Mechanical behavior of a total chest wall prosthesis with rib-like features.

The Department of Thoracic Surgery of the National Institute of Cancer in Milan developed a new rib-cage prosthesis which tries to combine flexibility, protection and bio-compatibility. This new replacement concept has been implanted in many patients, showing cheering results in term of reconstructions simplicity, postoperative complications reduction and patients comfort. This paper investigates and discusses in detail the mechanical behavior of the innovative rib cage prosthesis. Mechanical strength and stiffness are numerically evaluated in order to asses its limits and if it is fully compatible with patients 'normal' life.

Liposarcoma of the Spermatic Cord: Impact of Final Surgical Intervention--An Institutional Experience.

BACKGROUND: Paratesticular liposarcomas are almost always mistakenly diagnosed as inguinal hernias subsequently followed by inadequate operation. METHODS: 14 consecutive patients with paratesticular liposarcoma were retrospectively reviewed. Preoperative management was evaluated. Disease-free and overall survival were determined. RESULTS: In 11 patients primary and in 3 patients recurrent liposarcoma of the spermatic cord were diagnosed. Regarding primary treatment in primary surgical intervention resection was radical (R0) in 7 of 14 (50%) patients, marginal (R1) in 6 (43%) patients, and incomplete with macroscopic residual tumour (R2) in 1 (7%) patient. Primary treatment secondary surgical intervention was performed in 4 patients: resection was radical (R0) in 3 (75%) patients and marginal (R1) in 1 (25%) patient. Regarding secondary treatment in recurrent disease resection was marginal (R1) in 3 patients (100%). Final histologic margins were negative in 10 patients with primary disease (71%) and positive in 4 patients with subsequent recurrent disease. After radical resection disease-free survival rates at 3 years were 100%. Overall survival at 4.5 years (54 (18-180) months) was 64%. CONCLUSION: An incomplete first surgical step increases the number of positive margins leading to local recurrences and adverse prognoses. Aggressive surgery should be attempted to attain 3-dimensional negative margins.

Indications and limits for associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). Lessons Learned from 15 cases at a single centre.

INTRODUCTION: The ALPSS procedure has been recently introduced as an alternative to PVE for liver volume augmentation in cases of planned right trisectionectomy with small future RLV and high risk of PHLF. We retrospectively analysed our single centre experience with 15 ALPPS procedures in order to better assess the limits and indications of the procedure. PATIENTS AND METHODS: The following volumetric parameters were evaluated: total liver volume (TLV), remnant liver volume (RLV), remnant liver volume to total liver volume ratio (RLV/TLV), remnant liver volume to body weight ratio (RLV/BWR) and median volume gain. The ALPPS procedure was usually considered when RLV/TLV < 25 % or RLV/BWR < 0.5. The ALPPS procedure consisted of phase 1 (in situ splitting of the liver), interphase (waiting for liver regeneration) and phase 2 (completion of right trisectionectomy). Postoperative complications were reported according to the Dindo-Clavien classification. Patient survival, late complications and tumour recurrence were analysed. RESULTS: Between November 2010 and September 2013, we performed 15 ALPPS procedures in 10 patients with primary liver tumours (5 h-CCA, 4 i-CCA and 1 HCC) and in 5 with CRLM. The preoperative RLV/TLV ratio was 22.6 % (15.7 - 29.2) and the RLV/BWR 0.46 (0.22 - 0.66). After 10 days (range 8 - 16) the RLV/TLV ratio and RLV/BWR increased up to 36.3 % (30 - 59.2 %) and 0.67 (0.5 - 1.2) respectively, with a median volume gain of 87.2 % (23.8 - 161 %). The time interval between phases 1 and 2 was 13 days (9 - 18). An R0 status was reached in 13 patients and R1 in 2. The overall postoperative morbidity was 66.7 %. After phase 1, 8 patients experienced 19 complications and 7 none. After phase 2, 11 patients experienced 36 complications and 4 none. Four patients died postoperatively after 22 days (9 - 36 days) resulting in a postoperative mortality of 28.7 %. After a median follow-up of 17 months (1 - 33), 10 out of 15 patients are still alive (survival rate 66.6 %). Four patients (2 i-CCA, 1 CRLM, 1 HCC) developed tumour recurrences (2 intrahepatic and 2 extrahepatic). One patient with i-CCA died at POM 4 secondary to peritoneal carcinosis. DISCUSSION: The actual high morbidity and mortality rates related to the ALPPS procedure should lead us to a more cautious selection of the candidates for this operation and restriction of the indications through an accurate work-up based on interdisciplinary cooperation among hepatologists, oncologists, radiologists and surgeons.

[Gastrointestinal stromal tumours bigger than 20 cm: experience with imatinib chemotherapy in neoadjuvant intention]. / Gastrointestinale Stromatumore größer als 20 cm: Erfahrungen mit Imatinib in neoadjuvanter Intention.

The size of the primary tumour is considered the most important risk factor for the development of metastasis or local recurrence in case of gastrointestinal stromal tumour (GIST). Until now no prospective data are available in the literature about the role of neadjuvant therapy with Imatinib. Between 2009 and 2012 seven patients with a giant GIST > 20 cm underwent a neadjuvant treatment with Imatinib, a radical operation, followed by an adjuvant therapy. These patients were controlled with regard to peri- and postoperative morbidity and disease-free survival. Two patients were considered not resectable and one patient showed liver metastasis at the time of diagnosis. RECIST responses to the neoadjuvant Imatinib were: 2/7 patients with stable disease, 3/7 partial response, 2/7 partial response with down-staging (resectable disease). Because of the following tumour localisations (6 gastric and 1 rectal), six gastrectomies (one en-bloc with left pancreas) and one Holm operation were performed. The patient with simultaneous liver metastasis developed a tumour progression during the follow-up but the others are still tumour free after 2 years. We detected a significant tumour volume regression due to the neadjuvant chemotherapy in cases of GIST > 20 cm (30 %). Our series showed good results for a neadjuvant therapy in cases of giant GIST with the achievement of 100 % R0 resection without a high morbidity rate (in the literature a tumor size > 10 cm and poor localisation is associated to a high risk of R1 - 2 and high morbidity). Peri- and postoperative morbidity are acceptable and the tumour free survival at 2 years is 85 %.

Niguarda Trauma Team: outcome of three years of activity.

BACKGROUND: The aim of this study was to prove the existence of a direct relationship between the comprehensive strategy of trauma management and an enhancement in outcome. Tests were carried out on the impact of the Niguarda Trauma Team System on mortality rates due to severe trauma. METHODS: The epidemiological data was retrospectively reviewed along with, the severity scores: Abbreviated Injury Scale (AIS), Injury Severity Score (ISS), Revised Trauma Score (RTS), Probability of survival (Ps) and the outcome of severe trauma admitted to Niguarda hospital between October 2002 and September 2005. All data were collected from the Trauma Registry of the Niguarda Hospital. Two subsequent periods of 20 and 16 months were compared. RESULTS: Nine hundred forty-two severe traumas (94.05% blunt trauma) were recorded with an overtriage rate of 36.09%. Most patients were admitted for bone and muscular injuries (52.22%). Excluding the patients who were overtriaged, there were 129 patients who died. Comparing the two periods, the Authors observed a significant reduction in mortality from 22.56% to 19.75%, mainly related to a decrease in early mortality due to hemodynamic instability. Central nervous system injury was the main cause of death (65%). Average hospital stay significantly decreased from 17.01+/-12.07 days to 14.97+/-10.34 days. CONCLUSION: Introducing a comprehensive strategy of severe trauma management, the Niguarda Trauma Team System had a significant impact on mortality rates and hospital stay.

Evaluation of the tumor-promoting activity of two beta-adrenoreceptor blocking agents, propranolol and atenolol, in liver of Fischer 344 rats.

The tumor-promoting activity of two beta-adrenoreceptor blocking agents, propranolol and atenolol, was tested in a two-stage protocol of hepatocarcinogenesis in male and female Fischer 344 rats. Propranolol is a lipophilic non-selective beta-blocker mainly eliminated via the liver; atenolol is a hydrophilic beta 1-selective blocking agent, mainly eliminated via the kidney. Animals were initiated with a single dose of diethylnitrosamine (DEN, 200 mg/kg, i.p.) and, after 17 days of recovery, were continuously treated with propranolol (75-100 mg/kg) or atenolol (300 mg/kg) by gavage for up to 21 months. Rats given phenobarbital (0.05% in the diet) were used as positive controls. After 2, 4 and 8 months of promotion, preneoplastic lesions were quantified by staining sections of liver for gamma-glutamyltranspeptidase (GGT). In non-initiated rats, neither propranolol nor atenolol influenced the development of spontaneous preneoplastic or neoplastic liver lesions. The results obtained in DEN-initiated rats given propranolol cannot be unequivocally interpreted. In the male, propranolol seemed to be ineffective. In the female, there was weak enhancement of DEN-induced GGT foci at 4 and 8 months and of neoplastic lesions thereafter. However, there was great interindividual variability in focus and tumor yields. Unfortunately, due to the high incidence of liver tumors in rats given DEN alone and the small number of propranolol-treated rats that survived until the end of the experiment, no definite conclusion can be drawn about the modifying potential of this beta-blocker on liver carcinogenesis. There was no evidence of liver tumor promotion in DEN-initiated rats of either sex given atenolol.

Galanin-receptor ligand M40 peptide distinguishes between putative galanin-receptor subtypes.

The galanin-receptor ligand M40 [galanin-(1-12)-Pro3-(Ala-Leu)2-Ala amide] binds with high affinity to [mono[125I]iodo-Tyr26]galanin-binding sites in hippocampal, hypothalamic, and spinal cord membranes and in membranes from Rin m5F rat insulinoma cells (IC50 = 3-15 nM). Receptor autoradiographic studies show that M40 (1 microM) displaces [mono[125I]iodo-Tyr26]galanin from binding sites in the hippocampus, hypothalamus, and spinal cord. In the brain, M40 acts as a potent galanin-receptor antagonist: M40, in doses comparable to that of galanin, antagonizes the stimulatory effects of galanin on feeding, and it blocks the galaninergic inhibition of the scopolamine-induced acetylcholine release in the ventral hippocampus in vivo. In contrast, M40 completely fails to antagonize both the galanin-mediated inhibition of the glucose-induced insulin release in isolated mouse pancreatic islets and the inhibitory effects of galanin on the forskolin-stimulated accumulation of 3',5'-cAMP in Rin m5F cells; instead M40 is a weak agonist at the galanin receptors in these two systems. M40 acts as a weak antagonist of galanin in the spinal flexor reflex model. These results suggest that at least two subtypes of the galanin receptor may exist. Hypothalamic and hippocampal galanin receptors represent a putative central galanin-receptor subtype (GL-1-receptor) that is blocked by M40. The pancreatic galanin receptor may represent another subtype (GL-2-receptor) that recognizes M40, but as a weak agonist. The galanin receptors in the spinal cord occupy an intermediate position between these two putative subtypes.

Neuroleptics increase striatal acetylcholine release by a sequential D-1 and D-2 receptor mechanism.

In normal striata, pre-treatment with the D-1 antagonist SCH 23390 (250 and 25 micrograms kg-1, s.c.) completely and lastingly prevented the D-2 antagonist remoxipride (REM) from increasing acetylcholine (ACh) release; post-treatment did not affect REM action. In alpha-methyl-p-tyrosine (alpha-MpT) dopamine (DA)-depleted striata, however, pretreatment with SCH 23390 resulted in a transient impairment of REM induced stimulation of ACh release but post-treatment still had no effect. Two different mechanisms therefore seem to be involved in D-2 antagonist-induced stimulation of ACh release; the antagonists indirectly activate a D-1 receptor-mediated facilitatory mechanism regulating cholinergic function, and directly block a D-2 receptor-mediated inhibitory one. In normal rats, in an early phase after D-2 antagonist administration, only the first mechanism is operative; in a later phase, both mechanisms cooperate in the stimulation of ACh release. When DA release is impaired by alpha-MpT, the D-2 inhibitory receptor mechanism becomes more important than the D-1 facilitatory one in controlling ACh release.

N-terminal galanin fragments inhibit the hippocampal release of acetylcholine in vivo.

Using synthetic N-terminal fragments of galanin, galanin (1-7), galanin (1-9), galanin (1-12) and galanin (1-16), we have shown that the minimal sequence required for inhibition of acetylcholine release in vivo from rat ventral hippocampus corresponds to galanin (1-12). The fragment (1-9) displays activity in vivo but only at a very high concentration of 6.23 nmol while galanin (1-7) and C-terminal fragment (17-29) are without effect. Binding studies showed that galanin (1-16) and galanin (1-12) bind with submicromolar IC50 values to rat hippocampal galanin receptors. Galanin (1-9) has substantially lower affinity towards rat ventral hippocampal galanin receptor.