Cytogenetic analysis of 33 basal cell carcinomas.

Cytogenetic analysis of short-term cultures from 33 basal cell carcinomas (BCC), a type of neoplasm for which no previous karyological data exist, revealed clonal chromosome aberrations, all of them different, in 8 tumors. In 2 cases, 2 cytogenetically unrelated clones were detected, suggesting a multicellular origin in at least a subset of BCC. A remarkably high level of nonclonal structural rearrangements, mostly in the form of seemingly balanced translocations, was found in 23 tumors; namely, in 6 of 8 BCC with clonal karyotypic abnormalities and in 17 of 25 without. It is possible that some of these aberrations represent additional neoplastic clones, thus indicating an even higher level of cytogenetic heterogeneity in BCC. We think that the most likely interpretation of the results is that BCC may have a multicellular origin, reflecting field cancerization of the skin. During subsequent tumor development, the selection pressure narrows down the number of clones that infiltrate the surrounding tissue. The finding by karyotypic analysis of some apparently monoclonal, some polyclonal BCC, may reflect that different tumors have been examined at different points in the clonal evolution of the neoplastic cells.

The reciprocal translocation t(9;16)(q22;p13) is a primary chromosome abnormality in basal cell carcinomas.

The reciprocal translocation t(9;16)(q22;p13) was identified in three short-term cultured basal cell carcinomas (BCCs). The t(9;16) was the sole anomaly in one clone in two tumors and was accompanied by a second change that also affected the long arm of chromosome 9 in the third. In addition, other cytogenetically unrelated abnormal clones were also found in all three BCCs. The identification of t(9;16)(q22;p13) as a primary chromosomal abnormality in a subset of BCCs (we found it in 3 of 22 tumors) is especially intriguing against the background that the PTCH gene, which when mutated in the germ line presumably gives rise to the autosomal dominant basal cell nevus or Gorlin's syndrome, maps to chromosome band 9q22. None of the genes rearranged in the BCC-specific t(9;16)(q22;p13) translocation have been identified, but we hypothesize that the translocation represents the cytogenetic corollary of a tumorigenic recombination of PTCH with an as yet unknown gene in 16p13. If so, this would be the first time that a tumor suppressor gene causally involved in a hereditary cancer is shown to be frequently rearranged through a specific translocation in sporadic carcinomas of the same type.

Nonrandom karyotypic features in basal cell carcinomas of the skin.

Cytogenetic analysis of short-term cultured 44 basal cell carcinomas (BCC) revealed clonal karyotypic abnormalities in 38 tumors. Relatively complex karyotypes (at least four structural and/or numerical changes per clone) with unbalanced structural as well as numerical aberrations were found in eight (approximately 21%) of the BCC, while the remaining BCC (79%) had simple karyotypes (1 to 3 aberrations per clone). Numerical changes only were found in 16 tumors, 15 BCC displayed both numerical and structural aberrations, and the remaining 7 BCC showed only structural aberrations. Extensive intratumoral heterogeneity, in the form of cytogenetically unrelated clones, was found in 21 tumors, whereas related subclones were present in 10 tumors. In order to obtain an overall karyotypic picture in BCC, the findings of our previously published 25 BCC have been reviewed. Our combined data indicate that BCC are characterized by nonrandom karyotypic patterns. A large subset of BCC is characterized by nonrandom numerical changes, notably, +18, +X, +7, and +9. Structural rearrangements often affect chromosomes 1, 4, 2, 3, 9, 7, 16, and 17. A number of chromosomal bands are frequently involved, including 9q22, 1p32, 1p22, 1q11, 1q21, 2q11, 4q21, 4q31, 1p36, 2q37, 3q13, 7q11, 11p15, 16p13, 16q24, 17q21, and 20q13. When the genomic imbalance is assessed, it has been shown that several chromosome segments are repeatedly involved in losses, namely loss of the distal part of 6q, 13q, 4q, 1q, 8q, and 9p. A correlation analysis between the karyotypic patterns and the clinico-histopathologic parameters has been undertaken in the 44 BCC of the present series. The cytogenetic patterns show a significant correlation with tumor status (P=.025), that is, that cytogenetically more complex tumors are also those clinically the most aggressive. Also, the frequency of cytogenetically unrelated clones is significantly higher in recurrent BCC than that in primary lesions (P=.05). No clear-cut association has been found between the karyotypic patterns and histologic subtypes or tumor sites.

Nonrandom numerical chromosome abnormalities in basal cell carcinomas.

Clonal chromosome abnormalities were found in 22 of 23 short-term cultured basal cell carcinomas (BCC) of the skin. The karyotypic abnormalities were nonrandom and in several cases included evidence of clonal evolution. Especially in cultures showing an epithelial growth pattern, simple numerical changes, most commonly +18, +9, +20, +7, and +5, predominated and presumably constitute pathogenetically important aberrations present in the neoplastic parenchyma. Also, several structural rearrangements of chromosome arm 9q were seen, which may be of particular interest against the background that a gene for familial BCC (Gorlin syndrome), the PTCH gene, maps to this region. Finally, most of the clonal aberrations detected in predominantly fibroblast-like cultures are likely to reflect changes acquired by cells of the tumor stroma, which raises the question whether mutations also of this tumor component may play a pathogenetic role in BCC development.

Immune response in burn patients in relation to HIV infection and sepsis.

The post-burn immune dysfunction predisposes patients to sepsis and multiple organ failure leading to increased mortality. HIV infection also results in a depressed immune response. The combination of burn injury and HIV might therefore lead to an increased morbidity and mortality as compared to non-HIV infected burn patients. Twenty burn patients and 10 healthy volunteers were included in a prospective study. To evaluate their immune status, CD4+ and CD8+ T-lymphocyte counts were determined in peripheral blood. HIV serology samples were obtained on admission. Bacteriological cultures were obtained from wound surface samples and wound tissue biopsies. Six burn patients were HIV infected. Clinical signs of sepsis were observed in 10 patients. The number of CD4+ T-lymphocytes were lower in burn patients compared to healthy volunteers (P < 0.05). HIV infected burn patients had lower CD4+ lymphocyte counts than non-HIV infected patients (P < 0.05). Patients with clinical signs of sepsis had lower CD4+ counts compared to patients without sepsis (P < 0.05). There was no difference in the mortality rate or the length of hospitalisation between patient groups. Burn injury, HIV infection and sepsis independently result in immunosuppression.

A prospective study of suicidal burns admitted to the Harare burns unit.

The aim of this study was to obtain prospective information on suicidal (attempted suicide) burns patients admitted to the Harare burns unit during 1995-1998. Forty-seven patients, 42 females (89%) and five males (11%), evenly distributed throughout the period of study, were included. The median age was 25 years, range 13 to 50 years. Thirty were housewives (64%). Women married according to customary law were the group most at risk. All patients were burnt by flame after dousing themselves with paraffin or petrol. Conflict in love relationships was the most common circumstance leading to attempted suicide. The median Total Body Surface Area (TBSA) burnt was 60%, range 10-90%, for all patients, 25%, range 10-40%, for those who survived and 65%, range 20-95%, for those who died. Surgery was performed on 16 patients (34%). Mortality was 68%. The overall median hospital stay for all patients was 10 days, range 0-322 days, and 5 days, range 0-322 days, for those who died.

A Prospective study on the epidemiology of burns in patients admitted to the Harare burn units.

The purpose of this study was to record the causes and the magnitudes of burn injuries prospectively and to evaluate the outcome of treatment of patients admitted to the burn units in Harare. The median age of the 451 patients included was 6 years (range: 1 month to 71 years), 54% were female and 46% male. The burn injuries were caused by flame in 51% of the cases and hot liquids in 47%. The overall median total body surface area burnt was 13% (range: 0.5 to 99%). Parasuicidal burns (attempted suicides) were noted in 11% of the patients with a median total body surface area burnt of 30% and mortality of 73%. Lodgers were overrepresented in the material. Delayed split skin grafting was done on 26% of the patients and early primary excision and skin grafting on 3%. The overall median hospital stay was 15 days (range: 0 to 229 days). The median hospital stay for patients with delayed split skin grafting was 42 days and that for those with primary excision and split skin grafting was 17 days. The overall mortality was 22%. All patients with burns larger than 65% of the total body surface area died. Burn injuries were more frequent and larger with higher mortality in females than in males. Flame was the major cause of the burns. Self-inflicted burns, noted mainly in young women, resulted in 73% mortality. Primary excision and grafting reduced hospital stay by 60% compared to delayed skin grafting.

A prospective double blind randomized study comparing the need for blood transfusion with terlipressin or a placebo during early excision and grafting of burns.

INTRODUCTION: Early excision and skin grafting has become the standard of good burn management, but it is associated with major blood loss. AIM: To determine the haemostatic effect of terlipressin compared with placebo. MATERIAL AND METHODS: Fifty-one patients with burns of 10-20% total body surface area had early excision and split skin grafting of deep burns. The surface area of the burn wound and of the healed graft were measured by planimetry. The patients were randomly allocated to medication, either terlipressin or placebo. Blood loss and number of transfused units of blood were recorded. RESULTS: Twenty-one patients received terlipressin, 13 received terlipressin late (cross-over) and 17 received placebo. Six out of 21 patients exposed to terlipressin were transfused with eleven units of packed red blood cells. Seven out of 13 patients crossed over from placebo to terlipressin (late terlipressin) were transfused with 17 units of blood. Eight out of 17 patients exposed to the placebo were transfused with 22 units of blood (P < 0.05). Graft healing was 1055 +/- 609 cm2 out of 1452 +/- 11 cm2 in terlipressin and 914 +/- 633 cm2 out of 1288 +/- 720 cm2 in the placebo group (n.s.). CONCLUSION: Terlipressin reduced the need for blood transfusion by a factor of 2.5 compared to a placebo without impairment of graft healing.

Validation of a Norwegian version of the Burn Specific Health Scale.

BACKGROUND: The abbreviated Burn Specific Health Scale (BSHS-A) is an 80-item questionnaire that has proven useful in measuring physical, mental, social and general health in burn survivors. The aim of this study was to adapt the BSHS-A into Norwegian, including assessing reliability and validity. METHODS: Standard procedures for forward and backward translation including discussions with professionals and patients to ensure conceptual equivalence were used. A pilot study (11 burn patients) confirmed that the Norwegian version (BSHS-N) was clear, understandable and easy to self-administer. Subsequently, 95 adults admitted to the Burn Center, Haukeland University Hospital, between 1995 and 2000 entered a validation study by completing the BSHS-N and the general health measure SF-36. Sixty-nine of the 95 (72%) responders completed a retest. RESULTS: The overall internal consistency reliability (Cronbach's alpha=0.97) and the test-retest reliability (ICC=0.95) for the BSHS-N were satisfactory. Tests for criterion validity showed expected patterns for association between comparable domains in the BSHS-N and the SF-36, with correlations ranging from r=0.61 to 0.81. Tests for construct validity showed that patients with full thickness injury (P=0.003), patients hospitalised more than 10 days (P=0.003), patients undergoing more than two operations (P=0.001) and patients unemployed at the time of study (P<0.001), had significantly lower total scores than the rest of the patients. CONCLUSION: BSHS-N seems to be a reliable and valid instrument for use in the Norwegian population. The translation and cross-cultural adaptation of this instrument allows for comparative international studies.

Prevention of microvascular thrombosis with low-dose tissue plasminogen activator.

In a blind, randomized study, two groups, each of seven rabbits, were treated with either a very low dose of human melanoma cell line-derived tissue-type plasminogen activator (t-PA) or isotonic saline. t-PA (0.067 mg/kg of body weight) was administered intraaortically, 20 percent being given as a 30-second "bolus" infusion just prior to the reperfusion of intimectomized central ear arteries and the rest as a continuous infusion during the next 2 hours. Arteriotomic bleeding times, accumulations of 32P-labeled platelets, patency, and sizes of thrombus deposits 2 hours after reperfusion were recorded. To confirm the presence of tissue plasminogen activator in plasma, fibrin-plate lysis assays of arterial plasma were performed immediately before and 1/2 hour and 2 hours after starting drug infusion. Arteriotomic bleeding times were similar in both groups. Transient "oozing" from wound edges occurred in 40 percent of rabbits treated with tissue plasminogen activator. Patency was significantly increased and thrombus deposits were smaller in the tissue plasminogen activator group. Plasma from animals treated with tissue plasminogen activator caused massive lysis of fibrin plates, whereas plasma from control animals caused little or no lysis. Platelet accumulations were very similar in both groups, indicating that occlusive thrombi mainly consisted of other elements than platelets (e.g., fibrin and red cells). Scanning electron microscopy showed normally adhering and aggregating platelets in both groups. This study shows that mild fibrinolytic stimulation with tissue plasminogen activator significantly improves patency in severely traumatized small-caliber arteries and indicates that such treatment may be one approach to prevent thrombosis at microvascular anastomotic sites.

Mandibular reconstruction by secondary reimplantation of resected segments: a preliminary report.

This paper presents a new method of reconstructing the mandible after ablative surgery for cancer. This method uses autogenous grafts consisting of the respected part of the mandible, which is hollowed out, defatted in chloroform/methanol, sterilized with ethylene oxide, irradiated with beta-radiation (dose 25 kGy), and stored for 7-10 months. At reimplantation, they were filled with compressed, autogenous, particulate cancellous bone. All grafts took, and four of six host-graft junctions healed.

Comparison of surface swab cultures and quantitative tissue biopsy cultures to predict sepsis in burn patients: a prospective study.

This study aimed at evaluating the possibility of predicting septicemia in burn patients by using wound surface and tissue culture techniques as well as blood cultures. Fifty patients with full-thickness burn wounds covering at least 10% of the total body surface area were included. Signs of septicemia were noted in 21 patients (42%) and 29 patients died (58%). The bacterial colonization of the burn wounds consisted mainly of Staphylococcus aureus and Pseudomonas aeruginosa. Sepsis was better correlated to quantitative burn tissue biopsy cultures than surface swab cultures but the time needed for processing limits its predictive and therapeutic value.

How to dress donor sites of split thickness skin grafts: a prospective, randomised study of four dressings.

We investigated the effects of four dressings on donor sites of split thickness skin grafts. Eighty patients undergoing elective split thickness skin grafting were randomly allocated to one of four groups. The dressings were paraffin gauze, polyurethane foam, polyethane film, and polyurethane film. The main outcome measures were pain and discomfort, healing of donor sites, and time to remove dressings. Polyurethane film caused less pain and discomfort and was also easiest to remove. There were no differences in healing among the four groups.

Effects of streptokinase and urokinase on microarterial thrombosis and haemostasis. An experimental study in rabbits.

The effects of streptokinase and urokinase on haemostasis, accumulation of platelets radiolabelled with phosphorus (32P) and patency were studied after arteriotomy and deep vessel wall trauma of the central arteries of rabbits' ears. In one study, 12 rabbits were given 1700 IU/kg body weight of streptokinase or urokinase as intraaortic bolus injections five minutes before vascular reperfusion (opening of vascular clamps). A further six were given saline (controls). In the second, 12 further rabbits were each given 3,400 IU/kg of either substance, one fifth as a bolus before reperfusion and the remainder as a continuous infusion during the next two hours. A further six were given saline (controls). Irrespective of the dosage regimens, neither substance improved patency compared with saline-treated controls. Separate dose response studies with streptokinase showed that bolus or bolus+infusion doses larger than those given caused troublesome arteriotomy bleeding. Compared with controls, streptokinase increased, and urokinase decreased, accumulation of platelets. This was not reflected in differences in patency rates, which were similar in all groups. In conclusion, fibrinolytic stimulation with non-thrombolytic doses of streptokinase or urokinase did not prevent microarterial thrombosis in rabbits. The therapeutic index for these substances in clinical microvascular surgery is probably low, as haemorrhagic complications may be expected.

Platelet accumulation and thrombus formation after microarterial injury. An experimental study in rabbits.

Patency rats and accumulation of 32P-labelled platelets were studied in the central ear arteries of rabbits (which were not treated with antithrombotic agents) after three types of vascular injury: End to end anastomosis, arteriotomy and superficial injury to the vessel wall to expose the lamina elastica interna/juxtaluminal parts of the tunica media, arteriotomy and deep injury to the vessel wall to expose the deeper layers of the tunica media. The superficial and deep vessel injuries were 5 mm long. Patency rates were 100% after end to end anastomosis and superficial injury, and 48% after deep injury. In a separate group of vessels with deep injuries the time course of formation of occlusive thrombi was investigated: occlusion was already present 15 minutes after reperfusion in all but one of seven occluded vessels. Platelet accumulation ratios were significantly higher after deep injury than after end to end anastomosis or superficial injury. In deeply injured patent vessels, platelet accumulation reached a maximum after about 30 minutes, which was later followed by a gradual decrease. Platelet accumulation patterns indicating sustained thrombogenicity throughout the measurement interval (embolization/reaccumulation patterns or late increases in accumulation) were encountered in only three of 22 deeply injured vessels. We conclude that: to cause formation of occlusive thrombus in otherwise healthy arteries and animals, a deep injury to the tunica media is necessary, and following reperfusion after repair of damaged vessels the time course of the thrombotic challenge is short.

Pneumatocele after removal of squamous cell carcinoma in the scalp--a rare complication? Case reports.

Two patients with squamous cell carcinoma of scalp had the outer table of the skull opened with an osteotome and a drill. Split skin grafts were applied to the defect in one and delayed split skin grafts in the other. In both cases the lesions were on the vertex and resulted in leakage of cerebrospinal fluid and formation of intracranial pneumatoceles. In one case there was serious disturbance of the central nervous system. We conclude that deep resection within the vertex region overlying the lateral lacuna in close proximity to the sagittal sinus must be done with care and the residual defect should preferably be covered with local flaps.

Effect of low and ultra low oral doses of acetylsalicylic acid in microvascular surgery. An experimental study in the rabbit.

About 10 h after administering acetylsalicylic acid (ASA) orally in doses of 4 mg and 20 micrograms/kg b.w., the central arteries of rabbit ears were subjected to severe vascular trauma (arteriotomy/intimectomy). Bleeding times from the trauma regions at reperfusion were measured and the activities from accumulating 32P-labelled homologous platelets recorded until 2 h after reperfusion when patencies were determined. In other studies, the effects of ASA on ex vivo platelet aggregation (aggregometry), thromboxane production, euglobulin clot lysis time and bleeding time following arterial puncture were investigated. Relative to controls, the following parameters were changed: patency was increased, as were the bleeding times following arterial puncture and thromboxane production was reduced. The median values of platelet accumulation were lower, but the changes were not statistically significant. Aggregometry showed decreased rates of platelet aggregability following treatment with ASA 4 mg/kg.

International survey of current microvascular practices in free tissue transfer and replantation surgery.

The replies to a questionnaire about current microvascular practice circulated to microsurgeons worldwide are summarized and discussed. The material comprises results of 6,594 procedures performed during 1989. The survey topics dealt with include overall success rates in free flap transfer and replantation surgery, antithrombotic therapy, frequency of thrombosis, and frequency of reoperation. At centres not using antithrombotic therapy, the frequency of thrombosis in free flap procedures was higher than at centres using antithrombotic therapy, the result being a higher reoperation rate at the former. However, the final success rates for free flap transfers were about the same (95-96%). The success rate for replantation with antithrombotic therapy was 92%; few centres attempted replantation without such treatment, and at these centres, the success rate was 82%, and reoperation was not attempted. The same modes of antithrombotic therapy and postoperative monitoring are used worldwide.

Effects of the prostacyclin analogue iloprost on patency in small arteries and veins: an experimental study in the rabbit.

Arteriotomy/intimectomy and venotomy/intimectomy were performed in the ears of 43 rabbits. Twenty were treated with iloprost given as intravenous doses of 10 micrograms/kg body weight (bw) administered shortly before reperfusion followed by hourly infusions (3 micrograms/kg b w) until 12 hrs after reperfusion. At reperfusion venous and arterial bleeding times were noted. Patency was determined at 15-min intervals until 2 hrs after reperfusion and at 1 and 2 weeks postoperatively. As controls, 23 rabbits were given a single infusion of saline. Compared to controls, iloprost significantly prolonged arterial and venous bleeding times and significantly improved patency 2 hrs after reperfusion. One and two weeks later, however, virtually all vessels were occluded. Administered in this fashion, iloprost does not improve long-term patency in highly traumatized small veins and arteries.