Stem cells to restore insulin production and cure diabetes.

BACKGROUND: The advancement of knowledge in the field of regenerative medicine is increasing the therapeutic expectations of patients and clinicians on cell therapy approaches. Within these, stem cell therapies are often evoked as a possible therapeutic option for diabetes, already ongoing or possible in the near future. AIM: The purpose of this document is to make a point of the situation on existing knowledge and therapies with stem cells to treat patients with diabetes by focusing on some of the aspects that most frequently raise curiosity and discussion in clinical practice and in the interaction with the patient. In fact, at present there are no clinically approved treatments based on the use of stem cells for the treatment of diabetes, but several therapeutic approaches have already been evaluated or are being evaluated in clinical trials. DATA SYNTHESIS: It is possible to identify three large potential application fields: 1) the reconstruction of the ß cell mass; 2) the immunomodulation in type 1 diabetes (T1D); 3) the treatment of complications. In this study we will limit the discussion to approaches that have the potential for clinical translation, deliberately omitting aspects of basic biology and preclinical data. Also, we intentionally omit the treatment of the complications that will be the subject of a future document. Finally, an overview of the Italian situation regarding the storage of cord blood cells for the therapy of diabetes will be given.

[Utility and safety endoscopic digestive procedure in pediatric age]. / Utilità e sicurezza delle procedure endoscopiche digestive in età pediatrica.

The aim of this study is to verify the utility and safety of endoscopic procedures in the evaluation of children with clinically-significant gastrointestinal symptomatology. We report our experience of 87 pediatric endoscopy procedures including esophagogastroduodenoscopy, colonoscopy and tissue biopsies performed in 85 infants, children and adolescent, 3 months-15 years old, over a two-year period, june 2002-november 2004 after complete history, physical examination and basic investigations. General anesthesia was used in all patients after informed consent obtained from parents. Non significant complications were observed in this series of patients. In 81 cases (92.5%) with clinical symptoms and laboratory indications for gastrointestinal disease, the endoscopy and bioptical samples confirmed the utility and safety of procedure. Coeliac disease (39 cases), gastritis (11 cases), esophagitis (6 cases) were the most common organic cause of upper gastrointestinal disease. Allergic and indeterminate colitis (7 cases) were the most common cause of lower gastrointestinal disease. In 4.7% the procedures appear to be particularly helpful in the diagnosis of inflammatory lesions of the esophagus and stomach. In summary, the data demonstrate that endoscopy techniques show low morbidity, provide important diagnostic informations in pediatric gastrointestinal diseases and can be done safely in patients over 3 months of age.

Endothelial cell growth supplement: a cell cloning factor that promotes the growth of monoclonal antibody producing hybridoma cells.

The efficiency of endothelial cell growth supplement (ECGS), a commercially marketed extract of bovine neural tissue, human endothelial cell supernatant (HECS) derived from freshly isolated endothelial cells, and feeder layers of murine peritoneal cells (PEC), were compared for their ability to support cell fusion, clonal growth, and monoclonal antibody production of murine hybridoma cells. ECGS at 25-100 micrograms/ml was similar to a 1:5 dilution of HECS in supporting the growth of hybridoma colonies; both ECGS and HECS were superior to PEC feeder cells. Furthermore, hybridomas cloned in ECGS produced anti-lymphotoxin antibodies. The commercial availability and stability of ECGS together with its ability anti-lymphotoxin antibodies. The commercial availability and stability of ECGS a superior growth supplement for the fusion and growth of hybridoma cells in monoclonal antibody production.

Histologic changes in liver biopsy specimens produced by recombinant interferon alpha-2b therapy for chronic non-A,non-B viral hepatitis. A randomized controlled trial.

The effects of interferon therapy on liver histologic findings were assessed in a randomized controlled trial consisting of 80 patients with chronic non-A,non-B hepatitis. Twenty-eight patients received 1 million units of recombinant interferon alpha-2b; 25 patients received 3 million units, subcutaneously, three times a week for 24 weeks; and 21 patients were observed as untreated controls; all of them underwent liver biopsy within 6 months from the beginning of the study and on the last day of therapy. Six patients were withdrawn from the study because of inadequate liver biopsy specimens. Alanine aminotransferase levels were determined before, during, and after therapy. For each biopsy, a semiquantitative score of histologic features, the histologic activity index, and the overall histologic assessment were performed. Ninety-five percent of patients tested positive for hepatitis C virus antibody. Portal inflammation, piecemeal and spotty necrosis, and bile duct proliferation were significantly decreased in patients with normalized alanine aminotransferase. The effectiveness of therapy was dose dependent: piecemeal and spotty necrosis and the histologic activity index showed a significant decrease only in 3-million-unit-treated patients. Hepatocellular degeneration and fibrosis did not change significantly after treatment.

Randomized clinical trial comparing systemic interferon with diathermocoagulation in primary multiple and widespread anogenital condyloma.

Two hundred three patients (median age 26 years; range 18-45) with untreated multiple and widespread anogenital condyloma were randomly assigned to one of four study arms in order to compare the efficacy, toxicity, and tolerability of recombinant interferon alpha-2b with those of diathermocoagulation. Of 200 evaluable patients, 51 were treated intramuscularly (IM) with 3 x 10(6) U (3 MU)/m2 daily for 3 weeks (total dose 63 MU/m2), 50 received subcutaneous thrice-weekly injections of 3 MU/m2 for 4 weeks (total dose 36 MU/m2), 51 underwent diathermocoagulation, and 48 were not treated and were used as a control group. Six months after the end of treatment, the overall response rate (complete and partial responses) was 70%: 57 and 82% for patients receiving interferon alpha-2b (IM and subcutaneously) and diathermocoagulation, respectively, and 8% for the control group. After 6 months from therapy, no significant differences in complete response were found among the different types of treatment: 20, 20, and 35% for the two interferon groups and the diathermocoagulation group, respectively. Fifteen and two complete responders in the cauterization and interferon groups, respectively, experienced disease recurrence (P less than .01). All patients given interferon therapy complained of flu-like symptoms, which declined progressively after the first week of treatment. Fatigue, lasting as long as patients received interferon, was the most prevalent chronic side effect. We conclude that systemic recombinant interferon alpha-2b is active in treating patients with primary condyloma lesions and does so as well as cauterization.(ABSTRACT TRUNCATED AT 250 WORDS)

Complications and conversions of pediatric videosurgery: the Italian multicentric experience on 1689 procedures.

BACKGROUND: The aim of this study was to evaluate the incidence and management of complications of videosurgical procedures that occurred during a 4-year period in eight Italian pediatric surgery centers. METHODS: Between 1996 and 1999, 2305 videosurgical procedures were performed in 11 centers of pediatric surgery. The data from 3 centers, for a total of 616 procedures, were largely incomplete and were thus excluded from the study. We analyzed the data from 8 centers only, for a total of 1689 laparoscopic or thoracoscopic operations on patients aged between 15 days and 16 years. The type of operations performed ranged from basic videosurgical interventions, such as varicocelectomy and cryptorchidism, to advanced laparoscopic procedures, such as splenectomy, total colectomy, and esophageal achalasia. Each patient's file was examined for any complications that may have occurred during the surgical procedure and for a record of how these were managed. RESULTS: We recorded 79 complications (4.6%) in our series. In 57 cases (72.2%) the problem was solved by videosurgery. Twenty-two cases (27.8%) required conversion to open surgery. There was no mortality in our series. At a maximum follow-up of 4 years, all children were alive and had no problems related to the videosurgical complications. CONCLUSIONS: We believe that the routine use of open laparoscopy in pediatric patients is a key factor to avoiding complications related to the Veress needle and blind introduction of the first trocar. Moreover, the surgeon's laparoscopic experience, the correct indications for laparoscopic surgery, and the verification of the laparoscopic equipment before surgery are also important rules to follow to reduce the incidence of complications. In the beginning, it is preferable to have the assistance of an expert laparoscopic surgeon to decrease the complications related to the learning curve period.

Prenatal diagnosis and management of some fetal intrathoracic abnormalities.

Nine cases of fetal intrathoracic anomalies detected in utero and followed to birth are reviewed. There were 6 congenital diaphragmatic hernias (CDH), one congenital pleural effusion and two isolated cysts of the lung. All these conditions were potentially responsible for neonatal respiratory distress and received early intensive treatment after maternal transport and delivery had been arranged in a center with thoracic surgical facilities available. The risks of a delayed or missed diagnosis were thus avoided, especially for CDH. Despite intensive, traditional, respiratory support, started in the delivery room, mortality among prenatally detected cases of CDH was paradoxically high (83%), compared to mortality among 7 cases of CDH not detected in utero, referred in the same period to our Institution, and symptomatic within 6 h from birth (63%). With prenatal diagnosis the total number of CDH cases referred to a surgical center before birth increases. Many cases which would never have been treated in the past because of death before referral and treatment for severe pulmonary hypoplasia not compatible with life are thus observed and sometimes treated. Nevertheless, lung development continues to be a determining factor for survival even when intensive treatment at birth is available. Responsiveness to therapy is unpredictable before birth and proposed antenatal treatment is still far from being a realistic option. For the other three newborns, where a pleural effusion and pulmonary cysts were found, prenatal diagnosis helped to start appropriate treatment and to prevent neonatal hypoxia in two of them. In the third case, with an incommunicant, isolated pulmonary cyst, the outcome would have been favourable even without a prenatal diagnosis.

Two lines of Walker carcinoma 256: their peculiarities and different interactions with the host.

Two sublines of Walker 256 carcinoma have been characterized for their ability to metastasize and to induce cachexia. The invasive, metastasizing line A induced terminal anorexia in rats with a mean survival time of 27 +/- 1.5 days. The non-invasive line B induced early anorexia and cachexia with a mean survival time of only 15 +/- 1 days. At death, the line B tumor was still smaller than the line A one, and no metastases were detectable. These two sublines are discussed as a composite model for studying anorexia and cachexia together with invasion and metastasis.

The rationale for total hip replacement in over 60-year-old patients.

The total hip replacement (THR) survival potential is linked to the material, to surgical technique and to patient's characteristics. Cemented and cementless systems exist in a wide variety of shapes, sizes, configurations, materials and surface treatments. Aseptic loosening remain the principal mechanism of prosthetic failure and the choice of right matching for each prosthesis-patient is the main issue to obtain a very good long-term implant fixation. Cement fixation is always solidly achieved but it can break down under mechanical and biological pressure. Stability with cementless fixation must be created by the initial bone response to the implant. Clinical studies and long-term results with THR showed that in patients with age between 60 and 70 years, it is important to analyze several parameters (bone quality and morphology, life-limiting diseases and levels of activity) to make the appropriate selection of components and type of fixation.

Recurrent peptic stenosis of the esophagus: treatment with a self-expanding metallic stent.

A 12-year-old neurologically impaired boy with recurrent peptic stenosis of the esophagus was treated successfully with use of a self-expanding metallic stent that remained for 3 months.

Thyroid tumors in children and adolescents: preoperative study.

Several studies indicate that in young patients (less than 21 years of age at the time of diagnosis), the prognosis of thyroid carcinoma (TC) is more favorable than in older patients. However, a more radical treatment approach is recommended in children and adolescents due to the higher prevalence of local lymph-node involvement in these cases. Since the extent of primary surgical treatment is closely related to the overall prognosis, preoperative diagnosis becomes essential in the management of thyroid neoplasms in young patients. In this retrospective study (1987-1998), we analyzed a surgical series of 50 children and adolescents with thyroid nodules in an attempt to establish the role of diagnostic studies in detecting malignant lesions prior to surgery. Our diagnostic protocol for evaluating thyroid nodules was based on clinical evaluation, measurement of thyroid-hormone and thyroglobulin (TG) levels, anti-TG and anti-TPO antibody titers, calcitonin, CEA, and TPA levels, sonography, scintigraphy, and fine-needle aspiration cytology (FNAC) of the thyroid nodules and any enlarged lymph nodes. Eleven of the 15 cases of histologically confirmed carcinoma were preoperatively identified as malignant lesions with the aid of FNAC. The authors conclude that the preoperative work-up of children and adolescents with thyroid nodules requires the collaboration of an experienced team of professionals, and recommend FNAC as the initial test.

[A giant lymphangioma of the trunk with a fatal outcome]. / Linfangioma permagno del tronco ad esito infausto.

The authors describe the case of a 2-month-old male brought to the emergency room in a preagonal state cause by extensive septic necrosis of an enormous lymphangioma located on the left lateral trunk. In spite of emergency treatment the child expired shortly after admission. Our observation of this case prompted a review of the literature on the treatment approaches currently used for these tumors. Emphasis is placed on the necessity for early treatment in order to avoid infectious complications that, if neglected, can lead to unmanageable and possibly fatal sepsis.

Choledochal cyst in a pediatric patient: creation of a bilijejunal anastomosis with surgical staples. A case report.

Although the use of surgical staples is a well established practice in intestinal tract surgery on adults, their role in biliodigestive anastomoses in adults and children has been more limited. The Authors describe a 12-year-old girl with a type-IV choledochal cyst, who was successfully treated with cyst excision and Roux-en-Y hepaticojejunostomy created with a surgical stapler.

[Cryptorchidism: a study of histological changes in undescended testis related to age]. / Criptorchidismo: studio delle alterazioni istologiche nei testicoli ritenuti in rapporto all'età.

A total of 46 testicular biopsies were examined to define the histological characteristics of undescended testicle. Nine of the biopsied organs were normally positioned testicles from deceased pediatric patients (aged 2 months-14 years), and the remaining 37 were undescended testes from children with various degrees of cryptorchidism (aged 18 months-14 years). As reported by others, the degree of histological damage was directly proportional to the age of the subject. Close correlation between histological findings and the level of descent was not observed.

[Radioisotope study of urinary deformity pathology in childhood]. / Lo studio radioisotopico della patologia malformativa urinaria in età pediatrica.

The role of radionuclide investigation of urinary tract pathology in pediatric patients (computerized radionuclide urography and radionuclide cystogram) is discussed. Advantages of reliable morphological and functional study with a non invasive, low radiation procedure are emphasized.

[Echography in the study of renal pathology in childhood]. / L'ecografia nello studio della patologia renale in età pediatrica.

Results of US study in 30 children with various renal lesions are reported, and compared with clinical and surgical features. Different ultrasonographic aspects are discussed with special interest on cogenital abnormalities. US is proposed as first choice investigation in newborns with antenatal ultrasonographic demonstration of renal lesions and in all patients where a mass of renal origin is suspected. Renal function, nevertheless, must be investigated with radiologic and/or radioisotopic techniques. US have still a large indication in short term follow-up of renal lesions where surgical treatment is not indicated.

[Dumbbell neurogenic tumors in children]. / Tumori neurogenici a clessidra in età pediatrica.

Dumbbell neurogenic tumours are unusual neoplasms in the pediatric age group. Six cases all in children under 10 years of age, have been reviewed with respect to diagnosis, management and results. Neurologic deficits have been found in 4 patients only; in the other 2 cases the tumours were occasionally discovered. Myelograms, sometimes associated with CT scan, allowed a correct diagnosis in all the patients. Initial treatment consisted in all the cases in laminectomy or laminotomy with total excision of the extradural tumour. The primary paravertebral tumours have been removed in one patient during the same neurosurgical operation, and in other three patients at a second stage. Two patients did not require the second operation: one recovered after chemotherapy and the other died few days after the first surgical procedure. Five patients are still alive: two, who had the tumour occasionally discovered, are free from disease; among the other 3 patients, presenting with neurological symptoms, 1 is free from disease without neurological symptoms and 2 have still long lasting sequelae. The authors emphasize the role of early diagnosis to prevent neurologic abnormalities and to achieve better results.

Bilateral renal vein thrombosis as a complication of gangrenous appendicitis.

Bilateral renal vein thrombosis after an appendectomy has never been reported in the pediatric literature. We describe the case of a 10-year-old boy who developed this very unusual complication following appendectomy for gangrenous appendicitis with peritonitis. Color duplex Doppler is the most appropriate investigation to allow correct diagnosis and immediate medical treatment. Peritoneal dialysis is a simple and effective tool to prevent permanent damage to renal function.

[One-stage "forced" closure of large congenital defects of the abdominal wall with mechanical ventilation and curarization. Clinical evaluation]. / Chiusura "forzata" in tempo unico dei difetti congeniti maggiori della parete addominale con ventilazione meccanica e curarizzazione. Valutazione clinica.

Advantages of primary fascial closure of abdominal wall defects are mainly in reducing the number of staged procedures with related complications and the need of multiple operation. Nevertheless correction of large defects still remains a challenge to pediatric surgeon. Postoperative paralysis and mechanical ventilation after intraoperative milking of intestinal content and abdominal muscles stretching have been reported to reduce the risks of "forced" primary closure. A series of 64 Omphalocele and Gastroschisis has been reviewed. Associated anomalies are still the main cause of mortality among Omphalocele. Prematurity plays a secondary role on survival of Gastroschisis cases; deaths were mainly due to sepsis. Primary respiratory insufficiency affected a large number of Giant Omphalocele cases (larger than 5 cm with herniated liver) and was associated to a restricted chest structure. All these cases died in the first weeks of life. Primary closure with or without postoperative paralysis and mechanical ventilation showed to reduce in a significant way the postoperative complication rate compared to staged procedures. Mortality and hospital stay were not significantly influenced by different kinds of surgical treatment among Omphalocele. Associated anomalies are an unavoidable limiting factor to survival. Among Giant Omphalocele the use of aggressive primary fascial closure with ventilatory support showed in our hands to be a safe procedure provided that a preoperative selection of cases on the basis of chest X-ray and blood gases has been made.

[Sacrococcygeal teratoma: single center experience and functional long-term follow-up]. / Teratoma sacrococcigeo: esperienza monocentrica e follow-up funzionale a lungo termine.

OBJECTIVE: To propose long-term follow-up protocol to analyse clinical and functional aspects and evaluate the Quality of Life (QoL) of patients with Sacrococcygeal Teratoma (SCT). MATERIALS AND METHODS: The long-term follow-up of 14 out of 28 patients has been assessed through the retrospective review of data related to antenatal diagnosis, obstetric pathology and surgery, collected from July 1985 to December 2009. It has been accomplished by analysing functional and aesthetic outcomes and the QoL experienced by the patients with an average observation range of 121 months for each patient. RESULTS: Concerning the anorectal functionality, 14% of patients reported impairment of fecal continence while 36% had completely normal bowel habits. Other health problems varying from urinary incontinence to neurogenic bladder were reported by 36% of patients. Dealing with the functionality of lower limbs, 20% of patients exhibited minor dysfunctions while 7% major ones. Optimal aesthetic outcome of the surgical scar has been reported only by 21% of the specimen. The evaluation of QoL pointed out that 64% of patients are moderately satisfied while 36% presented problems. CONCLUSIONS: We believe that functional sequelae should play an important role during antenatal counselling and that the urological and anorectal follow-up for SCT patients should be long-term evaluated. Furthermore, aesthetic aspects and psychological support should be taken into account carefully especially during childhood.