; partial remission, 63.3%; stable disease, 3.3%. CONCLUSIONS: Our study demonstrates that cRCH is an effective and tolerable regimen in locally advanced cervical cancer treatment.

A feasibility study of chemically assisted endoscopic submucosal mechanical dissection using mesna for superficial esophageal squamous cell carcinomas.

BACKGROUND: Injection of mesna into submucosal layers was recently reported to chemically soften connective tissue and facilitate the gastric endoscopic submucosal dissection (ESD) procedure. This study aimed to evaluate the safety and feasibility of similarly using mesna for esophageal ESD (mesna ESD). METHODS: We performed mesna ESD in 20 consecutive patients with superficial esophageal squamous cell carcinomas (SESCCs). To do this, a submucosal fluid cushion was initially formed using sodium hyaluronate, and the esophageal lesion was circumferentially isolated with a short blade needle-knife. Mesna solution was then injected into the submucosal layer, which was dissected mechanically by cleavage using the tip of a cap-fitted endoscope. The number of electrosurgical incisions was recorded by computer software in real time. The data from 20 conventional ESD procedures without mesna (consecutive 10 SESCCs pre and post the 20 consecutive mesna ESD) were used for comparison to evaluate the mesna ESD. RESULTS: The mesna ESDs achieved en bloc and R0 resection success rates of 100 and 95 %, respectively. There was no perforation or uncontrollable hemorrhage during and after mesna ESD, and the median procedural time of submucosal dissection was significantly less with mesna ESD than with conventional ESD (median; 8 vs. 15 min, P < 0.05). There were also significantly fewer electrosurgical incisions made during the mesna ESD than with conventional ESDs (median; 65 vs. 183 times, P < 0.01). CONCLUSIONS: Mesna ESD for SESCCs is a safe procedure with the potential to facilitate esophageal ESD.

After myringotomy, can topical Mesna application be an alternative method to ventilation tube application?

Sodium-2-mercaptoethanesulfonate (Mesna) is a mucolytic substance that is also used for chemically assisted tissue dissection in otological surgery. We investigated the effects of Mesna as a chemical agent on the closing time of perforation of the eardrum in an experimental animal model. We performed simple myringotomy with a knife on 44 tympanic membranes of 22 rats. Four rats were excluded from the study because of serosity in their ears. Rats were divided into two study groups and a control group. These groups were the Mesna-administered group (Group A) (8 rats, 15 tympanic membranes), the saline-administered group (Group B) (8 rats, 14 tympanic membranes) and the control (native) group (6 rats, 11 tympanic membranes) (Group C). We applied Mesna locally for 20 min following myringotomy. Examination was made with an otoendoscope on days 1, 2, 3, 5, and 7, and patency rates were recorded. According to our results, we found that the closing time of the tympanic membrane was significantly longer in the Mesna group than in the saline administrated and native group. After myringotomy procedure, the application of a single dose of Mesna may contribute to the recovery duration of middle-ear pathologies by delaying the closing time of tympanic membrane perforation. However, Mesna cannot be an alternative method for the application of ventilation tubes.

Chemically assisted peroral endoscopic myotomy with submucosal mesna injection in a porcine model.

BACKGROUND: Peroral endoscopic myotomy (POEM) is a less invasive alternative to standard surgery for the treatment of achalasia. Previous studies have demonstrated that submucosal injections of mesna soften tissues and facilitate endoscopic submucosal dissection. MATERIAL AND METHODS: We studied the technical feasibility of a chemically assisted POEM procedure with mesna injection (CA-POEM) in ten pigs compared with POEM with saline injection in five pigs. We also compared two dissection techniques in CA-POEM, diathermy needle knife dissection (n = 5) and balloon mechanical dissection (n = 5). A 10 cm esophageal submucosal tunnel was created with a needle knife or with balloon mechanical dissection following mesna or saline submucosal injection. Approximately 5 cm of inner circular muscle was then dissected within the tunnel. The tunnel was closed with endoclip application at the mucosal endoscopic entry point. Pigs were sacrificed one week post procedure. RESULTS: All procedures were successful and all pigs survived for one week. Submucosal tunneling time was significantly shorter in the mesna group (363.8 sec for needle knife dissection and 294.2 sec for balloon dissection) than in the saline group (640 sec), regardless of the dissection method (p < 0.05). CONCLUSIONS: Our study demonstrated the technical feasibility of CA-POEM.

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

BACKGROUND: 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). OBJECTIVE: To evaluate whether mesna injection could reduce procedural times for gastric ESD. DESIGN: Double-blind, block-randomized, controlled trial. SETTING: University hospital. PATIENTS: 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. INTERVENTION: Traditional ESD was performed with a single bolus injection of mesna or saline solution. MAIN OUTCOME MEASUREMENTS: Time for submucosal dissection (TSD). RESULTS: 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). LIMITATIONS: Single-center study. CONCLUSION: 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. ( CLINICAL TRIAL REGISTRATION NUMBER: UMIN000003786.).

Factors determining pbsc mobilization efficiency and nonmobilization following ICE with or without rituximab (R-ICE) salvage therapy for refractory or relapsed lymphoma prior to autologous transplantation.

ICE/R-ICE (ifosfamide, carboplatin, and etoposide without or with rituximab) chemotherapy followed by autologous stem cell transplantation is an established regimen in refractory/relapsed lymphoma. Few studies have addressed which factors are important in determining peripheral blood stem cell (PBSC) mobilization efficiency or nonmobilization following ICE/R-ICE. Between 2004 and 2013, 88 patients with refractory/relapsed lymphoma who received ICE/R-ICE salvage-chemotherapy prior to granulocyte colony stimulating factor (G-CSF) stimulated PBSC mobilization at a single center were identified. Mobilization efficiency was assessed by time from ICE/R-ICE to day of harvest, duration of G-CSF use, days to peripheral blood (PB) CD34(+) ≥15/µL, PB CD34(+) number on harvest day, CD34(+) yield and nonmobilization rate. Median PB CD34(+) at harvest were 54/µL (7-524); median days to first apheresis was 15 (11-30); median harvested total CD34(+) were 5.46 × 10(6) /kg (0.96-44.36); 71 patients (80.7%) successfully mobilized; 20 (22.7%) patients were poor mobilizers; 14 (15.9%) patients were considered nonmobilizers with maximal PB CD34(+) <7/µL and did not proceed to apheresis. Six of 20 poor mobilizers were apheresed with PB CD34(+) 7-12/µL, 50% were successfully harvested. No differences were found between ICE and R-ICE regimens. Impaired mobilization efficiency was associated with age, remission status, >1 line of induction chemotherapy, four cycles ICE/R-ICE and grade 4 neutropenia. Prior bone marrow (BM) involvement was associated with nonmobilization. The majority of patients can be successfully mobilized with ICE/R-ICE. Prior BM involvement is associated with high rates of nonmobilization following ICE/R-ICE. Such patients may benefit from novel mobilization agents and/or alternative salvage regimens to ICE/R-ICE.

Physical and chemical stability of high-dose ifosfamide and mesna for prolonged 14-day continuous infusion.

PURPOSE: Ifosfamide plus mesna have been used recently in a high-dose regimen that allows this chemotherapy to be given to outpatients with less toxicity over 14 days using a portable pump. However, there is a need for published stability information. The aim of this study was to investigate the physicochemical stability of ifosfamide with mesna in normal saline at room temperature over a prolonged period of 14 days. METHODS: Infusion solutions of 1:1 ifosfamide and mesna at final concentrations of 10, 20 and 30 mg/mL were prepared with 0.9% sodium chloride in PVC bags. Solutions were stored at room temperature. Concentrations of ifosfamide and mesna were measured at 0 and 1, 3, 7 and 14 days using a stability-indicating reversed phase high-performance liquid chromatography (HPLC) assay with ultraviolet detection. RESULTS: Ifosfamide and mesna were both physicochemically stable (>94%) for 14 days in all tested infusion solutions (10, 20 and 30 mg/mL). CONCLUSIONS: Our stability data indicate that ifosfamide and mesna (1:1) combination can be administered as a prolonged continuous infusion with portable pump in an outpatient setting without replacement of the infusion bag. We suggest 20 mg/mL as a reasonable concentration for infusion rates of about 2-4 cc/hr over prolonged periods of time.

Effectiveness of MESNA on the success of cholesteatoma surgery.

IMPORTANCE: It is important that chronic otitis media with cholesteatoma be treated successfully in patients to protect them from having repeated surgeries with related surgical co-morbidities and hearing loss. OBJECTIVE: To evaluate the effectiveness of MESNA usage on the residual cholesteatoma rates of the patients who underwent surgery due to chronic otitis media with cholesteatoma. DESIGN: Retrospective single-institution study of a prospectively collected database. SETTING: Tertiary University Hospital. PARTICIPANTS: Nine hundred and thirty-four patients underwent surgery due to chronic otitis media between September 2000 and March 2012 by the same surgeon. One hundred and forty-one cases out of 934 patients were selected who had cholesteatoma for the study. These randomly selected 141 cases were divided into two groups as follows: I. Forty-six cases were applied MESNA (Sodium 2-mercaptoethanesulfonate) intraoperatively, and II. Ninety-five cases were not applied MESNA intraoperatively. The cases that were followed-up at least one year were included in this study. INTERVENTION: MESNA (Ureomitexan, MESNA, Baxter oncology, Germany) was diluted with saline (20% MESNA and 80% saline) that was applied, and then a waiting period of approximately 5 min followed to start to dissect cholesteatoma matrix. MAIN OUTCOMES AND MEASURES: Residual cholesteatoma rates between intraoperative MESNA, a disulfide bond breaking chemical agent, applied and MESNA non-applied cases in the postoperative follow-up period were compared for the success of the surgery. RESULTS: MESNA was used in 46 patients out of 141 cases intraoperatively. Twenty-four of these patients underwent CWD (canal wall down), and twenty-two patients underwent CWU (canal wall up) mastoidectomy. For the other 95 subjects, 56 patients with CWD and 39 with CWU mastoidectomy, MESNA was not applied. Residual cholesteatoma rates were found to be significantly higher in MESNA non-applied group than MESNA applied group (p<0.05). Residual cholesteatoma rates between CWD and CWU mastoidectomy procedures were not statistically significant (p>0.05). CONCLUSIONS AND RELEVANCE: MESNA application that breaks disulfide bonds in the structure of the matrix in cholesteatoma surgery may assist the elimination of the disease, and increase surgical success by facilitating the elevation of the epithelium. Thereby, it causes a decrease in the possibility of remaining residual epithelium after surgery, which decreases the need for second-look surgery. TRIAL REGISTRATION: The retrospective research protocol was approved by the Inonu University Clinical Research Ethics Committee. REGISTRATION NUMBER: ………

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.

Mesna, Doxorubicin, Ifosfamide and Dacarbazine (MAID) Combination Chemotherapy for Retroperitoneal Sarcoma: A Single-center Experience.

BACKGROUND/AIM: There is limited evidence regarding the systemic treatment of retroperitoneal soft-tissue sarcoma, and the current Japanese guidelines fail to make definitive suggestions. Here, we report our experience with combination chemotherapy of mesna, doxorubicin, ifosfamide, and dacarbazine (MAID) in this population. PATIENTS AND METHODS: We retrospectively reviewed the records of eight patients (three male and five female) who received MAID for pathologically diagnosed metastatic unresectable retroperitoneal sarcoma (either leiomyosarcoma or pleomorphic sarcoma) between October 2019 and January 2022. Treatment efficacy, tolerability (need for dose reduction), and safety profiles were evaluated and summarized. RESULTS: At initiation, the median age was 56.0 years, and the body mass index was 20.0 kg/cm2 Six patients had Eastern Cooperative Oncology Group performance status scores of 0. The net clinical benefit was a partial response in three (37.5%) patients, stable disease in four (50.0%), and progressive disease in one (12.5%). During the median 90.8 weeks of follow-up, disease in five patients progressed, resulting in a median progression-free survival of 48.4 weeks, and five deaths occurred, resulting in an overall survival of 95.1 weeks. Commonly observed adverse events were neutropenia (eight patients), anemia (eight patients), and decreased platelet count (seven patients), which led to dose reduction (60-80%) in six patients. CONCLUSION: MAID combination therapy may be an acceptable option for advanced retroperitoneal sarcoma; however, its benefits must be carefully assessed owing to its not insignificant toxicity.

Neoadjuvant and adjuvant chemotherapy with modified mesna, adriamycin, ifosfamide, and dacarbazine (MAID) regimen for adult high-grade non-small round cell soft tissue sarcomas.

BACKGROUND: Good local control of high-grade non-small round cell soft tissue sarcomas (NSRCSTSs) has been achieved with significant advances in surgical techniques and radiotherapy. However, the role of chemotherapy remains controversial. Our aim was to investigate the efficacy, feasibility and adverse effects of neoadjuvant and adjuvant chemotherapy with modified mesna, adriamycin, ifosfamide and dacarbazine (MAID) regimen for NSRCSTSs. METHODS: We conducted a retrospective review of 40 consecutive patients (29 men, 11 women; median age 47 years) with high-grade NSRCSTSs treated in two referral centers between 2004 and 2009 (median follow-up 38.5 months). Patients with distant or nodal metastases at diagnosis were excluded. The regimen consisted of ifosfamide 2,500 mg/m(2)/6 h (days 1-3), mesna 2,500 mg/m(2)/6 h (days 1-3), tetrahydropyranyl adriamycin 20 mg/m(2)/0.5 h (days 1-3), and dacarbazine 300 mg/m(2)/1 h (days 1-3). RESULTS: Among the 26 evaluable patients, there were 8 with a partial response, 15 with stable disease, and 3 with progressive disease. Two- and 5-year overall survival rates were 92 and 86%, respectively, and corresponding disease-free survival rates were 80 and 77%. All relapses were metastases without local recurrence. Grade 3-4 neutropenia, anemia and thrombocytopenia were observed in 38, 18, and 21 patients, respectively. No serious infectious complications occurred due to the administration of granulocyte colony-stimulating factor and prophylactic antibiotics. No other life-threatening serious adverse events were observed. CONCLUSION: The modified MAID regimen achieved a better outcome with less serious adverse events than previously reported and is a potential option in the management of NSRCSTSs. Further evaluation with long-term follow-up is required.

Patterns of chemotherapy-induced toxicities in younger children and adolescents with rhabdomyosarcoma: a report from the Children's Oncology Group Soft Tissue Sarcoma Committee.

BACKGROUND: Patients aged >10 years with rhabdomyosarcoma have an inferior outcome compared with patients ages 1 to 9 years, which may be explained by toxicities (adverse events [AEs]) that result in chemotherapy dose reductions. METHODS: AEs observed during 1 of 3 randomized chemotherapy regimens (vincristine, dactinomycin, and cyclophosphamide [VAC]; vincristine, dactinomycin, and ifosfamide [VAI]; or vincristine, ifosfamide, and etoposide [VIE]) in the Fourth Intergroup Rhabdomyosarcoma Study were recorded. The incidence of toxicities by age and treatment regimen was determined. The odds of developing AEs in a particular age group (ages 5-9 years, 10-14 years, and 15-20 years) were compared with the odds in the control group of patients ages 1 to 4 years. RESULTS: In total, 657 patients were eligible for analysis. The estimated 5-year event-free survival rates were 78%, 83%, 67%, and 58% for the groups ages 1 to 4 years, 5 to 9 years, 10 to 14 years, and 15 to 20 years, respectively. Patients ages 15 to 20 years experienced less neutropenia (odds ratio [OR], 0.43; P < .0001), thrombocytopenia (OR, 0.41; P < .0001), anemia (OR, 0.34; P < .0001), and infection (OR, 0.41; P < .0001) compared with younger patients, although they received similar amounts of chemotherapy. In contrast, peripheral nervous system toxicity was higher in adolescents aged >10 years (OR, 4.18; P < .0001). Females experienced more neutropenia (OR, 1.28; P = .05) and thrombocytopenia (OR, 1.26; P = .06) compared with males. CONCLUSIONS: Adolescents who received treatment for rhabdomyosarcoma experienced significantly less hematologic toxicity and more peripheral nervous system toxicity compared with younger children despite receiving similar amounts of chemotherapy. Although outcomes were inferior in adolescents, it was unclear whether the differences in toxicity observed in the current study had an impact on outcome. The authors concluded that future studies examining the age-related and sex-related differences in pharmacokinetics of chemotherapy are necessary.

Treatment of Burkitt lymphoma in equatorial Africa using a simple three-drug combination followed by a salvage regimen for patients with persistent or recurrent disease.

Prior to the introduction of the International Network for Cancer Treatment and Research (INCTR) protocol INCTR 03-06, survival of patients with Burkitt lymphoma at four tertiary care centres in equatorial Africa was probably no more than 10-20%. The results reported here for 356 patients have demonstrated marked improvement in survival through the use of a uniform treatment protocol consisting of cyclophosphamide, methotrexate, vincristine, and intrathecal therapy, and the introduction of non-cross resistant second-line (salvage) therapy, consisting of ifosfamide, mesna, etoposide and cytarabine, when patients failed to achieve a complete response to first-line therapy or relapsed early. Overall survival rates of 67% and 62% were observed at 1 and 2 years (relapse is rare after 1 year of remission). Of interest was the small impact of cerebrospinal fluid (CSF) and bone marrow involvement on outcome. However, the presence or absence of abdominal involvement clearly defined two prognostic groups. An additional finding was the association between CSF pleocytosis and orbital tumours, suggesting that spread of tumour cells to the central nervous system may sometimes occur via direct involvement of cranial nerves in the orbit. Survival rates may be increased in patients with abdominal involvement by combining first- and second-line therapy, but verification will require a further clinical study.

High-dose chemotherapy consolidation for chemosensitive advanced soft tissue sarcoma patients: an open-label, randomized controlled trial.

BACKGROUND: Metastatic soft tissue sarcoma (STS) prognosis remains poor and few cytotoxic agents offer proven efficacy. This randomized open phase III study examines whether high-dose (HD) chemotherapy with peripheral blood stem cells (PBSCs) could improve overall survival (OS) of chemosensitive patients. PATIENTS AND METHODS: Advanced STS patients aged 18-65 years received four courses of standard mesna, adryamycin, ifosfamide and dacarbazine (MAID) treatment. Chemotherapy-responding patients and patients with at least stable disease amenable to complete surgical resection were randomized to receive standard dose (SD) with two successive MAID cycles or HD treatments of one MAID then MICE intensification: mesna (3.6 g/m(2), day 1-5), ifosfamide (2.5 g/m(2), day 1-4), carboplatin [area under the curve (AUC) 5/day 2-4] and etoposide (300 mg/m(2), day 1-4) with PBSC reinjection at day 7. RESULTS: From 2000 to 2008, 207 patients received four cycles of MAID and 87 assessable patients were randomly assigned to receive the following: 46 SD, 41 HD, with 45 and 38 maintained for analyses after secondary centralized histological review. Futility analyses led to study closure in November 2008. Three-year OS was 49.4% for the SD group versus 32.7% for HD arm, hazard ratio= 1.26, 95% confidence interval 0.70-2.29; progression-free survival was 32.4% and 14.0%, respectively. HD treatment led to higher grades 3-4 toxicity. CONCLUSION: This study failed to show an OS advantage for advanced STS patients treated with dose-intensified chemotherapy with PBSC.

Adjuvant chemotherapy decreases and postpones distant metastasis in extremity stage IIB/III synovial sarcoma patients.

BACKGROUND AND OBJECTIVES: The role of adjuvant chemotherapy (AC) in treatment of synovial sarcoma remains controversial. Aim of our study is to investigate the influence of AC on disease-specific survival and metastasis free survival, the difference in time to metastasis (TTM) was also analyzed. MATERIALS AND METHODS: Seventy-six cases of stage IIB/III synovial sarcoma from January 1993 to December 2008 were retrospectively analyzed. All the 76 patients were treated with surgical resection. AC regimen included first line MAID or AIM, second line Gemcitabine + Docetaxel with sufficient dose intensity. The clinical, pathologic, and treatment variables were analyzed for disease specific survival (DSS), metastasis free survival (MFS) and TTM. RESULTS: Median follow up period was 68 months. 51 patients received AC (51/76, 67%), 25 received no adjuvant chemotherapy (NAC, 25/76, 33%). The 5-year DSS of the AC patients was 73%(58-87%) compared with 31%(19-52%) for the NAC patients (P = 0.001). AC was also independently associated with improved MFS (P = 0.008) and prolonged TTM (P = 0.001). CONCLUSIONS: Patients with stage IIB/III synovial sarcoma might benefit in DSS, MFS, and a prolonged TTM from AC.

[Long-term remission of Langerhans cell sarcoma by AIM regimen combined with involved-field irradiation].

A 67-year-old woman presented with a right inguinal mass in May 2006. CT scan showed lymph node involvement from the right inguinal to the common iliac and (18)F-FDG-PET revealed uptake in those areas. Biopsy results indicated Langerhans cell sarcoma (LCS). Interestingly, tumor cells expressed a high MIB1 index of 30%. We administered doxorubicin, ifosfamide, and mesna (AIM) chemotherapy, which were reported to effectively treat soft tissue sarcoma. After 5 courses of AIM therapy and involved-field radiation for residual diseases and a relapsed lesion on her right cervical node, she has remained in complete remission for more than 4 years. LCS is an intractable malignant disease and the optimal therapeutic strategy remains unclear. The AIM regimen combined with radiation therapy may be an effective treatment option for this disease.

Endoscopic submucosal dissection with a flexible Maryland dissector: randomized comparison of mesna and saline solution for submucosal injection (with videos).

BACKGROUND: Endoscopic submucosal dissection (ESD) is increasingly used for en bloc removal of GI lesions. Current ESD techniques have limitations including long procedure times, technical difficulty, and complications. OBJECTIVE: To compare mesna with saline solution for ESD. DESIGN: Blinded, randomized, controlled, porcine study in live animals. SETTING: Animal laboratory. INTERVENTION: Twelve gastric lesions were marked by using electrocautery. After submucosal injection, a circumferential mucosal incision was created, and ESD was performed by using a flexible Maryland dissector. Half of the ESDs were performed with submucosal injection of mesna. MAIN OUTCOME MEASUREMENTS: Primary outcome was the time to dissect the submucosal plane. Secondary outcomes were total ESD time, specimen size, and procedure related complications. RESULTS: The average (± SD) time for dissecting the submucosal plane was 15 minutes (range 10-22 ± 4.8 min) in the group with submucosal mesna injection and 16 minutes (range 8-29 ± 8.3 min) in the control group (P = 1.0). Complete en bloc resection including all of the electrocautery markings was achieved in all cases. Injection of mesna did not provide any benefit over saline solution in terms of overall ESD time (24 ± 7.3 min vs 28 ± 11 min; P = .42). There were no perforations. Four hemorrhages requiring intervention were encountered during the procedures in the control group, compared with no bleeding in the mesna group (P = .09). LIMITATIONS: Animal model, limited sample size. CONCLUSION: Submucosal mesna injection did not affect procedure times but was associated with a trend toward a lower incidence of intraprocedural bleeding.