Neoadjuvant FOLFIRI+bevacizumab in patients with resectable liver metastases from colorectal cancer: a phase 2 trial.

BACKGROUND: Preoperative treatment of resectable liver metastases from colorectal cancer (CRC) is a matter of debate. The aim of this study was to assess the feasibility and activity of bevacizumab plus FOLFIRI in this setting. METHODS: Patients aged 18-75 years, PS 0-1, with resectable liver-confined metastases from CRC were eligible. They received bevacizumab 5 mg kg(-1) followed by irinotecan 180 mg m(-)(2), leucovorin 200 mg m(-)(2), 5-fluorouracil 400 mg m(-)(2) bolus and 5-fluorouracil 2400 mg m(-)(2) 46-h infusion, biweekly, for 7 cycles. Bevacizumab was stopped at cycle 6. A single-stage, single-arm phase 2 study design was applied with 1-year progression-free rate as the primary end point, and 39 patients required. RESULTS: From October 2007 to December 2009, 39 patients were enrolled in a single institution. Objective response rate was 66.7% (95% exact CI: 49.8-80.9). Of these, 37 patients (94.9%) underwent surgery, with a R0 rate of 84.6%. Five patients had a pathological complete remission (14%). Out of 37 patients, 16 (43.2%) had at least one surgical complication (most frequently biloma). At 1 year of follow-up, 24 patients were alive and free from disease progression (61.6%, 95% CI: 44.6-76.6). Median PFS and OS were 14 (95% CI: 11-24) and 38 (95% CI: 28-NA) months, respectively. CONCLUSION: Preoperative treatment of patients with resectable liver metastases from CRC with bevacizumab plus FOLFIRI is feasible, but further studies are needed to define its clinical relevance.

[Small bowell volvulus - combined radiological findings]. / Volvolo dell'intestino tenue - diagnostica radiologica integrata.

PURPOSE: We retrospectively evaluated the radiological findings observed at plain abdominal film, abdominal sonography and abdominal CT performed in 66 patients with surgically proven small bowel volvulus. MATERIAL AND METHODS: Sixty-six patients (35 women and 31 men, ranging in age 38-77 years) with surgically proven small bowel volvulus were submitted to plain film, sonography and CT of the abdomen. Abdominal plain film was performed in the upright position (postero-anterior view) in 46 cases, and in the supine position in 20 cases. On plain abdominal film we evaluated the following findings: bowel loops dilatation, air-fluid levels and site of obstruction. At abdominal US, performed with 3.5 e 7.5 MHz probes, we retrospectively searched for: bowel loop dilatation, bowel wall thickening, peristalsis alteration, extraluminal fluid. CT was performed with a helical unit (thickness 4 mm, reconstruction interval 4 mm, pitch 1.5), after intravenous contrast agent (120 ml) infusion (3 ml/s, 55 s acquisition delay from bolus starting) and using a power injector. The following CT findings were searched for: whirl sign, beak sign, extraluminal fluid, bowel loop dilatation, bowel wall thickening, bowel wall or mesenteric alterations. RESULTS: Plain abdominal film showed the following findings: air-fluid levels (92.4% of cases), bowel loops dilatation (71.2%), site of obstruction (42.4%). Abdominal sonography demonstrated bowel loop dilatation (48.5%), extraluminal fluid (48.5%), peristalsis alteration (27.3%), bowel wall thickening (27.3%). The most frequent CT findings were: bowel loop dilatation (95.5%), bowel wall thickening (78.8%), beak sign (69.7%), mesenteric alterations (66.7%), extraluminal fluid (54.5%), whirl sign (13.6%). CONCLUSIONS: Air-fluid levels and bowel loop dilatation were the most frequent radiological findings in our series. Plain abdominal film allowed us to identify signs of obstruction, whereas signs of bowel wall necrosis were accurately shown by abdominal CT.

[Helical CT as preferred imaging modality in the diagnosis of pulmonary embolism]. / La tomografia computerizzata spirale come esame diagnostico di riferimento nella tromboembolia polmonare.

PURPOSE: We investigated the role of Helical Computed Tomography (CT) as primary screening imaging modality in the diagnosis of pulmonary embolic disease. MATERIAL AND METHODS: We retrospectively reviewed the CT examinations, resulted positive for pulmonary embolism, performed in 134 patients (69 men and 65 women, ranging in age 23-83 years) from June 1998 to June 1999. CT was performed with a helical unit (thickness 3 mm, reconstruction interval 2 mm, pitch 1.5) after intravenous contrast agent (120 mL) rapid infusion (4 mL/s, 15s acquisition delay from bolus starting) and using a power injector. The spiral acquisition was performed from the apex of the pulmonary trunk to the diaphragm. Pulmonary embolism was considered as complete when a filling defect was present in a main pulmonary artery, as moderate when a filling defect was observed in an interlobar pulmonary artery and as very small when a filling defect was identified in a segmental pulmonary artery. RESULTS: Helical CT allowed us to identify the presence of a filling defect in the main pulmonary artery in 60.4% of cases (complete pulmonary embolism), in an interlobar pulmonary artery in 27.6% of cases (moderate pulmonary embolism) and in a segmental pulmonary artery in 11.9% of cases (very small pulmonary embolism). At helical CT study, pulmonary embolus was identified as complete filling defect (92.5% of cases), thromboembolic mass floating freely in the lumen (28.3%) and partial filling defect (19.4%). Pleural effusion and pulmonary infarction were associated in 46.2% and 20.1% respectively. DISCUSSION AND CONCLUSIONS: Pulmonary embolic disease continues to be a major cause of morbidity and mortality. The clinical diagnosis of pulmonary embolism remains an important challenge: among the different imaging modalities, contrast-enhanced helical CT can be used as primary screening imaging modality in the diagnosis of pulmonary embolism, allowing us to detect the presence of pulmonary embolus in the main, lobar and segmental artery, as demonstrated in our experience.

[Spiral computed tomography in the assessment of vascular lesions of the pelvis due to blunt trauma]. / Contributo della Tomografia Computerizzata spirale nella valutazione delle lesioni vascolari della pelvi da trauma chiuso.

PURPOSE: We investigated the role of Helical Computed Tomography (CT) in the evaluation of low or high flow vascular injuries in patients with blunt pelvic trauma. MATERIAL AND METHODS: From May 1998 to December 1999, forty-nine patients (32 men and 17 women, ranging in age 14-59 years) with acute symptoms from blunt pelvic trauma were submitted to Computed Tomography (CT). A conventional radiography of the pelvis had been performed in all cases. CT was performed with a helical unit (thickness 8 mm, reconstruction interval 8 mm, pitch 1.5) after intravenous contrast agent (150-180 mL) rapid infusion (4-5 mL/s, 60 s acquisition delay from bolus starting) and using a power injector. A second spiral acquisition was performed in all cases from the iliac roofs to the inferior border of the pubic symphysis. Vascular hemorrhage was considered as low flow when the hematoma appeared as a focal homogeneous density area and as high flow when associated with contrast agent extravasation. Moreover, traumatic assessment included evaluation of the hematoma, of the leakage site and of the involved vessel. RESULTS: Radiologic examination of the pelvis revealed fractures in 35/49 patients (71.4%). Helical CT allowed us to identify low flow hemorrhage in 37 patients, affected with hematomas from fracture of the iliac wing or of the sacrum (14 cases), tear of the pelvic (3 cases) or extrapelvic (4 cases) muscular structures, or injury of the venous plexus (20 cases). In four patients two vascular injuries were detected. High flow hemorrhage was seen in 12 patients, who had Helical CT findings of contrast agent extravasation along the common iliac vein (3 cases), external iliac artery (3 cases), internal iliac artery (4 cases), internal pudendal artery (1 case), obturator artery (1 case), inferior epigastric artery (2 cases), superior gluteal artery (2 cases), inferior gluteal artery (1 case), cremasteric artery (1 case). In 6 patients with high flow hemorrhage, two vascular injuries were shown. In all these patients, an extraperitoneal hematoma was associated with the contrast agent extravasation. DISCUSSION AND CONCLUSIONS: Fractures of the pelvic ring generally result from severe trauma. Management of these injuries must include not only treatment of the skeletal trauma but also of the associated shock and complications. Major blood loss usually occurs as a result of bleeding from the branches of the internal iliac artery. With respect to pelvic plain radiography, CT provides superior detailing of fractures, position of fracture fragments and extent of diastasis of the sacroiliac joints and pubic symphysis. Moreover CT provides diagnostic information regarding the presence or absence of pelvic bleeding and can identify the site of bleeding. In our experience, Helical CT allows us to distinguish high flow hemorrhage, where vascular injuries must be treated first, from low flow hemorrhage which can be managed differently.

[The role of spiral computed tomography in sigmoid diverticulitis and the diagnostic-therapeutic implications]. / Ruolo della Tomorafia Computerizzata spirale nella diverticolite del sigma e implicazioni diagnostico-terapeutiche.

PURPOSE: Colonic diverticula are saccules made of colonic mucosa and submucosa that herniate from the colonic lumen through the muscular layer of the wall where straight vessels penetrate. Diverticula are localized in the sigmoid colon in 95% of cases. Bacteria pooling in the lumen may cause lumen erosion and eventually perforation. CT is a useful technique in this condition because it can demonstrate intra- and/or extramural inflammation. Aim of this retrospective study was to assess the capabilities of contrast-enhanced helical Computed Tomography (CT) in sigmoid diverticulitis, especially relative to selection of the appropriate treatment. MATERIAL AND METHODS: We retrospectively reviewed the findings of 41 patients referred to our emergency department for diverticulitis. CT scans were performed 65 seconds after i.v. injection of nonionic contrast material (3 mL/s, 120 mL in all) administered by a CT-power injector. The following 7 CT findings were considered at least suggestive of acute diverticulitis: focal wall thickening, intramural abscess, inflammatory changes in the sigmoid mesentery root, pericolic fat inflammation or pericolic abscess formation, fistula, peritonitis. CT results were compared with surgical and physical findings. RESULTS: Based on CT findings, diverticulitis was classified as mild (25 patients) or severe (15 patients). In mild diverticulitis we found: focal sigmoid wall thickening (6 patients), intramural abscess (3 patients), sigmoid mesentery root thickening (5 patients), edema fluid (8 patients) and phlegmon (3 patients). In severe diverticulitis we found: sigmoid mesentery abscess (6 patients), fistula (5 patients) and peritonitis (4 patients). CT findings were questionable in 1 case and thus we could not exclude a perforated carcinoma. CONCLUSION: Contrast-enhanced helical CT is the imaging modality of choice in assessing mild or severe acute diverticulitis because it provides useful information for appropriate treatment planning in the emergency setting. This technique is most useful in questionable cases and in patients with suspected severe diverticulitis where a choice must be made between different treatment options.

[Echography in the monitoring of bone callus in fractures treated with external fixation]. / L'ecografia nel monitoraggio del callo osseo nelle fratture trattate con fissatori esterni.

The authors report on the use of US in the evaluation of osteogenesis in the fractures treated with external fixation. From April 1991 to October 1992, fifty patients with diaphyseal fractures were submitted to real-time US examinations, with 7.5-5 MHz probes, mainly on longitudinal scans. The evolutive stage of bone callus was studied and, in the presence of periosteal bone bridge, its length and height were measured. In all but 4 patients US, unlike radiology, allowed the signs of osteogenesis to be detected as early as from day 10 on and the peculiar bilobate pattern known as primary callus response was clearly demonstrated. This stage is of fundamental importance because it allows, when periosteal callus is absent, direct intervention on the dynamic process, by varying the external fixation-bone complex so as to make it more flexible. In 80% of patients periosteal apposition was observed on day 24. Delayed osteogenesis depended on the patient's age and on fracture type. Such pathologic signs as hyperstimuli, pseudoarthrosis and/or hematoma persistence were quite unfrequent findings. Even though the study of US semiology is still in progress, our results are in substantial agreement with literature data and emphasize the role of US in the early evaluation of the bone callus and its evolution.

[Segmental ischemic lesions of the mesenteric small intestine]. / Le lesioni ischemiche segmentarie dell'intestino tenue mesenteriale.

Segmental ischemic disease consists of segmental infarctions and ischemic stenoses. Vasculitis (LES, polyarteritis nodosa, Schönlein-Henoch syndrome), thrombosis, arteriosclerotic changes, mechanical obstructions (adhesions, hernia, volvulus, traumas), hemorrhagic disorders are the most common causes of these intestinal lesions. The authors report their experience achieved during three years on 428 small bowel examinations; among these, 197 were double contrast enemas. Ten patients showed roentgenographic features referred to vascular diseases: 1 LES, 1 Schönlein-Henoch syndrome, 3 polyarteritis nodosa, 5 spontaneous hemorrhagic disorders or due to treatment with anticoagulants. The authors, after a review of the radiological findings, emphasize the high sensitivity and low specificity of double contrast small bowel enema. Furthermore they underline the usefulness of this method in demonstrating and monitoring intestinal pathologic changes.

[The role of enemas in the small intestine in the study of ileal subocclusion]. / Apporto del clisma del tenue allo studio delle subocclusioni ileali.

In mechanical subocclusions, when there isn't immediate urgency, is it possible and necessary to probe radiologic examination, for a better surgical evaluation. The authors describe their own experience, achieved in about 3 years, on small bowel double contrast enema. They examined 143 patients; 16 of them were suboccluded. The security and the diagnostic reliability of used method are stressed by the authors to define lesions' morphology and localization.

Activation of human basophils by staphylococcal protein A. I. The role of cyclic AMP, arachidonic acid metabolites, microtubules and microfilaments.

Protein A from Staphylococcus aureus (Staph A) induces histamine secretion from human basophil leucocytes in the concentration range 10(-4) - 10 micrograms/ml. This reaction has great similarities to that of antigen or anti-IgE-induced release. It is characterized by a two stage reaction, requires extracellular calcium and is optimal at 37 degrees C. The rate of release is similar to that of IgE-mediated reactions. Histamine release induced by Staph A is inhibited by metabolic inhibitors, drugs which increase intracellular cyclic AMP levels, inhibitors of lipoxygenase pathways and a phospholipase A2 inhibitor. D2O and cytochalasin B which affect microtubules and microfilaments respectively, enhance histamine release induced by Staph A. These results suggest that Staph A-induced release is modulated by intracellular cyclic AMP, arachidonic acid metabolites, requires energy and is enhanced by the disruption of microfilaments and stabilization of microtubules.