Propranolol in the treatment of infantile haemangiomas: lessons from the European Propranolol In the Treatment of Complicated Haemangiomas (PITCH) Taskforce survey.

BACKGROUND: Oral propranolol is widely prescribed as first-line treatment for infantile haemangiomas (IHs). Anecdotally, prescribing practice differs widely between centres. OBJECTIVES: The Propranolol In the Treatment of Complicated Haemangiomas (PITCH) Taskforce was founded to establish patterns of use of propranolol in IHs. METHODS: Participating centres entered data on all of their patients who had completed treatment with oral propranolol for IHs, using an online data capture tool. RESULTS: The study cohort comprised 1097 children from 39 centres in eight European countries. 76·1% were female and 92·8% had a focal IH, with the remainder showing a segmental, multifocal or indeterminate pattern. The main indications for treatment were periocular location (29·3%), risk of cosmetic disfigurement (21·1%) and ulceration and bleeding (20·6%). In total 69·2% of patients were titrated up to a maintenance regimen, which consisted of 2 mg kg(-1) per day (85·8%) in the majority of cases. 91·4% of patients had an excellent or good response to treatment. Rebound growth occurred in 14·1% upon stopping, of whom 53·9% were restarted and treatment response was recaptured in 91·6% of cases. While there was no significant difference in the treatment response, comparing a daily maintenance dose of < 2 mg kg(-1) vs. 2 mg kg(-1) vs. > 2 mg kg(-1) , the risk of adverse events was significantly higher: odds ratio (OR) 1 vs. adjusted OR 0·70, 95% confidence interval (CI) 0·33-1·50, P = 0·36 vs. OR 2·38, 95% CI 1·04-5·46, P = 0·04, Ptrend < 0·001. CONCLUSIONS: The PITCH survey summarizes the use of oral propranolol across 39 European centres, in a variety of IH phases, and could be used to inform treatment guidelines and the design of an interventional study.

[Medication-based therapy of infantile hemangioma and lymphatic malformations]. / Medikamentöse Behandlungsansätze für infantile Hämangiome und lymphatische Malformationen.

The therapy of vascular tumors and malformations should be interdisciplinary and performed according to available guidelines. Infantile hemangiomas (IH) are the most frequent vascular tumors of childhood and do not require treatment in most cases. If the IH is complicated by its location (e.g. facial or genital) or if the lesion threatens to cause loss of function, small localized IH should be treated by laser- or cryotherapy. If the IH is diffuse or rapidly growing it can be successfully treated using the ß blocker propranolol. The mechanism underlying the efficacy of this medication-based therapy is not completely understood and this still represents an experimental therapy. The results of molecular studies on vascular malformations have indicated new strategies for medical therapies. However, lymphatic malformations (LM) are still treated by surgery where possible, or sclerotherapy. Further investigations are necessary to determine whether new drugs such as the mTOR inhibitor rapamycin may be effective for treatment of diffuse LM. First case reports seem to be promising.

Successful treatment of ulcerated haemangioma with propranolol.

BACKGROUND: Ulceration is a frequent complication of proliferating haemangioma. METHODS: Four patients with ulcerated hemangioma aged 2, 4, 5 months and 5 weeks were treated with 2 mg/kg KG propranolol. RESULTS: Efficacy and safety of propranolol were excellent in all four cases. CONCLUSIONS: Propranolol may be the first-choice therapy for ulcerated haemangioma.

Predicting impaired glucose metabolism in women with polycystic ovary syndrome by decision tree modelling.

AIMS/HYPOTHESIS: Polycystic ovary syndrome (PCOS) is a risk factor of type 2 diabetes. Screening for impaired glucose metabolism (IGM) with an OGTT has been recommended, but this is relatively time-consuming and inconvenient. Thus, a strategy that could minimise the need for an OGTT would be beneficial. MATERIALS AND METHODS: Consecutive PCOS patients (n=118) with fasting glucose <6.1 mmol/l were included in the study. Parameters derived from medical history, clinical examination and fasting blood samples were assessed by decision tree modelling for their ability to discriminate women with IGM (2-h OGTT value >/=7.8 mmol/l) from those with NGT. RESULTS: According to the OGTT results, 93 PCOS women had NGT and 25 had IGM. The best decision tree consisted of HOMA-IR, the proinsulin:insulin ratio, proinsulin, 17-OH progesterone and the ratio of luteinising hormone:follicle-stimulating hormone. This tree identified 69 women with NGT. The remaining 49 women included all women with IGM (100% sensitivity, 74% specificity to detect IGM). Pruning this tree to three levels still identified 53 women with NGT (100% sensitivity, 57% specificity to detect IGM). Restricting the data matrix used for tree modelling to medical history and clinical parameters produced a tree using BMI, waist circumference and WHR. Pruning this tree to two levels separated 27 women with NGT (100% sensitivity, 29% specificity to detect IGM). The validity of both trees was tested by a leave-10%-out cross-validation. CONCLUSIONS/INTERPRETATION: Decision trees are useful tools for separating PCOS women with NGT from those with IGM. They can be used for stratifying the metabolic screening of PCOS women, whereby the number of OGTTs can be markedly reduced.

Use of GnRH antagonists in the treatment of endometriosis.

Endometriosis is an oestrogen-dependent disease that is treatable by oestrogen withdrawal, a therapy that has been effectively provided by the use of a gonadotrophin-releasing hormone (GnRH) agonist. Complete oestrogen withdrawal results in unacceptable side-effects, in particular in accelerated bone density loss. This problem has been effectively overcome with 'add-back therapy' using low-dose oestrogens and progestins in combination with a GnRH agonist to limit these side-effects, while still allowing regression of endometriotic lesions. The aim of this study was to determine the feasibility of using a subcutaneous injection of GnRH antagonist in the treatment of endometriosis. All patients (15/15; 100%) reported a symptom-free period during GnRH antagonist treatment, including mood changes, hot flushes, loss of libido, vaginal dryness and other symptoms. Serum oestradiol oscillated around a mean concentration of 50 pg/ml during therapy. Diagnostic laparoscopy before GnRH antagonist administration showed a mean stage III of disease. Regression occurred in 60% of cases (9/15) and the degree of endometriosis declined to stage II. Sequential administration of the GnRH antagonist cetrorelix (Cetrotide) in a 3 mg dosage once weekly over 8 weeks creates a new opportunity for medical treatment of symptomatic endometriosis. Preserving basic oestrogen production during the course of treatment apparently does not influence regression of disease, and has no major side-effects.

Use of frozen-thawed testicular sperm for intracytoplasmic sperm injection.

OBJECTIVE: To determine the feasibility of using frozen-thawed testicular spermatozoa for intracytoplasmic sperm injection. DESIGN: Prospective clinical study. SETTING: A university hospital. PATIENT(S): One hundred seventy-five azoospermic men participating in a routine intracytoplasmic sperm injection program. INTERVENTION(S): The men underwent testicular biopsy for cryopreservation of tissue to be used in consecutive intracytoplasmic sperm injection treatment cycles. Their female partners underwent controlled ovarian hyperstimulation for conventional IVF treatment. MAIN OUTCOME MEASURE(S): Fertilization and pregnancy rates. RESULT(S): In 77% of the patients, spermatozoa could be harvested from the testis by an open testicular biopsy technique and used for intracytoplasmic sperm injection after freezing and thawing of testicular tissue. Histopathologic evaluation revealed a Sertoli cell-only pattern in 21%, maturation arrest in 60%, and hypospermatogenesis in 19% of the patients. In 2. 9% of the patients, carcinoma in situ or a germ cell tumor was detected. In all patients, viable spermatozoa could be visualized after the tissue samples were thawed. One hundred thirty-five intracytoplasmic sperm injection treatment cycles were performed, with a fertilization rate of 45% and a clinical pregnancy rate of 30% per oocyte retrieved. CONCLUSION(S): The use of frozen-thawed testicular tissue allows ovarian stimulation of the female partner to be timed and avoids cancellation of ovum pick-up when spermatozoa cannot be retrieved.

Transcervical falloscopic dilatation of proximal tubal occlusion. Is there an indication?

Proximal tubal occlusion (PTO), until recently a domain of microsurgery, can also be treated by a transcervical balloon dilatation and/or tubal recanalization. The aim of our study was to evaluate the possibility of transcervical tubal dilatation during transcervical Falloposcopy. Transcervical Falloposcopy and tubal dilatation was performed under laparoscopic control. During a period of 48 months a total of 157 Falloposcopies was performed. Out of a total of 157 patients, 42 patients had PTO confirmed by dye-pertubation during laparoscopy. All patients were referred because of primary or secondary tubal infertility. A total of 18 patients had bilateral PTO by dye-pertubation and of these six patients had successful bilateral and seven patients successful unilateral recanalization. The remaining five patients were unable to recanalize. A total of 24 patients had an unilateral PTO by dye-pertubation, 13 of these patients had a contralateral diseased tube, seven of which could be recanalized. Four patients had contralateral normal tubes, with successful recanalization in one patient. Seven patients had an occluded or missing contralateral tube, five of which could be recanalized. A total of 60 tubes with PTO were diagnosed, of which 32 (53.3%) tubes could be recanalized. 20 of these had normal tubes. Only patients with healthy Fallopian tubes carried pregnancies to term (five pregnancies, 12% of all patients). All patients conceived within a period of 3-6 months. We observed no ectopic pregnancy.

Successful combination of transrectal electroejaculation and intracytoplasmic sperm injection in the treatment of anejaculation.

We describe the case of a couple whose infertility was caused by the absence of seminal emission following retroperitoneal surgery for testicular cancer. Ejaculate could be retrieved from the husband by rectal probe electroejaculation (RPE) but sperm quality was so poor that conventional in-vitro fertilization was impossible. With intracytoplasmic sperm injection of spermatozoa retrieved by RPE - a combination not reported previously - we were able to induce a pregnancy with successful outcome.

Hormone profiles under ovarian stimulation with human menopausal gonadotropin (hMG) and concomitant administration of the gonadotropin releasing hormone (GnRH)-antagonist Cetrorelix at different dosages.

PURPOSE: The premature LH surge in ART programs seems to be avoided by daily administration of the GnRH-antagonist Cetrorelix during the midcycle phase in controlled ovarian hyperstimulation with hMG. The dosage necessary for sufficient suppression of the pituitary gland is not yet defined. METHODS: To elucidate this question three daily dosages (3, 1, 0.5 mg) were administered and the hormone profiles obtained as well as the number of oocytes retrieved, the fertilization rate, and the consumption of HMG were compared. RESULTS: No premature LH surge could be observed at any of the three dosages administered. Both gonadotropins were deeply suppressed. The fertilization rates of the oocytes obtained were 45.3% in the 3-mg group, 53.1% in the 1-mg group, and 67.7% in the 0.5-mg group. The average uses of hMG ampoules were 30 in the 3-mg group, 27 in the 1-mg group, and 26 in the 0.5-mg group. CONCLUSIONS: Cetrolix, 0.5 mg/day, administered during the midcycle phase of controlled ovarian hyperstimulation with hMG is enough to prevent completely the premature LH surge. Perhaps even lower dosages would be sufficient. Regarding fertilization rates and use of hMG, the lower dosage seems to be the most favorable.