Multi-centre phase II clinical trial of yttrium-90 resin microspheres alone in unresectable, chemotherapy refractory colorectal liver metastases.

BACKGROUND: This multi-centre phase II clinical trial is the first prospective evaluation of radioembolisation of patients with colorectal liver metastases (mCRC) who failed previous oxaliplatin- and irinotecan-based systemic chemotherapy regimens. METHODS: Eligible patients had adequate hepatic, haemopoietic and renal function, and an absence of major hepatic vascular anomalies and hepato-pulmonary shunting. Gastroduodenal and right gastric arteries were embolised before hepatic arterial administration of yttrium-90 resin microspheres (median activity, 1.7 GBq; range, 0.9-2.2). RESULTS: Of 50 eligible patients, 38 (76%) had received > or =4 lines of chemotherapy. Most presented with synchronous disease (72%), >4 hepatic metastases (58%), 25-50% replacement of total liver volume (60%) and bilateral spread (70%). Early and intermediate (>48 h) WHO G1-2 adverse events (mostly fever and pain) were observed in 16 and 22% of patients respectively. Two died due to renal failure at 40 days or liver failure at 60 days respectively. By intention-to-treat analysis using Response Evaluation Criteria in Solid Tumours, 1 patient (2%) had a complete response, 11 (22%) partial response, 12 (24%) stable disease, 22 (44%) progressive disease; 4 (8%) were non-evaluable. Median overall survival was 12.6 months (95% CI, 7.0-18.3); 2-year survival was 19.6%. CONCLUSION: Radioembolisation produced meaningful response and disease stabilisation in patients with advanced, unresectable and chemorefractory mCRC.

Malignant glucagonoma. New options of treatment.

Few cases of malignant glucagonomas have been described in the literature. In this paper we present a case of a 77-year-old woman with necrolytic migratory erythema and high plasma glucagon and chromogranin A levels caused by a neuroendocrine tumour. An abdominal CT scan suggested a pancreatic lesion and two liver metastases. The patient underwent pancreatic debulking and liver metastasectomy. Histological and immunohistochemical investigations revealed a well differentiated neuroendocrine tumour with vascular invasion and scattered immunopositivity for somatostatin receptors. The patient was treated with octreotide (20 mg i.m. every 28 days) for three years without side effects. Three months after surgery symptoms of disease recurred accompanied by hyperglucagonaemia and newly diagnosed liver lesions. The patient was treated with octreotide (30 mg i.m. every 28 days) and interferon-alpha (6 MU s.cc 3 times per week) plus three cycles of hepatic chemoembolisation. Symptoms resolved after the first month of therapy, hormone levels decreased compared to untreated levels and metastatic growth slowed as observed by radiographic evidence. The patient is now asymptomatic with persistent hepatic disease and normal serum glucagon levels forty months after primary treatment. So far, only few immunohistochemical studies are reported on malignant glucagonoma and combined treatment schedules. We demonstrated, for the first time, a scattered immunopositivity for somatostatin receptors in a malignant glucagonoma. For this reason, the somatostatin analogs therapy was instituted. A combined antiproliferative medical treatment and the hepatic chemoembolization have been able to control tumor growth and disease symptoms for a long time after surgery.

A multicentric phase II clinical trial on intra-arterial hepatic radiotherapy with 90yttrium SIR-spheres in unresectable, colorectal liver metastases refractory to i.v. chemotherapy: preliminary results on toxicity and response rates.

BACKGROUND: In patients locally progressing after two lines of chemotherapy, some locoregional approaches showed encouraging results in terms of local control of disease. The aim of our study was to evaluate toxicity, clinical response and quality of life in 48 patients with unresectable colorectal liver metastases submitted to selective internal radiotherapy (SIRT). MATERIALS AND METHODS: Up to now 35 patients with unresectable colorectal liver metastases, refractory to two lines of chemotherapy, underwent intra-arterial infusion of resin microspheres with yttrium-90 (SIR-spheres). Pre-treatment evaluation included a CT scan, blood tests, a PET scan and arteriography of celiac trunk, hepatic and superior mesenteric artery; extrahepatic uptakes and pulmonary shunts more than 10% were excluded by a Scinti-scan. The gastroduodenal artery was embolized before the SIR-spheres injection. Other exclusion criteria were liver dysfunction and anatomical vascular anomalies. The clinical response was evaluated by CT-scan following the RECIST criteria. Median follow-up was 4 months. RESULTS: Median number of metastases was 4 (range, 1-15), 38% of cases presenting hepatic involvement < 25%. The median SIRT dose delivered was 1.7 GBq. Median pulmonary shunt was 6%. No operative mortality occurred; early toxicity (within 48 hours) was 20.6%, shown as fever, acute pain and leucocytosis. The late toxicity was 24.1% with chronic pain, jaundice and nausea being the most frequent. All the toxic events were graded 2 or 3 according to the WHO scale. Preliminary results were available in terms of clinical response after 6 weeks: 12.5% had a partial response, 75% a stable disease, while progression of disease, was observed in 12.5% of the patients. CONCLUSION: SIRT is a safe treatment in terms of acute and late toxicity. Intra-arterial microspheres could represent a good therapeutic option for patients with progressing liver metastases only, after two lines of systemic chemotherapy.

Cranioplasty performed with a new osteoconductive osteoinducing hydroxyapatite-derived material.

OBJECT: Cranioplasty is required to protect underlying brain, correct major aesthetic deformities, or both. The ideal material for this purpose is autogenous bone. When this is not available, alloplastic or artificial materials may be used. These materials should be malleable, strong, lightweight, inert, noncarcinogenic, nonferromagnetic, and, if possible, inexpensive. The authors reviewed their surgical experience with a new bone substitute and discuss outcomes in patients in whom it was used. METHODS: The 11 patients presented in this series had bone defects resulting from bone-involving tumor (eight cases), trauma (two cases), or aesthetic deformity due to repeated craniotomies (one case). The defects were repaired using Osprogel, a bone substitute that consists of calcium hydroxyapatite combined with synthetic, human bone-derived gelatin, glycerol, and water. Osprogel is not only a bioinert material but also an osteoconductive and osteoinducing substrate; when it is placed in contact with healthy cancellous bone, it induces osteogenesis and angiogenesis, thus permitting the regrowth of nearly normal bone. The sheet of Osprogel was modeled onto the cranial defect intraoperatively and was kept in place either by using a titanium micronet secured to surrounding bone with microscrews (first two cases) or by using a single- or double-layer titanium mesh secured with stitches. No complications due to the procedure were observed. The results, evaluated at least 6 months after surgery by using three-dimensional (3-D) reconstructed computerized tomography scans, were excellent in seven patients, good in three, and fair in one. In the patient with a fair result, the repair was unsatisfactory because there was lack of experience in using the material. In part of the area to be repaired, the Osprogel was used as filler; here it was washed out and resorbed. The cases deemed as having a good result had good bone replacement; however, the curvature was faulty. CONCLUSIONS: In the near future, this technique may be refined to achieve good or excellent results either without the use of supporting material or with the use of individual, computer-designed 3-D prostheses.

A double-blind comparative study of the safety and efficacy of iomeprol in renal intra-arterial digital subtraction angiography.

This randomised, double-blind, parallel group study was to compare the safety, tolerance and diagnostic efficacy of iomeprol and iopamidol, both at an iodine concentration of 150 mgI/ml, in 40 patients with arterial hypertension who required renal intra-arterial digital subtraction angiography (IA-DSA) for suspected renovascular stenosis. All patients underwent extensive pre- and post-contrast clinical, instrumental and laboratory controls for safety assessments. The tolerance to the test contrast media was evaluated in terms of discomfort associated with the injection of the test compounds. Image quality was prospectively graded by two independent readers according to a five-point scale as follows: 1, insufficient; 2, sufficient; 3, good; 4, excellent; E, excessive. The quality of vascular opacification in the region of interest was rated as diagnostic in 87.8% of radiographs obtained in the iomeprol group and in 84.5% in the iopamidol group, without significant differences between the two study groups. The results of angiography were always useful for subsequent patient management. The procedure was always well tolerated. There were no clinically significant changes in vital signs, ECG and laboratory parameters during the study in both groups. The results of our study show that iomeprol 150 mgI/ml, and iopamidol 150 mgI/ml are equally effective, well tolerated and safe contrast agents when used for IA-DSA.

Evaluation of hepatic metastases from colorectal carcinoma with MR-superparamagnetic iron oxide.

The purpose of this study was to compare the results obtained with superparamagnetic iron oxide-enhanced and unenhanced Magnetic Resonance at 1.5 T with that of spiral-computed tomography (CT) in order to select those patients suitable for liver resection; the intraoperative US (IOUS) comprised the gold standard. Thirty five candidates for liver resection with known colorectal neoplasm were studied; 26 patients underwent surgery, one patient underwent RF ablation and 8 of them were submitted to follow-up. MR examination was performed using a 1.5 T superconductive instrument, CT examination was performed on a Somatom-Plus (Siemens) scanner. Dimensions and number of the lesions were defined in all patients as well as the sensitivity of spiral CT and MR imaging, using either the plain technique or after Ferumoxides c.m.. In those patients submitted to surgery, results have been correlated to those of IOUS. From 26 patients, a total of 48 lesions were removed surgically. With CT, 34 lesions with 3 false positive cases were detected; 32 with plain MR imaging, while MR imaging with Ferumoxides detected 41 lesions. In the patients not submitted to surgery, MR iron-oxide imaging identified 15 lesions, while both plain MR imaging and CT showed 8 lesions. The smallest lesion was 6 mm. as shown by MR imaging with Ferumoxides. In the cases submitted to surgery, the CT sensitivity was 71%, plain MR imaging 66% and MR imaging with Ferumoxides 85%. In our experience, Ferumoxides-enhanced MR imaging of the liver shows increased sensitivity compared to plain and spiral-CT in the evaluation of hepatic metastases. We think that MR superparamagnetic iron oxide should be used in all patients selected for liver resection.

Leiomyosarcomas of the small intestine misdiagnosed as ovarian masses: report of three cases.

Leiomyosarcomas of the small intestine are rare lesions. Because of their aspecific symptoms, diagnosis is often made at a late stage and, in women, must be distinguished from ovarian tumors. Three cases of large, abdominal masses, evaluated preoperatively as being ovarian tumors, are presented. At histology all three were diagnosed as leiomyosarcomas of the small intestine.

[Lipiodol chemoembolization in the treatment of hepatic carcinoma. Our experience]. / La chemioembolizzazione con Lipiodol nel trattamento del carcinoma epatico. Nostra esperienza.

Of the alternative methods of treatment to surgery in the treatment of liver cancer, chemoembolization with Lipiodol appears to have obtained encouraging results. After a preoperative study to confirm the diagnosis and staging of the tumour, lipiodolisation is performed: a mix of Adriamycin, Iopamidol and Lipiodol is injected using selective catheterism of the hepatic artery; gelfoam is then added. Lipiodol selectively localises in the hepatocarcinoma and has a distal embolising effect on the vessels of the tumour, thus necrotising it, acting as a carrier for chemotherapy. Since july 1990 a total of 15 hepatocarcinoma have been observed: 6 in healthy livers and 9 in cirrhotic livers; 3 patients recovered after radical surgery, 1 patient underwent associated surgery and chemoembolization, whereas in 11 the only therapy was chemoembolization, at six monthly intervals. Lipiodolisation enabled a better diagnosis to be made and was found to be a valuable therapeutic aid both when used alone in Inoperable patients and in association with non-radical surgery.

[Incompetence of the m. gemellus veins in varicose veins: its incidence and phlebographic study]. / L'incontinenza delle vene gemellari nella malattia varicosa: incidenza e studio flebografico.

The authors report on 466 venographies of the lower limbs performed over the past 2 years on 412 patients affected with varicose veins. Pathologic reflux of the gastrocnemius veins was observed in 15.7% of cases: 9.7% in the group of non-operated patients and 25.3% in the group with recurrent varicose disease. Ascending venography (and eventual popliteal venography) is the ideal diagnostic approach to show gastrocnemius veins incompetence, eventual anatomic variations, and isolated/associated incompetence of the short and/or long saphenous vein territory. Moreover, venography allows the hemodynamic evaluation, and shows reversed flow in the gastrocnemius veins in case of incompetence.

[Aneurysmal disease. Initial clinical experience with spiral computerized tomography angiography]. / Patologia aneurismatica. Esperienza clinica iniziale con angiografia con tomografia computerizzata spirale.

This study was aimed to assess the comparative capabilities of CT angiography (CTA) and DSA in diagnosing aneurysms in different sites in a series of 20 patients. Volumes were measured during intravenous contrast agent infusion and images were then edited and reformatted as 2D and 3D displays (MPR, SSD, MIP techniques). Some of the main semiologic patterns of aneurysms were considered and the diagnostic accuracy of the 3 reconstruction techniques was assessed and compared with that of axial CT and DSA. Abdominal aortic aneurysms were analyzed separately to study the involvement of main collateral vessels. The best results were obtained with MIP and MPR in the assessment of aneurysm extent and neck. MPR is the only technique which could depict the thrombus and the best technique to demonstrate the relationships between aneurysm and adjacent structures. The MIP technique depicts calcifications and is the method of choice to demonstrate the involvement of collateral vessels by abdominal aortic aneurysms. SSD permits good assessment of the neck and of the longitudinal extent of the aneurysms but is severely limited in the analysis of the other variables.

[Selective arteriography in the study of arterial vasculogenic impotence]. / L'arteriografia selettiva nello studio dell'impotenza vasculogenica arteriosa.

According to the fundamental circulatory nature of penile erection, insufficiency of the arterial blood supply to the corpora cavernosa caused by an organic arterial disease is found in a large fraction of case, overall among the patients aged more than 40. It is possible to evaluate arterial origin of erectile dysfunction by using of noninvasive methods, but to obtain the necessary panoramicity and the characterization of the lesions it needs the use of angiography. Performance of standard arteriography leads to insufficient visualization of pudendal and penile vessels and risks false positive results. Because of penile hemodynamic variability in its different states is necessary the use of pharmacologic devices to perform a diagnostic arteriography. For the selective study of the pudenda and peniena vascularization we perform a selective arteriography bilaterally, with the catheter tip placed in the proximal part of the internal iliac artery. We use a contrast medium particularly diluted and mixed with xylocaine. We perform angiographic sequences after intracavernous injection of 8-10 mgr of papaverine to obtain the maximum blood flow and to prevent spasm of the terminal arterioles. Arteriography gives a complete study of the pudenda arterial tree and its terminal ramifications, and it is able to supply all the necessary informations regarding the planning of revascularization procedures. Treatment of arterial lesions is possible with surgical and radiologic methods. As in other arteries, percutaneous transluminal angioplasty (P.T.A.) can be applied in the therapy of impotence caused by arterial insufficiency. P.T.A. is the election treatment in the stenosis of the common iliac and internal iliac arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

Primary cancer of the urinary bladder: CT evaluation of the T parameter with different techniques.

The evaluation of mural invasion (T) in primary urinary bladder carcinoma is important in the planning of an appropriate surgical or radiochemotherapeutic strategy. Previous investigators using computed tomography (CT) have evaluated the bladder filled with urine, urine opacified with iodinated contrast material, or air insufflation. The purpose of this trial was to establish which of these three techniques was the most accurate by comparing data obtained in postoperative staging (pT). Sixty-five patients with primary bladder cancer were enrolled, all of whom were studied by spiral CT with these three techniques. Patients were assigned to four stage groups: Ta-T1, T2-T3a, T3b, and T4. The results demonstrated total accuracies of 95% for the air-insufflated bladder, 90.5% for opacified urine, and 87% for noncontrast studies. In conclusion, the air-insufflated bladder is the more accurate technique in the evaluation of the T parameter in primary bladder cancer, especially in the first and third stage groups.

[Temporary caval filters. Indications, problems and results]. / Filtri cavali temporanei. Indicazioni, problemi e risultati.

The authors report their experience with the temporary placement of inferior vena caval filters to prevent pulmonary embolism in acute deep venous thrombosis patients. Twenty devices--6 Filcard and 4 Bruneau type--were positioned and left in situ over a time period ranging 4 to 14 days (mean: 9.8). In one patient the filter was positioned and no adjunctive medical therapy given to provide protection before nephrectomy; five patients were treated with i.v. heparin that provided no vein patency but prevented disease progression. Due to failure in positioning infusion guide catheters within the thrombus, four patients were submitted to fibrinolysis and heparin therapy: when the thrombus stabilized on angiographic images, heparin alone was administered and then followed by orally administered coumarin anticoagulants. In two cases partial thrombosis resolution was achieved, but with no significant improvement in patency rate. Ten patients underwent in situ fibrinolysis: six of them exhibited moderate improvement in femoroiliac axis patency and in three patients the inferior vena cava was successfully recanalized. No patient had any clinical evidence of pulmonary embolism. One case had cranial thrombus spread which was successfully treated with fibrinolysis. In our opinion, to control possible thrombotic involvement of the device, the patients candidate for temporary inferior vena caval filters must be easy to "manage" and exhibit no contraindications fibrinolysis and anticoagulant treatment.

[Angiography with spiral computed tomography. The basic principles and clinical potentials]. / Angiografia con tomografia computerizzata spirale. Principi di base e possibilità cliniche.

Technical characteristics, acquisition modality and data representations as well as examination protocols and main clinical applications of spiral CT angiography (CTA) are described. The different methods of 2D (MPR, CPR) and 3D (SSD, MIP) data display and their advantages and limitations were investigated. We describe the examination technique representing an important tool to achieve good image quality and to make the correct diagnosis. The clinical effectiveness and the main applications in the body were studied. CTA already has a clinical role for arterial system study, while it is less indicated in the venous system because good and continuous contrast agent opacification is difficult to obtain. In our preliminary experience, CTA can be considered an effective alternative to DSA in the assessment of vascular conditions because it is easier to perform, more rapid and less invasive.

[Bi- and tridimensional reconstruction with spiral computerized tomography in esophageal neoplasms. Preliminary clinical applications]. / Ricostruzioni bi e tridimensionali con Tomografia Computerizzata spirale nelle neoplasie dell'esofago. Applicazioni cliniche preliminari.

Spiral CT allows rapid data acquisition in an entire anatomical region during a single breath-hold and permits to obtain 2D and 3D reconstructions with good diagnostic accuracy. We investigated the capabilities of spiral CT reconstructions in demonstrating esophageal cancers. Spiral CT was performed in 10 patients with esophageal cancers and in 3 patients who underwent endoprostheses placement with surgical or interventional procedures. Bidimensional (MPR, CPR, MIP) and three-dimensional reconstructions with Shaded Surface Display (SSD) were obtained at the end of each exam. In the analysis of the results, CT reconstructions were compared with previous barium esophagography. Some of the main semiologic patterns were considered: tumor visualization, longitudinal extent of the neoplasm and its relationships with adjacent structures. MPRs were obtained in 9 patients and allowed to visualize the esophageal lumen with a filling defect, the neoplastic mass and its longitudinal and extraluminal extent. SSD reconstructions was obtained in 7 patients and allowed a good assessment of longitudinal neoplasm extent in 6 patients. Neoplastic mass visualization and extraluminal tumor extent were difficult to assess in all cases. MIP reconstructions were obtained in all patients and demonstrated longitudinal neoplasm extent with good accuracy. Neo-plastic tissue was visualized only indirectly through the filling defect of the esophageal lumen. MIP allowed to define, in 5 patients, the relationships of the neoplasms with adjacent vascular structures after the intravenous administration of contrast agent. In conclusion, we consider that Spiral CT reconstructions can be useful for a more accurate staging of esophageal cancers.