Maria Antonietta Mazzei

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.

Safety and Potential Benefit of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Peritoneal Carcinomatosis From Primary or Recurrent Ovarian Cancer

To analyze the outcomes of cytoreductive surgery and HIPEC in patients with peritoneal carcinomatosis from ovarian cancer.

Diffusion-weighted magnetic resonance imaging in the evaluation of renal function: a preliminary study.

PurposeMagnetic resonance diffusion-weighted imaging (MR-DWI) is useful to assess proton motion by the computation of an apparent diffusion coefficient (ADC). This property could be used to assess renal damage, with special regard to unilateral dysfunction. The aim of this study was to estimate the correlation between ADC and the stage of chronic renal failure (CRF) using a spin-echo echo-planar imaging (SE-EPI) sequence with the sensitivity encoding (SENSE) technique.Materials and methodsFourteen patients (nine men and five women, mean age 49 years, range 22–66 years) underwent an MR examination on a 1.5-T system. Seven patients had a history of hypertension or CRF, one had Takayasu disease and one had nephrovascular hypertension. Five subjects without known kidney disease were used as controls. The glomerular filtration rate (GFR) assessed by Cockcroft-Gault’s equation was used as a functional marker. The imaging protocol consisted of T1- and T2-weighted sequences followed by a SE-EPI acquisition with a diffusion gradient of 600 s/mm2 and SENSE factor 2 and pixel-by-pixel ADC map reconstruction. In five patients, the SE-EPI-DWI sequence was repeated after i.v. administration of 1 mg of furosemide.ResultsADC was of 2.44±0.24×10−3 mm2/s in patients with normal GFR and of 2.05±0.33×10−3 mm2/s (p<0.05) in subjects with altered GFR; a significant difference was found between stage III and IV (p<0.01), whereas no differences were found between stage I and II (p=0.27) and between stage II and III (p=0.39). A good correlation was found between GFR and ADC (r=0.79; p<0.01), with no significant change after furosemide administration (p=0.7).ConclusionsDWI is a feasible MR technique for assessing renal damage. Further studies with scintigraphic correlation are needed to confirm these results and to establish reference values for this imaging technique.RiassuntoScopoLa risonanza magnetica (RM) in diffusione (diffusion weighted, DW) permette di ottenere dati quantitativi sul movimento dei protoni liberi di acqua determinando il coefficiente di diffusione apparente (apparent diffusion coefficient, ADC). Questa capacità potrebbe essere usata per stabilire il danno parenchimale renale, in particolare nelle disfunzione unilaterali. Scopo del presente lavoro è quello di valutare la correlazione tra ADC e grado di insufficienza renale cronica utilizzando una sequenza SE Eco-planare (SS-EPI) a cui è stato applicato la tecnica di SENSitivity Encoding (SENSE).Materiali e metodiQuattordici pazienti (9 maschi e 5 femmine, età media 49 anni, range 22–66) sono stati sottoposti ad esame RM con sistema ad alto campo 1,5 T; in 5 pazienti non vi erano dati anamnestici e bioumorali di nefropatia, mentre in 7 era presente storia di ipertensione arteriosa e/o IRC ingravescente, in 1 di malattia di Takayasu e in 1 di ipertensione nefrovascolare. Il protocollo prevedeva acquisizioni T1 e T2 dipendenti, nonché una sequenza SE-EPI pesata in diffusione (b-factor 600 s/mm2) con fattore SENSE 2 e ricostruzione di mappe dell’ADC. In 5 casi la SS-EPI-DW è stata ripetuta dopo somministrazione di furosemide. Il filtrato glomerulare è stato ottenuto mediante metodo di Cockroft-Gault.RisultatiL’ADC nei soggetti normali ed i pazienti in stadio I è stato di 2,44±0,24×10−3 mm2/s, mentre quello dei pazienti in stadio II–IV è stato di 2,05±0,33×10−3 mm2/s (p<0,05). Non è stata rilevata una differenza significativa dell’ADC tra stadio I e stadio II (p=0,27) e tra stadio II e stadio III (p=0,39), mentre la differenza è stata significativa tra pazienti in stadio III e IV(p<0,01). Si è rilevata una significativa correlazione tra la clearance della creatinina (ClCr(CG)) e l’ ADC parenchimale (r=0,79; p<0,01). La furosemide non ha determinato modificazioni dell’ADC (p=0,7).ConclusioniLa RM-DW permette di ottenere valori quantitativi del coefficiente di diffusione correlabili con la funzione renale separata, senza somministrare mezzo di contrasto e con rapidi tempi d’esame. Ulteriori studi di correlazione con i dati scintigrafici e su più ampie casistiche sono necessari al fine di confermare tali risultati e stabilire valori di riferimento per questa metodica.

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.

Computed tomographic evaluation of mesentery: diagnostic value in acute mesenteric ischemia.

Objective To evaluate the computed tomographic appearances of mesentery in acute mesenteric ischemia (AMI) to recognize characteristic features and their prognostic values. Methods Computed tomographic examinations of 34 patients with a confirmed diagnosis of AMI were retrospectively reviewed to evaluate the number of mesenteric vessels, diameter of the superior mesenteric artery and superior mesenteric vein, mesenteric fat stranding, mesenteric vessel pneumatosis and ascites. Results Overall, at least one of these mesenteric signs was present in all but 1 patient. In all AMI of arterial occlusive type and in 68% of nonocclusive mesenteric ischemia, the number of arterial vessels was reduced (P = 0.067). Mesenteric vessel pneumatosis and reduced number of venous vessels were significantly associated with higher mortality (P = 0.027 and P = 0.042, respectively). Reperfusion signs were associated with a reduced mortality (28.7% vs 65.5%). Conclusion Considering its characteristic features and its possible prognostic value, the evaluation of mesentery will supply additional information in the interpretation of computed tomography in AMI.

High accuracy of multislices computed tomography (MSCT) for para-aortic lymph node metastases from gastric cancer: a prospective single-center study.

BackgroundThe purpose of this study is to analyze the diagnostic accuracy of MSCT in the identification of para-aortic lymph node metastases from gastric cancer.MethodsA total of 92 consecutive patients with primary gastric cancer were prospectively submitted to preoperative MSCT staging according to a standard protocol in the period 2003–2010. All diagnostic procedures were performed by dedicated radiologists who were unaware of the final pathological nodal status. Subsequently all patients underwent potentially curative (R0) resection with extended lymphadenectomy plus para-aortic nodal dissection. Lymph node mapping in different stations and retrieval of single lymph nodes were performed by the surgeon on the fresh specimen and then submitted for pathological examination. Clinical, radiological, and pathological data were prospectively stored on database.ResultsA median number of 47 (range: 18–114) total lymph nodes and 7 (range: 3–29) para-aortic lymph nodes were removed. In 13 of 92 included patients (14%), histological examination demonstrated para-aortic nodal metastases; MSCT was correctly positive in 11 of these cases (sensitivity: 85%). In 79 patients para-aortic nodes were not involved, and MSCT resulted correctly negative in 75 of these patients (specificity: 95%). Positive (PPV) and negative (NPV) predictive values were 73 and 97%, with a global accuracy of 93%.ConclusionsMSCT performed according to a standard protocol by dedicated radiologists demonstrated high accuracy in preoperative identification of para-aortic nodal metastases from gastric cancer. These results may be useful in planning surgical approach or during clinical staging before neoadjuvant chemotherapy.

The Italian Research Group for Gastric Cancer (GIRCG) guidelines for gastric cancer staging and treatment: 2015

This article reports the guidelines for gastric cancer staging and treatment developed by the GIRCG, and contains comprehensive indications for clinical management, including radiological, endoscopic, surgical, pathological, and oncological paths.

Magnetic resonance imaging: is there a role in clinical management for acute ischemic colitis?

AIM To validate the utility of magnetic resonance imaging (MRI) for the clinical management of acute ischemic colitis (IC). METHODS This is a magnetic resonance (MR) prospective evaluation of 7 patients who were proved to have acute IC on the basis of clinical, endoscopic and computed tomography (CT) findings and who were imaged in our institution between February 2011 and July 2012. The mean age of the patients was 72.28 years. Abdominal CTs were obtained using a 64-detector row configuration for all patients with un-enhanced and contrast-enhanced scans, in the late arterial phase (start delay 45-50 s) and in the portal venous phase (start delay 70-80 s). The MR examinations were performed using a 1.5T superconducting magnet, using Fast Imaging Employing Steady State Acquisition and T2-weighted fast-recovery fast-spin echo sequences in axial and coronal plane. CT and MRI examinations were analysed for the presence of colonic abnormalities and associated findings. RESULTS Segmental involvement was seen in 6 patients (85.71%), with a mean length of involvement of 412 mm (range 145.5-1000 mm). Wall thickness varied between 6 mm and 17.5 mm (mean 10.52 mm) upon CT examinations and from 5 to 15 mm (mean 8.8 mm) upon MR examinations. The MRI appearance of the colonic wall varied over the time: Type I appearance with a 3 layer sandwich sign was seen in 5 out of 12 examinations (41.66%), patients underwent MR within a mean of 36 h (ranging from 1 to 54 h) after the CT examination. Type II and III appearance with a 2 layer sign, was seen in 4 examinations (33.33%), patients underwent MR within a mean of 420.5 h (ranging from 121 to 720 h) after the CT examination. In the remaining three MRI examinations, performed within a mean of 410 h (ranging from 99.5 to 720 h) the colonic wall appeared normal. CONCLUSION MRI, only using precontrast images, may be used as a substitute for invasive procedures in diagnosis and follow-up of acute IC.

CT Findings in Acute, Subacute, and Chronic Ischemic Colitis: Suggestions for Diagnosis

Purpose. This paper aims at evaluating CT findings of occlusive and nonocclusive ischemic colitis (IC), in correlation with the etiology and the different phases of the disease. Materials and Methods. CT examination and clinical history of 32 patients with proven IC were retrospectively reviewed. The CT findings were analyzed according to the different phases of the disease (acute, subacute, and chronic). Results. Among the 32 CT examinations performed in the acute phase, 62.5% did not present signs of occlusion of the superior mesenteric artery (SMA) or inferior mesenteric artery (IMA), whereas IMA occlusion was detected in 37.5% of CT examinations. In the acute phase, the presence of pericolic fluid was found in 100% of patients undergoing progressive resorption from acute to subacute phase if an effective reperfusion occurred; the bowel wall thickening was observed in 28.1% patients in acute phase and in 86.4% patients evaluated in subacute phase. The unthickened colonic wall was found in all conditions where ischemia was not followed by effective reperfusion (71.9% of cases), and it was never found in chronic phase, when the colon appeared irregularly thickened. Conclusion. CT allows determining the morphofunctional alterations associated with the IC discriminating the occlusive forms from the nonocclusive forms. CT, furthermore, allows estimating the timing of ischemic damage.

Nonocclusive mesenteric ischaemia: think about it

Abstract Nonocclusive mesenteric ischaemia (NOMI) is an acute mesenteric circulatory disorder that is not caused by an organic occlusion of blood vessels. It could involve all the abdominal parenchymas and viscera and the whole gastrointestinal tract (from the oesophagus to the rectum), insomuch that the involvement of the entire colon should be considered a distinctive tract in diagnosing this condition in respect of the occlusive forms of ischaemia. The aim of this article is to review the role of imaging in the diagnosis of NOMI and in particular its CT appearances. Recognition of the characteristic CT appearances and the variations associated with a reperfusion event may help in the accurate interpretation of CT in the diagnosis and management of NOMI.