Impact of age and gender on the efficacy and safety of upfront therapy with panitumumab plus FOLFOX followed by panitumumab-based maintenance: a pre-specified subgroup analysis of the Valentino study.

BACKGROUND: The safety and efficacy outcome of elderly metastatic colorectal cancer (mCRC) patients fit enough to receive combination chemotherapy plus biological agents is an issue of growing interest. Also, gender-specific differential toxicity and efficacy of anti-epidermal growth factor receptor (EGFR)-based upfront treatments need to be explored. PATIENTS AND METHODS: Valentino was a multicenter, randomized, phase II trial, investigating two panitumumab-based maintenance strategies following first-line panitumumab plus FOLFOX in RAS wild-type mCRC patients. We carried out a subgroup analysis, aimed at assessing the differences in efficacy, safety and quality of life (QoL) according to age (<70 versus ≥70 years) and gender (male versus female). Efficacy endpoints were progression-free survival (PFS), overall survival (OS) and overall response rate (ORR); safety endpoints were rates of any grade and grade 3/4 adverse events (AEs). RESULTS: No significant differences in terms of PFS, OS and ORR were observed between patients aged <70 or ≥70 years and the effect of the maintenance treatment arm on survival outcomes was similar in the two subgroups. The safety profile of both induction and maintenance treatment and the impact on QoL were similar in elderly and younger patients. No significant differences in PFS, OS, ORR or clinical benefit rate were observed according to gender. A significantly higher rate of overall grade 3/4 AEs (P = 0.008) and of grade 3/4 thrombocytopenia (P = 0.017), any grade and grade 3/4 neutropenia (P < 0.0001) and any grade conjunctivitis (P = 0.033) was reported in female as compared to male patients. Conversely, we reported a significantly higher incidence of any grade skin rash (P = 0.0007) and hypomagnesemia (P = 0.029) in male patients. CONCLUSIONS: The upfront choice of an anti-EGFR-based doublet chemotherapy followed by a maintenance strategy represents a valuable option in RAS wild-type mCRC irrespective of gender and age, though a careful evaluation of patients to maximize the risk/benefit ratio is warranted.

Immune cell engagers in solid tumors: promises and challenges of the next generation immunotherapy.

In the landscape of cancer immunotherapy, immune cell engagers (ICEs) are rapidly emerging as a feasible and easy-to-deliver alternative to adoptive cell therapy for the antitumor redirection of immune effector cells. Even if in hematological malignancies this class of new therapeutics already hit the clinic, the development of ICEs in solid tumors still represents a challenge. Considering that ICEs are a rapidly expanding biotechnology in cancer therapy, we designed this review as a primer for clinicians, focusing on the major obstacles for the clinical implementation and the most translatable approaches proposed to overcome the limitations in solid tumors.

Innovative therapy, monoclonal antibodies, and beyond: Highlights from the eighth annual meeting.

The eighth annual conference of "Innovative therapy, monoclonal antibodies, and beyond" was held in Milan on Jan. 26, 2018, and hosted by Fondazione IRCCS-Istituto Nazionale dei Tumori (Fondazione IRCCS INT). The conference was divided into two main scientific sessions, of i) pre-clinical assays and novel biotargets, and ii) clinical translation, as well as a third session of presentations from young investigators, which focused on recent achievements within Fondazione IRCCS INT on immunotherapy and targeted therapies. Presentations in the first session addressed the issue of cancer immunotherapy activity with respect to tumor heterogeneity, with key topics addressing: 1) tumor heterogeneity and targeted therapy, with the definition of the evolutionary Index as an indicator of tumor heterogeneity in both space and time; 2) the analysis of cancer evolution, with the introduction of the TRACERx Consortium-a multi-million pound UK research project focused on non-small cell lung cancer (NSCLC); 3) the use of anti-estrogen agents to boost immune recognition of breast cancer cells; and 4) the high degree of functional plasticity within the NK cell repertoire, including the expansion of adaptive NK cells following viral challenges. The second session addressed: 1) the effectiveness of radiotherapy to enhance the proportion of patients responsive to immune-checkpoint blockers (ICBs); 2) the use of MDSC scores in selecting melanoma patients with high probability to be responsive to ICBs; and 3) the relevance of the gut microbiome as a predictive factor, and the potential of its perturbation in increasing the immune response rate to ICBs. Overall, a picture emerged of tumor heterogeneity as the main limitation that impairs the effectiveness of anti-cancer therapies. Thus, the choice of a specific therapy based on reproducible and selective predictive biomarkers is an urgent unmet clinical need that should be addressed in order to increase the proportion of long-term responding patients and to improve the sustainability of novel drugs.

RET fusions in a small subset of advanced colorectal cancers at risk of being neglected.

Background: Recognition of rare molecular subgroups is a challenge for precision oncology and may lead to tissue-agnostic approval of targeted agents. Here we aimed to comprehensively characterize the clinical, pathological and molecular landscape of RET rearranged metastatic colorectal cancer (mCRC). Patients and methods: In this case series, we compared clinical, pathological and molecular characteristics of 24 RET rearranged mCRC patients with those of a control group of 291 patients with RET negative tumors. RET rearranged and RET negative mCRCs were retrieved by systematic literature review and by taking advantage of three screening sources: (i) Ignyta's phase 1/1b study on RXDX-105 (NCT01877811), (ii) cohorts screened at two Italian and one South Korean Institutions and (iii) Foundation Medicine Inc. database. Next-generation sequencing data were analyzed for RET rearranged cases. Results: RET fusions were more frequent in older patients (median age of 66 versus 60 years, P = 0.052), with ECOG PS 1-2 (90% versus 50%, P = 0.02), right-sided (55% versus 32%, P = 0.013), previously unresected primary tumors (58% versus 21%, P < 0.001), RAS and BRAF wild-type (100% versus 40%, P < 0.001) and MSI-high (48% versus 7%, P < 0.001). Notably, 11 (26%) out of 43 patients with right-sided, RAS and BRAF wild-type tumors harbored a RET rearrangement. At a median follow-up of 45.8 months, patients with RET fusion-positive tumors showed a significantly worse OS when compared with RET-negative ones (median OS 14.0 versus 38.0 months, HR: 4.59; 95% CI, 3.64-32.66; P < 0.001). In the multivariable model, RET rearrangements were still associated with shorter OS (HR: 2.97; 95% CI, 1.25-7.07; P = 0.014), while primary tumor location, RAS and BRAF mutations and MSI status were not. Conclusions: Though very rare, RET rearrangements define a new subtype of mCRC that shows poor prognosis with conventional treatments and is therefore worth of a specific management.

Negative hyper-selection of metastatic colorectal cancer patients for anti-EGFR monoclonal antibodies: the PRESSING case-control study.

BACKGROUND: Refining the selection of metastatic colorectal cancer patients candidates for anti-epidermal growth factor receptor (EGFR) monoclonal antibodies beyond RAS and BRAF testing is a challenge of precision oncology. Several uncommon genomic mechanisms of primary resistance, leading to activation of tyrosine kinase receptors other than EGFR or downstream signalling pathways, have been suggested by preclinical and retrospective studies. PATIENTS AND METHODS: We conducted this multicentre, prospective, case-control study to demonstrate the negative predictive impact of a panel of rare genomic alterations [PRESSING (PRimary rESiStance IN RAS and BRAF wild-type metastatic colorectal cancer patients treated with anti-eGfr monoclonal antibodies) panel], including HER2/MET amplifications, ALK/ROS1/NTRK1-3/RET fusions and PIK3CA mutations. Hypothesizing a prevalence of candidate alterations of 15% and 0% in resistant and sensitive RAS and BRAF wild-type patients, respectively, with two-sided α and ß errors of 0.05 and 0.20, 47 patients per group were needed. RESULTS: Forty-seven patients per group were included. PRESSING panel alterations were significantly more frequent in resistant (24 out of 47, 51.1%) than in sensitive (1 out of 47, 2.1%) patients (P < 0.001) and in right- (12 out of 29, 41.4%) than left-sided (13 out of 65, 20.0%) tumours (P = 0.03). The predictive accuracy of PRESSING panel and sidedness was 75.3% and 70.2%, respectively. Among hyper-selected patients, right-sidedness was still associated with resistance (P = 0.002). The predictive accuracy of the combined evaluation of PRESSING panel and sidedness was 80.4%. As a secondary analysis, 8 (17.0%) resistant and 0 sensitive patients showed microsatellite instability (P < 0.001). CONCLUSION: The investigated panel of genomic alterations allows refining the selection of RAS and BRAF wild-type metastatic colorectal cancer patients candidates for anti-EGFRs, partially explaining and further corroborating the predictive ability of primary tumour sidedness.

Microvascular characteristics of the human interdental papilla.

The aim of this study was to observe the microcirculation characteristics of the human interdental papilla in healthy patients in vivo. Twenty healthy patients were examined. Capillaroscopy was used to investigate the characteristics of microcirculation of the human periodontal mucosa. Visibility, course, tortuosity, as well as the average caliber of the capillary loops and the number of visible capillary loops per square millimeter were evaluated for each patient. The investigation of gingival mucosa revealed capillary loops with a course both parallel and perpendicular to the surface. Our study has pointed out that capillaroscopy is a reliable method to study periodontal microcirculation in vivo. This method could be applied to the study of microcirculation in periodontal diseases. Future studies might evaluate whether microcirculation in that area is compromised or not during systemic pathologies involving peripheral microcirculation alterations.

Oral diseases in a patient affected with Prader-Willi syndrome.

BACKGROUND: A case of Prader-Willi syndrome (PWS) in a 13-year-old girl is reported. The patient presents with systemic and oral manifestations of the disease. Case report The patient shows: obesity, hypotonia, mental retardation, small hands, prominent forehead, strabismus, hypoplastic teeth, poor oral hygiene, caries, oral candidiasis and thick, sticky saliva. This case is reported to underline the importance of the oral and dental problems of these patients. Caries and oral candidiasis are correlated with the reduced secretion of saliva and with poor oral hygiene. The role of paediatric dentistry is considered to be necessary for the prevention of oral complications of this syndrome.

Development of heart failure in bradycardic sick sinus syndrome.

Mounting evidence shows that elevated resting sinus rate is an independent predictor of cardiovascular morbidity and mortality in the general population, in elderly subjects, and in patients with myocardial infarction or hypertension. Therefore, a rather slow sinus rate appears to be a protecting factor acting through several mechanisms. The present contribution focuses on the relationship between sinus rate and heart failure. Its major objectives are to discuss whether in patients with heart failure a rather slow heart rate is advisable and whether a sinus bradycardia secondary to sinus node dysfunction can facilitate the development of heart failure. It has been reported that among patients with left ventricular dysfunction, increased sinus rate was a predictor of cardiovascular death at univariate analysis; however, a multivariate analysis to verify whether sinus rate was an independent predictor of mortality was not performed. Randomized trials carried out by utilizing beta-blockers or amiodarone in patients with heart failure showed that heart rate reduction by these drugs was a marker of their ability to reduce mortality. However, beta-blockers and amiodarone have additional pharmacological effects which interfere with the disease substrate. So, at present, though the results of these trials show that a rather slow sinus rate is advisable, we do not know whether in patients with heart failure sinus rate represents an independent predictor of mortality as in patients with myocardial infarction or hypertension and whether the reduction of sinus rate per se is beneficial. The results of the recent randomized THEOPACE trial showed, for the first time, that in a patient population with symptomatic sinus bradycardia (sinus rate < 50 b/min), an increase in heart rate, induced by DDD pacing or oral theophylline, reduced the incidence of overt heart failure. Therefore, sinus bradycardia seems to play a role in the genesis of heart failure. In a post-hoc analysis of the results of this trial it emerged that in the control (not treated) group, the subjects with sinus bradycardia more prone to develop heart failure were those of old age, about 80 years, with organic heart disease and severe chronotropic incompetence. However, this conclusion needs further validation.

Efficacy and safety of out-of-hospital self-administered single-dose oral drug treatment in the management of infrequent, well-tolerated paroxysmal supraventricular tachycardia.

OBJECTIVES: We tested the efficacy of two drug treatments, flecainide (F) and the combination ofdiltiazem and propranolol (D/P), administered as a single oral dose for termination of the arrhythmic episodes. BACKGROUND: Both prophylactic drug therapy and catheter ablation are questionable as first-line treatments in patients with infrequent and well-tolerated episodes of paroxysmal supraventricular tachycardia (SVT). METHODS: Among 42 eligible patients (13% of all screened for SVT) with infrequent (< or =5/year), well-tolerated and long-lasting episodes, 37 were enrolled and 33 had SVT inducible during electrophysiological study. In the latter, three treatments (placebo, F, and D/P) were administered in a random order 5 min after SVT induction on three different days. RESULTS: Conversion to sinus rhythm occurred within 2 h in 52%, 61%, and 94% of patients on placebo, F and D/P, respectively (p < 0.001). The conversion time was shorter after D/P (32 +/- 22 min) than after placebo (77 +/- 42 min, p < 0.001) or F (74 +/- 37 min, p < 0.001). Four patients (1 placebo, 1 D/P, and 2 F) had hypotension and four (3 D/P and 1 F) a sinus rate <50 beats/min following SVT interruption. Patients were discharged on a single oral dose of the most effective drug treatment (F or D/P) at time of acute testing. Twenty-six patients were discharged on D/P and five on F. During 17 +/- 12 months follow-up, the treatment was successful in 81% of D/P patients and in 80% of F patients, as all the arrhythmic episodes were interrupted out-of-hospital within 2 h. In the remaining patients, a failure occurred during one or more episodes because of drug ineffectiveness or drug unavailability. One patient had syncope after D/P ingestion. During follow-up, the percentage of patients calling for emergency room assistance was significantly reduced as compared to the year before enrollment (9% vs. 100%, p < 0.0001). CONCLUSIONS: The episodic treatment with oral D/P and F, as assessed during acute testing, appears effective in the management of selected patients with SVT. This therapeutic strategy minimizes the need for emergency room admissions during tachycardia recurrences.

Echocardiographic prediction of clinical outcome in medically treated patients with aortic stenosis.

BACKGROUND: The onset of symptoms is crucial in the natural history of severe aortic stenosis. In contrast, the impact of the degree of valve obstruction and left ventricular dysfunction on clinical outcome in terms of progression of symptoms and mortality is undefined. METHODS AND RESULTS: Between April 1989 and June 1996, 108 patients (75% male, aged 68.7 +/- 10.3 years) with pure and isolated aortic stenosis of at least moderate degree had a complete Doppler echocardiography. Left ventricular end-diastolic and end-systolic diameters, thickness of ventricular septum, mass and ejection fraction, and maximal instantaneous aortic gradient were measured. Patients were followed up through March 1999. Sixty-five patients who underwent aortic valve replacement were censored at the time of surgery. The end point was considered to be death or symptomatic progression (onset of new symptoms or worsening of symptoms). At the time of diagnosis 64 (59%) were in New York Heart Association (NYHA) class I-II and 44 (41%) in NYHA class III-IV. After a mean follow-up of 46 +/- 21 months 6 patients died and 45 had worsening of symptoms. Univariate predictors of clinical outcome (death and worsening of symptoms) included left ventricular end-diastolic diameter (hazard ratio 1.03, P =.08), left ventricular end-systolic diameter (HR 1.04, P =.012), and left ventricular septum thickness (HR 1.14, P =.009) but not the degree of aortic obstruction. Multivariate predictors of clinical outcome were left ventricular septum thickness (P =.016) and left ventricular end-systolic diameter (P =.008). CONCLUSION: In patients with various degrees of aortic stenosis the rate of clinical outcome is predicted by left ventricular function and septum thickness. Therefore both the left ventricular and aortic valve gradients should be taken into account when choosing the timing of intervention.

Significance of newly acquired negative T waves after interruption of paroxysmal reentrant supraventricular tachycardia with narrow QRS complex.

Sixty-three patients with paroxysmal supraventricular tachycardia were studied and 25 patients (39%) showed newly acquired negative T waves after tachycardia termination. Silent coronary artery disease could not be found in about 90% of these patients; moreover, age, sex, organic heart disease, and tachycardia duration and rate did not predict the appearance of negative T waves.

Atrioventricular nodal versus atrioventricular supraventricular reentrant tachycardias: characterization by an integrated Doppler electrophysiological hemodynamic study.

During reentrant supraventricular tachycardias involving the atrioventricular node (AVN-SVT) or an AV bypass tract (AV-SVT), atrial pressure increases. While in AVN-SVT this increase relates to atrial contraction during ventricular systole, the mechanism remains unclear in AV-SVT. This study sought to clarify this mechanism. During 11 AVN-SVTs and 9 AV-SVTs, anterograde flow through the AV valves and retrograde flow in the pulmonary and hepatic veins were studied by pulsed-wave (PW) Doppler measuring the time interval between the ECG-R wave and (1) the end of venous retrograde flows, and (2) the beginning of valvular anterograde flows. The positive or negative difference between these two time intervals guided recognizing the atrial contraction against open or closed AV valves. Intracavitary pressures and cardiac index were also measured. During AVN-SVTs, venous retrograde flows always ended before the anterograde valvular flows, indicating atrial contraction against closed AV valves. During AV-SVTs, pulmonary retrograde flow ended before the beginning of mitral anterograde flow in five cases, began before but ended during the anterograde flow in three cases, and overlapped to the anterograde flow in one case. A corresponding behavior was observed at the right side of the heart. In both SVTs, atrial pressures increased and end-diastolic ventricular pressure and cardiac index decreased similarly. During AVN-SVT, the atrial contraction always occurs against closed AV valves, and during AV-SVT it generally occurs against totally or partially closed AV valves, explaining similar atrial pressure and cardiac index changes in both SVTs.

Atrial and ventricular pressures in atrial flutter.

The hemodynamic effects of atrial flutter (AF) are unknown. The purpose of the present study was to investigate the changes in atrial and ventricular pressures after induction of AF. In 23 patients with paroxysmal AF (age 59 +/- 9 years), a hemodynamic study was performed both during sinus rhythm and after induction of the tachyarrhythmia. During AF, 13 patients showed a fixed 2:1 AV conduction and 10 patients showed variable conduction. Mean right and left atrial pressures increased (P < 0.001) and right and left ventricular end-diastolic pressures decreased (P < 0.001) after induction of AF. Both the increase in mean atrial pressures and the decrease in ventricular end-diastolic pressures were present either in the patients with fixed 2:1 AV (heart rate: 133 +/- 15 beats/min) or in those with variable conduction (heart rate 96 +/- 15 beats/min), but were more marked in the former. AF produces an impairment of atrial function, as evidenced by the increase in mean atrial pressures and reduction in ventricular end-diastolic pressures in the absence of an elevated heart rate. The mechanisms responsible for the increase in mean atrial pressures are unknown; however, atrial contractions against closed AV valves seem to play an important role.

Short-term hemodynamic effects of DDD pacing from ventricular apex, right ventricular outflow tract and proximal septum.

Recently, short-term hemodynamic benefits of right ventricular outflow tract (RVOT) or proximal septum (His bundle area) pacing have been reported in comparison with traditional apical stimulation in preliminary investigations. The purpose of the present study was to compare the hemodynamics obtained during DDD pacing from ventricular apex, RVOT and proximal septum in patients with normal left ventricular function. A simultaneous hemodynamic and Doppler-echocardiographic study was performed in 21 patients (age 67 +/- 7 years) with sick-sinus syndrome (8 pts) or 2nd-3rd degree atrioventricular (AV) block (13 pts). The three stimulation sites were randomized and pacing was applied at an identical rate (84 +/- 5 beats/min) and at a constant AV delay (150 ms). Electrocardiographic, hemodynamic and Doppler-echocardiographic investigations were performed during stimulation from each site. The QRS duration did not show significant differences during DDD pacing from ventricular apex, RVOT and proximal septum. The hemodynamic measurements (systemic pressures, mean pulmonary wedge pressure, pulmonary pressures, right ventricular end-diastolic pressure, mean right atrial pressure, cardiac index, systemic vascular resistance and arteriovenous O2 difference) did not show significant differences during pacing from the three sites. Moreover, no significant differences were observed for the Doppler-echocardiographic measurements of systolic function (aortic stroke distance, left ventricular ejection fraction) and diastolic function (isovolumetric relaxion time, mitral E/A ratio, deceleration rate of the E wave). The results suggest that in patients with normal left ventricular function DDD pacing from RVOT or proximal septum does not improve cardiac function with regard to apical pacing.

Effects of intravenous propranolol on cardiovascular hemodynamics during supraventricular tachycardia.

Hemodynamic variables were evaluated in 10 patients during supraventricular tachycardia before and after administration of intravenous propranolol. The drug markedly worsened the already compromised hemodynamic pattern of supraventricular tachycardia.

Hemodynamics of idiopathic paroxysmal atrial fibrillation.

The hemodynamics of induced atrial fibrillation (AF) was investigated in 15 patients (ages 58 +/- 11 years) with paroxysmal AF presenting without organic heart disease or hypertension. A hemodynamic study was performed both during sinus rhythm and after the induction of AF. The mean heart rate increased from 73 +/- 11 to 128 +/- 18 beats/min (P < 0.001) after AF. Systolic and mean aortic pressures did not significantly change, and diastolic aortic pressure increased (78 +/- 11 vs 89 +/- 12 mmHg, P < 0.01). Left ventricular end-diastolic pressure decreased during AF (9 +/- 3 vs 6 +/- 2.6 mmHg, P < 0.005), whereas mean pulmonary wedge pressure increased (8 +/- 2 vs 12 +/- 4 mmHg, P < 0.001). Systolic pulmonary arterial pressure did not show significant variations, and there was a slight but statistically significant increase in the diastolic and mean pulmonary arterial pressures (P < 0.01). The right ventricular end-diastolic pressure decreased during AF (5.6 +/- 2 vs 3.8 +/- 2 mmHg, P < 0.01), whereas mean right atrial pressure showed a trend toward an increase. Stroke volume markedly decreased (P < 0.001) while the cardiac index did not significantly change. Systemic vascular resistance, pulmonary arteriolar resistance, and the arteriovenous O2 difference showed no significant variations after the induction of AF. These results suggest that in subjects without organic heart disease, paroxysmal AF is well tolerated hemodynamically, and the rise in the atrial pressures during AF is not related to an increase in the ventricular end-diastolic pressure.

Hemodynamic effects of oral sotalol during both sinus rhythm and atrial fibrillation.

OBJECTIVES: This study investigated the hemodynamic effects of oral sotalol during both sinus rhythm and paroxysmal atrial fibrillation. BACKGROUND: The hemodynamic effects of most antiarrhythmic drugs have been characterized in subjects during sinus rhythm. However, there are no data concerning these effects on the paroxysmal tachyarrhythmias. METHODS: In 17 patients with paroxysmal atrial fibrillation and without heart failure (aged 62 +/- 11 years, ejection fraction 51 +/- 4%), an electrophysiologic-hemodynamic study was performed twice. In the first study, hemodynamic variables were evaluated both during sinus rhythm and after the induction of atrial fibrillation. Sotalol (160 or 240 mg/day) was administered for 6 to 7 days and the study was then repeated with the same methods. RESULTS: The drug significantly diminished heart rate during both sinus rhythm and atrial fibrillation. During sinus rhythm, sotalol did not change systemic pressures and significantly increased left and right ventricular end-diastolic, left and right atrial and pulmonary pressures. Cardiac index decreased, whereas stroke volume was unchanged after the drug. Ejection fraction and left ventricular end-diastolic and end-systolic volumes evaluated by echocardiography were unchanged after sotalol. During atrial fibrillation, the drug had less evident effects on cardiac function. Left ventricular end-diastolic, left atrial and pulmonary pressures did not increase significantly. CONCLUSIONS: The hemodynamic changes induced by oral sotalol appear to be mainly related to an involvement of ventricular distensibility; this effect is less evident during atrial fibrillation than during sinus rhythm. In patients with paroxysmal atrial fibrillation without heart failure treated with oral sotalol, a recurrence of the tachyarrhythmia is hemodynamically well tolerated.

Reproductive performance in women with uterus didelphys.

The reproductive history of 19 women with the diagnosis of uterus didelphys is reported. With this goal the patients were divided into two groups: A) composed of 15 patients who did not undergo any surgical correction of uterine anomaly; B) composed of 4 patients where metroplasty was performed. Diagnosis was made in 17 cases (85.9%) for reasons not related to the uterine anomaly, only in 2 cases did patients present with infertility complaints. Vaginal malformation was associated in 16 (85%) cases; in 11 cases longitudinal septum was present; whereas in 5 hemivagina atretica was found. Eleven group A patients had a total of 23 pregnancies of which 3 (13%) ended in spontaneous abortions, 2 (8.7%) were voluntarily interrupted, 3 ended in premature birth and 15 in term births, with 17 live babies for a live birth rate of 74%. If we consider that two pregnancies were voluntarily interrupted, we had 17 live babies out of 21 naturally evolved pregnancies, for a live birth rate of 81%. In group B 3 patients before treatment had 3 pregnancies all ending in spontaneous abortion. After treatment all had a live baby. Reproductive and gestational performances of women with uterus didelphys are preserved. In patients with infertility complaints, all associated causes must be ruled out before surgical correction. If these are present its correction must be attempted as first therapeutic step, and term pregnancy with live baby is the rule. Only if repeated abortions are not related to any other cause, can metroplasty, according to Bret-Palmer technique, be performed.