Laryngopharyngeal reflux as a potential cause of persistent local neck symptoms after total thyroidectomy.

PURPOSE: Local neck symptoms (LNS) may be related to goiter, but are also reported by patients suffering from laryngeal-pharyngeal reflux (LPR). The aim of this study was to investigate whether LPR could play a role in the persistence of some LNS after total thyroidectomy (TT). METHODS: A consecutive case series of 160 patients with multinodular goiter (MNG) candidate for TT were included in this study. Each patient was closely studied for both the thyroid pathology and reflux disease before and 6 months after surgery to assess the persistence of LNS after surgery. RESULTS: Only throat discomfort showed a significant improvement (p = 0.031) after surgery. On the other hand, swallowing and voice disorders persisted after surgery in 82.3% and 77.3% of patients, respectively (p = 0.250 and p = 0.062), such as the correlated reflux laryngopharyngitis (p = 0.5). CONCLUSIONS: LPR can be considered a predisposing factor or an important concurrent causa to the persistence of LNS after TT, in particular for swallowing disorders and voice disorders. In patients with non-toxic MNG who complain of local neck symptoms, the investigation of a possible coexistence of a reflux disease is appropriate before surgery. Patients should be informed about the possibility that some symptoms can persist even after removal of the goiter.

The value of total thyroidectomy as the definitive treatment for Graves' disease: A single centre experience of 594 cases.

PURPOSE: Thyroidectomy is the preferred approach as the definitive treatment for Graves' disease. The outcomes for total thyroidectomy in a large series of 594 patients, who were observed in the last decade, will be presented in this study. METHODS: The study concerned a retrospective review of 594 patients, undergoing a total thyroidectomy for Graves' disease. The incidence of complications and outcomes on hyperthyroidism and correlated symptoms resolution were also evaluated. RESULTS: The mean age of the patients was of 44.7 ±â€¯12.7 years and 456 patients (76.7%) were females. The mean gland weight was 67.3 ±â€¯10.8 g (range: 20-350 g) and, in 397 patients (66.8%), the gland weighed >40 g. The mean operative time was 125 ±â€¯23.1 min (range: 65-212 min). Temporary and permanent hypocalcaemia developed in 241 (40.6%) and 3 patients (0.5%), respectively. Temporary and permanent recurrent laryngeal nerve palsy were recorded in 31 (5.2%) and 1 patients (0.16%) respectively. No patient developed a thyroid storm. On multivariate analysis, patient age ≤50 years (Odds ratio: 1; 95% Confidence Interval: 0.843-0.901) and thyroid weight >40 g (Odds ratio: 1; 95%, Confidence Interval: 0.852-0.974), were mainly associated with the occurrence of complications. CONCLUSION: This high-volume surgeon experience demonstrates that total thyroidectomy is a safe and effective treatment for Graves' disease. It is associated with a very low incidence rate of post-operative complications, most of which are transitory; therefore, it offers a rapid and definitive control of hyperthyroidism and its related symptoms.

Analysis of tissue and circulating microRNA expression during metaplastic transformation of the esophagus.

Genetic changes involved in the metaplastic progression from squamous esophageal mucosa toward Barrett's metaplasia and adenocarcinoma are almost unknown. Several evidences suggest that some miRNAs are differentially expressed in Barrett's esophagus (BE) and esophageal adenocarcinoma. Among these, miR-143, miR-145, miR-194, miR-203, miR-205, miR-215 appear to have a key role in metaplasia and neoplastic progression. The aim of this study was to analyze deregulated miRNAs in serum and esophageal mucosal tissue biopsies to identify new biomarkers that could be associated with different stages of esophageal disease. Esophageal mucosal tissue biopsies and blood samples were collected and analyzed for BE diagnosis. Quantitative Real-time PCR was used to compare miRNA expression levels in serum and 60 disease/normal-paired tissues from 30 patients diagnosed with esophagitis, columnar-lined esophagus (CLO) or BE. MiRNA expression analysis showed that miR-143, miR-145, miR-194 and miR-215 levels were significantly higher, while miR-203 and miR-205 were lower in BE tissues compared with their corresponding normal tissues. Esophageal mucosa analysis of patients with CLO and esophagitis showed that these miRNAs were similarly deregulated but to a lesser extent keeping the same trend and CLO appeared as intermediate step between esophagitis and BE. Analysis on circulating miRNA levels confirmed that miR-194 and miR-215 were significantly upregulated in both BE and CLO compared to esophagitis, while miR-143 was significantly upregulated only in the Barrett group. These findings suggest that miRNAs may be involved in neoplastic/metaplastic progression and miRNA analysis might be useful for progression risk prediction as well as for monitoring of BE/CLO patients.

Nintedanib in NSCLC: evidence to date and place in therapy.

The treatment of advanced non-small cell lung cancer (NSCLC) is currently driven by the detection of targetable oncogenic drivers, i.e. epidermal growth factor receptor, echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase, etc. Those patients who are wildtype for known and valuable oncogenes can receive standard chemotherapy as first-line treatment, with the possibility of adding bevacizumab. With regard to second-line treatment, nintedanib can improve the efficacy of docetaxel. Nintedanib is a tyrosine kinase inhibitor targeting three angiogenesis-related transmembrane receptors. The usefulness of nintedanib as an anticancer agent for NSCLC has been proved by both preclinical and clinical phase I and II trials; however, its approval for the use in clinical practice has been possible because of the positive results of the LUME-Lung 1 trial (nintedanib + docetaxel versus docetaxel alone) in terms of progression-free survival and overall survival, and a manageable tolerability profile. Therefore, the good results seen in the clinical trials with nintedanib in the second-line setting for NSCLC patients with adenocarcinoma subtype are encouraging enough to recommend it in clinical practice.

HepatomiRNoma: The proposal of a new network of targets for diagnosis, prognosis and therapy in hepatocellular carcinoma.

The diagnosis and treatment of hepatocellular carcinoma (HCC) underwent a huge advancement in the last years. Recently, microRNAs (miRNAs) have been also studied to provide a new tool for early diagnosis of high risk patients, for prognostic classification to identify those patients who benefit cancer treatment and for predictive definition to select the right targeted drug. In this review we revised all the available data obtained to explore the role of miRNAs in HCC. This analysis led to identification of miRNAs which could gain a diagnostic, prognostic or predictive role. The results of studies on miRNAs involved in HCC are initial and far from providing scientific evidences to translate into clinical practice. We propose a classification of these miRNAs, that we could name HepatomiRNoma as a whole. Anyway prospective studies have to be designed to clarify the real clinical impact of this new tool.

What can platinum offer yet in the treatment of PS2 NSCLC patients? A systematic review and meta-analysis.

BACKGROUND: Randomized phase III trials showed interesting, but conflicting results, regarding the treatment of NSCLC, PS2 population. This meta-analysis aims to review all randomized trials comparing platinum-based doublets and single-agents in NSCLC PS2 patients. MATERIALS AND METHODS: Data from all published randomized trials, comparing efficacy and safety of platinum-based doublets to single agents in untreated NSCLC, PS2 patients, were collected. Pooled ORs were calculated for the 1-year Survival-Rate (1y-SR), Overall Response Rate (ORR), and grade 3-4 (G3-4) hematologic toxicities. RESULTS: Six eligible trials (741 patients) were selected. Pooled analysis showed a significant improvement in ORR (OR: 3.243; 95% CI: 1.883-5.583) and 1y-SR (OR: 1.743; 95% CI: 1.203-2.525) in favor of platinum-based doublets. G3-4 hematological toxicities were also more frequent in this group. CONCLUSION: This meta-analysis suggests that platinum-combination regimens are superior to singleagent both in terms of ORR and survival-rate with increase of severe hematological toxicities.

Farletuzumab for NSCLC: exploiting a well-known metabolic pathway for a new therapeutic strategy.

Introduction: The therapeutic options for NSCLC are limited barring targeted drugs, such as EGFR tyrosine-kinase inhibitors and anaplastic lymphoma kinase inhibitors, for patients bearing oncogenic mutations. Platinum-based chemotherapy remains the best strategy for most patients. New targeted drugs, including mAbs and small molecules, are currently under clinical investigation for treating NSCLC patients. Areas covered: The authors of this article focus on farletuzumab , a mAb targeting folate receptor, which has been studied in ovarian cancer and various other malignancies. In this review, the authors review its potential as therapy for NSCLC, because of the biological rationale provided by the expression of folate receptor α in most of lung adenocarcinoma. The authors provide details of farletuzumab's mechanism of action and discuss the results from completed Phase I and Phase II clinical trials. They also highlight ongoing trials. Expert opinion: There are an increasing number of treatment options for NSCLC and it is hoped that farletuzumab could be added to them. That being said, further evidence for its use with NSCLC patients is still needed. It could have a synergic effect with pemetrexed, because these two drugs have a similar target, namely the folate pathway. This combined action could provide an improved efficacy, although there are some concerns about increased toxicity. However, the authors do note that the combination of farletuzumab with other cytotoxic drugs has not been shown to increase toxicity alone.

The role of targeted therapy for gastrointestinal tumors.

Many targeted drugs have been studied to target the molecular pathways involved in the development of gastrointestinal cancers. Anti-VEGF, anti-EGFR agents, and recently also multi-kinase inhibitor regorafenib, have already been available for the treatment of metastatic colorectal cancer patients. To date, Her-2 positive, gastric cancer patients, are also treated with trastuzumab, while the multi-targeted inhibitor, sorafenib, represents the standard treatment for hepatocellular carcinoma patients. Finally, sunitinib and everolimus, have been approved for the treatment of the neuroendocrine gastroenteropancreatic tumors. Actually a great number of further drugs are under preclinical and clinical development. The aim of this review is to provide a comprehensive overview of the state of art, focusing on the new emerging strategies in the personalized treatment of gastrointestinal tumors.

Immunotherapy for recurrent ovarian cancer: a further piece of the puzzle or a striking strategy?

INTRODUCTION: Treatment of ovarian cancer has been long standardized with the inclusion of surgery and chemotherapy based on platinum and taxanes, this strategy reaching high remission rates. However, when this treatment fails, further options are available with little benefit. Since ovarian cancer has specific immunologic features, actually immunotherapy is under evaluation to overcome treatment failure in patients experiencing recurrence. AREAS COVERED: Immunogenicity of ovarian cancer and its relationship with clinical outcomes is briefly reviewed. The kinds of immunotherapeutic strategies are summarized. The clinical trials investigating immunotherapy in recurrent ovarian cancer patients are reported. EXPERT OPINION: The results of these clinical trials about immunotherapy are interesting, but little clinical benefit has been achieved until now. For this reason, we could conclude that immunotherapy is quite different from other treatment options and it could change the global approach for recurrent ovarian cancer treatment. However, to date only fragmentary findings are available to define the real role of immunotherapy in this setting.

Are erlotinib and gefitinib interchangeable, opposite or complementary for non-small cell lung cancer treatment? Biological, pharmacological and clinical aspects.

Gefitinib and erlotinib are the two anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) approved for treatment of advanced NSCLC patients. These drugs target one of the most important pathways in lung carcinogenesis and are able to exploit the phenomenon of 'oncogene addiction', with different efficacy according to EGFR gene mutational status in tumor samples. Gefitinib has been approved only for EGFR mutation bearing patients regardless the line of treatment, while erlotinib is also indicated in patients without EGFR mutation who undergo second- or third-line treatment. Some studies evaluated the main differences between these drugs both for direct comparison and to improve their sequential use. In particular, toxicity profile resulted partially different, and these observations may be explained by several molecular and pharmacokinetic features. Therefore, this review integrates preclinical data with clinical evidences of TKIs to guide the optimization of currently available treatments in advanced NSCLC patients.

Monoclonal antibodies in gastrointestinal cancers.

INTRODUCTION: Among gastrointestinal cancers, colorectal and gastric neoplasms are the most frequent. The development of new targeted drugs improved the efficacy of systemic therapy in advanced stages of those malignancies. AREAS COVERED: This review highlights the main biological processes implicated in gastrointestinal cancer development and progression, such as angiogenesis and epidermal growth factor receptor (EGFR) signaling pathway. On these bases, anti-EGFR and anti-vascular endothelial growth factor (VEGF) monoclonal antibodies in colorectal and gastric cancer are discussed. Data about further monoclonal antibodies in development are also reported. EXPERT OPINION: The use of monoclonal antibodies in colorectal and gastric cancers showed the best outcomes when combined with chemotherapy, even though single agent anti-EGFR antibodies seem active in particular setting of metastatic colorectal cancer (CRC) patients. It is not well defined whether the addition of anti-VEGF and anti-EGFR to chemotherapy could improve outcome in those patients susceptible to CRC-related metastases resection. Little and conflicting data are available about the role of these drugs in adjuvant setting. Tests are available to select patients with higher probability to get benefit from these treatments. Further biomarkers need to be evaluated to improve this selection and achieve "tailorization" of systemic therapy.

The role of microRNAs in cancer: diagnostic and prognostic biomarkers and targets of therapies.

INTRODUCTION: miRNAs are noncoding RNAs that target specific mRNA with subsequent regulation of particular genes, implicated in various biological processes. In cancer, miRNAs could show a different expression from normal tissues. miRNAs have a role as oncogenes when they target tumor suppressor genes and similarly they are tumor suppressors when they target oncogenes. AREAS COVERED: In this review, areas covered include the role of miRNAs in cancer diagnosis, prognosis and research for achievement of therapeutic strategies implicating miRNAs in oncology. As biogenesis of miRNAs is fundamental to understand their usefulness, this has also been discussed. Both miRNA expression profiles in cancer tissues and miRNA levels in peripheral blood were studied for improvement in the management of cancer patients. EXPERT OPINION: miRNAs have the potential for better understanding of tumor biology, but could also provide clinical advancement in management and therapy of various malignancies. The possibility of miRNA detection in peripheral blood would allow an eager expansion of their application in various clinical settings for cancer. The applicability of miRNA expression profiles still needs to be defined.

Local neck symptoms before and after thyroidectomy: a possible correlation with reflux laryngopharyngitis.

Local symptoms in the neck such as swallowing and voice disorders, and throat discomfort might be related to a goiter if present, but are also reported by patients suffering from reflux laryngopharyngitis. The aim of our study was to investigate the presence of reflux laryngopharyngitis in patients with nodular goiter before and after uncomplicated total thyroidectomy (TT) using a prospective study in University Hospital setting. We considered 25 patients, affected by non-toxic nodular goiter and candidates for TT, who complained of local symptoms in the neck. All the patients were carefully interviewed, with emphasis on swallowing and voice disorders, throat discomfort and reflux-related symptoms and underwent a videolaryngoscopy (VLS) and a videofluoroscopic swallowing study (VFSS) before and 3 months after TT. Before thyroidectomy, reflux laryngopharyngitis-related alterations were present in 68 and 50% at VLS and VFSS, respectively. After thyroidectomy, the swallowing and voice disorders persisted in 79 and 75%, respectively, while throat discomfort persisted in 91%. The results show that patients with a non-toxic nodular goiter who complain of local neck symptoms, before surgery it is appropriate to see if a reflux laryngopharyngitis is present; VLS and VFSS could be indicated for this and if necessary an antireflux treatment should be administered.

A minor modification of Lichtenstein repair of primary inguinal hernia: postoperative discomfort evaluation.

The aim of this study was to evaluate the usefulness of a modification of the Lichtenstein hernioplasty procedure by evaluating its impact on postoperative discomfort. From December 1999 to May 2006, the Lichtenstein inguinal hernioplasty was performed in 406 patients with noncomplicated unilateral inguinal hernia. During reconstruction, the mesh was fixed to the inguinal canal floor without stitching its upper margin to the internal oblique muscle. Control of postoperative pain proved to be satisfactory; 72 hours after surgery, 26.1 per cent of patients no longer felt any pain, whereas 54.4 per cent had slight pain without the need for painkillers; on Day 7, 92.8 per cent felt no pain at all. After 10 days, 86.7 per cent of those with sedentary jobs were able to return to work, whereas 79.1 per cent of those with heavier jobs resumed work in 11 to 15 days. Our modification of the original Lichtenstein procedure permitted us to obtain satisfactory results with regard to the control of postoperative chronic pain and a rapid reprisal of normal working activity.

Accuracy of the water-siphon test associated to barium study in a high prevalence gastro-oesophageal reflux disease population: a novel statistical approach.

RATIONALE, AIMS AND OBJECTIVES: Gastro-oesophageal reflux disease (GORD) is 'a condition which develops when the reflux of gastric content causes troublesome symptoms or complications'. Instrumental diagnostic tests generally used for GORD are 24-hour pH-metry and upper gastrointestinal (GI) endoscopy but barium study associated with provocative manoeuvres such as the water-siphon test (WST), has also been used for GORD. The aim of this paper was to estimate the accuracy of several tests in patients with GORD in a tertiary care setting, focusing on WST, which is rapid and non-invasive, simple to perform and well-tolerated by patients. METHOD: A total of 172 consecutive patients, symptomatic for reflux referred to a tertiary medical centre, were considered and data regarding the WST, 24-hour pH-metry, upper GI endoscopy with histology were analysed using latent class analysis, a multivariable statistical method for estimating the accuracy of tests when a gold standard is not available. RESULTS: The overall proportion of GORD in the sample was estimated at 0.664 [95% confidence interval (CI) = (0.589; 0.731)]. WST proved to be the most sensitive [Se = 0.886; 95% CI = (0.688; 1.000)] compared with pH-metry [Se = 0.620; 95% CI = (0.493; 0.745)] and endoscopy with histology [Se = 0.534; 95% CI = (0.273; 0.789)]. It was less specific [Sp = 0.537; 95% CI = (0.003; 1.000)] than pH-metry [Sp = 0.547; 95% CI = (0.281; 0.813)], and even less than endoscopy with histology [Sp = 0.862; 95% CI = (0.495; 1.00)]. Positive predictive values were estimated at 0.792 [95% CI = (0.721; 0.862)] for WST, 0.731 [95% CI = (0.643; 0.819)] for pH-metry and 0.886 [95% CI = (0.811; 0.961)] for endoscopy with histology. Negative predictive values were estimated at 0.707 [95% CI = (0.573; 0.841)] for WST, 0.422 [95% CI = (0.310; 0.534)] for pH-metry and 0.484 [95% CI = (0.387; 0.581)] for endoscopy with histology. CONCLUSION: Water-siphon test might possibly be useful in patients with suspected GORD because it is highly sensitive and predictive. A positive outcome of the WST associated with a barium study can certainly justify upper GI endoscopy and support any pharmacological treatment of GORD.

Gastro-oesophageal reflux and "epileptic" attacks: casually associated or related? Efficiency of antireflux surgery: a case report.

Although a possible link between gastro-oesophageal reflux disease (GORD) and obstructive sleeping apnoea has already been reported in the literature, there has never been any suggestion of an association with epilepsy, and epileptic attacks have not so far been included among gastro-oesophageal reflux disease symptoms. We report the case of a patient with gastro-oesophageal reflux disease associated with a sliding hiatus hernia, a short oesophagus and oesophagitis, who for the last ten years had not only presented the typical symptoms of gastrooesophageal reflux, but also symptoms of obstructive sleep apnoea and epileptic-like attacks occurring occasionally and only during sleep. Partial posterior fundoplication was performed and considerably reduced the reflux symptoms, and in addition brought about a drastic decrease in the number of epileptic-like attacks. Our case suggests that epileptic-like episodes in patients with obstructive sleeping apnoea may well be linked to the simultaneous presence of GORD associated with hiatus hernia, and surgical treatment of GORD may bring about an improvement of the neurological problems.

Keratin 7 expression as an early marker of reflux-related columnar mucosa without intestinal metaplasia in the esophagus.

BACKGROUND: The role of Barrett esophagus in carcinogenesis is widely accepted, but the significance of esophageal columnar mucosa without histological intestinal metaplasia, known as columnar-lined esophagus, is debated. MATERIAL/METHODS: We studied 128 patients free of Helicobacter pylori with reflux-related symptoms and columnar mucosa in the esophagus at endoscopy, 106 patients with Barrett esophagus (referred to as the Barrett group) and 22 patients without intestinal metaplasia (columnar group). Samples from 20 subjects free of H. pylori were used as controls. Immunostaining for keratin 7 (KRT7), keratin 20 (KRT20), caudal type homeobox 2 (CDX2), mucin 2, oligomeric mucus/gel-forming (MUC2), and tumor protein p53 (TP53) was assessed. RESULTS: Samples taken 1 cm above the gastroesophageal junction showed KRT7 staining in all cases in the Barrett and columnar groups and none in the control group. Immunostaining for TP53 was absent in the control group, and more frequent in the columnar group (7, 31.8%) compared with the Barrett group (14, 13.2%, P=0.033). In the columnar group, low grade dysplasia and TP53 expression was seen in 7 of 22 biopsy specimens (31.8%) at baseline and in 4 additional specimens after 2 years, for a total of 11 specimens (50.0%). CONCLUSIONS: The expression of KRT7 might help to explain the pathological, reflux-related nature of columnar-lined esophagus, as aberrant expression in a very early stage of the multistep Barrett esophagus progression. Expression of KRT7 may occur in basal glandular cells as a result of their multipotentiality and susceptibility to immunophenotype changes induced by reflux.

Trans-visceral migration of retained surgical gauze as a cause of intestinal obstruction: a case report.

INTRODUCTION: A retained surgical sponge in the abdomen is uncommon although it is likely that this finding is underreported in the medical literature. The intravisceral migration of retained surgical gauze is even rarer, as demonstrated by the very few cases reported. CASE PRESENTATION: Three years after undergoing anterior resection of the rectum, a 75-year-old man presented with symptoms of small bowel obstruction. Plain abdominal radiography and CT showed a radio-opaque marker; a foreign body was suspected, probably a piece of retained surgical gauze. An ileotomy of about 5 cm. was performed to confirm this diagnosis and remove the gauze. CONCLUSION: Although rare, retained gauze in the abdomen is a complication of surgery. The authors consider that this event may be more frequent than it appears from reports in the literature, probably because of its medico-legal implications. If all such cases were reported, it would be possible to estimate their exact number, classify the occurrence as a possible surgical complication and thus modify its medico-forensic consequences.