Sigma 2 receptor expression levels in blood and bladder from healthy and bladder cancer cattle.

The expression of sigma-2 receptor (S2R) was assayed in blood and bladder samples from healthy cattle and in blood and bladder of cattle with deltapapillomavirus-associated urothelial tumors. Samples of bladder from cattle with neoplasia had significantly higher S2R than samples of bladder from healthy cattle (95% CI 0.31-0.82, P < 0.05). In addition, significantly higher S2R was detected in the blood of cattle with bladder cancer than blood from healthy cattle (95% CI 0.22-0.41, P < 0.05). The results provide evidence that increased expression of SR2 in blood could be useful as circulating biomarker for bladder cancer in cattle. PGRMC1 protein levels were also found to be increased in blood and bladder from cattle with cancer and increased expression of PGRMC1 transcripts was detected by quantitative real time PCR in samples from cattle neoplasia. Furthermore, electron microscopy revealed phagophores and numerous autophagosomes, ultrastructural hallmark of autophagy.

Activatable fluorescent probes: a new concept in optical molecular imaging.

Activatable fluorescent probes share the unique feature of being turned on only under specific conditions: they are "silent" when not interacting with a specific target protein, microenvironment, or reactive species. Several activatable fluorescence probes have demonstrated their potential in cell biology study, disease study and diagnosis, and even in the rapidly expanding field of image-guided surgery. In this review, we will summarize progress in the design of activatable probes and their application in studying cell biology or in optical imaging. Some of the most effective examples of activatable fluorescent probes will be presented and their application will be discussed.

[Loco-regional fibrinolysis in the treatment of acute, non-traumatic ischemia of an artery. Use of PTFE, homologous vein, and Dacron in the treatment of acute thrombosis]. / La fibrinolisi loco-regionale nel trattamento dell'ischemia acuta non traumatica di un arto. Utilità nella trombosi acuta di bypass in PTFE, vena omologa e Dacron.

The acute thrombosis of a bypass graft can always be a common and challenging problem for the vascular surgeon, since surgical revascularization procedures can often result in failure, limb loss and infection. Since over the past 15 years literature reports emphasize the efficacy of intraarterial thrombolytic therapy (IATT) in achieving clot lysis and initial patency of thrombosed arteries and grafts, the purpose of this study is to verify if IATT with urokinase represents a valid alternative procedure to surgery. From our experience of 18 cases of lower limb ischemia, 9 of which graft thrombosis and 9 native artery occlusions, 3 cases of acute thrombosis of lower extremity bypass grafts, successfully treated with IATT are considered. After arteriography proof of lower extremity artery or bypass graft occlusion, thrombolytic therapy with urokinase was delivered at a rate of 100,000 UI/hour for 24/48 hours. At the conclusion of the thrombolytic treatment, percutaneous transluminal angioplasty (PTA) was performed on any residual stenosis of the bypass graft. In all three cases complete clot lysis within 48 hours was obtained, with patency of the bypass graft at two years follow-up. Urokinase in our experience, has always given good results. In many cases restoration of normal blood flow was obtained in bypass grafts thrombosed a three days. Urokinase has also been helpful in defining the causes of the occlusion (stenosis proximal or distal to the bypass) or of the anastomosis itself. Regional urokinase thrombolytic therapy, even if expensive, represents a primary tool for the vascular surgeon, since excellent results may be obtained, especially in cases where surgery is of high risk.

Mitoxantrone in the treatment of recurrent ascites of pretreated ovarian carcinoma.

In this study we treated 19 patients with relapsed ovarian cancer with malignant peritoneal effusion. All patients were previously treated with cisplatin-containing regimens. Intraperitoneal mitoxantrone was administered at a dosage of 20-30 mg/mq repeated every 28 days if ascites was still present. No patient was treated with systemic chemotherapy during the study. In 15 of 19 patients progressive ascites reduction was obtained. Moreover, in 4 of 15 responsive patients, a progressive reduction of the quantity of ascites was observed even though the abdominal masses demonstrated an increase in volume. Serum concentrations of Mitoxantrone (MXN) were determined, in ten patients, by high performance liquid chromatography with spectrophotometric detection, and low serum levels (1-30 ng/ml) with a maximum at the first or second hour were revealed. In conclusion, in patients with ovarian carcinoma and recurrent neoplastic ascites, palliative treatment with mitoxantrone was effective and well tolerated. The reduction of ascites and frequency of paracentesis represents a marked advantage for these patients and improves their quality of life.

Accelerated chemotherapy with mitoxantrone plus g-csf in heavily pretreated patients with metastatic breast-cancer.

Twenty-two women with metastatic breast cancer, previously submitted to one or more lines of chemotherapy, were treated with mitoxantrone as single agent delivered at full dosage (14 mg/m(2)) every other week (accelerated chemotherapy). This dose was possible with concomitant subcutaneous administration of granulocyte colony stimulating factor (G-CSF) on days 5 to 12 of each 14 day cycle. Although grade III-IV leukopenia, anemia and thrombocytopenia were observed in 50%, 13%, and 27% of cases, respectively, a complete recovery of neutrophils, due to G-CSF administration, permitted on time cycle delivery in the majority of cases. Partial response was observed in 6/22 patients (27%). In conclusion, accelerated chemotherapy with mithoxantrone plus G-CSF is both feasible and effective for patients with previously treated breast cancer.

Bulky mediastinal Hodgkin's disease: results of a combined modality approach (ABVD/MOPP alternating chemotherapy plus radiation therapy).

BACKGROUND: Bulky mediastinal involvement is a challenging presentation of Hodgkin's disease (HD). Radiotherapy alone has provided a good response rate but also a high percentage of recurrences, and therefore many studies have been initiated to evaluate combined modality treatment. METHOD: In a prospective study 23 stage IIA/IIIB HD patients treated with ABVD/MOPP alternating chemotherapy and radiotherapy were evaluated with regard to overall (OS) and disease-free survival (DFS), acute and long-term toxicity. RESULTS: A 95% CR rate was obtained. Ten-year actuarial OS and DFS were 83 and 91%, respectively. Two patients (8.8%) relapsed 8 and 9 months after achieving CR. One patient (4.4%) died following severe bone marrow failure 25 months after diagnosis. No clinically evident acute or chronic cardiac or pulmonary toxicity was evident, and no second malignancies were observed. At the end of therapy 7/14 evaluable women became amenorrheal and remained so at their last follow-up. Two male patients were considered azoospermic on the basis of laboratory evaluation at the end of therapy, and after 68 and 122 months, respectively; 4 of 5 male patients had sexual intercourse freely but did not fertilize their partners. CONCLUSIONS: In our opinion and in agreement with available literature, chemotherapy has a fundamental place alongside radiotherapy in the treatment of bulky mediastinal HD. Combined modality treatment improves the disease-free survival obtained with radiotherapy or chemotherapy alone. In our experience a high percentage of patients (83%) can be considered cured without the need for second-line therapy. However, long-term and especially gonadal toxicity greatly influence the quality of life of these patients. Therefore treatment must be personalized according to age, sex, cardiopulmonary status and desire to preserve reproductive function.

M-VECA (methotrexate, vinblastine, epidoxorubicin and carboplatin) in the treatment of advanced urothelial carcinoma.

AIMS AND BACKGROUND: Urothelial cancer is a chemosensitive disease. However, cisplatin or anthracycline-containing regimens still provoke severe toxicity mainly due to reduced renal function and poor performance status (PS) of patients. The aim of this study was to verify the possibility of substituting carboplatin for cisplatin and epirubicin for doxorubicin in the M-VAC regimen in order to reduce toxicity and improve patient tolerance. METHODS: Twenty patients with advanced urothelial tract tumors were treated with a chemotherapeutic regimen composed of methotrexate (30 mg/mq iv on days 1, 15, 22), vinblastine (3 mg/m2 iv on days 2, 15, 22), epidoxorubicin (35 mg/m2 iv on day 2) and carboplatin (250 mg/m2 iv on day 2) every four weeks (M-VECA). All patients had bidimensionally measurable disease. RESULTS: Of the 18 evaluable patients, 3 (17%) obtained complete response and 7 (33%) obtained partial response (50% overall response). The median duration of response was 50 weeks (range, 28-88+). Grade III-IV toxicity (leukothrombocytopenia and mucositis) was observed in 20% of cases. Nevertheless, recovery was prompt in all but 2 patients with poor PS who died of nadir sepsis. CONCLUSIONS: M-VECA was an effective regimen for the treatment of patients with metastatic urothelial tumors and was safely employed in patients with a good PS. However, the possibility of substituting carboplatin for cisplatin as neoadjuvant therapy for less advanced stages needs further investigation in randomized studies.

Fec (Fluorouracil, epirubicin, cyclophosphamide) plus granulocyte macrophage-colony-stimulating factor (gm-csf) in advanced or inflammatory breast-cancer - a dose-finding study.

Seven patients with inflammatory and 11 with metastatic breast cancer were treated with high dose FEC chemotherapy plus GM-CSF; 5-fluorouracil and cyclophosphamide were administered at 500 mg/m2/iv/day 1, epirubicin at three dose levels: 100 mg, 120 mg and 140 mg/m2/iv/day 1 every three weeks (six patients per level). GM-CSF was administered at a dosage of 5 mg/kg/sc from day 5 to 12 of each cycle. The overall response rate was 83% (95% CI: 66%-100%) with 22% complete response. The median response duration for patients with metastatic disease was 7 months (range: 4-10). The hematological toxicity was moderate but reversible due to GM-CSF rescue; mucositis represented the dose limiting toxicity. In conclusion, the increase of dose intensity resulted in a higher response rate but not longer response duration, which must be taken into account when administering high-dose chemotherapy with growth factor rescue.

Prognostic relevance of ploidy and proliferative activity evaluation by flow cytometry in poor prognosis non-Hodgkin's lymphomas.

The DNA content and S-phase fraction (SPF) of pathological paraffin-embedded lymph node tissue from 47 patients with poor prognosis non-Hodgkin's lymphoma (NHL) were analyzed by flow cytometry (FCM). Fifteen of 42 evaluable cases proved to be aneuploid. The DNA aneuploidy was not correlated with age, histology, stage, presence of systemic symptoms, clinical response or overall survival (OS) of patients. Mean SPF evaluated in 35 cases was 22.9%. After 78 months of follow-up, nine patients with diploid low SPF tumors had a significantly longer disease-free survival (DSF) with respect to the group of patients (33 cases) with aneuploid or diploid high SPF tumors (100% vs 59%; log rank test, p = 0.04).

Metastatic involvement of the stomach secondary to breast carcinoma. A case report.

The Authors describe a case of gastric metastases from breast cancer. The staging procedures in breast cancer do not usually include the endoscopic examination of the gastroenteric tract; nevertheless the complaint of persistent gastric disorders in patients affected by metastatic breast cancers must not be underestimated. In this case the finding of gastric neoplastic involvement led to effective treatment of the above mentioned disorders and consequently to an improvement in the patient's quality of life. Moreover, the evaluation of this clinical case shows that chemotherapeutic treatment of this metastatic localisation does not differ from that of metastases in other sites.

Ifosfamide plus mitoxantrone as salvage treatment in non-Hodgkin's lymphomas.

Twenty-two patients affected by relapsed or refractory non-Hodgkin's lymphoma (NHL) were treated with a combination of ifosfamide (IFO) at the dose of 1.2 g/m2 intravenous (i.v.) (1 h infusion) for 5 consecutive days with mesna as uroprotector plus mitoxantrone (NOV) at the dose of 12 mg/m2 i.v. on day 1; both drugs were recycled every 3-4 weeks. Of 21 evaluable patients, overall response observed was 57% (38% complete response and 19% partial response with a median duration of response of 7 months (5-23+). Dose-limiting toxicity was represented by leukopenia (grade III-IV in 43% of cases); severe thrombocytopenia was observed less frequently (grade III-IV in 19% of cases). This hematologic toxicity prevented administration of therapy every 3 weeks as initially planned. However, the complete hematological recovery, usually observed at the fourth week, permitted therapy administration to all patients without dose reduction. Low-grade lymphomas responded to treatment as well as intermediate or high grade lymphomas. Moreover, patients treated with third- or fourth-line chemotherapy also responded. However, response was observed in 11/13 (85%) relapsed patients as compared to 2/8 (25%) refractory cases. The combination of IFO plus NOV is active in heavily pretreated patients with NHL. Nevertheless, the study of a larger number of patients is necessary to better define the exact role of this combination as "salvage" therapy for NHL.

[Rupture of the pericardium caused by closed thoracic injuries]. / Rottura del pericardio da trauma chiuso del torace.

Rupture of the pericardium due to closed thoracic trauma is a very rare event which is hard to diagnose. It occurs in the form of two main clinical pictures: 1) severe chest trauma with massive haematoma requiring surgery and which permits diagnosis, and 2) precordial pain and clinical signs of pericardiac origin. Surgery is essential in view of the risk of lethal complications from cardia luxation. Operation consists of closure of the pericardiac lesion.

[Benign tumors of the stomach]. / I tumori benigni dello stomaco.

Personal experience in cases of benign tumour of the stomach is presented. Diagnosis cannot be based on the clinical evidence alone, but must be supported by radiological examination and, more particularly, by endoscopic biopsy. Endoscopic resection and continuous follow-up examinations provide an alternative to radical surgery and gastrotomic resection.

[Stenosis of the left angle of the colon caused by chronic pancreatitis]. / La stenosi dell'angolo sinistro del colon da pancreatite cronica.

Case of stenosis of the left flexure of the colon caused by pancreatitis is reported. The relevant literature is surveyed and an account is given of the pathogenesis of this forms, and the examinations required in its diagnosis, particularly coloscopy. A preference is expressed for an internal colic derivation (colon-colon anastomosis) rather than resection, on account of the smaller degree of risk involved.