Hemangioblastoma of the gastrointestinal tract: A first case

We present the first documented case of hemangioblastoma located in the left colon. A 75-year-old woman undergoing adjuvant chemotherapy for breast cancer experienced rectal bleeding. Colonoscopy revealed a roundish mass covered with normal mucosa in the sigmoid colon. Endoscopic ultrasound showed an isoechoic lesion originating from the third layer of the intestinal wall; underlying layers were normal. Endoscopic ultrasound features were not suggestive of either cancer or malignant stromal tumor. Left hemicolectomy was subsequently performed due to repeated episodes of lower gastrointestinal bleeding. Grossly, a circumscribed submucosal yellowish nodule (13 mm) was observed, which was not attached to any peripheral nerve. Histologically, the lesion was composed of large, atypical cells traversed by a network of blood vessels. Immunohistochemically, the cells showed positivity for inhibin and NSE and weak positivity for S-100. A diagnosis of hemangioblastoma was made. This case highlights that hemangioblastoma of the gastrointestinal tract can also occur. © The Author(s) 2013

KRAS, BRAF and PIK3CA status in squamous cell anal carcinoma (SCAC)

Anti-EGFR therapy appears to be a potential treatment option for squamous cell anal carcinoma (SCAC). KRAS mutation is a rare event in SCAC, indicating the absence of the principal mechanism of resistance to this type of therapy. However, no information is available from the literature regarding the status of BRAF or PIK3CA in this cancer type. We analysed KRAS, BRAF and PIK3CA status in SCAC patients in relation to the clinical-pathological characteristics of patients and to the presence of the human papilloma virus (HPV). One hundred and three patients were treated with the Nigro scheme for anal cancer from March 2001 to August 2012. Fifty patients were considered for the study as there was insufficient paraffinembedded tumour tissue to perform molecular analysis the remaining 53. DNA was extracted from paraffin-embedded sections. KRAS, BRAF and PIK3CA gene status and HPV genotype were evaluated by pyrosequencing. KRAS and BRAF genes were wild-type in all cases. Conversely, PIK3CA gene was found to be mutated in 11 (22%) cases. In particular, 8 mutations occurred in exon 9 and 3 in exon 20 of the PIK3CA gene. These findings suggest that SCAC could potentially respond to an anti-EGFR drug. PIK3CA mutation may be involved in the process of carcinogenesis in some cases of SCAC. \ua9 2014 Casadei Gardini et al

Dynamic contrast-enhanced ultrasonography (D-CEUS) for the early prediction of bevacizumab efficacy in patients with metastatic colorectal cancer

Objectives: To investigate early changes in tumour perfusion parameters by dynamic contrast-enhanced ultrasonography (D-CEUS) and to identify any correlation with survival and tumour response in patients with metastatic colorectal cancer (CRC) treated with bevacizumab (B). Methods: Thirty-seven patients randomized to either chemotherapy (C) plus B or C alone were considered for this study. D-CEUS was performed at baseline and after the first treatment cycle (day 15). Four D-CEUS perfusion parameters were considered: derived peak intensity (DPI), area under the curve (AUC), slope of wash-in (A) and time to peak intensity (TPI). Results: In patients treated with C plus B, a ≥22.5 % reduction in DPI, ≥20 % increase in TPI and ≥10 % reduction in AUC were correlated with higher progression-free survival in the C+B arm (p = 0.048, 0.024 and 0.010, respectively) but not in the C arm. None of the evaluated parameter modifications had a correlation with tumour response or overall survival. Conclusions: D-CEUS could be useful for detecting and quantifying dynamic changes in tumour vascularity as early as 15 days after the start of B-based therapy. Although these changes may be predictive of progression-free survival, no correlation with response or overall survival was found. Key Points: • D-CEUS showed early changes in liver metastasis perfusion in colorectal cancer. • A decrease in tumour perfusion was associated with longer progression-free survival. • The decrease in perfusion was not correlated with higher overall survival

Systematic versus on-demand early palliative care: results from a multicentre, randomised clinical trial

Background Early palliative care (EPC) in oncology has been shown to have a positive impact on clinical outcome, quality-of-care outcomes, and costs. However, the optimal way for activating EPC has yet to be defined. Methods This prospective, multicentre, randomised study was conducted on 207 outpatients with metastatic or locally advanced inoperable pancreatic cancer. Patients were randomised to receive ‘standard cancer care plus on-demand EPC’ (n = 100) or ‘standard cancer care plus systematic EPC’ (n = 107). Primary outcome was change in quality of life (QoL) evaluated through the Functional Assessment of Cancer Therapy – Hepatobiliary questionnaire between baseline (T0) and after 12 weeks (T1), in particular the integration of physical, functional, and Hepatic Cancer Subscale (HCS) combined in the Trial Outcome Index (TOI). Patient mood, survival, relatives' satisfaction with care, and indicators of aggressiveness of care were also evaluated. Findings The mean changes in TOI score and HCS score between T0 and T1 were −4.47 and −0.63, with a difference between groups of 3.83 (95% confidence interval [CI] 0.10–7.57) (p = 0.041), and −2.23 and 0.28 (difference between groups of 2.51, 95% CI 0.40–4.61, p = 0.013), in favour of interventional group. QoL scores at T1 of TOI scale and HCS were 84.4 versus 78.1 (p = 0.022) and 52.0 versus 48.2 (p = 0.008), respectively, for interventional and standard arm. Until February 2016, 143 (76.9%) of the 186 evaluable patients had died. There was no difference in overall survival between treatment arms. Interpretations Systematic EPC in advanced pancreatic cancer patients significantly improved QoL with respect to on-demand EPC

Development of buccal films as novel dosage form for paediatric use

Introduction: The development of child-appropriated dosage forms represents one of the most important topics of new European regulations and recent WHO recommendations on paediatric medicines. Purpose: The aim of this study was the preparation and characterization of mucoadhesive polymeric films as suitable dosage form for transmucosal drug delivery. Method: An aqueous solution of hyaluronic acid (Mr 1800-2300 kDa; D-glucuronic acid > 42 %) and an acidic solution of chitosan (Mr 150 kDa; deacetylation degree 97 %) were separately added to an aqueous solution of hydroxypropylmethylcellulose (HPMC; methoxyl content 19-24 %; hydroxypropyl content 7-12 %) at different weight ratios (1:1, 3:7, 1:9, 0:10; hyaluronate/HPMC or chitosan/HPMC). Each mixture was stirred at room temperature for 24 hours, spreaded on a Petridish and dried at 50 \ub0C for 6 h. Drug-free films and films with a child-appropriated dose of ondansetron hydrochloride were investigated. Physiochemical properties of the films (thickness, drug content, water uptake ability and mucoadhesion potential) and in vitro drug release were performed. Moreover, in vitro permeation studies will carry out in order to evaluate drug permeation through biological membranes. Results: Films were smooth and transparent, with good flexibility. The thickness was found to be uniform and drug content was close to the theoretical one (1 mg/cm2 for each film). Moreover, films showed good mucoadhesive properties and in particular the presence of hyaluronate allowed the highest mucoadhesion potential. Finally, the inclusion of chitosan in polymeric mixtures enhanced in vitro drug release with respect to the inclusion of hyaluronate, although chitosan/HPMC mixture showed the lowest water uptake. This behaviour could be attibuted to the high viscosity of the hyaluronate/HPMC films in the gel state. Conclusions: Our results indicate that buccal films based on different chitosan/HPMC and hyaluronate/HPMC mixtures could be used as a novel technological platform for paediatric medicines

Impact of second-line cetuximab-containing therapy in patients with KRAS wild-type metastatic colorectal cancer: results from the ITACa randomized clinical trial

Abstract The ITACa trial was designed to define the role of cetuximab (Cet) and bevacizumab (Bev) in combination with standard chemotherapy (CT, FOLFIRI or FOLFOX4) as first- and second-line treatment in metastatic colorectal cancer. All patients with WT KRAS tumors who had been enrolled in the first-line trial were randomized onto two independent second-line trials: CT or CT + Cet (study 2A) and CT + Bev or CT + Bev + Cet (study 2B). Patients with mutated KRAS were not eligible for randomization and were treated with CT alone (study 2A) or CT + Bev (study 2B). The primary endpoint was progression-free survival (PFS). 48 and 56 KRAS WT patients were randomized while 31 and 40 KRAS mutated patients were treated without randomization. Study 2A: median PFS was 3.4 (95%CI 2.3–4.6) and 6.2 (95%CI 4.3–7.8) months for the CT and CT + Cet arms, respectively, with a hazard ratio (HR) = 0.64 (95%CI 0.35–1.16, p = 0.144). Study 2B: median PFS was 7.7 (95%CI 4.1–10.1) and 4.9 (95%CI 3.2–7.0) months for CT + Bev and CT + Cet + Bev arms, respectively, with a HR = 1.31 (95%CI 0.76–2.26, p = 0.330). Notwithstanding limitations due to the small sample size, among patients with WT KRAS the addition of Cet to second-line CT increased PFS, whereas the addition of Cet to CT + Bev was associated with worse PFS

Taxanes as a Risk Factor for Acute Adverse Reactions to Iodinated Contrast Media in Cancer Patients

BACKGROUND. The impact of cytotoxic agents on the risk of acute allergy-like adverse reactions (ARs) to intravenous iodinated contrast media (ICM) injections is unknown. METHODS. We retrospectively reviewed 13,565 computed tomography (CT) scans performed in a consecutive cohort of cancer patients from January 1, 2010 to December 31, 2012. Episodes of acute ICM-related ARs were reported to the pharmacovigilance officer. The following matched comparisons were made: tax code, gender, primary tumor, antineoplastic therapy, and date of last cycle. Concomitant antineoplastic treatment was classified into five groups: platinum, taxane, platinum plus taxane, other, and no treatment group (no therapy had been administered in the previous 24 months). Logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (CI) to evaluate the risk of acute ICM-related ARs. RESULTS. Of 10,472 contrast-enhanced CT scans, 97 (0.93%; 95% CI: 0.74–1.11) ICM-related ARs were reported, 11 of which (0.1%) were severe, including one fatality. The overall incidence was significantly higher in patients aged <65 years (p = .0062) and in the platinum plus taxane and taxane groups (p = .007), whereas no correlation was found with gender, number of previous CT scans, site of disease, or treatment setting. Multivariate analysis confirmed an increased risk for patients aged <65 years (OR: 1.73; 95% CI: 1.14–2.63) and for the taxane group (in comparison with the no treatment group; OR: 2.06; 95% CI: 1.02–4.16). CONCLUSION. Among cancer patients, concomitant treatment with taxanes and younger age would seem to be risk factors for ICM-related ARs

Predictive role of multiple gene alterations in response to cetuximab in metastatic colorectal cancer: A single center study

<p>Abstract</p> <p>Background</p> <p><it>KRAS</it> mutations negatively affect outcome after treatment with cetuximab in metastatic colorectal cancer (mCRC) patients. As only 20% of <it>KRAS</it> wild type (WT) patients respond to cetuximab it is possible that other mutations, constitutively activating the EGFR pathway, are present in the non-responding <it>KRAS</it> WT patients. We retrospectively analyzed objective tumor response rate, (ORR) progression-free (PFS) and overall survival (OS) with respect to the mutational status of <it>KRAS</it>, <it>BRAF</it>, <it>PIK3CA</it> and PTEN expression in mCRC patients treated with a cetuximab-based regimen.</p> <p>Methods</p> <p>67 mCRC patients were enrolled onto the study. DNA was extracted from paraffin-embedded sections derived from primary or metastatic lesions. Exon 2 of <it>KRAS</it> and exon 15 of <it>BRAF</it> were analyzed by direct sequencing, <it>PIK3CA</it> was evaluated by pyrosequencing and PTEN expression by immunohistochemistry.</p> <p>Results</p> <p><it>BRAF</it> and <it>PIK3CA</it> mutations were independently associated with worse PFS (<it>p</it> = 0.006 and <it>p</it> = 0.028, respectively) and OS (<it>p</it> = 0.008 and <it>p</it> = 0.029, respectively). No differences in clinical outcome were found between patients who were positive or negative for PTEN expression. Conversely, patients negative for <it>KRAS</it>, <it>BRAF</it> and <it>PIK3CA</it> mutations were characterized by significantly better ORR, PFS and OS than patients with at least one of these mutations.</p> <p>Conclusions</p> <p><it>BRAF</it> and <it>PIK3CA</it> mutations would seem to be independent predictors of anti-EGFR therapy effectiveness and could be taken into consideration during treatment decision making.</p