Relugolix for the treatment of uterine fibroids.

INTRODUCTION: Uterine fibroids (UF) are benign tumors common in premenopausal women, with strong impact on the health-care systems. For many years, surgery represented the only therapy for symptomatic fibroids. However, clinicians are observing a switch from surgery to noninvasive methods; in particular, medical treatment has been shown to be efficacious in obtaining a bleeding reduction and in ameliorating patient conditions. AREAS COVERED: The authors review the current options available for the treatment of women with UF, with a special focus on the newest one, relugolix. It is an orally active non-peptide Gonadotropin-releasing hormone (GnRH)-receptor antagonist recently licensed for women with symptomatic fibroids. Relugolix is a well-tolerated safe drug; it is effective in inducing a dose-dependent decrease in menstrual blood loss, with faster reduction of heavy menstrual bleeding (HMB) and a greater shrinkage in fibroid volume compared to the current standard of GnRH agonist treatment. EXPERT OPINION: Relugolix is a promising drug for the non-surgical treatment of women with UF. To date, the only published data come from a well-selected Japanese female population study while results from worldwide ongoing studies are ongoing in order to confirm the efficacy of this GnRH agonist receptor.

Systemic treatment with adipose-derived mesenchymal stem cells ameliorates clinical and pathological features in the amyotrophic lateral sclerosis murine model.

Therapeutic strategies for the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS) are actually minimally effective on patients' survival and quality of life. Although stem cell therapy has raised great expectations, information on the involved molecular mechanisms is still limited. Here we assessed the efficacy of the systemic administration of adipose-derived mesenchymal stem cells (ASC), a previously untested stem cell population, in superoxide-dismutase 1 (SOD1)-mutant transgenic mice, the animal model of familial ALS. The administration of ASC to SOD1-mutant mice at the clinical onset significantly delayed motor deterioration for 4-6 weeks, as shown by clinical and neurophysiological tests. Neuropathological examination of ASC-treated SOD1-mutant mice at day 100 (i.e. the time of their best motor performance) revealed a higher number of lumbar motorneurons than in phosphate-buffered saline-treated SOD1-mutant mice and a restricted number of undifferentiated green fluorescent protein-labeled ASC in the spinal cord. By examining the spinal cord tissue factors that may prolong neuronal survival, we found a significant up-regulation in levels of glial-derived neurotrophic factor (GDNF) and basic fibroblast growth factor (bFGF) after ASC treatment. Considering that ASC produce bFGF but not GDNF, these findings indicate that ASC may promote neuroprotection either directly and/or by modulating the secretome of local glial cells toward a neuroprotective phenotype. Such neuroprotection resulted in a strong and long-lasting effect on motor performance and encourages the use of ASC in human pathologies, in which current therapies are not able to maintain a satisfying neurological functional status.

[Gastric atresia, diaphragmatic hernia, and gastroesophageal reflux: a rare malformation requiring a multiple approach]. / Atresia del corpo gastrico, ernia diaframmatica laterale sinistra, reflusso gastro-esofageo. Malformazione rara e complessa trattata in più stadi con tecnica mista.

The first cases of atresia or web in the pyloric and prepyloric regions were described in the literature since 1937. To date, only one case of atresia at the junction between the fundus and the body of the stomach has been reported. We want to describe a complex case with incomplete atresia between fundus and gastric body, with left lateral diaphragmatic hernia, treated in several stages by endoscopic, open surgery and minimally invasive surgery

Determination of the anal position in newborns and in children with chronic constipation: comparative study in two European healthcare centres.

INTRODUCTION: The objective of this study was to determine the normal anal position index (API) in neonates and in a group of older children with chronic constipation, and to identify the incidence of anterior ectopic anus (AEA) in the two groups. MATERIALS AND METHODS: A prospective random study was carried out in two European hospitals determining the API in 1,012 neonates (529 in Group A, and 483 in Group B) and in 64 children suffering chronic constipation of ages between 3 months and 12 years (Group C). The API is defined as the ratio between the fourchette-anal and fourchette-coccygeal distances in girls and the scroto-anal and scroto-coccygeal distances in boys. The gestational age, weight, meconium evacuation and anal calibre were recorded in Groups A and B, and age, sex, and API in Group C. Statistical comparisons were made using Student's t test and Welch's t test for independent sample groups. RESULTS: The mean API in Group A was 0.53 ± 0.06 in males and 0.40 ± 0.05 in females, and in Group B 0.51 ± 0.06 in males and 0.39 ± 0.08 in females, with significant differences between the sexes (p < 0.0001) in both groups; 1.7% of the neonates in Group A and 2.4% of Group B presented AEA. 4/13 newborns females with AEA presented with severe constipation during their first months of life. For the 64 patients in Group C: 59.3% were female; the mean API was 0.47 ± 0.1 in males and 0.36 ± 0.1 in females (p < 0.0001). The incidence of AEA was 47% in females and 35% in males. CONCLUSIONS: In the neonates (Groups A and B), the position of the anus in the perineum was more anterior in females than in males (p < 0.0001); 31% of the newborns females with AEA presented with constipation in their first months of life. In the Group C patients, there was a high incidence of AEA, especially in the females, and we consider it to be the probable cause of this defecation disorder.

Anorectal malformations (ARM): quality of life assessed in the functional, urologic and neurologic short and long term follow-up.

UNLABELLED: Imperforate anus represents a wide spectrum of anorectal malformations associated with urologic, neurologic and orthopedic malformations. The outcome from the various corrective measures has improved due to new surgical techniques as well as to a better understanding of the pathology. Other factors which influence the overall outcome include the degree of patient acceptance, family support as well as the ability of the health care structure to support the patient's needs on a clinical, functional and psychologic level. AIM OF THE STUDY: Assess (with the new techniques available) the quality of life in the adult patient with ARM and compare it to that experienced by a younger patient; also we wish to determine the correlation between the observed abnormalities with the functional, neurologic and urologic outcome. MATERIALS & METHODS: Sixty-six patients were subjected to PSARP (36 M; 30 F). Six presented with cloaca and 60 with ARM (23 high and 37 low). All patients underwent the same workup to include L/S MRI diagnostics, evaluation for incontinence (urinary and bowel), a urology screening, and if required, a subsequent urodynamic study with rehabilitation and/or bowel management. All answered questionnaires (AIMAR: Italian parent's association of ARM) in order to assess their satisfaction with the current health condition, with the information received and with the treatment and follow-up sessions. The patients were classified into one of two groups. Group A, totaled 33 patients (4 cloacae) with an age range between 2 and 12 years who were operated after 1995. The second, group B, was made up of 33 patients who had been surgically treated before 1995 (age range 15-41 years), had followed the study protocol and had also a neuropsychiatry consult. RESULTS: Overall fecal continence was 69% and of this number 37% were clean without constipation. Twe2nty-one patients (32%) suffered from some form of constipation. Constipation was the most common functional disorder observed in patients who have undergone PSARP. The highest incidence of constipation was found in the ARM (low type), a favorable prognostic group with 43% constipation. Patient with "high" defects and a cloaca had a lower incidence of constipation (18%). Of the 59 patients evaluated, 85% were urinary continent and 15% were incontinent. All of the incontinent patients were in the unfavorable prognostic group of malformations. Urodynamic studies showed 7 neurogenic bladders (NB) and 2 patients with a neurovescical dysfunction (NVD). Of the 50 "dry" patients. 20 had voiding disturbances due to a voiding dysfunction, in the absence of neurologic abnormalities, and presented occasional daytime or nighttime wetting. There was no correlation between the level of the anatomic defect and the urodynamic patterns in the group. Abnormal MRI findings were observed in thirty out of fifty-two patients evaluated. The MRI findings were classified as follows. Severe abnormalities: 7 patients (13%) presented with a combination of skeletal (sacral/lumbar) and spinal cord anomalies. Only spinal cord abnormalities: 12 patients (21%). Only skeletal abnormalities: 11 (19%) patients. Patients were divided into high, low and cloacal malformations. A high degree of statistical correlation was noted between the patients belonging to the cloacae and high defect groups and the abnormal MRI findings. No significant correlation was found between the low defect group and dysrafism, abnormal MRI results and the severity of the malformation. The incidence of Tethered Cord (TC) in our limited number of patients was limited in our study (9% in the high and 7% in the low defect group) when compared to the current literature. Furthermore there was no statistically conclusive evidence that TC by itself affects the urinary or fecal control in our patients. Our recommendation is nevertheless to obtain an MRI study in all patients with ARM. CONCLUSION: All patients 17 and older reported a "good quality of life". Four are married, two with children. Aclose working relationship with the medical personnel is not only necessary but is also well received by the family particularly when younger patients are involved. The adult patient easily adapts even when information is initially scarce. He quickly reaches autonomy with personalized solutions but prefers a longer follow-up time during which, specialized medical facilities will play an important role in the treatment of ARM. Our findings illustrate the importance of both global disease-specific functioning and perceived psychosocial competencies for enhancing the QL of these patients.

[Non-invasive urodynamic approach to the diagnosis, treatment and follow-up of voiding disorders in pediatric patients]. / Approccio urodinamico non invasivo nella diagnosi, trattamento e follow-up dei disturbi minzionali in età pediatrica.

The authors reports their experience on 248 patients affected by minctional disorders isolated or related to UTI (upper tract infections) and VUR (vesico-ureteral reflux). All the patients were assessed throught a predominantly non invasive diagnostic approach which included: pediatric urologic examination with aimed anamnestic and clinical freaming, functional examination of the lower urinary tract using uroflowmetry + EMG of the perineal plane muscles (UR + EMG), kidney and bladder ultrasound. This methodology has permitted a widening of the indications in the study of vesical function as well as limiting the selected cases (hight UTI, uncertain diagnosis) of mini-invasive examination, such as flow pressure study, minctional cystourethrogram (MC) and or renal scintigraphy. An MNR of the lumbo-sacral medulla (cord) and a neurological and/or neurosurgery evaluation were only carried out were there was a suspected occult neurological pathology. The clinical sintomatogy was as follows: approximately 70% of the patients suffered from partial diurnal incontinence, 42% were affected by secondary nocturnal enuresis while 58.6% suffered from recurrent UTI. In those patients with UTI, 11% (16 patients, 24 ureteral units) suffered from associated VUR while 3.5% suffered from either congenital or acquired urethral stenosis. From the urodynamic examination, we determined the presence of detrusorial instability in 158 patients (64%) and lazy bladder or vescical hypotonia in 84 patients (34%). The suggested therapy foresees the use of: hospital home-based uroriabilitation (minctional biofeedback), endoscopic therapy (sub-ureteral bulking, urethral dilatation) and corrective VUR surgery (only in those cases that did not respond to medical treatment). The percentage of total recovery in patients with detrusorial instability was 80%, the minctional biofeedback both associated and unassociated with drug therapy lead to complete recovery in 66% of patients with lazy and uncordinated bladder, wile 26% showed improvement and 7 patients (8.4%) did not respond. All the patients with VUR (24 reflux units) recovered; and endoscopic therapy and or surgery (12 reflux units) was carried out in some of this patients.

[Surgery of congenital malformations in developing countries: experience in 13 humanitarian missions during 9 years]. / Chirurgia delle Malformazioni Congenite nei paesi in via di sviluppo: esperienze maturate nel corso di 13 missioni umanitarie in 9 anni.

The authors report their surgical experience concerning seriously impaired children due to congenital malformations or other non-congenital anomalies such as burns and traumas. All the patients were operated in one of 13 humanitarian missions undertaken in four developing countries. Throughout the "Third World" the demand for reconstructive surgery is extremely high due to the high birth rate and consequently large number of patients, as well as the shortage of both medical staff and supplies. In developing countries Primary Health Care has always been considered a priority and so hospitals, which are used mainly for emergency operations, are usually few in number and badly equipped; elective surgery is considered a luxury. Children with congenital diseases and/or other non-congenital anomalies who are fortunate enough to reach a hospital will often be treated by general surgeons lacking specific training; those children suffering from disabling conditions are often neglected and left to live with their anomalies for the rest of their lives. Our surgical missions have always been undertaken at the request of Catholic missionaries and/or secular organizations which contribute to the individual health schemes of each country. Highly experienced volunteer staff took part in the missions; medical teams are made up of 2 surgeons, one or two anaesthetists and two scrub nurses. The assistance and cooperation of local medical staff was essential in the preselection of cases to be operated while each single medical team provided all the necessary supplies for surgery, which took place in small but well-equipped missionary hospitals provided by the local authorities. A total of 1140 children were operated on during the 13 missions: 32% of these had routine procedures performed in day surgery and 54% underwent major plastic and reconstructive surgery for facial, uro-genital and anorectal malformations or for serious consequences of burns or traumas. The proportion of emergencies was only 3% as these were normally excluded because of the short duration of the missions. 26 patients had to be reoperated as a result of complications or surgical failure and long-term follow-up provided by either the local staff or as a part of later missions was given in over 70% of the major surgery performed. On the whole, the surgical results were highly satisfactory even if a final evaluation should be made taking the cultural factors and the socio-environmental conditions of each individual country into consideration. Such an evaluation should most importantly be made on the basis of the well-being of the patient, general satisfaction of the families involved and improved quality of life of these children.

Reoperative orchiopexy: surgical aspects and functional outcome.

Over a 14-year period, a total of 40 patients underwent surgical revision after an unsuccessful orchiopexy attempt. Overall, 34 reorchiopexies (1 bilateral) and 7 orchiectomies were performed. All reorchiopexies were carried out using extensive mobilization of the testis and spermatic cord. This approach was sufficient for scrotal placement of the testis in 23 instances; however, it was necessary to transpose the spermatic vessels medially in the remaining 11 (incision of the transversalis fascia in 5, incision of the transversalis fascia and division of the inferior epigastric vessels in 6). Only 1 prepuberal boy developed testicular atrophy (2%). Functional long-term assessment was done in 20 postpuberal patients using testicular ultrasound and sperm analysis. The reoperated cryptorchid testes were significantly smaller than the controls (P < 0.005), but decreased fertility was only noted in 3 patients (18.7%). We conclude that testicular volume in adulthood is not directly related to fertility, so that accurate reorchiopexy seems to be the best way to preserve fertility in this special group of cryptorchid patients.

Pneumatosis cystoides intestinalis: a rare cause of nonsurgical pneumoperitoneum in an infant.

The authors describe a 3-year-old boy with pneumatosis cystoides intestinalis (PCI) and associated duodenal stenosis who came to them with abdominal pain, significant abdominal distension, large gastric residue, and pneumoperitoneum. PCI is a rare condition in children characterized by the presence of multiple gas-filled cysts within the wall of some part of gastrointestinal tract that may break and cause pneumoperitoneum without an intestinal perforation. Even if in most cases the standard treatment is surgical, to keep in mind this rare condition could be useful to adopt a most rational treatment approach and avoid unnecessary operation in case of "benign" pneumoperitoneum.

[Fecal incontinence in pediatric age: diagnostic-therapeutic protocol and possible surgical procedures]. / Incontinenza fecale in età pediatrica: protocollo diagnostico-terapeutico e prospettive chirurgiche.

Fecal incontinence or soiling always endangers the personality development of a children. For very severe cases, the patient will be limited on his educational and professional training as well as on his sexal life. The outlook of severe cases, the chances of completing school, the choice of professional training and of sexual life in the future will be limited. A corrective procedure for anorectal incontinence depends on the exact investigation of all factors contributing to continence. The aim of this paper is to analyze the diagnostic aspects concerning continence in order to choose for each patient the most appropriate procedure for the treatment of all disturbance of stool control. A long term review of 312 patient with MAR, Myelomeningocele and severe stipsis with soiling was undertaken to determine the level of continence achieved. The choice between conservative measures and surgical procedures depends on clinical and manometric findings.

Embryonal rhabdomyosarcoma of the lung arising in cystic adenomatoid malformation: case report and review of the literature.

Rhabdomyosarcoma (RMS) of the lung is a very rare lesion, but the association with cystic adenomatoid malformation (CCAM) is unlikely to be a coincidence. Although the etiologic factors predisposing infants and children to pulmonary neoplasms are unknown, pulmonary developmental abnormalities may play a pathogenetic role. A case of embryonal pulmonary RMS is described, which was discovered within a congenital CCAM in a 22-month-old child. The hypothesis regarding histogenesis of this neoplasm are also briefly discussed. Because of the risk of malignant change, early removal of the congenital cystic lesions of the lung is advisable.

Juxta-adrenal malignant schwannoma.

A case of malignant schwannoma occurring in an 11-year-old boy is described. To our knowledge, this is the third case of malignant juxta-adrenal schwannoma reported in the literature. It was misdiagnosed at the onset of the disease as a post-traumatic renal hematoma. Angiography revealed that the tumor derived its blood supply from collateral vessels of the aorta, splenic, and left gastric arteries. An analysis of the diagnosis, clinical course, and prognostic factors of this rare tumor is performed.

Laparoscopic surgery for adolescent varicocele: preliminary report on 80 patients.

Laparoscopic clipping and division of the internal spermatic vessels was performed without complications in 80 adolescents to treat varicocele. In four cases the procedure had to be converted to open surgery. Two of the cases were converted because of technical errors during CO2 insufflation and in two cases because dissection of the vessels was impossible owing to abnormal adhesion of sigmoid colon. At 6 months' follow-up there was only one relapse. Only one hydrocele was noted postoperatively, and testicular size did not decrease in any patient. The authors believe that laparoscopic varicocelectomy is a simple, safe, and effective surgical procedure, which could be proposed as an alternative to open surgical or percutaneous embolization approaches. However, much more experience is needed to obtain a definitive conclusion.

[Cystic-papillary neoplasm of the pancreas: a case report in childhood]. / Neoplasia cistico-papillare del pancreas: descrizione di un caso in età pediatrica.

A solid and cystic tumor of the pancreas in a 11-year-old girl is reported. The child presented with abdominal pain and vomiting. A voluminous tumor, arising from the pancreas tail, was removed with distal pancreatectomy. These neoplasma occur predominantly in girls and young women, the prognosis is usually good in spite of histologic finding of apparent malignancy. The histochemical, immunohistochemical and electron examinations of this tumor show polymorphic differentiation, which means that part of the all can differentiate into duct epithelium, acinar or endocrine line. So up to, recently this tumor has been misclassified within other pancreatic tumors, and frequently has been managed with aggressive surgery. But as the neoplasm usually behaves like a very low grade malignancy, its complete removal is the treatment of choice for the tumors arising anywhere in the pancreas. The authors emphasize the importance of accurate diagnosis and of extirpative surgery in children with pancreatic malignancy.

Timing of surgery after acute myocardial infarction.

OBJECTIVE: We wished to determine if timing of surgery, when other co-morbid variables are controlled, influenced outcome after operations for acute myocardial infarction. DESIGN: Between 3/20/1990 and 6/17/1994, data was prospectively collected on 338 patients undergoing operation for either evolving infarcts (n=73) or up to 21 days after infarction (mean 7.9 days). SETTING: Tertiary hospital referral center. PATIENTS: Infarction was diagnosed by CK enzymes or EKG Q-waves preoperatively in 338 patients undergoing surgery. The mean age of the patients was 66.1 years (SD+/-10.5 years), 76 had emergency operations immediately after catheterization (50 following PTCA complications), 223 had urgent operations, and 39 were elective. INTERVENTIONS: Seventy-three had preoperative ballon pumps, and 259 had one or more mammary artery bypasses with a mean of 3.27 (SD+/-1.0) distal anastomoses. RESULTS: In-hospital and 30-day survival rate was 95.6% (323/338). Of the 73 variables evaluated by step-wise logistic regression analysis, the multivariate independent preoperative predictors of death were: aortic valve regurgitation, chronic pulmonary disease, preoperative diuretic administration, preoperative balloon pump, preoperative inotropes, and the need for additional concomitant noncardiac surgery. Including the operative variables, the predictors were: preoperative balloon pump, preoperative inotropes, the presence of left main stenosis, preoperative renal failure, chronic pulmonary disease, valve disease, ischemic arrhythmia, pump perfusion time, valve surgery, and homologous blood transfusion volume required. When the postoperative variables were included, the predictors were: preoperative inotropes, postoperative balloon pump, postoperative epinephrine, postoperative permanent stroke, and postoperative acute renal failure. The time between infarction and operation was not an independent prediction (p>0.4) in any of the logistic regression models. CONCLUSION: Early operation after acute infarction is not in itself a risk factor, rather comorbid disease and preoperative hemodynamic status determine outcome after surgery.