Rolland Gyulai

Electrochemotherapy of cutaneous metastases of melanoma - A case series study and systematic review of the evidence

OBJECTIVES Electrochemotherapy (ECT) is a novel therapeutic option for the treatment of cutaneous and subcutaneous metastases of malignant melanoma. During the treatment, electric pulses are applied to tumor nodules to deliver nonpermeant or poorly permeant chemotherapeutic agents into the cells, increasing local cytotoxicity of anticancer drugs. We compared the clinical effectiveness of ECT as an alternative palliative treatment option for unresectable metastatic lesions of malignant melanoma with a systematic review of reported outcomes. METHODS One hundred fifty-eight cutaneous and subcutaneous metastases of nine patients were treated with ECT. All treatments were performed under general anesthesia using intravenous bleomycin injection. Median follow-up was 195 days. RESULTS In our case series, complete response rate was 23%, and partial response rate was 39%. We observed no change in 30% and progressive disease in 8% of cases. CONCLUSIONS ECT is a simple and effective treatment of single or multiple cutaneous and subcutaneous metastases of melanoma with minimal side effects. Our results provide further data for the growing body of evidence in recently published studies that ECT used for palliation has clinical benefit. The authors have indicated no significant interest with commercial supporters.

Kaposi’s sarcoma–associated herpesvirus/human herpesvirus-8: A new virus in human pathology☆☆☆

The discovery of a new human herpesvirus in Kaposis sarcoma (KS) tissue of patients with AIDS has opened up new vistas in virology and oncology. This herpesvirus was first descriptively named KS-associated herpesvirus (KSHV), but was recently renamed human herpesvirus 8 (HHV8). KSHV/HHV8 DNA has been found in all forms of KS, suggesting that it might be involved in the pathogenesis of KS. In addition, KSHV/HHV8 can be detected in both malignant and benign lymphoproliferative disease. KSHV/HHV8 was also found in patients with angiosarcoma of the face and angiolymphoid hyperplasia with eosinophilia. Although only a limited portion of the virus has been sequenced, KSHV/HHV8 is equipped with genes that could confer oncogenic potential. The virus can now be cultured, providing the possibility for studies of viral replication and the mode of transmission. The recently developed serologic assays for antiviral antibodies suggest that infection with KSHV/HHV8 is not ubiquitous because KSHV/HHV8 seropositivity is limited to a small proportion of the population.

Utility of serum TNF-α, infliximab trough level, and antibody titers in inflammatory bowel disease

AIM To assess tumor necrosis factor-α (TNF-α), infliximab (IFX) concentrations, and antibodies against IFX molecules in patients with inflammatory bowel disease (IBD) who develop loss of response, side effects, or allergic reaction during anti TNF-α therapy. METHODS Blood samples of 36 patients with response loss, side effects, or hypersensitivity to IFX therapy (Group I) and 31 patients in complete clinical remission (Group II) selected as a control group were collected to measure trough serum TNF-α level, IFX, and anti-IFX antibody (ATI) concentration. We examined the correlation between loss of response, the development of side effects or hypersensitivity, and serum TNF-α, IFX trough levels, and ATI concentrations. RESULTS The serum TNF-α level was shown to be correlated with the presence of ATI; ATI positivity was significantly correlated with low trough levels of IFX. ATIs were detected in 25% of IBD patients with loss of response, side effects, or hypersensitivity, however no association was revealed between these patients and antibody positivity or lower serum IFX levels. Previous use of IFX correlated with the development of ATI, although concomitant immunosuppression did not have any impact on them. CONCLUSION On the basis of the present study, we suggest that the simultaneous measurement of serum TNF-α level, serum anti TNF-α concentration, and antibodies against anti TNF-α may further help to optimize the therapy in critical situations.

Drug-induced erythema multiforme-like bullous pemphigoid.

Sir, Bullous pemphigoid (BP) is a common autoimmune blistering disease in the elderly, with an early manifestation of urticarialike and pruritic erythematous lesions which subsequently lead to the formation of bullae. The diagnosis is con¢rmed by the histological and immuno£uorescence ¢ndings (1). Despite its autoimmune origin, some reports demonstrate a clear induction of BP by PUVA and drugs (2). We report here a case in which BP was induced by antipsychotics and antidepressant drugs. During the recovery period, doxycycline was observed to exert a positive e¡ect on the BP.

Photodynamic Therapy of Non-melanoma Skin Cancer with Methyl Aminolaevulinate is Associated with Less Pain than with Aminolaevulinic Acid

© 2012 The Authors. doi: 10.2340/00015555-1223 Journal Compilation

Higher levels of autoantibodies targeting mutated citrullinated vimentin in patients with psoriatic arthritis than in patients with psoriasis vulgaris.

Antibodies against citrullinated proteins/peptides (ACPAs), and especially antibodies targeting mutated citrullinated vimentin (anti-MCVs), are novel biomarkers of rheumatoid arthritis (RA). Whereas ACPAs are specific and sensitive markers for RA, there have hardly been any reports relating to ACPAs in psoriatic arthritis (PsA) or in psoriasis without joint symptoms (PsO). The aim of the present study was to investigate the prevalence of anti-MCVs in PsA and PsO. Serum anti-MCV titers were measured in 46 PsA and 42 PsO patients and in 40 healthy controls by means of a commercial enzyme-linked immunosorbent assay. The potential correlations of the serum autoantibody levels with several clinical and laboratory parameters were examined. The anti-MCV levels in the PsA patients were significantly higher than those in the PsO group. Among the clinical variables, the presence of tender knee joints and nail psoriasis was significantly associated with anti-MCV positivity in the PsA patients. Higher anti-MCV titers in the PsO patients were associated with a more severe disease course and with the early onset of psoriatic skin symptoms. Our results suggest that anti-MCVs can be used as novel markers in the diagnosis of PsA and in a subset of PsO patients.

Successful treatment of multiple basaliomas with bleomycin-based electrochemotherapy: a case series of three patients with Gorlin-Goltz syndrome.

Gorlin-Goltz syndrome is a rare multisystemic disease, characterized by numerous basal cell carcinomas. The ideal approach for patients with the syndrome would be a treatment with a high cure rate, minimal scarring, short healing time and mild side-effects. Electrochemo-therapy is a novel therapeutic option that ablates tumours with electrical current and simultaneously administered anticancer drugs. Three patients with Gorlin-Goltz syndrome were treated with electrochemotherapy using intravenous bleomycin. Clinical response was obtained in 98 (99%) of the lesions, 86 (87%) of them showed complete response. In 2 tumours, regression was confirmed with histological examination. Long-term cosmetic results were excellent. We consider electrochemotherapy to be an additional tool in the therapeutic armamentarium for Gorlin-Goltz syndrome, and suggest using it as early as possible in selected patients to avoid disfiguring scarring.

Smoking as a permissive factor of periodontal disease in psoriasis

Background Population-based studies have identified smoking as a pathogenetic factor in chronic periodontitis. At the same time, chronic periodontal disease has also been found to occur more often in persons suffering from psoriasis than in controls with no psoriasis. It is known that smoking aggravates both periodontal disease and psoriasis, but so far it has not been investigated how smoking influences the occurrence and severity of periodontal disease in psoriasis. Methods A hospital-based study was conducted to investigate this question. The study population consisted of 82 psoriasis patients and 89 controls. All patients received a full-mouth periodontal examination, and a published classification based on bleeding on probing, clinical attachment level and probing depth was utilized for staging. Both patients and controls were divided into smoker and non-smoker groups, and the resulting groups were compared in terms of periodontal status. Beyond the descriptive statistics, odds ratios were computed. Results Psoriasis in itself increased the likelihood of severe periodontal disease to 4.373 (OR, as compared to non-smoker controls, p<0.05), while smoking increased it to 24.278 (OR, as compared to non-smoker controls, p<0.001) in the studied population. In other words, the risk of severe periodontal disease in psoriasis turned out to be six times higher in smokers than in non-smokers. Conclusions The results of this study corroborate those of other studies regarding the link between psoriasis and periodontal disease, but they also seem to reveal a powerful detrimental effect of smoking on the periodontal health of psoriasis patients, whereby the authors propose that smoking may have a permissive effect on the development of severe periodontal disease in psoriasis.

Interleukin-1 receptors are differentially expressed in normal and psoriatic T cells

This study was carried out to examine the possible role of interleukin-1 (IL-1) in the functional insufficiency of regulatory T cells in psoriasis, by comparing the expression of IL-1 receptors on healthy control and psoriatic T cells. Patients with moderate-to-severe chronic plaque psoriasis and healthy volunteers, matched in age and sex, were selected for all experiments. CD4+CD25− effector and CD4+CD25+CD127low regulatory T cells were separated and used for the experiments. Expression of the mRNA of IL-1 receptors (IL-1R1, IL-1R2, and sIL-1R2) was determined by quantitative real-time RT-PCR. Cell surface IL-1 receptor expression was assessed by flow cytometry. Relative expression of the signal transmitting IL-1 receptor type 1 (IL-1R1) mRNA is higher in resting psoriatic effector and regulatory T cells, and activation induces higher IL-1R1 protein expression in psoriatic T cells than in healthy cells. Psoriatic regulatory and effector T cells express increased mRNA levels of the decoy IL-1 receptors (IL-1R2 and sIL-1R2) upon activation compared to healthy counterparts. Psoriatic T cells release slightly more sIL-1R2 into their surrounding than healthy T cells. In conclusion, changes in the expression of IL-1 receptors in psoriatic regulatory and effector T cells could contribute to the pathogenesis of psoriasis.

Fluorescence diagnosis of non-melanoma skin cancer

Photodynamic therapy involves - in dermatological practice usually exogenous - application of a photosensitizer then activation of accumulated protoporphyrin IX by light with an appropriate wavelength after a short incubation period. It is an evidence based method to treat certain non-melanoma skin cancers. During treatment when the excited protoporphyrin IX returns to base state, reactive oxygen species are formed leading to cell death in rapidly proliferating cells. Fluorescence of excited protoporphyrin IX can be used in diagnostics as well. In ultraviolet light, the photodamaged or neoplastic areas show coral red fluorescence which can clearly be distinguished from the much lower fluorescence of adjacent normal tissue. This process is suitable for exact determination of tumor margins so it can be used for planning surgical procedures or after photodynamic therapy at a follow up visit for the visualization of the therapeutic result. The present article reviews the literature of photodynamic diagnosis that is also used by the authors.