Intra-operative radiotherapy management for breast cancer treatment in patients with pseudoxanthoma elasticum: A case report.

Pseudoxanthoma elasticum is a systemic metabolic disease presenting calcifications and progressive fragmentation of elastic fibers. Actually, no targeted therapies are available for the treatment; only prevention of complications is possible. Classically, pseudoxanthoma elasticum is a "benign" disease, without cancer association. Herein, we reported a singular association of pseudoxanthoma elasticum with breast carcinoma, describing the clinical management, in particular intra-operative treatment, focusing on intra-operative radiotherapy since no specific guidelines are available in literature.

Clinical utility and interobserver agreement of autofluorescence imaging and magnification narrow-band imaging for the evaluation of Barrett's esophagus: a prospective tandem study.

BACKGROUND: New endoscopic imaging techniques, such as autofluorescence imaging (AFI) and narrow-band imaging (NBI), have been developed to improve the detection of neoplastic lesions in Barrett's esophagus (BE). OBJECTIVE: To evaluate the clinical utility of AFI and magnification NBI to detect high-grade dysplasia (HGD) and early esophageal adenocarcinoma (EAC) and the interobserver agreement. DESIGN: Prospective tandem study of eligible patients. SETTING: Single, academic tertiary care center. PATIENTS: Forty-two patients with a history of confirmed BE were prospectively enrolled. INTERVENTIONS: The BE segment was examined under high-definition white-light endoscopy, and the presence of visible lesions was recorded. Subsequently, AFI and magnification NBI were performed in tandem on areas of the BE segment away from visible lesions; images obtained by these 2 systems were graded according to the color of reflected light and surface patterns, respectively. Biopsy specimens were obtained at the end of the procedure. MAIN OUTCOME MEASUREMENTS: The sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of the AFI and NBI patterns for the detection of HGD/EAC and interobserver agreement. RESULTS: Of the 42 patients enrolled, 14 (33%) had HGD/EAC. On patient-based analysis, AFI alone had a sensitivity, specificity, and NPV of 50%, 61%, and 71%, respectively, and the overall accuracy for the detection of HGD/EAC patients was 57%. By using magnification NBI in tandem fashion, the sensitivity and NPV improved to 71% and 76%, respectively, with a decrease in specificity to 46% and in overall accuracy to 55%. The 2 techniques had moderate interobserver agreement for both the patterns and prediction of histology. LIMITATIONS: Uncontrolled study performed at an academic center by expert endoscopists in a high-risk population. CONCLUSIONS: By using a multimodality endoscope, both AFI and magnification NBI had limited clinical accuracy and moderate overall interobserver agreement. AFI does not appear to be useful as a broad-based technique for the detection of neoplasia in patients with BE.

Prevalence and predictors of columnar lined esophagus in gastroesophageal reflux disease (GERD) patients undergoing upper endoscopy.

OBJECTIVES: Chronic gastroesophageal reflux disease (GERD) is a risk factor for Barrett's esophagus (BE), the most important surrogate marker for the development of esophageal adenocarcinoma (EAC). The need to document the presence of intestinal metaplasia in esophageal biopsies from a columnar lined esophagus (CLE) to diagnose BE is debated. The objective of this study was to prospectively evaluate the prevalence and risk factors of CLE in a large cohort of GERD patients undergoing upper endoscopy. METHODS: Consecutive patients presenting to the endoscopy unit at a tertiary referral center for their index upper endoscopy for evaluation of GERD symptoms were enrolled in this prospective cohort study. Patients were asked to complete a validated GERD questionnaire that documents the onset of GERD symptoms (heartburn and acid regurgitation) and grades the frequency and severity of symptoms experienced over the past year. Demographic information, body mass index, and use of aspirin/nonsteroidal antiinflammatory drugs were recorded. Endoscopic details including length of CLE, presence and size of hiatal hernia were noted. Patients with CLE (cases) were compared with those without CLE (controls) using Fischer's exact test and t-test. All factors that were statistically significant (P<0.05) were then entered into stepwise logistic regression to evaluate for independent predictors of CLE. RESULTS: A total of 1058 patients with GERD symptoms were prospectively enrolled. On index endoscopy, the prevalence of CLE was 23.3%, whereas of CLE with documented intestinal metaplasia was 14.1%. On univariate analysis, male gender, Caucasian race, heartburn duration of >5 years, presence and size of hiatal hernia were significantly associated with the presence of CLE compared with controls (P<0.05). On multivariate analysis, heartburn duration >5 years (odds ratio (OR): 1.50, 95% confidence interval (CI): 1.07-2.09, P=0.01), Caucasian race (OR: 2.40, 95% CI: 1.42-4.03, P=0.001), and hiatal hernia (OR: 2.07, 95% CI: 1.50-2.87, P<0.01) were found to be independent predictors for CLE. CLE length was significantly associated with the presence of intestinal metaplasia (P<0.001). CONCLUSIONS: If BE is defined by the presence of CLE alone on upper endoscopy, up to 25% of GERD patients are diagnosed with this lesion. Enrolling all these patients in surveillance programs would have significant ramifications on health-care resources.

Breast Cancer Surgery in the COVID-19 Pandemic: Validation of a Preventive Program for Patients and Health Care Workers.

BACKGROUND/AIM: The perspective validation of a selective approach in patients undergoing breast cancer surgery was performed in order to assess whether patients as well as Health Care Workers (HCWs) were exposed to any undue risk of COVD-19 infection. PATIENTS AND METHODS: From March 9th to June 9th 2020, 207 patients were phone-triaged by a dedicated Breast Care Nurse; a patient-tailored program was adopted with the aim of avoiding hospitalization of SARS-CoV-2 symptomatic patients, with a careful prioritization of surgical procedures according to specific disease features. RESULTS: Two hundred and three out of 207 patients underwent operation; seven patients were temporarily excluded because they tested positive at phone triage (n=3), or in-hospital triage (n=3); another asymptomatic patient with negative NP swab tested IgM Ab-positive so that surgery was re-scheduled two weeks later. Four patients had no surgery; one of them was reconsidered for neoadjuvant chemotherapy (NAC) after testing positive at phone triage; three patients were excluded because they were already hospitalized for COVID-19. Overall, mean in-hospital stay was 2.2 days (±SD, 0.7) and, after hospital discharge, no patient required readmission. CONCLUSION: This preventive program avoided any COVID-19 infection among patients and HCWs, so that an elective breast cancer surgical procedure can be safely and timely pursued without affecting the oncologic outcome.

Breast Cancer Surgery During the COVID-19 Pandemic: An Observational Clinical Study of the Breast Surgery Clinic at Ospedale Policlinico San Martino - Genoa, Italy.

BACKGROUND: COVID-19 pandemic required a marked re-allocation of healthcare resources, including at Breast Units. A patient-tailored program was developed to assess its efficacy regarding prevention of COVID-19 infection among patients with breast cancer undergoing surgery and healthcare workers (HCWs). PATIENTS AND METHODS: From March 9th to April 9th 2020, 91 patients were selected for elective surgery by means of: i) Pre-hospital screening aimed at avoiding hospitalization of symptomatic or suspicious COVID-19 patients, and ii) prioritisation of surgical procedure according to specific disease features. RESULTS: Eighty-five patients (93.4%) were fit for surgery, while five patients (5.5%) were temporarily excluded through 'telephone triage'; another two patients were excluded at in-hospital triage. A total of 71 out of 85 patients (83.5%) were diagnosed with invasive cancer, most of whom were undergoing breast-conserving surgery (61 out of 85 patients, 71.8%). The mean in-hospital stay was 2.2 days (SD=0.7 days). After hospital discharge, no patient needed re-admission due to post-operative complications; moreover, no COVID-19 infection among patients or HCWs was detected. CONCLUSION: Safe breast cancer surgery was accomplished for both patients and HCWs by means of a careful preoperative selection of patients and in-hospital preventative measures. This screening program can be transferred to high-volume Breast Units and it may be useful in implementing European Community recommendations for prevention of COVID-19 infection.

Patterns of antiplatelet agent use in the US.

BACKGROUND: The American Society of Gastrointestinal Endoscopy (ASGE) published updated guidelines in 2009 to help endoscopists manage the treatment of their patients who have been prescribed antiplatelet therapy (APT). STUDY AIM: To assess the use of APT among endoscopists, and to identify factors guiding their use of APT while treating their patients. METHOD: A survey questionnaire was distributed to endoscopists at two national meetings to assess their usage of APT while treating patients during the peri-endoscopic period. RESULTS: The survey was provided to 400 attendees of whom 239 (60 %) responded. Only 30 % of respondents followed the ASGE guidelines for treating their patients and 26 % percent of respondents withheld all APT before engaging in any patient procedure. Endoscopists' decisions appeared to be influenced by their own particular experiences rather than any specific APT usage guidelines (46 % vs 22 %; P < 0.05). As expected, more endoscopists (P < 0.05) continued APT for patients who underwent low risk procedures (90 %) than for patients who underwent high risk procedures (47 %). Approximately 50 % of the respondents did not perform high risk procedures for patients prescribed aspirin therapy. CONCLUSIONS: About one-fourth of endoscopists surveyed discontinued APT treatment of patients who underwent any endoscopic procedure, and one-half of them discontinued use of non-steroidal anti-inflammatory drug treatment of patients who underwent a high risk endoscopic procedure. Inappropriate withdrawal of APT medications may expose patients to unnecessary risks, and efforts to improve endoscopists' application of ASGE guidelines for the use of APT to treat patients during the peri-endoscopic period are warranted.

Long-term results of the mucosal ablation of Barrett's esophagus: efficacy and recurrence.

BACKGROUND AND STUDY AIMS: It has been postulated that the endoscopic ablation of Barrett's esophagus can lead to complete eradication of the disease. This study was undertaken to evaluate the efficacy of endoscopic eradication therapy for Barrett's esophagus and the rates of recurrence of intestinal metaplasia. PATIENTS AND METHODS: As part of an initial randomized controlled trial, patients with nondysplastic or low grade dysplastic Barrett's esophagus underwent mucosal ablation. Following ablation, the patients had annual surveillance endoscopies. Recurrence was defined as the presence of intestinal metaplasia after initial complete eradication had been achieved. RESULTS: A total of 28 patients with Barrett's esophagus were followed for a mean of 6.4 years after ablation therapy. At baseline, the majority of the patients had nondysplastic Barrett's esophagus (79 %). Initial complete eradication of intestinal metaplasia was achieved at a mean of 4.1 months. During long-term follow-up, initial recurrence of intestinal metaplasia was seen in 14 of the 28 of patients (50 %) at a mean of 40 months, and further maintenance ablation therapy was applied. At the final follow-up, 36 % of the patients had complete eradication of intestinal metaplasia, 18 % of the patients had intestinal metaplasia, and 21 % had died of unrelated causes; invasive esophageal adenocarcinoma had developed in 1 patient. CONCLUSIONS: The long-term results of this study demonstrate a recurrence rate of 50 % after complete eradication of Barrett's esophagus with endoscopic eradication therapy. In addition, re-recurrence (in 36 %), even after further maintenance endoscopic eradication therapy, and deaths unrelated to the disease (21 %) occurred. Complete remission of Barrett's esophagus appears to be a difficult goal to achieve. These results call into question the role of ablation in patients with low risk Barrett's esophagus.

Esophageal motility abnormalities in gastroesophageal reflux disease.

Esophageal motility abnormalities are among the main factors implicated in the pathogenesis of gastroesophageal reflux disease. The recent introduction in clinical and research practice of novel esophageal testing has markedly improved our understanding of the mechanisms contributing to the development of gastroesophageal reflux disease, allowing a better management of patients with this disorder. In this context, the present article intends to provide an overview of the current literature about esophageal motility dysfunctions in patients with gastroesophageal reflux disease. Esophageal manometry, by recording intraluminal pressure, represents the gold standard to diagnose esophageal motility abnormalities. In particular, using novel techniques, such as high resolution manometry with or without concurrent intraluminal impedance monitoring, transient lower esophageal sphincter (LES) relaxations, hypotensive LES, ineffective esophageal peristalsis and bolus transit abnormalities have been better defined and strongly implicated in gastroesophageal reflux disease development. Overall, recent findings suggest that esophageal motility abnormalities are increasingly prevalent with increasing severity of reflux disease, from non-erosive reflux disease to erosive reflux disease and Barrett's esophagus. Characterizing esophageal dysmotility among different subgroups of patients with reflux disease may represent a fundamental approach to properly diagnose these patients and, thus, to set up the best therapeutic management. Currently, surgery represents the only reliable way to restore the esophagogastric junction integrity and to reduce transient LES relaxations that are considered to be the predominant mechanism by which gastric contents can enter the esophagus. On that ground, more in depth future studies assessing the pathogenetic role of dysmotility in patients with reflux disease are warranted.

Distinction between patients with non-erosive reflux disease and functional heartburn.

Non-erosive reflux disease (NERD) and functional heartburn (FH) are two different clinical entities and the clear distinction between the two forms is actually possible thanks to the use of impedance-pH monitoring. NERD is the more common manifestation of gastro-esophageal reflux disease (GERD), one of the most widespread chronic gastrointestinal disorders in Western countries. The absence of visible lesions on endoscopy and the presence of troublesome reflux-associated (to acid, weakly acidic or non-acid reflux) symptoms are the two key factors for the definition of NERD. FH is an exclusive diagnosis and is defined by the Rome III criteria as a burning retrosternal discomfort, excluding GERD and esophageal motility disorders as a cause of the symptom. FH does not have any type of reflux underlying symptoms and psychological factors seem to be more expressed in FH patients than in patients with reflux-provoked disturbances. The aim of our review is to report the state-of-the-art knowledge about NERD and FH, to clarify their features and differences and to stimulate new research in this field.

Dysmotility and reflux disease.

PURPOSE OF REVIEW: In the last decade, with the advent of new oesophageal testing [i.e. 24-h impedance-pH monitoring, combined impedance-manometry, high-resolution manometry (HRM)], relevant progress in understanding the mechanisms contributing to the development of gastro-oesophageal reflux disease (GORD) has been made, allowing a better management of patients with this disorder. The aim of our review is to report the state-of-the-art about oesophageal motor disorders in patients with reflux disease and to stimulate new research in this field. RECENT FINDINGS: Hypotensive lower oesophageal sphincter (LOS), transient LOS relaxations, impairment of oesophagogastric junction including hiatal hernia, oesophageal bolus transit abnormalities and presence of ineffective oesophageal motility have been strongly implicated in GORD development. In particular, the majority of recent studies carried out with HRM and impedance-pH testing reported that these motor abnormalities are increasingly prevalent with increasing severity of GORD, from nonerosive reflux disease and erosive oesophagitis to Barrett's oesophagus. SUMMARY: Defining and characterizing oesophageal dysmotility in patients with reflux disease is of maximum importance in order to properly diagnose these patients and to treat them with the best management of care. New studies are needed in order to better understand the physiomechanic basis of oesophageal dysmotility in GORD patients.

The pharmacokinetics of ilaprazole for gastro-esophageal reflux treatment.

INTRODUCTION: Approximately 20% of the Western population is affected by gastro-esophageal reflux disease (GERD). To date, proton pump inhibitors (PPIs) represent the mainstay of GERD medical treatment. However, despite their undoubted benefit, about 40% of GERD patients display an inadequate response to these drugs. Recently, a new PPI, ilaprazole , at oral doses of 10 mg has shown higher suppression of gastric acid secretion, more prolonged plasma half-life, and similar safety compared to 20 mg omeprazole. AREAS COVERED: This review provides an update on the following points: pharmacokinetic profile and metabolism of ilaprazole in relation to its pharmacodynamic properties; comparative data on the pharmacokinetics and pharmacodynamics of ilaprazole with currently available PPIs; and implications for studies on the therapeutic efficacy of ilaprazole in GERD. EXPERT OPINION: Different studies show that ilaprazole, a benzimidazole derivative, has an extended plasma half-life in comparison with all other approved PPIs. In addition, ilaprazole metabolism is not significantly influenced by CYP2C19, compared to the available PPIs. Furthermore, the pharmacological characteristics of ilaprazole confer theoretical advantages that are expected to translate into an improved acid control, particularly at night time. However, studies comparing the clinical pharmacokinetics and pharmacodynamics of ilaprazole with those of second-generation PPIs are insufficient. Moreover, further investigations assessing the efficacy of ilaprazole in the management of GERD are required. In healthy volunteers, as well as in patients with gastric or duodenal ulcers, ilaprazole has not shown clinically relevant changes in hematology and biochemistry testing, nor significant treatment-related adverse symptoms.

Cigarette smoking is a modifiable risk factor for Barrett's oesophagus.

BACKGROUND: Cigarette smoking has been associated with an increased risk of oesophageal adenocarcinoma (OAC). However, the impact of smoking and more importantly smoking cessation on Barrett's oesophagus (BO) is unclear. OBJECTIVE: The aim of the study is to evaluate the association between cigarette smoking and presence of BO in a large prospective cohort of patients with gastro-oesophageal reflux disease (GORD). METHODS: Patients presenting to the endoscopy unit for upper endoscopy completed a validated GORD questionnaire and information on demographics (age, gender, and ethnicity), cigarette smoking [status (current/past), amount (pack years) and duration of smoking cessation], clinical data [medication history, body mass index (BMI), and family history] and endoscopic findings [BO and hiatal hernia] were recorded. Cigarette smokers (current and past) and nonsmokers were compared using Fisher's Exact test for categorical variables and Mann-Whitney test for continuous variables. Effects of cigarette smoking and smoking cessation on BO risk was assessed by stepwise logistic regression analysis. RESULTS: A total of 1056 patients were included in the analysis [mean age: 57.2 ± 12.7years, Caucasian 880 (83.3%), male 985 (93.3%), and mean BMI 29.6 (SD: ± 5.6)]. 827 (78.3%) were smokers and 229 (21.6%) were nonsmokers. 474 subjects (44.9%) had a previous history of smoking. Anytime smokers were more likely to have BO (adjusted OR: 3.3; 95 CI: 1.7-6.3; p < 0.01). Higher smoking burden (pack years) was associated with higher risk of BO in this GORD cohort (p for trend < 0.01). Duration of smoking cessation was inversely associated with risk of BO (p for trend: 0.01). CONCLUSION: This study shows that smokers with reflux symptoms have about threefold higher risk of BO compared with nonsmokers, whereas discontinuing smoking is associated with a significant reduced risk. Smoking cessation appears to be a viable option to reduce BO risk in patients with reflux disease.