Carbamoyl phosphate synthetase 1 deficiency in Italy: clinical and genetic findings in a heterogeneous cohort.

Carbamoyl Phosphate Synthetase 1 deficiency (CPS1D) is a rare autosomal recessive urea cycle disorder, potentially leading to lethal hyperammonemia. Based on the age of onset, there are two distinct phenotypes: neonatal and late form. The CPS1 enzyme, located in the mitochondrial matrix of hepatocytes and epithelial cells of intestinal mucosa, is encoded by the CPS1 gene. At present more than 220 clear-cut genetic lesions leading to CPS1D have been reported. As most of them are private mutations diagnosis is complicated. Here we report an overview of the main clinical findings and biochemical and molecular data of 13 CPS1D Italian patients. In two of them, one with the neonatal form and one with the late form, cadaveric auxiliary liver transplant was performed. Mutation analysis in these patients identified 17 genetic lesions, 9 of which were new confirming their "private" nature. Seven of the newly identified mutations were missense/nonsense changes. In order to study their protein level effects, we performed an in silico analysis whose results indicate that the amino acid substitutions occur at evolutionary conserved positions and affect residues necessary for enzyme stability or function.

Giant Sigmoid Diverticulum: A Rare Presentation of a Common Pathology.

Although colonic diverticulum is a common disease, affecting about 35% of patients above the age of 60, giant sigmoid diverticulum is an uncommon variant of which only relatively few cases have been described in the literature. We report on our experience with a patient affected by giant sigmoid diverticulum who was treated with diverticulectomy. Resection of the diverticulum is a safe surgical procedure, provided that the colon section close to the lesion presents no sign of flogosis or diverticula; in addition, recurrences are not reported after 6-year follow-up.

[Prevention and treatment of congenital toxoplasmosis: organization protocol]. / Prevenzione e trattamento della toxoplasmosi congenita. Modello organizzativo.

AIM: Prevention and treatment of congenital toxoplasmosis are still a matter of debate among obstetricians, pediatricians and epidemiologists. There is no consensus about antenatal screening and diagnostic tests, nor there is about treatment for presumed infection in pregnancy. As an example of this type of organisation for health care delivery, a regional model has been promoted as a multidisciplinary approach for prenatal diagnosis of congenital toxoplasmosis. The model had been designed on the national guidelines of the National Health Institute (Istituto Superiore di Sanità, ISS). METHODS: Suspected maternal infections are referred and seen as outpatients at our centre on a specific day of the week; maternal investigation (specific IgG, IgM, IgA and IgG avidity titres) are performed at the Institute of Virology of the University of Bari, and patients are started on spiramycin. All cases of true or presumed seroconversion are counselled for amniotic fluid sampling and the sample is sent to ISS. In cases of late seroconversion and positive amniotic fluid results, patients are prescribed pyrimethamine+sulphonamide+folinic acid and alternate spiramycin until the end of pregnancy. A fetal-neonatal follow-up is performed in all cases. RESULTS: During the period 1999-2001, 180 cases of presumed toxoplasmosis infection have been referred (average 60 cases per year). We have been able to reclute, since the adoption of the national network protocol, 1/3 of presumed regional cases with a positive increasing trend. CONCLUSION: The service for prenatal diagnosis of toxoplasma gondii infection has definitely benefitted from the adoption of this protocol, which combines adherence to a national network and pays respect to regional requirements.

Italian Group for Lap-Band System: results of multicenter study on patients with BMI < or =35 kg/m2.

BACKGROUND: The Lap-Band System is the most common bariatric operation world-wide. Current selection criteria do not include patients with BMI < or = 35. We report the Italian multicentre experience with BMI < or = 35 kg/m(2) over the last 5 years. PATIENTS AND METHODS: Data were obtained from 27 centres involved in the Italian Collaborative Study Group for Lap-Band System. Detailed information was collected on a specially created electronic data sheet (MS Access 2000) on patients operated in Italy since January 1996. Items regarding patients with BMI < or = 35 were selected. Data were expressed as mean +/- SD except as otherwise indicated. RESULTS: 225 (6.8%) out of 3,319 Lap-Band patients were recruited from the data-base. 15 patients, previously submitted to another bariatric procedure (BIB =14; VBG= 1) were excluded. 210 patients were eligible for study (34M/176F, mean age 38.19+/-11.8, range 17-66 years, mean BMI 33.9+/-1.1, range 25.1-35 kg/m(2), mean excess weight 29.5+/-7.1, range 8-41). 199 comorbidities were diagnosed preoperatively in 55/210 patients (26.2%). 1 patient (0.4%) (35 F) died 20 months postoperatively from sepsis following perforation of dilated gastric pouch. There were no conversions to laparotomy. Postoperative complications presented in 17/210 patients (8.1%). Follow-up was obtained at 6, 12, 24, 36, 48 and 60 months. At these time periods, mean BMI was 31.1+/-2.15, 29.7+/-2.19, 28.7+/-3.8, 26.7+/-4.3, 27.9+/-3.2, and 28.2+/-0.9 kg/m(2) respectively. Co-morbidities completely resolved 1 year postoperatively in 49/55 patients (89.1%). At 60 months follow-up, only 1 patient (0.4%) has a BMI >30. CONCLUSIONS: Although surgical indications for BMI < or = 35 remain questionable, the Lap-Band in this study demonstrated that all but 1 patient achieved normal weight, and most lost their co-morbidities with a very low mortality rate.

Facial hemangioma and malformation of the cortical development: a broadening of the PHACE spectrum or a new entity?

Facial hemangioma is usually isolated but its association with craniocervical arterial anomalies and structural brain malformations is well known. The acronym PHACE syndrome (posterior fossa malformation, facial hemangiomas, arterial anomalies, cardiac/aortic anomalies, and eye abnormalities) has been used to indicate that disorder in which brain anomalies are mainly represented by the Dandy-Walker malformation. We report on a 10-month-old boy affected by facial hemangioma and a complex cortical dysplasia located in the left frontal region. The lesion was characterized by a deeply infolding pachygyric cortex and a band of gray matter lining the wall of the lateral ventricle. The entire left cerebral hemisphere appeared hypoplastic. No anomalies of the posterior fossa structures or cardiac/aortic malformations were present. An overlapping clinical/pathological pattern was previously reported in another patient with facial hemangioma and cerebrovascular anomalies. These observations seem to indicate that the facial hemangiomas may be associated with disorders of the cortical development.

The Italian Group for LAP-BAND: predictive value of initial body mass index for weight loss after 5 years of follow-up.

BACKGROUND: Laparoscopic of the LAP-BAND System placement stage of obesity is a safe operation, but its indication in terms of stage of obesity is controversial. The aim of this study was to evaluate the 5 years stage of obesity results for weight loss in patients with varying preoperative ranges of body mass index (BMI). METHODS: Data were obtained from the Italian Collaborative Study Group for LAP-BAND System (GILB) registry. Detailed information was collected on a specifically created database (MS Access 2000) for patients operated on in Italy from January 1996 to 2003. Patients operated on between January 1996 and December 1997 were allocated to four groups according to preoperative BMI range: 30-39.9 kg/m(2) (group A), 40-49.9 kg/m(2) (group B), 50-59.9 kg/m(2) (group C), and =60 kg/m(2) (group D) percent estimated weight loss respectively. Postoperative complications, mortality, BMI, BMI loss, and (%EWL) were considered in each group. Data are expressed as mean +/- SD, except as otherwise indicated. Statistical analysis was done by means of Fisher's exact test, and p < 0.05 was considered significant. RESULTS: After 5 years from LAP-BAND System surgery, 573 of 3,562 patients were eligible for the study. One hundred fifty-five of 573 (27.0%) were lost to follow-up, 24 of 418 (5.7%) underwent band removal due to complications (gastric pouch dilation, band erosion), eight of 418 (1.9%) were converted to other bariatric procedures, five of 418 (1.2%) died of causes not related to the operation or the band, and 381 of 573 (66.5%) were available for follow-up. Based on 96, 214, 64, and seven patients their preoperative BMI, Were allocated to groups A, B, C, and D, respectively. At time of follow-up mean BMI was 27.5 +/- 5.2 in group A, 31.6 +/- 4.7 in group B, 37.6 +/- 17.3 in group C, and 41.4 +/- 6.9 kg/m(2) in group D. Mean BMI loss was 9.8 +/- 5.4, 12.9 +/- 5.2, 15.8 +/- 8.1, and 23.2 +/- 4.9 kg/m(2), respectively, in groups A, B, C, and D. Mean %EWL at the same time was 54.6 +/- 32.3 in group A, 54.1 +/- 17.2 in group B, 51.6 +/- 35 in group C, and 59.l +/- 17.1 in group D. CONCLUSION: Initial BMI in this series did not correlate with %EWL 5 years after the operation. In fact %EWL was almost the same in each group, independent of preoperative weight. Initial BMI was an accurate indicator of the results obtained 5 years after LAP-BAND in group C (50-59.9 kg/m(2)) and D (=60 kg/m(2)) patients, who remained morbidly obese despite their %EWL.

Lap Band adjustable gastric banding system: the Italian experience with 1863 patients operated on 6 years.

BACKGROUND: The Lap Band system procedure is currently the most common bariatric surgical procedure worldwide. This is an interim report of the experience of the 27 Italian centers participating in the national collaborative study group for Lap Band (GILB). METHODS: An electronic database was specifically created. It was mailed and e-mailed to all of the surgeons now performing the laparoscopic gastric banding operation in Italy. RESULTS: Beginning in January 1996, 1893 patients were recruited for the study. There were 1534 women and 359 men with a mean body mass index (BMI) of (range 30.4-83.6) and a mean age of 37.8 +/- 10.9 years (range; 17-74). The mortality rate has been 0.53% (n = 10), mainly due to cardiovascular complications (myocardial infarction, pulmonary embolism). The laparotomic conversion rate has been 3.1% (59/1893) and was higher in superobese patients (BMI>50) than in to morbidly obese patients (BMI <50) (p <0.05). Postoperative complications occurred in 193 patients (10.2%), including tube port failure (n = 79; 40.9%), gastric pouch dilation (GPD) (n = 93; 48.9%), and gastric erosion (n = 21, 10.8%). Most GPD (65.5%) occurred during the first 50 patients treated at each center. The incidence of GPD decreased as the surgeons acquired more experience. Surgery for complications was often performed by laparoscopic access, rarely via laparotomy. No death was recorded as a consequence of surgery to treat complications. Weight loss has been evaluated at the following intervals: 6, 12, 24, 36, 48, 60, and 72 months, with BMI 37.9, 33.7, 34.8, 34.1, 32.7, 34.8, and 32. CONCLUSIONS: The Lap Band system procedure has a very low mortality rate and a low morbidity rate and it yields satisfactory weight loss. Surgery for complications can be performed safely via laparoscopic access.

Results of the Italian multicenter study on 239 super-obese patients treated by adjustable gastric banding.

BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) is the most common bariatric operation. This study is a retrospective analysis of the multicenter Italian experience in patients with BMI > 50 over the last 4 years. METHODS: An electronic data sheet made for LAGB-operated patients since January 1996, was mailed and e-mailed to all surgeons involved in this kind of procedure in Italy. Items regarding patients with BMI > 50 were selected. Analysis used Fisher's exact test and logarithmic regression analysis (P < 0.05 significant). Data were expressed as mean +/- SD. RESULTS: 239 patients (13.3%), out of 1,797 Lap-Band operated patients entered the study (179F / 60M), with mean age 37.6 +/- 11.3 years (19-69) and mean BMI 54.6 +/- 4.8 (50.1-83.6). Laparotomic conversion rate was 5.4% (44/239). Postoperative complications occurred in 24 / 239 patients (9.0%). Follow-up was obtained in 218 / 218, 198 / 198, 121 /147, 75 / 93, 30 / 38 LAGB patients at 6,12, 24, 36, and 48 months respectively. At these time periods, mean BMI was 46.7, 43.9, 42.2, 41.9, and 39.3 kg/m2. At the same intervals, mean %EWL was 24.1, 34.1, 38.8, 38.9, and 52.9%. The number of patients with < 25% EWL at 12, 24, 36, and 48 months follow-up were 34, 10, 4, and 0. Serious co-morbidities (189 in 124 of 239, 57%) had completely resolved 1 year postoperatively in 74 / 124 of the patients (59.6%). CONCLUSION: Although super-obese patients following the LAGB remain obese with BMI > 35, in the short-term most lose their co-morbidities, with a very low morbidity and mortality rate.

Mild ventriculomegaly as a counselling challenge.

OBJECTIVE: Our purpose was to evaluate the outcome of a group of fetuses with mild ventriculomegaly. METHODS: We retrospectively collected all cases of antenatally diagnosed mild enlargement of the lateral cerebral ventricles (transverse diameter of the atrium between 10 and 15 mm) between 1992 and 1997. Cases were included in the study if no other ultrasonic anomalies (including soft markers) were found. TORCH screening, karyotyping, search for associated anomalies and neurological examination (including imaging) were performed. Outcome information was available for all cases up to 30 months. RESULTS: Fourteen cases were examined. TORCH was always negative, 1 case with a microdeletion of chromosome 1 was identified. During the course of pregnancy, 2 fetuses showed progression to frank hydrocephalus. Five cases of agenesis of the corpus callosum, 1 of lissencephaly and 1 of heterotopia were eventually diagnosed. After birth 2 syndromes were identified. Three babies died during the follow-up period, among the survivors 4 had severe neurological damage, 2 of them had no associated dysmorphic findings. DISCUSSION: A heterogeneous group of central nervous system disorders may manifest antenatally as mild ventriculomegaly. The current management may not be able to identify dangerous conditions that present subtle dysmorphic features, or be able to predict abnormal outcome in most of the cases.

Laparoscopic Italian experience with the Lap-Band.

BACKGROUND: An increasing number of surgeons with different levels of experience with laparoscopic surgery and open obesity surgery have started to perform laparoscopic implantation of the Lap-Band. METHODS: An electronic patient data sheet was created and was mailed and e-mailed to all surgeons performing laparoscopic adjustable silicone gastric banding (LASGB) in Italy. Patients were recruited since January 1996. Data on 1,265 Lap-Band System operated patients (258 M/1,007 F; mean BMI 44.1, range 27.0-78.1; mean age 38, range 17-74 years) were collected from 23 surgeons performing this operation. RESULTS: Intra-operative mortality was absent. Post-operative mortality was 0.55% (7 patients) for causes not specifically related to LASGB implantation. The laparotomic conversion rate was 1.7% (22 patients). LASGB related complications occurred in 143 patients (11.3%). Pouch dilatation was diagnosed in 65 (5.2%), and 28 (2.2%) of these underwent re-operation. Band erosion was observed in 24 patients (1.9%). Port or connecting tube-port complications occurred in 54 patients (4.2%), 12 of whom required revision under general anesthesia. Follow-up was obtained at 6, 12, 18, 24, 36 and 48 months, and mean BMI was respectively 38.4, 35.1, 33.1, 30.2, 32.1 and 31.5. The percentage of patients observed at each follow-up was > 60%. There was no intra-operative mortality and no complication-related mortality, with acceptable weight loss. CONCLUSION: The LASGB operation is safe and effective, and deserves wider use for treatment of morbid obesity.

Initial experience with laparoscopic adjustable gastric banding and pouch dilatation: two cases.

BACKGROUND: Late proximal pouch dilatation (LPPD) has occurred occasionally following gastric banding for morbid obesity. At present, laparoscopic conservative resetting and oversuturing of the band is considered the standard procedure for pouch dilatation without any important posterior component. METHODS: Two cases of LPPD are presented, which occurred in our initial experience with the Lap-Band, corrected via a laparoscopic approach. RESULTS: The reintervention was necessary in both patients, with conservative laparoscopic repositioning and oversuturing of the band in the first case and laparoscopic substitution of the gastric band in the second. We have not observed further complications, and weight loss has been maintained in a midterm outcome in both cases (30 and 18 months follow-up). CONCLUSIONS: LPPD can be corrected with a conservative laparoscopic surgical approach, without complications and negative functional effects on mid-term outcome.

Familial medullary thyroid carcinoma (FMTC). Study of one family (treatment criteria).

AIM: The nosology of familial medullary thyroid carcinoma (FMTC) has been described as a distinct pathology, genetically determined and with autosomal dominant transmission with a gene penetrance of almost 100%. The diagnosis of this morbid condition can be made if at least four members of the same family are affected by calcitonin-secreting C-cell carcinoma. METHODS AND RESULTS: We report the analysis of a family in which FMTC was diagnosed between 1993 and 1998. Of the five patients we confirmed as being affected by FMTC, we were able to perform a prophylactic thyroidectomy in only one case. The high possibility of lymph-node metastasis at the time of clinical diagnosis (52-75%), and the high morbidity and radio-chemo-resistance to adjuvant therapies, indicate total thyroidectomy with central lymph-node dissection. CONCLUSION: It appears that preventive lymphadenectomy does not substantially improve survival, while pre-clinical diagnosis is of greater importance than surgery in improving survival and preventing recurrence. Total preventive thyroidectomy has been recommended in all carriers of ret genetic defects, even in families at risk with mutations of the 618 or 620 codon, because the penetrance of FMTC approaches 100%, and a 100% accordance between presence of the disease and gene carrier status is reported. This procedure would therefore represent the only possibility of achieving a 100% cure in subjects affected by familial medullary thyroid carcinoma.

Bariatric surgery: early results with a multidisciplinary team.

BACKGROUND: Bariatric surgery depends on complete preoperative study of morbid obesity, in order to obtain the treatment of choice. A multidisciplinary group was founded in 1998 at the University of Siena. METHODS: During 1998, 16 patients, with median weight 121.8 +/- 31 kg and median body mass index (BMI) 43 +/- 6, underwent bariatric surgery. A multidisciplinary assessment was used in order to evaluate psychological status, food intake problems and patient compliance, and hemodynamic, respiratory, metabolic and arthritic functions. 13 patients were submitted to laparoscopic surgery: in 11 adjustable gastric banding was performed and 2 were submitted to a vertical gastroplasty plus adjustable gastric banding. Three patients were operated via traditional laparotomy, due to previous abdominal surgery in 2 cases (submitted to an adjustable gastric banding) and one woman was submitted to a bilio-intestinal bypass according to the Hallberg technique, for her psychiatric troubles and coexisting systolic hypertension and uncontrolled diabetes. Monthly follow-up for each patient continues after 6 months. RESULTS: No morbidity or mortality has occurred. The median weight loss at three months, was 19.5 kg. Two cases required injection of 1 ml more of fluid into the port, respectively at 4 and 9 months. Fifteen days after surgery, seven patients (46%) had vomiting episodes, due to rapid food intake. All patients have shown an improvement of their comorbidities after surgery. CONCLUSION: Early results via the multidisciplinary team and laparoscopic banding have been satisfactory thus far.

[Follow-up of the preterm child at 1 year of correct age: assessment of development risk]. / Follow-up del bambino nato pretermine a 1 anno di età corretta: valutazione del rischio di sviluppo.

Longitudinal follow-up of preterm neonates after discharge from Intensive Care satisfies the family's need for support and ensures an ongoing link with the hospital concerned, but must be based on a specific, sensitive and predictive screening program. We report a prospective cohort study in a tertiary neonatal intensive care unit (NICU) using the Perinatal Risk Inventory (PERI)1, at discharge. Of 87 consecutive newborn referred to the tertiary NICU at the Pediatrics Department of Padua University in 1993 (gestational age > or = 25 weeks, weight at birth < 1500 g), 65 (75%) survived: 54 cases complied with the Fitzhardinge '80 criteria and were followed up to at least 1 year (corrected age). A further 18 neonates with neonatal cerebral problems were also considered. The PERI at discharge was combined with neonatological and neuro-evolutional evaluation and examination of neuro-sensorial development indicators at the corrected ages of 0, 3, 6 and 12 months. PERI scores were: < or = 7 in 36; 8-11 in 22; > 11 in 14. The cut off point at 7 to 11 increases the sensitivity, the specificity and the predictive values of the test. At 1 year (corrected age), 6 patients (8.3%) had a diagnosis of spastic diplegia and 2 (2.7%) had spastic hemiplegia. The relative risk of cerebral paralysis was 4.5 in the neonates with IVH 4 degrees, odds ratio 6.7, and 3.6 in the 16 patients with bronchopulmonary dysplasia (BPD), odds ratio 4.7. 72 patients were selected for follow-up by the Fitzhardinge '80 criteria, whereas with the PERI (cut off point 7) only 44 neonates would have been selected. This confirms the need for new criteria in recruiting preterm neonates for longitudinal follow-up to quantify neurological risks, particularly in view of the socioeconomic impact of the problem.

[Diverticulosis and neoplasms of the colon]. / Diverticolosi e neoplasie del colon.

About half of the carcinomas and polyps of the large intestine is placed in the descendent colon and in the sigma, where most frequently the diverticula are found. Literature refers to them as varying percentage of association diverticulosis-carcinoma between 2 to 8 percent. The increase of the frequency of neoplasms and diverticula in the same population classes may indicate common factors in their development. The study includes 1149 cases of colo-rectal neoplasms examined in the Department of Scienze Chirurgiche--University of Siena, from january 1981 to december 1993. The association of carcinomas and diverticula has been found in 8.96% of the cases (103 pts) and the tumours with stenosis in 59,2% of the cases. The colonoscopy is very important for a more precise differential diagnosis especially in occlusive forms, in which a multiple biopsy is indispensable. Referring to the data of literature, the authors consider that patients with symptomatic diverticular disease have a major general risk for cancer of the large intestine; the existence of certain common symptoms in either disease (especially the bleeding) may not exclude the presence of a tumor in patients with diverticular disease.

[Surgical treatment of neoplasms in geriatric patients]. / Il trattamento chirurgico delle neoplasie nei pazienti in età geriatrica.

The Authors report their experience in the surgical management of cancer in the aged (over 65 year old patients), during the period 1988-1992 at the Istituto Policattedra di Scienze Chirurgiche, University of Siena. They consider colon and rectum, breast, stomach, pancreas and biliary tract neoplasms in relation to site, staging, emergency or delayed surgical treatment, and early postoperative results. Finally, they outline the frequently encountered problems in treating old patients and the most appropriate surgical approach.

[Ischemic colitis localized in the right colon. A clinical case report]. / La colite ischemica localizzata al colon destro. Osservazioni su di un caso clinico.

Ischemic colitis shock-associated still is a not well-defined clinical entity. The authors describe symptoms, clinical course and treatment in a case recently observed. They outline the difficulties of preoperative diagnosis and the need of a not postponable surgical treatment due to shock and peritonitis.

[Antropyloric preservation in pancreatic excisions]. / La conservazione antro-pilorica nelle exeresi pancreatiche.

The authors report 11 consecutive partial or total pancreatectomies with preservation of the pylorus. They believe this technique is to be preferred because it allows a better digestion and reduces complication rate.