The genome of chemorefractory chronic lymphocytic leukemia reveals frequent mutations of NOTCH1 and SF3B1.

Next-generation whole-exome sequencing has revealed two novel genes, namely NOTCH1 and SF3B1, whose mutations predict poor outcome and preferentially associate with chemorefractory chronic lymphocytic leukemia (CLL). Analysis of 539 CLL cases documents that NOTCH1 mutations i) represent one of the most frequent cancer gene mutations involved at presentation; ii) cluster with cases harboring trisomy 12 and tend to be mutually exclusive with TP53 disruption among genetic subgroups; iii) identify high-risk patients showing poor survival similar to that associated with TP53 abnormalities; and iv) exert a prognostic role independent of widely accepted clinical and genetic risk factors. Mutations of SF3B1, a splicing factor that is a critical component of the spliceosome, recurrently associate with fludarabine-refractory CLL, occur at a low rate at CLL presentation and have a minor role in Richter transformation, corroborating the notion that CLL histological shift is molecularly distinct from chemorefractory progression without the Richter transformation.

Comparison between 2D and 3D computed tomography evaluation of glenoid bone defect in unilateral anterior gleno-humeral instability.

PURPOSE: This study evaluated the agreement between 2D and 3D computed tomography (CT) measurements in identifying the size and type of glenoid-bone defect in anterior glenohumeral instability. MATERIALS AND METHODS: One hundred patients affected by unilateral anterior glenohumeral instability underwent a CT of both shoulders. Images were processed with both 2D [multiplanar reconstruction (MPR)] and 3D [volumerendering (VR)] methods. The area of the missing glenoid was calculated in comparison with the healthy glenoid and expressed as a percentage. Agreement between the two measurements was assessed according to the Bland-Altman method; a 5% mean difference was considered as clinically relevant. RESULTS: Analysis of agreement between MPR and VR measurements of the percentage of missing glenoid showed a mean difference equal to 0.62%±1.96%. Percent agreement between the two measurements in detecting the presence of bone defect was 97% (p<0.0001). Percent agreement between the two measurements in discriminating the type of bone defect was 97% (p<0.0001). CONCLUSIONS: Agreement between 2D (MPR) and 3D (VR) CT measurements to identify the size and type of glenoid-bone defect in anterior glenohumeral instability was so high that the two measurements can be considered interchangeable.

Utility of STR markers for the molecular diagnosis of a large Brazilian family with Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth type 1A disease (CMT1A) is most frequently caused by a tandem DNA duplication of a 1.4-Mb genomic fragment in the 17p11.2-12 chromosomal region. The disease is probably the product of a dosage effect of the peripheral myelin protein 22 gene located within the duplicated segment. We sought to study the largest reported Brazilian family with suspected diagnosis of CMT1A using eight short tandem repeat microsatellite markers. In addition, we analyzed the informativeness of these markers in the normal Brazilian population. The duplication was found in 12 members of the family. In two patients with CMT1A symptoms, the duplication was not detected, and one asymptomatic subject showed the duplication. D17S2230, D17S9B, D17S2220, D17S2227, D17S9A, and D17S4A markers showed the highest heterozygosity rates, and D17S2228 and D17S2224 markers were the least informative in our analysis.

[Diffuse post-traumatic calcification of the anterior longitudinal ligamentum of cervical and dorsal spine]. / Diffusa calcificazione post-traumatica del legamento longitudinale anteriore a livello cervico-dorsale.

Among the different conditions causing inflammation and calcification/ossification of the soft tissues of the spinal cord, single or recurrent traumatic events are included. Within the international literature, the involvement of the posterior longitudinal ligament, following spinal cord injuries is frequently reported, especially in the elders. The Authors describe here an uncommon calcification/ossification of the anterior longitudinal ligament occurred after a double traumatic event in a young man, followed clinically and radiologically for a long-term period. On the basis of clinical, laboratory and radiological findings, the differential diagnosis with other possible aetiologies, especially DISH (Diffuse idiopathic skeletal hyperostosis) and ankylosing spondylitis, is discussed.

[Prenatal diagnosis of congenital diaphragmatic hernia: an update]. / Aggiornamento in tema di diagnosi prenatale di ernia diaframmatica congenita.

Congenital diaphragmatic hernia (CDH) has an incidence of approximately 1:4000 live births. Most frequently the diaphragmatic defect is a left and posterolateral (Bochdalek) one. Prenatal diagnosis is made at ultrasonography; the relevant sonographic features will be described in the paper. Cystic adenomatoid malformation of the lung (CAML), pulmonary sequestration, bronchogenic cysts, pulmonary hypoplasia/agenesia need to be considered in differential diagnosis. In some cases, diagnosis of CDH is not possible "in utero": in such cases, herniation of abdominal viscera into the thorax takes place presumably just at delivery through a small diaphragmatic defect. CDH may be associated with intrauterine growth retardation (IUGR), chromosomal abnormalities (3%) and/or other malformations (10-50%): such as Central Nervous System, digestive, cardiac and urogenital anomalies. Therefore, search of associated malformations and amniocentesis with analysis of fetal karyotype are mandatory, whenever a CDH is diagnosed. CDH is still at present characterised by a high mortality (reportedly, about 45%). Many prognostic factors have been correlated to postnatal outcome of CDH: some of them are valuable prenatally by ultrasonography. However, the role of sonography in the prediction of neonatal outcome is still controversial: in particular, although many ultrasonographic parameters have been proposed, prenatal evaluation of pulmonary hypoplasia (a crucial factor related to postnatal survival) has not proved to be very accurate so far. Nevertheless, it is undisputable that prenatal diagnosis itself represents a crucial prognostic factor for CDH, since it allows birth of the affected fetuses in 3d level Perinatologic Centres provided with a Neonatal Intensive Care Unit and Neonatal Surgery.

Laparoscopic surgery in treatment of stage IIb cervical cancer after neoadjuvant chemotherapy. A case report and review of the literature.

BACKGROUND: A detailed operative procedure of laparoscopic radical hysterectomy (type III) with pelvic and aortic lymphadenectomy after neoadjuvant chemoterapy in treatment of Stage IIb cervical cancer is described. CASE REPORT: A 50-year-old patient with Stage IIb squamous cell carcinoma of the uterine cervix, who initially was not surgically resectable, received three courses of neoadjuvant chemotherapy that included ifosfamide 5 g/m2, cisplatin 50 mg/m2 and paclitaxel 175 mg/m2 (TIP). Following a partial clinical response to chemotherapy, the patient underwent laparoscopic type III radical hysterectomy with bilateral salpingo-oophorectomy and pelvic and paraaortic lymphadenectomy. The surgical procedure lasted 250 minutes. Blood loss was 310 ml. The patient was discharged on postoperative day 4. The mean length of the resected parametria and paracolpia was 4.1 cm and 2.0 cm, respectively. The number of dissected lymph nodes was 48:29 pelvic and 19 paraaortic nodes. No major intraoperative or postoperative complications occurred. The patient also underwent adjuvant radiation therapy. Follow-up was performed at six months so far. CONCLUSIONS: This experience suggests that such a surgical procedure is safe. Laparoscopic radical hysterectomy potentially allows for decreased perioperative morbidity and blood loss, faster recovery and better cosmetic results. Large studies with long term follow-up are needed to confirm that this approach may be proposed as an alternative to conventional surgery.

[Asthma and pregnancy]. / Asma e gravidanza.

During pregnancy the asthma has an incidence of 1-4%. In addition to this pathology we find, during pregnancy, an increased incidence of complications both maternal and fetal. These complications, often serious, happen nearly exclusively in patients with severe asthma and/or badly controlled. Therefore, to reduce the risk of beginning of these complications it's necessary to assess correctly the gravity of asthma before becoming pregnant, to make a careful and periodic control of the respiratory function of the patient, to effect a suitable preventive and/or symptomatic pharmacological therapy and to establish specific sanitary-action measures able to prevent the disease becomes acute.

Multidisciplinary management of fetal surgical anomalies: the impact on maternal anxiety.

AIM: To assess the impact on maternal anxiety of a multidisciplinary approach in prenatal management of fetal surgical anomalies. DESIGN: A case-control study was undertaken: Group A (cases) consisted of 16 couples receiving a prenatal multidisciplinary counselling, Group B (controls) was represented by 16 couples, who received diagnosis of the fetal anomaly and the relevant counselling by an obstetrician only. The fetuses were affected by the following gastrointestinal anomalies: gastroschisis, omphalocele, intestinal atresia. METHODS: The Italian version of the Spielberger State-Trait Anxiety Inventory was utilized to assess maternal anxiety. In Group A maternal anxiety level was assessed after the first antenatal counselling and at birth, whereas in Group B only at birth. RESULTS: At birth, Group A presented STAI-S scores significantly lower than after the first antenatal consultation with the team (Mean +/- SD = 39.87 +/- 6.46 versus 68.93 +/- 5.81; p < 0.01). At the end of the first day spent with the baby in the Neonatal Surgery Unit, Group A presented STAI-S scores significantly lower than Group B (Mean +/- SD = 39.87 +/- 6.46 versus 70.62 +/- 4.12; p < 0.01). CONCLUSIONS: This study provides evidence of the positive impact on maternal anxiety of a multidisciplinary approach in prenatal management of fetal surgical anomalies.

[Female genital mutilation: FGM patients treated at the "Umberto I" polyclinic of Rome: 1985-1996]. / Mutilazioni genitali femminili: pazienti con esiti di FGM ricoverate nel Policlinico "Umberto I" di Roma: periodo 1985-1996.

The article deals with the medical aspect regarding female genital mutilations (FGM). The cultural origin of this tradition is also considered. Such a practice lies in the partial or complete excision of the external genitalia: it is highly widespread in Central Africa, especially in Ethiopia and Somalia. Currently, approximately 130,000,000 women are involved worldwide. In Italy, it is estimated that about 30,000 women amongst the immigrant population are involved (1). Due to the increasing immigration of women from Countries with FGM tradition, knowledge of the pathologies related to such a practice has become urgently necessary to physicians of western Countries. The aim of this study was to analyze the short-term complications of FGM, which are severe and often even deadly, as well as the long-term ones, which are more likely to be faced in the clinical practice of a western Country physician. In particular, a sample of nine women who had undergone infibulation, amongst the patients admitted at the Departments of Obstetrics and Ginaecology of university of Rome "La Sapienza" during the period 1 January 1985-31 december 1996, has been analyzed. Five out of these women suffered form gynaecological pathologies, whilst four from obstetrical pathologies. Our data on complications associated with FGM are in agreement with those of the world literature and highlight how a more specific expertise is necessary for a correct health care of these women.

[Current clinical features of septic abortion in Western countries. A series of cases observed during 1998 at the 1st and 2nd department of obstetrics and gynecology of the University of Rome La Sapienza]. / Attuali caratteristiche cliniche dell'aborto settico nei paesi occidentali. Casistica 1998 del I e II istituto di clinica osterica e ginecologica dell'Università di Roma "La Sapienza".

BACKGROUND: Advances in diagnostic techniques and therapy and the institution of both legislative measures and Centres for the protection of mother-infant health are major factors to which the reduced incidence of septic abortion in should probably be ascribed in Western Countries, where it reaches approximately 10%. The aim of this study was to analyse the current problems related to this pathology in a Western Country, such as Italy. METHODS: Cases of septic abortion observed at the I and II Department of Obstetrics and Gynaecology of University of Rome La Sapienza during 1998 were retrospectively analysed. RESULTS: 42 cases of septic abortion were observed. Fever was present in 100 % of cases, genital bleeding in 57 %, abdominal-pelvic pain in 16.7%, genital purulent discharge in one case (2.4%), pain of the fornices at vaginal examination in another (2.4%). Leucocytosis was detected in 21.5% of patients. Disseminated intravascular coagulation (DIC) occurred in one patient (2.4%). No maternal deaths were observed. Antibiotic therapy was carried out in 81% of cases, a uterine curettage in 95.2%. CONCLUSIONS: Currently, the possibility of early diagnosis of abortion due to the routine use of ultrasonography and, as a consequence, of early antibiotic therapy, whenever a sepsis is suspected, account for the predominance of mild or even doubtful clinical pictures of this pathology in Western Countries. Nevertheless, severe complications are possible in the case of septic abortion, including septicaemia, septic shock, DIC, renal insufficiency. Thus, a correct and careful attitude of prophylaxis and therapy is required.

Dynamic contrast enhanced magnetic resonance imaging subtraction in evaluating osteosarcoma response to chemotherapy.

PURPOSE: To evaluate the results of a new technique of dynamic contrast enhanced Magnetic Resonance (MR) imaging subtraction in the assessment of osteosarcoma response to chemotherapy. METHODS: 24 patients with high grade osteosarcoma, treated with preoperative neo-adjuvant chemotherapy, underwent MR at high field strength (1.5 T). Both unenhanced conventional SE T1- and T2-weighted sequences in the coronal and axial plane and dynamic Gd-DTPA-enhanced SE T1-weighted sequences in the coronal plane were performed. Image postprocessing included subtraction of unenhanced image from enhanced images (arbitrary called "angiographic subtraction") and subtraction of each enhanced image from the last-enhanced image (arbitrary called "pathologic area" subtraction). The early enhancing areas detected in the angiographic subtraction and the pathologic areas detected in the pathologic area subtraction were correlated with histopathological findings on histological macrosections obtained from the resected specimen. The sensitivity, specificity, accuracy, positive and negative predictive value of both the subtraction techniques were calculated. RESULTS: The early enhancing areas of angiographic subtraction were related not only to viable tumor but also to the host reactions such as flogosis and granulation tissue. The pathologic areas detected at the pathologic area subtraction correlated in most cases with viable tumor, while in 3 cases they did not correspond to viable tumor tissue and in 1 case a small area of residual viable tumor was missed. In assessing response to chemotherapy, pathologic areas subtraction had an accuracy of 95% (specificity: 100%, sensitivity: 93%, PPV: 100%, NPV: 88%), whereas angiographic subtraction had an accuracy of 79% (specificity: 37%, sensitivity: 100%, PPV: 76%, NPV: 100%). CONCLUSIONS: Pathologic area subtraction may be a useful technique for assessing the response of osteosarcoma to chemotherapy and for detecting residual viable tumor tissue.

[Current epidemiologic features of septic abortion]. / Attuali caratteristiche epidemiologiche dell'aborto settico.

BACKGROUND: This article deals with the current epidemiological features of septic abortion. METHODS: Forty-two of 431 abortions (9,74%) were diagnosed as septic abortions during 1998 at the I and II Institute of Obstetrics and Gynecology, University of Rome La Sapienza , and are retrospectively analyzed. RESULTS: Thirty-four women (81%) came from an EEC country, whereas 8 (19%) from a developing country. Their mean age was 31,4 years (range: 18-43 years). Eighteen patients (43%) were nulliparous; 24 (57%) multiparous; 14 (33%) had previous abortions, none had previous septic abortions. Among risk factors, premature rupture of membranes was found in 5 cases (12%); whereas amniocentesis, HIV positivity, diabetes, positive urine culture and illegal pregnancy termination procedures were found in 5 further cases. No risk factors were found in 76% of patients. CONCLUSIONS: It is observed that, due to medical-scientific advances, previously unknown risk factors have emerged during the last three decades in Western Countries, such as invasive procedures of prenatal diagnosis, IUD contraception and AIDS immunodepression. However, other previously frequent risk factors, such as sepsis from illegal abortion, may emerge again in Countries where abortion is legal (such as Italy), due to massive immigration of clandestine women from developing Countries.

The impact of the factor V Leiden mutation on pregnancy.

A resistance to the anticoagulant activity of activated protein C (APC), most frequently due to a point mutation in the Factor V gene (the Leiden mutation), represents the most common genetic cause of thrombophilia. The Leiden mutation has been significantly related to pregnancy complications associated with hypercoagulation, e.g. deep vein thrombosis during pregnancy (8-fold increased risk), pre-eclampsia (prevalence of the mutation up to 26%), placental infarction extending to > 10% of the placenta (10-fold increased risk), abruptio placentae (prevalence of the mutation up to 29.6%), and second- and third-trimester pregnancy failure (prevalence of the mutation up to 31.3%). An association of the maternal mutation with recurrent first-trimester miscarriage does not emerge from the literature, although fetal mutation (frequency higher than twice compared with that of the general population) has been related to early spontaneous miscarriage. Although some evidence suggests an association between APC resistance and intrauterine growth retardation, no significant relationship emerges currently from the literature. Screening for the Leiden mutation would seem advisable in women with previous pregnancy complications amongst those associated with APC resistance. Carriers of the mutation should be given appropriate counselling. The screening of asymptomatic women is not recommended at present.

Prenatal diagnosis of a bronchogenic cyst in an unusual site.

We report a rare case of a subdiaphragmatic cyst, diagnosed prenatally during routine ultrasound screening at 25 weeks' gestation. Serial ultrasonographic evaluation demonstrated a slight increase in the size of the cyst during pregnancy. On the basis of the anatomic site and the sonographic features of the lesion, four diagnostic hypotheses were postulated: cystic neuroblastoma, adrenal hemorrhage, duplication of the inferior third of the esophagus and retroperitoneal cystic lymphangioma. A healthy baby, weighing 3300 g and with Apgar scores of 8 and 9, was delivered vaginally at term. He underwent successful surgery at the age of 3 months. The post-operative course was uneventful and the baby is currently doing well. Histology revealed a bronchogenic cyst.

[Female genital mutilation and legislation]. / Mutilazioni genitali femminili e legislazione.

This article deals with the legal aspect concerning female genital mutilations (FGM). Such a practice (a partial excision of the external genitalia) is highly widespread in Central Africa, especially in Ethiopia and Somalia, and currently involves approximately 130,000,000 women worldwide and, in Italy, about 30,000 women amongst the immigrant population. Since 1982 the World Health Organization (WHO), which condemns such a practice as injurious to women's rights and health, proposed that laws and professional codes prohibit it in all countries. Legislation, although insufficient as a sole measure, is considered indispensable for the elimination of FMG. Since a long time some western countries (Sweden, Great Britain, Belgium and Norway), involved by immigration from countries with FGM tradition, legislated with regard to FGM. In Italy, a specific law does not exist; however, FGM are not allowed by the article 5 of the Civil Code. Nevertheless, recently, several cases of mutilations took place: this led some members of the Parliament to introduce a bill in order to specifically forbid FGM. The authors believe that legislation could effectively support the job of prevention and education, which physicians may carry out in order to save little girls from the risk of familial tradition of genital mutilations.

[Etiology and epidemiology of extrauterine pregnancy]. / Eziologia ed epidemiologia della gravidanza extrauterina.

In the last years, ectopic pregnancy has become a frequent problem, especially in the industrialized countries. Women aged 30-40 years are mostly affected. Infact, in this ten-years period, more and more women feel the desire of pregnancy at ripe age, first of all because of their job. This study shows 136 cases of extrauterine pregnancy, observed at our hospital, I and II Institute of Obstetric and Gynecological Clinic of "Policlinico Umberto I" in Rome from January 1997 to December 1999. The object of this analysis is to determine the characteristics and ethiologic factors of this pathology.

Cystic adenomatoid malformation of the lung: clinical evolution and management.

UNLABELLED: Cystic adenomatoid malformation of the lung (CAML) is a rare pulmonary maldevelopment resulting from an abnormal growth of the terminal bronchial structures. This study proposes a possible management of prenatally diagnosed CAML. A group of nine cases of CAML diagnosed prenatally between January 1990 and December 1995 was studied retrospectively. The evolution of lesions was followed in utero by serial ultrasound monitoring. Chest X-ray was performed at birth in all neonates and CT only in the symptomatic ones. CAML was macrocystic in three cases and microcystic in six. No polyhydramnios, hydrops or associated malformations were seen. In four cases, CAML was confirmed at birth and required surgery. The lesion decreased in size prenatally in five fetuses, of whom only one underwent surgery. In two further cases a prenatal diagnosis of CAML was changed to diaphragmatic hernia. CONCLUSION: Given the possible clinical disappearance or resolution of cystic adenomatoid malformation of the lung, we believe that surgery is justified at birth only in symptomatic and radiologically positive neonates. It could be safely delayed in those asymptomatic patients with either positive or negative chest X-ray. The former need computed tomography at birth, whereas, in the latter, it should be performed at 6 months of age for a more definitive assessment of the patient.