Use of a proline-specific endopeptidase to reintroduce gluten in patients with non-coeliac gluten sensitivity: A randomized trial.

BACKGROUND: A gluten-free diet (GFD) is the main therapy for non-coeliac gluten sensitivity (NCGS). However, the availability of novel enzymes with the ability to digest gluten could represent a therapeutic opportunity for NCGS patients to avoid a GFD. AIMS: To evaluate the controlled reintroduction of gluten with or without the endopeptidase P1016 in NCGS patients. METHODS: This is a randomized, double-blind, placebo-controlled monocentric study, Registered under ClinicalTrials.gov Identifier no. NCT01864993. Gluten was reintroduced incrementally over a 3-week period under nutritional control. NCGS patients were randomized into two groups and administered P1016 or placebo during gluten reintroduction. We evaluated symptoms (visual analogue scale, VAS), quality of life (SF-36) and mental health symptoms (SCL-90) on a weekly basis. RESULTS: We enrolled a total 23 patients who were allocated to a placebo group (n = 11, age 38.4 ± 2.9) or an intervention group (n = 12, age 39.5 ± 3.1). No effect of P1016 on symptoms was found. During gluten reintroduction, patients reported a significant increase in abdominal pain and a worsening of stool consistency. Furthermore, no differences were found between the groups regarding SCL-90 and SF-36 scores. CONCLUSIONS: Our results demonstrate a lack of effect of P1016 in the management of NCGS patients and the possible reintroduction of gluten.

Untreated adult GH deficiency is not associated with the development of metabolic risk factors: a long-term observational study.

PURPOSE: Uncertainties exist about the predictors of the severity of the clinical picture of GH deficiency (GHD) syndrome. Aim of the study was to evaluate, in adult patients with GHD, the predictors of the development of hypercholesterolemia, hypertension, diabetes mellitus, and osteoporosis. METHODS: We retrospectively studied 327 adult patients (age 47.1 ± 17.1 years) with untreated severe GHD (mean follow-up 110.9 ± 56.8 months). GHD was defined by GHRH + arginine test using BMI cut-offs. The possible development of hypercholesterolemia, hypertension, diabetes mellitus, and osteoporosis was investigated by Kaplan-Meier survival analysis. For each clinical outcome, either a univariate or multivariate analysis according to the Cox proportional-hazards model was performed to identify those factors that were associated with the development of the event. RESULTS: GH secretion parameters were not associated with the outcomes. Hypercholesterolemia was positively and negatively predicted by a BMI ≥ 30 kg/m2 (HR 2.50, p 0.00) and the dose of l-thyroxine possibly in place (HR 0.98, p 0.02), respectively. Hypertension was positively predicted by a BMI ≥ 30 kg/m2 (HR 2.64, p 0.00) and IGF-I SDS values (HR 2.26, p 0.00). Diabetes mellitus was positively predicted by hypertension (HR 11.76, p 0.01). Osteoporosis was positively and negatively predicted by hypercholesterolemia (HR 3.25, p 0.01) and hypertension (HR 0.21, p 0.00), respectively. CONCLUSIONS: The severity of the impairment of GH secretion does not predict the development of the clinical picture of GHD syndrome: untreated adult GHD does not increase the development of metabolic risk factors in hypopituitaric patients.

Are the dietary habits of treated individuals with celiac disease adherent to a Mediterranean diet?

BACKGROUND AND AIMS: The only treatment for celiac disease (CD) is strict, lifelong adherence to a gluten-free (GF) diet. To date, there are contrasting data concerning the nutritional adequacy of GF products and diet. There have been no studies that have assessed the adherence of individuals with CD to a Mediterranean diet (MD), a protective dietary regimen against major non-communicable diseases (NCDs). Therefore, we examined the adherence to an MD of a group of Italian individuals with CD and compared it with that of a healthy control group. METHODS AND RESULTS: In a cross-sectional study, a sample of individuals with CD and a group of healthy subjects were included. The dietary habits of all participants were recorded using a validated food frequency questionnaire, and the adherence to an MD was determined using the Italian Mediterranean Index. Typical Mediterranean food consumption was not significantly different between individuals with CD and the healthy participants, except for fruits (P = 0.017). However, individuals with CD consumed significantly higher amounts of potatoes (P = 0.003) and red and processed meat (P = 0.005) than healthy participants. The resulting mean Italian Mediterranean Index was significantly higher in healthy participants than in individuals with CD (P < 0.001). CONCLUSION: The results raise questions concerning the food choices of individuals with CD, suggesting the need of encouraging them to make better food choices more in line with an MD, which would improve their nutritional status and better protect them from NCDs at long term. PROTOCOL REGISTRATION: ClinicalTrials.gov (ID NCT01975155) on November 4 2013.

The impact of bariatric surgery on health outcomes, wellbeing and employment rates: analysis from a prospective cohort study.

PURPOSE: Morbid obesity is associated with several comorbidities that often impair patients' ability to obtain and keep a job and that, eventually, could hinder their fitness to work. This study aimed at determining whether the employment status of morbidly obese patients may be positively affected by bariatric surgery. METHODS: A total of 30 morbidly obese patients who underwent Roux-en-Y gastric bypass (RYGB) from March 2014 to March 2015 were prospectively evaluated. All patients underwent a pre-operative assessment including the collection of personal and occupational data and the evaluation of musculoskeletal system. All evaluations were repeated at the end of a 24-month follow up. RESULTS: After RYGB, employment rates increased from 15/30 (50.0%) to 25/30 (83.3%, p = 0.012). Patients who were working at the end of follow-up referred lower rates of comorbidities, in particular of musculoskeletal complaints (4/25 vs. 4/5, p < 0.001), and presented significantly increased scores of energy/vitality at SF-36 assessment. CONCLUSIONS: Our study suggests that RYGB can increase employment rates, increasing tolerance to effort and reducing prevalence and severity of obesity-related symptoms and complaints.

Congenital anomalies and variations of the bile and pancreatic ducts: magnetic resonance cholangiopancreatography findings, epidemiology and clinical significance.

PURPOSE: The objective of this paper is to document the magnetic resonance cholangiopancreatography (MRCP) findings and the epidemiology of congenital anomalies and variations of the bile and pancreatic ducts and to discuss their clinical significance. MATERIALS AND METHODS: Three-hundred and fifty patients of both sexes (150 females, 200 males, age range 0-76 years, average age 38 years) underwent MRCP for clinically suspected lithiasic, neoplastic or inflammatory disease of the bile and pancreatic ducts. Patients were imaged with a 1.5-T superconductive magnet (Magnetom Vision, Siemens, Erlangen, Germany), a four-channel phased-array body coil, breath-hold technique, with multislice T2-weighted half-Fourier acquisition single-shot turbo spin echo (HASTE), MIP reconstructions, and a single-shot T2-weighted turbo-spin-echo sequence rapid acquisition with relaxation enhancement (RARE) with different slice thicknesses. Studies in oncological patients were completed with fat saturation 3D T1 gradient-echo sequences during the intravenous injection of gadolinium diethylene triamine pentaacetate acid (DTPA) (0.2 ml/kg). RESULTS: MRCP demonstrated recurrent and therefore normal bile and pancreatic ducts in 57% of patients. In the remaining 42.3%, it documented anatomical variants (41%) and congenital anomalies (1.3%). Variants of the intrahepatic bile duct were seen in 21% of cases: crossover anomaly (6.7%), anterior branch of the right hepatic duct draining the IV and VII segments that flow together with the left bile duct (3.1%) and anterior and posterior branches of the right hepatic duct that flow together with the common hepatic duct (3.3%). Variants of the extrahepatic bile ducts were present in 8.8% of patients: low insertion of the cystic duct into the common hepatic duct (4.5%), emptying of the cystic duct into the right hepatic duct (2.7%) and a second-order large branch draining into the cystic duct (1.6%). MRCP identified a double gall bladder in 3% of patients and anatomical variants of the biliopancreatic system in 8.2%: pancreas divisum (5.2%) and a long sphincter of Oddi (3%). Finally, congenital anomalies were diagnosed in 1.3% of cases: bile duct cysts (0.3%), atresia of the bile ducts (0.3%) and multiple biliary hamartomatosis (0.7%). CONCLUSIONS: The congenital anomalies and anatomical variants of the bile and pancreatic ducts present a complex spectrum of frequent alterations, which are worthy of attention in both the clinical and surgical settings and are readily identified by MRCP.

Endoscopic treatment of bilateral pheochromocytoma in MEN 2A syndrome: case report and review of the literature.

The benefits of laparoscopic adrenalectomy for single adrenal lesion have been well documented in literature; less experience though has been reported with simultaneous bilateral laparoscopic adrenalectomy. This operation is indicated in case of primary hypercortisolism caused by bilateral adrenocortical hyperfunction, Cushing's disease after failure of pituitary surgery, ectopic adrenocorticotropic hormone (ACTH) production by a tumour inaccessible for surgical intervention, and pheochromocytoma when it occurs bilaterally in case of multiple endocrine neoplasia type 2A and 2B. Different laparoscopic approaches have been described to perform this operation, such as the "anterior" approach (transperitoneal), the "lateral" approach (transperitoneal and retroperitoneal), and the "posterior" approach (retroperitoneal). We report a case of bilateral laparoscopic adrenalectomy in a 33 years old female affected with bilateral pheochromocytoma due to multiple endocrine neoplasia type 2A treated with a bilateral transperitoneal laparoscopic adrenalectomy and disease free after 18 months follow-up.

Routine laparoscopic cholecystectomy after endoscopic sphincterotomy for choledocholithiasis in octogenarians: is it worth the risk?

BACKGROUND: No unanimous consensus has been reached as to the need for routine laparoscopic cholecystectomy (LC) after endoscopic sphincterotomy (ES) for choledocholithiasis in very elderly patients, who are considered as high-risk subjects for surgery. METHODS: From 1991 through 1997, 170 patients were referred to undergo preoperative ES and routine LC for common bile duct (CBD) stones. The results for 27 patients (age 80 years or older) were compared with those achieved for younger patients. Successively, in a retrospective case-control study, the results for the selected patients were compared with those for 27 very elderly patients who underwent endoscopic retrograde cholangiopancreatography (ERCP), but did not receive LC. The mean follow-up period was 126 months. RESULTS: Octogenarians showed longer surgery time (79 vs 51 min) and postoperative hospital stay (2.8 vs 1.2 days), as well as more early low-grade complications (15% vs 3%), whereas there were no differences in conversion rate or serious complications. Recurrent symptoms or complications developed in 48% of octogenarians not undergoing routine LC, and 30% finally needed surgery. One patient in the control group died after emergency cholecystectomy for acute cholecystitis. The results of surgery were significantly poorer for the control group. CONCLUSIONS: Although a "wait-and-see" policy allowed two-thirds of LCs to be avoided in octogenarians, biliary-related events developed for every second patient, often requiring delayed surgery, with poorer results. Sequential treatment (ES followed by elective LC) is a safe procedure for octogenarians, and should be considered as a standard, definitive treatment for cholecystocholedocholithiasis even after the age of 80 years.

Intraoperative cholangiography and bile duct injury.

We are not in agreement with the opinion that the credit for excellent results after laparoscopic cholecystectomy is to be attributed to the routine performing of intraoperative cholangiography. We performed 2538 laparoscopic cholecystectomies without routine intraoperative cholangiography and we obtained very low rate and severity of common bile duct injuries: there was a total of four common bile duct injuries (0.16%), in no case was the injury a major transaction, and injuries were detected intraoperatively and easily repaired with a T-tube. Cholangiography could prevent bile duct transaction, but that it is not necessary for intraoperative cholangiography to be routinely performed for this purpose. It is sufficient for intraoperative cholangiography to be performed whenever the surgeon is in doubt as to the biliary anatomy or common bile duct clearance, and that when dissection of the cholecystic peduncle proves difficult he does not hesitate to convert to open access.

Anorectal reconstruction by electrostimulated graciloplasty as part of abdominoperineal resection.

AIMS: To report the outcomes of anorectal reconstruction by electrostimulated graciloplasty as part of abdominoperineal resection, on data prospectively collected over 10 years. PATIENTS AND METHODS: Twenty-three abdominoperineal resections were associated to coloperineal pull through, double graciloplasty and loop abdominal stoma. Fifteen patients also received an implantable pulse generator, either for unsatisfactory result after external-source intermittent electrostimulation and biofeedback (five cases) or during graciloplasty (10 cases). Follow-up was to a maximum of 10 years. Functional outcome was followed up in sixteen patients who underwent stoma takedown. RESULTS: Mean actuarial survival at 5 years was 72.3%. Satisfactory results (score < or =8) occurred in 75% of patients (three without and 13 with stimulator) in the early stages, decreasing to 57% at 1 year and gradually increasing up to 100% at 5 years and over. CONCLUSIONS: Total anorectal reconstruction yields a good functional outcome over time. Thus, despite, and because of, a high complication rate and a great drain on resources, it should be considered a suitable procedure only for selected, strongly motivated patients.

Quality of life assessment in geriatric surgery.

An excessive number of studies on health-related quality of life (HRQOL) has rendered results often contradictory and difficult to interpret. HRQOL evaluation in the aged is even more difficult, due to intrinsic conceptual and methodological problems. Since no structured instruments are available for use in geriatric surgery, it would be necessary either to work out a new specific instrument or to adapt/adopt an already existing method. Properties and methodological steps for development and validation are set forth. The Functional Assessment for Cancer Therapy (FACT) scale was developed for patients with cancer and has been recently validated also in the elderly. The Multidimensional Assessment for Cancer in the Elderly (MACE) was originally developed for elderly cancer patients. Since both methods are irrespective of subjects undergoing surgery, its use requires further validation. The MACE gives a broad information spectrum, but in geriatric surgery it seems too complex. The FACT-G is a simple core item questionnaire which can be integrated by disease-specific items and seems more compliant. A disease-specific and treatment-specific application of FACT questionnaires by multicenter studies might be useful in evaluating surgical procedures in patients in whom significant advantages in survival cannot be expected, but QOL can still significantly improve.

Randomized clinical trial of laparoscopic cholecystectomy performed with mini-instruments.

BACKGROUND: The outcomes after traditional laparoscopic cholecystectomy (LC; one 10-mm port, one 12-mm port and two 5-mm ports) and minilaparoscopic cholecystectomy (MLC; three 3-mm ports and one 12-mm port) for gallstone disease were compared. METHODS: The study was a randomized, single-blind trial comparing LC with MLC. Only elective patients were eligible for inclusion. LC was a routine procedure at the institution in which the study was performed, whereas MLC was introduced after a short training period. The randomization period was from January to December 2001. RESULTS: Of 175 patients who had elective minimal access cholecystectomy during the randomization period, 135 entered the trial: 68 underwent LC and 67 underwent MLC. The groups were matched for age, sex and preoperative characteristics. Median (range) operating times for LC and MLC were similar (45 (20-120) and 50 (20-170) min respectively). Intraoperative and postoperative complication rates, the time for the patient to resume walking, eating and passing stools, and median hospital stay were the same in the two groups. The level of postoperative pain was lower in the MLC group at 1 h (P = 0.011), 3 h (P = 0.012), 6 h (P = 0.003), 12 h (P = 0.052) and 24 h (P = 0.034). Patients who had MLC received fewer injections of analgesic (P = 0.036) and more patients in this group expressed satisfaction with the cosmetic result (P = 0.001). CONCLUSION: MLC took a similar time to perform and caused less postoperative pain than the standard laparoscopic procedure. Reducing the port size further enhanced the advantages of laparoscopic over open cholecystectomy.

Scoring system to predict asymptomatic choledocholithiasis before laparoscopic cholecystectomy. A matched case-control study.

BACKGROUND: The purpose of this prospective study was to evaluate if a recently proposed score system based on six preoperative parameters [history of colic pain and/or jaundice, dyspepsia, cholecystitis, ultrasound (US), evidence of common bile duct stones (CBDS), number and size of gallbladder stones at US, level of serum glutamic oxalacetic transaminase and/or alkaline phosphatase is effective in the selection of patients undergoing laparoscopic cholecystectomy (LC) with asymptomatic CBDS and could allow a significant reduction of the total number of preoperative examinations. METHODS: In the case group, 408 patients were categorized into low-, medium-, and high-risk classes and underwent, respectively, no further preoperative assessment of the bile duct, intravenous cholangiography (IVC), and endoscopic retrograde cholangiography (ERC). Intraoperative cholangiography (IOC) was performed whenever the surgeon was in doubt as to biliary anatomy or bile duct clearance. These patients were compared with 408 retrospectively matched patients (control group) undergoing routine preoperative IVC and/or ERC. RESULTS: In the case group, significantly lower numbers of IVC (120 vs 392) and IOC (3 vs 16) were performed ( p < 0.005), whereas no difference in the total number of ERCs was noted. One patient in the control group had retained CBDS detected during follow-up evaluation, whereas none occurred in the case group. CONCLUSION: The proposed scoring system allows selective use of IVC, ERC, and/or IOC in patients undergoing elective LC.

Bread wheat gliadin cytotoxicity: a new three-dimensional cell model.

BACKGROUND: In an attempt to clarify the role of gliadin toxicity in the pathogenesis of gluten intolerance (celiac disease), previous in vitro studies have been based on two-dimensional human cell cultures. However, the specific morphological and biochemical properties of in vivo tissue are better maintained in three-dimensional cell cultures (multicellular spheroids, MCS). The aim of this study was to develop a three-dimensional in vitro model to investigate the effects of gliadin on epithelial cells and broaden our understanding of the early tissue damage occurring in celiac disease. METHODS: The three-dimensionally growing Lovo cell line was exposed to increasing concentrations of peptic-tryptic-digested bread wheat gliadin (from 125 to 1000 microg/mL) for 7 days in order to evaluate cell viability (colony-forming assay), and at the standard concentration of 500 microg/mL for 7 days in order to evaluate MCS diameters, volumes and cell morphology using light and electron microscopy. RESULTS: In comparison with the controls, the cell viability of the gliadin-treated MCS was significantly reduced (20-80%), but there was no difference in size. Various degrees of cell damage (autophagic vacuoles and intra-cytoplasmic lipid-like droplets) were detected by both light and electron microscopy. CONCLUSION: This is the first study investigating the effects of gliadin on MCS. Lovo MCS seem to be responsive to gliadin exposure, thus confirming previous results obtained using two-dimensional cell cultures. The data suggest that three-dimensional cell cultures may be useful in broadening our understanding of some of the early effects of gliadin peptides on epithelial cells.

Laparoscopy in the last decade of the millennium: have we really improved?

BACKGROUND: The aims of the study were to evaluate the evolution of laparoscopic surgery during the past decade in terms of variations in the quality (complexity) of the procedures performed and of modifications in patient outcome. METHODS: A retrospective analysis was performed of 3022 consecutive patients undergoing 99 different laparoscopic procedures at a center specialized in laparoscopic abdominal surgery. All the procedures were classified according to three classes of complexity. Results relating to the first 1511 patients were compared to those of the last 1511 patients. RESULTS: In the second group, medium- to high-class complexity procedures significantly increased, conversion rate was higher only for straightforward procedures, duration of low- to medium-class complexity procedures decreased, only the rate of slight complications increased, and mean postoperative hospital stay was longer. Frequency of conversion in medium- to high-class complexity procedures and severe complications was not different in the two periods. CONCLUSIONS: The quality of laparoscopic surgery has improved during the past decade, with no increase in the frequency of conversion or of major complications.

Gallstone cholangitis: a 10-year experience of combined endoscopic and laparoscopic treatment.

BACKGROUND: To date, no procedure has yet been identified as the gold standard for the treatment of gallstone cholangitis in the laparoscopic era. METHODS: The data of 109 consecutive patients with acute cholangitis were prospectively entered into a computerized database. All patients were managed according to a standard protocol. The main treatments were endoscopic retrograde cholangiography (ERC) combined with endoscopic sphincterotomy (ES), followed by interval laparoscopic cholecystectomy (LC). Patients in whom ERC or endoscopic stone clearance failed were managed by emergency open common bile duct exploration. LC was performed with a standardized four-cannula technique. The mean duration of surgery, conversion rate, and postoperative outcome of these patients were evaluated. RESULTS: ERC was successful in 103 patients (94.5%). In five of these patients (4.8%), no bile duct stones were found. The 98 patients (95.2%) with common bile duct stones were referred for ES. The bile duct stones were successfully removed after ES in 93 cases (94.9%). The overall failure rate of ERC and ES for choledocholithiasis was 10.1%. Self-limiting pancreatitis occurred in four patients (4.3%). Overall, two of the 109 patients died (1.8%). After ES, 81 patients underwent LC. LC was performed successfully in 74 patients (91.3%). Conversion to open surgery was required in seven patients (8.7%). The morbidity rate after cholecystectomy was 7.4%; the morbidity rate after open bile duct exploration was 36.4% (p<0.05). Fifteen patients were managed conservatively after initial endoscopic management of their cholangitis. The overall incidence of recurrent biliary symptoms was significantly higher among patients with gallbladder in place than for patients who underwent cholecystectomy (38.5% vs 1.5%, p<0.001). CONCLUSIONS: ES followed by LC is a safe and effective approach for the management of gallstone cholangitis; cholecystectomy should be performed in patients with gallstone cholangitis unless the operative risk is extremely high. These high operative risk patients and those who refuse surgery after ES should be warned that they are at high risk for recurrent biliary symptoms.

Alteration of elastin, collagen and their cross-links in abdominal aortic aneurysms.

OBJECTIVES: although the mechanism of arterial dilation and aneurysm development has not been clarified, the degradation of elastin and collagen plays undoubtedly a critical role. We evaluated the elastin and collagen content through the detection of their cross-links in aneurysmal and non-aneurysmal abdominal aortic walls. MATERIALS AND METHODS: in 26 human abdominal aortic aneurysm specimens obtained during surgery and in 24 autopsy control samples of non-aneurysmal abdominal aorta the tissue content of elastin and collagen cross-links were measured by HPLC. Collagen was also detected by evaluating two characteristic amino acids, 4-hydroxyproline (4-hypro) with a colorimetric method and 5-hydroxylysine (5-hylys) by gas chromatography. RESULTS: significantly fewer elastin cross-links were found in aneurysm samples compared to controls (desmosines and isodesmosines: 90% reduction; p<0.01). The opposite was true for pyridinoline collagen cross-links (350% increase) and deoxypyridinolines (100% increase, p=0.01). Tissue content of 5-hylys, 4-hypro and total amino acids were reduced significantly by 50% in aneurysmal samples. CONCLUSIONS: beside confirming decreased elastin content in aneurysmal walls, these results show a concurrent increase of collagen cross-links. Since total collagen markers were decreased (decreased 4-hypro and 5-hylys) it is reasonable to suggest that in aneurysmal aortic walls old collagen accumulates cross-links while new collagen biosynthesis is somehow defective.