Prophylactic mesh reinforcement for midline incisional hernia prevention: systematic review and updated meta-analysis of randomized controlled trials.

BACKGROUND: Incisional hernia (IH) is a common complication after abdominal surgery. Prevention of IH is matter of intense research. Prophylactic mesh reinforcement (PMR) has been shown to be promising in the minimization of IH risk after elective midline laparotomy. METHODS: Systematic review and meta-analysis of randomized controlled trials (RCTs) comparing PMR vs. primary suture closure (PSC). Risk ratio (RR) and standardized mean difference (MD) were used as pooled effect size measures whereas 95% confidence intervals (95%CI) were used to assess relative inference. RESULTS: Fourteen RCTs (2332 patients) were included. Overall, 1280 (54.9%) underwent PMR while 1052 (45.1%) PSC. Postoperative follow-up ranged from 12 to 67 months. The incidence of IH was reduced for PMR vs. PSC (13.4% vs. 27.5%). The estimated pooled IH RR for PMR vs. PSC is 0.38 (95% CI 0.24-0.58; p < 0.001). Stratified subgroup analysis according to mesh location shows a risk reduction for intraperitoneal (RR = 0.65; 95% CI 0.48-0.89), preperitoneal (RR = 0.18; 95% CI 0.04-0.81), retromuscular (RR = 0.47; 95% CI 0.24-0.92) and onlay (RR = 0.24; 95% CI 0.12-0.51) compared to PSC. The seroma RR was higher for PMR (RR = 2.05; p = 0.0008). No differences were found for hematoma (RR = 1.49; p = 0.34), surgical site infection (SSI) (RR = 1.17; p = 0.38), operative time (OT) (MD = 0.27; p = 0.413), and hospital length of stay (HLOS) (MD = -0.03; p = 0.237). CONCLUSIONS: PMR seems effective in reducing the risk of IH after elective midline laparotomy compared to PSC in the medium-term follow-up. While the risk of postoperative seroma appears higher for PMR, hematoma, SSI, HLOS and OT seems comparable.

Paraesophageal hernia repair with laparoscopic Toupet fundoplication: impact on pulmonary function, respiratory symptoms and quality of life.

BACKGROUND: Paraesophageal hiatal hernia (PEH) is characterized by protrusion of intra-abdominal organs into the posterior mediastinum. Respiratory symptoms and reduced pulmonary function have been described as possibly related to lung compression. OBJECTIVE: To assess the effect of laparoscopic Toupet fundoplication (LTF) for PEH repair on pulmonary function, measured with pulmonary function tests (PFTs), and respiratory symptoms. METHODS: Retrospective, single-center, cohort study (November 2015-2020). All patients that completed pre- and postoperative (12 months) PFTs assessment were included. The gastroesophageal reflux disease health-related quality of life (GERD-HRQL), reflux symptom index (RSI) and short form-36 (SF-36) were used. RESULTS: Overall, 71 patients were included. The median age was 67.1 years and the majority were females (78.8%). Baseline PFTs were within normal limits in 91% of patients. At 12 month follow-up, total lung capacity (TLC) (4.77 vs. 5.07 L; p = 0.0251), vital capacity (VC) (2.97 vs. 3.31 L; p = 0.0065), forced expiratory volume in one second (FEV1) (2.07 vs. 2.44 L; p < 0.001) and forced vital capacity (FVC) (2.78 vs. 3.19 L; p < 0.001) were significantly improved. No significant differences were found for diffusing capacity of lung for carbon monoxide (DLCO) (17.09 vs. 17.24; p = 0.734), and FEV1/FVC (0.77 vs. 0.77; p = 0.967). Interestingly, improvements were more pronounced in patients with large PEH (type IIIb and IV). At 12 month follow-up, both gastrointestinal and respiratory symptoms were significantly improved and 94% of patients were satisfied with the operation. The GERD-HRQL (18.1 ± 7.9 vs. 4.01 ± 2.4; p = 0.001), RSI (37.8 ± 9.7 vs. 10.6 ± 8.9; p < 0.001) and all SF-36 items were improved. CONCLUSIONS: LTF for the treatment of PEH is safe and seems to be effective up to 12 month follow-up with improved lung volumes, spirometry values, quality of life, gastrointestinal and respiratory symptoms.

Medium-term safety and efficacy profile of paraesophageal hernia repair with Phasix-ST® mesh: a single-institution experience.

BACKGROUND: Hernia recurrence after laparoscopic repair is a perplexing problem. In an effort to reduce anatomical and clinical recurrences, different type of meshes have been used to bolster the esophageal hiatus. OBJECTIVE: The aim of this study was to assess safety, medium-term efficacy, and quality of life improvement after laparoscopic repair of hiatal hernia reinforced with a biosynthetic absorbable mesh (Phasix-ST®). METHODS: Observational single-center retrospective single-arm cohort study (November 2015-February 2021). We included all adult patients (> 18 years old) who underwent laparoscopic paraesophageal hernia repair with Phasix-ST® mesh and Toupet fundoplication. RESULTS: Sixty-eight patients were included. The median postoperative stay was 3.2 days (range 2-9) and the postoperative complication rate was 11.7%. The median follow-up time was 27 months (range 1-53). No mesh-related complications were detected. Hernia recurrence was diagnosed in six patients (8.8%). The recurrence-free probability at 34 months was 0.89 (95% CI 0.807-0.988) while at 60 months was 0.86 (95% CI 0.76-0.97). Hernia recurrences were mostly observed between 21 and 36 months after the operation. None of the patients required surgical revision and all were managed with PPI. Postoperative dysphagia requiring endoscopic balloon dilatation occurred in 2.9% of patients. Compared to baseline, both the GERD-HRQL (15.2 ± 6.2 vs. 3.2 ± 3.1; p = 0.026) and all SF-36 items were significantly improved (p < 0.001). CONCLUSIONS: Laparoscopic crura augmentation with Phasix-ST® mesh combined with a Toupet fundoplication is safe and seems effective in the medium-term follow-up. Phasix-ST® crural reinforcement resulted in low hernia recurrence rate with a sustained symptoms and quality of life improvement.

Prevalence and risk factors for diastasis recti abdominis: a review and proposal of a new anatomical variation.

PURPOSE: Diastasis recti abdominis (DRA) or rectus diastasis is an acquired condition in which the rectus muscles are separated by an abnormal distance along their length, but with no fascia defect. To data there is no consensus about risk factors for DRA. The aim of this article is to critically review the literature about prevalence and risk factor of DRA. METHOD: A total of 13 papers were identified. RESULTS: The real prevalence of DRA is unknown because the prevalence rate varies with measurement method, measurement site and judgment criteria, but it is certainly an extremely frequent condition. Numbers of parity, BMI, diabetes are the most plausible risk factors. We identified a new anatomical variation in cadaveric dissection and in abdominal CT image evaluation: along the semilunar line the internal oblique aponeurosis could join the rectus sheath with only a posterior layer, so without a double layer (anterior and posterior) as usually described. We conducted a retrospective review of abdominal CT images and the presence of the posterior insertion only could be considered as a risk factor for DRA. CONCLUSION: Further studies with large sample size, including nulliparous, primiparous, pluriparous and men too, are necessary for identify the real prevalence.

An extraperitoneal approach for complex flank, iliac, and lumbar hernia.

PURPOSE: The aim of this paper is to propose our four-step technique, an open extraperitoneal approach for complex flank, lumbar, and iliac hernias. METHODS: A big polypropylene mesh is placed, covering and reinforcing all the lateral abdominal wall in an extraperitoneal space. Its borders are retroxiphoid fatty triangle and the costal arch cranially and the retropubic space caudally, psoas muscle, and paravertebral region posteriorly and contralateral rectus muscle medially. Mesh dimensions do not depend from the defect size, but prosthesis has to cover all the lateral abdominal wall. RESULTS: No major complications have been reported. The mean length of stay is 4.8 days (range 3-11). Mean follow-up is 44.8 months (range 5-92). One recurrence (4.5%) has been reported at the 1-year clinical evaluation. CONCLUSION: In conclusion, we believe that regardless size and location of the defect, every complex lateral hernia requires the same extensive repair because of the critical anatomy of the region with a big medium-heavyweight polypropylene mesh placed in an extraperitoneal plane, the only one that allows adequate covering of the visceral sac. Our technique is a safe, feasible, and reproducible treatment for this challenging surgical problem.

Open mesh vs. suture umbilical hernia repair: systematic review and updated trial sequential meta-analysis of randomized controlled trials.

PURPOSE: To examine the updated evidence on safety, effectiveness, and outcomes of mesh versus suture elective umbilical hernia (UH) repair and to explore the timely tendency variations favouring one treatment over another. METHODS: MEDLINE and CENTRAL databases were consulted. A systematic review, pairwise meta-analysis, and trial sequential analysis (TSA) were conducted. RESULTS: Six RCTs were included for a total of 742 patients. Overall, 383 (51.6%) underwent mesh, while 359 (48.4%) underwent suture repair. The estimated pooled postoperative recurrence RR was 0.27 (95% CI 0.13-0.53; p < 0.001). The TSA showed a statistically significant timely tendency in favour of mesh repair with a boundary cross curve (Z = 1.96) before reaching the information size. The estimated pooled seroma, haematoma, and wound infection RR were 1.45 (p = 0.368), 0.54 (p = 0.196), and 0.71 (p = 0.375), respectively. The TSA for wound-related complications showed partial, non-significant results. CONCLUSIONS: Elective UH mesh repair seems to be associated with reduced risk of postoperative recurrence compared to simple suture repair with a statistically significant timely trend endorsed by the TSA. Definitive considerations concerning the cumulative effect for seroma, haematoma, and wound infection are premature. Further studies are warranted to endorse these results and deeply investigate the timely tendency variations.

Original concepts in anatomy, abdominal-wall surgery, and component separation technique and strategy.

BACKGROUND: The abdominal wall can be considered comprised of two compartments: an anterior and a posterior compartment. The anterior compartment includes the anterior rectus sheath and the rectus muscle. The posterior compartment comprises the posterior rectus sheath, the transversalis fascia, and the peritoneum. When a large defect in the anterior compartment has to be corrected, for example, a rectus diastasis or large incisional hernia, an action on the anterior compartment is necessary; therefore, an anterior component separation has to be considered. If a loss of substance is present in the posterior compartment, a trasversus abdominis release should be accomplished. METHODS: We propose an original anterior compartment mobilisation, by a posterior approach. Dissection of the posterior rectus sheet proceeds until the linea semilunaris is reached. Incision of the anterior rectus sheath permits a mobilisation of the anterior compartment by a posterior approach. A mesh is placed in a sublay position. If the abdominal wall presents a loss of substance of the posterior compartment, a transversus abdominis release (TAR) can be performed in the same time. RESULTS: No hernia recurrences, no wound infection, and no mesh infection have been reported. CONCLUSIONS: The anterior compartment mobilization permits mobilization towards the midline of rectus muscle and restoration of anterior compartment, with low morbidity rate; it can be easily associated to a large sublay mesh placement, it allows the preservation of the neurovascular bundles and rectus muscle trophism, and it can be associated with a concomitant TAR procedure for the restoration of the PC, if necessary.

Robotic inguinal hernia repair: is technology taking over? Systematic review and meta-analysis.

PURPOSE: To examine the current evidence on the therapeutic role and outcomes of robotic Transabdominal Preperitoneal Inguinal hernia repair (rTAPP) to better define its risk-benefit ratio and guide clinical decision-making. METHODS: PubMed, EMBASE, and Web of Science were consulted. A Frequentist single-arm study-level random effect meta-analysis was performed. RESULTS: Twelve studies published between 2015 and 2018 met the inclusion criteria (1645 patients). Patients' age ranged from 16 to 96, the BMI ranged from 19 to 35.6 kg/m2, and 86.1% were males. Unilateral hernia repair was performed in 69.6% while bilateral hernia repair was performed in 30.4% of patients. The operations were all conducted using the da Vinci Xi or Si robotic system (Intuitive Surgical, Inc., Sunnyvale, CA, USA). The rTAPP was successfully completed in 99.4% of patients and the operative time ranged from 45 to 180.4 min. The postoperative follow-up ranged from 16 to 368 days. The estimated pooled prevalence of intraoperative complications and conversion were 0.03% (95% CI 0.00-0.3) and 0.14% (95% CI 0.0-0.5%), respectively. The estimated pooled prevalence of urinary retention, seroma/hematoma, and overall complications were 3.5% (95% CI 1.6-5.8%), 4.1% (95% CI 1.6-7.5%), and 7.4% (95% CI 3.4-10.9%). The estimated pooled prevalence of hernia recurrence was 0.18% (95% CI 0.00-0.84%). CONCLUSIONS: Robotic technology has been progressively entering surgical thinking and gradually changing surgical procedures. Based on the results of the present study, the rTAPP seems feasible, safe, and effective in the short term for patients with unilateral and bilateral inguinal hernias. Further prospective studies and randomized controlled trials are needed to validate these findings.

Primary inguinal hernia: systematic review and Bayesian network meta-analysis comparing open, laparoscopic transabdominal preperitoneal, totally extraperitoneal, and robotic preperitoneal repair.

PURPOSE: The Open Lichtenstein technique, the Laparoscopic Trans-Abdominal PrePeritoneal (TAPP), the Totally Extra Peritoneal (TEP), and the robotic TAPP (rTAPP) are commonly performed. The aim of the present network meta-analysis was to globally compare short-term outcomes within these major surgical techniques for primary unilateral inguinal hernia repair. METHODS: PubMed, EMBASE, and Web of Science were consulted. A fully Bayesian network meta-analysis was performed. RESULTS: Sixteen studies (51.037 patients) were included. Overall, 35.5% underwent Open, 33.5% TAPP, 30.7% TEP, and 0.3% rTAPP. The postoperative seroma risk ratio (RR) was comparable considering TAPP vs. Open (RR 0.91; 95% CrI 0.50-1.62), TEP vs. Open (RR 0.64; 95% CrI 0.32-1.33), TEP vs. TAPP (RR 0.70; 95% CrI 0.39-1.31), and rTAPP vs. Open (RR 0.98; 95% CrI 0.37-2.51). The postoperative chronic pain RR was similar for TAPP vs. Open (RR 0.53; 95% CrI 0.27-1.20), TEP vs. Open (RR 0.86; 95% CrI 0.48-1.16), and TEP vs. TAPP (RR 1.70; 95% CrI 0.63-3.20). The recurrence RR was comparable when comparing TAPP vs. Open (RR 0.96; 95% CrI 0.57-1.51), TEP vs. Open (RR 1.0; 95% CrI 0.65-1.61), TEP vs. TAPP (RR 1.10; 95% CrI 0.63-2.10), and rTAPP vs. Open (RR 0.98; 95% CrI 0.45-2.10). No differences were found in term of postoperative hematoma, surgical site infection, urinary retention, and hospital length of stay. CONCLUSIONS: This study suggests that Open, TAPP, TEP, and rTAPP seem comparable in the short term. The surgical management of inguinal hernia is evolving and the effect of the adoption of innovative minimally invasive techniques should be further investigated in the long term. Ultimately, the choice of the most suitable treatment should be based on individual surgeon expertise and tailored on each patient.

Primary unilateral not complicated inguinal hernia with an effective, cheap, less invasive, and easy operation: the Trabucco repair.

BACKGROUND: In modern abdominal wall hernia surgery, the achievement of the most effective tailored repair for each specific defect with the less possible invasiveness, the quicker recovery, the lower costs and the fewer risk of local occurrences, recurrences and chronic pain is the most desirable and cutting-edge goal. METHODS: Since 1989 about 4219 primary unilateral not complicated inguinal hernias have been treated with specific indications with a sutureless and minimally invasive anterior open approach. The great majority of these procedures were performed under local anaesthesia in a day surgery regimen, with a systematic and careful nerve sparing, preservation of cremasteric muscle, and with a 3-5 cm skin incision. RESULTS: The minimally invasive sutureless nerve sparing open approach has shown a very low rate of seromas (0.45%), haematomas (0.24%) and infections (0.07%) while the width of skin incision challenges even laparoscopy. A significant reduction of both postoperative pain (2.7%) and chronic neuralgia (0.047%) has led to excellent outcomes in patients, also in terms of quality of life. Compared to the Lichtenstein's tension-free technique, which is at now the gold standard open treatment for primary inguinal hernia worldwide, there are no significant differences in the observed recurrence rate (well below 1%). CONCLUSION: In our experience of almost 30 years we have been able to experiment and refine more and more the sutureless technique proposed by Trabucco for the treatment of primitive inguinal hernia, peer to peer, improving the local anaesthesia and the ability to detect hidden defects during the repair (Spigelian included), reducing the width of the incisions and tractions on the tissues, introducing the concept of a gentle and bloodless "finger surgery" according to a minimally invasive, extremely anatomic, safe, inexpensive, very effective anterior open approach.

Giant inguinal hernia: the challenging hug technique.

PURPOSE: Giant inguinoscrotal hernia are a real challenge for every kind of surgeon. The technique that we adopt is suggested as a good option to deal with this cases. We report our experience in five cases of giant inguinoscrotal hernia with loss of domain from 2005 to 2012. METHOD: Five patients with hernia that descended below the knees in the standing position, with an anteroposterior diameter not inferior to 30 cm and a laterolateral diameter of about 50 cm. Penis was not visible. We did the same procedure for all the five patients: single pararectus incision extended to groin region until proximal half of scrotum, isolation of the entire large sac out of the scrotal cavity, paying attention to not opening it, progressive reduction of the viscera without opening the sac with the hug technique, as shown in the video, placement of a heavyweight polypropylene meshes in the preperitoneal space, scrotal skin reductive plastic. In three of our five cases we obtained restoration of herniated viscera without resection of them. Orchiectomy was performed in all cases. RESULTS: No general neither wound complications were recorded. Long term follow up ranges from 8 years to 18 months: we did not record recurrence or chronic groin pain and scrotal size is normal in each patient. CONCLUSION: The technique proposed permits to treat with success giant inguinaoscrotal hernia, avoiding the use of further specific procedure such as the preoperative progressive pneumoperitoneum. All our patients were satisfied with the surgeries and their quality of daily life had definitely improved.

Optimization of systemic treatments for chronic plaque psoriasis. Recommendations for switching and transitioning.

AIM: The aim of this study was to provide practical recommendations for optimizing the use of conventional and biological systemic treatments for moderate-severe chronic plaque psoriasis, particularly in case of transitioning and switching. METHODS: A total number of 147 dermatologists from 33 different countries including Italy achieved consensus in providing practical recommendations for the use of conventional and biological treatments for moderate to severe psoriasis based on systematic literature review and/or expert opinion. RESULTS: In general, the continuous treatment regimen should be preferred in order to achieve a complete and long-term control of psoriasis. However, the treatment could be stopped or the dose reduced in case of complete disease clearance. A conventional drug could be associated to biological treatment in selected cases. Transitioning and/or switching could be considered in case of inefficacy or intolerance. A period of wash up is required if transitioning or switching is due to safety issues. CONCLUSION: This study provides practical suggestions for the optimal use of conventional and biological treatments for chronic plaque psoriasis.

The sphingosine kinase activator K6PC-5 stimulates C2C12 myoblast differentiation.

Previously, K6PC-5, a synthetic derivative of ceramide, was demonstrated to activate sphingosine kinase (SK)-1 in keratinocytes. In this study its potential biological effect in mouse myoblasts was examined. The obtained results show that K6PC-5 promotes myogenic differentiation by enhancing myogenic marker expression, differentiation index and fusion index. Interestingly, its biological action was prevented by pharmacological inhibition of SK or S1P2 receptor, in full agreement with their recognized role in myoblast differentiation. This is the first evidence that pharmacological activation of SK accelerates myogenesis and suggests that this new therapeutic strategy could be possibly employed in skeletal muscle disorders where muscle regeneration is deficient.

Sphingosine 1-phosphate induces differentiation of adipose tissue-derived mesenchymal stem cells towards smooth muscle cells.

Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid which regulates multiple biological parameters in a number of cell types, including stem cells. Here we report, for the first time, that S1P dose-dependently stimulates differentiation of adipose tissue-derived mesenchymal stem cells (ASMC) towards smooth muscle cells. Indeed, S1P not only induced the expression of smooth muscle cell-specific proteins such as alpha-smooth muscle actin (alpha SMA) and transgelin, but also profoundly affected ASMC morphology by enhancing cytoskeletal F-actin assembly, which incorporated alpha SMA. More importantly, S1P challenge was responsible for the functional appearance of Ca(2+) currents, characteristic of differentiated excitable cells such as smooth muscle cells. By employing various agonists and antagonists to inhibit S1P receptor subtypes, S1P(2) turned out to be critical for the pro-differentiating effect of S1P, while S1P(3) appeared to play a secondary role. This study individuates an important role of S1P in AMSC which can be exploited to favour vascular regeneration.

Pleiotropic effects of sphingolipids in skeletal muscle.

Studies of the last two decades have demonstrated that sphingolipids are important signalling molecules exerting key roles in the control of fundamental biological processes including proliferation, differentiation, motility and survival. Here we review the role of bioactive sphingolipids such as ceramide, sphingosine, sphingosine 1-phosphate, ganglioside GM3, in the regulation of skeletal muscle biology. The emerging picture is in favour of a complex role of these molecules, which appear implicated in the activation of muscle resident stem cells, their proliferation and differentiation, finalized at skeletal muscle regeneration. Moreover, they are involved in the regulation of contractile properties, tissue responsiveness to insulin and muscle fiber trophism. Hopefully, this article will provide a framework for future investigation into the field, aimed at establishing whether altered sphingolipid metabolism is implicated in the onset of skeletal muscle diseases and identifying new pharmacological targets for the therapy of multiple illnesses, including muscular dystrophies and diabetes.

Histological and microscopy FT-IR imaging study on the proliferative activity and angiogenesis in head and neck tumours.

Micro Fourier transform infrared spectroscopy enables one to study small samples because of the high quality spectra that can be obtained. Biochemical and morphological changes between control and pathological tissues of head and neck tumours have been monitored drawing three-dimensional chemical maps of the main vibrational modes in the regions of interest. Comparison between spectral and histological data shows a satisfactory degree of accordance. Among all, proliferating and regressive states of the tumours can be identified.

Sphingosine 1-phosphate induces cell contraction via calcium-independent/Rho-dependent pathways in undifferentiated skeletal muscle cells.

We have previously shown that sphingosine 1-phosphate (S1P) can induce intracellular Ca(2+) mobilization and cell contraction in C2C12 myoblasts and that the two phenomena are temporally unrelated. Although Ca(2+)-independent mechanisms of cell contraction have been the focus of numerous studies on Ca(2+) sensitization of smooth muscle, comparatively less studies have focused on the role that these mechanisms play in the regulation of skeletal muscle contractility. Phosphorylation and activation of myosin by Rho-dependent kinase mediate most of Ca(2+)-independent contractile responses. In the present study, we examined the potential role of Rho/Rho-kinase cascade activation in S1P-induced C2C12 cell contraction. First, we showed that depletion of Ca(2+), by pre-treatment with BAPTA, did not affect S1P-induced myoblastic contractility, whereas it abolished S1P-induced Ca(2+) transients. These results correlated with the absence of troponin C and with the immature cytoskeletal organization of these cells. Experimental evidence demonstrating the involvement of Rho pathway in S1P-stimulated myoblast contraction included: the activation/translocation of RhoA to the membrane in response to agonist-stimulation in cells depleted of Ca(2+) and the inhibition of dynamic changes of the actin cytoskeleton in cells where Rho functions had been inhibited either by overexpression of RhoGDI, a physiological inhibitor of GDP dissociation from Rho proteins, or by pretreatment with Y-27632, a specific Rho kinase inhibitor. Contribution of protein kinase C in this cytoskeletal rearrangement was also evaluated. However, the pretreatment with Gö6976 or rottlerin, specific inhibitors of PKC alpha and PKC delta, respectively, failed to inhibit the agonist-induced myoblastic contraction. Single particle tracking of G-actin fluorescent probe was performed to statistically evaluate actin cytoskeletal dynamics in response to S1P. Stimulation with S1P was also able to increase the phosphorylation level of myosin light chain II. In conclusion, our results strongly suggest that Ca(2+)-independent/Rho-Rho kinase-dependent pathways may exert an important role in S1P-induced myoblastic cell contraction.

Structure of self-assembled liposome-DNA-metal complexes.

We have studied the structural and morphological properties of the triple complex dioleoyl phosphatidylcholine (DOPC)-DNA-Mn2+ by means of synchrotron x-ray diffraction and freeze-fracture transmission electron microscopy. This complex is formed in a self-assembled manner when water solutions of neutral lipid, DNA, and metal ions are mixed, which represents a striking example of supramolecular chemistry. The DNA condensation in the complex is promoted by the metal cations that bind the polar heads of the lipid with the negatively charged phosphate groups of DNA. The complex is rather heterogeneous with respect to size and shape and exhibits the lamellar symmetry of the L(c)(alpha) phase: the structure consists of an ordered multilamellar assembly similar to that recently found in cationic liposome-DNA complexes, where the hydrated DNA helices are sandwiched between the liposome bilayers. The experimental results show that, at equilibrium, globules of the triple complex in the L(c)(alpha) phase coexist with globules of multilamellar vesicles of DOPC in the L(alpha) phase, the volume ratio of the two structures being dependent on the molar ratio of the three components DOPC, DNA, and Mn2+. These complexes are of potential interest for applications as synthetically based nonviral carriers of DNA vectors for gene therapy.

Characterization of 2 novel and 2 recurring BRCA1 germline mutations in breast and/or ovarian carcinoma patients from the area of Naples.

We have analyzed 18 families with high incidence of breast cancer or breast and ovarian cancer for the presence of BRCA1 mutations. We identified 4 mutations in the BRCA1 gene in 4 unrelated probands who belong to families with at least 1 case of breast and 1 case of ovarian cancer. Two of the mutations reported in this study are novel (GAA(1172)-->TAA in family Naples 14, GAA(1765)-->TAA in family Naples 20) whereas the others are already present in the Breast Cancer Information Core Electronic Database (http://nchgr.nih.gov/ Intramural research/Lab transfer/Bic/) (5382insC in family Naples 18 and 2080delA in family Naples 19). Conversely, no mutation in the BRCA1 gene was detected in 14 families characterized by 2 or more cases of breast cancer only, even if bilateral and with early-onset. These results indicate that germline mutations in the BRCA1 gene highly predispose for a cancer syndrome that involves the presence of both breast and ovarian cancer.