Alitretinoin: a useful agent in the treatment of hidradenitis suppurativa, especially in women of child-bearing age.

AIM: Despite a better insight into its pathogenesis, hidradenitis suppurativa (HS) remains very frustrating to treat. Acitretin has been described as one of the agents with the highest effective profile. Acitretin however, due to its teratogenicity and prolonged half-life (up to three years) is not an option in young women of fertile age who, unfortunately, are the target of this disease. Alitretinoin has a similar pharmacology action to acitretin, but much shorter half-life (only four weeks), making it a far much more attractive option compared to acitretin for women of child-bearing age. The aim of this paper was to evaluate the use of alitretinoin in treating recalcitrant cases of HS, which have not been responsive to standard treatments. METHODS: Fourteen patients (all female, of child-bearing age), who persistently failed traditional treatments, were treated with alitretinoin 10 mg/day for 24 weeks. The disease trend was evaluated by using both Sartorius and Dermatology Life Quality Index scores at time 0, at week 12 and at week 24. RESULTS: A significant improvement was recorded in 78.5% of the cases. CONCLUSION: Although more studies are necessary, this preliminary study shows that alitretinoin may have a role in the treatment of HS specifically in women of fertile age.

Metformin for the treatment of hidradenitis suppurativa: a little help along the way.

BACKGROUND: Despite recent insights into its aetiology, hidradenitis suppurativa (HS) remains an intractable and debilitating condition for its sufferers, affecting an estimated 2% of the population. It is characterized by chronic, relapsing abscesses, with accompanying fistula formation within the apocrine glandbearing skin, such as the axillae, ano-genital areas and breasts. Standard treatments remain ineffectual and the disease often runs a chronic relapsing course associated with significant psychosocial trauma for its sufferers. OBJECTIVE: To evaluate the clinical efficacy of Metformin in treating cases of HS which have not responded to standard therapies. METHODS: Twenty-five patients were treated with Metformin over a period of 24 weeks. Clinical severity of the disease was assessed at time 0, then after 12 weeks and finally after 24 weeks. Results were evaluated using Sartorius and DLQI scores. RESULTS: Eighteen patients clinically improved with a significant average reduction in their Sartorius score of 12.7 and number of monthly work days lost reduced from 1.5 to 0.4. Dermatology life quality index (DLQI) also showed a significant improvement in 16 cases, with a drop in DLQI score of 7.6. CONCLUSION: Metformin helps control HS with minimal side effects and good patient compliance and can represent a further agent in the spectrum of treatments available in the treatment of this disease.

CTACK /CCL27 expression in psoriatic skin and its modification after administration of etanercept.

BACKGROUND: Tumour necrosis factor-alpha upregulates the expression of a cutaneous T cell-attracting chemokine (CTACK/CCL27), that promotes migration of cutaneous lymphocyte-associated antigen-positive lymphocytes into the skin. The role of CTACK/CCL27 in pathogenesis of psoriasis has recently been documented but no data are available at the present time on its modification in psoriatic cutaneous tissue after administration of etanercept. OBJECTIVES: To evaluate modifications of CTACK/CCL27 expression in skin of patients with psoriasis after administration of etanercept and their relation with disease activity. METHODS: Twenty-two patients with moderate to severe psoriasis underwent clinical, histological and immunohistochemical evaluations of disease activity at baseline and at 12 and 24 weeks after starting treatment with etanercept. RESULTS: All selected patients experienced an improvement of Psoriasis Area and Severity Index (PASI) score (P < 0.001) and Dermatology Life Quality Index score (P < 0.001) during the treatment. Skin histological abnormalities showed statistically significant modifications during treatment (P < 0.001). Immunohistochemical expression of CTACK/CCL27 decreased significantly (P < 0.001) and its relation with final PASI score was statistically significant (P < 0.05); the pattern of distribution of CTACK/CCL27 immunoreactivity significantly moved from diffuse and predominantly suprabasal to basal (P < 0.001) and the restoration of basal distribution of CTACK/CCL27 was also significantly related to clinical improvement of cutaneous disease (P < 0.001). CONCLUSIONS: Etanercept induces a clinical and histological improvement of psoriatic disease, promoting a reduction in CTACK/CCL27 cutaneous immunostaining and favouring the restoration of physiological CTACK/CCL27 epidermal expression. Moreover, CTACK/CCL27 reduction in cutaneous expression during administration of etanercept could be considered a favourable prognostic marker.

Old fashioned sodium bicarbonate baths for the treatment of psoriasis in the era of futuristic biologics: an old ally to be rescued.

BACKGROUND: For centuries, medicated baths have been one of the first lines of treatment for psoriasis. Even today, with sophisticated immunosuppressive treatments available, Dead Sea salts and spa waters are recognized to be beneficial in the management of psoriatic patients. OBJECTIVE: To assess statistically the efficacy of sodium bicarbonate (NaHCO3) baths in psoriasis patients. METHODS: Thirty-one patients with mild-moderate psoriasis were admitted to this study; Nineteen patients were treated with sodium bicarbonate baths and compared with twelve patients who were administered a placebo. Assessments were made on days 0 and 21. RESULTS: Almost all patients who used NaHCO3 reported a statistically valuable improvement. NaHCO3 baths reduced itchiness and irritation; in general, the patients themselves recognized a beneficial impact on their psoriasis, so much so that they have continued to bathe in NaHCO3 even after the end of the study. CONCLUSION: We maintain that even with sophisticated immunosuppressive and highly specific anti-cytokine and anti-chemokines treatments available for the treatment of psoriasis, an older and often forgotten treatment can still play a role.

Density of neoplastic lymphoid infiltrate, CD8+ T cells, and CD1a+ dendritic cells in mycosis fungoides.

BACKGROUND/AIMS: CD8+ T cells and epidermal/dermal dendritic cells expressing CD1a are found among neoplastic CD4+ T cells in mycosis fungoides (MF) lesions. This study analysed the relation of CD8+ tumour infiltrating lymphocytes (TILs), CD1a+ epidermal Langerhan's cells (LCs), and dermal dendritic cells (DDCs) to clinicopathological parameters in 46 MF cases. METHODS: Pretreatment diagnostic biopsy specimens of 46 MF cases were submitted to histological analysis and immunohistochemistry. Four histological grades were defined based on the density of the neoplastic infiltrate: grade 1 (mild superficial perivascular infiltrate), grade 2 (moderate superficial perivascular infiltrate with some tendency to confluence), grade 3 (pronounced superficial band-like infiltrate), and grade 4 (deep nodular infiltrate). Epidermotropism was scored as low, moderate, or high. Numbers of CD8+ T cells and of dermal and epidermal CD1a+ cells were scored as 1 (low), 2 (moderate), and 3 (high). Correlations between these parameters and clinical data (age, sex, clinical type of lesions, stage, response to treatment, and recurrence) were analysed by the chi(2) test. RESULTS: Numbers of TILs and DDCs were associated with subepidermal infiltrates, being lower in less dense infiltrates, whereas there was no association between epidermal CD1a+ cells and the analysed parameters. Complete remission in treated patients was related to subepidermal infiltrates but not to TILs, LCs, or DDCs. CONCLUSIONS: These results support the notion that CD8+ cells and dermal CD1a+ cells are active against tumour cells. MF with low numbers of TILs could represent an early stage of the disease, before TILs are activated against tumour specific antigens.

A clinicopathological study of 152 surgically treated primary gastric lymphomas with survival analysis of 109 high grade tumours.

AIMS: To describe the clinicopathological features of a large number of surgically treated and followed up primary gastric lymphomas and thereby gain a better understanding of their biology, with particular reference to the prognostic factors of high grade tumours. METHODS: A retrospective study of 152 patients. RESULTS: High grade gastric lymphomas, both pure and with a residual low grade component, differed from low grade mucosa associated lymphoid tissue (MALT)-type lymphomas in that they were more frequently large, ulcerated, at an advanced stage, and highly proliferating. In addition, patients were older and had a worse outcome. The prognosis of high grade lymphomas was influenced by patient age, tumour stage, depth of infiltration in the gastric wall, and the invasion of adjacent organs. Adjuvant postsurgical treatment prolonged survival only in patients with advanced stage and deep neoplastic infiltration. CONCLUSIONS: There is a sharp distinction between low grade MALT-type lymphomas and tumours with a high grade component, justifying their different treatment approach. The postsurgical management of high grade lymphomas should be based on the accurate evaluation of the neoplastic extension.

Cutaneous carcinomas and preinvasive neoplastic lesions. Role of MMP-2 and MMP-9 metalloproteinases in neoplastic invasion and their relationship with proliferative activity and p53 expression.

BACKGROUND: Metalloproteinases (MMPs) are thought to be involved in the process of destruction of basement membranes and stromal invasion by neoplastic epithelial cells. AIMS: In order to investigate the role of MMPs in cutaneous oncogenesis we studied the expression of MMP-2 and MMP-9 in 34 cases of epidermal preinvasive neoplastic lesions and invasive carcinomas. We also studied their relationship with the expression of tissue inhibitors of MMPs and with proliferative activity and p53 expression in neoplastic epithelial cells. RESULTS: MMP-9 was found to be focally expressed by neoplastic epithelial cells at the infiltrative edges in microinvasive carcinomas and in dyskeratotic foci in Bowen's disease and widely invasive carcinomas. Gradation of Mib-1 positivity and p53 expression was found with increasing abnormality in the spectrum of malignancy. CONCLUSIONS: Our results seem to suggest the involvement of MMPs in microinvasive carcinomas, which show also low proliferative activity and p53 expression, whether other factors seem to be more important in widely invasive carcinomas.

Ploidy, proliferative activity, p53 and bcl-2 expression in bronchopulmonary carcinoids: relationship with prognosis.

Bronchopulmonary well-differentiated neuroendocrine carcinoma (WDNEC) represents a more aggressive neoplasm than does typical carcinoid. Its biological behavior is variable and cannot be predicted on the basis of histopathological features. Nineteen typical carcinoids and 23 WDNECs were studied in order to obtain multiple parameters that should be used in the differential diagnosis between these two lesions and as prognostic markers of WDNEC. Flow-cytometry was performed on paraffin-embedded sections. Mutant p53 protein, the bcl-2 oncoprotein and the Ki-67 antigen were detected by immunohistochemical methods and evaluated quantitatively. WDNEC was more frequently aneuploid than typical carcinoid, had a higher percentage of Ki-67 positive nuclei and presented more frequently the mutant p53 protein. In WDNEC, the mutant p53 (p = 0.001), the bcl-2 oncoprotein (p = 0.002) and the high expression (> or = 16%) of Ki-67 (p = 0.0021) were associated with poor prognosis. The prognostic significance of mutant p53 and bcl-2 oncoprotein could be confirmed by Cox multiple regression survival analysis (p = 0.0005). It seems to be advisable to evaluate these features for the management of the patients affected by WDNEC.

Normal echocardiographic characteristics of the Sorin Bicarbon bileaflet prosthetic heart valve in the mitral and aortic positions.

Doppler echocardiographic characteristics of normally functioning Sorin Bicarbon prostheses were prospectively assessed in 226 consecutive patients (135 male and 91 female patients, mean age 61 +/- 10 years) with 233 valves in the mitral (n = 67) and aortic (n = 166) positions whose function was considered normal by clinical and echocardiographic evaluation. Patterns of "normal" transprosthetic leakage were assessed with transthoracic echocardiography in all valves and with transesophageal echocardiography in six selected mitral valve prostheses. For the mitral valve prostheses, we found that peak and mean gradient, as well as pressure half-time, were not significantly different in either the 25 or the 31 mm valves (median values from 15 to 10 mm Hg, from 4 to 4 mm Hg, and from 70 to 83 ms; p = Not significant for all). On transthoracic study, 12 patients (17%) with a Sorin Bicarbon valve in the mitral position showed minimal transprosthetic leakage. On transesophageal study, all patients showed a transprosthetic leakage whose spatial distribution had a complex pattern: in planes orthogonal to the leaflet axis, two to four jets arising from the hinge points and converging toward the center of the valve plane could be visualized; in planes parallel to the leaflet axis, there were three jets, the two lateral ones diverging and the central one perpendicular to the valve plane. For the aortic valve prostheses, there was a significant decrease in transprosthetic gradients and an increase in effective orifice areas as prosthesis size increased. Peak and mean gradients decreased from a median value of 25 and 13 mm Hg in the 19 mm valves to 9 and 5 mm Hg in the 29 mm valves, respectively. Effective prosthetic valve area calculated with the continuity equation increased from a median value of 0.97 cm2 for the 19 mm size valves to 3.45 cm2 for the 29 mm size. With analysis of variance, effective prosthetic aortic valve area differentiated various valve sizes (F = 40.9, p < 0.0001) better than peak (F = 10.3, p < 0.0001) or mean (F = 8.04, p < 0.0001) gradients alone did. Furthermore, effective prosthetic aortic valve area correlated better than peak and mean gradients with prosthetic size (r = 0.76, r = -0.45, and r = -0.39, respectively). On transthoracic study, 109 patients (66%) showed minimal transprosthetic leakage. These normal values, obtained in a large number of patients with normofunctioning mitral and aortic Sorin Bicarbon valves, may help to identify Sorin Bicarbon prosthesis dysfunction.

A flow cytometric study of early gastric cancer. The detection of high proliferative activity adds important information to the prognosis.

The prognostic value of DNA ploidy and proliferative activity has been rarely investigated in early gastric carcinoma (EGC). In the present study the ploidy pattern and cell cycle related parameters were evaluated in formalin-fixed paraffin-embedded specimens of 71 followed-up EGCs and compared with that of 20 advanced gastric carcinomas (AGC) using flow cytometry. The results showed that ploidy pattern did not affect patient outcome. On the contrary, EGC with a high S-phase had a worse prognosis. No significant differences in proliferative activity were detected between EGC and AGC. Fatal EGC had an S-phase higher than AGC. In conclusion, proliferative activity seems to affect the prognosis of EGC independent of the stage and could contribute to the identification of aggressive types of EGC.

Long-term follow-up in early gastric cancer: evaluation of prognostic factors.

Four hundred and fourteen cases of early gastric cancer (EGC), diagnosed between 1977 and 1993, were studied. The percentage of EGC increased from 1977 to 1984, but thereafter remained more or less stable, despite a continuous increase in the number of endoscopic examinations. Three hundred and ninety-six patients were followed up. Twenty-nine patients died from the tumour, giving a 5-year survival rate of 82.8 per cent. The 'large' size type of EGC, the presence of submucosal penetration, and lymph-node metastasis showed a highly significant association with a lower survival rate. A small number of patients died despite the presence of 'favourable' prognostic factors. Other still unknown factors may therefore be important in determining the aggressive behaviour of certain EGCs.

Natural killer cell activity in patients with invasive cervical carcinoma: importance of a longitudinal evaluation in follow-up.

OBJECTIVE: To analyze longitudinally the basal natural killer cell activity in patients with invasive cervical carcinoma, the natural cytotoxicity was related to the most important known prognostic factors, and evaluated with respect to the clinical outcome of cervical disease. MATERIALS AND METHODS: Forty-six patients with histologically proven invasive cervical carcinoma treated and followed at the Institute of Gynecology and Obstetrics, Ancona University, Salesi Hospital, were consecutively recruited from 1989 to 1992 and included into the study. For immunologic investigation, natural killer cell activity and peripheral blood T-lymphocyte subsets were tested before primary treatment and during the follow-up period, every 6 months. Natural killer activity was determined by target cell retention of the fluorescent dye carboxyfluorescein diacetate; the K 562 cell line was used as target cells. RESULTS: A significant inverse relationship was observed between natural killer activity and disease stage (p = 0.001); patients with stage IV disease had the lowest level of natural cytotoxicity. The reduction of natural cytotoxicity was not accompanied by any alteration of lymphocyte distribution. The longitudinal analysis showed an increase of natural killer activity after surgical removal of the tumor, persisting during the follow-up, but all the 9 patients who recurred showed, at the time of disease recurrence, a significant decrease of their natural cytotoxic potential. CONCLUSION: Natural killer cell activity seems to be a functional index of immune status, significantly related to the stage and the clinical outcome of disease.

Gastric dysplasia: a ten-year follow-up study.

The results of a ten-year follow-up study on gastric dysplasia (GD) are reported. A total of 260 cases were diagnosed, 125 of which had an adequate follow-up, 81 Low Grade Dysplasia (LGD) and 44 High Grade Dysplasia (HGD). Patients with LGD were younger than patients with HGD, while no significant difference in the mean age was found between HGD and carcinoma. LGD regressed in 49.4% of cases, persisted in 18.5% and progressed in 32.1%. HGD regressed in 4.6%, persisted in 13.6% and progressed in 81.8%. In some cases dysplasia reappeared after a long-time interval of apparent regression. In 58 cases progression to cancer was observed: in 35 cases dysplasia was associated with carcinoma (8 LGD and 27 HGD), while in 23 cases dysplasia evolved into carcinoma (14 LGD and 9 HGD). There was a good correlation between the accuracy in following up the patients and the chance of diagnosing the carcinoma at an early stage. The importance of gastric dysplasia as a marker for carcinoma, its precancerous nature and the treatment of the patients are discussed.

Epithelial dysplasia of the gastric mucosa. A morphometric and ploidy pattern study.

60 cases of gastric dysplasia (20 mild, 20 moderate and 20 severe) were quantitatively studied and compared with cases of hyperplastic polyp (No 10), intestinal metaplasia (No 20), peptic ulcer (No 10) and invasive adenocarcinoma (No 20). In each case the area, the perimeter and the integrated optical density of 100 nuclei were measured in Feulgen stained tissue sections by means of a Leitz TAS. The stepwise discriminant analysis demonstrates that severe dysplasia and adenocarcinoma can be well distinguished from mild and moderate dysplasia. The ploidy pattern study demonstrates that the presence of severe dysplastic changes corresponds to a sharp increase in the degree of aneuploidy. In peptic ulcer, intermediate values between "benign" and "malignant" lesions were found.

Quantitative study of the precancerous and malignant lesions in colorectal adenomas.

150 endoscopically removed colorectal adenomas are quantitatively studied. In 90 cases dysplastic glands constituted the entire lesion (30 mild, 30 moderate, 30 severe); in 60 cases foci of adenocarcinoma were present (30 intramucosal, 30 submucosal). In each case the area, the perimeter and the integrated optical density of 100 nuclei were measured from Feulgen-stained paraffin sections. The results show a continuous neoplastic progression in the trends of the morphometric parameters as well as in the ploidy pattern. The stepwise discriminant analysis defined the morphometric features of the atypical nuclei, which were present in small numbers also in mild dysplasia; they progressively increased in number, reaching the maximum in submucosal carcinoma.

[Emergency surgical treatment of infectious endocarditis. Experience developed on 19 consecutive cases]. / Terapia chirurgica di urgenza dell'endocardite infettiva. Esperienza svolta su 19 casi consecutivi.

Our experience with the emergency surgical treatment of 19 consecutive cases of infective endocarditis (IE) is reported. The aortic valve was always affected, either alone (n = 16) or together with the mitral valve (n = 3). All patients were male. In 10 cases it was possible to identify the infecting agent (a staphylococcus was found in 6). Congestive heart failure (CHF) was the principal indication for surgery in 14 cases (in 6 active IE was associated). Five patients (1 with CHF) underwent operative treatment because of systemic emboli. Fifteen patients were in New York Heart Association (NYHA) functional class IV, 3 in class III and 1 was in class II. Two patients (10.5%), both operated on for CHF, died in the early postoperative period. Early prosthetic valve dehiscence occurred in 2 cases, reoperation was successful in both. Follow-up of operative survivors ranges between 7 and 108 months (mean = 53.24 +/- 41.89). One patients died 10 months after operation with CHF following late prosthetic dehiscence. Out of 16 currently surviving patients 14 are in NHYA functional class I, 1 is in class II and 1 in class III. No one of them has had relapse of IE.