Prior immunisation of patients with malignant melanoma with vaccinia or BCG is associated with better survival. An European Organization for Research and Treatment of Cancer cohort study on 542 patients.

There is increasing evidence that infections and vaccinations play an important role in the normal maturation of the immune system. It was therefore of interest to determine whether these immune events also affect the prognosis of melanoma patients. A cohort study of 542 melanoma patients in six European countries and Israel was conducted. Patients were followed up for a mean of 5 years and overall survival was recorded. Biometric evaluations included Kaplan-Meier estimates of survival over time and Hazard Ratios (HRs), taking into account all known prognostic factors. During the follow-up between 1993 and 2002, 182 of the 542 patients (34%) died. Survival curves, related to Breslow's thickness as the most important prognostic marker, were in accordance with those observed in previous studies where the cause of death was known to be due to disseminated melanoma. In a separate analysis of patients, vaccinated with vaccinia or Bacille Calmette-Guerin (BCG), HRs and the corresponding 95% Confidence Intervals (CIs) were 0.52 (0.34-0.79) and 0.69 (0.49-0.98), respectively. Joint analyses yielded HRs (and 95% CIs) of 0.55 (0.34-0.89) for patients vaccinated with vaccinia, 0.75 (0.30-1.86) with BCG, and 0.41 (0.25-0.69) with both vaccines. In contrast, infectious diseases occurring before the excision of the tumour had little, or, at the most, a minor influence on the outcome of the melanoma patients. These data reveal, for the first time, that vaccination with vaccinia in early life significantly prolongs the survival of patients with a malignant tumour after initial surgical management. BCG vaccination seems to have a similar, although weaker, effect. The underlying immune mechanisms involved remain to be determined.

Impact of vaccinations and infectious diseases on the risk of melanoma--evaluation of an EORTC case-control study.

A significant correlation between a reduced risk of melanoma and BCG and vaccinia vaccination in early childhood or infectious diseases later in life has already been reported from the FEBrile Infections and Melanoma (FEBIM) multicentre case-control study. This correlation is further evaluated in this study based on 603 incident cases of malignant melanoma and 627 population controls in six European countries and Israel by means of a joint analysis of the influence of vaccinations and infectious diseases. In addition, the previously unconsidered impact of influenza vaccinations is evaluated for the whole study population. The strong effects of the frequently given BCG and vaccinia vaccinations in early childhood, as well as of uncommon previous severe infectious diseases, were apparently not cumulative. With the Odds Ratio (OR) being set at 1 in the absence of vaccinations and infectious diseases, the OR dropped to 0.37 (95% Confidence Interval (CI): 0.10-1.42) when subjects had experienced one or more severe infectious diseases, associated with a fever of > 38.5 degrees C, and had not been vaccinated with BCG or vaccinia. The OR was 0.29 (CI: 0.15-0.57) in those who had had a severe infectious disease and were vaccinated with either BCG or vaccinia and 0.33 (CI: 0.17-0.65) for those with 1 or more severe infectious diseases and who had received both vaccinations. We conclude that both vaccinations as well as previous episodes of having a severe infectious disease induced the same protective mechanism with regards to the risk of melanoma. Because of a 'masking effect' by the vaccinia vaccination, the protective effect of the BCG vaccination and of certain infectious diseases against cancer has remained undetected. The vaccinations contributed more to the protection of the population than a previous episode of having an infectious disease. In view of the termination of vaccinations with vaccinia in all countries and of BCG in many of them, these findings call for a re-evaluation of vaccination strategies.

Monitoring of the infrared radiation emitted from skin layers during CO2 laser resurfacing: a possible basis for a depth navigation device.

CO2 laser resurfacing is very accurate, but it is not free of complications such as scarring. The objectives of the present study were to evaluate the pattern of the infrared (IR) radiation emitted from skin layers and to use this pattern to distinguish between these layers during resurfacing. A CO2-resurfacing laser (Sharplan SilkTouch) was used for the de-epithelialisation of skin. A silver halide optical fibre delivered the radiation emitted from the skin during resurfacing to an IR photonic detector. Time-dependent curves of the signals emitted from the skin layers were statistically evaluated and showed significant differences between the epidermis and the dermal layers. Similar results were obtained during in-vivo and ex-vivo measurements. The difference between the skin layers emission may be used for depth navigation during laser resurfacing.

Walk-through injuries: glass door facial injuries.

During 1998, 13 patients were treated in the Tel-Aviv Sourasky Medical Center for complex facial soft-tissue injuries caused by passing through large, clear glass doors. All epidemiological details were gathered and analyzed. Of 1,100 soft-tissue facial injury admissions in 1 year, 13 patients had a substantial soft-tissue facial injury after passing through a glass barrier. Nine were injured during leisure time activity, five in a shopping mall, and four in their residence. Interestingly, the authors found a common pattern of facial injuries in all patients. It consisted of large, irregular, composite skin and soft-tissue flaps as well as large, tom, irregular skin lacerations. The nose was injured predominantly, and the injury was particularly complex. Their recommended management of these injuries is a thorough and careful evaluation of flap viability. Surgical management of avulsed, viable flaps includes margin debridement and repositioning. If the flap is narrow enough, it can be debrided and the margins adapted primarily. If viability of part of the flap is in doubt, that part should be debrided and used as a composite graft. When this graft dies, a full-thickness graft is taken from another facial site. The cosmesis of such a graft is better than using the debrided, thin segment as a skin graft that is too thin. The authors emphasize that there is a need to encourage authorities to reinforce regulations relating to injury prevention from architectural glass. The first is to use special glazing, either tempered glass, laminated glass, or both. The other method of improving safety is by indicating glass using decorations or warning stickers, or by making it partly translucent. Unless these regulations are obeyed, fatal or complex trauma may occur.

Use of sunscreen is linked with elevated naevi counts in Israeli school children and adolescents.

Epidemiological evidence indicates that a fair complexion and exposure to solar radiation in early years contribute to the proliferation of naevi and subsequent melanoma risk. To determine whether protection from sunlight is associated with lower naevi counts, we examined the prevalence and risk factors of naevi in a sample of Israeli school pupils. Whole body counts of naevi were recorded in 974 out of 1312 (74.2%) recruited pupils (7 and 12 year olds) from Ramat-Gan and Jerusalem. Host characteristics and habits of sun exposure were obtained using questionnaires. In each age group and geographic area, the mean whole body naevi counts, adjusted for confounders, were higher among males, pupils of European-American descent, and those susceptible to sunburn. The contributions to naevi risk of fair skin colour and frequent recreational sun exposure were higher among 7 year olds. Regular sunscreen use contributed to the naevi risk for both age strata in Ramat-Gan (at age 7, rate ratio [RR] = 1.7, 95% confidence interval [CI] = 1.3-2.2; at age 12, RR = 1.5, 95% CI = 1.1-2.1). Among the younger age group in Ramat-Gan, even seldom compared with no use of sunscreen was associated with higher naevi counts (RR= 1.5, 95% CI = 1.2-2.0). Similar patterns were noted with the pupils from Jerusalem. In conclusion, the elevated naevi count with increased sunscreen use indicates that sunscreens apparently do not modify the genetic predisposition to naevi proliferation. For better protection of children and adolescents, including those who use sunscreens, from the naevogenic effect of solar radiation, they should be encouraged to limit their exposure and wear protective clothing when in the sun.

Abdominal recovery after laparotomy and omental transposition into a grossly contaminated median sternotomy wound.

Grossly contaminated median sternotomy wounds are frequently treated with transposed omental flaps. A laparotomy adjacent to such an infected wound carries the risk of peritonitis. It has been suggested that this risk may increase when the omentum, which has anti-infective properties, is removed from the abdominal cavity and is transposed to the chest. The authors evaluated abdominal recovery after laparotomy and omental transposition into an adjacent, grossly contaminated median sternotomy wound. The study group included 15 patients who had sternal wound reconstruction with an omental flap between 1990 and 1998. All patients underwent median sternotomy reconstruction according to a "two-compartment" operative sequence protocol, which included division of the surgical field into an upper (thoracic) contaminated zone and a lower (abdominal) clean zone. The control group was comprised of 15 patients who underwent elective laparotomy for splenectomy during the same time period. The effect of the surgical procedure on the abdomen was compared between the two groups. The timing of the reappearance of peristalsis and regular bowel function, and the incidence of bowel obstruction and postoperative peritonitis were similar in the two groups. The findings indicate that laparotomy and omental transposition in the presence of a grossly contaminated median sternotomy wound is a safe procedure, and is associated with a low rate of abdominal complications.

Two p16 (CDKN2A) germline mutations in 30 Israeli melanoma families.

Germline mutations in the p16 (CDKN2A) tumour suppressor gene have been linked to inherited predisposition to malignant melanoma (MM). Variable frequencies of p16 germline mutations were reported in different collections of melanoma families but it can be as high as 50%. Here we describe the results of p16 mutation screening in 30 melanoma kindreds in Israel. The entire coding region of the p16 gene, including exons 1, 2 and 3, flanking exon/intron junctions, and a portion of the 3' untranslated (UTR) region of the gene were examined by single-stranded conformation polymorphism (SSCP) analysis and direct sequencing. Two p16 germline mutations were identified: G101W, which has been previously observed in a number of melanoma kindreds, and G122V, a novel missense mutation. Thus, the frequency of mutations identified in this collection of Israeli families was 7%. Functional analysis indicated that the novel G122V variant retained some capacity to interact with cyclin dependent kinases (CDKs) in vitro, yet it was significantly impaired in its ability to cause a G1 cell cycle arrest in human diploid fibroblasts. This partial loss of function is consistent with the predicted impact of G122V substitution on the 3-dimensional structure of the p16 protein.

Infections and melanoma risk: results of a multicentre EORTC case-control study. European Organization for Research and Treatment of Cancer.

Immune function plays a prominent role in the defence against cutaneous malignant melanoma and the increased risk of melanoma development during immunosuppression. Since the immune system is challenged beyond its routine activity by an infection, the effect of previous infectious diseases on the risk of melanoma may also be crucial. In a European Organization for Research and Treatment of Cancer (EORTC) case-control study performed in six European countries and Israel, we compared the history of severe infections in 603 melanoma patients with that in 627 population controls. We calculated adjusted odds ratios (ORs) to estimate the effect of infectious diseases on melanoma risk. The ORs for melanoma risk were below 1 for nearly all types of infections (except two) if body temperature was not taken into consideration, and for all infections with a body temperature above 38.5 degrees C. In the latter category significantly lowered ORs were found for pulmonary tuberculosis (0.16; 95% confidence interval [CI] 0.01-0.98), Staphylococcus aureus infections (0.54; 95% CI 0.31-0.94), sepsis (0.23; 95% CI 0.06-0.70), influenza and related infections (0.65; 95% CI 0.48-0.86) and pneumonia (0.45; 95% CI 0.27-0.73). Analysis of the cumulative influence revealed a consistent pattern of results pointing to a reduction in melanoma risk with increasing numbers of recorded infections and fever height. This apparent dose-response relationship suggests a causal association. Speculations on the underlying mechanism include a Shwartzman-like phenomenon when melanoma formation precedes the infection and/or an infection-related Th1-cell activation preventing the establishment of the tumour.

Comparison of flash lamp pulsed-dye laser (585 nm) and conventional surgery in the delay of random dorsal rat flaps.

BACKGROUND AND OBJECTIVE: Delay is a basic surgical technique used by flap surgeons to improve the blood supply to the distal parts of a random skin flap. The aim of this study was to determine whether a scarless delay can be done by the use of the flash lamp pulsed-dye laser operating at a wavelength of 585 nm. STUDY DESIGN/MATERIALS AND METHODS: The pilot study showed that 6 J/cm(2) had a selective photothermolysis effect and therefore was chosen for testing the delay procedure on 15 rats. The percentage of flap necrosis of this group was compared to the results of 15 rats that underwent delay by surgery and 15 rats that were not treated prior to flap surgery (control group). RESULTS: Laser delay of McFarlane flaps resulted in an average of 15.5% smaller necrotic area compared to the control group (52.7% +/- 14.4% and 68.2% +/- 9.6%, respectively, P < 0.01) and was as effective as surgical delay (53.3% +/- 13.6%). CONCLUSIONS: The results indicate that the flash lamp pulsed-dye laser operating at 585 nm is effective for delaying cutaneous flaps in the rat model.

Blindness as a complication of subcutaneous nasal steroid injection.

Blindness as a result of steroid injection into areas adjacent to the eyes, namely the interior of the nose and eyelids, has been described in the otolaryngologic and ophthalmologic literature but at no time in the plastic surgery literature. We describe a case of permanent visual loss at the time of injection of a long-acting steroid to the dorsum of the nose for postrhinoplasty scarring. We suggest that before steroid injection for elective procedures, the patient be informed of all possible consequences of complications even if their occurrence is very rare.

Recommended guidelines for optimal design of a plastic surgery service during mass casualty events.

OBJECTIVE: The objectives of the study were to evaluate the pattern of plastic surgery (PS) team intervention during the first 12 hours after a mass casualty blast. METHODS: The records of 272 civilians injured from 1994 to 1997 in Tel Aviv were reviewed. Patients' injuries were classified according to the nature of their PS injury and the type of PS intervention. The procedure time and number of plastic surgeons involved were recorded in 20-minute intervals. The average and standard deviation of the peak demand (PD) timing for PS intervention were calculated. Linear correlation between the PD and the total number of wounded transferred to the Tel Aviv Sourasky Medical Center was evaluated by the correlation coefficient. RESULTS: A distinct "double-peak" and five phases pattern of PS team intervention were observed. A linear correlation and a 1:5 ratio were found between the total number of wounded transferred to the Tel Aviv Sourasky Medical Center and the PD for PS intervention. CONCLUSIONS: PS involvement has a predicted pattern related to the patient volume. Guidelines based on the conclusions drawn from this study can ensure an ordered, efficacious level of PS care during these events. A triple team plan is suggested, and adjustments in medical resources according to the specific nature of the event are described.

Screening for tumour suppressor p16(CDKN2A) germline mutations in Israeli melanoma families.

Approximately ten percent of patients with malignant melanoma have family histories of the disease, suggesting a genetic predisposition. Germline mutations in tumour suppressor p16 gene have been implicated as disease causing mutations in some of the melanoma families. The frequency of families with p16 germline mutations among melanoma prone families varies from eight to fifty percent. The range of the variability is influenced apparently by the number of melanoma affected individuals within the family, as well as by other, yet unidentified factors. Ethnic background is known to determine both the frequency and the nature of germline alterations. Recently, specific mutations in tumour suppressor genes involved in breast cancer and in colon cancer were found at elevated frequency among Ashkenazi Jews. This report describes results of a screening for p16 germline alterations in a collection of Israeli melanoma families. We have analyzed genomic DNA from thirty one Ashkenazi and non-Ashkenazi Jewish melanoma families, as well as from thirty melanoma patients without an apparent family history of the disease. The entire coding region of the p16 gene was screened by single strand conformation polymorphism analysis and direct DNA sequencing. We have detected a number of carriers with the Ala148 Thr polymorphism at the end of the second exon and several instances of 500(G=>C) substitution at the 3' untranslated portion of the gene.

Single-injection gamma probe-guided sentinel lymph node detection in 40 melanomatous lymphadenectomies.

The aim of the study was to evaluate single-injection gamma probe-guided sentinel lymph node (SLN) detection, applied in 40 melanomatous selective sentinel lymphadenectomies (SSLNDs). Thirty-four patients underwent preoperative lymphoscintigraphy, intraoperative SLN identification by a gamma-detecting probe and blue dye, and SLN sampling. The first 11 patients underwent formal lymphadenectomy. The following 23 patients underwent formal lymphadenectomy only when the SLN was involved with tumor. Evaluation included hematoxylin-eosin-stained slide microscopy, monoclonal antibodies to S-100 protein, and the melanoma-associated antigen HMB45. In all patients, single or multiple SLNs were identified by the gamma-detecting probe. However, only 82.5% of these specimens included blue-stained nodes. None of the non-SLN specimens were the exclusive site of metastases. Four patients had metastases in their SLN specimen without non-SLN involvement. We conclude that SSLND can be performed easily and precisely with the exclusive use of the gamma-detecting probe. A single injection is feasible, and decreases operating room contamination and patient discomfort.