Long-Term Follow-up Results of the DANTE Trial, a Randomized Study of Lung Cancer Screening with Spiral Computed Tomography.

RATIONALE: Screening for lung cancer with low-dose spiral computed tomography (LDCT) has been shown to reduce lung cancer mortality by 20% compared with screening with chest X-ray (CXR) in the National Lung Screening Trial, but uncertainty remains concerning the efficacy of LDCT screening in a community setting. OBJECTIVES: To explore the effect of LDCT screening on lung cancer mortality compared with no screening. Secondary endpoints included incidence, stage, and resectability rates. METHODS: Male smokers of 20+ pack-years, aged 60 to 74 years, underwent a baseline CXR and sputum cytology examination and received five screening rounds with LDCT or a yearly clinical review only in a randomized fashion. MEASUREMENTS AND MAIN RESULTS: A total of 1,264 subjects were enrolled in the LDCT arm and 1,186 in the control arm. Their median age was 64.0 years (interquartile range, 5), and median smoking exposure was 45.0 pack-years. The median follow-up was 8.35 years. One hundred four patients (8.23%) were diagnosed with lung cancer in the screening arm (66 by CT), 47 of whom (3.71%) had stage I disease; 72 control patients (6.07%) were diagnosed with lung cancer, with 16 (1.35%) being stage I cases. Lung cancer mortality was 543 per 100,000 person-years (95% confidence interval, 413-700) in the LDCT arm versus 544 per 100,000 person-years (95% CI, 410-709) in the control arm (hazard ratio, 0.993; 95% confidence interval, 0.688-1.433). CONCLUSIONS: Because of its limited statistical power, the results of the DANTE (Detection And screening of early lung cancer with Novel imaging TEchnology) trial do not allow us to make a definitive statement about the efficacy of LDCT screening. However, they underline the importance of obtaining additional data from randomized trials with intervention-free reference arms before the implementation of population screening.

Prognostic value of CT integrated with clinical and laboratory data during the first peak of the COVID-19 pandemic in Northern Italy: A nomogram to predict unfavorable outcome.

PURPOSE: To evaluate the prognostic role of chest computed tomography (CT), alone or in combination with clinical and laboratory parameters, in COVID-19 patients during the first peak of the pandemic. METHODS: A retrospective single-center study of 301 COVID-19 patients referred to our Emergency Department (ED) from February 25 to March 29, 2020. At presentation, patients underwent chest CT and clinical and laboratory examinations. Outcomes included discharge from the ED after improvement/recovery (positive outcome), or admission to the intensive care unit or death (poor prognosis). A visual quantitative analysis was formed using two scores: the Pulmonary Involvement (PI) score based on the extension of lung involvement, and the Pulmonary Consolidation (PC) score based on lung consolidation. The prognostic value of CT alone or integrated with other parameters was studied by logistic regression and ROC analysis. RESULTS: The impact of the CT PI score [≥15 vs. ≤ 6] on predicting poor prognosis (OR 5.71 95 % CI 1.93-16.92, P = 0.002) was demonstrated; no significant association was found for the PC score. Chest CT had a prognostic role considering the PI score alone (AUC 0.722) and when evaluated with demographic characteristics, comorbidities, and laboratory data (AUC 0.841). We, therefore, developed a nomogram as an easy tool for immediate clinical application. CONCLUSIONS: Visual analysis of CT gives useful information to physicians for prognostic evaluations, even in conditions of COVID-19 emergency. The predictive value is increased by evaluating CT in combination with clinical and laboratory data.

A randomized study of lung cancer screening with spiral computed tomography: three-year results from the DANTE trial.

RATIONALE: Screening for lung cancer with modern imaging technology may decrease lung cancer mortality, but encouraging results have only been obtained in uncontrolled studies. OBJECTIVES: To explore the effect of screening with low-dose spiral computed tomography (LDCT) on lung cancer mortality. Secondary endpoints are incidence, stage at diagnosis, and resectability. METHODS: Male subjects, aged 60 to 75 years, smokers of 20 or more pack-years, were randomized to screening with LDCT or control groups. All participants underwent a baseline, once-only chest X-ray and sputum cytology examination. Screening-arm subjects had LDCT upon accrual to be repeated every year for 4 years, whereas controls had a yearly medical examination only. MEASUREMENTS AND MAIN RESULTS: A total of 2,811 subjects were randomized and 2,472 were enrolled (LDCT, 1,276; control, 1,196). After a median follow-up of 33 months, lung cancer was detected in 60 (4.7%) patients receiving LDCT and 34 (2.8%) control subjects (P = 0.016). Resectability rates were similar in both groups. More patients with stage I disease were detected by LDCT (54 vs. 34%; P = 0.06) and fewer cases were detected in the screening arm due to intercurrent symptoms. However, the number of advanced lung cancer cases was the same as in the control arm. Twenty patients in the LDCT group (1.6%) and 20 controls (1.7%) died of lung cancer, whereas 26 and 25 died of other causes, respectively. CONCLUSIONS: The mortality benefit from lung cancer screening by LDCT might be far smaller than anticipated.

Validation of the Red Flags Index for Early Diagnosis of Crohn's Disease: A Prospective Observational IG-IBD Study Among General Practitioners.

INTRODUCTION: Diagnostic delay >12 months is frequent in Crohn's disease [CD]. Recently, the International Organization for Inflammatory Bowel Disease [IO-IBD] developed a tool to identify early CD and reduce diagnostic delay. Subjects with an index ≥8 are more likely to have suspected CD (odds ratio [OR] 205, p <0.0001). We aimed to validate this questionnaire at the community level in patients seen by the general practitioners [GPs] in two large areas of Lombardy, Italy. METHODS: Consecutive adult patients referring to the GP were screened. The GPs administered the Red Flags [RF] questionnaire to the eligible patients. All patients were referred to the nearest participating centre to confirm or exclude the diagnosis of CD. Sensitivity, specificity, and positive and negative predictive values [PPV, NPV] of the RF index [RFI] were calculated. Patients lost to follow-up after the first gastroenterological visit were analysed using a non-responder imputation, assuming they were negative for CD diagnosis. RESULTS: From November 2016 to November 2019, 112 patients were included. A total of 66 subjects [59%] completed the study after the first gastroenterological visit. The prevalence of CD was 3.6% in the study population [4/112]. The RF index had 50% sensitivity, 58% specificity, 4% PPV, and 97% NPV. A combined diagnostic strategy with faecal calprotectin [FC] [RFI ≥8 and/or FC >250 ng/g] resulted in significantly improved accuracy: sensitivity 100% [29-100%], specificity 72% [55-85%], PPV = 21% [5-51%], NPV = 100% [88-100%]. CONCLUSIONS: The RF Index combined with FC is a valid tool to identify patients with high probability of having CD at early stage.

Lung cancer screening with spiral CT: baseline results of the randomized DANTE trial.

BACKGROUND: Despite the high survival rates reported for screening-detected cases, the potential of screening of high-risk subjects for reducing lung cancer mortality is still unproven. We herewith present the baseline results of a randomized trial comparing screening for lung cancer with annual spiral computed tomography (CT) versus a yearly clinical review. METHODS: Male subjects, 60-74 years old, and smokers of 20+ pack-years were enrolled. All participants received a baseline medical examination, chest X-rays (CXR) and sputum cytology upon accrual. Subjects randomized in the spiral CT group received a spiral CT scan at baseline, then yearly for the following 4 years. For controls, a yearly clinical examination was scheduled for the following 4 years. RESULTS: 2472 subjects were randomized (1276 spiral CT arm, 1196 controls). Age, smoking exposure and co-morbid conditions were similar in the two groups. In the spiral CT group, 28 lung cancers were detected, 13 of which were visible in the baseline chest X-rays (overall prevalence 2.2%). Sixteen out of 28 tumours (57%) were stage I, and 19 (68%) were resectable. In the control group, eight cases were detected by the baseline chest X-rays (prevalence rate 0.67%), four (50%) were stage I, and six (75%) were resectable. CONCLUSIONS: Baseline lung cancer detection rate in the spiral CT arm was higher than in most published studies. The stage I detection rate was increased four-fold by spiral CT versus chest X-rays. However, more tumours in an advanced stage were also detected by CT. The high resection rate of screening-detected patients suggests a possible increase in cure rate. However, longer follow-up is required for definitive conclusions. This trial has been registered at www.Clinicaltrials.gov, registration No. NCT00420862.

Lung cancer screening with low-dose spiral computed tomography: evidence from a pooled analysis of two Italian randomized trials.

The benefits and harms of lung cancer (LC) screening with low-dose computed tomography (LDCT) are debatable. Positive results from the US National Lung Screening Trial were not evident in the European trials, possibly due to their smaller sample sizes. To address this issue, we conducted a patient-level pooled analysis of two Italian randomized controlled trials. Data from DANTE and MILD trials were combined for a total of 3640 individuals in the LDCT arm and 2909 in the control arm. LC and overall mortality were analyzed using multivariate hazard ratios (HRs) and log-rank tests stratified by study. The median follow-up was 8.2 years, with a total of 30 480 person-years in the LDCT arm and 22 157 in the control arm. A total of 192 patients developed LC in the LDCT arm and 105 in the control arm. Half of the LC cases in the LDCT arm had stage IA or IB cancer, as compared with 21% in the control arm. Overall mortality rates/100 000 person-years were 925 in the LDCT arm and 1074 in the control arm, and LC mortality rates were 299 and 357, respectively. The multivariate pooled overall mortality HR was 0.89 (95% confidence interval: 0.74-1.06) and the LC mortality HR was 0.83 (95% confidence interval: 0.61-1.12) for the LDCT arm as compared with the control arm. The present pooled analysis shows a nonsignificant 11% reduction in overall mortality in individuals undergoing LDCT screening as compared with the control arm. A pooled analysis of all European trials would be a useful contribution to assess the real benefit of LDCT screening.

Minimal focal steatosis of liver after islet transplantation in humans: a long-term study.

Several reports have been published on islet transplantation in humans, but few data are available on the effect of islet infusion on the hepatic structure. Our aim was to evaluate in a longitudinal study the impact on the liver of intrahepatic islet transplantation. Clinical outcome and liver imaging were evaluated in 31 cases of islet-kidney transplantation (follow-up 38 +/- 4 months, range 12-96 months). Patients were divided into three groups: full function (FF, 9 cases: established insulin independence); partial function (PF, 16 cases: transient insulin independence, prolonged C-peptide secretion): no function (NF, 6 cases: exhaustion of C-peptide secretion within the first year). Upper abdomen sonogram was regularly performed during the whole follow-up period. Percutaneous liver biopsy was performed in case of echographic abnormalities. Multiple small areas of focal hyperechogenicity were observed in nine cases after 6-12 months. These findings were observed only in FF (two) and in PF (seven) patients. Fasting C-peptide levels at the time of echography were higher in negative than in positive patients (2.42 +/- 0.16 vs. 1.51 +/- 0.10 ng/ml, p = 0,0001). Liver biopsies showed focal macrovesicular steatosis, surrounded by normal liver parenchyma. Normal liver function was maintained. In conclusion, our results indicate that islet transplantation can lead to structural changes of the liver parenchyma (focal steatosis). It is more often observed in patients with partial function. Sonogram can be considered a specific method to reveal liver changes after islet transplantation.

Percutaneous vs. surgical placement of hepatic artery indwelling catheters for regional chemotherapy.

BACKGROUND/AIMS: Intra-arterial hepatic chemotherapy based on floxuridine infusion is an effective treatment for hepatic metastases from colorectal cancer. The aim of the present study is the comparative analysis of surgical and percutaneous transaxillary approaches to implant a catheter into the hepatic artery for intra-arterial hepatic chemotherapy with floxuridine. METHODOLOGY: Fifty-six patients received an arterial device for intra-arterial hepatic chemotherapy. Twenty-eight patients (LPT group) underwent laparotomy to implant the catheter into the hepatic artery, the other 28 patients (PCT group) received a percutaneous catheter into the hepatic artery through a transaxillary percutaneous access. Safety and efficacy of surgical and percutaneous transaxillary approaches were comparatively analyzed in terms of number of intra-arterial hepatic chemotherapy cycles administered, device-related complications causing suppression of intra-arterial hepatic chemotherapy, and biological costs of the procedures. RESULTS: Mean postoperative hospitalization was 8.2 +/- 2.2 days in the LPT group and 1.8 +/- 0.7 days in the PCT group (P < 0.0001), while mean analgesic requirements were 9.7 +/- 3.2 doses in the LPT group and 2 +/- 0.9 doses in the PCT group (P < 0.0001). Mean number of intra-arterial hepatic chemotherapy cycles administered was 6.5 +/- 4.2 in the LPT group and 4.3 +/- 3.4 in the PCT group (P = 0.038). The overall incidence of device-related complications causing suppression of intra-arterial hepatic chemotherapy was 42.7% in the PCT group and 7.1% in the LPT group (P = 0.005). CONCLUSIONS: Surgical implantation is still recommended when laparotomy has to be performed for other contextual procedures, such as colorectal or hepatic resection, while percutaneous transaxillary catheter placement is indicated for palliative or neoadjuvant intra-arterial hepatic chemotherapy.

[Impact of preoperative locoregional chemotherapy with fluorodeoxyuridine on the outcome of liver resection]. / Impatto della chemioterapia locoregionale preoperatoria con fluorodesossiuridina (FUDR) sulla chirurgia resettiva epatica.

The aim of the study was to evaluate the effects of preoperative intra-arterial hepatic chemotherapy (IAHC) on the outcome of liver resections for hepatic metastases from colorectal cancer. Twelve patients (IAHC group) treated by IAHC with fluorodeoxyuridine (FUdR) and subsequent liver resection and 40 patients who underwent liver resection without preliminary IAHC (non-IAHC group) were analysed comparatively in terms of age, gender, concomitant diseases, previous abdominal surgery, type of hepatic resection, use of portal clamping, and associated surgical procedures. For the purposes of the study, length of operation, intraoperative blood losses, perioperative transfusions, length of hospitalisation, complications and mortality were also recorded. The two groups were comparable (p = n.s.) for those variables affecting the perioperative course. As regards the end points of the study, no significant differences were recorded in length of operation, intraoperative blood losses, perioperative transfusions [except for more postoperative plasma transfusions in the IAHC group (16.7% vs 5.0%, p = 0.009)] and postoperative complications (9.1% vs 17.5%, p = 0.415). Postoperative mortality consisted in one patient in the IAHC group. Postoperative hospitalization was significantly longer in the non-IAHC group (median: 8 vs 10, range: 6-13 vs 5-33 days; p = 0.004). IAHC does not negatively affect the outcome of subsequent liver resection.

Technique, complications, and therapeutic efficacy of percutaneous transplantation of human pancreatic islet cells in type 1 diabetes: the role of US.

PURPOSE: To retrospectively evaluate the role of ultrasonography (US) with regard to the technique, complications, and therapeutic efficacy of percutaneous intrahepatic transplantation of human pancreatic islet cells with combined US and fluoroscopic guidance. MATERIALS AND METHODS: The institutional review board approved the study, and informed consent was obtained from all patients. After kidney transplantation, 34 uremic diabetic patients (20 men, 14 women; mean age, 40.9 years; age range, 29-61 years) underwent percutaneous intrahepatic transplantation of islet cells. Portal vein patency and liver echotexture were preliminarily assessed with color Doppler US. US also was used to identify early complications and presence (group A patients) or absence (group B patients) of hepatic parenchymal changes. Differences between the two groups in C peptide serum level and range were analyzed (Mann-Whitney test). Therapeutic efficacy of transplantation was assessed with regard to insulin independence period (rate and duration), exogenous insulin requirement, glycated hemoglobin, and C peptide level. A C peptide level of more than 0.5 ng/mL was considered to indicate well-functioning islet cells. RESULTS: Fifty-eight procedures were technically successful, with a single puncture used in 51 of 58 patients. Complications occurred in three of 58 patients (hemoperitoneum, hemothorax, and thrombosis in one patient each) and were conservatively treated and resolved. Duration of insulin independence in 12 patients was more than 3 months (mean, 21 months). Well-functioning islet cells at 6 years were found in 19 of 34 patients. Hyperechoic parenchymal changes were evident at US in 12 of 34. No statistically significant difference in C peptide level was found between groups (P > .05), but a wider range of values was recorded in group B. CONCLUSION: Complication rate of transplantation with US and fluoroscopic guidance was low. Well-functioning islet cells were found in about 50% of patients at 6 years of follow-up. Hepatic implantation of islet cells was evident on US images in more than one-third of patients.

Hemorrhage from a right hepatic artery pseudoaneurysm: endovascular treatment with a coronary stent-graft.

PURPOSE: To report a novel case demonstrating the successful endovascular treatment of a right hepatic artery pseudoaneurysm using a balloon-expandable coronary stent-graft. CASE REPORT: A 60-year-old woman underwent surgical treatment for a Klatskin tumor, but her postoperative course was complicated by serious blood loss. An emergent celiac angiogram through a right transfemoral approach demonstrated a small iatrogenic pseudoaneurysm in the proximal right hepatic artery. A 7-F guiding catheter was positioned at the origin of the celiac trunk, and a Jostent coronary stent-graft mounted on a 2.7-F, 4-mm x 30-mm balloon catheter was successfully placed across the aneurysm neck. The final angiogram demonstrated total exclusion of the pseudoaneurysm with preservation of the arterial lumen. The hemodynamic condition of the patient became stable. At 12-month follow-up, duplex scanning confirmed regular right hepatic artery patency and absence of thrombotic tissue or signs of infection around the stent-graft. CONCLUSION: For hepatic artery pseudoaneurysms, endovascular repair using small covered stents may be a viable alternative to transcatheter embolization. The use of coronary instruments facilitates treatment of vascular lesions in small caliber visceral vessels.

Complications after percutaneous transaxillary implantation of a catheter for intraarterial chemotherapy of liver tumors: clinical relevance and management in 204 patients.

OBJECTIVE: The purposes of the study were to evaluate the complications of patients who underwent percutaneous transaxillary implantation of a permanent catheter-port system for intraarterial hepatic chemotherapy and determine their clinical relevance and specific management. SUBJECTS AND METHODS. Catheter-port systems were placed in 204 patients with liver tumors (86.7% from colorectal metastases). Under sonographic and fluoroscopic guidance, a 5.8-French catheter was placed in the hepatic artery and connected to a subcutaneous reservoir after embolization of the gastroduodenal and right gastric arteries. Floxuridine plus dexamethasone and systemic low-dose heparin were administered. During the follow-up period, complications were classified as clinically not significant (type 1), clinically significant not requiring interruption of intrahepatic chemotherapy (type 2), clinically significant needing temporary suppression of intrahepatic chemotherapy (type 3), and clinically significant causing permanent suppression of intrahepatic chemotherapy (type 4). RESULTS: No complications occurred during the implantation procedures. The mean number of intrahepatic chemotherapy cycles was 8.1. The mean follow-up period was 270 days. Primary and secondary patency rates of the system were 71.6% and 91.2%, respectively. Temporary suppression of intrahepatic chemotherapy was necessary in 19.6% of the patients and definitive suppression, in 8.8%. Hepatic artery thrombosis, not recanalized by local thrombolysis, was the main cause of permanent intrahepatic chemotherapy interruption (4.4%). Catheter occlusions and cerebral complications were not observed. In 91.2% of the patients, intrahepatic chemotherapy could be completed. CONCLUSION: Percutaneous implantation of a removable and reimplantable catheter-port system for intrahepatic chemotherapy can be a safe procedure to treat unresectable liver metastases from colorectal cancer. Technical and pharmacologic complications with variable clinical relevance occurred, and various specific management strategies were necessary to reduce their incidence.