Arturo Cuomo

Ten-Year Experience on 644 Patients Undergoing Single-Port (Uniportal) Video-Assisted Thoracoscopic Surgery

BACKGROUND Uniportal video-assisted thoracic surgery (VATS) technique has been described both for diagnostic and therapeutic indications. Outcomes after uniportal VATS have never been reported in large series. METHODS Between January 2000 and December 2010, 644 uniportal VATS procedures (334 male and 310 female patients; median age, 55.5 years; range, 16 to 85) were performed by a single surgeon. This figure represents 27.7% of all the thoracic surgical procedures in the study period (2,369). Of the 644 uniportal VATS, 329 (51.1%) were diagnostic procedures for pleural conditions. Of the remaining 315 uniportal VATS procedures, 14 (2.2%) were performed for pre-thoracotomy exploration for lung cancer, and 115 (17.8%) for miscellaneous conditions including diagnosis of mediastinal masses. In addition, 186 nonanatomic wedge resections (28.9% of the total uniportal VATS procedures) were performed for pulmonary conditions; of these, 146 were done for pulmonary nodules. RESULTS Median operative time was 18 and 22 minutes for uniportal VATS for diagnostic non-pulmonary indications and for wedge resections, respectively. Out of 644 patients, conversion to either 2 or 3 port VATS or minithoracotomy was necessary in 3.7% of the patients, often due to incomplete lung collapse (92%). Inclusive of the day of insertion, the chest drain was removed after a median of 4.3 (range, 2 to 20) and 2.4 days (range, 0 to 6) after uniportal VATS for pleural effusions and uniportal VATS lung wedge resections, respectively. Mortality and major morbidity after uniportal VATS was 0.6% and 2.8%, respectively. All deaths reported after uniportal VATS were for pleural effusions. Inclusive of the operative day, median hospitalization after surgery for uniportal VATS for pleural effusions and for wedge resections were 5.3 and 3.4 days, respectively. CONCLUSIONS In our experience, uniportal VATS was performed in one third of our surgical candidates with limited operative time, a very low conversion rate to conventional VATS or minithoracotomy, a very low morbidity and mortality, and, short hospitalization. Uniportal VATS is an underappreciated procedure that can be reliably used in the diagnostic pathways of several intrathoracic conditions and to resect small pulmonary nodules with either diagnostic or therapeutic purposes. As such, uniportal VATS represents a consolidated addition to the surgical armamentarium.

Reflux oesophagitis in adult coeliac disease: beneficial effect of a gluten free diet

Background: Coeliac disease patients show a number of gastrointestinal motor abnormalities, including a decrease in lower oesophageal sphincter pressure. The prevalence of endoscopic oesophagitis in these subjects however is unknown. Aim: To evaluate whether untreated adult coeliac patients had an increased prevalence of reflux oesophagitis and, if so, to assess whether a gluten free diet exerted any beneficial effect on gastro-oesophageal reflux disease (GORD) symptoms. Patients and methods: We retrospectively studied 205 coeliac patients (females/males 153/52, median age 32 years) who underwent endoscopy for duodenal biopsy and 400 non-coeliac subjects (females/males 244/156, median age 37 years) referred for endoscopy for upper gastrointestinal symptoms. Each patient was given a questionnaire for evaluation of GORD symptoms prior to and 4–12 months after endoscopy. Coeliac patients were given a gluten free diet. Oesophagitis patients of both groups, following an eight week course of omeprazole, were re-evaluated for GORD symptoms at four month intervals up to one year. Significance of differences was assessed by Fisher’s exact test. Results: Oesophagitis was present in 39/205 (19%, 95% confidence interval (CI) 13.8–25.0%) coeliac patients and in 32/400 (8%, 95% CI 5.5–11.1%) dyspeptic subjects. At the one year follow up, GORD symptoms relapsed in 10/39 (25.6%, 95% CI 13–42.1%) coeliacs with oesophagitis and in 23/32 (71.8%, 95% CI 53.2–86.2%) non-coeliac subjects with oesophagitis. Conclusion: Coeliac patients have a high prevalence of reflux oesophagitis. That a gluten free diet significantly decreased the relapse rate of GORD symptoms suggests that coeliac disease may represent a risk factor for development of reflux oesophagitis.

Efficacy and Gastrointestinal Tolerability of Oral Oxycodone/Naloxone Combination for Chronic Pain in Outpatients With Cancer An Observational Study

Combination opioid agonist/antagonist therapy has been shown to preserve bowel function in patients with chronic cancer pain. This retrospective study evaluated the efficacy and tolerability of prolonged-released fixed-dose oxycodone-naloxone (PR OXN) in consecutive outpatients with chronic cancer pain. Of 206 patients prescribed PR OXN (mean age 61.3 ± 12.9 years; 52.9% female), 31.5% were opioid naïve. PR OXN was associated with a significant decrease in pain score measured on a visual analogue scale over 28 days (P < .0001), without adverse effects on bowel function, nor change in laxative use. PR OXN efficacy and tolerability were similar in opioid-naïve and -experienced patients, and among age-stratified subgroups. No severe side effects occurred. In a real-life outpatient setting, PR OXN provided analgesia without bowel dysfunction in patients with chronic cancer pain.

Morphine Promotes Tumor Angiogenesis and Increases Breast Cancer Progression

Morphine is considered a highly potent analgesic agent used to relieve suffering of patients with cancer. Several in vitro and in vivo studies showed that morphine also modulates angiogenesis and regulates tumour cell growth. Unfortunately, the results obtained by these studies are still contradictory. In order to better dissect the role of morphine in cancer cell growth and angiogenesis we performed in vitro studies on ER-negative human breast carcinoma cells, MDA.MB231 and in vivo studies on heterotopic mouse model of human triple negative breast cancer, TNBC. We demonstrated that morphine in vitro enhanced the proliferation and inhibited the apoptosis of MDA.MB231 cells. In vivo studies performed on xenograft mouse model of TNBC revealed that tumours of mice treated with morphine were larger than those observed in other groups. Moreover, morphine was able to enhance the neoangiogenesis. Our data showed that morphine at clinical relevant doses promotes angiogenesis and increases breast cancer progression.

Breakthrough Pain in Patients Referred to Pain Clinics: The Italian Pain Network Retrospective Study

IntroductionDespite breakthrough pain (BTP) being one of the most severe forms of pain, there are no definitive data on its prevalence.MethodsThe authors performed a retrospective survey of the prevalence of BTP in consecutive patients in four Italian pain clinics, subsequent to application of an Italian law mandating detailed clinical records on pain characteristics, treatment, and results. Mean pain intensity was assessed with a numerical rating scale from 0 to 10.ResultsThe authors analyzed records of 1,401 patients (58% women, 33.1% patients with cancer). Transient episodes of severe pain or BTP were referred by 790 patients (56.4%), including 58.2% of the men (342 of 588) and 55.1% of the women (448 of 813). Among the 464 patients with cancer, 70.3% reported daily exacerbation of pain. The mean BTP intensity was 8.31 ± 1.58 and 31.1% of patients reported experiencing three episodes per day.ConclusionDespite some limitations of the study, the authors show that transient episodes of severe pain or BTP are significantly present both in cancer and other diseases, and that many patients are not yet receiving appropriate opioid therapy. The authors need validated tools at international level for the diagnosis and treatment of BTP in patients with cancer and for transitory and patients with severe non-cancer pain. A survey at national level is needed to estimate the prevalence of BTP in different settings, to plan specific medical education.

The efficacy of Epigallocatechin-3-gallate (green tea) in the treatment of Alzheimer's disease: An overview of pre-clinical studies and translational perspectives in clinical practice

Alzheimer’s disease (AD) is a neurodegenerative disorder and the most common form of dementia characterized by cognitive and memory impairment. One of the mechanism involved in the pathogenesis of AD, is the oxidative stress being involved in AD‘s development and progression. In addition, several studies proved that chronic viral infections, mainly induced by Human herpesvirus 1 (HHV-1), Cytomegalovirus (CMV), Human herpesvirus 2 (HHV-2), and Hepatitis C virus (HCV) could be responsible for AD’s neuropathology. Despite the large amount of data regarding the pathogenesis of Alzheimer’s disease (AD), a very limited number of therapeutic drugs and/or pharmacological approaches, have been developed so far. It is important to underline that, in recent years, natural compounds, due their antioxidants and anti-inflammatory properties have been largely studied and identified as promising agents for the prevention and treatment of neurodegenerative diseases, including AD. The ester of epigallocatechin and gallic acid, (−)-Epigallocatechin-3-Gallate (EGCG), is the main and most significantly bioactive polyphenol found in solid green tea extract. Several studies showed that this compound has important anti-inflammatory and antiatherogenic properties as well as protective effects against neuronal damage and brain edema. To date, many studies regarding the potential effects of EGCG in AD’s treatment have been reported in literature. The purpose of this review is to summarize the in vitro and in vivo pre-clinical studies on the use of EGCG in the prevention and the treatment of AD as well as to offer new insights for translational perspectives into clinical practice.

Immediate adverse reactions to gadolinium-based MR contrast media: A retrospective analysis on 10,608 examinations

Background and Purpose. Contrast media (CM) for magnetic resonance imaging (MRI) may determine the development of acute adverse reactions. Objective was to retrospectively assess the frequency and severity of adverse reactions associated with gadolinium-based contrast agents (GBCAs) injection in patients who underwent MRI. Material and Methods. At our center 10608 MRI examinations with CM were performed using five different GBCAs: Gd-BOPTA (MultiHance), Gd-DTPA (Magnevist), Gd-EOBDTPA (Primovist), Gd-DOTA (Dotarem), and Gd-BTDO3A (Gadovist). Results. 32 acute adverse reactions occurred, accounting for 0.3% of all administration. Twelve reactions were associated with Gd-DOTA injection (0.11%), 9 with Gd-BOPTA injection (0.08%), 6 with Gd-BTDO3A (0.056%), 3 with Gd-EOB-DTPA (0.028%), and 2 with Gd-DTPA (0.018%). Twenty-four reactions (75.0%) were mild, four (12.5%) moderate, and four (12.5%) severe. The most severe reactions were seen associated with use of Gd-BOPTA, with 3 severe reactions in 32 total reactions. Conclusion. Acute adverse reactions are generally rare with the overall adverse reaction rate of 0.3%. The most common adverse reactions were not severe, consisting in skin rash and hives.

Liver p53 expression in patients with HCV-related chronic hepatitis.

Summary. Mutated p53 acts as a dominant oncogene and alterations in the p53 gene are described in a large number of patients with hepatocellular carcinoma (HCC). It has been demonstrated that hepatitis C virus (HCV)‐core protein regulates transcriptionally cellular genes, as well as cell growth and apoptosis. This study was undertaken to evaluate whether p53 may be expressed also in a precocious stage of HCV‐related liver damage.

Dissecting the mechanisms and molecules underlying the potential carcinogenicity of red and processed meat in colorectal cancer (CRC): an overview on the current state of knowledge

Meat is a crucial nutrient for human health since it represents a giant supply of proteins, minerals, and vitamins. On the opposite hand, the intake of red and processed meat is taken into account dangerous due to its potential of carcinogenesis and cancer risk improvement, particularly for colorectal cancer (CRC), although it has been reported that also the contaminations of beef infected by oncogenic bovine viruses could increase colorectal cancer’s risk. Regarding the mechanisms underlying the potential carcinogenicity of red and processed meat, different hypotheses have been proposed. A suggested mechanism describes the potential role of the heterocyclic amines (HACs) and polycyclic aromatic hydrocarbons (PHAs) in carcinogenesis induced by DNA mutation. Another hypothesis states that heme, through the lipid peroxidation process and therefore the formation of N-nitroso compounds (NOCs), produces cytotoxic and genotoxic aldehydes, resulting in carcinogenesis. Furthermore, a recent proposed hypothesis, is based on the combined actions between the N-Glycolylneuraminic acid (Neu5Gc) and genotoxic compounds. The purpose of this narrative review is to shed a light on the mechanisms underlying the potential carcinogenicity of red and processed meat, by summarizing the data reported in literature on this topic.

Role of Nigella sativa and Its Constituent Thymoquinone on Chemotherapy-Induced Nephrotoxicity: Evidences from Experimental Animal Studies

Background: Most chemotherapeutic drugs are known to cause nephrotoxicity. Therefore, new strategies have been considered to prevent chemotherapy-induced nephrotoxicity. It is of note that Nigella sativa (NS), or its isolated compound Thymoquinone (TQ), has a potential role in combating chemotherapy-induced nephrotoxicity. AIM: To analyze and report the outcome of experimental animal studies on the protective effects of NS/TQ on chemotherapy-associated kidney complications. Design: Standard systematic review and narrative synthesis. Data Sources: MEDLINE, EMBASE databases were searched for relevant articles published up to March 2017. Additionally, a manual search was performed. Criteria for a study’s inclusion were: conducted in animals, systematic reviews and meta-analysis, containing data on nephroprotective effects of NS/TQ compared to a placebo or other substance. All strains and genders were included. Results: The database search yielded 71 studies, of which 12 (cisplatin-induced nephrotoxicity 8; methotrexate-induced nephrotoxicity 1; doxorubicin-induced nephrotoxicity 2; ifosfamide-induced nephrotoxicity 1) were included in this review. Conclusions: Experimental animal studies showed the protective effect of NS, or TQ, on chemotherapy-induced nephrotoxicity. These effects are caused by decreasing lipid peroxidation and increasing activity of antioxidant enzymes in renal tissue of chemotherapy-treated animals.