A case of medicine in disguise: motion sickness patches sold as medical devices containing active pharmaceutical substances.

INTRODUCTION: A case study is reported on anti-motion sickness transdermal patches sold in the Internet, claiming to contain only natural ingredients but, actually, containing undeclared medicinal active substances. The visual inspection of the samples evidenced many inconsistencies in secondary and primary packaging, missing of various legal information and a non-compliant "CE" mark. METHODS: The qualitative analysis was performed by liquid chromatography - high resolution mass spectrometry and the quantitative by liquid chromatography with diode array detector. RESULTS: The analyses evidenced the presence of the antihistaminic drug Diphenhydramine and of other active substances (Capsaicin, a transdermal absorption enhancer, and Diclofenac in traces, probably a contaminant from other productions of the same plant). Moreover, the presence of several trace elements, including those potentially toxic to humans, was assessed by ICP-MS analysis. CONCLUSIONS: The case discussed is a new case of "medicines in disguise" never reported in literature, and shows the presence of tangible risks for public health.

Enantioselective HPLC analysis of escitalopram oxalate and its impurities using a cellulose-based chiral stationary phase under normal- and green reversed-phase conditions.

Normal-phase and reversed-phase high-performance liquid chromatography methods for the separation of the active pharmaceutical ingredient escitalopram from its (R)-enantiomer impurity have been developed on the cellulose-based Chiralcel OJ-H chiral stationary phase. Both methods share two features: they use ethanol as a cosolvent and are able to give a complete enantioseparation without interference from other associated chiral impurities. With the green eluent mixture ethanol-water-diethylammine 70:30:0.1 (v/v/v), the resolution between escitalopram and (R)-enantiomer was 2.09 at 30°C. The limits of quantification for the (S) and (R) enantiomers were 4.5 and 3.8 µg mL-1 , respectively.

A special case of medicine in disguise: Tattoo inks containing anaesthetics.

This paper describes a case of medicine in disguise: seized tattoo inks containing lidocaine and tetracaine at high concentration. Identification of anaesthetics was performed by LC MS Q-TOF with ESI+ source, by accurate mass measurement and by comparing the fragmentation patterns of molecular ions, at 30 V and 10 V of collision-offset voltage, with reference standards. Quantification was also performed by LC MS Q-TOF on the chromatographic peaks in the extracted ion chromatograms, by calibration curves obtained at different standard concentrations and by standard additions approach. The measurement uncertainty was estimated from validation data. The paper gives also chromatographic parameters, MS and MS/MS data and a quantitation method, with a full validation, of other six "caines". Thus the paper intends to provide a tool for identification and quantitation of the most common local anaesthetics that could be fraudulently added to tattoo inks. The results here reported show that the seized samples of inks represent a serious health risk owing to the high anaesthetic content - therapeutic-like dosage - found.

Chemotherapy rechallenge after regorafenib treatment in metastatic colorectal cancer: still hope after the last hope?

INTRODUCTION: The introduction of biological agents in cancer therapy is changing the progression of metastatic colorectal cancer. Currently, resistance to biological agents is an emerging problem; the progression of the disease is caused by the development of resistant clones. According to some authors, these clones can be re-sensitized to traditional and previously utilized chemotherapy agents. The results of the CORRECT study demonstrated the efficacy of regorafenib monotherapy in both KRAS wild type and mutant pretreated patients (pts). Two recent reports showed the potential of reintroduction of chemotherapy, even after treatment with regorafenib. PATIENTS AND METHODS: We performed a retrospective review of clinical data from patients treated with regorafenib at our institution between March 2012 and March 2013. We analysed patient characteristics, KRAS/NRAS status, response to treatment (evaluated by RECIST v1.1 criteria) and survival. RESULTS: Regorafenib was administered to 128 patients, and 11 (8.6%) received post-regorafenib therapy (to our knowledge). Seven (63.6%) patients were wild type for KRAS/NRAS. Post-regorafenib therapy represented for all the patients at least the fourth line: all the pts received both oxaliplatin- and irinotecan-based chemotherapy, all of them were treated with bevacizumab, and 7 patients also received cetuximab. Eight patients (72.7%) were treated with standard chemotherapy after regorafenib (irinotecan monotherapy, capecitabine plus oxaliplatin or irinotecan, dacarbazine or raltitrexed), while 3 patients received an experimental therapy (clinical trial). Nine of the 11 (81.8%) patients had PD and 2 patients had SD. The median progression-free survival was 1.6+ months (range 0.5-3.5), the median OS post-regorafenib was 2.1+ months (range 0.5-10.2) and the 6-month OS was 27.3%. CONCLUSION: Our retrospective analysis showed that after regorafenib therapy, re-introduction of chemotherapy is possible. Unfortunately, we reported a high percentage of disease progression beyond regorafenib, which is likely due to the high percentage of heavily pretreated patients (some received four or five types of therapy before regorafenib). We think that regorafenib could represent a chemotherapy resensitizing agent; however, additional studies are needed in patients who have received less pretreatment.

Parents with cancer: Searching for the right balance between telling the truth and protecting children.

OBJECTIVE: Recent scientific approaches to cancer patients draw attention to the psychological aspects of the disease and the involvement of their families, who are forced to reorganize themselves in order to manage the patient's illness. Functional responses to a stressful event facilitate open communication between family members and empathy for the patient's children, who need to be involved and informed about the illness in a clear and open fashion. The primary goal of this observational study was to explore the communication styles used by cancer-stricken parents with their children and to identify a correlation with the patient's levels of anxiety and depression and their ability to cope. We also sought to understand whether location, severity, and time from diagnosis influenced communication, coping, anxiety, or depression. METHOD: From September of 2011 to July of 2015, 151 questionnaires were given to patients who had received at least one course of chemotherapy. The instruments that we employed were the Openness to Discuss Cancer in the Nuclear Family Scale, the Hospital Anxiety and Depression Scale, and the Mini-Mental Adjustment to Cancer Scale. Our sample included patients with children aged from 3 to 18 years. The patients had different types of cancer, mainly gastrointestinal and breast cancer. Their disease was at the metastatic stage in approximately 20% of patients. RESULTS: Our results showed statistically significant correlations between higher levels of anxiety and depression and more closed communication styles. The coping styles "hopelessness/helplessness," "cognitive avoidance," and "anxious preoccupation" were associated with a closed communication style that is correlated with higher levels of anxiety and depression. Tumor location, time from diagnosis, and stage of disease did not show statistically significant correlations with anxiety, depression, coping mechanisms, or communication styles. SIGNIFICANCE OF RESULTS: Our study confirmed what has been reported in the literature: high levels of anxiety and depression affect communication among family members. Not surprisingly, the "fighting spirit" coping style engenders open communication.

GEMOX: An Active Regimen for the Treatment of Luminal and Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer.

BACKGROUND: Pretreated metastatic breast cancer (MBC) remains a formidable challenge with unmet needs both in terms of prolonged survival and quality-of-life-related issues. METHODS: We collected data from 27 MBC patients treated with gemcitabine and oxaliplatin (GEMOX) at our institution between June 2009 and April 2015. The patients were heavily pretreated, and all had previously been exposed to anthracyclines and taxanes. RESULTS: We achieved a complete response in 1 patient (4%), a partial response in 7 patients (26%) and stable disease in 12 patients (44%), while 6 patients (22%) experienced progressive disease. The response of 1 patient (4%) could not be evaluated because she interrupted her treatment during the first cycle due to a major reaction to oxaliplatin. We observed grade 4 hypertransaminasaemia in only 1 patient (4%) and grade 2 neuropathy in 16 patients (59%). Grade 3 leuconeutropenia was observed in 5 patients (18%). The median progression-free survival was 5.9 months and the median overall survival was 9.6 months. CONCLUSIONS: GEMOX is an efficient and well-tolerated salvage regimen for MBC patients.

Current Role of Minimally Invasive Radical Cholecystectomy for Gallbladder Cancer.

Background. For Tis and T1a gallbladder cancer (GbC), laparoscopic cholecystectomy can provide similar survival outcomes compared to open cholecystectomy. However, for patients affected by resectable T1b or more advanced GbC, open approach radical cholecystectomy (RC), consisting in gallbladder liver bed resection or segment 4b-5 bisegmentectomy, with locoregional lymphadenectomy, is considered the gold standard while minimally invasive RC (MiRC) is skeptically considered. Aim. To analyze current literature on perioperative and oncologic outcomes of MiRC for patients affected by GbC. Methods. A Medline review of published articles until June 2016 concerning MiRC for GbC was performed. Results. Data relevant for this review were presented in 13 articles, including 152 patients undergoing an attempt of MiRC for GbC. No randomized clinical trial was found. The approach was laparoscopic in 147 patients and robotic in five. Conversion was required in 15 (10%) patients. Postoperative complications rate was 10% with no mortality. Long-term survival outcomes were reported by 11 studies, two of them showing similar oncologic results when comparing MiRC with matched open RC. Conclusions. Although randomized clinical trials are still lacking and only descriptive studies reporting on limited number of patients are available, current literature seems suggesting that when performed at highly specialized centers, MiRC for GbC is safe and feasible and has oncologic outcomes comparable to open RC.

Pancreatic cancer: New hopes after first line treatment.

Pancreatic cancer is the fourth leading cause of cancer-related death worldwide. Extensive research has yielded advances in first-line treatment strategies, but there is no standardized second-line therapy. In this review, we examine the literature trying to establish a possible therapeutic algorithm.

TAS-102 (Lonsurf) for the Treatment of Metastatic Colorectal Cancer. A Concise Review.

Within the past several years, no chemotherapy has been sufficient to increase the overall survival of patients with chemorefractory colorectal cancer. TAS-102 (Lonsurf) is an oral fluoropyrimidine that is formed by the combination of 2 active drugs: trifluridine (a nucleoside analog) and tipiracil hydrochloride (a thymidine phosphorylase inhibitor). This drug extended the median overall survival by approximately 2 months compared with placebo in a randomized phase III trial composed of Asian and non-Asian patients with refractory (or intolerant) metastatic colorectal cancer. The clinical development of TAS-102 began approximately a decade ago and included 2 pivotal randomized studies, which are discussed in this review. This drug has just been approved in Japan, and as soon as possible, it will be marketed in Western countries as well; it will therefore become the standard of care for this patient population. The optimal combination of TAS-102 with other agents, as well as the mechanism of resistance to this regimen should be defined in the near future.

TAS-102, the first "cardio-gentle" fluoropyrimidine in the colorectal cancer landscape?

BACKGROUND: Cardiotoxicity in the form of cardiac arrhythmia, myocardial infarction, and angina-like symptoms are not rare complications of fluoropyrimidines as 5-Fluorouracil (5FU) and capecitabine. DISCUSSION: Tas-102, a novel oral fluoropyrimidine, was recently approved by FDA for the treatment of advanced and refractory colorectal cancer. Its unique mechanism of action doesn't seem linked with cardiotoxicity in clinical trials reported so far. TAS 102 may represent one of the drugs of choice for patients with advanced colorectal cancer with cardiac disease. This intriguing and clinically relevant issue is briefly examined.

Health risks related to illegal and on-line sale of drugs and food supplements: results of a survey on marketed products in Italy from 2011 to 2013.

OBJECTIVES: The increasing illegal and on-line market of medicines and food supplements is helping the widespread diffusion of harmful counterfeit and forbidden products among consumers of developed countries. The objectives of this survey were the description of the main frauds recognized by public officers and the detection of illegal or counterfeit drugs and food supplements. METHODS: Medicines and food supplements found by Police forces on the illegal market or resulting from seizures made by Italian Customs authorities were visually inspected and analysed to evaluate their quality and the presence of other undeclared substances. RESULTS: The visual inspection and the chemical analysis revealed unsuitable packaging (mostly lacking of adequate information for consumers), absence of the declared active substances and presence of undeclared active substances. Products containing doping agents, illegal substances and active ingredients requiring medical supervision were found. CONCLUSION: The present work confirmed the health risk associated with assumption of medicines purchased on the Internet and from the illegal supply chain and evidenced a new threat to consumer safety related to the presence of pharmaceutical active ingredients in food supplements claiming to contain only "natural ingredients".

Pancreatic Cancer: Promises and Failures of Target Therapies.

Currently, few efficient therapies are available to battle pancreatic cancer. Mechanisms underlying this cancer are not well known and researchers are trying to identify new therapeutic targets. Here, we present a review of new treatments and their results in recent years.

Gemcitabine Plus Nab-Paclitaxel as Second-Line and Beyond Treatment for Metastatic Pancreatic Cancer: a Single Institution Retrospective Analysis.

Metastatic pancreatic cancer still represent one of the most deadly disease for which there are few therapeutic options, especially in second line and beyond setting. Nabpaclitaxel plus gemcitabine activity was demonstrated in first line setting, but there are no clear evidence suggesting its use after that. We report a retrospective data analysis of 23 patients who received nab-paclitaxel plus gemcitabine after first line treatment at our Oncology Department. We observed a significant clinical benefit (43,5%) with a median overall survival of 5 months. In addition, manageable side effects were reported. Our data, despite the small sample, seem to indicate that nab- paclitaxel plus gemcitabine is an active and well tolerated regimen even in pretreated patients.

The Modified Glasgow Prognostic Score and Survival in Colorectal Cancer: A Pooled Analysis of the Literature.

BACKGROUND: It has been reported that the combination of inflammation parameters, such as albumin and C-reactive protein, in the modified Glasgow prognostic score (m-GPS) is a poor prognostic indicator in several malignancies. Here, we quantify the prognostic impact of this score and assess its value in colorectal cancer. METHODS: A systematic review of electronic databases was conducted to identify publications exploring the association of m-GPS with outcome in colorectal cancer. Overall survival (OS) was the primary outcome, and cancer-specific survival (CSS), progression-free survival, and disease-free survival were secondary outcomes. Data from studies reporting a hazard ratio (HR) and 95% confidence interval (CI) were included in a metaanalysis. Pooled HRs were computed and weighted using generic inverse-variance and random effects modeling. All statistical tests were two-sided. RESULTS: Nine studies, which included a total of 2,227 patients, were included in the analysis. Overall, according to multivariate analysis, m-GPS≥1 was independently associated with an HR for OS of 1.69 (95% CI=1.4-2.04; P<0.00001), an effect observed in all stages of disease. Six studies including a total of 1,751 patients reported HR for CSS. Overall, a high m-GPS was associated with an HR for CSS of 1.84 (95% CI=1.43-2.37; P<0.00001). CONCLUSIONS: A high m-GPS is associated with poor OS in colorectal cancer. The m-GPS is a cheap and easily evaluable biomarker, and its incorporation into known prognostic scores for clinical decision making warrants further investigation in this setting.

Clear cell thymic carcinoma: a case report.

Clear cell thymic carcinoma is a rare and invasive tumor of the mediastinum for which there are no uniform treatment guidelines. The combination of carboplatin plus paclitaxel seems to be the most effective regimen for this disease. We report a case of locally advanced clear cell thymic carcinoma treated with this schedule, in which we observed a relevant and rapid tumor shrinkage.

Oxaliplatin-induced hypersensitivity reaction: underlying mechanisms and management.

Hypersensitivity reactions are rare but feared drugs adverse effect. These reactions are not uncommon with anticancer drugs, such as taxanes, monoclonal antibodies, and platinum compounds. Oxaliplatinum, a third-generation platinum compound, one of the mainstay drugs in the treatment of many gastrointestinal cancers, can give rise to hypersensitivity reactions, sometimes with fatal outcomes. In this paper, we reviewed the incidence and mechanisms underlying the occurrence of this event, highlighting the most recent advances concerning the pathogenesis of the reaction and also reporting possible risk factors identified and the most effective treatment in preventing the onset of this event.

Assessing cancer caregivers' needs for an early targeted psychosocial support project: The experience of the oncology department of the Poliambulanza Foundation.

OBJECTIVE: Caregivers play a key role in the management of patients with cancer. However, some studies have suggested that caregivers have even more unmet needs than the patients. METHOD: To better identify the needs and changes in the lifestyles of the caregivers in our practice and to plan a targeted support project to decrease caregiver burden, we administered the Caregiver's QoL Index-Cancer (CQoLC) to 200 consecutive caregivers. This questionnaire assesses psychological well-being, the relationship with healthcare professionals, administration of finances, lifestyle disruption, and positive adaptation. RESULTS: Our data showed that being a caregiver to a patient with metastatic disease negatively affected females mostly with regard to mental and emotional burden, while men complained more about their sexual life (42.3 vs. 33.6%), although this result was not significant. Some 93.5% of caregivers reported that they were pleased with their role, while 83.4% were concerned about financial difficulties. SIGNIFICANCE OF RESULTS: We strongly believe that early supportive care directed not only at patients but also to caregivers may improve the quality of life (QoL) in this population. We are currently developing a targeted support project to decrease caregiver burden.

Thyroid carcinoma showing thymus-like differentiation: Case presentation of a young man.

Ectopic thymic tissue can be present in the thyroid gland and a carcinoma showing thymus-like differentiation (CASTLE) may arise from such tissue. We are reported the case of a 26-year-old man with CASTLE, with cervical subcutaneous nodules relapse, who showed a good response to treatment with surgery, chemotherapy and radiotherapy. The problematic aspect of this case was the diagnosis; only on review were we able to make a final diagnosis. CASTLE is a very rare neoplasm. It is important to differentiate this cancer from others tumors such as primary or metastatic squamous cell carcinoma of the head and neck or squamous cell thyroid carcinoma, because the therapy and prognosis are different. Diagnosis is complicated and requires careful histological analysis (CD5- and P63-positive with presence of Hassall's corpuscles); unfortunately there is no gold standard treatment so, in this case, we administered a sandwich of chemotherapy and radiotherapy.

Tyrosine Kinase Inhibitors in EGFR-Mutated Large-Cell Neuroendocrine Carcinoma of the Lung? A Case Report.

Large-cell neuroendocrine carcinoma (LCNEC) of the lung is a high-grade carcinoma belonging to the neuroendocrine tumors of the lung and is different from typical lung large-cell carcinoma. It represents about 3% of all pulmonary malignancies and is characterized by neuroendocrine cytologic features. The treatment usually is platinum-based chemotherapy, however the outcome remains poor. Therefore new therapeutic options are needed. Tyrosine kinase inhibitors have demonstrated greater efficacy and better tolerability than standard chemotherapy in non-small-cell lung cancer harboring epidermal growth factor receptor (EGFR) mutations. EGFR gene mutations were also rarely identified in LCNEC. We report a patient with lung LCNEC activating EGFR mutations who showed an impressive response to gefitinib.

Natural history of malignant bone disease in hepatocellular carcinoma: final results of a multicenter bone metastasis survey.

BACKGROUND: Bone is an uncommon site of metastasis in patients with advanced hepatocellular carcinoma (HCC). Therefore, there are few studies concerning the natural history of bone metastasis in patients with HCC. PATIENTS AND METHODS: Data on clinicopathology, survival, skeletal-related events (SREs), and bone-directed therapies for 211 deceased HCC patients with evidence of bone metastasis were statistically analyzed. RESULTS: The median age was 70 years; 172 patients were male (81.5%). The median overall survival was 19 months. The median time to the onset of bone metastasis was 13 months (22.2% at HCC diagnosis); 64.9% patients had multiple bone metastases. Spine was the most common site of bone metastasis (59.7%). Most of these lesions were osteolytic (82.4%); 88.5% of them were treated with zoledronic acid. At multivariate analysis, only the Child Score was significantly correlated with a shorter time to diagnosis of bone metastases (p = 0.001, HR = 1.819). The median survival from bone metastasis was 7 months. At multivariate analysis, HCC etiology (p = 0.005), ECOG performance status (p = 0.002) and treatment with bisphosphonate (p = 0.024) were associated with shorter survival after bone disease occurrence. The site of bone metastasis but not the number of bone lesions was associated with the survival from first skeletal related event (SRE) (p = 0.021) and OS (p = 0.001). CONCLUSIONS: This study provides a significant improvement in the understanding the natural history of skeletal disease in HCC patients. An early and appropriate management of these patients is dramatically needed in order to avoid subsequent worsening of their quality of life.