Luca Volterrani

Therapeutic efficacy of ipilimumab, an anti-CTLA-4 monoclonal antibody, in patients with metastatic melanoma unresponsive to prior systemic treatments: clinical and immunological evidence from three patient cases

The management of unresectable metastatic melanoma is a major clinical challenge because of the lack of reliably effective systemic therapies. Blocking cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) has recently been proposed as a strategy to enhance cell-mediated immune responses to cancer, and clinical trials have demonstrated that anti-CTLA-4 therapy can produce durable outcomes with different response patterns than cytotoxic chemotherapy. We enrolled eight out of 155 patients with advanced melanoma in a multicentre phase II trial that evaluated the activity and tolerability of ipilimumab, a fully human, anti-CTLA-4 monoclonal antibody (www.clinicaltrials.gov; NCT00289627; CA184-008). Here we report our experience with three of these patients, who experienced progressive disease after a variety of previous therapies, including prior immunotherapies, and who achieved good outcomes with ipilimumab. One patient had a partial response ongoing at 17+ months on ipilimumab despite failure with four prior therapies, and the other two patients showed durable stable disease, both still ongoing at 17+ and 20+ months, respectively. The patient achieving a partial response experienced no side effects while receiving ipilimumab. The other two patients developed immune-related adverse events (irAEs) including rash (one case; grade 2) and diarrhoea (both cases; grades 1 and 2, respectively); the histopathology of colon biopsy samples from both was suggestive of colitis, with an abundant CD8+ T-cell infiltrate. Nausea, vomiting and acute pancreatitis were also observed in one patient. In addition, immunohistochemical findings of a dense CD8+, TIA1+ and granzyme B+ lymphoid infiltrate within a biopsied lesion provide indirect evidence of functional T-cell activation induced by treatment. These case reports highlight the potential for anti-CTLA-4-based therapy in previously treated patients with advanced melanoma. Moreover, because the patterns of response to ipilimumab differ from chemotherapy, we need to understand how and when patients may respond to treatment so that appropriate clinical decisions can be made.

The role of US examination in the management of acute abdomen

Acute abdomen is a medical emergency, in which there is sudden and severe pain in abdomen of recent onset with accompanying signs and symptoms that focus on an abdominal involvement. It can represent a wide spectrum of conditions, ranging from a benign and self-limiting disease to a surgical emergency. Nevertheless, only one quarter of patients who have previously been classified with an acute abdomen actually receive surgical treatment, so the clinical dilemma is if the patients need surgical treatment or not and, furthermore, in which cases the surgical option needs to be urgently adopted. Due to this reason a thorough and logical approach to the diagnosis of abdominal pain is necessary. Some Authors assert that the location of pain is a useful starting point and will guide a further evaluation. However some causes are more frequent in the paediatric population (like appendicitis or adenomesenteritis) or are strictly related to the gender (i.e. gynaechologic causes). It is also important to consider special populations such as the elderly or oncologic patients, who may present with atypical symptoms of a disease. These considerations also reflect a different diagnostic approach. Today, surely the integrated imaging, and in particular the use of multidetector Computed Tomography (MDCT) has revolutionised the clinical approach to this condition, simplyfing the diagnosis but burdening the radiologists with the problems related to the clinical management. However although CT emerging as a modality of choice for evaluation of the acute abdomen, ultrasonography (US) remains the primary imaging technique in the majority of cases, especially in young and female patients, when the limitation of the radiation exposure should be mandatory, limiting the use of CT in cases of nondiagnostic US and in all cases where there is a discrepancy between the clinical symptoms and negative imaging at US.

Sigmoid diverticulitis: US findings

Acute diverticulitis (AD) results from inflammation of a colonic diverticulum. It is the most common cause of acute left lower-quadrant pain in adults and represents a common reason for acute hospitalization, as it affects over half of the population over 65 years with a prevalence that increases with age. Although 85% of colonic diverticulitis will recover with a nonoperative treatment, some patients may have complications such as abscesses, fistulas, obstruction, and /or perforation at presentation. For these reasons, different classifications were introduced through times to help clinicians to develop a correct diagnosis and guide the treatment and for the same reasons imaging is used in most cases both to realise a differential diagnosis and to guide the therapeutic management. US and CT are both usefull in diagnosis of diverticolitis, and their sensibility and specificity are similar. However CT scanning is essential for investigating complicated diverticular disease especially where there are diffuse signs and clinical suspicion of secondary peritonitis; instead in most uncomplicated cases the experienced sonographer may quickly confirm a diagnosis guided by the clinical signs. US is to be recommended in premenopausal women, and in young people to reduce dose exposure.

Three–dimensional analysis of pulmonary nodules by MSCT with Advanced Lung Analysis (ALA1) software

Purpose.The purpose of this study was to test the reproducibility of the three–dimensional (3D) Advanced Lung Analysis software (3D–ALA, GE Healthcare) in the estimation of pulmonary nodule volume.Materials and methods.We retrospectively reviewed the unenhanced multislice CT scans (Lightspeed Pro 16 GE) of 77 patients with a solitary pulmonary nodule (n=71) or metastatic pulmonary disease (n=6). A total of 103 pulmonary nodules (19 well–circumscribed, 45 juxtavascular and 39 juxtapleural) were analysed grouped into five classes based on diameter: <5 mm, 10 nodules (9.7%); ≥5 to <10 mm, 25 nodules (24.2%); ≥10 mm to <15 mm, 41 nodules (39.8%); ≥ 5 to <18 mm, 14 nodules (13.6% ); ≥ 8 to <30 mm, 13 nodules (12.62%). The following acquisition parameters were used: slice thickness 0.625 mm, reconstruction interval 0.4 mm, pitch 0.562:1, 140 kV, 300 mAs, field of view 13 cm, bone kernel. For each of the 103 nodules three, 3D volume measurements were obtained by the 3D–ALA software. The reproducibility of nodule segmentation was evaluated according to a visual score (1=optimal, ≥95%; 2=fair, 90–95%; 3=poor, ≤90%) by three observers working in consensus. The reproducibility of volume estimation was evaluated by comparing all 3D volume measurements and all segmentations obtained for each pulmonary nodule using the ANOVA test.Results.ALA–1 software allowed segmentation in all nodules (type 1 segmentation n=43, type 2 n=35, type 3 segmentation n=25). ALA–1 provided an identical 3D volume measurement in 62 nodules: [16 out of 19 well circumscribed (84.2%), 31 out of 45 juxtavascular (68.8%), 15 out of 39 juxtapleural (38.4%)]. Repeatability of 3D volume measurement was not possible in 41 out of 103 nodules [3 out of 19 (15.7%) well–circumscribed, 14 out of 45 (31.1%) juxtavascular, 24 out of 39 (61.5%) juxtapleural]. Among the 41 nodules with nonrepeatable 3D volume measurement, segmentation was scored as 1 in 2 out of 41 (4.8%), as 2 in 15 out of 41 (36.5%) and as 3 in 24 out of 41 (58.5%). The difference between the mean volume on three measurements and each type of nodule was not statistically significant (p>0.05).Conclusions.Three–dimensional volume measurement with ALARiassunto 1 software is reproducible for all nodules as regards dimension and site. ALA–1 software provided a good and reproducible volume measurement in well–circumscribed and most juxtavascular nodules. Volumetric evaluation and reproducibility of volume estimation in juxtapleural pulmonary nodules, particularly those adjacent to diaphragmatic pleura, is inadequate, and software improvement is needed.

Role of computed tomography in the diagnosis of acute lung injury/acute respiratory distress syndrome.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a complex pulmonary pathology with high mortality rates, manifesting over a wide range of severity. Clinical diagnosis relies on the following 4 criteria stated by the American-European Consensus Conference: acute onset of impaired gas exchange, severe hypoxemia defined as a PaO2 to FiO2 ratio <300 (PaO2 in mmHg), bilateral diffuse infiltration on chest X-ray; pulmonary artery wedge pressure of ≤18 mmHg to rule out cardiogenic causes of pulmonary edema. The aim of this study was to determine the usefulness of CT in the diagnosis and management of this condition.

Water/cortical bone decomposition: A new approach in dual energy CT imaging for bone marrow oedema detection. A feasibility study

INTRODUCTIONnMany studies aimed at validating the application of Dual Energy Computed Tomography (DECT) in clinical practice where conventional CT is not exhaustive. An example is given by bone marrow oedema detection, in which DECT based on water/calcium (W/Ca) decomposition was applied. In this paper a new DECT approach, based on water/cortical bone (W/CB) decomposition, was investigated.nnnMATERIALS AND METHODSnEight patients suffering from marrow oedema were scanned with MRI and DECT. Two-materials density decomposition was performed in ROIs corresponding to normal bone marrow and oedema. These regions were drawn on DECT images using MRI informations. Both W/Ca and W/CB were considered as material basis. Scatter plots of W/Ca and W/CB concentrations were made for each ROI in order to evaluate if oedema could be distinguished from normal bone marrow. Thresholds were defined on the scatter plots in order to produce DECT images where oedema regions were highlighted through color maps. The agreement between these images and MR was scored by two expert radiologists.nnnRESULTSnFor all the patients, the best scores were obtained using W/CB density decomposition.nnnCONCLUSIONSnIn all cases, DECT color map images based on W/CB decomposition showed better agreement with MR in bone marrow oedema identification with respect to W/Ca decomposition. This result encourages further studies in order to evaluate if DECT based on W/CB decomposition could be an alternative technique to MR, which would be important when short scanning duration is relevant, as in the case of aged or traumatic patients.

[Small renal oncocytoma (≤ 4 cm): enhancement patterns on triphasic spiral computed tomography].

In 18 patients with 19 RO, 9 hypervascularity and hypovascularity was identified in 9 and 10 RO, respectively, in the cortico-medullary phase (CMP). Hypervascular RO showed increased density in the CMP (151.4±38.5 HU) and a gradual wash-out in the nephrographic phase (133.8±34.6 HU) and excretory phase (79±23 HU). Hypovascular RO showed increased density in the CMP (87.8±20.1 UH) and a gradual wash-out in the nephrographic phase (100.3±33 UH) and excretory phase (20.9±86.9 UH).

Three-dimensional Volumetric Assessment with Thoracic CT: A Reliable Approach for Noncalcified Lung Nodules?

I thank Dr Lee for his interest in our study ( 1 ) and for informing us that our 16th reference has been retracted from the Journal of the American Medical Association. We were unaware of this at the time of submission of our revised article. In our study, 23 (25%) of 93 HCC nodules were sized 2–3 cm (combined treatment group, n = 15; RFA group, n = 8). Of these 23 nodules, local tumor progression was seen in three tumors in the combined treatment group and in four tumors in the RFA group. The rates of local tumor progression at 1, 2, 3, and 4 years were 13%, 24%, 24%, and 24% , respectively, in the combined treatment group and were 50% at all four times in the RFA group. There was no signifi cant difference ( P = .08 with log-rank test). However, as the number of 2–3-cm nodules was small and the P value was 0.08, we believe the further comparative study with larger number of 2–3-cm nodules might be recommended. Our ablation technique for HCCs sized 2.8–3.0 cm was insertion of two electrodes into the nodule. An adequate ablative margin is an important factor in preventing local tumor progression ( 2 ), but it may be diffi cult to obtain an adequate ablative margin in all nodules treated with RFA. At the start of our study, we expected that combined RFA and TACE would be helpful in achieving complete local control in nodules in which an adequate ablation margin was not obtained with RFA alone. However, better results with the combined treatment were not seen. Furthermore, macroscopic HCC type is important. Nakashima et al ( 3 ) reported that single nodular type with extranodular growth and confl uent multinodular Three-dimensional Volumetric Assessment with Thoracic CT: A Reliable Approach for Noncalcifi ed Lung Nodules?

Structured reporting for fibrosing lung disease: a model shared by radiologist and pulmonologist

ObjectivesTo apply the Delphi exercise with iterative involvement of radiologists and pulmonologists with the aim of defining a structured reporting template for high-resolution computed tomography (HRCT) of patients with fibrosing lung disease (FLD).MethodsThe writing committee selected the HRCT criteria—the Delphi items—for rating from both radiology panelists (RP) and pulmonology panelists (PP). The Delphi items were first rated by RPs as “essential”, “optional”, or “not relevant”. The items rated “essential” byxa0<xa080% of the RP were selected for the PP rating. The format of reporting was rated by both RP and PP.ResultsA total of 42 RPs and 12 PPs participated to the survey. In both Delphi round 1 and 2, 10/27 (37.7%) items were rated “essential” by more than 80% of RP. The remaining 17/27 (63.3%) items were rated by the PP in round 3, with 2/17 items (11.7%) rated “essential” by the PP. PP proposed additional items for conclusion domain, which were rated by RPs in the fourth round. Poor consensus was observed for the format of reporting.ConclusionsThis study provides a template for structured report of FLD that features essential items as agreed by expert thoracic radiologists and pulmonologists.

Role of CT in the preoperative diagnosis of a giant benign solitary fibrous tumor of the pleura

The authors emphasize the role of CT in the preoperative diagnosis of a giant benign solitary fibrous tumor of the pleura. CT can provide evidence of complete resection of the lesion, showing a pedunculated stalk. Aspiration cytology is not a reliable diagnostic approach.