Traumatic renal artery dissection: from imaging to management.

Injury to the renal artery following blunt trauma is detected increasingly due to widespread and early use of multidetector computed tomography (CT), but optimal treatment remains controversial as no guidelines are available. This review illustrates the spectrum of imaging findings of traumatic renal artery dissection based on our experience, with the aim of understanding the physiopathology of ischaemic damage to the kidney, and the process of choosing the best therapeutic strategy (conservative, endovascular, surgical). Five main patterns of traumatic renal artery dissection are described: avulsion of renal hilum; dissection of the segmental renal branches; preocclusive main renal artery dissection; renal artery stenosis without flow limitation; thrombogenic renal artery intimal tear. In the polytrauma patient, management depends on various factors (haemodynamic status, associated lesions, time of diagnosis) rather than on the degree of renal artery stenosis. Non-operative management (NOM) is the preferred option in case of non-flow-limiting dissection of the renal artery and angio-embolisation is an important adjunct to NOM in cases of active bleeding. Embolisation of the renal artery stump may be the best option in cases of occlusive dissection, as catheter manipulation carries a high risk of vessel rupture. The therapeutic window for kidney revascularisation in cases of flow-limiting dissection of main renal artery may be variable. Endovascular stenting >4 h after trauma should be performed only if residual flow with preserved parenchymal perfusion is detected at angiography. Antiplatelet therapy administration is recommended in cases of stenting, but conditioned by the bleeding risk of the patient.

Direct magnetic resonance (MR) shoulder arthrography: posterior approach under ultrasonographic guidance and abduction (PAUGA).

PURPOSE: This study was undertaken to assess the reliability of the posterior approach under ultrasonographic guidance (PAUGA), with the arm abducted, before performing direct magnetic resonance (MR) arthrography of the shoulder. MATERIALS AND METHODS: A total of 111 (82 men, 29 women; mean age, 24 years) underwent direct MR arthrography of the shoulder. Patients were enrolled because of glenohumeral instability (n=71), chronic shoulder pain (n=25), suspicion of rotator cuff tear (n=13) and adhesive capsulitis (n=2). Patients were placed in the lateral position, on the contralateral side to that being examined; the arm of the shoulder undergoing the examination was placed in slight internal rotation with the hand under the contralateral armpit. A gadolinium-based solution was injected into the articular capsule under cryoanaesthesia and sonographic guidance. A posterior approach was systematically applied. For each patient, the number of injection attempts, room time, complications and pain, as recorded on a 10-point visual analogue scale (VAS), were noted. For quantitative parameters (room time and pain intensity), the mean and standard deviation (SD) were calculated. RESULTS: Direct MR arthrographies were performed successfully in all patients; no immediate or late major complications were observed. Fourteen patients (12.6%) reported temporary and self-limiting compromise of arm movements, and 13 patients (11.7%) reported a vagal reaction not requiring medication. In 102 cases (92%), the injection was successful at the first attempt, whereas in the remaining nine cases (8%), needle repositioning without any additional puncture was required to obtain clear sonographic depiction of the position of the needle tip. Mean room time was 7.2±1.4 min. Mean pain intensity was 3.2±0.4 on the 10-point VAS scale. CONCLUSIONS: PAUGA is a reliable and rapid technique that is well tolerated by patients and easy for the radiologist to perform.

Radiofrequency ablation of renal cell carcinoma in patients with a solitary kidney: a retrospective analysis of our experience.

PURPOSE: This study was done to evaluate the feasibility and safety of radiofrequency ablation (RFA) of renal cell carcinomas (RCCs) in patients with solitary kidney. MATERIALS AND METHODS: Seven patients (two men, five women; age range 52-70 years; mean age 59.7 years) were treated under computed tomography (CT) and ultrasound (US) guidance. Three patients had single lesions, and the remaining four had multiple lesions. Seventeen lesions (4 cortical, 13 exophytic, maximum diameter range 12-40 mm, mean 21.0 mm) not located close to the renal pelvis were treated. CT or magnetic resonance (MR) imaging follow-up studies were obtained for all patients at the end of the procedure and at 1, 3, 6 and 12 months; serum creatinine was also monitored. RESULTS: Ten ablation sessions were performed. In two patients, a perinephric haematoma was detected, and one of these patients had two episodes of self-limiting haematuria. Contrast-enhanced CT and MR imaging at the end of the procedure and at 1 month demonstrated 100% technical success; these results were confirmed at 3, 6 and 12 month. Fisher's test comparing serum creatinine obtained 1 day before and 1 day after the procedure showed no case of acute renal failure (mean serum creatinine 24 h before the procedure 1.02 mg/dl; mean serum creatinine 24 h after the procedure 0.95 mg/dl; p=0.114; not significant). Serum creatinine at follow-up was always within the normal range. CONCLUSIONS: Radiofrequency ablation in the solitary kidney is a safe and effective procedure for treating RCC.

FOLFOX6 and bevacizumab in non-optimally resectable liver metastases from colorectal cancer.

BACKGROUND: In patients with colorectal liver metastases (CLM) R0 resection significantly improves overall survival (OS). METHODS: In this report, we present the results of a phase II trial of FOLFOX6+bevacizumab in patients with non-optimally resectable CLM. Patients received six cycles of FOLFOX6+ five of bevacizumab. Patients not achieving resectability received six additional cycles of each. A PET-CT was performed at baseline and again within 1 month after initiating treatment. RESULTS: From September 2005 to July 2009, 21 patients were enrolled (Male/Female: 15/6; median age: 65 years). An objective response (OR) was documented in 12 cases (57.1%; complete responses (CRs): 3, partial response (PR): 9); one patient died from toxicity before surgery. Thirteen patients underwent radical surgery (61.9%). Three (23%) had a pathological CR (pCR). Six patients (46.1%) experienced minor postsurgical complications. After a median 38.8-month follow-up, the median OS was 22.5 months. Patients achieving at least 1 unit reduction in Standard uptake value (SUV)max on PET-CT had longer progression-free survival (PFS) (median PFS: 22 vs 14 months, P=0.001). CONCLUSIONS: FOLFOX6+bevacizumab does not increase postsurgical complications, yields high rates of resectability and pCR. Early changes in PET-CT seem to be predictive of longer PFS.

Sorafenib in patients with advanced biliary tract carcinoma: a phase II trial.

BACKGROUND: Advanced biliary tract carcinoma has a very poor prognosis, with chemotherapy being the mainstay of treatment. Sorafenib, a multikinase inhibitor of VEGFR-2/-3, PDGFR-beta, B-Raf, and C-Raf, has shown to be active in preclinical models of cholangiocarcinoma. METHODS: We conducted a phase II trial of single-agent sorafenib in patients with advanced biliary tract carcinoma. Sorafenib was administered at a dose of 400 mg twice a day. The primary end point was the disease control rate at 12 weeks. RESULTS: A total of 46 patients were treated. In all, 26 (56%) had received chemotherapy earlier, and 36 patients completed at least 45 days of treatment. In intention-to-treat analysis, the objective response was 2% and the disease control rate at 12 weeks was 32.6%. Progression-free survival (PFS) was 2.3 months (range: 0-12 months), and the median overall survival was 4.4 months (range: 0-22 months). Performance status was significantly related to PFS: median PFS values for ECOG 0 and 1 were 5.7 and 2.1 months, respectively (P=0.0002). The most common toxicities were skin rash (35%) and fatigue (33%), requiring a dose reduction in 22% of patients. CONCLUSIONS: Sorafenib as a single agent has a low activity in cholangiocarcinoma. Patients having a good performance status have a better PFS. The toxicity profile is manageable.

Prognostic role of EGFR gene copy number and KRAS mutation in patients with locally advanced rectal cancer treated with preoperative chemoradiotherapy.

BACKGROUND: Epidermal growth factor receptor (EGFR), evaluated by immunohistochemistry, has been shown to have prognostic significance in patients with colorectal cancer. Gene copy number (GCN) of EGFR and KRAS status predict response and outcome in patients treated with anti-EGFR therapy, but their prognostic significance in colorectal cancer patients is still unclear. METHODS: We have retrospectively reviewed the baseline EGFR GCN, KRAS status and clinical outcome of 146 locally advanced rectal cancer (LARC) patients treated with preoperative chemoradiotherapy. Pathological response evaluated by Dworak's tumour regression grade (TRG), disease-free survival (DFS) and overall survival (OS) were analysed. RESULTS: Tumour regression grade 4 and TRG3-4 were achieved in 14.4 and 30.8% of the patients respectively. Twenty-nine (19.9%) and 33 patients (19.2%) had an EGFR/nuclei ratio >2.9 and CEP7 polisomy >50% respectively; 28 patients (19.2%) had a KRAS mutation. Neither EGFR GCN nor KRAS status was statistically correlated to TRG. 5-year DFS and OS were 63.3 and 71.5%, respectively, and no significant relation with EGFR GCN or KRAS status was found. CONCLUSION: Our data show that EGFR GCN and KRAS status are not prognostic factors in LARC treated with preoperative chemoradiation.

Contrast-enhanced MRI and PET-CT in the evaluation of patients with suspected local recurrence of rectal carcinoma.

PURPOSE: This study aimed to evaluate the role of contrast-enhanced magnetic resonance imaging (MRI) and positron emission tomography-computed tomography (PET-CT) in the assessment of local recurrence of rectal cancer. MATERIALS AND METHODS: Among 200 patients scheduled for CT follow-up, 60 (48 low risk; 12 high risk) were selected due to CT findings suspicious for or suggestive of local recurrence. Patients underwent contrast-enhanced MRI and PET-CT within 2 weeks. Biopsy was considered the gold standard in 39 cases and follow-up at 6 and 12 months in the remaining 21. RESULTS: Local recurrence was confirmed by histology in 15 cases (7 low risk; 8 high risk) and was excluded in 21 cases by long-term follow-up and in 24 by histology. Sensitivity, specificity, positive and negative predictive value and accuracy were 86.7%, 68.9%, 48.1%, 93.9% and 73.3% for contrast-enhanced MRI and 93.3%, 68.9%, 50%, 96.9% and 75% for PET-CT. CONCLUSIONS: Contrast-enhanced MRI and PET-CT can help in the detection of local recurrence of rectal cancer, even though their roles in early detection remains debatable, as the value of these techniques in current surveillance protocols is still to be defined.

Epidermal growth factor receptor gene copy number, K-ras mutation and pathological response to preoperative cetuximab, 5-FU and radiation therapy in locally advanced rectal cancer.

BACKGROUND: Cetuximab improves activity of chemotherapy in metastatic colorectal cancer (mCRC). Gene copy number (GCN) of epidermal growth factor receptor (EGFR) has been suggested to be a predictive factor of response to cetuximab in patients (pts) with mCRC; on the contrary, K-ras mutation has been associated with cetuximab resistance. PATIENTS AND METHODS: We have conducted a phase II study with cetuximab administered weekly for 3 weeks as single agent and then with 5-fluorouracil and radiation therapy as neo-adjuvant treatment for locally advanced rectal cancer (LARC). EGFR immunohistochemistry expression, EGFR GCN and K-ras mutation were evaluated on diagnostic tumor biopsy. Dworak's tumor regression grade (TRG) was evaluated on surgical specimens. RESULTS: Forty pts have been treated; 39 pts are assessable. TRG 3 and 4 were achieved in nine (23.1%) and three pts (7.7%) respectively; TRG 3-4 rate was 55% and 5.3% in case of high and low GCN, respectively (P 0.0016). Pts with K-ras mutated tumors had lower rate of high TRG: 11% versus 36.7% (P 0.12). In pts with wild-type K-ras, TRG 3-4 rate was 58.8% versus 7.7% in case of high or low GCN, respectively (P 0.0012). CONCLUSIONS: In pts with LARC, EGFR GCN is predictive of high TRG to cetuximab plus 5-FU radiotherapy. Moreover, our data suggest that a wild-type K-ras associated with a high EGFR GCN can predict sensitivity to cetuximab-based treatment.

Fluorouracil, doxorubicin, and mitomycin combination versus PELF chemotherapy in advanced gastric cancer: a prospective randomized trial of the Italian Oncology Group for Clinical Research.

PURPOSE: The combination of cisplatin, epirubicin, and leucovorin preceding fluorouracil (PELF) includes three novel agents compared with the standard combination of fluorouracil, doxorubicin, and mitomycin (FAM) in the treatment of advanced gastric carcinoma. We report the results of a prospective randomized comparison of the two combinations in previously untreated patients. PATIENTS AND METHODS: One hundred thirty assessable patients were entered onto the trial; 52 received FAM and 85 PELF. A 1:2 unbalanced randomization in favor of the experimental treatment was chosen. Approximately 90% of patients had measurable tumor masses. RESULTS: The overall response rates (complete responses [CRs] and partial responses [PRs]) were 15% and 43% for the FAM and the PELF regimens, respectively, with a statistically significant advantage for the experimental treatment (P = .001). Time to progression (median, 2.6 and 4.7 months), duration of response (median, 10.7 and 10.2 months), and survival durations (median, 5.6 and 8.1 months) were not significantly different between the FAM and PELF regimens, respectively. The PELF combination was more toxic compared with FAM, but generally tolerable. CONCLUSION: This study showed that the PELF combination is about three times more effective than the FAM combination in inducing objective responses. Due to tolerability, it is not recommended for routine clinical use. However, it should be considered, among other second-generation chemotherapy combinations, in future randomized studies aimed to improve the therapeutic outcome in gastric carcinoma.

The value of c-kit mutational analysis in a cytokeratin positive gastrointestinal stromal tumour.

The expression of cytokeratins in gastrointestinal stromal tumours (GISTs) is rare and may lead to diagnostic confusion when it occurs. This report describes a metastatic GIST that stained strongly for cytokeratins, CD117, and CD34 in a patient who was previously diagnosed with gastric epithelioid angiosarcoma. A review of both tumours showed the same histological and immunohistochemical profiles, and c-kit molecular analysis revealed an insertional mutation at codon 558 of exon 11 in both tumours. Thus, pathologists should be aware that GISTs can occasionally express cytokeratins, and that c-kit mutational investigations may have a key diagnostic role and may prevent diagnostic mistakes that could have important clinical implications.

[Benign tumors and pseudotumors of temporo-mandibular joint: radiologic aspects]. / Tumori benigni e pseudotumori dell'articolazione temporo-mandibolare: aspetti radiologici.

Benign tumors and tumor-like lesions that involve temporo mandibular joint are very rare. Those more frequent are osteochondroma, chondroma, osteoma, pigmented villonodular synovitis and synovial chondromatosis. The Authors report six cases of patients affected by these pathologies in which imaging, such as TC, MRI and/or ortopantomography have been useful to have a diagnosis.

Brain metastases: an overview.

So far brain metastases represent a critical stage of a disease course and the frequency is increasing over the years. The treatment of brain metastases should be individualized for each patient: in case of single brain metastasis, surgery or radiosurgery should be considered as first options of treatment; in case of multiple lesions, whole-brain radiotherapy is the standard of care in association with systemic therapy or surgery/radiosurgery. Chemotherapy should be considered when surgery or radiation therapy are not possible. In the last decades, TKIs or monoclonal antibodies have shown increase in overall response rate and overall survival in Phase II-III trials. The aim of this paper is to make an overview of the current approaches in management of patients with brain metastases.

Interventional Radiologist's perspective on the management of bone metastatic disease.

Bone metastases can be treated by interventional radiologists with a minimally invasive approach. Such treatments are performed percutaneously under radiological imaging guidance. Different interventional techniques can be applied with curative or palliative intent depending on lesions and patients' status. In the whole, available interventional techniques are distinguished into "ablative" and "consolidative". Ablative techniques achieve bone tumor necrosis by dramatically increasing or decreasing intra-tumoral temperature. This option can be performed in order to alleviate pain or to eradicate the lesion. On the other hand, consolidative techniques aim at obtaining bone defect reinforcement mainly to alleviate pain and prevent pathological fractures. We herein present evidence supporting the application of each different interventional technique, as well as common strategies followed by interventional radiologists while approaching bone metastases.

Urinary neopterin in malignant lymphoma.

Urinary neopterin levels were studied in 96 patients with malignant lymphomas. Twenty-eight had Hodgkin's disease and 68 non-Hodgkin's lymphoma. Neopterin excretion was significantly related to the clinical stage of the disease. Mean neopterin excretion in patients with active disease (634 +/- 527 mumol neopterin/mol creatinine) was significantly higher (p = 0.000) than in patients in complete remission (198 +/- 105 mumol neopterin/mol creatinine). Mean neopterin levels of patients in stage III-IV were higher than for patients in stage I-II. These findings were the same in patients with Hodgkin's disease and those with non-Hodgkin's lymphoma (659 +/- 593-425 +/- 316 mumol neopterin/mol creatinine), regardless of the histological subtype. A significant correlation was found between neopterin excretion, ESR (r = 0.31; p = 0.003) and hemoglobin (r = -0.40; p = 0.000). Longitudinal analysis showed a trend towards a correlation between response to therapy and neopterin excretion. These findings suggest that neopterin may be a useful prognostic marker in non-Hodgkin's lymphoma.

Modulation of fluorouracil by methotrexate, leucovorin, and cisplatin (M-FLP) in the treatment of advanced pancreatic cancer: a phase II study of the Italian Oncology Group for Clinical Research (GOIRC).

The objective of this trial was to evaluate the activity and tolerability of biomodulation of 5-fluorouracil by leucovorin, methotrexate, and platinum in patients with advanced measurable disease. Thirty-five patients with histologically or cytologically proven adenocarcinoma of the pancreas were treated with methotrexate (100 mg/m2 in 500 ml 5% dextrose in a 2-hour infusion, day 1), 5-fluorouracil (800 mg/m2/day, i.v. in continuous infusion from days 2 to 5) plus 1-leucovorin (7.5 mg/m2 given per os every 6 hours, from days 2 to 5) and platinum (60 mg/m2 i.v., day 2), every 28 days. Four partial responses (12%; exact 95% confidence interval: 1-23%) were obtained in 34 evaluable patients with a median survival time of 49 weeks (range, 20-77 weeks). Ten (29%) of 34 patients had stable disease. Median time to treatment failure from the beginning of therapy was 11 weeks (range, 4-59 weeks) and median survival time was 20 weeks (range, 4-77 weeks). The most common grade III-IV toxicities were diarrhea (15%), stomatitis (41%), and vomiting (17%). Hematologic toxicity was mild. There were no therapy-related deaths. In conclusion, this trial did not report an increase or improvement in response rate and survival rates, and this regimen cannot be recommended as effective therapy for advanced pancreatic cancer.

High-dose folinic acid and 5-fluorouracil alone or combined with hydroxyurea in advanced colorectal cancer: a randomized trial of the Italian Oncology Group for Clinical Research.

Patients with histologically confirmed advanced colorectal cancer were randomized to receive folinic acid (FA; 500 mg/mq in 2-hour intravenous infusion) and 5-fluorouracil (5FU; 600 mg/mq given as an intravenous bolus 1 hour after FA), beginning every week for 6 weeks, followed by a 2-week rest period, either without hydroxyurea (HU, arm A) or with HU (35 mg/kg per day) given orally in three administrations (every 8 hours) starting 6 hours after 5FU administration (arm B). Six weekly doses were considered one course. One hundred eighty-two patients were randomized in this trial and 162 (89%) were evaluable for response: 81 patients in arm A and 81 patients in arm B. Objective response was observed in 18 (one complete response and 17 partial responses) of 81 evaluable patients (22%; 95% confidence interval, 13-31%) in arm A, and 24 (nine complete responses and 15 partial responses) of 81 patients (30%; 95% confidence interval, 20-40%) in arm B. There was no difference in terms of median time to progression and median survival. Gastrointestinal toxicity was the most frequently observed toxicity in both arms. The double modulation of 5FU, FA plus HU does not appear to be better than the classic 5FU plus FA schedule. This trial confirms that 5FU and FA reached a plateau of 20% to 30%.

Randomised trial of gemcitabine versus flec regimen given intra-arterially for patients with unresectable pancreatic cancer.

Gemcitabine is considered the golden standard treatment for unresectable pancreatic adenocarcinoma. Intra-arte-rial drug administration had shown a deep rationale with some interesting results. In a multicenter phase III trial, we compared gemcitabine given weekly with a combination of 5-fluoruracil, leucovorin, epirubicin, carboplatin (FLEC) administered intra-arteriously as first-line therapy in unresectable pancreatic adenocarcinoma. Patients were randomly assigned to receive gemcitabine at a dose of 1,000 mg/m2 over 30 minutes intravenously weekly for 7 weeks, followed by 1 week of rest, then weekly for 3 weeks every 4 weeks or 5-fluoruracil 1,000 mg/m2, leucovorin 100 mg/m2, epirubicin 60 mg/m2, carboplatin 300 mg/m2 infused bolus intra-arteriously at three-weekly interval for 3 times. The primary end point was overall survival, while time to treatment failure, response rate, clinical benefit response were secondary endpoints. Sixty-seven patients were randomly allocated gemcitabine and 71 were allocated FLEC intra-arterially. Patients treated with FLEC lived for significantly longer than patients on gemcitabine (p=.036). Survival at 1 year was increased from 21% in the gemcitabine group to 35% in the FLEC group. Median survival was 7.9 months in the FLEC group and 5.8 months in the gemcitabine group. Median time to treatment failure was longer with FLEC (5.3 vs 4.2 months for FLEC vs gemcitabine respectively; p=.013). Clinical benefit was similar in both groups (17.9% for gemcitabine and 26.7% for FLEC; p=NS). CT-scan partial response was similar in both group (5.9% for gemcitabine and 14% for FLEC; p=NS). Toxicity profiles were different. Compared with gemcitabine, FLEC regimen given intra-arteriously, improved survival in patient with unresectable pancreatic adenocarcinoma.

Gemcitabine versus FLEC regimen given intra-arterially to patients with unresectable pancreatic cancer: a prospective, randomized phase III trial of the Italian Society for Integrated Locoregional Therapy in Oncology.

Gemcitabine is considered the gold standard treatment for unresectable pancreatic adenocarcinoma. Intra-arterial drug administration had shown some interesting results in small phase II studies. In this study, patients were randomly assigned to receive gemcitabine at a dose of 1,000 mg/m2 over 30 minutes intravenously weekly for 7 weeks, followed by 1 week of rest, then weekly for 3 weeks every 4 weeks or FLEC: 5-fluoruracil 1,000 mg/m2, leucovorin 100 mg/m2, epirubicin 60 mg/m2, carboplatin 300 mg/m2 infused bolus intra-arterially into celiac axis at a 3-week interval 3 times or 5-fluorouracil 400 mg/m2 plus folinic acid 20 mg/m2 for 5 days every 4 weeks for 6 cycles. The primary endpoint was overall survival, while time to treatment failure, response rate, clinical benefit response were secondary endpoints. Sixty-seven patients were randomly allocated gemcitabine and 71 were allocated FLEC intra-arterially. Patients treated with FLEC lived for significantly longer than patients on gemcitabine (p=0.036). Survival at 1 year increased from 21% in the gemcitabine group to 35% in the FLEC group. Median survival was 7.9 months in the FLEC group and 5.8 months in the gemcitabine group. Median time to treatment failure was longer with FLEC (5.3 vs 4.2 months for FLEC vs gemcitabine respectively; p=0.013). Clinical benefit was similar in both groups (17.9% for gemcitabine and 26.7% for FLEC; p=NS). CT-scan partial response was similar in both groups (5.9% for gemcitabine and 14% for FLEC; p=NS). Toxicity profiles were different. Compared with gemcitabine, the FLEC regimen given intra-arterially improved survival in patients with unresectable pancreatic adenocarcinoma.

Tegafur chemotherapy for the treatment of gut and liver cancer.

Thirteen patients with cancer of the gut, six with hepatocellular carcinoma and three with cancer of the bile duct have been treated with tegafur. All the patients were in an advanced stage of the disease with metastases to lymph-nodes or elsewhere. Each patient was given tegafur (oral daily dose of 600-1200 mg for 15-30 days with a dose-free interval of 25 days). Tegafur with other antiblastic drugs (such as cyclophosphamide, methotrexate, vincristine, doxorubicin, mitomycin) was given to ten patients. The results observed after the first treatment were as follows: partial remission in 14 patients (64%), no change in 4 (18%) and progression of the disease in 4 (18%). Only 10 patients among the 22 who were first treated, underwent one to three subsequent cycles of therapy obtaining with resultant partial remission in four cases, no change in two and progression of the disease in four patients. Side-effects (nausea and vomiting) during the treatment were recorded only in 14% of the patients. No significant impairment of blood functional tests has been documented. A comparison of the results obtained with tegafur and intravenous 5-fluorouracil has been made: the therapeutic effects of these two drugs are similar, but side-effects seem to be less during tegafur treatment.