iloprost and Adenocarcinoma

Systemic sclerosis (SSc) is a chronic disease of unknown etiology which affects the vascular system and connective tissue. A wide series of studies showed an increased prevalence of cancer in patients with SSc than the normal population. Prostacyclin (PGI2) is an endogenously produced element that is basically synthesized by arachiodonic acid through prostacyclin synthesis in vascular system endothelial cells. Iloprost is a stable analogue of PGI2 which is used in the treatment of pulmonary arterial hypertension (PAH). In a limited number of animal models, the anti-metastatic activity of PGI2 is observed. Herein, we report iloprost treatment of a 60-year-old-woman with SSc, who lately developed PAH as a complication of her disease and lung adenocarcinoma as a co-incidence simultaneously. These two mortal complications were both treated successfully with inhaled iloprost until her death due to gastrointestinal complications of SSc.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Administration, Inhalation; Antihypertensive Agents; Antineoplastic Agents; Biopsy; Disease Progression; Familial Primary Pulmonary Hypertension; Fatal Outcome; Female; Gastrointestinal Diseases; Humans; Hypertension, Pulmonary; Iloprost; Immunohistochemistry; Lung Neoplasms; Middle Aged; Multimodal Imaging; Positron-Emission Tomography; Scleroderma, Systemic; Tomography, X-Ray Computed; Treatment Outcome; Vasodilator Agents

We report one new case of hemolytic-uremic syndrome (HUS) and one case of digital necrosis after treatment with gemcitabine (Gemzar). Case 1, a 34-year-old man, was given first-line metastatic treatment with gemcitabine for a adenocarcinoma of the pancreas. After a cumulative dose of 10 000 mg/m2 gemcitabine, the onset of subacute renal failure associated with hemolytic anemia of mechanical origin was observed. A diagnosis of probable gemcitabine-induced thrombotic microangiopathy was arrived at. Symptoms resolved after stopping the chemotherapy, in spite of the progression of the disease. Case 2, a 61-year-old man, was administered a combination of gemcitabine and a platinum salt as first-line metastatic treatment for carcinoma of the bladder urothelium. Following a cumulative dose of 10 000 mg/m2 of gemcitabine, the patient suffered from bilateral peripheral vascular disease of somewhat acute onset with hemorrhagic lesions of the finger pads that became necrotic. The work-up was negative and a causal relationship was attributed to gemcitabine. The patient made good progress when given an i.v. infusion of Ilomedine (iloprost trometamol) and chemotherapy was withdrawn. We conclude that gemcitabine must be added to the list of drugs that cause HUS and necrotizing vasculitis.

Topics: Adenocarcinoma; Adult; Antimetabolites, Antineoplastic; Carcinoma, Transitional Cell; Deoxycytidine; Fingers; Gangrene; Gemcitabine; Hemolytic-Uremic Syndrome; Humans; Iloprost; Male; Middle Aged; Pancreatic Neoplasms; Urinary Bladder Neoplasms; Vasodilator Agents

The properties of specific prostaglandin I2 (prostacyclin, PGI2) binding sites in normal thyroid tissue have been characterised. Tissue samples obtained intraoperatively from patients with 'cold' solitary thyroid nodules (as preoperatively selected by thyroid gland scintigraphy, thyroid gland ultrasonography and Papanicolaou cytology following fine needle aspiration of the nodule area) have been used for thyroid membrane preparation. Employing [3H]iloprost, a chemically stable PGI2-analogue as a radioligand, saturation experiments for comparative binding studies have been attempted. Scatchard analysis of the binding data obtained for normal thyroid parenchyma distant to the nodule area revealed heterogeneity of the [3H]iloprost sites exhibiting a high-affinity binding capacity (Bmax) of 613.2 +/- 130.4 fmol mg-1 membrane protein and a low-affinity binding capacity of 5.1 +/- 1.6 pmol mg-1 membrane protein. The equilibrium dissociation constant (Kd) amounted to 18.9 +/- 8.9 nM and to 131.5 +/- 39.2 nM, respectively. Scatchard analysis of the binding data obtained for benign thyroid adenoma indicated significant lower binding capacities exhibiting a Bmax of 325.8 +/- 110.0 fmol mg-1 membrane protein (Kd: 31.0 +/- 7.5 nM) for the high-affinity sites and of 3.9 +/- 2.5 pmol mg-1 membrane protein (Kd: 364.9 +/- 183.6) for the low affinity sites. In cancer tissue a selective loss of the low affinity sites and a significant diminution of the high-affinity sites was observed: in well differentiated cancer the high-affinity sites showed a Bmax of 299.7 +/- 46.0 fmol mg-1 membrane protein (Kd: 38.9 +/- 7.3 nM), in anaplastic cancer, less differentiated papillar and follicular cancers of 180.6 +/- 25.1 fmol mg-1 membrane protein (Kd: 54.6 +/- 16.7 nM). Well differentiated papillar and follicular cancers did not differ from each other.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenocarcinoma; Adenoma; Adult; Aged; Aged, 80 and over; Carcinoma; Epoprostenol; Female; Humans; Iloprost; Male; Middle Aged; Receptors, Prostaglandin; Thyroid Neoplasms