Dario Raimondo

Second-line levofloxacin-based triple schemes for Helicobacter pylori eradication

BACKGROUND The recommended second-line therapy for Helicobacter pylori (H. pylori) eradication is a quadruple regimen that fails in up to 30% of patients. Several recent studies suggest levofloxacin-based triple therapies as an alternative rescue treatment. However, dosage and length of levofloxacin-based regimens have not been established. AIM To compare the efficacy and tolerability of four second-line levofloxacin-based schemes for H. pylori eradication. METHODS One hundred and sixty patients (aged 18-70 years, 72 male patients) who were H. pylori positive after standard triple therapies were randomised to receive esomeprazole 20mg b.d. and amoxicillin 1g b.d. plus levofloxacin 500 mg o.d., for 7 or 10 days (Groups A and B) or levofloxacin 500 mg b.d. for 7 days or 10 days (Groups C and D). H. pylori status was assessed by 13-C Urea Breath Test or rapid urease test, before and 6 weeks after therapy. Incidence of side effects was evaluated by a questionnaire. RESULTS No dropouts were observed. Eradication of H. pylori infection was successful in: 65% of patients in Group A; 90% in Group B; 70% in Group C; 85% in Group D. Based upon duration of treatment, eradication rates were: 67.5% in 7 days groups and 87.5% in 10 days groups (p=0.004). Dosage of levofloxacin did not affect the eradication rates (77.5% both in the once daily and twice daily groups). Mild adverse events were reported overall in 16% of patients (22.5% in 7 days groups; 27.5% in 10 days groups; p=0.58; 12% in the once daily group; 32.5% in the twice daily group; p=0.04). CONCLUSIONS 10 days levofloxacin-based second-line regimens were effective in curing H. pylori infection in more than 85% of patients with a lower incidence of adverse effects in levofloxacin single-dosage scheme. The 10 days levofloxacin-based regimens were more effective than 7 days course of treatment showing that duration of therapy is the crucial factor affecting eradication rate.

INFLAMMATION IN IRRITABLE BOWEL SYNDROME: MYTH OR NEW TREATMENT TARGET?

Low-grade intestinal inflammation plays a key role in the pathophysiology of irritable bowel syndrome (IBS), and this role is likely to be multifactorial. The aim of this review was to summarize the evidence on the spectrum of mucosal inflammation in IBS, highlighting the relationship of this inflammation to the pathophysiology of IBS and its connection to clinical practice. We carried out a bibliographic search in Medline and the Cochrane Library for the period of January 1966 to December 2014, focusing on publications describing an interaction between inflammation and IBS. Several evidences demonstrate microscopic and molecular abnormalities in IBS patients. Understanding the mechanisms underlying low-grade inflammation in IBS may help to design clinical trials to test the efficacy and safety of drugs that target this pathophysiologic mechanism.

Self-expandable metal stents for malignant colonic obstruction: Data from a retrospective regional SIED-AIGO study

BACKGROUND Self-expandable metal stents are a non-surgical option for the treatment of symptomatic malignant colorectal obstruction as palliative treatment or as a bridge to surgery. AIMS To report data from a regional study on self-expandable metal stent (SEMS) placement for malignant colorectal obstruction. METHODS Two hundred and four patients (male 54.9%, mean age of 69.5 ± 14.2) were retrospectively evaluated and data on technical and clinical success, and complications, were analyzed. RESULTS Technical and clinical success rates were 99% and 94.6% respectively, with 36.7% treated on an emergency basis and 63.3% electively. Palliative treatment was administered to 70.1%, and as a bridge to surgery for 29.9%. Complications were 17 neoplastic ingrowths, 10 stent migrations, and 4 perforations. Palliative treatment was associated with a higher risk of stent ingrowth (p=0.003), and chemotherapy with a lower risk of stent ingrowth (p=0.009). CONCLUSION This regional study, although it has certain limitations, confirms the positive role of self-expandable metal stents in the treatment of symptomatic malignant colorectal obstruction, and that chemotherapy decreases the risk of ingrowth.

Advanced endoscopic imaging for surveillance for dysplasia and colorectal cancer in inflammatory bowel disease: could the pathologist be further helped?

Patients with inflammatory bowel disease (IBD) have an increased risk of developing intestinal cancer. The magnitude of that increased risk as well as how best to mitigate it remain a topic of ongoing investigation in the field. It is important to quantify the risk of colorectal cancer in association with IBD. The reported risk varies widely between studies. This is partly due to the different methodologies used in the studies. Because of the limitations of surveillance strategies based on the detection of dysplasia, advanced endoscopic imaging and techniques involving the detection of alterations in mucosal antigens and genetic abnormalities are being investigated. Development of new biomarkers, predicting future occurrence of colonic neoplasia may lead to more biomarker-based surveillance. There are promising results that may lead to more efficient surveillance in IBD patients and more general acceptance of its use. A multidisciplinary approach, involving in particular endoscopists and pathologists, together with a centralized patient management, could help to optimize treatments and follow-up measures, both of which could help to reduce the IBD-associated cancer risk.

Self-Expandable Metal Stent Placement for Closure of a Leak after Total Gastrectomy for Gastric Cancer: Report on Three Cases and Review of the Literature

In the setting of the curative oncological surgery, the gastric surgery is exposed to complicated upper gastrointestinal leaks, and consequently the management of this problem has become more critically focused than was previously possible. We report here three cases of placement of a partially silicone-coated SEMS (Evolution Controlled Release Esophageal Stent System, Cook Medical, Winston-Salem, NC, USA) in patients who underwent total gastrectomy with Roux-en-Y end-to-side esophagojejunostomy for a gastric adenocarcinoma. The promising results of our report, despite the small number of patients, suggest that early stenting (through a partially silicone-coated SEMS) is a feasible alternative to surgical treatment in this subset of patients. In fact, in the treatment of leakage after total gastrectomy, plastic stents and totally covered metallic stents may not adhere sufficiently to the esophagojejunal walls and, as a result, migrate beyond the anastomosis. However, prospective studies with a larger number of patients might assess the real effectiveness and safety of this procedure.

Could JC virus provoke metastasis in colon cancer

AIM To evaluate the prevalence of John Cunningham virus (JC virus) in a small cohort of patients with colon cancer and to assess its presence in hepatic metastasis. METHODS Nineteen consecutive patients with histologically diagnosed colon cancer were included in our study, together with ten subjects affected by histologically and serologically diagnosed hepatitis C virus infection. In the patients included in the colon cancer group, JC virus was searched for in the surgical specimen; in the control group, JC virus was searched for in the hepatic biopsy. The difference in the prevalence of JC virus in the hepatic biopsy between the two groups was assessed through the χ(2) test. RESULTS Four out of 19 patients with colon cancer had a positive polymerase chain reaction (PCR) test for JC virus, and four had liver metastasis. Among the patients with liver metastasis, three out of four had a positive PCR test for JC virus in the surgical specimen and in the liver biopsy; the only patient with liver metastasis with a negative test for JC virus also presented a negative test for JC virus in the surgical specimen. In the control group of patients with hepatitis C infection, none of the ten patients presented JC virus infection in the hepatic biopsy. The difference between the two groups regarding JC virus infection was statistically significant (χ(2) = 9.55, P = 0.002). CONCLUSION JC virus may play a broader role than previously thought, and may be mechanistically involved in the late stages of these tumors.

Does glatiramer acetate provoke hepatitis in multiple sclerosis

An association between multiple sclerosis and autoimmune hepatitis has been described. The latter can also be unmasked or exacerbated by a variety of therapies used in multiple sclerosis, such as beta-Interferon or glatiramer acetate. Two cases of hepatitis occurring after exposure to glatiramer acetate are described here: the first, was possibly due to autoimmune hepatitis, rather than glatiramer acetate induced liver injury, the second was definite autoimmune hepatitis. Both occurred in patients who had already experienced hepatitis exacerbations during previous beta-Interferon treatment. We suggest that glatiramer acetate can unmask hepatitis. Thus, liver enzyme monitoring should be undertaken frequently in those patients with multiple sclerosis receiving glatiramer acetate, with a history of hepatitis during treatment with Interferon beta-1a.

Minimally invasive surgical approach for radicalization of incidental post-cholecystectomy gallbladder carcinoma: safety, feasibility and outcomes

Abstract Background and aims: Gallbladder carcinoma is a rare but aggressive malignant neoplasm. The incidence of intra- or post-operative incidental gallbladder carcinoma diagnosis following laparoscopic cholecystectomy is estimated to be 1–2%. Aggressive re-resection is warranted as the majority of patients have residual disease either in the liver or the lymph nodes. However the use of a minimally invasive surgical approach (MISA) to perform a radicalization in these patients has not been investigated yet. We retrospectively analyzed surgical and oncologic outcome of a small selected cohort of patients with incidental gallbladder carcinoma whom underwent redo radicalization surgery by MISA. Material and methods: From April 2012 to June 2014 at our department six patients (three females and three males) with incidental findings of gallbladder carcinoma pT1b (stage I) following laparoscopic cholecystectomy, and referred to our center from other secondary-level referral hospitals, underwent a redo surgery for radicalization by means of laparoscopic (n. 3) or robotic approach (n. 3). A retrospective analysis of prospective collected data was performed. Results: The redo procedure consisted of a liver resection (segments IVb + V) and lymph nodes clearance of hepatoduodenal hilum and common hepatic artery. Conversion rate was zero. Median operative time was 290 (250–310) min. Estimate blood loss was 175 (100–350) ml. Total hospital stay was 6 (5–10) days. All liver resections were performed without inflow vascular clamping. One patient was re-operated for hemoperitoneum while peri-operative mortality was zero. Oncologically, an R0 resection was always achieved with a mean number of lymph nodes retrieved of 17,5 (14–22). The stage of the neoplasm was confirmed in all cases but one, who was found to have a pN1 status (stage IIIb). At 21 (6–32) months follow-up all patients are alive and no recurrence has been observed. Conclusions: Our data suggest that radicalization of patients with stage I incidental postoperative gallbladder carcinoma can be done by a MISA without compromising the oncologic outcome. Larger studies are needed to validate these results.

Superior Mesenteric Artery Syndrome: Clinical, Endoscopic, and Radiological Findings

Background The superior mesenteric artery (SMA) syndrome is a rare entity presenting with upper gastrointestinal tract obstruction and weight loss. Studies to determine the optimal methods of diagnosis and treatment are required. Aims and Methods This study aims at analyzing the clinical presentation, diagnosis, and management of SMA syndrome. Ten cases of SMA syndrome out of 2074 esophagogastroduodenoscopies were suspected. A contrast-enhanced computed tomography (CECT) scan was performed to confirm the diagnosis. After, a gastroenterologist and a nutritionist personalized the therapy. Furthermore, we compared the demographical, clinical, endoscopic, and radiological parameters of these cases with a control group consisting of 10 cases out of 2380 EGDS of initially suspected (but not radiologically confirmed) SMA over a follow-up 2-year period (2015-2016). Results The prevalence of SMA syndrome was 0.005%. Median age and body mass index were 23.5 years and 21.5 kg/m2, respectively. Symptoms developed between 6 and 24 months. Median aortomesenteric angle and aorta-SMA distance were 22 and 6 mm, respectively. All patients improved on conservative treatment. In our series, a marked (>5 kg) weight loss (p = 0.006) and a long-standing presentation (more than six months in 80% of patients) (p = 0.002) are significantly related to a diagnosis of confirmed SMA syndrome at CECT after an endoscopic suspicion. A “resembling postprandial distress syndrome dyspepsia” presentation may be helpful to the endoscopist in suspecting a latent SMA syndrome (p = 0.02). The narrowing of both the aortomesenteric angle (p = 0.001) and the aortomesenteric distance (p < 0.001) was significantly associated with the diagnosis of SMA after an endoscopic suspicion; however, the narrowing of the aortomesenteric distance seemed to be more accurate, rather than the narrowing of the aortomesenteric angle. Conclusion SMA syndrome represents a diagnostic and therapeutic challenge. Our results show the following findings: the importance of the endoscopic suspicion of SMA syndrome; the preponderance of a long-standing and chronic onset; a female preponderance; the importance of the nutritional counseling for the treatment; no need of surgical intervention; and better diagnostic accuracy of the narrowing of the aorta-SMA distance. Larger prospective studies are needed to clarify the best diagnosis and management of the SMA syndrome.

New therapeutic perspectives in irritable bowel syndrome: Targeting low-grade inflammation, immuno-neuroendocrine axis, motility, secretion and beyond

Irritable bowel syndrome (IBS) is a chronic, recurring, and remitting functional disorder of the gastrointestinal tract characterized by abdominal pain, distention, and changes in bowel habits. Although there are several drugs for IBS, effective and approved treatments for one or more of the symptoms for various IBS subtypes are needed. Improved understanding of pathophysiological mechanisms such as the role of impaired bile acid metabolism, neurohormonal regulation, immune dysfunction, the epithelial barrier and the secretory properties of the gut has led to advancements in the treatment of IBS. With regards to therapies for restoring intestinal permeability, multiple studies with prebiotics and probiotics are ongoing, even if to date their efficacy has been limited. In parallel, much progress has been made in targeting low-grade inflammation, especially through the introduction of drugs such as mesalazine and rifaximin, even if a better knowledge of the mechanisms underlying the low-grade inflammation in IBS may allow the design of clinical trials that test the efficacy and safety of such drugs. This literature review aims to summarize the findings related to new and investigational therapeutic agents for IBS, most recently developed in preclinical as well as Phase 1 and Phase 2 clinical studies.