Erythema nodosum.

Erythema nodosum is an acute inflammatory dermatosis characterized by painful nodules which are generally symmetrical and non ulcerative and are mainly located to the extensor surface of the lower legs. The nodules, due to septal panniculitis, are often accompanied by fever and resolve without permanent sequelae. Arthralgia occurs in more than 50% of patients and begins during the eruptive phase or precedes the eruption by 2-4 weeks. Erythema nodosum is presumed to be a hypersensitivity reaction and may occur in association with several systemic diseases or drug therapies, or it may be idiopathic. The most common cause of erythema nodosum is streptococcal infection in children and streptococcal infection and sarcoidosis in adults. Peak incidence occurs at age 18-34 years. Age and sex distributions vary according to etiology and race; women are affected more often than men. It is possible to distinguish between an acute and a chronic form of erythema nodosum; in the acute form, an early stage and a late stage can be detected, both clinically and histologically. Laboratory and instrumental examinations to be performed in case of erythema nodosum are varied and are intended to identify any underlying trigger disease. Erythema nodosum is a self-limited disease, so the therapy is often only symptomatic. Even if the erythema nodosum quickly responds to systemic steroids, in most cases their use is not recommended, nor necessary; is usually sufficient to use NSAIDs (eg, acetyl salicylic acid, ibuprofen, naproxen, indomethacin).

Superficial acral fibromyxoma: a clinicopathological and immunohistochemical analysis of 12 cases of a distinctive soft tissue tumor with a predilection for the fingers and toes.

AIM: Superficial acral fibromyxoma (SAFM) is a rare soft tissue tumor, recently delineated and documentated as a separate entity. We report 12 cases of SAFM observed in our department from June 2004 to June 2010 and highlight pathological features and differential diagnosis. METHODS: Radiographic examination of the affected digit was performed in all patients. All the tumors were surgically excised under local anesthesia. Follow-up was made every 6-8 months for a maximum period of five years. RESULTS: The patients consisted of 8 men and 4 women, age range 28-76 years (mean 51), presenting with a solitary mass or nodule located in the toes and fingers. Histologically the lesions were well circumscribed dermal nodules composed of stellate and spindle cells, arranged in a myxoid matrix. Very low grade atypia and a few mitotic figures were found in only one case. Neoplastic cells showed immunoreactivity for CD34 (12 patients). In contrast focally positive or negative staining was shown for the epithelial membrane antigen (EMA) and CD 99. Actin, S100 protein, HMB45 and cytokeratin were negative. In three cases marked hyperkeratosis and acanthosis of the epidermis was present. Pathological analysis confirmed the diagnosis of superficial acral fibromyxoma. No recurrences were observed even in a long term, 2-5 year follow-up. CONCLUSION: Complete surgical excision of the tumors and a careful follow-up is suggested, despite the benign course previously reported.

Circulating levels of soluble intercellular adhesion molecule-1 in non-small cell lung cancer patients.

Intercellular adhesion molecule-1 has been implicated in tumor progression and metastasis. Like soluble forms of other membrane receptors, a circulating form of intercellular adhesion molecule-1 (sICAM-1) has been identified in the serum of healthy subjects and it has been found in malignant diseases at increased levels. This study evaluated the serum concentration of sICAM-1 in 112 patients with non-small cell lung cancer (NSCLC). Soluble ICAM-1 levels were significantly higher in all patients when compared with the controls; serum concentration of sICAM-1 correlated with clinical stage and tumor progression. These results suggest that elevated levels of serum ICAM-1 could be of prognostic importance in patients with NSCLC.

Serum levels of interleukin-6 as a prognostic factor in advanced non-small cell lung cancer.

Serum levels of interleukin-6 (IL-6) were evaluated in a group of advanced non-small cell lung cancer (NSCLC) patients using an enzyme-linked immunosorbent assay. The data were related to clinical status and to cisplatin-based chemotherapy response. The mean IL-6 concentrations were higher than the controls (p<0.0001); patients with metastatic tumor had higher levels than those with undisseminated disease (p<0.006). Tumor progression was associated with an increase of IL-6 levels. Patients who responded to chemotherapy had lower serum IL-6 levels compared with unresponsive patients (p<0.0001). These data suggest that NSCLC patients with high levels of IL-6 have a worse clinical outcome and may manifest resistance to cisplatin chemotherapy.

Amifostine: A selective cytoprotective agent of normal tissues from chemo-radiotherapy induced toxicity (Review).

Patients receiving systemic cancer chemotherapy must often have their dose intensity of therapeutic agents reduced, because a broad range of organs are adversely affected. Therefore, research and the development of agents protecting the normal tissues from the toxicity of antineoplastic therapy, without reducing the antitumour efficacy, are very important. Amifostine, a prodrug that forms an activated free thiol, when dephosphorylated by alkaline phosphatase, appears selective in its entry in non-malignant cells, and exerts a protective effect from toxicity induced by chemo- or radiotherapy on normal tissues, through free radical scavenging, hydrogen donation and inhibition of DNA damage. Studies in vitro and experimental models have confirmed the protective properties of amifostine in normal cells. In clinical trials pretreatment with amifostine reduced the frequency of cyclophosphamide induced neutropenia and nephro-, oto- and neurotoxicity of platinum compounds. In some cases the use of amifostine have also potentiated the effects of several drugs, such as alkylating agents and, in recent studies, taxanes. The main potentially dose-limiting adverse effect is hypotension, that is often asymptomatic. Amifostine is thus usefully employed in order to obtain a better quality of life in patients receiving oncologic treatments.

Analysis of recovery time indexes in 5-fluorouracil-treated cancer patients.

Based on our previous experience in doxorubicin-treated patients, in whom we observed a significant increase of ventricular recovery time indexes, we analyzed these non- invasive parameters of myocardium electrical instability in forty-three 5-fluorouracil-treated patients, to test the hypothesis of a mechanoelectrical disarrangement occurring in 5-fluorouracil (5FU) cardiotoxicity. All patients enrolled were studied at the first presentation and following chemotherapy. The study showed the absence of any significant changes in recovery time indexes or in other electrocardiographic parameters. Our data suggest that 5FU does not interfere with electrical properties of myocardial fibers.

Increased serum levels of tumor necrosis factor-alpha are correlated to soluble intercellular adhesion molecule-1 concentrations in non-small cell lung cancer patients.

Tumor necrosis factor (TNF)-alpha has been shown to induce shedding of ICAM-1. Experimental studies report that soluble intercellular adhesion molecule-1 (sICAM-1) may interfere with the host immunesurveillance system. Serum levels of TNF-alpha and sICAM-1 were determined by ELISA in 112 non-small cell lung cancer (NSCLC) patients. Serum concentration of TNF-alpha and sICAM-1 were related to tumor burden and progression; a significant correlation was observed between circulating levels of TNF-alpha and sICAM-1. Our study suggests that ICAM-1 could be a marker of TNF-alpha activity and that high levels of these molecules may have a prognostic value in lung cancer.

Soluble interleukin-2 receptor and soluble CD8 antigen levels in serum from patients with solid tumors.

High levels of soluble lymphocyte antigens have been described in a large number of tumors and, particularly, in hematopoietic neoplasms. As previously reported, many antitumor immune responses are IL-2 dependent: clinical observations indicate that a worse survival in advanced tumor patients is related with a decrease of soluble IL-2 levels. A soluble form of CD8 has been described: as found in Hodgkin's disease and acute lymphoblastic leukemia, sCD8 levels have a prognostic value. To explain the significance of these soluble molecules in solid tumors, we a) determinated sIL-2R and sCD8 in 84 patients; b) correlated the expression of p55 chain of IL-2R and CD8 antigen on the cell-surface of peripheral lymphocytes to sIL-2R and sCD8 levels; c) analyzed endogenous IL-2R levels in patients with lung cancer. An increase of sIL-2R was found in 82% of cases, while high levels of sCD8 were observed in 32%; no correlation was observed between sIL-2R and the expression of p55 on the surface of peripheral lymphocytes: IL-2 levels in patients with NSCLC were significatively reduced, when compared to healthy controls, with an inverse relationship between endogenous IL-2 concentration and sIL-2R levels. Whatever may be the physiopathological mechanism of the increase of sIL-2 observed in solid tumors, this rise may contribute to the immunodepression correlated to neoplastic disease. Therefore, higher levels of sIL-2R/IL-2 ratio has a negative biologic prognostic significance. We think that determinating CD8 antigen in the serum can offer a more sensitive and specific measurement of activation of suppressor/cytotoxic T-lymphocytes.

A pilot study of adjuvant chemotherapy with double modulation of 5-fluorouracil by methotrexate and leucovorin in gastric cancer patients.

BACKGROUND: Thirty-four patients with gastric cancer in stage II and III were enrolled, after curative resection, in a pilot study to assess the feasibility and the impact on relapse of a double modulation of 5-Fluorouracil (5FU) by Methotrexate (MTX) and 1-Leucovorin (LFA) as adjuvant chemotherapy. METHODS: The schedule was: MTX 500 mg/m2d. 1, LFA 250 mg/m2d.2, 5FU 600 mg/m2d.2. Cycles were repeated every two weeks for 16 times. Quality of life during treatment was evaluated with the EORTC QLQ-C30. RESULTS: At a median follow-up of 24 months, 21 (61%) patients treated with postoperative chemotherapy, were disease-free. Toxicity was primarily gastrointestinal, but its intensity was usually mild. The feasibility of treatment was also confirmed from the results of QLQ-C30 questionnaire. CONCLUSIONS: This study demonstrates that the schedule tested is feasible as postoperative treatment in curatively resected gastric cancer patients and prompts the initiation of a randomized trial with a no-treatment control arm.

Serum concentrations of proinflammatory cytokines in advanced non small cell lung cancer patients.

To assess the relationship between serum concentrations of proinflammatory cytokines and prognosis of non small cell lung cancer (NSCLC), we evaluated the serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1-beta (IL-1-beta) and interleukin-6 (IL-6) in 60 patients with untreated advanced NSCLC. Mean cytokines concentrations in patients were significantly higher than in the control population. Patients with metastatic disease had higher levels than those with undisseminated disease. Finally, in patients with tumor progression we observed an increase of cytokines serum levels. These results suggest that in NSCLC elevated serum levels of proinflammatory cytokines may have prognostic value being associated with a worse prognosis.

A phase II study of biweekly oxaliplatin plus infusional 5-fluorouracil and folinic acid (FOLFOX-4) as first-line treatment of advanced gastric cancer patients.

The aim of the study was to assess the toxicity and the clinical activity of biweekly oxaliplatin in combination with infusional 5-fluorouracil (5-FU) and folinic acid (FA) administered every 2 weeks (FOLFOX-4 regimen) in patients with advanced gastric cancer (AGC). A total of 61 previously untreated AGC patients were treated with oxaliplatin 85 mg m(-2) on day 1, FA 200 mg m(-2) as a 2 h infusion followed by bolus 5-FU 400 mg m(-2) and a 22 h infusion of 5-FU 600 mg m(-2), repeated for 2 consecutive days every 2 weeks. All patients were assessable for toxicity and response to treatment. Four (7%) complete responses and 19 partial responses were observed (overall response rate, 38%). Stable disease was observed in 22 (36%) patients, with progressive disease in the other six (10%) patients. Median time to progression (TTP) and median overall survival (OS) were 7.1 and 11.2 months, respectively. National Cancer Institute Common Toxicity Criteria grade 3 and 4 haematologic toxicities were neutropenia, anaemia and thrombocytopenia in 36, 10 and 5% of the patients, respectively. Grade 3 peripheral neuropathy was recorded in three (5%) patients. FOLFOX-4 is an active and well-tolerated chemotherapy. Response rate (RR), TTP and OS were comparable with those of other oxaliplatin-based regimens, suggesting a role for this combination in gastric cancer.

Behaviour of interleukin-2 serum levels in advanced non-small-cell lung cancer patients: relationship with response to therapy and survival.

Interleukin(IL)-2 is a T helper (Th) 1 type cytokine that has been shown to play an important role in antitumour immune responses. In this study, the prognostic significance of serum IL-2 levels was investigated in 60 advanced non-small-cell lung cancer (NSCLC) patients. IL-2 serum levels were determined before chemotherapy, at the end of chemotherapy and during follow-up, using a commercially available enzyme-linked immunoadsorbent assay kit. The results were analysed according to the response to therapy and were used to generate a model predicting overall survival and time to treatment failure. All 60 patients were shown to have higher IL-2 serum levels than controls (P < 0.0001). Stage IV patients had significantly lower IL-2 levels than stage III patients (P < 0.0001), although they were still significantly higher than controls (P < 0.0001). It is interesting that, when patients were divided into responders and non-responders according to the response to therapy, the former were shown to have significantly higher pre-chemotherapy levels than the latter (P < 0.0001). Moreover, a further significant increase in IL-2 serum levels (P = 0.004) and a significant decrease (P < 0.0001) were shown in responders and non-responders, respectively at the end of the therapy. Using univariate and multivariate analyses, both overall survival and time to treatment failure were shown to be affected by the mean pathological levels of IL-2. Furthermore, the prognostic significance of the serum level of IL-2 was confirmed by the stepwise regression analysis. In conclusion, determination of pre-treatment IL-2 serum levels was shown to be of independent prognostic utility in patients with advanced NSCLC; therefore, its possible use for prediction of outcome is proposed.

Serum interleukin-10 levels in patients with advanced gastrointestinal malignancies.

BACKGROUND: Interleukin-10 (IL-10) is a cytokine with immunosuppressive properties. In this study, the authors investigated the prognostic significance of IL-10 levels in the sera of 58 patients with advanced gastric or colorectal carcinoma. METHODS: IL-10 serum levels were measured before chemotherapy, on completion of chemotherapy, and at follow-up by means of a commercially available enzyme-linked immunoadsorbent assay kit. The results then were analyzed in comparison with other prognostic variables and a model predicting overall survival (OS) and time to disease progression (TTP) was generated. RESULTS: Elevated levels of serum IL-10 were found in carcinoma patients compared with healthy controls (19.6 +/- 6.8 pg/mL vs. 9.2 +/- 1.5 pg/mL; P < 0.0001), with those patients with metastatic disease showing significantly higher levels than patients with undisseminated disease (21.9 +/- 6. 7 pg/mL vs. 15.5 +/- 3.6 pg/mL; P = 0.0003). Retrospective analysis of prechemotherapy IL-10 serum levels showed a significant difference between responders and nonresponders (15.8 +/- 2.5 pg/mL vs. 21.6 +/- 7.6 pg/mL; P < 0.0001). Moreover, a further significant increase in IL-10 serum levels was observed in nonresponders at the end of therapy (21.6 +/- 7.6 pg/mL prechemotherapy vs. 31.3 +/- 11.6 pg/mL postchemotherapy; P < 0.0001) whereas no significant differences were observed in responders. Using univariate analysis, both OS and TTP were shown to be affected by the median pathologic levels of IL-10; multivariate analysis related to OS and TTP identified performance status and IL-10 serum level as the relevant prognostic factors, respectively. Finally, stepwise regression analysis identified IL-10 serum level and metastases as the prognostic factors related to both OS and TTP. CONCLUSIONS: The results of the current study show that measurement of pretreatment serum levels of IL-10 is of independent prognostic utility in patients with advanced gastrointestinal carcinoma and may be useful for the detection of disease progression.