Yttrium-90 radioembolization for intermediate-advanced hepatocellular carcinoma: a phase 2 study.

UNLABELLED: Yttrium-90 radioembolization (Y90RE) is a novel approach to radiation therapy for hepatocellular carcinoma (HCC), never tested in phase 2 studies. Fifty-two patients with intermediate (n.17) to advanced (n.35) HCC were prospectively recruited to assess, as the primary endpoint, efficacy of Y90RE on time-to-progression (TTP). Secondary endpoints were tumor response, safety, and overall survival (OS). All patients were Eastern Cooperative Oncology Group (ECOG) score 0-1, Child-Pugh class A-B7. Y90RE treatments aimed at a lobar delivery of 120 Gy. Retrospective dosimetric correlations were conducted and related to response. Fifty-eight treatments were performed on 52 patients. The median follow-up was 36 months. The median TTP was 11 months with no significant difference between portal vein thrombosis (PVT) versus no PVT (7 versus 13 months). The median OS was 15 months (95% confidence interval [CI], 12-18 months) with a nonsignificant trend in favor of non-PVT versus PVT patients (18 versus 13 months). Five complete responses occurred (9.6%), and the 2 year-progression rate was 62%. Objective response was 40.4%, whereas the disease control rate (78.8%) significantly affected survival (responders versus nonresponders: 18.4% versus 9.1%; P = 0.009). Tumor response significantly correlated with absorbed dose in target lesions (r = 0.60, 95% CI, 0.41-0.74, P < 0.001) and a threshold of 500 Gy predicted response (area under the curve, 0.78). Mortality at 30-90 days was 0%-3.8%. Various grades of reduction in liver function occurred within 6 months in 36.5% of patients, with no differences among stages. On multivariate analysis, tumor response was the sole variable affecting TTP (P < 0.001) and the second affecting survival (after Child-Pugh class). CONCLUSION: Y90RE is an effective treatment in intermediate to advanced HCC, particularly in the case of PVT. Further prospective evaluations comparing Y90RE with conventional treatments are warranted.

Use of a retrievable vena cava filter with low-intensity anticoagulation for prevention of pulmonary embolism in patients with cancer: an observational study in 106 cases.

PURPOSE: To evaluate a retrievable inferior vena cava (IVC) filter in combination with low-intensity oral anticoagulation for prevention of pulmonary embolism (PE) in patients with malignancy complicated by thromboembolic disease. MATERIALS AND METHODS: From October 2005 to December 2009, 107 Bard G2 filters were placed in 106 patients. Forty-eight patients had deep vein thrombosis (DVT) alone, 53 had PE with DVT, and five had PE with no evidence of DVT. After an initial period of anticoagulation with heparin, low-intensity oral anticoagulant therapy to achieve a target International Normalized Ratio of 1.5-2.0 was instituted. Follow-up computed tomography to evaluate the pulmonary circulation, IVC, and lower limbs was performed at 3 and 6 months. RESULTS: PE recurred in three of 58 patients (5.2%). None of the 48 patients with DVT alone developed PE, nor was there any recurrence of DVT. The filter was removed in 14 patients (13.2%). No complications occurred during the retrieval procedure. A total of 16 complications occurred in seven patients: one migration (0.9%); four cases of vena cava thrombosis (3.7%), three of which were associated with recurrent PE (2.8%); one filter fracture (0.9%); and one IVC penetration (0.9%). Filter tilting greater than 15° occurred in six patients (5.7%) and was associated with other complications in five (4.7%). CONCLUSIONS: In patients with malignancies complicated by venous thromboembolic disease, an IVC filter together with low-intensity anticoagulation may be a possible treatment strategy for PE prophylaxis. Controlled studies are warranted.

Spontaneous bronchobiliary fistula: Case report.

Bronchobiliary fistula (BBF) is a rare condition that results from the communication between the bile ducts and the bronchial tree. It is characterized by the presence of bile in the sputum as pathognomonic symptom, and it is often associated with suspicious pneumonia. The most common causes include infections (e.g. echinococcosis), hepatobiliary surgery, blunt torso traumas, tumors and percutaneous transhepatic procedures. Opinions about BBF treatment are still controversial as it can be treated by both conservative and surgical procedures, while pharmacological treatments are only rarely used. This case report presents a patient who had been diagnosed with chronic BBF of unknown cause, underwent several ineffective conservative procedures and was at last surgically treated.

Pulmonary nodules: volume repeatability at multidetector CT lung cancer screening.

PURPOSE: To assess in vivo volumetric repeatability of an automated software algorithm in pulmonary nodules detected during a lung cancer screening trial. MATERIALS AND METHODS: This study was approved by an institutional review board. Written informed consent was obtained from all participants. Data were collected from the Multicentric Italian Lung Detection project, a randomized controlled lung cancer screening trial. The first 1236 consecutive baseline computed tomographic (CT) studies performed at the Istituto Nazionale Tumori of Milan were evaluated. Among the enrolled participants, those who underwent repeat low-dose CT after 3 months and had at least one indeterminate nodule with a volume of more than 60 mm(3) (diameter of 4.8 mm or greater) were considered. Nonsolid, part-solid, and pleural-based nodules were excluded from this study. A descriptive analysis was performed by calculating means and standard deviations of nodule volumes at three assessment times (at baseline and 3 and 12 months later). The volume measurement repeatability was determined by using the approach described by Bland and Altman. RESULTS: One hundred one subjects (70 men, 31 women; mean age, 58 years) with 233 eligible nodules (mean volume, 98.3 mm(3); range, 5-869 mm(3)) were identified. The 95% confidence interval for difference in measured volumes was in the range of +/-27%. About 70% of measurements had a relative difference in nodule volume of less than 10%. No malignant lesions were registered during the follow-up of these subjects. CONCLUSION: Semiautomatic volumetry is sufficiently accurate and repeatable and may be useful in assisting with lung nodule management in a lung cancer screening program.

Self-expanding metal stents in gastrointestinal interventional radiology: technical problems.

AIMS AND BACKGROUND: To analyze the procedural difficulties in the placement of metal stents in stenoses of the digestive tract and optimize the technique. METHODS: Twenty-nine patients with digestive tract stenoses were treated from January 1999 to December 2004. In 14 cases the stricture was anastomotic (9 colorectal, 3 esophageal, 1 gastroesophageal and 1 gastrojejunal), in 13 esophageal, in 1 gastric and in 1 duodenal. The stenosis was due to scarring in 5 patients and was malignant in 24 patients (primary in 17 cases and secondary in 7 cases). RESULTS: The procedure achieved technical success in all cases but 2. For each of the different segments the technical difficulties and the adopted procedural solutions were analyzed. CONCLUSIONS: The interventional radiology approach yielded results comparable to those reported for the endoscopic method and was always well tolerated. The need to rely on materials mostly designed for endoscopic use can make radiological use difficult in some cases.

Clinical activity of androgen deprivation therapy in patients with metastatic/relapsed androgen receptor-positive salivary gland cancers.

BACKGROUND: Androgen deprivation therapy has some clinical activity in selected salivary gland cancer histotypes, with androgen receptor expression. METHODS: We retrospectively analyzed patients with androgen receptor-expressing recurrent/metastatic salivary gland cancer, treated with androgen deprivation therapy. Protein expression of androgen receptor and ErbB family members was investigated. Progression-free survival (PFS) and overall survival (OS) were the main endpoints. RESULTS: Seventeen patients were identified. No significant toxicities were reported. Overall response rate was 64.7%; 3-year PFS and 5-year OS were 11.8% and 19.3%, respectively. Androgen receptor overexpression may be sustained by gain of chromosome X (58%) and TP53 mutation (44%). No association between response to androgen deprivation therapy and epidermal growth factor receptor (EGFR), human epidermal growth factor receptor (HER)2, HER3 expression, PIK3CA mutations, or phosphatase and tensin homolog (PTEN) deletion was identified. CONCLUSION: We confirm the activity of androgen deprivation therapy in androgen receptor-expressing recurrent/metastatic salivary gland cancers. The hypothesis that an androgen receptor increased gene copy number may represent a possible mechanism of primary resistance should be further investigated.

Transarterial chemoembolization for hepatocellular carcinoma with a new generation of beads: clinical-radiological outcomes and safety profile.

PURPOSE: To evaluate the short-term safety and efficacy of the new generation of 70-150 µm drug-eluting beads (M1 DEB) in patients with hepatocellular carcinoma undergoing transarterial chemoembolization (TACE) as a primary therapy or as a bridge to liver transplantation (LT). METHODS: Forty-five consecutive patients underwent TACE with M1 DEB loaded with doxorubicin (DEBDOX/M1). Clinical data were recorded at 12, 24, and 48 h, 7 and 30 days after treatment. Response was assessed by computed tomographic scan according to the modified response evaluation criteria in solid tumors criteria, and a second DEBDOX/M1 TACE was scheduled within 6 weeks in case of a noncomplete response. RESULTS: All patients had well-compensated cirrhosis (97.7 % Child A, 44.4 % hepatitis C virus, median age 61 years). Twenty patients (44.4 %) had Barcelona Clinic for Liver Cancer class B disease; the median number of nodules and their sum of diameters were 2 (range 1-6) and 43 mm (range 10-190), respectively. The mean number of TACE procedures per patient was 1.4. Objective response rate (complete + partial response) was 77.7 % with a median time to best response of 3 months (95 % confidence interval 2-4). In 13 patients, DEBDOX/M1 TACE served as a bridge/downstaging to LT/surgery. Pathology showed that more than 90 % necrosis was achieved in 10 of 28 nodules. DEBDOX/M1 TACE was well tolerated, and the grade 3/4 adverse event rate was low (1 of 65 procedures). CONCLUSION: DEBDOX/M1 TACE is an effective procedure with a favorable safety profile and promising results in terms of objective response rate, tumor downstaging, and necrosis.

Intrahepatic flow redistribution in patients treated with radioembolization.

INTRODUCTION: In planning Yttrium-90 ((90)Y)-radioembolizations, strategy problems arise in tumours with multiple arterial supplies. We aim to demonstrate that tumours can be treated via one main feeding artery achieving flow redistribution by embolizing accessory vessels. METHODS: One hundred (90)Y-radioembolizations were performed on 90 patients using glass microspheres. In 19 lesions/17 patients, accessory branches were found feeding a minor tumour portion and embolized. In all 17 patients, the assessment of the complete perfusion was obtained by angiography and single photon emission computerized tomography-computerized tomography (SPECT-CT). Dosimetry, toxicity, and tumor response rate of the patients treated after flow redistribution were compared with the 83 standard-treated patients. Seventeen lesions in 15 patients with flow redistribution were chosen as target lesions and evaluated according to mRECIST criteria. RESULTS: In all patients, the complete tumor perfusion was assessed immediately before radioembolization by angiography in all patients and after the (90)Y-infusion by SPECT-CT in 15 of 17 patients. In the 15 assessable patients, the response rate in their 17 lesions was 3 CR, 8 PR, and 6 SD. Dosimetric and toxicity data, as well tumour response rate, were comparable with the 83 patients with regular vasculature. CONCLUSIONS: All embolization procedures were performed successfully with no complications, and the flow redistribution was obtained in all cases. Results in term of toxicity, median dose administered, and radiological response were comparable with standard radioembolizations. Our findings confirmed the intratumoral flow redistribution after embolizing the accessory arteries, which makes it possible to treat the tumour through its single main feeding artery.

Correlation between radiotherapy and suture fistulas following colo-anal anastomosis for carcinoma of the rectum evaluation of 152 consecutive patients.

INTRODUCTION: The aim of this study was to evaluate the prevalence of suture fistulas and their possible correlation with adjuvant therapy in patients who underwent colo-anal anastomosis and J pouch reconstruction with a protective colostomy. The reliability of the radiological screening and monitoring program was also verified. METHODS: One hundred and fifty-two consecutive patients were evaluated radiologically with water-soluble radio-opaque contrast enema before surgery for closure of the protective colostomy. Fifty-seven patients were treated with surgery alone (group A) and 95 patients received adjuvant treatment (group B). RESULTS: A total of 54 fistulas were seen: 17 in group A (28.9% of patients in group A) and 37 in group B (38.9% of patients in group B). Six fistulas involved the rectovaginal septum. All fistulas were managed medically. The time to resolution was 30 days in 76.4% of patients in group A and about 50 days in 82% of patients in group B. Rectovaginal fistulas always took much longer to heal in both groups and failed to heal in two of the four cases in group B. CONCLUSIONS: Two factors appear to contribute to the high prevalence of fistulas in this series: extension of radiological screening to all operated patients and adjuvant radiotherapy. However, the postoperative course was not compromised by radiotherapy in that these fistulas resolved with medical treatment alone, although healing took longer. The incidence of rectovaginal fistulas was substantially the same in the two groups, but two of the four occurring in group B did not heal. Postoperative monitoring with water-soluble contrast enema appears to be the diagnostic procedure of choice because it is well tolerated, non-invasive and a reliable aid in planning surgical bowel recanalization since no false negative cases were detected clinically after closure of the colostomy.

Activity of abiraterone in rechallenging two AR-expressing salivary gland adenocarcinomas, resistant to androgen-deprivation therapy.

Androgen-deprivation therapy (ADT) has been reported to be active in androgen receptor (AR)-expressing, relapsed/metastatic (RM), salivary gland cancers (SGCs). Abiraterone, an inhibitor of androgen synthesis, has recently been approved as a second-line treatment in hormone-resistant (HR) prostate cancer (PCa) patients. Two patients with AR-positive HR-RM adenocarcinoma, NOS of the salivary glands have been treated with abiraterone. This is the first time that this agent has been reported to be active in tumors other than HRPCa. Immunohistochemical analysis showed overexpression of EGFR, HER2, and HER3 in both untreated primary tumors. Sequencing analysis revealed a TP53 non-functional mutation in one case and a PIK3CA-activating mutation in the other. In conclusion, second line activity of ADT in AR-expressing, adenocarcinoma, NOS of salivary glands further strengthens the pathogenic and therapeutic role of AR signaling in AR-positive SGCs.

CT cholangiography: assessment of feasibility and diagnostic reliability.

OBJECTIVE: To assess the reliability of computed tomography (CT) cholangiography in evaluating the anatomy of the intrahepatic biliary ducts. MATERIALS AND METHODS: Twenty-eight patients underwent CT cholangiography at the National Cancer Institute of Milan, Italy. Twenty-one patients were candidates for liver surgery and seven had suspected postoperative biliary complications. The patients had not dilatation of the intrahepatic biliary ducts at US examination and bilirubin levels were not higher than 2 mg/dl. To define the reability of the CT cholangiography, a scoring system (from 0 to 3) was used for each order of biliary branches. RESULTS: In all cases, it was technically possible to carry out the CT cholangiography according to the protocol. There were no adverse reactions to the contrast agent. Two radiologists gave the maximum score of 3 for visualisation of the first- and second-order biliary branches in all cases. For visualisation of third- and fourth-order biliary branches the maximum score of 3 was given in 18 patients, a score of 2 in 8 patients and a score of 1 in 2 patients. Three anatomical variants of biliary ducts were detected. CT cholangiography was diagnostic in all seven cases of suspected postoperative biliary complications. CONCLUSION: Our work confirms the high spatial resolution and reability of CT cholangiography in evaluating the intrahepatic biliary anatomy of patients who are candidates for liver surgery, with non-dilated biliary ducts and with bilirubin levels no higher than 2 mg/dl.

Percutaneous transhepatic biliary drainage in the management of postsurgical biliary leaks in patients with nondilated intrahepatic bile ducts.

PURPOSE: To assess the feasibility of percutaneous transhepatic biliary drainage (PTBD) for the treatment of postsurgical biliary leaks in patients with nondilated intrahepatic bile ducts, its efficacy in restoring the integrity of bile ducts, and technical procedures to reduce morbidity. METHODS: Seventeen patients out of 936 undergoing PTBD over a 20-year period had a noncholestatic liver and were retrospectively reviewed. All patients underwent surgery for cancer and suffered a postsurgical biliary leak of 345 ml/day on average; 71% were in poor condition and required permanent nutritional support. An endoscopic approach failed or was excluded due to inaccessibility of the bile ducts. RESULTS: Established biliary leaks and site of origin were diagnosed an average of 21 days (range 1-90 days) after surgery. In all cases percutaneous access to the biliary tree was achieved. An external (preleakage) drain was applied in 7 cases, 9 patients had an external-internal fistula bridging catheter, and 1 patient had a percutaneous hepatogastrostomy. Fistulas healed in an average of 31 days (range 3-118 days ) in 15 of 17 patients (88%) following PTBD. No major complications occurred after drainage. Post-PTBD cholangitis was observed in 6 of 17 patients (35%) and was related to biliary sludge formation occurring mostly when drainage lasted >30 days and was of the external-internal type. Median patient survival was 17.7 months and in all cases the repaired biliary leaks remained healed. CONCLUSIONS: PTBD is a feasible, effective, and safe procedure for the treatment of postsurgical biliary leaks. It is therefore a reliable alternative to surgical repair, which entails longer hospitalization and higher costs.

The role of interventional radiology in biliary complications after orthotopic liver transplantation: a single-center experience.

This study evaluated interventional radiological experience in the management of biliary complications of OLT at the National Cancer Institute of Milan. Seventeen patients who had undergone orthotopic liver transplantation in various hospital were referred to our unit with biliary complications. Group I consisted of 8 patients with anastomotic biliary fistula who came to our attention a short time after transplantation. Group II consisted of 9 patients with anastomotic strictures who came to our attention in a longer period. Two different interventional radiological approaches were used: (a) percutaneous transhepatic biliary drainage (PTBD) in the presence of fistulas in patients of group I; and (b) percutaneous transhepatic biliary drainage combined with dilatation of the strictures with a balloon catheter in patients of group II. On the whole resolution of the biliary complications was achieved in 13 of the 17 cases treated (76.5%), 5 of 8 in group I and 8 of 9 in group II. No secondary stenosis after PTBD were observed in group I, whereas two patients of group II needed a second dilatation. Percutaneous biliary drainage is indicated as a valid treatment in the management of biliary complications, either to allow closure of the fistula either to perform balloon dilatation of stenosis.