Tumor heparanase expression in predicting response to induction chemotherapy in patients with locally advanced laryngeal cancer.

PURPOSE: Induction chemotherapy is a feasible alternative to surgery for the treatment of locally advanced laryngeal cancer. Determining predictive factors associated with a better response to chemotherapy would help choose the patients most likely to benefit from larynx preservation. METHODS: Eighty-four patients diagnosed with locally advanced laryngeal cancer (stage III-IV) between April 1999 and May 2006 were retrospectively reviewed. Eightytwo of them received 2 cycles and 2 received only 1 cycle of cisplatin and 5-fluorouracil (5-FU) chemotherapy. Patients were then grouped, based on response to treatment, as either having complete response (CR), partial response (PR), stable (SD) or progressive disease (PD). Factors predicting response to treatment were evaluated. Paraffin blocks were immunohistochemically examined for heparanase activity to see for any link between heparanase expression and response to treatment. RESULTS: There were 73 males and 11 females with a mean age of 59 years. After induction chemotherapy (cisplatin and 5-FU), 33 patients achieved PR and 20 CR. SD and PD occurred in 9 and 21 patients, respectively. Patients with stage III disease had better overall (CR and PR) response rates when compared with those with stage IV disease. Moreover, development of bone marrow suppression and heparanase positivity were both associated with better overall response rates. CONCLUSION: This study supports the hypothesis that heparanase positivity is associated with better responses to induction chemotherapy, regardless of TNM stage. Furthermore, a higher overall response rate was observed in patients who developed myelosuppression secondary to chemotherapy.

Malignancy in Behçet's disease: a report of 13 cases and a review of the literature.

Behçet's disease (BD) has rarely been reported in association with malignant diseases. In most cases the autoimmune nature of the disease itself or immunosuppressive drug use has been blamed for malignant transformation. We report 13 cases of BD concurrent with neoplastic disease as well as treatment-related morbidities in this particular patient group. Between 1986 and 1999, 400 patients were diagnosed as having BD in Hacettepe University Hospitals. Of these 13 patients, 3.25% developed malignant diseases within a median follow-up time of 9.8 years. Solid tumors were diagnosed in 10 patients and haematological or lymphoid malignancies in three. Surgery was performed in seven patients, whereas radiotherapy was applied in six and chemotherapy in eight. A literature review revealed 27 cases of BD associated with malignancies, mostly lymphoid or haematological. Ten of our cases were solid tumors, and to our knowledge most of these are the first reported cases of specific malignancies concurrent with BD. Treatment-related morbidities were wound infection as surgical morbidity in one patient (1/7) and radiotherapy-related morbidity in three (3/6) patients in a median follow-up time of 2 years. Solid tumors in addition to lymphoid and haematological malignancies are also seen during the course of BD. Radiation therapy may cause severe late toxicities in the presence of BD. Chemotherapy and surgery are fairly safe for the treatment of malignancies in BD patients.

Why hepatocellular carcinoma cells are unlikely to metastasize: is there a role for tissue inhibitor of metalloproteinase-1?

The question 'Why hepatocellular carcinoma cells are unlikely to metastasize although they have a high proliferative activity?' is a major point of interest from a cancer physiopathological viewpoint. Recent articles about the roles and relationships of some cytokines with matrix degrading enzymes and their inhibitors in various types of normal tissues and malignancies give rise to another question: 'Does tissue inhibitor of metalloproteinase-1 prevent the extrahepatic metastasis of hepatocellular carcinoma cells?' On the basis of many evidences, it is highly probable that under the effect of a possible inducing mechanism of the cytokines interleukin-6, -1 beta and transforming growth factor beta, the increase in concentration of tissue inhibitor of metalloproteinase-1 in hepatocellular carcinoma cause increased type I collagen accumulation and consequent prevention of cellular detachment, which explains why highly proliferative malignant hepatocytes have less metastatic ability.

Is there a relationship between tissue inhibitor of metalloproteinase-1 and transforming growth factor-beta 1 with respect to malignant melanoma progression?

Recent articles about the roles and relationships of tissue inhibitor of metalloproteinase-1 and transforming growth factor-beta 1 in various types of normal tissues and malignancies give rise to the question: 'Is there a relationship between them with regard to malignant melanoma progression?' In the light of many references, it seems to be highly probable that the tissue inhibitor of metalloproteinase-1, -- being a multifunctional protein -- functions as a growth factor with possible stimulation by transforming growth factor-beta 1 in progression of malignant melanoma, rather than its other existing functions in many different normal and cancer tissues (e.g. inhibition of the matrix metalloproteinases or functioning as an insignificant inhibitor of angiogenesis).

Serum L-selectin and P-selectin levels in lymphomas.

The migration of normal and malignant lymphoid cells is governed by specific adhesion molecules. Selectins comprise a family of adhesion receptors expressed by leukocytes, platelets and endothelial cells. In this study, the serum levels of soluble L-selectin and P-selectin were measured in patients with non-Hodgkin's lymphoma and Hodgkin's disease and found to be significantly elevated in both patient groups compared to healthy controls. This result provides evidence that alterations in the expression and function of adhesion molecules may play an important role in the progression of lymphomas. Further studies are awaited to establish the exact roles of these adhesion molecules in distinct patterns of growth and spread of lymphomas.

Primary breast lymphomas--a retrospective analysis of twelve cases.

This study was undertaken to define the natural history and treatment results of patients with primary breast non-Hodgkin's lymphoma (NHL). Twelve female patients who had been followed at Hacettepe University Hospital between 1973 and 1997 were retrospectively evaluated. All patients presented with breast masses (6 in the right breast and 6 in the left) that had recently enlarged. The most common histologic subtype was diffuse, small cleaved-cell lymphoma. Chemotherapy regimens were employed in 9 patients. Radiotherapy was delivered to the breast and its lymphatics in 8 patients. Lumpectomy, simple or modified radical mastectomy was performed in 5 cases. An objective response was attained with surgery, chemotherapy, or radiotherapy alone in 2, 1, and 1 cases, respectively. Combined modality treatment including either two or three modalities was successful in 7 cases. The median progression-free and overall survival times were 49 and 56 months, respectively. Although primary NHL of the breast is a rare disease compared to carcinoma, it should be considered in the differential diagnosis of breast masses.

Circulating intercellular adhesion molecule-1 and E-selectin levels in gastric cancer.

A diversity of adhesive interactions occur between the cancer cell and host extracellular matrix which potentiate neoplastic expansion and metastatic dissemination. In miscellaneous malignant diseases, tumour progression has been observed to be associated with alterations in adhesion molecule expression. Recently, circulating soluble intercellular adhesion molecules have been identified. In this study, serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble E-selectin (sE-selectin) were determined in patients with gastric cancer. The study group consisted of 27 patients with previously untreated gastric adenocarcinoma. Four patients had stage II, two patients stage III and 21 patients stage IV disease according to the TNM classification. Nineteen patients had distant metastasis. The sera obtained from 18 healthy volunteers served as controls. Serum sICAM-1 and sE-selectin concentrations were determined by enzyme-linked immunosorbent assay (ELISA). In addition, we also studied other tumour-associated antigens, i.e. CEA and CA 19-9. Serum sICAM-1 levels were significantly increased in patients with gastric cancer (P < 0.0001). However, sE-selectin levels did not differ from the controls. sICAM-1 concentrations were also significantly higher in patients with distant metastasis and peritoneal spread (P = 0.0045 and P = 0.0157 respectively), whereas sE-Selectin levels were elevated only in patients with peritoneal metastasis (P = 0.033). Serum concentrations of sICAM-1 and sE-selectin correlated with CEA levels (P = 0.0013 and P = 0.003 respectively). Elevated levels of sE-selectin were associated with poorer prognosis (P = 0.0099), whereas sICAM-1 had no significant impact on survival. Our results suggest that increased sICAM-1 serum levels may reflect widespread disease and contribute directly to the progression of gastric cancer. Further investigation of the molecular mechanisms of adhesive tumour-host interactions may lead to a better understanding of the natural history of gastric cancer.

A comparison of two nonsteroidal antiinflammatory drugs (diflunisal versus dipyrone) in the treatment of moderate to severe cancer pain: a randomized crossover study.

The efficacy of diflunisal in cancer pain was evaluated and compared with dipyrone. Diflunisal was given at the dosage of 500 mg perorally twice a day, and dipyrone was given at the dosage of 500 mg perorally three times a day. Duration of each treatment was 7 days; after a 12-hour wash-out period, patients were given the other drug for another 7 days. A total of 50 patients were enrolled in the study. Pain intensity was assessed by 10-point visual analog scale (VAS). Patients who had a VAS score higher than 5 were included. A total of 47 patients were evaluable. Initial VAS score was a mean of 8.57+/-1.33. Diflunisal reduced the pain score by a mean of 4.65+/-3.10, whereas dipyrone reduced the pain score by a mean of 3.25 < or = 2.85 (p < 0.001). Patients were also analyzed in three subgroups according to the presence of nonmetastatic, metastatic, and bone metastatic diseases. In each of these subgroups, diflunisal reduced the pain score more than dipyrone; however, the difference was statistically significant only in patients who had bone metastasis. Adverse reactions were rare and acceptable with both drugs. Diflusinal is superior to dipyrone at this dosage and schedule in the treatment of moderate to severe cancer pain.

Hippocratic fingers in Behçet's disease.

Digital clubbing has been a well recognised feature of several distinct clinical conditions, including respiratory, cardiac, and gastrointestinal diseases since the Hippocratic era. However, clubbing associated with Behçet's disease has not been reported before. We describe a case of clubbing in a young man with Behçet's disease, in the absence of any other apparent aetiology and propose that clubbing might be an accompanying feature of Behçet's disease.