Epidemiological trends in the diagnosis of melanoma in a Southern European population: analysis of a large database from a tertiary referral center.

The aim of this study was to present the epidemiological, clinicopathological, and treatment characteristics of patients diagnosed and treated in a tertiary referral center and to analyze independent factors associated with these characteristics. In this cohort study, epidemiological, clinicopathological, and treatment characteristics of 1461 consecutive melanoma patients diagnosed and treated in a tertiary referral center in 1987-2015 were prospectively collected in a registry. All patients underwent resection of their melanoma lesion. Multiple logistic regression analysis was used to examine independent correlations between characteristics. Internal validation of these correlations was performed by the bootstrap method. The median age of the patients was 53 years. Female sex had a slight predominance, whereas the majority were of Southern European origin. Superficial spreading melanoma was associated with younger age (P<0.001), whereas the nodular melanoma histological subtype was associated independently with indoor occupation (P=0.021) and diagnosis in the years 2004-2015 (P=0.002). Melanomas with Breslow thickness above 1.0 mm were associated with skin type III-IV (P=0.021) and diagnosis in the years 1987-2003 (P=0.046). In addition, histological ulceration was associated with older age (P=0.004) and diagnosis in the years 1987-2003 (P<0.001), whereas histological regression was associated independently with older age (P=0.001). This study presented independent associations between epidemiological, histopathological, and treatment characteristics, which might help to better understand melanoma disease and treatment practices in Southern Europe.

Comparing oil based ointment versus standard practice for the treatment of moderate burns in Greece: a trial based cost effectiveness evaluation.

BACKGROUND: The local treatment of burn wounds has long been a subject of debate. The objective of this study was to compare the cost and the effectiveness of Moist Exposed Burn Ointment -MEBO versus a combination of povidone iodine plus bepanthenol cream for partial thickness burns. METHODS: The study was carried out in the Burn Center of a state hospital in Athens, Greece. 211 patients needing conservative therapy were prospectively selected according to the depth of the burn wound. The treatment was allocated according to the Stratified Randomization Design. The outcomes measured were mean cost of in-hospital stay, rate of complications, time of 50% wound healing, pain scores, in hospital stay diminution. We have adopted a societal perspective. RESULTS: In the total groups MEBO presented lower cost, (although not significantly different: p = 0.10) and better effectiveness. The data suggest that MEBO is the dominant therapy for superficial partial burn wound with significantly lower costs and significantly higher effectiveness due to a lesser time of recovery and consequently lower time of hospitalization and follow-up. MEBO presented similar percentages of complications with the comparator, lower pain levels and smaller time of no healthy appearance of the burn limits for superficial partial thickness burns. CONCLUSIONS: The data suggested that topical application of MEBO may be considered for further investigation as a potential first-line treatment modality for superficial partial thickness burns. TRIAL REGISTRATION: The trial has been registered on the International Standard Randomised Controlled Trial Number Register (ISRCTN) and given the registration number ISRCTN74058791.

Randomized phase III study of 1 month versus 1 year of adjuvant high-dose interferon alfa-2b in patients with resected high-risk melanoma.

PURPOSE: A high-dose interferon alfa (IFN-alpha) regimen as reported in E1684 was unique for the incorporation of an induction phase of maximally tolerated dosages of intravenous (IV) therapy for the initial 4 weeks. This is the only trial that has shown prolongation of overall survival and relapse-free survival (RFS) in comparison with observation. Analysis of the hazard curves for RFS and overall survival (OS) in E1684 revealed separation of the high-dose and observation arms, suggesting that the induction phase may represent a critical component of this regimen, although this has not been tested prospectively. PATIENTS AND METHODS: We conducted a prospective randomized study of IV induction therapy versus a full year of high-dose IFN, with primary end points of RFS and OS for patients with stage IIB, IIC, and III melanoma, within 56 days of curative surgery. Patients were randomly assigned to receive IFN-alpha-2b 15 x 10(6) U/m2 IV x 5/7 days weekly x 4 weeks (arm A) versus the same regimen followed by IFN-alpha-2b 10 x 10(6) U (flat dose) administered subcutaneously three times a week for 48 weeks (arm B). RESULTS: Between 1998 and 2004, 364 patients were enrolled (353 eligible: arm A, n = 177; arm B, n = 176). At a median follow-up of 63 months (95% CI, 58.1 to 67.7), the median RFS was 24.1 months versus 27.9 months (P = .9) and the median OS was 64.4 months versus 65.3 months (P = .49). Patients in arm B had more grade 1 to 2 hepatotoxicity, nausea/vomiting, alopecia, and neurologic toxicity. CONCLUSION: There were no significant differences in OS and RFS between the regimens of 1 month and 1 year of treatment.

Prognostic significance of autoimmunity during treatment of melanoma with interferon.

BACKGROUND: Immunotherapy for advanced melanoma induces serologic and clinical manifestations of autoimmunity. We assessed the prognostic significance of autoimmunity in patients with stage IIB, IIC, or III melanoma who were treated with high-dose adjuvant interferon alfa-2b. METHODS: We enrolled 200 patients in a substudy of a larger, ongoing randomized trial. Blood was obtained before the initiation of intravenous interferon therapy, after 1 month of therapy, and at 3, 6, 9, and 12 months. Serum was tested for antithyroid, antinuclear, anti-DNA, and anticardiolipin autoantibodies, and patients were examined for vitiligo. RESULTS: The median duration of follow-up was 45.6 months. Relapse occurred in 115 patients, and 82 patients died. The median relapse-free survival was 28.0 months, and the median overall survival was 58.7 months. Autoantibodies and clinical manifestations of autoimmunity were detected in 52 patients (26 percent). The median relapse-free survival was 16.0 months among patients without autoimmunity (108 of 148 had a relapse) and was not reached among patients with autoimmunity (7 of 52 had a relapse). The median survival was 37.6 months among patients without autoimmunity (80 of 148 died) and was not reached among patients with autoimmunity (2 of 52 died). In univariate and multivariate regression analyses, autoimmunity was an independent prognostic marker for improved relapse-free survival and overall survival (P<0.001). CONCLUSIONS: The appearance of autoantibodies or clinical manifestations of autoimmunity during treatment with interferon alfa-2b is associated with statistically significant improvements in relapse-free survival and overall survival in patients with melanoma.

Effect of genetically modified Schwann cells with increased motility in end-to-side nerve grafting.

Taking into account that Schwann-cell (SC) motility is a prerequisite for myelination during peripheral nerve regeneration, the present study was designed with the intention to increase SC motility in vitro and to evaluate the effect of transduced SC on nerve regeneration in vivo, through silicone tubes after end-to-side nerve repair. Our in vitro study demonstrated that SC transduction with the pREV-HW3 retrovirus, encoding for sialyl-transferase-X (STX), significantly increased their motility compared to the control. In the in vivo study, 45 Wistar rats were randomized into three groups of 15 each. In all animals, the left peroneal nerve was severed, and a 10-mm segment was removed. The distal stump of the peroneal nerve was connected end-to-side to a perineurial window in the ipsilateral tibial nerve with either a silicone tube lined with SC (group A) or a silicone tube lined with STX-transduced SC (groups B and C). Fluorescence and light microscopy in group C showed that SCs were viable the first critical 15 postoperative days. After 90 days, light microscopy in group B demonstrated that STX-transduced SCs with increased motility ensured nerve regeneration, through silicone tubes, in all cases. Furthermore, STX-transduced SCs increased significantly fiber diameter and myelin thickness, and most importantly enhanced significantly the functional outcome compared to non-transduced SCs.

Comparison of transthecal digital block and traditional digital block for anesthesia of the finger.

A randomized, double-blind study was performed in 50 patients to compare the transthecal and traditional subcutaneous infiltration techniques of digital block anesthesia regarding the onset of time to achieve anesthesia and pain during the infiltration. All the patients had sustained injury involving two or four fingers of the hand. Each patient served as his or her own control, having one finger infiltrated with the transthecal technique and the other with the subcutaneous infiltration technique. Time to loss of pinprick sensation and pain (at the time of the infiltration and 24 hours postoperatively) were assessed using a visual analogue scale and verbal response score. A total of 104 blocks (52 transthecal and 52 subcutaneous infiltration) were performed. All of these blocks were successful. Mean time to achieve anesthesia with the transthecal block was 165 seconds, compared with 100 seconds for the subcutaneous infiltration block. The mean analogue pain score was higher for transthecal blocks than for subcutaneous infiltration blocks (3.2 +/- 0.19 versus 1.6 +/- 0.14). Twenty-four hours postoperatively, 24 patients who had the transthecal block experienced pain at the injection site of the digit. However, none of the patients who received the subcutaneous infiltration block complained of pain at the digit. The technique of anesthesia preferred by patients for their finger was the subcutaneous infiltration block, because it causes less pain. Our results confirm the efficacy of the transthecal block for achieving anesthesia of the finger; however, because it is a more painful procedure, it is not recommended.

Beneficial effect of nerve growth factor-7S on peripheral nerve regeneration through inside-out vein grafts: an experimental study.

This study investigated the effect of local administration of nerve growth factor-7S (NGF-7S) on the axonal regrowth of mixed peripheral nerves through inside-out vein grafts. Sixty male Wistar rats were randomized into two groups (n = 30). A defect 12 mm long in the right sciatic nerve was created and repaired with an inside-out vein graft from the right jugular vein. NGF-7S (group A) or phosphate-buffered saline (group B; control) was locally administered daily during the first 3 weeks. Walking-track analysis and electrophysiological and histological-morphometric studies were carried out 4, 6, 8, 10, and 12 weeks postoperatively (subgroups a, b, c, d, and e, respectively, n = 6 each). Data analysis showed that 1) the recovery of motor function, as measured by walk pattern analysis and evoked muscle action potential, and 2) the orientation, number, myelin thickness, and diameter of myelinated fibers were better in the NGF-7S than in the control group. These findings present strong evidence of the beneficial effect of NGF-7S on peripheral nerve regeneration through inside-out vein grafts.

Tolerability of adjuvant high-dose interferon alfa-2b: 1 month versus 1 year--a Hellenic Cooperative Oncology Group study.

BACKGROUND: High-dose interferon alfa-2b (IFN-alpha2b) as adjuvant therapy for melanoma is associated with substantial dose-limiting toxicity. It has been suggested that the 1-month intravenous (i.v.) induction regimen may be sufficient to reduce the risk of relapse and death. PATIENTS AND METHODS: The Hellenic Cooperative Oncology Group is conducting a multicenter, randomized trial of 1-month i.v. induction versus 1 year of adjuvant IFN-alpha2b therapy in patients with stage IIB/III melanoma. Adverse events reported by the first 200 patients to complete therapy are described. RESULTS: Both induction and maintenance regimens were well tolerated. The most common toxicities were flu-like and gastrointestinal symptoms, neutropenia, liver toxicity, and neurologic toxicity. The incidence of grade 3/4 toxicity was low and occurred mainly during the induction phase in both arms. Dose was reduced in 31% of patients during induction. Only 2% of patients discontinued. Dose was reduced in 8% of patients during maintenance and only 5% of patients discontinued. CONCLUSION: Intravenous induction with 15 MIU/m2/day IFN-alpha2b is well tolerated. Efficacy results from this trial are eagerly anticipated.

Early escharotomy as a measure to reduce intraabdominal hypertension in full-thickness burns of the thoracic and abdominal area.

Intraabdominal hypertension (IAH) can occur in critically ill patients who have undergone surgery, who have required fluid resuscitation after intraabdominal operations, or whose abdominal surgical wound closure was under tension. If IAH remains unrelieved, it can lead to development of the abdominal compartment syndrome (ACS). The latter presents with severe cardiorespiratory and urinary symptoms such as hypotension, hypoventilation, and oliguria, and it can become fatal if it is not diagnosed early and treated properly. Moreover, IAH has been documented in the context of major burns, complicating the initial resuscitation of these patients. This study was set up to investigate the role of full-thickness burns of the thoracic and abdominal areas in IAH during the early resuscitation period, to determine whether escharotomy could influence its levels. During the past 2 years 10 burn patients were enrolled in this study, as they fulfilled the necessary criteria: >35% total body surface area (TBSA) full-thickness burn affecting the anterior, lateral, and most of the posterior surface of the thorax and abdomen (torso), no respiratory mechanical support at admission, and initial evaluation at another facility and transfer to our burn center 2-6 h postburn. Upon admission, the following parameters (indicative of intraabdominal hypertension, IAH) were measured: bladder pressure and gastric pressure. Also, we monitored inferior vena cava pressure, and as a routine, central venous pressure, systolic blood pressure, and arterial blood gases. Elevated intraabdominal pressure to hazardous levels was documented in all patients included in our study. The same escharotomy pattern was performed in every case, and 5-10 min after the procedure all measurements were repeated. Immediate improvement of all the parameters measured was recorded, and the alterations were found statistically significant. These results were indicative of significant relief of the elevated intraabdominal pressure in all patients after escharotomy, as well as the efficacy of the procedure. It is thus demonstrated that full-thickness burns of the thoracic and abdominal areas can cause a significant early increase in intraabdominal pressure that, if left untreated, can lead to the development of ACS. However, the application of simple decompression techniques can offer remarkable, immediate, and often lifesaving results and is absolutely indicated for this reason, as well as for its well-known beneficial effects on respiratory function.

Microvascular repair following crush-avulsion type injury with vein grafts: effect of direct inhibitors of thrombin on patency rate.

The aim of this study was to develop a standardized effective thrombogenic arterial anastomosis model, as usually encountered in clinical practice, and to offer a detailed evaluation of the antithrombotic effect of thrombin's direct inhibitors, antithrombin III and hirudin, as locally applied. Wistar rats were divided into four groups of 12 animals each. The carotid artery sustained a standardized crush-avulsion-type injury (groups B-D). A segment of the afflicted area was removed and replaced by a microvenous graft. Group A had no crush-avulsion injury inflicted; a microvenous graft replaced a simple resection from the center of the carotid artery. During microvascular anastomoses, normal saline (groups A and B), recombinant hirudin (group C), or antithrombin III (group D) were locally applied. Bleeding times were recorded, and patency tests were performed 20 min, 48 h, and 1 week after blood flow reestablishment. All grafts were harvested and examined histologically. Patency tests, 1 week postrevascularization, demonstrated that this experimental crush-avulsion injury model ensured low patency in group B (25%), whereas group A, which had no injury inflicted, achieved a 100% patency rate. The local application of hirudin and antithrombin III significantly increased bleeding times as well as the patency rate (92% and 75%, respectively) compared to group B. These findings indicate the efficiency of the experimental model and the potential use of thrombin's direct inhibitors in microvascular surgery.

Lymphocyte subpopulations and interleukin levels in high-risk melanoma patients treated with high-dose interferon A-2B.

Immunologic effects of high-dose interferon are still unclear. We have evaluated changes in blood lymphocyte subpopulations, immunoglobulins, and multiple interleukin in patients with high-risk cutaneous melanoma on adjuvant treatment with high-dose interferon and compared pretreatment values with normal controls. Samples were obtained before treatment, 1 month after induction treatment and at 3, 6, and 12 months of maintenance treatment from 24 patients with high-risk melanoma. Lymphocyte subpopulations were measured by flow cytometry and interleukin and immunoglobulin levels by radioimmunoassay. A statistically significant reduction in B-lymphocytes (p < 0.001), natural killer (NK) cells (p = 0.0004), and monocytes (p = 0.04), and an elevation in CD4/CD8 ratio (p < 0.0001) was observed after 1 month of intravenous interferon. No changes were seen in CD3, CD4, and CD8 lymphocytes. No changes in interleukin (IL)-2, -4, or -5 were observed during 1 year of treatment. IL-2 pretreatment levels were significantly lower than healthy blood donors (p = 0.001), and IL-5 pretreatment levels were significantly higher (p = 0.0056). IL-10 levels significantly dropped after 6 months of treatment (p = 0.01). Immunoglobulins (IgG, IgA, IgM) remained within normal ranges. Three patients had elevated pretreatment levels of IgE. There is a time- and dose-dependent impact of interferon on numbers of circulating B lymphocytes, NK cells, monocytes, and CD4/CD8 ratio. Defects in cellular and humoral immunity are suggested by the low IL-2 and high IL-5 levels, measured in patients with melanoma as compared with healthy controls.

Management of acute and chronic open wounds: the importance of moist environment in optimal wound healing.

The history of wound care and management closely parallels that of military surgery which has laid down the principles and dictated the practices of wound cleansing, debridement and coverage. From a treatment standpoint, there are essentially two types of wounds: those characterized by loss of tissue and those in which no tissue has been lost. In the event of tissue loss it is critical to determine whether vital structures such as bone, tendons, nerves and vessels have been exposed. It is also important to determine the amount of soft tissue contusion and contamination. In any case primary wound healing by early closure either primarily or with the help of grafts or flaps is preferred to secondary healing and wound contraction with subsequent contractures which interfere with range of motion and function. Whether the wound is acute or chronic, essential principles of wound care must be observed in order to avoid wound sepsis and achieve rapid and optimal wound healing. - Tissues must be handled gently. - Caustic solutions capable of sterilizing the skin should never be applied to the wound. It is desirable never to put anything in the wound that cannot be tolerated comfortably in the conjunctival sac. - All devitalized tissues must be debrided either hydrodynamically, chemically, mechanically or surgically. - All dead space must be obliterated. - Exposed vital structures must be covered by well vascularized tissues. An essential part of any wound management protocol is wound dressing. It cannot be too strongly emphasized that a wound dressing may have a profound influence on healing particularly of secondary type healing, a critical feature being the extent to which such dressing restricts the evaporation of water from the wound surface. A review of available dressing materials is reported with emphasis on the newly developed concept of moist environment for optimal healing. a practical guide for dressing selection is also proposed.

Improving scar quality: a prospective clinical study.

Following traumatic or surgical injury to the skin, wounds do not heal by tissue regeneration but rather by scar formation. Though healing is definitely a welcomed event, the resultant scar, very often, is not aesthetically pleasing, and not infrequently, may be pathologic causing serious deformities and contractures. Management of problematic scars continues to be a frustrating endeavor with less than optimal results. Prophylactic methods of wound management to minimize serious scarring are being developed. In a previously published study, we have demonstrated improved healing of split thickness skin graft donor sites following treatment with Moist Exposed Burn Ointment (MEBO, Julphar Gulf Pharmaceutical Industries, Ras Al-Khaimah, UAE). At present, we are reporting the results of a comparative clinical prospective study evaluating scar quality following primary healing of elective surgical and traumatic facial wounds with prophylactic MEBO application, topical antibiotic ointment application, and no topical therapy at all. Scars were evaluated according to the Visual Analogue Scale for scar assessment. Statistical analysis of scar assessment scores demonstrated marked prevention of unfavorable scars with improved cosmetic results following MEBO prophylactic therapy.