Ex vivo adult stem cell characterization from multiple muscles in ambulatory children with cerebral palsy during early development of contractures.

Cerebral palsy (CP) is one of the most common conditions leading to lifelong childhood physical disability. Literature reported previously altered muscle properties such as lower number of satellite cells (SCs), with altered fusion capacity. However, these observations highly vary among studies, possibly due to heterogeneity in patient population, lack of appropriate control data, methodology and different assessed muscle. In this study we aimed to strengthen previous observations and to understand the heterogeneity of CP muscle pathology. Myogenic differentiation of SCs from the Medial Gastrocnemius (MG) muscle of patients with CP (n = 16, 3-9 years old) showed higher fusion capacity compared to age-matched typically developing children (TD, n = 13). Furthermore, we uniquely assessed cells of two different lower limb muscles and showed a decreased myogenic potency in cells from the Semitendinosus (ST) compared to the MG (TD: n = 3, CP: n = 6). Longitudinal assessments, one year after the first botulinum toxin treatment, showed slightly reduced SC representations and lower fusion capacity (n = 4). Finally, we proved the robustness of our data, by assessing in parallel the myogenic capacity of two samples from the same TD muscle. In conclusion, these data confirmed previous findings of increased SC fusion capacity from MG muscle of young patients with CP compared to age-matched TD. Further elaboration is reported on potential factors contributing to heterogeneity, such as assessed muscle, CP progression and reliability of primary outcome parameters.

Mycotoxin sequestering agent: Impact on health and performance of dairy cows and efficacy in reducing AFM1 residues in milk.

The objectives of this study were to evaluate the exposure to a diet naturally contaminated with mycotoxins on lactation performance, animal health, and the ability to sequester agents (SA) to reduce the human exposure to AFM1. Sixty healthy lactating Holstein cows were randomly assigned to two groups: naturally contaminated diet without and with the addition of a SA (20 g/cow/d AntitoxCooPil® -60% zeolite-40% cell wall-). Each cow was monitored throughout lactation. The concentration of aflatoxin B1 (AFB1) in feed and M1 (AFM1) in milk, health status, and productive and reproductive parameters were measured. AFB1 concentration in feed was very low (2.31 µg/kgDM). The addition of SA reduced the milk AFM1 concentrations (0.016 vs. 0.008 µg/kg) and transfer rates (2.19 vs. 0.77%). No differences were observed in health status, production and reproduction performance. The inclusion of SA in the diet of dairy cows reduce the risk in the most susceptible population.

Incidental cancer in patients surgically treated for benign thyroid disease. Our experience at a single institution.

Increased incidence of incidental cancer in patients operated for benign thyroid disease has been reported. We report our experience about incidental thyroid cancer (ITC) in order to better characterize this nosologic entity. Between 2001 and 2009 a total of 568 patients underwent surgery for benign thyroid disease. Patients with preoperative cytology undetermined or positive for malignancy were excluded. The most frequent indication for surgery was multinodular or diffuse nontoxic goiter. We performed total thyroidectomy in 499 cases and emithyroidectomy in 69 cases. Final histology revealed ITC in 53 patients (9.3%): 44 had papillary carcinoma (20 classic variant and 24 follicular variant), 4 follicular carcinoma, 4 medullary carcinoma and 1 primitive thyroid paraganglioma. The preoperative diagnosis was multinodular or diffuse goiter in 45 cases of ITC and uninodular goiter in 8 cases. We performed total thyroidectomy in 46 case, emithyroidectomy in 4 patients with past history of lobectomy, emithyroidectomy in 3 patients with following radicalization and central neck dissection. In 14 patients the tumor was multifocal and in 12 of these patients the tumor foci were bilateral. The lesion was a microcarcinoma in 34 cases. Mean diameter of the ITC was 1.14 cm. We retrospectively reconsidered the results of preoperative ultrasound examinations in relation to the exact position of the tumor in the specimens and we found a statistically significant association between echogenicity and papillary histotype. Twenty-six patients were followed up at our Hospital. The mean follow-up period was 38.2 months. A relapse was observed in 3/26 patients. Incidental thyroid cancer in patients operated for benign disease has its own surgical and oncological relevance. A correct preoperative assessment, with a careful selection of nodules for fine-needle aspiration cytology on the basis of ultrasound pattern, could better address the choice of surgical procedure. The non irrelevant incidence of incidental thyroid cancer, the eventuality of multifocality and bilaterality and the possible occurrence of relapse, support that total thyroidectomy without residuum is a valuable option for treating benign thyroid conditions such as multinodular goitre. When an incidental cancer is diagnosed after emithyroidectomy, a radicalization with central neck dissection could be considered. We suggest that natural history of papillary microtumors and the correct surgical approach for these lesions could be better defined with a more extensive use of "Porto proposal" criteria.

Serous cystadenofibroma of the fallopian tube: case report and literature review.

INTRODUCTION: Cystadenofibromas of the Fallopian tube are very rare benign tumors of the female genital tract. These tumours are usually asymptomatic and are found incidentally. CASE REPORT: We describe a Fallopian serous cystadenofibroma in a 50 year-old woman operated for uterine leiomyoma. The histopathologic finding revealed a cystic lesion connected to the salpinx. The cyst was composed of connective stroma lined by epithelial cuboidal cells, without pleomorfism or detectable mitoses. Pseudopapillary structures were observed in the lumen of the cyst. The patient is well on follow-up. CONCLUSION: The origin of serous cystadenofibroma of the Fallopian tube is not clear. The tumor is considered an embryologic remnant rather than a proliferating neoplastic process. These tumours seem to have a benign course and a malignant potential has not been described.

Breast cancer metastatic to the submandibular gland. Case report.

Metastatic disease in the major salivary glands is rare and the parotid gland is most frequently involved. Secondary deposits in the submandibular gland are very uncommon. We report a case of a 50-year-old woman who developed a metastasis from breast cancer in the right submandibular gland, 9 years after primary surgery for G3 T1c N0 ipsilateral breast carcinoma. The peculiarity of the case was the unusual site of the metastatic disease and the difficulty in differential diagnosis with primitive ductal salivary carcinoma.

Quantitative risk assessment for aflatoxin M1 associated with the consumption of milk and traditional dairy products in Argentina.

A quantitative risk assessment for exposure to aflatoxin M1 (AFM1) related to the consumption of milk and traditional dairy products of Argentina was developed. The frequency and concentration of AFM1 was modelled at various stages through the milk processes, considering Argentinean practices. Concentration of AFM1 (0.046 µg/l, 95%CI = 0.002-0.264 µg/l) in raw milk was estimated. The AFM1 concentration in milk was sensitive to the carry-over rate (r = 0.80), and milk yield in the first third of lactation during the spring-summer season (r = 0.11). AFB1 levels in silage (r = 0.22), pasture during the spring-summer season (r = 0.11), concentrate (r = 0.08), and cotton seed (r = 0.05) were the factors most correlated with AFM1 concentrations. Although the results showed that MoE values for the mean and median exposure to AFM1 were < 10,000 in infants, toddlers, and other children, the additional cancer risk due to exposure to AFM1 in infants, toddlers, and other children was 0.007, 0.005, and 0.0009 additional cases per year per 100,000 individuals, respectively, which indicates no health concern. In addition, the percentages of the population exceeding HI values (HI > 1) for exposure to AFM1 for infants, toddlers, and other children were 45%, 49.1%, and 40.6%, respectively. Under this scenario, the most susceptible population at risk was children < 10 years old; therefore, it is necessary to establish measures to prevent contamination of AFM1 in milk and milk products.

Fine-needle aspiration cytology for breast lesions and cytopathologic correlations. An Italian peripheral hospital experience with 440 cases (from 2000 to 2007).

Fine-needle aspiration cytology for breast lesions and cytopathologic correlations. An Italian peripheral hospital experience with 440 cases (from 2000 to 2007). S. Erra, D. Costamagna In the present study, we evaluate our experience with Fine-Needle Aspiration Cytology (FNAC) for the diagnosis of breast tumor. Our intent is to correlate the diagnostic accuracy of FNAC for breast lesions on the basis of their respective histopathologic results. We retrospectively examined 440 cases of breast lesions who underwent FNAC and subsequently had definitive histopathologic diagnosis. The patients were observed over a period of eight years (from January 2000 to December 2007) at the "Santo Spirito" Hospital of Casale Monferrato, a general peripheral hospital in the North-West Italy (Piemonte Region). The results of FNAC were expressed using the five diagnostic categories recommended by European Guidelines on breast tumors as follows: 159 C5 cases (36,1%), 88 C4 (20%), 51 C3 (11,6%), 42 C2 (9,5%), and 100 C1 (22,7%). The statistical analysis revealed these values: sensitivity 93.8% (C5+C4), specificity 79.6%, C5 positive predictive value 97.5%, C2 negative predictive value 83.3%, false positive fraction 2.5%, false negative fraction 16.6%, diagnostic accuracy 71.2%. In consideration to the low cost and the low disconfort for patients, we consider FNAC a safe and feasible procedure, in particular in the context of peripheral hospitals, where a sophisticated technology is not available. We remark the importance of a good selection of patients to obtain the best results from the procedure.

A rare case of extraskeletal osteosarcoma of the esophagus: an example of difficult diagnosis.

Sarcomatous lesions of the esophagus are rare. We describe a controversial case of a malignant aggressive tumor of the aesophagus, with a very poor prognosis and rapid outcome for the patient. A 74-year-old man underwent endoscopic examination for recurrent thoracic pain and dysphagia. A 8 cm mass was found in the cervical esophagus. A sarcomatous tumor with osteoid aspects was observed on the histopathological examination, without any carcinomatous component.

Sporadic flat ileal adenocarcinoma: an intriguing challenge in the comprehension of a rare neoplasia and its genesis. Case report and review of literature.

Small bowel adenocarcinoma is a rare tumor, with a still not well studied tumorigenesis process, usually presenting in an advanced stage. The clinical diagnosis is often difficult; surgery is the treatment of choice when feasible, while the chemotherapeutic approach is still not well standardized. We describe the case of a 71-yr-old male patient, presenting with an acute right abdomen. At laparotomy the terminal ileum appeared chronically inflamed and thickened. An ileocecal resection with latero-lateral ileocolic anastomosis was performed. The gross appearance resembled an inflammatory bowel disease, but microscopic examination revealed the extensive presence of an infiltrating ileal adenocarcinoma. Literature about small bowel adenocarcinoma has been reviewed for better understanding its pathogenesis.

Acute abdomen in the elderly. A peripheral general hospital experience.

We reviewed our experience on 291 consecutive patients aged over 65 years who were operated on for acute abdomen during the period 2003-2007 at "Santo Spirito" Hospital of Casale Monferrato, a peripheral hospital in the Piedmont region. The mean age of the patients was 78 years and the male/female ratio was 149/142. A total of 126 patients (43%) had one or more associated disease. The most common causes for an emergency operation were mechanical bowel obstruction (45%), hollow viscus perforation (18%) and strangulated hernia (18%). 234 patients (80%) recovered and were free from major complications. The remaining 57 (20%) developed at least one major complication (including death). The 30-days postoperative deaths were 33 (11%). Nonlethal major complications were 24 (8%). The commonest complications were cardio-respiratory. Septic complications were 15. Total reoperations for surgical complications were 5. Mesenteric ischaemia and secondary peritonitis were the most important causes of fatal outcome (respectively 42 and 17% of mortality). We also reported high mortality among patients with peritoneal carcinomatosis (24%). Emergency surgery was relatively safe for the remaining groups of patients, with a complexive mortality ratio of 5.3%. We conclude that "acute abdomen" is still an appreciably frequent cause of death in the older age group. A high level of vigilance and early attention is therefore advocated. Anyway, excluding some severe conditions, the overall success of surgical interventions for abdominal emergency is satisfactory in the majority of older people. About the debated role of peripheral hospitals in the health care system, we conclude that the surgical treatment of the acute abdomen in the elderly is safe and feasible in the peripheral hospitals, and that these hospitals play a determining role in the management of old patients, especially in emergency.

Quantification of aflatoxin M1 carry-over rate from feed to soft cheese.

From January to December 2016, samples of milk and feeds of dairy cattle were monthly collected. The concentration of mycotoxins in all matrices was determined using the enzymatic immunoassay technique. The average concentration of aflatoxin B1 (AFB1), deoxynivalenol (DON) and zearalenone (ZEA) in feed was 3.01, 218.5 and 467 ug/kg, respectively. The average AFB1 carry-over rate was 0.84% with a variation between 0.05 to 5.93%. Particle size of the feed (P = 0.030) and individual milk production (P = 0.001) affected this rate. Mini-soft cheeses were produced using milk naturally contaminated with aflatoxin M1 (AFM1) as raw material to study its distribution both in whey and in cheese. The average level of AFM1 in milk was 0.014 µg/l. None of milk samples exceeded the maximum level accepted for AFB1 by the Southern Common Market (MERCOSUR) legislation (0.5 µg/l) and only 5.5% of samples exceeded the European Union (UE) regulations (0.05 µg/l). After the cheese elaboration, the concentration of AFM1 was determined in whey and in cheese. The greatest proportion (60%) was detected in whey while 40% AFM1 remained in the cheese. However, the concentration of AFM1 was higher in the cheese compared to the original milk.

Treatment of pseudomyxoma peritonei with two times--cytoreduction and hypertermic antiblastic peritoneal perfusion (HAPP).

Pseudomyxoma peritonei is a rare neoplasia with a low grade of clinical malignity in which neoplastic masses product large amount of mucinous material. Its treatment advocates an aggressive cytoreduction of all visceral and peritoneal lesions and Hyperthermic Antiblastic Peritoneal Perfusion (HAPP). In three cases we programmed a two stage surgical approach for the massive amount of peritoneal implants. Two times we achieved our aim, while one time, the wide progression of the disease during the two surgical procedures made useless our efforts to have a complete cytoreduction and the following HAPP. This last patient refused systemic chemotherapy between the two surgeries and we think that this should be one of the reasons of the failure.

[Treatment of peritoneal mesothelioma using cytoreduction and intraperitoneal hyperthermic chemotherapy]. / Trattamento del mesotelioma peritoneale mediante citoriduzione e chemioipertermia intraperitoneale (CIIP).

UNLABELLED: Malignant mesothelioma of the peritoneum is a rare tumor for which the therapeutic approach has not yet been standardized. Cytoreductive surgery and hyperthermic antiblastic peritoneal perfusion (HAPP) may be effective in the treatment of this neoplasm. From 1995 to March 2003, we operated 24 patients with malignant peritoneal mesothelioma. Nineteen times we were able to perform radical surgery and HAPP: 6 CC-0, 10 CC-1 and 3 CC-2 (nodules smaller than 1 cm). HAPP was performed by the original "semi-closed" technique, using MMC+ CDDP in 3 patients, CDDP + doxorubicin in 15 patients, only doxorubicin in 1 patient). RESULTS: Operating mortality was 11% and postoperative morbidity was 26%. 4 patients are DOD (40, 20, and 2 at 2 months); 5 patients are AWD (72, 34, 25, and 2 at 15 months); 8 patients are NED (81, 47, 2 at 20 months, 16, 13, 12 months, 1 patient recently operated). The median survival is 40 months. The high rate of morbidity and mortality is due to the presence of postoperative paraneoplastic syndromes, with alterations of coagulation and onset of ARDS. Therefore the good survival results make the methodic one of the best options in the treatment of the disease.

[Treatment of pseudomyxoma peritonei using cytoreduction and intraperitoneal hyperthermic chemotherapy]. / Il trattamento dello pseudomixoma peritonei (PMP) mediante citoriduzione e chemioipertermia intraperitoneale (CIIP).

Pseudomixoma peritonei (PMP) is a rare neoplasia with a low grade of clinical malignity. Generally, the main treatment of this tumor is the surgical debulking. Best results are obtained combining surgery and hyperthermic antiblastic peritoneal perfusion (HAPP) with CDDP and MMC. From April '97 to March 2003, we operated on 132 patients, 8 times with a palliative intent. In 27 times we achieved a complete cytoreduction (17 CC0 and 10 CC1) followed by HAPP. As regards results, no post-operative mortality was reported and 19% of major morbidity was observed. 26 patients are NED at maximum follow-up of 6 years and 1 patient had recurrence 6 months after primary resection. We believe that cytoreduction and HAPP is the golden standard of PMP therapy when it is possible to achieve a complete cytoreduction. Most of the times, the disease is not radically treated and therefore, after diagnosis, patients should be only referred to specialized centers.

[Use of pentaglobin in the treatment of sepsis in the patient undergoing intraperitoneal hyperthermic chemotherapy]. / Utilizzo del pentaglobin nel trattamento della sepsi nel paziente sottoposto a chemioipertermia intraperitoneale (CIIP).

In patients subjected to cytoreduction and hyperthermic antiblastic peritoneal perfusion (HAPP), their immunocompromized conditions claim a very aggressive therapeutic approach in case of periotonitis and sepsis. Therefore, we use an adjuvant therapy of severe bacterial infections additional to antibiotic therapy by using Pentaglobin. It contains human plasma proteins, of which immunoglobulin at least 95%, with high rate of IgG, IgM and IgA, infused intravenously at 12 mL/h for 3 days continuously. From November 2000 to March 2003, we combined this approach for the treatment of peritonitis/sepsis in 11 patients. In 10 patients we obtained a complete control of the infective status in 8 days, while 1 patient died for MOFF. So, even with the exiguity of our casuistry, we obtained a better and more rapid clinical control of the patients respect to the previous period when the Pentaglobin was not used.

[Cytoreductive surgery and intraperitoneal hyperthermic-antiblastic therapy (HAPP) in peritoneal carcinomatosis]. / Chirurgia citoriduttiva e chemioipertermia intraperitoneale (CIIP) nel trattamento delle carcinosi peritoneali.

Peritoneal carcinosis often occurs during the evolution of many neoplasias either abdominal or extra-abdominal. The free time survival of the patients affected by carcinosis is poor (about 6 months) as regards gastric and colorectal cancer. In the last ten-year period a combined surgical technique aiming at the total removal of parietal and visceral peritoneal lesions (peritonectomy) and at the perfusion of peritoneal cavity with chemo-drugs in hyper-thermia had developed. This method is based on the presence of the peritoneal-plasmatic barrier that holds back high molecular weight drugs, keeping from passing at the systemic circulation; in this way it is possible to use higher and more concentrate chemo-drug doses in a very limited area than in the systemic chemotherapy. The association between chemotherapy and hyperthermia produces a synergic effect: hyperthermia, infarct, makes chemo-drugs more effective and selective, improving their capability of penetration in tumoral masses; heat has furthermore an intrinsic anti-neoplastic action, being altered the reparation mechanisms of the tumoral cells. A WEB research on Medline site has been conducted choosing especially those articles referable at the 1999-2000 period. The selected articles have been briefly analysed in the "Clinical experience" section. Authors' experiences have been divided, as far as possible, on the basis of the tumors treatable with cytoreduction and HAPP: 1) Colon-rectal Cancer; 2) Pseudomyxoma peritonei/Appendicular Adenocarcinoma; 3) Gastric Cancer; 4) Ovarian Cancer; 5) Peritoneal Mesothelioma. The determinant variables in the analysis of the results are basically three: 1) Selection of the patients, 2) Characteristics of the surgical operation, 3) Characteristics of the HAPP. Colon-rectal carcinoma: the survival time of the recurrent disease, obtained by some authors like P.H. Sugarbaker, is surely remarkable (50% at 5 years in the patients where a complete cytoreduction was possible to perform), but the result obtained in patients affected by peritoneal carcinosis, subjected to this technique at the first clinical presentation (100% at 5 years) is much more interesting. For this type of neoplasia, it is important to underline that not all the authors report the same results, with a median survival time lower than that of the American author. Pseudomyxoma peritonei: about this rare neoplasia, the "golden standard" treatment consists on cytoreduction of all visceral and peritoneal macroscopical lesions, with a homogeneous distribution of the data obtained by most authors: median survival time included among 70% and 90% at 5 years. Gastric cancer: there is a considerable difference between the data of Japanese authors and others. In the treatment of peritoneal carcinosis the results are, on average, rather poor; better results have been obtained using this technique as an adjuvant presidium for the prevention of the onset of peritoneal carcinosis. Ovarian cancer: the results about the recurrent ovarian cancer are good; in the future, it will be useful to start a phase III study to render effective the use of this technique in the ovarian cancer at the beginning of its clinical story. Peritoneal mesothelioma: till now, a standardized alternative, approaching this neoplasia, does not exist; the results are encouraging, with good median and free time survival.

Notch signaling regulates myogenic regenerative capacity of murine and human mesoangioblasts.

Somatic stem cells hold attractive potential for the treatment of muscular dystrophies (MDs). Mesoangioblasts (MABs) constitute a myogenic subset of muscle pericytes and have been shown to efficiently regenerate dystrophic muscles in mice and dogs. In addition, HLA-matched MABs are currently being tested in a phase 1 clinical study on Duchenne MD patients (EudraCT #2011-000176-33). Many reports indicate that the Notch pathway regulates muscle regeneration and satellite cell commitment. However, little is known about Notch-mediated effects on other resident myogenic cells. To possibly potentiate MAB-driven regeneration in vivo, we asked whether Notch signaling played a pivotal role in regulating MAB myogenic capacity. Through different approaches of loss- and gain-of-function in murine and human MABs, we determined that the interplay between Delta-like ligand 1 (Dll1)-activated Notch1 and Mef2C supports MAB commitment in vitro and ameliorates engraftment and functional outcome after intra-arterial delivery in dystrophic mice. Furthermore, using a transgenic mouse model of conditional Dll1 deletion, we demonstrated that Dll1 ablation, either on the injected cells, or on the receiving muscle fibers, impairs MAB regenerative potential. Our data corroborate the perspective of advanced combinations of cell therapy and signaling tuning to enhance therapeutic efficaciousness of somatic stem cells.

[Complications of cytoreductive surgery associated with intraperitoneal chemohyperthermia: prevention and treatment]. / Complicanze della chirurgia citoriduttiva associata a chemioipertermia intraperitoneale (CIIP) prevenzione e trattamento.

New approach to peritoneal carcinomatosis combining cytoreductive surgery and hypertermic intraperitoneal chemotherapy suggest improved survival when it is possible to achieve a complete cytoreduction. In this study we consider the major complications related to this procedure and purpose our approach for their prevention and treatment.

[Cytoreduction and intraoperative peritoneal chemohyperthermia in carcinomatosis from colonic carcinoma and in peritoneal pseudomyxoma]. / Citoriduzione e chemioipertermia intraoperatoria peritoneale (CIIP) nella carcinosi da carcinoma del colon e nello pseudomixoma peritonei.

New approach in treatment of peritoneal carcinomatosis combining cytoreductive surgery and intraperitoneal chemotherapy suggests improved survival when it is possible to achieve a complete cytoreduction. In this study we consider the carcinomatosis from colorectal and appendiceal adenocarcinoma. In all cases, patients in whom cytoreductive surgery was complete had a median survival much longer compared with patients in whom was not possible and, as perfusion works on minimal residual disease, peritonectomy is the only surgical technique that aim at total removal of parietal and visceral peritoneal lesions.