Emanuela Cagnano

IL-1 is required for tumor invasiveness and angiogenesis

Here, we describe that microenvironmental IL-1β and, to a lesser extent, IL-1α are required for in vivo angiogenesis and invasiveness of different tumor cells. In IL-1β knockout (KO) mice, local tumor or lung metastases of B16 melanoma cells were not observed compared with WT mice. Angiogenesis was assessed by the recruitment of blood vessel networks into Matrigel plugs containing B16 melanoma cells; vascularization of the plugs was present in WT mice, but was absent in IL-1β KO mice. The addition of exogenous IL-1 into B16-containing Matrigel plugs in IL-1β KO mice partially restored the angiogenic response. Moreover, the incorporation of IL-1 receptor antagonist to B16-containing plugs in WT mice inhibited the ingrowth of blood vessel networks into Matrigel plugs. In IL-1α KO mice, local tumor development and induction of an angiogenic response in Matrigel plugs was less pronounced than in WT mice, but significantly higher than in IL-1β KO mice. These effects of host-derived IL-1α and IL-1β were not restricted to the melanoma model, but were also observed in DA/3 mammary and prostate cancer cell models. In addition to the in vivo findings, IL-1 contributed to the production of vascular endothelial cell growth factor and tumor necrosis factor in cocultures of peritoneal macrophages and tumor cells. Host-derived IL-1 seems to control tumor angiogenesis and invasiveness. Furthermore, the anti-angiogenic effects of IL-1 receptor antagonist, shown here, suggest a possible therapeutic role in cancer, in addition to its current use in rheumatoid arthritis.

Differential effects of IL-1 alpha and IL-1 beta on tumorigenicity patterns and invasiveness

In this study, we show that distinct compartmentalization patterns of the IL-1 molecules (IL-1α and IL-1β), in the milieu of tumor cells that produce them, differentially affect the malignant process. Active forms of IL-1, namely precursor IL-1α (pIL-1α), mature IL-1β (mIL-1β), and mIL-1β fused to a signal sequence (ssIL-1β), were transfected into an established fibrosarcoma cell line, and tumorigenicity and antitumor immunity were assessed. Cell lines transfected with pIL-1α, which expresses IL-1α on the membrane, fail to develop local tumors and activate antitumor effector mechanisms, such as CTLs, NK cells, and high levels of IFN-γ production. Cells transfected with secretable IL-1β (mIL-1β and ssIL-1β) were more aggressive than wild-type and mock-transfected tumor cells; ssIL-1β transfectants even exhibited metastatic tumors in the lungs of mice after i.v. inoculation (experimental metastasis). In IL-1β tumors, increased vascularity patterns were observed. No detectable antitumor effector mechanisms were observed in spleens of mice injected with IL-1β transfectants, mock-transfected or wild-type fibrosarcoma cells. Moreover, in spleens of mice injected with IL-1β transfectants, suppression of polyclonal mitogenic responses (proliferation, IFN-γ and IL-2 production) to Con A was observed, suggesting the development of general anergy. Histologically, infiltrating mononuclear cells penetrating the tumor were seen at pIL-1α tumor sites, whereas in mIL-1β and ssIL-1β tumor sites such infiltrating cells do not penetrate inside the tumor. This is, to our knowledge, the first report on differential, nonredundant, in vivo effects of IL-1α and IL-1β in malignant processes; IL-1α reduces tumorigenicity by inducing antitumor immunity, whereas IL-1β promotes invasiveness, including tumor angiogenesis, and also induces immune suppression in the host.

Acute generalized exanthematous pustulosis mimicking toxic epidermal necrolysis

A 91‐year‐old patient presented with a nonfebrile, pruritic, widespread eruption that appeared 10 days after starting therapy with cefuroxime tablets, 1000 mg/day, due to stasis dermatitis with secondary infection. The patient was also treated with paracetamol tablets,

Risk Factors for Incomplete Excision of Basal Cell Carcinomas

Incomplete excision of basal cell carcinomas (BCCs) may be followed by recurrence of the tumor. In order to detect risk factors for incomplete excision of BCCs we performed a cross-sectional study of 1278 patients who underwent a primary excision of BCCs, during a four-year period, within an ambulatory and hospital plastic surgery department setting. Incomplete excision occurred in 159 of 1478 primary excisions of BCCs (10.8%) and was significantly associated with location of the tumors in the eyelids (OR 3.64, 95% CI 1.96-6.71), ears (OR 2.51, 95% CI 1.25-4.94), naso-labial folds (OR 2.26, 95% CI 0.99-5.04) and nose (OR 1.88, 95% CI 1.30-2.71). There was an inverse association with location of the tumors in the upper limbs (OR 0.44, 95% CI 0.21-0.90), back (OR 0.12, 95% CI 0.02-0.48) or chest (OR 0.09, 95% CI 0.00-0.57). Baso-squamous differentiation was associated with incomplete excision of BCCs (p = 0.03). No association was observed between incomplete excision of BCCs and gender, age, setting of the operation (ambulatory vs. hospital), clinical appearance of the lesion (suspected BCCs vs. other diagnoses) or diameter of the lesions. In conclusion, incomplete excision of BCCs was associated with location of the tumors in the eyelids, ears, naso-labial folds and nose. We recommend that in patients with BCCs located in these sites, surgeons should commence particular surgical measures to avoid inadequate excisions of the tumors.

Histological assessment of tangentially excised burn eschars

BACKGROUND The burn eschar serves as a medium for bacterial growth and a source of local and systemic infection. To prevent or minimize these complications, it is important to debride the eschar as early as possible. OBJECTIVE To identify the presence of viable skin within the excisions by examining tangentially excised burn eschars. METHODS A total of 146 samples of burned human tissue were removed during 54 routine sharp tangential excision procedures (using dermatomes). The samples were histologically examined to identify the relative thickness of the dead, intermediate and viable layers. RESULTS The mean (± SD) thickness of the excised samples was 1.7±1.1 mm. The sacrificed viable tissue (mean thickness 0.7±0.8 mm) occupied 41.2% of the entire thickness of the excision. In 32 biopsies (21.8%; 95% CI 16.0 to 29.3), the excision did not reach viable skin. Only eight biopsies (5.4%; 95% CI 2.8 to 10.1) contained all of the necrotic tissue without removing viable tissue. CONCLUSIONS The thickness of a single tangentially excised layer of eschar is not much greater than the actual thickness of the entire skin and often contains viable tissue. Because surgical debridement is insufficiently selective, more selective means of debriding burn eschars should be explored.

Cherry angiomas associated with exposure to bromides.

Cherry angiomas are the most common vascular proliferation; however, little is known about the pathogenesis and etiology of these lesions. We present two laboratory technicians who were exposed to brominated compounds for prolonged periods and who developed multiple cherry angiomas on the trunk and extremities. We suggest that the association between exposure to bromides and cherry angiomas should be investigated by a controlled study.

Risk factors for incomplete excision of squamous cell carcinomas

Objective: The aim of this study was to identify risk factors for incomplete excision of squamous cell carcinomas (SCCs). Patients and methods: A cross‐sectional study of 369 patients who underwent a primary excision of SCCs was performed within an outpatient and a hospital plastic surgery department setting. Results: Incomplete excision occurred in 25 of 369 primary excisions of SCC (6.8%). Location of the tumors on the forehead, temples, peri‐auricular region, ears, cheeks, nose, lips or neck was significantly associated with incomplete excision of the tumors. In particular, high incomplete excision proportions were observed for tumors located on the ears (16.7%), neck (16.7%), temples (11.1%), nose (10.8%) or lips (7.1%). Incomplete excision of SCC was associated with the setting of the operation in the hospital as compared to ambulatory settings (p = 0.046) and was inversely associated with the specimen thickness (p = 0.002). There was no statistically significant association between incomplete excision of SCC and gender, age, clinical appearance of the lesion (suspected SCC vs other diagnoses), differentiation pattern, diameter of the tumor, length or width of the excised specimen, solar changes or ulceration. Conclusion: We recommend that in patients with SCCs located in the forehead, temples, periauricular region, ears, cheeks, nose, lips or neck surgeons should commence particular surgical measures to avoid inadequate excisions of the tumors. In particular, surgeons should use wider excisional margins in tumors located in the embryonic fusion planes (e.g. eyelids and naso‐labial folds).

Treatment of multiple miliary osteoma cutis of the face with local application of tretinoin (all- trans retinoic acid): a case report and review of the literature

BACKGROUND Multiple miliary osteoma cutis of the face represents primary extra-skeletal bone formation that arises within the skin of the face. METHODS A 60-year-old woman with multiple miliary osteoma cutis of the face was treated by application of 0.05% tretinoin (all-trans-retinoic acid) cream nightly. RESULTS After 3 months of therapy there were fewer papules and a decrease in size of remaining lesions. In a literature search, it was found that local application of tretinoin was successful and achieved a decrease in the number of papules over the face in all patients with multiple miliary osteoma cutis of the face; however, the length of time to achieve response varied from a few weeks to 6 months. CONCLUSION It is suggested that local application of tretinoin cream should be considered in the therapy of multiple miliary osteoma cutis of the face, particularly when the lesions are small and superficial.BACKGROUND: Multiple miliary osteoma cutis of the face represents primary extra-skeletal bone formation that arises within the skin of the face. METHODS: A 60-year-old woman with multiple miliary osteoma cutis of the face was treated by application of 0.05% tretinoin (all- trans -retinoic acid) cream nightly. RESULTS: After 3 months of therapy there were fewer papules and a decrease in size of remaining lesions. In a literature search, it was found that local application of tretinoin was successful and achieved a decrease in the number of papules over the face in all patients with multiple miliary osteoma cutis of the face; however, the length of time to achieve response varied from a few weeks to 6 months. CONCLUSION: It is suggested that local application of tretinoin cream should be considered in the therapy of multiple miliary osteoma cutis of the face, particularly when the lesions are small and superficial.

Development of a Novel Animal Burn Model Using Radiant Heat in Rats and Swine

OBJECTIVES The objective was to develop a novel animal model of burns in rats and pigs. METHODS The model uses heat that is delivered via a radiant heater with an opening of 5 cm by 5 cm, set at 400 degrees C, for 20 seconds. An advantage of this model is that the heating source does not come into direct contact with the animal, and the heat dispersion surrounding its center is very constant. The device was evaluated in 40 rats and seven pigs. With rats, three to four burns were created on each rat, resulting in a burn covering a total body surface area of 30% to 50%. In pigs, 16 burns were created on each animal. RESULTS In rats, infliction of burns resulted in mortality rates of 0%-50% depending on the size of the burns and the rats. In pigs, the burns reepithelialized within approximately 3 weeks and resulted in hourglass contracted scars in two of three burns within 1 month. CONCLUSIONS The authors describe a novel animal burn model that utilizes radiant heat to create consistent burns that maximizes safety to the investigators and animals.

Unexpected location of pilonidal sinuses

Pilonidal sinuses usually occur in the sacrococcygeal area in young men, and occasionally can be found in other ectopic sites. We present a retrospective case review on unusual locations of pilonidal sinuses in the past 4 years. The lesion sites were as follows: one on the penis, two on the scalp, two on the abdomen, one on the neck, two in the groin and two in the axilla. Abdominal and penile lesions are uncommon, but the other locations reported are unusually rare. To our knowledge, the groin has not been reported previously as a site of a pilonidal sinus, although the histological appearance of hidradenitis suppurativa may well resemble it. When trying to clarify the pathogenesis of these occurrences, we found that recurrent hair removal was a common characteristic of the patients we contacted, and this may have been the initiating trauma.