Thyroid anaplastic carcinoma: the impact of multimodality treatment on survival. The experience of a referral center for endocrine surgery.

AIM: Anaplastic thyroid carcinoma (ATC) is characterized by local invasiveness, risk of recurrence and very poor prognosis. METHODS: We retrospectively reviewed 79 consecutive patients treated between 1996 and 2012. We analysed the multimodality treatment of ATC considering the impact of surgery and radiotherapy on survival. RESULTS: Patients were divided in groups A and B (tumor less and larger than 5 cm). Surgery was carried out in 44 patients, radiotherapy in 48 patients. Tracheostomy and endoprosthesis were used respectively in 48.1% and in 25.3% of patients. The mean survival was 5.35 (± 3.2) months with no significant difference in group A vs. group B. Considering patients undergone surgery, significant impact on survival was observed comparing A vs. B (P=0.013). Combination of surgery and radiotherapy significantly improves outcome comparing A vs. B (P=0.017). Improvement in survival compared to no treatment at all was observed in both groups respectively for surgery (P=0.001 and P=0.0001) and radiotherapy (P=0.047 and P=0.0001). CONCLUSION: Although the severity of prognosis of ATC, multimodality treatment still significantly improves local control of the disease achieving acceptable survival in selected patients and adequate palliation of symptoms for the others. Surgery is still a fundamental treatment.

Total thyroidectomy and central lymph node dissection. Experience of a referral centre for endocrine surgery.

AIM: Thyroid cancer prognosis is determined by several variables, even with extremely elevated survival rate. The most debated issues are the type of thyroidectomy and extension of lymphadenectomy. Aim of the study is the analysis of benefits of level VI lymphadenectomy associated to total thyroidectomy in the treatment of thyroid cancer. PATIENTS AND METHODS: 316 total thyroidectomy with central node dissection were carried out in the Unit of Endocrine Surgery, University of Perugia. Direct parathyroid auto-implantation was carried out if damage or accidental excision occurred. High risk patients received radioiodine treatment. RESULTS: Lymph node metastases in the VI level were observed in 42% of cases with a significant difference (p 0.0042) of positive lymph node in level VI comparing tumor larger than 1 cm vs smaller than 1 cm. No significant differences were observed when considering difference of sex, and age. Significant difference (p 0.005) was shown when considering over 45 years old male patients with tumor larger than 1 cm vs smaller ones. The 78% of patients underwent iodine ablation after surgery. Recurrence rate in these patients was 3.2%, with no significant difference compared to not treated patients. Bilateral temporary recurrent nerves palsy were observed in 0.6% of cases, unilateral temporary recurrent nerves palsy in 3.4%, unilateral permanent palsy in 1.5%, temporary hypoparathyroidism in 17%, permanent hypoparathyroidism in 4.4%. CONCLUSIONS: Total thyroidectomy combined to central node dissection, even in absence of risk factors and without clinical evident nodes, is the treatment of choice offering clear indications to radioiodine ablation.

Differentiated thyroid tumors: surgical indications.

Thyroid gland tumors represent 1% of malignant tumors. In Italy their incidence is in constant growth. The aggressiveness depends on the histological type. The relative non-aggressive grade of different forms of tumors is the basis for discussing the treatment of choice: total thyroidectomy vs lobectomy with or without lymphadenectomy of the sixth level in the absence of metastasis. Authors report about their experience, and they advocate, given the high percentage of multicentric forms, total thyroidectomy as treatment of choice.

Pre-culturing human adipose tissue mesenchymal stem cells under hypoxia increases their adipogenic and osteogenic differentiation potentials.

OBJECTIVES: Hypoxia is an important factor in many aspects of stem-cell biology including their viability, proliferation, differentiation and migration. We evaluated whether low oxygen level (2%) affected human adipose tissue mesenchymal stem-cell (hAT-MSC) phenotype, population growth, viability, apoptosis, necrosis and their adipogenic and osteogenic differentiation potential. MATERIALS AND METHODS: hAT-MSCs from four human donors were cultured in growth medium under either normoxic or hypoxic conditions for 7 days and were then transferred to normoxic conditions to study their differentiation potential. RESULTS: Hypoxia enhanced hAT-MSC expansion and viability, whereas expression of mesenchymal markers such as CD90, CD73 and endothelial progenitor cell marker CD34, remained unchanged. We also found that pre-culturing hAT-MSCs under hypoxia resulted in their enhanced ability to differentiate into adipocytes and osteocytes. CONCLUSIONS: This protocol could be useful for maximizing hAT-MSC potential to differentiate in vitro into the adipogenic and osteogenic lineages, for use in plastic and reconstructive surgery, and in tissue engineering strategies.

Hypoxia increases Sca-1/CD44 co-expression in murine mesenchymal stem cells and enhances their adipogenic differentiation potential.

Mesenchymal stem cells (MSCs) are usually cultured under normoxic conditions (21% oxygen). However, in vivo, the physiological "niches" for MSCs have a much lower oxygen tension. Because of their plasticity, stem cells are particularly sensitive to their environments, and oxygen tension is one developmentally important stimulus in stem cell biology and plays a role in the intricate balance between cellular proliferation and commitment towards differentiation. Therefore, we investigated here the effect of hypoxia (2% oxygen) on murine adipose tissue (AT) MSC proliferation and adipogenic differentiation. AT cells were obtained from the omental fat and AT-MSCs were selected for their ability to attach to the plastic dishes, and were grown under normoxic and hypoxic conditions. Prior exposure of MSCs to hypoxia led to a significant reduction of ex vivo expansion time, with significantly increased numbers of Sca-1(+) as well as Sca-1(+)/CD44(+)double-positive cells. Under low oxygen culture conditions, the AT-MSC number markedly increased and their adipogenic differentiation potential was reduced. Notably, the hypoxia-mediated inhibition of adipogenic differentiation was reversible: AT-MSCs pre-exposed to hypoxia when switched to normoxic conditions exhibited significantly higher adipogenic differentiation capacity compared to their pre-exposed normoxic-cultured counterparts. Accordingly, the expression of adipocyte-specific genes, peroxisome proliferator activated receptor gamma (Ppargamma), lipoprotein lipase (Lpl) and fatty acid binding protein 4 (Fabp4) were significantly enhanced in hypoxia pre-exposed AT-MSCs. In conclusion, pre-culturing MSCs under hypoxic culture conditions may represent a strategy to enhance MSC production, enrichment and adipogenic differentiation.

[The abdominal compartment syndrome and the importance of decompressive re-laparotomy]. / La sindrome compartimentale addominale ed il ruolo della re-laparotomia decompressiva.

BACKGROUND: the Abdominal Compartment Syndrome (ACS) is an increasingly recognized complication of both medical and surgical patients. The World Society of the Abdominal Compartmental Syndrome defined Intra Abdominal Hypertension (IAH) as a mean Intra Abdominal Pressure (IAP) ≥ 12 mm Hg and the ACS as IAP ≥ 20 mmHg (with or without an abdominal perfusion pressure < 60 mm Hg) that is associated with dysfunction or failure of one or more organ systems that was not previously present. The IAH contributes to organ failure in patients with abdominal trauma and sepsis and leads to the development of ACS. OBJECTIVES: This study aims to investigate the clinical significance of IAH, the prevalence of ACS and the importance to the effects to the abdominal decompressive re-laparotomy. Patients and methods. The study included 10 patients, 4 men and 6 women with an average age of 68 years (range, 38-86) operated and and treated with xifo-pubic laparotomy between January 2007 and December 2008. According to gold-standard methods, we measured the IAP by indirect measurement using the transvescical route via Foley bladder catheter. RESULTS: among 10 patients with laparotomy, 8 patients (80%) developed IAH < 20 mm Hg but they have not reported significant organ dysfunction , while 2 patients (20%) developed an IAH > 20 mm Hg associated whit organ dysfunction. For this reason, the last 2 patients were undergoing to the decompressive re-laparotomy with temporary closure. CONCLUSION: in according to our experience and the results of the literature, we believe essential monitoring abdominal pressure in patients with abdominal laparotomy. The abdominal decompressive re-laparotomy is a useful procedure to reduce symptoms and improve the health of the patient.

Postural control and risk of falling in bipodalic and monopodalic stabilometric tests of healthy subjects before, after visuo-proprioceptive vestibulo-postural rehabilitation and at 3 months thereafter: role of the proprioceptive system.

Nine healthy volunteers (6 males, 3 females), mean age 34.5 years (SD = 11.52), underwent a vestibulo-postural rehabilitation cycle with a visuo-proprioceptive-type stimulus. All subjects in the study group were evaluated by means of stabilometric bipodalic and monopodalic tests both before and immediately after treatment, and again 3 month thereafter. The Delos Postural Proprioceptive System®, DPPS (Delos, srl, Turin, Italy), was used in performing these stabilometric tests and in the rehabilitation exercises. The first aim of the study was to evaluate to what extent the functional level of the proprioceptive system was reliable, in healthy subjects, in the control of postural stability; the second was to demonstrate the possibility to increase this level by means of a novel visuo-proprioceptive feedback training; the last was to establish whether or not the increase achieved was permanent. The bipodalic test did not reveal any deficit in posture either before or after rehabilitation. The monopodalic test prior to treatment, with eyes closed, revealed, in 2/3 of the study group, evidence of the risk of falling, expressed as the precautional strategy (8.57 ± 6.18% SD). An increase in the proprioceptive activity, obtained in the subjects examined immediately after the visuo-proprioceptive vestibulo-postural rehabilitation, led, in the monopodalic test, with eyes closed, to a significant reduction in the risk of falling (with the precautional strategy equal to 1.09 ± 2.63% SD, p = 0.004). The monopodalic test, with eyes closed, 3 months after rehabilitation, demonstrated results not unlike those pre-treament with values, therefore, not more significant than those emerging from the pre-treatment test. Thus, from the above-mentioned data, it can be observed that, also in healthy subjects, there may be different levels of postural proprioceptive control related to a high risk of falling. These levels can be maintained constant for a certain period of time, until a significant reduction in the risk of falling is achieved, only if continuously stimulated by appropriate sensorial information.

Colovesical fistulae in the sigmoid diverticulitis.

In most cases Colovesical fistulae are complications of diverticular disease and representing the most common kind of colodigestive fistula; less common are colovaginal, colocutaneous, coloenteric and colouterine fistula. In this article we review the literature concerning colovesical fistulae in colorectal surgery for sigmoid diverticulitis and report on two cases that required a surgical treatment, one elective and the other in emergency. In both cases we performed a sigmoid resection with a primary anastomosis and small vesical window-ectomy placing a Foley catheter for about 10 days.

[The variation of the vestibular response vs. the variations of the auditory threshold after administration of glycerol in patients with Meniere's disease]. / Variazione della risposta vestibolare versus variazioni di soglia tonale dopo somministrazione di glicerolo in pazienti menierici.

Vestibular and auditory functions after glycerol intake were assessed correlated in twenty-eight patients diagnosed as menieric according to AAOO criteria. All patients had unilateral Ménière's disease confirmed by monolateral hypoacusia and labyrinthine hypofunction. Hearing thresholds were tested by tone-audiometry, according to the standard glycerol test. Variation in vestibular response were assessed comparing the VOR during the rotatory sinusoidal test as well as the caloric test, before glycerol intake and 2 hours after drug administration. Slow phase angolar velocity, directional preponderance percentile and percentile variation between basic and control observation were calculated. The audiometric glycerol test was positive in 58% of the cases. The vestibular glycerol test was positive in 30% of the cases and no correlation between and individual results hearing threshold result was found. The findings reported by other Authors regarding auditory and vestibular responses to glycerol intake were verified. Possible reasons which may account for variation with regard to reaction patterns in the acoustic and non acoustic labyrinth after glycerin administration are discussed. In the Authors' view, incoherence between vestibular and cochlear response might be linked to differences in the physiology of the fluid in the two labyrinths. In the vestibular district, glycerol might induce an early depletive effect and a later paradoxal effects due to mechanical modification of the ampulla function.

On the stimulation by insulin of tryptophan transport across the blood-brain barrier.

Following previous studies showing that in vivo insulin administration increases brain tryptophan levels, we have tested the effect of insulin on tryptophan uptake by isolated bovine brain capillaries, which represent the in vitro equivalent of the blood-brain barrier. In the presence of insulin and Na+ ions, the uptake of 14C-labelled tryptophan was significantly increased with respect to controls, this increase being essentially due to a higher affinity of the transport system for the amino acid, while the Vmax was not affected. Insulin increased also, to a similar extent, the uptake of alpha-methylaminoisobutyrate in the presence of Na+ ions, while the uptake of beta-aminobicyclo(2.2.1)heptane carboxylic acid was not affected. Addition of phloretine, or of anti-insulin antibodies, as well as omission of Na+ ions from the buffer abolished the effect of insulin. Insulin appears therefore to increase specifically the substrate affinity of the A-system for neutral amino acid transport, without exerting any influence on the L-system. The absence of the A-system from the luminal side of the microvessels, and the high insulin concentrations needed, raise however some problems as to the physiological significance of this effect.

Brain microvessels take up large neutral amino acids in exchange for glutamine. Cooperative role of Na+-dependent and Na+-independent systems.

Some regulatory aspects of neutral amino acid transport were investigated in isolated brain microvessels, an in vitro model of the blood-brain barrier. Preloading of the microvessels with glutamine stimulated the subsequent uptake of other neutral amino acids by way of the Na+-independent L system, but had no effect on the uptake of either basic or acidic amino acids. Moreover, this stimulation was abolished when the loading step was carried out in the absence of Na+ ions or in the presence of a high concentration of alpha-methylaminoisobutyric acid, indicating that the microvessels were able to concentrate glutamine via the A system of amino acid transport. Since the presence of the A system of neutral amino acid transport has not been detected in studies of blood-brain transport performed in vivo, the A system is probably associated with the antiluminal side of brain microvessels. Our results indicate, therefore, that the concentrative Na+-dependent A system and the exchanging Na+-independent L system can cooperate in the uptake of the large neutral hydrophobic amino acids. Such a cooperation may be relevant in the pathogenesis of some neurological disturbances such as hepatic encephalopathy, in which brain glutamine concentration is unusually high.