Eosinophilic granulocytes as a potential prognostic marker for cancer progression and therapeutic response in malignant melanoma.

The importance of eosinophilic granulocytes in cancer has been widely discussed in recent years. The current study reviews the evidence on the role of eosinophilic granulocytes in melanoma as a prognostic marker for cancer progression and the efficacy of treatment with modern immune checkpoint inhibitors. A total of 33 human clinical studies were included in the review, with heterogeneous data due to differences in patients populations, study design and inclusion of small study groups. However, 28 of the 33 studies suggested that eosinophilic granulocytes could be used as a prognostic biomarker for outcome and/or potential response to systemic treatment and/or occurrence of adverse events in melanoma patients. Nevertheless, the exact role of eosinophils remains to be elucidated. Further prospective, larger and better controlled studies are warranted to clarify the significance of eosinophilic granulocytes in patients with melanoma, in more details.

Melanoma Prognosis and Associated Risk Factors: A Retrospective Cohort Study Using Semantic Map Analysis.

The overall patterns of correlations among various melanoma risk factors have not yet been examined. The aim of this study was to assess the impact of different parameters on disease-free and melanoma-related overall survival. A retrospective cohort study was conducted encompassing all patients with a primary cutaneous melanoma diagnosed in a university referral centre. Associations were explored using semantic map analysis, which uses graph theory to find the strongest path of connections between variables. A total of 1,110 melanoma patients (median follow-up 10.6 years) were included. The analysis revealed a clustering of variables around 2 main hubs: Breslow thickness < 1 mm and ≥ 4 mm. Factors connected with high melanoma thickness were: older age, positive sentinel lymph node biopsy findings, presence of ulceration, nodular melanoma type, and light skin phototype. Both disease-free and melanoma-related overall survival were in this cluster and connected with positive sentinel lymph node biopsy and Breslow ≥ 4 mm. Patients with Breslow between 1 and 3.9 mm were also in this cluster and linked with negative sentinel lymph node biopsy, nodular melanoma and safety distance > 10 mm. This semantic analysis confirmed the close link between Breslow thickness, age, sentinel lymph node biopsy findings, skin type, melanoma subtype and prognosis, and provides prognostic information useful for the further stratification and management of patients with melanoma.

The Immunohistochemical Assessment of Neoangiogenesis Factors in Squamous Cell Carcinomas and Their Precursors in the Skin.

Cutaneous squamous cell carcinoma (cSCC) is a common skin cancer. Well-limited forms can be easily treated with excision, but locally advanced cancers can, unfortunately, progress to metastasis. However, it is difficult to establish the prognosis for cutaneous squamous cell carcinoma and its potential to metastasize. Therefore, this study aimed to evaluate neoangiogenesis in cSCC, as it plays a major role in the dissemination of neoplasia. A literature review was performed on selected neoangiogenic factors (VEGF, ANG1/2, Notch1, CD31/34/105, EGF, etc.). Most of them, including VEGF, EGFR, and CD105, had more elevated levels in the advanced stages of the lesion. The same is true for Notch1, p53, and TGFß, which are the most frequently mutated tumor suppressors in this type of skin cancer. In addition, the inhibition of some of these markers, using Ang1 analogs, inhibitors of EGFR, TRAF6, or combined inhibitors of EGFR and IGF-IR, may lead to a decrease in tumor size. In conclusion, this literature review identified diagnostic and prognostic markers, as well as possible factors that can be used for the targeted therapy of spinaliomas.

Noncontrast-enhanced 3-Tesla MRI using surface coil as a complementary test for assessment of distribution and depth of locoregional cutaneous metastases of malignant melanoma.

Locoregional and distant metastases account for most cases of morbidity and mortality associated with melanoma. In addition, local recurrences of melanoma might be the onset of disseminated disease. Therefore, precise diagnosis and therapy are warranted to minimize morbidity and increase survival in a subset of patients. However, the correct distribution of the metastatic lesions on the skin is often difficult to estimate. We present the application of noncontrast-enhanced 3-Tesla MRI using surface coil to detect locoregional cutaneous metastases of malignant melanoma on the basis of the topographic assessment of skin lesions. Furthermore, in a systematic review, we summarize the current knowledge about application of MRI in assessment of location, distribution, and depth of cutaneous primary malignant melanoma. MRI might be applied to evaluate the location, distribution, size, and depth of the locoregional cutaneous metastasis of malignant melanoma to identify the optimal cost-effective treatment strategies and monitor their effects.

Nonavalent human papillomavirus vaccination as alternative treatment for genital warts.

Genital warts caused by the human papillomavirus (HPV) are the most common sexually transmitted disease and have a negative impact on quality of life. Of the more than 200 different types of HPV, low-risk types 6 and 11 are mainly responsible for the development of condyloma acuminata. Despite a large arsenal of local therapies such as numerous topical agents, CO2 laser ablation, and surgical removal, genital warts tend to be recalcitrant. HPV vaccination is mainly used as a preventive strategy to prevent genital warts, cervical cancer, and other anogenital cancers. However, in a few cases, HPV vaccination has been shown to be a good treatment alternative for patients with recalcitrant skin warts. Here we report five cases of recalcitrant genital warts that responded well to treatment with the nonavalent HPV vaccine. HPV vaccines could be beneficial as a noninvasive treatment alternative for recalcitrant genital warts.

Siglec-9 Regulates an Effector Memory CD8+ T-cell Subset That Congregates in the Melanoma Tumor Microenvironment.

Emerging evidence suggests an immunosuppressive role of altered tumor glycosylation due to downregulation of innate immune responses via immunoregulatory Siglecs. In contrast, human T cells, a major anticancer effector cell, only rarely express Siglecs. However, here, we report that the majority of intratumoral, but not peripheral blood, cytotoxic CD8+ T cells expressed Siglec-9 in melanoma. We identified Siglec-9+ CD8+ T cells as a subset of effector memory cells with high functional capacity and signatures of clonal expansion. This cytotoxic T-cell subset was functionally inhibited in the presence of Siglec-9 ligands or by Siglec-9 engagement by specific antibodies. TCR signaling pathways and key effector functions (cytotoxicity, cytokine production) of CD8+ T cells were suppressed by Siglec-9 engagement, which was associated with the phosphorylation of the inhibitory protein tyrosine phosphatase SHP-1, but not SHP-2. Expression of cognate Siglec-9 ligands was observed on the majority of tumor cells in primary and metastatic melanoma specimens. Targeting the tumor-restricted, glycosylation-dependent Siglec-9 axis may unleash this intratumoral T-cell subset, while confining T-cell activation to the tumor microenvironment.

Self-Burns in Fars Province, Southern Iran.

BACKGROUND: The alarming incidence of self- burning provoked to set up a multidisciplinary preventive program to decrease the incidence and complications of this harmful issue. This study investigated the incidence and the preventive measures in self-burn in Fars Province, southern Iran. METHODS: This study was a longitudinal prospective design on trend of self-inflicted burn injuries in Fars province after setting up a regional multidisciplinary preventive plan (2009-2012). RESULTS: From 18862 admitted patients, 388 (2%) committed self-burning. While the incidence showed a constant decrease in proportion of suicidal cases among all admitted patients (2.5% to 1.6%). The mean age of self-burning victims ranged from 28.3±10.8 to 30.3±11.7 years. The female victims comprised 67.4% of all suicidal burn patients (Female to male ratio: 2.18). The leading causes of suicide commitment were familial conflicts (75.6%) and psychological problems (16.7%). CONCLUSION: It is crucial to continue the regional preventive programs and pave the way to set up national, and even international collaborations to alleviate relevant financial, social, cultural and infrastructural difficulties in order to have lower incidence for this dramatic issue.

Detection of blaPER-1 & blaOxa10 among imipenem resistant isolates of Pseudomonas aeruginosa isolated from burn patients hospitalized in Shiraz Burn Hospital.

BACKGROUND AND OBJECTIVES: Pseudomonas aeruginosa is one of the most important Gram negative opportunistic bacteria which causes infection among burn patients. Resistance to the antibiotics in this group of bacteria is increased due to the activity of extended spectrum ß-lactamase (ESBLs) genes. In the current study, we investigated the prevalence of two genes (blaPER-1 & blaOxa10 ) related ß-lactamase genes among imipenem resistance clinical isolates of P. aeruginosa in hospitalized patients. MATERIALS AND METHODS: From May 2010 to March 2011, 270 P. aeruginosa isolated from hospitalized burned patients' wounds in Shiraz Burn Hospital, were tested for Imipenem resistance by disk diffusion method. Presence of ESBLs exo-enzyme, blaPER-1 and blaOxa10 genes were also evaluated in the resistant isolate. RESULTS: 210 (77.7%) of 270 P. aeruginosa isolates were resistant to imipenem. blaPER-1 and blaOxa10 were detected among 168 (80.0%) of imipenem resistant isolates. Furthermore, 160 (76.2%) of them had blaOxa10 gene and 84 (40.0%) of them had blaPER-1 while 63 (30.0%) resistant isolates contained both genes simultaneously. CONCLUSION: This study showed a high prevalence of blaPER-1 and blaOxa10 genes in hospitalized burn patients in south west of Iran. Therefore, it's highly recommended to perform such tests routinely to evaluate the resistance pattern in order to better antibiotic selection in the burned patients.

Evaluation of Medical Students' Attitudes and Performance of Basic Surgery Skills in a Training Program Using Fresh Human skin, Excised During Body Contouring Surgeries.

BACKGROUND: Learning surgical skills in the operating room may be a challenge for medical students. Therefore, more approaches using simulation to enable students to develop their practical skills are required. OBJECTIVES: We hypothesized that (1) there would be a need for additional surgical training for medical students in the pre-final year, and (2) our basic surgery skills training program using fresh human skin would improve medical students' surgical skills. DESIGN: We conducted a preliminary survey of medical students to clarify the need for further training in basic surgery procedures. A new approach using simulation to teach surgical skills on human skin was set up. The procedural skills of 15 randomly selected students were assessed in the operating room before and after participation in the simulation, using Objective Structured Assessment of Technical Skills. Furthermore, subjective assessment was performed based on students' self-evaluation. The data were analyzed using SPSS, version 21 (SPSS, Inc., Chicago, IL). SETTING: The study took place at the Inselspital, Bern University Hospital. PARTICIPANTS: A total of 186 pre-final-year medical students were enrolled into the preliminary survey; 15 randomly selected medical students participated in the basic surgical skills training course on the fresh human skin operating room. RESULTS: The preliminary survey revealed the need for a surgical skills curriculum. The simulation approach we developed showed significant (p < 0.001) improvement for all 12 surgical skills, with mean cumulative precourse and postcourse values of 31.25 ± 5.013 and 45.38 ± 3.557, respectively. The self-evaluation contained positive feedback as well. CONCLUSION: Simulation of surgery using human tissue samples could help medical students become more proficient in handling surgical instruments before stepping into a real surgical situation. We suggest further studies evaluating our proposed teaching method and the possibility of integrating this simulation approach into the medical school curriculum.

Effect of burn sites (upper and lower body parts) and gender on extensive burns' mortality.

Our recent literature survey indicated a lack of clinical assessment of the influence of gender and site of burn injury on the outcome of patients with extensive burns. This report examines the effect of burn sites and gender on extensive burns' mortality. Data was gathered from 283 patients with burns larger than 65% of the total body surface area (TBSA) above the belt line or below the belt line; and without underlying diseases and inhalation burn injury. Patients were classified according to gender, site of injury (upper and lower body parts) and hospital stay period. Mortality rates of each category were then compared with each other. The hospital stay period in the female group was significantly higher compared with the male group (P<0.001) and the mortality rate among the female patients was higher compared with the male patients (P=0.004). Although the mortality rate in lower body part of the male group was significantly higher in comparison with the upper body part burn (P=0.001), there was no difference in mortality rate of upper versus lower body part in the female group. The mortality rate was generally higher among the female patients. Additionally, higher mortality rate was observed among male patients with lower body part burn compared with injuries of male patients with upper body part burn.

Metabolic effects of tourniquet application in burn patients.

BACKGROUND: Despite several studies investigating the pathophysiologic effects of tourniquet usage in extremity surgeries, there are not enough data about these effects in adhesion release surgeries of burn patients. In the light of numerous metabolic changes of burn tissues, we tried to determine whether there are any significant differences in metabolic responses of burn tissues to tourniquet ischemia in comparison to the findings of other studies in non burn tissue responses during tourniquet usage in extremity surgeries. METHODS: From March 2009 to April 2011, eighteen patients who were candidates for performing upper extremity adhesion release surgeries were enrolled. Patients with renal, hepatic, metabolic and any other underlying diseases were excluded from the study. Blood samples for determination of pH, pCO2 and HCO3 were obtained from the occluded hand (as the local response indicator of the body to ischemia) and the other hand too (as the systemic response indicator). The time for blood sampling was just before tourniquet inflation, 30 seconds, one minute, three minutes and five minutes after cuff inflation. RESULTS: Thirty seconds after tourniquet release, a rapid decrease was noticed in pH values (7.38±0.04-->7.21±0.08). This decrease was seen after 60s in the opposite hand (7.38±0.04-->7.27±0.01) and returned to the baseline values after 5 minutes in both hands. The blood PCO2 value in the occluded hand was found to be increased 30s after tourniquet release (34.93±3.96-->50.06±11.78), while this increase was seen after 180s in the opposite hand too (34.93±3.96-->38.98±9.21). HCO3 value increased after 30s (19.79±2.31-->20.62±2.37) in the occluded hand, but this increase was visible after 60s in the opposite hand. We found no significant difference in the response of burn patients to tourniquet ischemia in comparison to non-burn patients. CONCLUSION: There was no extra risk in the application of tourniquet in extremity surgeries of burn patients in comparison to non-burn patients. So current protocols of tourniquet application in non-burn patients can be used for adhesion release surgeries in burn patients without any extra caution.

Trichoepithelioma: a rare but crucial dermatologic issue.

Trichoepithelioma is a rare benign skin lesion that originates from hair follicles. Trichoepitheliomas are mostly seen in the scalp, nose, forehead, and upper lip. We present a large family of Iranian origin with 15 individuals affected with multiple familial trichoepithelioma in four generations, and treated with three different methods. Trichoepithelioma is histologically similar to basal cell carcinoma and has a rare risk of malignant transformation. In addition, most frequent incidence of this disease in young to elderly women may lead to social and psychological issues. Precise diagnosis and management of this rare disease seem necessary.

Effects of recombinant human erythropoietin on revascularization of full thickness skin grafts in rat.

BACKGROUND: Autologous skin graft is frequently used in the field of plastic, and reconstructive surgery. The engraftment is dependent upon revascularization and angiogenesis, which can be regulated by different factors. In addition to its hematopoietic effects, erythropoietin is shown to positively affect the wound healing process. OBJECTIVES: We studied effects of human erythropoietin on revascularization of full thickness skin grafts in rat. MATERIALS AND METHODS: Forty adult Albino male rats were selected for this study. Full thickness skin graft was performed for them, and the effects of systemic, and localized administration of erythropoietin on vascularization of the graft area were evaluated in four groups as following: inverse group underwent full thickness skin graft; in normal saline group normal saline was injected under the fascia of grafted area for seven days; systemic EPO group received systemic erythropoietin for seven days after the surgery; and in graft EPO group, erythropoietin was injected under the fascia of grafted area after full thickness skin grafting for seven days. RESULTS: Forty adult Albino male rats (n = 40), with weights ranging from 356 to 469 g (mean 391.5 ± 29.6 g) were included. The vascular densities of central margins were significantly different between inverse group and graft EPO groups (P value = 0.01), and vascular density of central margins of normal saline group and graft EPO groups were significantly different too (P value = 0.04). CONCLUSIONS: EPO can stimulate angiogenesis which has an important role in wound healing. So, local administration of EPO seems to be beneficial in engraftment.

Spontaneous Fracture of the Humerus 18 Months after a High Voltage Electrical Injury: A Case Report.

Electrical burn occurs when a current passes through the body, interfering with the function of internal organs or sometimes burning tissue. Four major mechanisms of electricity-induced injuries are presently known. In this case report, a 29-year-old farmer sustained electrical trauma to extremities from a high voltage transformer, followed by a major, deep burn wound on upper lateral aspect of his left arm, and a deep burn wound over the left medial ankle. After a few months, the patient developed left arm fracture with complete separation of two segments, and plantar wound with purulent discharge accompanied by complete destruction of the head of 4th metatarsal bone which was in favor of chronic osteomyelitis. In this case, passage of the high voltage current and direct trauma could destroy metaphyseal, medullary and periosteal blood supply. Patients with high voltage electrical-induced bone injuries who underwent reconstructive surgery seem to be susceptible to osteonecrosis and pathologic fractures; therefor, these patients should be under close follow-up and periodic radiologic evaluations may be recommended.

Risk of burn trauma during circumcision with radiofrequency scalpel: case report and review of literature.

Male circumcision, one of the oldest and most frequent operations performed all over the world, removes 33-50% of the penile skin. Like each surgical procedure, circumcision can leads to complications ranging from the insignificant to the tragic. Circumcision methods can be done with different ways. The radiofrequency (RF) scalpel, an innovative instrument, can be used in circumcision. Here, we present three boys who sustained sever burn injuries during circumcision with RF method. In sum, interesting characteristics made RF procedures so popular in different fields of surgery. Although having low incidence, the important complications of this technology such as burns should raise our attentions. Performing radiofrequency circumcision by an experienced operator, selection of proper size of ground pads, and elimination of any interface between the skin and ground pad are the factors that can prevent such tragedies.

Efficacy of debridement and wound cleansing with 2% hydrogen peroxide on graft take in the chronic-colonized burn wounds; a randomized controlled clinical trial.

BACKGROUND: Severe burns are associated with dramatic outcomes which are potentially detrimental. Nowadays the standard treatment for deep partial thickness and full-thickness burn is early excision and grafting, which is not always feasible this leads to chronicity and microbial colonization of burn wounds. Interesting properties of hydrogen peroxide 2% soaked gauze convinced us to use it in management of chronic burn wounds. METHODS: From January 2009 to September 2011, in a prospective clinical trial, 49 patients (98 limbs) with chronic-colonized burn wounds in both limbs were included in this study. Tissue cultures were taken from all the wounds. For the right, after debridement of granulation tissue and washing with hydrogen peroxide 2% soaked gauze for 5min followed by normal saline irrigation, grafting was done; debridement and skin grafting was performed in the conventional method in left limb wounds. The success rate of graft take was compared between two groups, after 21 days by the surgeon using the formula: Graft take surface area (cm2) x 100%/Total grafted area (cm2). RESULTS: The study group was composed of 98 limbs in 49 patients with mean age of 26.44±5.66 and burn in 28.3±7.23% TBSA. The most common causes of the burn wounds chronicity was delayed admission associated with poor compliance. (44.8%) Staphylococcus was the most frequent isolate bacterial wounds colonization in our patients. (59.2%) Mean graft take was 82.85% in right limbs, and 65.61% in left limbs; which was significantly different (P<0.05). CONCLUSIONS: Our study showed that, administration of hydrogen peroxide intraoperatively appears to be safe and significantly increases the mean success rate graft take in chronic-colonized wounds. Therefore, it can be recommended in management of chronic burn wounds management.

Effect of fresh human amniotic membrane dressing on graft take in patients with chronic burn wounds compared with conventional methods.

BACKGROUND: Burns are among the most devastating forms of injury. Nowadays the standard treatment for deep partial thickness and full-thickness burn is early excision and grafting, but this technique is not always feasible; and this leads to chronicity and microbial colonization of burn wounds. Interesting properties of human amniotic membrane made us use it in management of chronic infected burn wounds. METHODS: From January 2008 to September 2010, in a prospective clinical trail, 38 patients (76 limbs) with symmetric chronic burn wounds in both upper or lower limbs included in this study. Tissue cultures were taken from all the wounds. For the right, after debridement of granulation tissue and meshed split thickness skin grafting, the graft surfaces were covered with amniotic membrane dressing and in left limb wounds, after debridement, skin grafting was done in conventional method. 21 days later, the success rate of graft take was compared between two groups. RESULTS: The study group was composed of 76 limbs in 38 patients with mean age of 27.18±6.38 and burn in 29.18±7.23 TBSA%. The most common causes of the burn wounds chronicity in the selected patients was delayed admission due to poor compliance of the patients (44.8%). Staphylococcus was the most frequent isolate in wounds in our patients (62.85%). Mean graft take was observed in 90.13% of right upper limbs, and 67.36% of left upper limbs; which was significantly different (P<0.001). CONCLUSIONS: Our study showed that human amniotic membrane dressing significantly increases the success rate of graft take in chronic wounds, and it can be recommended as an important dressing in chronic burn wounds management, due to interesting anti-microbial, and better graft take effects.

Surgical excision followed by low dose rate radiotherapy in the management of resistant keloids.

BACKGROUND: Depending on the cause, 40-90% of every deep dermis insult ends up in scar formation. Several modalities have been suggested as a treatment but a high rate of recurrence is reported in most of those interventions. High dose radiotherapy has been shown to be effective in reducing the recurrence rate. This study tried to determine the effectiveness of low dose rate radiotherapy following surgical excision in treating resistant keloids. METHODS: Between January 2008 and April 2011, seventeen patients (mostly burn patients) with 26 keloids went through surgical resection followed by radiotherapy. A total dose of 15 Gy in 5 fractions was administered to the areas of scar formation. RESULTS: All patients were followed for at least 11 months (mostly for 20 months). No recurrence occurred. There was no complication or adverse effect. CONCLUSION: Surgical excision followed by low dose postoperative radiotherapy was an efficient treatment for keloids that were resistant to many other modalities.