Regenerative medicine in the treatment of gastro-esophageal reflux disease and laryngo-pharyngeal reflux. From research to cure.

We present our observational study on 40 patients treated with the medical device containing sodium hyaluronic acid and magnesium alginate, performing a lubricating and hydrating action. This device is in the form of a gel, with topical action to contrast gastroesophageal reflux and to exert a mechanical role of protection of the mucosal tissues (mouth-pharyngo-esophageal mucosa and gastric mucose.). Forty patients were recruited aged between 22- and 72-years-old with painful dyspeptic Gastro Esophageal Reflux Disease (GERD) symptomatology in acute or in clinical phase (25 patients) and with pharyngolaryngo- tracheal symptomatology (15 patients). Patients were divided into two clinical groups: Group A was treated with the medical device, while Group B with conventional treatments without the medical device. Subjects of both groups were also treated with proton pump inhibitors (PPIs). Follow-up was at 10, 20 and 30 days and patients were evaluated for reduction of their subjective symptoms, reduction of symptomatic and occasional therapies, reduction of inflammatory process or disappearance of epithelial lesions of the examined mucosa, healing process. The reduction of subjective symptoms was observed at 10 days in the patient with food bolus (disappearance after 5 days) and in patients with a reduction of 70%. A relevant reduction in the use of symptomatic drugs was noted. Our data are relevant considering symptom relief (heartburn, reflux and dyspepsia). New scenarios for the treatment of inflammatory diseases of the digestive and respiratory tract mucosa are at the horizon. Interdisciplinary translational research brings to the development of novel medical devices (as the one described in this study) with a high safety profile, and extremely active on the inflammation-repair-regeneration complex of different tissues and organs.

The use of double lasso, fully covered self-expandable metal stents with new "anchoring flap" system in the treatment of benign biliary diseases.

BACKGROUND: Many benign biliary diseases (BBD) can be treated with fully covered, self-expandable metal stents (FCSEMS) but stent migration occurs in up to 35.7 %. The aim of this study was to prospectively assess the rate of, safety and effectiveness and stent migration of a new biliary FCSEMS with an anti-migration flap (FCSEMS-AF) in patients with BBD. PATIENTS AND METHODS: This was a prospective study from four Italian referral endoscopy centers of 32 consecutive patients (10 females and 22 males; mean age: 60.1 ± 14.8 years; range: 32-84 years) with BBD who were offered endoscopic placement of a FCSEMS-AF as first-line therapy. RESULTS: Were 24 strictures and 8 leaks. Stent placement was technically successful in 32/32 patients (100 %). Immediate clinical improvement was seen in all 32 patients (100 %). One late stent migration occurred (3.3 %). FCSEMS-AF were removed from 30 of the 32 patients (93.7 %) at a mean (± SD) of 124.4 ± 84.2 days (range: 10-386 days) after placement. All patients remained clinically and biochemically well at 1- and 3-month follow-up. One patient (3.3 %) with a post-laparoscopic cholecystectomy stricture developed distal stent migration at 125 days. CONCLUSION: This new FCSEMS with anti-migration flap seems to be a safe and effective first-line treatment option for patients with BBD.

GastroPanel® test for non-invasive diagnosis of atrophic gastritis in patients with dyspepsia.

AIM: Atrophic gastritis (AG), first step in the cascade leading to gastric adenocarcinoma, is related to Helicobacter pylori (H. pylori) infection. Currently, the gold standard for the diagnosis of AG is esophagogastroduodenoscopy (EGD) with histological examination of the biopsy specimens. However, since the latter are taken in random order and the distribution of AG is often patchy, histology is only representative of mucosal status. Considering this limitation, a test named GastroPanel®, that measures the blood concentrations of pepsinogen I and II, gastrin-17 and H. pylori antibodies, has been developed as a potential non-invasive biopsy. Aim of this study has been to assess the accuracy of GastroPanel® in patients with AG. METHODS: Forty-seven dyspeptic patients (24 males, mean age 52.2±9.3 years), in follow-up for antral or diffuse AG, were enrolled. All underwent at least two EGDs with random biopsies and blood collection for GastroPanel® parameters examination. RESULTS: Of the 47 patients, 16 (34.1%) had histological diagnosis of antral and 31 (65.9%) multifocal AG; 17 (36.2%) patients had mild and 30 (63.8%) had moderate-severe AG. H. pylori was detected in 39 (82.9%) and intestinal metaplasia was found in all patients. GastroPanel® showed 82.9% sensitivity for the diagnosis of AG and 53.8% for the diagnosis of H. pylori infection. The prediction of advanced atrophy was not sufficiently accurate, neither in patients with antral nor in those with multifocal AG. CONCLUSION: GastroPanel® can be useful for detecting patients with AG. However, it does not reflect the severity of atrophy.

Endoscopic mucosal resection in high- and low-volume centers: a prospective multicentric study.

BACKGROUND: Endoscopic mucosal resection (EMR) is an effective therapeutic technique well-standardized worldwide for the treatment of gastrointestinal neoplasm limited to the mucosal layer. To date, no study has compared technical and clinical differences based on the number of EMRs performed per year. This study aimed to compare EMR technical success, complications, and clinical outcome between low-volume centers (LVCs) and high-volume centers (HVCs). A total of nine endoscopic centers were included in the study. METHODS: This prospective study investigated consecutive patients with sessile polyps or flat colorectal lesions 1 cm or larger referred for EMR. RESULTS: A total of 427 lesions were resected in 384 patients at nine endoscopic centers. Males accounted for 60.4% and females for 39.6% of the patients. Most of the EMRs (84.8%) were performed in HVCs and only 15.2% in LVCs. All the lesions were resected in only one session. Argon plasma coagulation was performed on the margins of piecemeal resection in 15.7% of the patients in HVCs only. Complete excision was achieved for 98.6% of the lesions in HVCs and 98.8% of the lesions in LVCs. The complication rate was 4.4% in HVCs and 4.6% in LVCs (p = 0.94). Delayed bleeding occurred in 2.5% of the HVC cases and 3.1% of the LVC cases. Perforation occurred in 1.9% of the HVC cases and 1.5% of the LVC cases (p = 1.00). Recurrences were experienced with 15% of the lesions: 15.5% in HVCs and 14% in LVCs (p = 0.79). CONCLUSIONS: The study showed that EMR can be performed also in LVC.

Fully covered self-expandable metallic stents in benign biliary strictures: a multicenter study on efficacy and safety.

BACKGROUND AND STUDY AIM: Benign biliary diseases include benign biliary stricture (BBS), lithiasis, and leaks. BBSs are usually treated with plastic stent placement; use of uncovered or partially covered metallic stents has been associated with failure related to mucosal hyperplasia. Some recently published series suggest the efficacy of fully covered self-expandable metal stents (FCSEMSs) in BBS treatment. We aimed to assess the efficacy and safety of FCSEMS in a large series of patients with BBS and a long follow-up.  PATIENTS AND METHODS: Prospective multicenter clinical study at three tertiary referral centers: ISMETT/UPMC Italy, Palermo, San Paolo Hospital, Milan, and the ARNAS Civico Hospital, Palermo, Italy. All consecutive patients with BBS were treated with placement of FCSEMS rather than plastic stents, as first approach (11 patients, 17.7 %), or as a second approach after failure of other treatments (51 patients, 82.2 %). RESULTS: From January 2008 to March 2011, 62 patients (40 male) were included. Mean period of FCSEMS indwelling was 96.7 days (standard deviation [SD] 6.5 days). In 15 patients (24.2 %) the SEMS migrated. Resolution of BBS occurred in 56 patients (90.3 %), while in 6 (9.6 %) the treatment failed. Mean (SD) follow-up after SEMS removal was 15.9 (10) months. FCSEMS placement as first- or second-line approach showed no difference in failure. Recurrence was observed in 4 /56 patients (7.1 %); all were transplant recipients: P = 0.01; odds ratio (OR) 1.2, confidence interval (CI) 1.1 - 1.3. CONCLUSIONS: Despite the noteworthy migration rate, FCSEMSs should be considered effective for refractory benign biliary strictures. Further studies are needed to assess their role as a first approach in the management of BBS.

Investigation of Oddi sphincter structure by optical coherence tomography in patients with biliary-type 1 dysfunction: a pilot in vivo study.

BACKGROUND: Type 1 sphincter of Oddi dysfunction is a clinical entity characterised by biliary-type pain, elevated liver biochemical tests, and common bile duct dilation. Sphincter fibrosis is a common finding in this type of dysfunction and may require in some cases a differential diagnosis with a malignant intra-papillary disease. Optical coherence tomography permits high-resolution, real-time imaging of the sphincter of Oddi microstructure by a probe inserted into the common bile duct through an ERCP catheter. No data exist on the evaluation of sphincter of Oddi fibrosis by optical coherence tomography during ERCP in vivo. OBJECTIVE: To assess the feasibility of optical coherence tomography investigation of the sphincter of Oddi structure and assess its potential for diagnosing type 1 sphincter of Oddi dysfunction. PATIENTS: Ten consecutive patients, five with biliary-type 1 sphincter of Oddi dysfunction and five with pancreatic head/mid-body adenocarcinoma not involving the papillary region, who underwent both endoscopic ultrasound and therapeutic ERCP, were investigated by optical coherence tomography immediately before biliary sphincterotomy or stenting. RESULTS: In all sphincter of Oddi dysfunction patients optical coherence tomography recognised a hyper-reflective intermediate, fibro-muscular layer, significantly thicker than in patients with non-pathological sphincter of Oddi (p<0.0001). CONCLUSIONS: Optical coherence tomography imaging recognised an increased thickness and reflectance of the fibro-muscular layer of the sphincter of Oddi, very likely determined by fibrosis, and was not time-consuming; it can be safely used during ERCP to confirm the diagnosis in difficult cases. Its use in clinical practice has one important limitation since it requires magnification in the post-procedure computer analysis to obtain images useful for diagnosis.

Optical coherence tomography in pediatric patients: a feasible technique for diagnosing celiac disease in children with villous atrophy.

BACKGROUND AND AIM: Celiac disease is a common condition with many atypical manifestations, where histology serves as the "gold standard" for diagnosis. A useful new technique, optical coherence tomography, can depict villous morphology in detail, using light waves. This study examined the correlation between the sensitivity and specificity of optical coherence tomography in pediatric patients undergoing esophago-gastro-duodenoscopy for the diagnosis of celiac disease. MATERIALS AND METHODS: A total of 134 children were prospectively enrolled, 67 with a serological suspicion of celiac disease (group 1) and 67 with negative histology for celiac disease (group 2). During a diagnostic esophago-gastro-duodenoscopy we acquired multiple images and films in the four quadrants of the second part of the duodenum, and biopsies were taken in the area where optical coherence tomography had been done. Three patterns of villous morphology were considered: pattern 1=no atrophy (types 0, 1 or 2 of the Marsh classification); pattern 2=mild atrophy (type 3a or 3b); pattern 3=marked atrophy (type 3c). RESULTS: The diagnosis of celiac disease was histologically confirmed in all 67 children with positive antiendomysium and/or antitransglutaminase antibodies. Optical coherence tomography correlated with pattern 1 histology in 11/11 cases, pattern 2 in 30/32 (93.8%) and pattern 3 in 22/24 (91.6%). Sensitivity and specificity were 82% and 100%. In the control group there was 100% concordance between optical coherence tomography and histology. The overall concordance between optical coherence tomography and histology in determining patchy lesions was 75%. CONCLUSION: Optical coherence tomography could be a helpful diagnostic tool in children with mild or marked villous atrophy for diagnosing celiac disease during upper gastrointestinal (GI) endoscopy, avoiding biopsies. However, duodenal biopsies are mandatory if the optical coherence tomography shows normal villous morphology in patients with positive antibodies.

Optical coherence tomography compared with histology of the main pancreatic duct structure in normal and pathological conditions: an 'ex vivo study'.

BACKGROUND AND STUDY AIMS: Optical coherence tomography permits high-resolution imaging of tissue microstructures by a probe inserted into the main pancreatic duct through a standard ERCP catheter. The aim of this study was to compare optical coherence tomography images of the main pancreatic duct with histology and identify the optical coherence tomography pattern of the normal and pathological structure of the main pancreatic duct. PATIENTS AND METHODS: Multiple sections of neoplastic and non-neoplastic segments of 10 consecutive surgical pancreatic specimens obtained from patients with pancreatic head adenocarcinoma were investigated by optical coherence tomography scanning within 1h of resection. One hundred optical coherence tomography findings were then compared with the corresponding histopathological diagnoses. RESULTS: Main pancreatic duct wall architecture appeared at optical coherence tomography investigation as a three-layer structure with a different back-scattered signal from each layer. Optical coherence tomography imaging was concordant with histology in 81.8% and 18.75% of sections with normal tissue and chronic inflammatory changes. The K statistic between the two procedures was equal to 0.059 for non-neoplastic main pancreatic duct wall appearance. In all neoplastic sections optical coherence tomography showed a subverted layer architecture with heterogeneous back-scattering of the signal and was concordant with histology. CONCLUSIONS: Optical coherence tomography provided images of main pancreatic duct wall structure that were concordant with histology in 100% of cases in presence of neoplastic ductal changes and did not have false-positive or negative results. Optical coherence tomography images were also concordant with histology in about 80% of cases with normal main pancreatic duct structure; however, the differential diagnosis between normal tissue and chronic pancreatitis or dysplastic changes appeared very difficult.