TAK-228 (formerly MLN0128), an investigational dual TORC1/2 inhibitor plus paclitaxel, with/without trastuzumab, in patients with advanced solid malignancies.

PURPOSE: This phase I trial evaluated the safety, pharmacokinetic profile, and antitumor activity of investigational oral TORC1/2 inhibitor TAK-228 plus paclitaxel, with/without trastuzumab, in patients with advanced solid malignancies. METHODS: Sixty-seven patients received TAK-228 6-40 mg via three dosing schedules; once daily for 3 days (QDx3d QW) or 5 days per week (QDx5d QW), and once weekly (QW) plus paclitaxel 80 mg/m2 (dose-escalation phase, n = 47) and with/without trastuzumab 2 mg/kg (expansion phase, n = 20). Doses were escalated using a modified 3 + 3 design, based upon dose-limiting toxicities in cycle 1. RESULTS: TAK-228 pharmacokinetics exhibited dose-dependent increase in exposure when dosed with paclitaxel and no apparent differences when administered with or 24 h after paclitaxel. Dose-limiting toxicities were dehydration, diarrhea, stomatitis, fatigue, rash, thrombocytopenia, neutropenia, leukopenia, and nausea. The maximum tolerated dose of TAK-228 was determined as 10-mg QDx3d QW; the expansion phase proceeded with 8-mg QDx3d QW. Overall, the most common grade ≥3 drug-related toxicities were neutropenia (21%), diarrhea (12%), and hyperglycemia (12%). Of 54 response-evaluable patients, eight achieved partial response and six had stable disease lasting ≥6 months. CONCLUSION: TAK-228 demonstrated a safety profile consistent with other TORC inhibitors and promising preliminary antitumor activity in a range of tumor types; no meaningful difference was noted in the pharmacokinetics of TAK-228 when administered with or 24 h after paclitaxel. These findings support further investigation of TAK-228 in combination with other agents including paclitaxel, with/without trastuzumab, in patients with advanced solid tumors. CLINICALTRIALS. GOV IDENTIFIER: NCT01351350.

[Outcomes of catheter ablation of atrial fibrillation in patients over 65 years of age]. / Výsledky katetrové ablace fibrilace síní u pacientu nad 65 let.

PURPOSE: This study assessed ablation techniques, recurrent arrhythmias, long-term outcomes, and complications of catheter ablation for atrial fibrillation (AF) in patients 65 years of age. METHODS: Consecutive patients aged < 65 years (n = 653) vs 65 years (n = 213), who underwent catheter ablation of AF in the course of eight years, were compared. Ablation strategy and procedure endpoints were left at the operators discretion. RESULTS: The group of patients 65 years comprised more females (p < 0.001), and more frequently presented with persistent AF (p = 0.010). These patients less frequently underwent simple pulmonary vein isolation (p = 0.017); on the contrary, extensive ablation including coronary sinus intervention was more common (p = 0.020). There was no difference in repeat ablation procedures (25 % vs 26 % patients; p = 0.823, or 1.4 vs 1.5 ablation procedures/1 patients; p = 0.479, respectively). Spectrum of recurrent arrhythmias did not differ between the groups except for more frequent paroxysmal AF before the first repeat ablation in patients < 65 years (p = 0.050). At the end of 49 ± 26 month total follow-up, stable sinus rhythm (SR) was achieved in 85 % patients < 65 years vs 76 % patients 65 years (p = 0.318). To maintain stable SR, older patients more often continued to take antiarrhythmic medication (p = 0.054). More serious complication occurred in 3.8 % of the patients 65 years vs 2.1 % of the patients < 65 years of age (p = 0.207). CONCLUSION: Patients 65 years of age achieved insignificantly worse long-term outcome after insignificantly fewer repeat ablation procedures, and with more frequent use of antiarrhythmic drugs. SR maintenance and risk of complications were, however, favorable.

[A comparison of two methods of long-term external ECG telemonitoring in patients after ablation for atrial fibrillation]. / Srovnání dvou metod dlouhodobého externího telemonitorování EKG po ablaci fibrilace síní

AIM: The aim of the study was to compare two methods of long-term ECG monitoring after atrial fibrillation (AF) ablation. METHODS: The study included 279 patients with paroxysmal (n = 163) or persistent (n = 116) AF, who were followed up for 1 year after the first catheter ablation for AF. All patients were provided with episodic ECG recorder for 1 year and instructed to send at least 2 random ECG recordings per day and whenever they sensed symptoms. They were also provided with external loop recorder for 2-3 weeks at 6 and 12 months to enable more continuous ECG monitoring. RESULTS: At the end of 39 ± 12 (12-60) month follow-up, 143 (88%) patients with paroxysmal AF, and 105 (91%) patients with persistent AF, respectively, remained in stable sinus rhythm. The efficacy of episodic recorder expressed as a ratio of patients with identified AF/atrial tachycardia (AT) out of all patients with a documented episode of AF/AT was superior to the efficacy of loop recorder. No AF/AT episode was recorded with the loop recorder that was not also documented by the episodic recorder. Of the patients with the AF/AT recurrence detected by the episodic recorder, the arrhythmia was also revealed by the loop recorder in 70% of the patients after paroxysmal AF ablation (p < 0.001), and in 52% of the patients after persistent AF ablation (p = 0.006). Asymptomatic AF/AT was present in 42 (26%) of patients with paroxysmal AF, and in 28 (24%) patients with persistent AF (p = 0.810). From conventional follow-up unexpected and clinically significant episode of AF/AT that required change in therapy was detected in 9 (5.5%) patients after ablation for paroxysmal AF, and in 4 (3.4%) patients after ablation for persistent FS. CONCLUSION: More episodes of AF/AT after ablation were detected by 1-year daily ECG monitoring using episodic recorder as compared to periodic ECG monitoring with loop recorder. Identification of clinically significant episodes of AF/AT unrecognized from conventional follow-up was low.

[Catheter ablation of atrio-ventricular accessory pathways in the era of ablation therapy of complex arrhythmias: a changing perspective for oncoming generation of electrophysiologists]. / Katetrová ablace atrioventrikulárních prídatných drah v ére ablacní lécby komplexních arytmií: menící se perspektiva pro nastupující generaci elektrofyziologu

INTRODUCTION: Catheter ablation of atrio-ventricular accessory pathways has become a routine treatment method. However, its perspective has been changing in the era of ablation of complex arrhythmias. This study was aimed at evaluating accessory pathways ablation efficacy within the last nine years at one center. METHODS: From February 2002 to June 2011, catheter ablation of accessory pathways was performed in 247 patients (100 females, 42 ± 16 years). Elimination of accessory pathways conduction in both directions was the procedure endpoint. RESULTS: Immediate accessory pathways conduction elimination at the first ablation was achieved in 228 (92%) patients. Ablation failed to eliminate accessory pathways conduction in 19 (8%) patients, or accessory pathways conduction subsequently recurred in another 7 (3%) patients. Repeat ablation was completed in 20 (8%) patients, 2 patients underwent a third ablation procedure. In total, accessory pathway was permanently eliminated in 238 (96%) patients. Ablation failure was connected with a risky position in the vicinity of atrio-ventricular conduction system in 6 (67 %) out of 9 patients. By the individual A, B, C, D operators experience, efficacy of the first procedure/total efficacy, was 97%/99%, 90%/96%, 87%/87%, and 91%/91%, respectively (comparison of inter-operator efficacy of the first and repeat ablation by Kruskal-Wallis ANOVA test: p = 0,19 and 0,05, respectively). CONCLUSION: Accessory pathways ablation efficacy exceeds 95%, and ablation failure is dominantly related to the accessory pathways location close to the atrio-ventricular conduction system. Individual operator's experience was associated with a certain disparity between high and nearly absolute accessory pathways ablation efficacy.

Efficacy and safety of bortezomib in patients with renal impairment: results from the APEX phase 3 study.

Renal impairment is associated with poor prognosis in multiple myeloma (MM). This subgroup analysis of the phase 3 Assessment of Proteasome Inhibition for Extending Remissions (APEX) study of bortezomib vs high-dose dexamethasone assessed efficacy and safety in patients with relapsed MM with varying degrees of renal impairment (creatinine clearance (CrCl) <30, 30-50, 51-80 and >80 ml min(-1)). Time to progression (TTP), overall survival (OS) and safety were compared between subgroups with CrCl < or =50 ml min(-1) (severe-to-moderate) and >50 ml min(-1) (no/mild impairment). Response rates with bortezomib were similar (36-47%) and time to response rapid (0.7-1.6 months) across subgroups. Although the trend was toward shorter TTP/OS in bortezomib patients with severe-to-moderate vs no/mild impairment, differences were not significant. OS was significantly shorter in dexamethasone patients with CrCl < or =50 vs >50 ml min(-1) (P=0.003), indicating that bortezomib is more effective than dexamethasone in overcoming the detrimental effect of renal impairment. Safety profile of bortezomib was comparable between subgroups. With dexamethasone, grade 3/4 adverse events (AEs), serious AEs and discontinuations for AEs were significantly elevated in patients with CrCl < or =50 vs >50 ml min(-1). These results indicate that bortezomib is active and well tolerated in patients with relapsed MM with varying degrees of renal insufficiency. Efficacy/safety were not substantially affected by severe-to-moderate vs no/mild impairment.

[Catheter ablation of chronic atrial fibrillation using circumferential and complex linear lesions in the left atrium: modes of arrhythmia termination and long-term clinical outcome]. / Katetrová ablace pro chronickou fibrilaci síní metodou obkruzujících a komplexních lineárních lézí v levé srdecní síni. Ukoncení arytmie pri ablaci a dlouhodobé klinické výsledky.

OBJECTIVE: The aim of the article is to present the method and results of catheter ablation for chronic atrial fibrillation. METHOD: Catheter ablation for chronic atrial fibrillation was performed in 82 patients (18 females, aged 54 +/- 10 years), in 112 ablation procedures. Mean duration of the chronic phase of atrial fibrillation was 28 +/- 28 months. Before ablation, amiodarone was administered without effect to 74 (90%) patients, and was counter-indicated in 8 (10%) patients. Ablation strategy consisted of circumferential lesions around the pulmonary veins and of complex linear lesions in the left atrium. Full pulmonary vein antra isolation, and sinus rhythm restoration, or at least converting atrial fibrillation into the left atrial tachycardia, were the procedure end points. RESULTS: Sinus rhythm was restored by ablation at least in one of the ablation procedures in 43 (52%) patients. During the follow-up period spanning 17.3 +/- 11.6 months after the last ablation, stable sinus rhythm was achieved in 63 (77%) patients, of whom 38 (60%) had their sinus rhythm restored by ablation and another 14 (22%) their atrial fibrillation converted into the left atrial tachycardia. Of the 63 patients with stable sinus rhythm, class I or III antiarrhythmic medication has been maintained in 21 (33%) patients, and amiodarone has been taken by 13 (21%) patients. CONCLUSION: Catheter ablation of chronic atrial fibrillation is potentially highly effective in long-term restoration of sinus rhythm.

[Long term effectiveness of surgical cryoablation for chronic atrial fibrillation in patients undergoing surgery for severe mitral valve regurgitation]. / Dlouhodobá úcinnost chirurgické kryoablace chronické fibrilace síní provedené pri operaci pro závaznou mitrální regurgitaci.

OBJECTIVE: The objective of the study was to evaluate effectiveness of surgical cryoMAZE ablation for chronic atrial fibrillation (AF) in patients undergoing mitral valve surgical intervention. METHODOLOGY: Forty-seven patients (31 females), aged 67.3 +/- 7.3 years who underwent surgical intervention for severe mitral regurgitation were studied. Mitral valvuloplasty was performed in 21 patients, and mitral valve replacement in 26 patients. Combined procedure was employed in 35 patients; simultaneous aortocoronary bypass was performed in 16 patients, tricuspid valvuloplasty (TVP) in 5 patients, and aortic valve replacement (AVR) in 5 patients. RESULTS: The mean follow-up time was 19 +/- 10 months. After 6 or 12 months 36 or 32 patients were seen and 23 (64%) or 22 (69%) of them were in stable sinus rhythm (SR), respectively. In the subset of 24 patients with simultaneous intervention on a different valve (TVP or AVR), after 6 or 12 months, 14 (74 %) or 15 (83 %) patients had stable SR, respectively. In the follow-up period, 2 patients underwent successful catheter ablation for type I atrial flutter or for a residual left atrial atypical flutter. CONCLUSION: In the study using the method of cryoMAZE ablation for chronic AF performed during the mitral valve surgical intervention, a long-term stable SR was achieved in a high proportion of patients, particularly in patients with simultaneous intervention on two or three different valves.

[Recurrent arrhythmias after catheter ablation of originally paroxysmal atrial fibrillation and results of repeat ablation]. / Recidivující arytmie po katetrové ablaci puvodne paroxyzmální fibrilace síní a výsledky opakované ablace.

AIMS: The aim is a description of the recurrent arrhythmias after previous ablation of paroxysmal atrial fibrillation (AF), and the results of a repeat catheter ablation. METHODS: A repeat ablation was performed in 76 patients (18 females, 54 +/- 11 years) in 96 procedures, which was 21% out of 362 patients, who had undergone the first ablation for a paroxysmal AF. The endpoints of the repeat ablation were re-isolation of the pulmonary veins (PV) and termination of a spontaneous or induced arrhythmia and restoration of a stable sinus rhythm (SR), and possibly achievement of noninducibility of any arrhythmia. RESULTS: Clinical left atrial tachycardia (LAT) was present in 10 (13%) patients before the first, and in 5 (25%) patients before the second repeat ablation. Arrhythmia arising from an arrhythmogenic PV due to the conduction recovery into the left atrium (LA) was found in 50 (66%) patients during the first, and in 7 (35%) patients during the second repeat ablation. Arrhythmias, predominantly of the reentry mechanism and originating in the LA free wall, were found in 26 (34%), respectively 13 (65%) during the first or the second repeat ablation. All arrhythmias from PVs were terminated by a PV encircling ablation. Substrate-related arrhythmias were terminated by ablation except for 2 (3%) patients during the first and 3 (15%) patients during the second repeat ablation. Persistent AF was mainly terminated via conversion into a LAT. In these cases, the ablation sites leading to the SR restoration were, similarly to the primary LATs, located predominantly in the LA anterior wall. During the 22 +/- 13 months follow-up, 68 (89%) patients were free of AF, 54 (71%) patients off the antiarrhythmic drugs and 14 (18%) patients with the class I or III antiarrhythmic drugs. CONCLUSION: AF associated with PV-LA re-connection dominated prior to the first repeat ablation, then the proportion of the substrate-related arrhythmias from the LA free wall increased. Clinical efficacy of the repeat ablation is high.

[Sustained monomorphic ventricular tachycardia in patients with structural heart disease. Different arrhythmogenic substrates, different options of palliative and curative treatment in the era of three-dimensional mapping]. / Setrvalá monomorfní komorová tachykardie u patientu se strukturalnim postizenim srdce. Ruzné arytmogenní substráty, ruzné moznosti paliativní nebo kurativní lécby katetrovou ablací v ere trojrozmerného mapování.

UNLABELLED: Results of catheter ablation of sustained monomorphic ventricular tachycardia (SMVT) in patients with structural heart disease are presented. METHODS: Catheter ablation was performed in 34 patients (5 females), aged 63 +/- 11 years. One (3%) patient had a permanent SMVT resistant to electric cardioversion, 13 (38%) patients had incessant SMVT, 4 (12%) patients had SMVT at least once a day, 9 (26%) patients at least once a week, and 7 (21%) patients at least once a month. Twenty-nine (85%) patients were treated with amiodarone. Twenty-seven (79%) patients had a history of remote myocardial infarction, 2 (6%) patients presented with dilated cardimyopathy, 4 (12%) patients had arrhythmogenic right ventricular cardimyopathy, and 1 (3%) patient was after surgery for tetralogy of Fallot. Left ventricular ejection fraction was 35 +/- 13%. Ablation was mostly performed as a palliative approach with the purpose to eliminate clinically significant forms of SMVT leading to frequent ICD discharges, respectively to the worsening of heart failure. Less frequently, ablation was accomplished as a curative therapy. For the SMVT ablation, electroanatomic mapping was used, and, target or substrate mapping and ablation or their combinations were employed. RESULTS: Clinical form of SMVT was successfully eliminated in 33 (97%) patients, all inducible ventricular tachyarrhythmias were eliminated in 14 (41%) patients. Any ventricular tachycardia did not recur in 29 (85%) patients during 22 +/- 17 months follow-up. Twenty-three (68 %) patients had eventually implanted ICD. Ablation was performed as a curative procedure in 11 (32 %) patients. Average procedure duration was 213 +/- 56 minutes, fluoroscopy time was 18 +/- 9 minutes, and number of radiofrequency applications was 23 +/- 13. CONCLUSION: Catheter ablation in patients with structural heart disease offers a highly effective method in elimination of clinical forms of SMVT. In long-term perspective, it is associated with low recurrence of any ventricular tachyarrhythmia. Efficacy of the ablation in elimination of all inducible forms of ventricular tachyarrhythmia is lower and therefore it should be mostly viewed as a palliative method, particularly in patients with left ventricular dysfunction and incomplete revascularization.

[Idiopathic premature ventricular complexes--catheter ablation as a therapeutic alternative]. / Idiopatická komorová extrasystolie--katetrová ablace jako lécebná alternativa.

UNLABELLED: Frequent isolated ventricular premature complexes (VPCs) in patients without major structural heart disease are generally associated with benign prognosis, however can lead to serious symptoms and also to the development of left ventricular dysfunction. Purpose of this study is to present mapping findings and immediate results of catheter ablation of frequent idiopathic VPCs, and evaluation of long-term clinical outcome and the role of catheter ablation in clinical practice. METHODS: Twenty-seven patients, aged 48 +/- 14 years without major structural heart disease, presenting with frequent VPCs, were investigated electrophysiologically in 28 procedures. Twenty-five patients underwent catheter ablation. RESULTS: In 19 patients, the ectopic focus was found in the right ventricular outflow tract (RVOT) and could be reached from the endocardial approach. In these patients, VPCs were successfully eliminated by the ablation. Comparison of 24-hour Holter ECG recordings showed complete elimination of the target VPCs in all the cases [18,483 +/- 12,790 (2,152-48,820)/17 +/- 10 (3-42) % VPCs before ablation vs. 94 +/- 219 (0-763)/0.01 +/- 0.2 (0-0.7) % VPCs after ablation]. In 5 patients, mapping revealed epicardial localization of the ectopic focus in the OT. Ablation endocardially from the RVOT failed in 2 of the patients, cryoablation epicardially from the venous system was partially successful in 1 patient, and no ablation was attempted in 2 patients. In another 3 patients, ectopic foci were found in other parts of the ventricles and ablation was completely successful in one case. During the 14 +/- 9 (1-34) month follow-up period, full elimination of the target VPCs and elimination or significant reduction of symptoms was achieved in 20 (74%) patients. The procedures were accomplished without complications and with fluoroscopy time of 8,2 +/- 5,9 minutes. CONCLUSION: Catheter ablation of frequent idiopathic VPCs was performed effectively and safely, particularly, if the ectopic focus was localized on the endocardial aspect of the RVOT. Efficacy of catheter ablation ofVPCs arising from the epicardium of ventricular OT or other atypical sites is limited by inaccessibility or proximity to the conduction system. Indication to more aggressive mapping and ablation methods like intrapericardial approach or ablation from inside the venous system should be always critically considered with regard to the symptoms or other clinical risk factors.

Phase I trial of lobradimil (RMP-7) and carboplatin in children with brain tumors.

PURPOSE: To determine the maximum tolerated dose (MTD), the incidence and severity of toxicities, and the pharmacokinetics of lobradimil administered intravenously over 10 min in combination with carboplatin in children with refractory brain tumors. METHODS: A group of 25 children with primary brain tumors received carboplatin and lobradimil on two consecutive days every 28 days. The 10-min lobradimil infusion began 5 min before the end of the carboplatin infusion. Four lobradimil dose levels (100, 300, 450 and 600 ng/kg ideal body weight, IBW) were studied in cohorts of 4 to 13 patients. Carboplatin was adaptively dosed based on the glomerular filtration rate to achieve a target plasma area under the concentration-time curve (AUC) of 7.0 mg min/ml per course (5.0 mg min/ml for patients who had previously received craniospinal radiation or myeloablative chemotherapy). RESULTS: Lobradimil toxicity was immediate, tolerable and rapidly reversible. The most frequent toxicities were hypotension, flushing, headache and gastrointestinal complaints. One patient on the 600 ng/kg dose level had a seizure during the lobradimil infusion. The incidence and severity of lobradimil toxicities were not dose-related and the lobradimil dose was not escalated beyond the 600 ng/kg IBW dose level. Two patients had partial responses and ten patients had stable disease. Myelosuppression (thrombocytopenia more prominent than neutropenia) was the primary toxicity attributed to carboplatin. Lobradimil pharmacokinetics were characterized by rapid clearance from the plasma compartment and substantial interpatient variability. CONCLUSIONS: The combination of carboplatin and lobradimil is safe and tolerable. An MTD for lobradimil was not defined because toxicity was not dose-related. The recommended pediatric phase II dose of lobradimil is 600 ng/kg IBW.

A multicenter study of the efficacy and safety of sustained release GH in the treatment of naive pediatric patients with GH deficiency.

Treatment of naive children with GH deficiency has relied upon long-term replacement therapy with daily injections of GH. The daily schedule may be inconvenient for patients and their caregivers, possibly promoting nonadherence with the treatment regimen or premature termination of treatment. We studied a new sustained release GH formulation, administered once or twice monthly, to determine its efficacy and safety in this population. Seventy-four prepubertal patients with documented GH deficiency were randomized to receive sustained release recombinant human GH at either 1.5 mg/kg once monthly or 0.75 mg/kg twice monthly by sc injection in a 6-month open-label study. Efficacy was determined by growth data from 69 patients completing 6 months and 56 patients completing 12 months in an extension study. Growth rates were significantly increased over baseline and were similar for the two dosage groups. The mean (+/-SD) annualized growth rate (pooled data) was 8.4 +/- 2.1 cm/yr at 6 months, and the growth rate was 7.8 +/- 1.8 at 12 months compared with 4.5 +/- 2.3 at baseline. Standardized height, bone age, and predicted adult height assessments demonstrated catch-up growth without excessive skeletal maturation. Injection site-related events (including pain, erythema, and nodules) were the most commonly reported adverse events; no serious adverse events related to treatment were reported. Laboratory studies documented no accumulation of trough GH or IGF-I levels during treatment, nor did glucose intolerance or persistent hyperinsulinism develop. Sustained release recombinant human GH is safe and effective for long-term GH replacement in children with GH deficiency. Patients achieved similar growth velocities when sustained release GH was given once or twice monthly. The enhanced convenience of this dosage form may result in greater long-term adherence to the treatment regimen.

Cost effective management of heavy uterine bleeding: ablative methods versus hysterectomy.

The treatment of menorrhagia in the twentieth century changed after 1960 with the introduction of hormonal therapy as well as an array of laboratory, imaging and minimal access tests for more accurate diagnosis. Since 1981, hysteroscopy has been used for diagnosis as well as the control of thermoablative treatments of bleeding non-malignant endometrium, including laser, electrocoagulation and electroresection. The success rates, complications, intermediate range outcome and cost comparisons with hysterectomy favor hysteroscopic methods. But the long term data on both hysteroscopic ablation and hysterectomy are not yet complete. In an effort to simplify techniques, reduce costs, and reduce complications, a variety of non-hysteroscopic methods and devices have appeared. Only two balloon devices have satisfactory success data as well as sufficient field experience to provide some degree of reliability regarding complications, which appear to be very low. Most of the devices have had clinical trials, which suggest equivalence to hysteroscopic endometrial ablation, but the determination of clinical safety requires at least several thousand cases. However, the levels of effectiveness for most of these devices make them candidates for commercial use. Hysterectomy may move from a primary surgical treatment of menorrhagia to a second-line treatment after ablation, particularly if some of the non-hysteroscopic methods become well accepted. If they are found to be safe, the costs and ease of use for the gynecologist and patient will make them attractive as a first-line surgical option. Hysterectomy, whether abdominal, vaginal, or laparoscopic will then be applied to ablation failures or non-candidates. This has the potential to change gynecological training and practice significantly in the future.

Adenocarcinoma of the endometrium after endometrial ablation.

BACKGROUND: Endometrial ablation is a relatively new technique for treating abnormal uterine bleeding not associated with malignancy. Long-term outcome data after endometrial ablation are limited, and incidence of endometrial adenocarcinoma after ablation is unknown. CASE: A 55-year-old black woman who had endometrial ablation for abnormal uterine bleeding after excluding uterine cancer presented 5 years later with similar symptoms and a histologic diagnosis of well-differentiated adenocarcinoma of the uterus. She refused surgery and had radiation treatment for probable stage I endometrial adenocarcinoma. CONCLUSION: It is unlikely in this high-risk patient that the endometrial ablation masked an undetected malignancy or delayed the diagnosis. Given the interval, the adenocarcinoma might have occurred de novo.

Pregnancy rates after hysteroscopic polypectomy and myomectomy in infertile women.

OBJECTIVE: To compare reproductive benefits of hysteroscopic myomectomy and polypectomy for infertility to outcomes in infertile couples with normal hysteroscopic findings. METHODS: Women with diagnoses of infertility who had hysteroscopic evaluations by a single surgeon between 1975 and 1996 were sent a routine follow-up questionnaire regarding their reproductive histories. All 92 subjects who were located responded to the questionnaire, and 78 met inclusion criteria: age under 45 years, at least 12 months of infertility, and at least 18 months of follow-up with attempts to conceive, including in vitro fertilization in women with bilateral tubal occlusion. RESULTS: Of the 78 subjects, 36 had myomectomies, 23 had polypectomies, and 19 had normal cavities. Among the three groups, there were no significant differences in age, type of infertility, length of infertility, or follow-up after the procedure. Polypectomy subjects had significantly higher pregnancy and live birth rates than women with normal cavities. Women who had myomectomies larger than 2 cm had significantly higher pregnancy and live birth rates, achieving statistical significance at a myoma size of 3 cm or greater for live births. Spontaneous abortion rates among first pregnancies after myomectomy, polypectomy, or normal study were similar: 31.5%, 27.7%, and 37.5%, respectively. CONCLUSION: Both hysteroscopic polypectomy and hysteroscopic myomectomy appeared to enhance fertility compared with infertile women with normal cavities. Despite concern that hysteroscopic resection of a large myoma might ablate a large surface area of the endometrial cavity, the reproductive benefit appears greater than the risk.

Uterine thermal balloon therapy for the treatment of menorrhagia: the first 300 patients from a multi-centre study. International Collaborative Uterine Thermal Balloon Working Group.

OBJECTIVE: To evaluate the safety and efficacy of thermal balloon therapy for menorrhagia. DESIGN: Prospective, observational study. SETTING: Fifteen centres in Canada and Europe. POPULATION: Two hundred and ninety-six eligible women for whom follow up data were available for three months or more. Eligible women included those for whom further fertility was not a concern, were not postmenopausal, suffered from intractable menorrhagia, had a normal uterine cavity, and who were fully informed regarding the investigational nature of uterine thermal balloon therapy. METHODS: Three hundred and twenty-one procedures of balloon endometrial ablation were performed using the same protocol between June 1994 and August 1996. Exclusion criteria included structural uterine abnormality or (pre) malignant lesions. Treatment entailed controlled heating of fluid in an intrauterine balloon. General anaesthesia was employed in the 61% of procedures while local anaesthesia with or without sedation was used in 39% of cases. ANALYSIS: Follow up data at 3 and/or 6, and/or 12 months were required for inclusion in the analysis. A paired t test, Wilcoxon signed-ranks test, and multiple and logistic regression analyses were used to evaluate the changes in bleeding and dysmenorrhoea patterns, and possible confounding variables, respectively. Success was defined as the subjective reduction of menses to eumenorrhoea or less. RESULTS: No intra-operative complications occurred, and post-operative morbidity was minimal. Success of the procedure was constant over the year (range 88%-91%). Treatment led to a significant decrease in the duration of menstrual flow and severity of pain (P < 0.0001). Increasing age, higher balloon pressure, smaller uterine cavity, and a lesser degree of pre-procedure menorrhagia were associated with significantly improved results. Pre-treatment with gonadotrophin releasing hormone agonists increased amenorrhoea and spotting rates (P = 0.03), but was only used in 5% of cases. CONCLUSION: Thermal balloon endometrial ablation appears to be safe, as well as effective in properly selected women with menorrhagia and is potentially an outpatient procedure.

Pregnancy rates following hysteroscopic polypectomy, myomectomy, and a normal cavity in infertile patients.

Objective: To assess the reproductive benefits of hysteroscopic myomectomy and polypectomy for infertility when compared to infertile couples with a normal cavity at hysteroscopy.Material and Methods: All patients with a diagnosis of infertility who underwent hysteroscopic evaluation by a single surgeon between 1975 and 1996 were sent a questionnaire as routine follow-up regarding their reproductive history. All 100 subjects who were located responded to the questionnaire, and 78 subjects met the inclusion criteria; age <45 years, 12 months of infertility, and 18 months of follow-up with attempts to conceive including in vitro fertilization in patients with bilateral tubal occlusion.Results: Of the 78 subjects, 36 had undergone a myomectomy, 23 a polypectomy, and 19 had a normal cavity. Among the three groups there was no significant difference in their ages, types of infertility, length of infertility, or follow-up after the procedure. Using the Cox proportional hazard model, and adjusting for age, polypectomy patients had a significantly higher pregnancy rate (RR 3.89, P <.01) and a higher live birth rate (RR 2.42, P =.06) than patients with a normal cavity. Patients who had undergone a myomectomy also had a higher pregnancy rate (RR 2.02, P =.11) and live birth rate, but this did not achieve statistical significance. Pregnancy following a hysteroscopic myomectomy was associated with a larger fibroid resection (3.15 cm vs 2.5 cm P =.05). The spontaneous abortion rate following the myomectomy, polypectomy, or a normal study was equivalent, 28.1%, 23.1%, and 29.2%, respectively.Conclusions: Both hysteroscopic polypectomy and hysteroscopic myomectomy appear to enhance fertility when compared to infertile patients with a normal cavity. Despite concern that hysteroscopic resection of a large myoma may ablate a large surface area of the endometrial cavity, patients with larger myomas were more likely to conceive following resection.

Update on transcervical sterilization.

Transcervical sterilization techniques as of 1980 are reviewed. A personal and literature search is reported on developments between 1980 and 1992. The potential of endometrial ablation for a transcervical method of fertility control is explored. An appraisal of the more promising methods for future study is made, including silastic tubal plugs, quinacrine, Femcept delivery of an iodine mixture and endometrial ablation.

Hysteroscopic submucous myomectomy.

Symptomatic submucous myomata are now diagnosed and evaluated with hysteroscopy in the office or operating room. Excision under hysteroscopic control using a resectoscope or other equipment and techniques is described and the long term outcome is reported. The hysteroscopic approach to the symptomatic submucous myoma has dramatically changed the treatment options for patients who classically would be offered abdominal myomectomy or hysterectomy.