Dosimetric and NTCP advantages of robust proton therapy over robust VMAT for Stage III NSCLC in the immunotherapy era.

AIMS: To assess the robustness and to define the dosimetric and NTCP advantages of pencil-beam-scanning proton therapy (PBSPT) compared with VMAT for unresectable Stage III non-small lung cancer (NSCLC) in the immunotherapy era. MATERIAL AND METHODS: 10 patients were re-planned with VMAT and PBSPT using: 1) ITV-based robust optimization with 0.5 cm setup uncertainties and (for PBSPT) 3.5 % range uncertainties on free-breathing CT 2) CTV-based RO including all 4DCTs anatomies. Target coverage (TC), organs at risk dose and TC robustness (TCR), set at V95%, were compared. The NTCP risk for radiation pneumonitis (RP), 24-month mortality (24MM), G2 + acute esophageal toxicity (ET), the dose to the immune system (EDIC) and the left anterior descending (LAD) coronary artery V15 < 10 % were registered. Wilcoxon test was used. RESULTS: Both PBSPT methods improved TC and TCR (p < 0.01). The mean lung dose and lung V20 were lower with PBSPT (p < 0.01). Median mean heart dose reduction with PBSPT was 8 Gy (p < 0.001). PT lowered median LAD V15 (p = 0.004). ΔNTCP > 5 % with PBSPT was observed for two patients for RP and for five patients for 24 MM. ΔNTCP for ≥ G2 ET was not in favor of PBSPT for all patients. PBSPT halved median EDIC (4.9/5.1 Gy for ITV/CTV-based VMAT vs 2.3 Gy for both ITV/CTV-based PBSPT, p < 0.01). CONCLUSIONS: PBSPT is a robust approach with significant dosimetric and NTCP advantages over VMAT; the EDIC reduction could allow for a better integration with immunotherapy. A clinical benefit for a subset of NSCLC patients is expected.

Leopoldia comosa prevents metabolic disorders in rats with high-fat diet-induced obesity.

PURPOSE: Obesity is the main feature of a complex illness known as metabolic syndrome. Anti-obesogenic therapies are often associated with side effects and represent a high cost in conventional pharmacological approaches. New strategies based on natural remedies are under continuous investigation. Leopoldia comosa (L.) Parl. (L. comosa) is a spontaneous plant with diuretic, anti-inflammatory and antioxidant properties. Recently, a hypoglycemic activity mediated by inhibition of carbohydrate digestion has been identified. The aim of this study was to evaluate the effects of a diet supplemented with L. comosa extracts on a rat model of diet-induced obesity. METHODS: Leopoldia comosa bulb extracts were obtained using a dynamic extractor. Phytochemical properties and in vitro determination of the antioxidant activity and of the inhibitory effects on lipase and pancreatic amylase were performed. Rats were fed (12 weeks) a standard diet, or a high-fat diet (HFD), or an HFD plus L. comosa (20 or 60 mg/die) extracts. The metabolic and anthropometric parameters were recorded. RESULTS: Results indicated that L. comosa inhibited lipase and pancreatic amylase activities. In vivo data showed that the supplementation with both doses of L. comosa extracts counteracted the HFD-dependent effects. It reduced body weight, abdominal obesity and dyslipidemia, and improved glucose tolerance with a reduction of lipidic tissue hypertrophy and liver steatosis, as compared to HFD-fed rat. In liver, L. comosa reduced protein expression levels of PEPCK and G6Pase. CONCLUSION: We suggest that L. comosa extracts prevent obesity-dependent metabolic disorders. This paves the way for their therapeutic application as a natural anti-obesity drug.

The innovative "Bio-Oil Spread" prevents metabolic disorders and mediates preconditioning-like cardioprotection in rats.

BACKGROUND AND AIMS: Obesity is often associated with an increased cardiovascular risk. The food industry and the associated research activities focus on formulating products that are a perfect mix between an adequate fat content and health. We evaluated whether a diet enriched with Bio-Oil Spread (SD), an olive oil-based innovative food, is cardioprotective in the presence of high-fat diet (HFD)-dependent obesity. METHODS AND RESULTS: Rats were fed for 16 weeks with normolipidic diet (ND; fat: 6.2%), HFD (fat: 42%), and ND enriched with SD (6.2% of fat + 35.8% of SD). Metabolic and anthropometric parameters were measured. Heart and liver structures were analyzed by histochemical examination. Ischemic susceptibility was evaluated on isolated and Langendorff-perfused cardiac preparations. Signaling was assessed by Western blotting. Compared to ND rats, HFD rats showed increased body weight and abdominal obesity, dyslipidemia, and impaired glucose tolerance. Morphological analyses showed that HFD is associated with heart and liver modifications (hypertrophy and steatosis, respectively), lesser evident in the SD group, together with metabolic and anthropometric alterations. In particular, IGF-1R immunodetection revealed a reduction of hypertrophy in SD heart sections. Notably, SD diet significantly reduced myocardial susceptibility against ischemia/reperfusion (I/R) with respect to HFD through the activation of survival signals (Akt, ERK1/2, and Bcl2). Systolic and diastolic performance was preserved in the SD group. CONCLUSIONS: We suggest that SD may contribute to the prevention of metabolic disorders and cardiovascular alterations typical of severe obesity induced by an HFD, including the increased ischemic susceptibility of the myocardium. Our results pave the way to evaluate the introduction of SD in human alimentary guidelines as a strategy to reduce saturated fat intake.

Signal molecule changes in the gills and lungs of the African lungfish Protopterus annectens, during the maintenance and arousal phases of aestivation.

African lungfishes are obligate air breathers, with reduced gills and pulmonary breathing throughout their life. During the dry season they aestivate on land, with the collapse of secondary lamellae of their gills and the establishment of an exclusive aerial ventilation through the vascularization and expansion of their lungs. To date, the mechanisms underlining the respiratory organ remodeling in aestivating lungfishes are unknown. This study aimed to identify key switch components of the stress-induced signal transduction networks implicated in both rapid and medium-long term remodeling of the gills and lungs of the African lungfish Protopterus annectens during aestivation. Through immunofluorescence microscopy and Western blotting, the localization and the expression of nitric oxide synthase (NOS), Akt, Hsp-90 and HIF-1α were evaluated in both gills and lungs exposed to three experimental conditions: freshwater (FW), 6 months of experimentally induced aestivation (6mAe), and 6 days after arousal from 6 months of aestivation (6mAe6d). After 6mAe, the expression of NOS (p-eNOS antibody), Akt (p-Akt antibody), and Hsp-90 decreased in the gills, while NOS and Hsp-90 expression increased with Akt remained unchanged in the lungs. Upon 6mAe6d, NOS, Akt and Hsp-90 expression in the gills returned to the respective FW values. In the lungs of the aroused fish, NOS and Akt decreased to their respective FW levels, while Hsp-90 expression was enhanced with respect to aestivation. In both respiratory organs, the qualitative and quantitative patterns of HIF-1α expression correlated inversely to those of NOS. Overall, our findings suggest that the molecular components of the NOS/NO system changed in a tissue-specific manner in parallel with organ readjustment in the gills and lungs of P. annectens during aestivation and arousal.

Nitric oxide synthase-dependent "on/off" switch and apoptosis in freshwater and aestivating lungfish, Protopterus annectens: skeletal muscle versus cardiac muscle.

African lungfishes (Protopterus spp.) are obligate air breathers which enter in a prolonged torpor (aestivation) in association with metabolic depression, and biochemical and morpho-functional readjustments during the dry season. During aestivation, the lungfish heart continues to pump, while the skeletal muscle stops to function but can immediately contract during arousal. Currently, nothing is known regarding the orchestration of the multilevel rearrangements occurring in myotomal and myocardial muscles during aestivation and arousal. Because of its universal role in cardio-circulatory and muscle homeostasis, nitric oxide (NO) could be involved in coordinating these stress-induced adaptations. Western blotting and immunofluorescence microscopy on cardiac and skeletal muscles of Protopterus annectens (freshwater, 6months of aestivation and 6days after arousal) showed that expression, localization and activity of the endothelial-like nitric oxide synthase (eNOS) isoform and its partners Akt and Hsp-90 are tissue-specifically modulated. During aestivation, phospho-eNOS/eNOS and phospho-Akt/Akt ratios increased in the heart but decreased in the skeletal muscle. By contrast, Hsp-90 increased in both muscle types during aestivation. TUNEL assay revealed that increased apoptosis occurred in the skeletal muscle of aestivating lungfish, but the myocardial apoptotic rate of the aestivating lungfish remained unchanged as compared with the freshwater control. Consistent with the preserved cardiac activity during aestivation, the expression of apoptosis repressor (ARC) also remained unchanged in the heart of aestivating and aroused fish as compared with the freshwater control. Contrarily, ARC expression was strongly reduced in the skeletal muscle of aestivating lungfish. On the whole, our data indicate that changes in the eNOS/NO system and cell turnover are implicated in the morpho-functional readjustments occurring in lungfish cardiac and skeletal muscle during the switch from freshwater to aestivation, and between the maintenance and arousal phases of aestivation.

IMRT or 3D-CRT in glioblastoma? A dosimetric criterion for patient selection.

Intensity modulated radiation therapy (IMRT) is increasingly employed in glioblastoma (GBM) treatment. The present work aimed to assess which clinical-dosimetric scenario could benefit the most from IMRT application, with respect to three-dimensional conformal radiation therapy (3D-CRT). The number of organs at risk (OARs) overlapping the planning target volume (PTV) was the parameter describing the clinical-dosimetric pattern. Based on the results, a dosimetric decision criterion to select the most appropriate treatment technique is provided. Seventeen previously irradiated patients were retrieved and re-planned with both 3D-CRT and IMRT. The prescribed dose was 60 Gy/30fx. The cases were divided into 4 groups (4 patients in each group). Each group represents the scenario where 0, 1, 2 or 3 OARs overlapped the target volume, respectively. Furthermore, in one case, 4 OARs overlapped the PTV. The techniques were compared also in terms of irradiated healthy brain tissue. The results were evaluated by paired t-test. IMRT always provided better target coverage (V95%) than 3D-CRT, regardless the clinical-dosimetric scenario: difference ranged from 0.82% (p = 0.4) for scenario 0 to 7.8% (p = 0.02) for scenario 3, passing through 2.54% (p = 0.18) and 5.93% (p = 0.08) for scenario 1 and 2, respectively. IMRT and 3D-CRT achieved comparable results in terms of dose homogeneity and conformity. Concerning the irradiation of serial-kind OARs, both techniques provided nearly identical results. A statistically significant dose reduction to the healthy brain in favor of IMRT was scored. IMRT seems a superior technique compared to 3D-CRT when there are multiple overlaps between OAR and PTV. In this scenario, IMRT allows for a better target coverage while maintaining equivalent OARs sparing and reducing healthy brain irradiation. The results from our patients dataset suggests that the overlap of three OARs can be used as a dosimetric criterion to select which patients should receive IMRT treatment.

Effects of temperature on the nitric oxide-dependent modulation of the Frank-Starling mechanism: the fish heart as a case study.

The Frank-Starling law is a fundamental property of the vertebrate myocardium which allows, when the end-diastolic volume increases, that the consequent stretch of the myocardial fibers generates a more forceful contraction. It has been shown that in the eel (Anguilla anguilla) heart, nitric oxide (NO) exerts a direct myocardial relaxant effect, increasing the sensitivity of the Frank-Starling response (Garofalo et al., 2009). With the use of isolated working heart preparations, this study investigated the relationship between NO modulation of Frank-Starling response and temperature challenges in the eel. The results showed that while, in long-term acclimated fish (spring animals perfused at 20 °C and winter animals perfused at 10 °C) the inhibition of NO production by L-N5 (1-iminoethyl)ornithine (L-NIO) significantly reduced the Frank-Starling response, under thermal shock conditions (spring animals perfused at 10 or 15 °C and winter animals perfused at 15 or 20 °C) L-NIO treatment resulted without effect. Western blotting analysis revealed a decrease of peNOS and pAkt expressions in samples subjected to thermal shock. Moreover, an increase in Hsp90 protein levels was observed under heat thermal stress. Together, these data suggest that the NO synthase/NO-dependent modulation of the Frank-Starling mechanism in fish is sensitive to thermal stress.

Morpho-functional characterization of the goldfish (Carassius auratus L.) heart.

Using morphological and physiological approaches we provided, for the first time, a structural and functional characterization of Carassius auratus L. heart. Besides to the classical four chambers, i.e. sinus venosus, atrium, ventricle, bulbus, we described two distinct structures corresponding to the atrio-ventricular (AV) region and the conus arteriosus. The atrium is very large and highly trabeculated; the ventricle shows an outer compacta, vascularized by coronary vessels, and an inner spongiosa; the bulbus wall is characterized by a high elastin/collagen ratio, which makes it extremely compliant. Immunolocalization revealed a strong expression of activated "eNOS-like" isoforms both at coronary endothelium and, to a lesser extent, in the myocardiocytes and the endocardial endothelium (EE). The structural design of the heart appears to comply with its mechanical function. Using an in vitro working heart preparation, cardiac performance was evaluated at different filling and afterload pressures. The hearts were very sensitive to filling pressure increases. Maximum Stroke volume (SV=1.08 ± 0.09 mL/kg body mass) was obtained with an input pressure of 0.4 kPa. The heart was not able to sustain afterload increases, values higher than 1.5 kPa impairing its performance. These morpho-functional features are consistent with a volume pump mechanical performance.

Stereotactic Irradiation of GH-Secreting Pituitary Adenomas.

Radiotherapy (RT) is often employed in patients with acromegaly refractory to medical and/or surgical interventions in order to prevent tumour regrowth and normalize elevated GH and IGF-I levels. It achieves tumour control and hormone normalization up to 90% and 70% of patients at 10-15 years. Despite the excellent tumour control, conventional RT is associated with a potential risk of developing late toxicity, especially hypopituitarism, and its role in the management of patients with GH-secreting pituitary adenomas remains a matter of debate. Stereotactic techniques have been developed with the aim to deliver more localized irradiation and minimize the long-term consequences of treatment, while improving its efficacy. Stereotactic irradiation can be given in a single dose as stereotactic radiosurgery (SRS) or in multiple doses as fractionated stereotactic radiotherapy (FSRT). We have reviewed the recent published literature on stereotactic techniques for GH-secreting pituitary tumors with the aim to define the efficacy and potential adverse effects of each of these techniques.

Clinical target volume delineation in glioblastomas: pre-operative versus post-operative/pre-radiotherapy MRI.

OBJECTIVES: Delineation of clinical target volume (CTV) is still controversial in glioblastomas. In order to assess the differences in volume and shape of the radiotherapy target, the use of pre-operative vs post-operative/pre-radiotherapy T(1) and T(2) weighted MRI was compared. METHODS: 4 CTVs were delineated in 24 patients pre-operatively and post-operatively using T(1) contrast-enhanced (T1(PRE)CTV and T1(POST)CTV) and T(2) weighted images (T2(PRE)CTV and T2(POST)CTV). Pre-operative MRI examinations were performed the day before surgery, whereas post-operative examinations were acquired 1 month after surgery and before chemoradiation. A concordance index (CI) was defined as the ratio between the overlapping and composite volumes. RESULTS: The volumes of T1(PRE)CTV and T1(POST)CTV were not statistically different (248 ± 88 vs 254 ± 101), although volume differences >100 cm(3) were observed in 6 out of 24 patients. A marked increase due to tumour progression was shown in three patients. Three patients showed a decrease because of a reduced mass effect. A significant reduction occurred between pre-operative and post-operative T(2) volumes (139 ± 68 vs 78 ± 59). Lack of concordance was observed between T1(PRE)CTV and T1(POST)CTV (CI = 0.67 ± 0.09), T2(PRE)CTV and T2(POST)CTV (CI = 0.39 ± 0.20) and comparing the portion of the T1(PRE)CTV and T1(POST)CTV not covered by that defined on T2(PRE)CTV images (CI = 0.45 ± 0.16 and 0.44 ± 0.17, respectively). CONCLUSION: Using T(2) MRI, huge variations can be observed in peritumoural oedema, which are probably due to steroid treatment. Using T(1) MRI, brain shifts after surgery and possible progressive enhancing lesions produce substantial differences in CTVs. Our data support the use of post-operative/pre-radiotherapy T(1) weighted MRI for planning purposes.

Phospholamban S-nitrosylation modulates Starling response in fish heart.

The Frank-Starling mechanism is a fundamental property of the vertebrate heart, which allows the myocardium to respond to increased filling pressure with a more vigorous contraction of its lengthened fibres. In mammals, myocardial stretch increases cardiac nitric oxide (NO) release from both vascular endothelium and cardiomyocytes. This facilitates myocardial relaxation and ventricular diastolic distensibility, thus influencing the Frank-Starling mechanism. In the in vitro working heart of the eel Anguilla anguilla, we previously showed that an endogenous NO release affects the Frank-Starling response making the heart more sensitive to preload. Using the same bioassay, we now demonstrate that this effect is confirmed in the presence of the exogenous NO donor S-nitroso-N-acetyl penicillamine, is independent from endocardial endothelium and guanylate cyclase/cGMP/protein kinase G and cAMP/protein kinase A pathways, involves a PI(3)kinase-mediated activation of endothelial NO synthase and a modulation of the SR-CA(2+)ATPase (SERCA2a) pumps. Furthermore, we show that NO influences cardiac response to preload through S-nitrosylation of phospholamban and consequent activation of SERCA2a. This suggests that in the fish heart NO modulates the Frank-Starling response through a beat-to-beat regulation of calcium reuptake and thus of myocardial relaxation. We propose that this mechanism represents an important evolutionary step for the stretch-induced intrinsic regulation of the vertebrate heart, providing, at the same time, a stimulus for mammalian-oriented studies.

The Antarctic hemoglobinless icefish, fifty five years later: a unique cardiocirculatory interplay of disaptation and phenotypic plasticity.

The teleostean Channichthyidae (icefish), endemic stenotherms of the Antarctic waters, perennially at or near freezing, represent a unique example of disaptation among adult vertebrates for their loss of functional traits, particularly hemoglobin (Hb) and, in some species, cardiac myoglobin (Mb), once considered to be essential-life oxygen-binding chromoproteins. Conceivably, this stably frigid, oxygen-rich habitat has permitted high tolerance of disaptation, followed by subsequent adaptive recovery based on gene expression reprogramming and compensatory responses, including an alternative cardio-circulatory design, Hb-free blood and Mb-free cardiac muscle. This review revisits the functional significance of the multilevel cardio-circulatory compensations (hypervolemia, near-zero hematocrit and low blood viscosity, large bore capillaries, increased vascularity with great capacitance, cardiomegaly with very large cardiac output, high blood flow with low systemic pressure and systemic resistance) that counteract the challenge of hypoxemic hypoxia by increasing peripheral oxygen transcellular movement for aerobic tissues, including the myocardium. Reconsidered in the context of recent knowledge on both polar cold adaptation and the new questions related to the advent of nitric oxide (NO) biology, these compensations can be interpreted either according to the "loss-without-penalty" alternative, or in the context of an excessive environmental oxygen supply at low cellular cost and oxygen requirement in the cold. Therefore, rather than reflecting oxygen limitation, several traits may indicate structural overcompensation of oxygen supply reductions at cell/tissue levels. At the multilevel cardio-circulatory adjustments, NO is revealing itself as a major integrator, compensating disaptation with functional phenotypic plasticity, as illustrated by the heart paradigm. Beside NOS-dependent NO generation, recent knowledge concerning Hb/Mb interplay with NO and nitrite has revealed unexpected functions in addition to the classical respiratory role of these proteins. In fact, nitrite, a major biologic reservoir of NO, generates it through deohyHb- and deoxyMb-dependent nitrite reduction, thereby regulating hypoxic vasodilation, cellular respiration and signalling. We suggest that both Hb and Mb are involved as nitrite reductases under hypoxic conditions in a number of cardiocirculatory processes. On the whole, this opens new horizons in environmental and evolutionary physiology.

NO modulation of myocardial performance in fish hearts.

In the mammalian heart, intracardiac nitric oxide (NO) regulates in an autocrine-paracrine manner cardiac function in the beat-to-beat response (Starling's law of the heart), short-term response (phasic control, e.g. excitation-contraction coupling, responses to neurotransmitters and endocrines) and long-term response (tonic control by altering gene expression). This trio of NO temporal-dependent actions has a long evolutionary history, as we have documented in the prototypic vertebrate heart, the teleost heart. This heart shares a common structural and functional scenario with higher vertebrate hearts exhibiting, at the same time, differences in myoarchitecture (trabecular vs. compact type), blood supply (lacunary vs. vascular) and pumping performance (sensitivity to filling pressure), thus providing challenging opportunities for revealing aspects of unity and diversity of cardiac NO in vertebrates. Using in vitro working teleost heart preparations we have shown that, under basal conditions, NO through a cGMP-mediated mechanism modulates ventricular performance (negative inotropism) and remarkably increases the sensitivity to filling pressure (i.e. the Frank-Starling response). NO-cGMP mechanism also influences the short-term response elicited by inotropic agents such as acetylcholine and angiotensin II. A role of NO in long-term cardiac adaptation is illustrated by morphologic evidence (e.g. NOS immuno-localization in phylogenetically distant species) which emphasizes the importance of NO in reshaping the angio-myoarchitecture of the fish heart ventricle (i.e. compensation for regional heterogeneity). Finally, by studying the avascular hearts of teleosts and amphibians that lack vascular endothelium, a relevant role of endocardial endothelium-NO signalling in intracavitary regulation of myocardial performance has been firmly established, thus revealing its early evolutionary role in non-mammalian vertebrates.

Cardiac morphodynamic remodelling in the growing eel (Anguilla anguilla L.).

The morphodynamic changes occurring during growth were evaluated in the eel (Anguilla anguilla L.) heart. Using an in vitro working heart preparation, cardiac performance of small (body mass 96.76 +/- 27.49 g; mean +/- s.d.) and large (body mass 656 +/- 12 g; mean +/- s.d.) eels was compared under basal conditions and under loading (i.e. preload and afterload) challenges. A parallel morphometric evaluation of the ventricle was made using light and transmission electron microscope images. The small eel hearts show a basal cardiac output lower than their large counterparts (heart rate fh, 38.93 +/- 2.82 and 52.7 +/- 1.8 beats min(-1), respectively; stroke volume Vs, 0.27 +/- 0.017 and 0.37 +/- 0.016 ml kg(-1), respectively; means +/- s.e.m.). The two groups show similar responses at increasing preload, but differ remarkably at increasing afterload. Small eel hearts decreased Vs at afterload greater than 3 kPa, in contrast to larger hearts, which maintained constant Vs up to 6 kPa. These changes in mechanical performance are related to structural differences. Compared with the small eels, the large eels show an increase in the compacta thickness and in the diameter of the trabeculae in the spongiosa, together with reduction of the lacunary spaces. The increased compacta thickness is attained by enlargements of both the muscular and vascular compartments and reduction of the interstitium; consequently, this layer appears more compacted. Both compacta and spongiosa show higher number of myocytes together with reduced cross-sectional area and myofibrillar compartment. The compacta also shows an increased mitochondrial compartment. Our results document a cardiac morphodynamic remodelling in the growing eel.

The conus valves of the adult gilthead seabream (Sparus auratus).

The conus (bulbo-ventricular) valves of teleosts perform a key function in the control of blood backflow during ventricular diastole. However, the structural characteristics of these valves are almost unknown. This paper presents a systematic anatomical, histological and structural study of the conus valves of the adult gilthead seabream (Sparus auratus). S. auratus shows two major left and right valves consisting of the leaflet and the supporting sinus. Each valvar leaflet can be divided into a stout proximal body and a flap-like distal region. The proximal body is structured into three layers: a luminal fibrosa, a dense cellular core and a parietal fibrosa. The luminal fibrosa is a collagenous structure extending the entire length of the leaflet, while the parietal fibrosa is restricted to the most proximal area. The dense cellular core consists of fibroblastic cells and a matrix rich in glycoconjugates, collagen and elastin. The histochemical and structural data suggest that the luminal fibrosa bears most of the force associated with valvar closure, while the cellular core acts as a cushion dampening vibrations and absorbing the elastic recoil. The sinus wall is a fibrous layer which shows proximal-distal differences in thickness. It also shows compositional differences that can be related to mechanical function. We describe the presence of a fibrous cylinder formed by the sinus wall, the fibrous interleaflet triangles and the fibrous layer that covers the inner surface of the conus myocardium. This fibrous cylinder constitutes the structural nexus between the ventricle, the conus and the bulbus arteriosus, provides support for the conus valves and separates the valvar complex from the surrounding tissues. The structure of the conus valves in S. auratus is different from that found in other vertebrates. Anatomical similarities between the conus valves and the mammalian arterial valves are emphasized. Each phyletic group appears to have developed specific structures in order to perform similar functions.

The modified buried vertical mattress suture. A new technique of buried absorbable wound closure associated with excellent cosmesis for wounds under tension.

BACKGROUND: Recent modifications of mattress suturing techniques have been reported producing rapid and effective skin eversion and excellent tensile strength while producing cosmetically elegant results. OBJECTIVE: Presented here is a new modification of the buried vertical mattress suture. Results employing this technique compared with conventional bi-layered wound closure are presented. METHODS: One hundred patients were analyzed in a double-blind randomized study where excision was carried out on benign pigmented lesions of the upper back. Fifty patients were treated by a conventional bi-layered closure technique while another 50 patients were treated by the newly described buried vertical mattress suture technique. Parameters of infection, hypertrophic scar/keloid formation, dehiscence, suture reaction, wound spread, and patient satisfaction were examined. RESULTS: The modified buried vertical mattress suture technique produced less hypertrophic scar/keloid formation (2% vs 16%) as well as less wound scar spread (6% vs 24%) compared with conventional bi-layered suturing techniques. In addition, it was associated with a high degree of patient satisfaction (96%). CONCLUSION: The modified buried dermal mattress suture technique produces excellent cosmetic results in closing elliptical excisions on thick dermal cutaneous anatomic areas under considerable wound tension. Its decreased requirement for postoperative wound care makes it an excellent alternative for patients living long distances from physician referral centers.