Celiac disease: role of intestinal compartments in the mucosal immune response.

Different approaches have been used to study the pattern of cytokines in celiac disease (CD). Laser capture microdissection (LCM) is a powerful tool for the isolation of specific tissue compartments. We aimed to investigate the mucosal immune response that takes place in different intestinal compartments of CD patients, dissected by LCM, analyzing cytokine expression profile. Frozen section of jejunum was obtained from 15 untreated CD and 15 control. Surface epithelium and lamina propria compartment were isolated by LCM. RNA from each LCM sample was extracted and, after a retrotranscription step, messenger RNA levels for MxA, IL-15, TNF-α, IFN-γ, IL-17α, IL-21, IL-10, and TGF-ß were determined by quantitative reverse transcriptase-PCR. Increased gene expression levels of MxA, IL-15, TNF-α, IL-10, and TGF-ß was observed in the surface epithelium of untreated CD with respect to control. Furthermore, all the cytokines investigated were upregulated in the lamina propria of untreated CD as compared to control. Within the untreated CD group the expression of IL-15 was higher, in the surface epithelium than in the lamina propria, whereas the expression levels of IL-17 and IL-21 were higher in the lamina propria than in the surface epithelium. Finally, high levels of IL-10 and TGF-ß were detected in both compartments of untreated CD biopsies. In CD, surface epithelium and lamina propria compartments, play a prominent role in determining innate and adaptive immunity, respectively. Conversely, surface epithelium and lamina propria produce high levels of anti-inflammatory cytokines, suggesting that both compartments are involved in the immunoregulatory response.

Comparison of the 6th and 7th editions of the AJCC/UICC TNM staging system for gastric cancer focusing on the "N" parameter-related survival: the monoinstitutional NodUs Italian study.

BACKGROUND: A large number of Asian population studies examined the difference between the 6th and the 7th tumor, node, metastasis (TNM) while it is still poorly validated among Caucasian populations. This is a retrospective study aimed at investigating the efficacy of the 7th edition American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) staging system for gastric cancer focusing on the "N" parameter-related survival for prognostic assessment in gastric cancer patients of a single Western high-volume institution. METHODS: From January 2002 to December 2009, the data of 274 patients with gastric cancer who underwent gastric surgery at the 8th General and Gastrointestinal Surgical Centre of the Second University of Naples were analyzed retrospectively. We collected data for patient demographics, tumor characteristics, surgical characteristics, and TNM stage. Particularly, the nodal status, with the number of dissected nodes and metastatic nodes, was reviewed from the pathology records. The same patient dataset was used to stage patients according to both the 6th and 7th edition criteria. RESULTS: Age at surgery, tumor location, histological grade, Lauren's classification subtypes, and 6th and 7th AJCC/UICC N categories were found to have statistically significant associations with overall survival on univariate analysis. In the 6th edition staging system, the Kaplan-Meier plot did not show significant overlapped survival curves: significant differences were found between N0 and N1, P<.001; N1 and N2, P=.04; and N2 and N3, P<.001. On the contrary, in the 7th edition, among all five substages, there were similar survival curves between N categories 2 and 3a (P=.98) with a statistically significant discriminatory ability only between N1 versus N3b and N2 versus N3b (P=.02 and .04, respectively). CONCLUSIONS: Based on analysis, we found that several clinicopathological variables, especially histological grade and Lauren's classification, were significant prognostic factors in our database. The 6th and 7th AJCC/UICC N classifications represent significantly independent prognostic factors, and the 6th AJCC/UICC N classification seems to be superior to the 7th AJCC/UICC N classification in terms of uniformity, differentiation, and monotonicity of gradients.

The laparoscopic hiatoplasty with antireflux surgery is a safe and effective procedure to repair giant hiatal hernia.

BACKGROUND: Although minimally invasive repair of giant hiatal hernias is a very surgical challenge which requires advanced laparoscopic learning curve, several reports showed that is a safe and effective procedure, with lower morbidity than open approach. In the present study we show the outcomes of 13 patients who underwent a laparoscopic repair of giant hiatal hernia. METHODS: A total of 13 patients underwent laparoscopic posterior hiatoplasty and Nissen fundoplication. Follow-up evaluation was done clinically at intervals of 3, 6 and 12 months after surgery using the Gastro-oesophageal Reflux Health-Related Quality of Life scale, a barium swallow study, an upper gastrointestinal endoscopy, an oesophageal manometry, a combined ambulatory 24-h multichannel impedance pH and bilirubin monitoring. Anatomic recurrence was defined as any evidence of gastric herniation above the diaphragmatic edge. RESULTS: There were no intraoperative complications and no conversions to open technique. Symptomatic GORD-HQL outcomes demonstrated a statistical significant decrease of mean value equal to 3.2 compare to 37.4 of preoperative assessment (p < 0.0001). Combined 24-h multichannel impedance pH and bilirubin monitoring after 12 months did not show any evidence of pathological acid or non acid reflux. CONCLUSION: All patients were satisfied of procedure and no hernia recurrence was recorded in the study group, treated respecting several crucial surgical principles, e.g., complete sac excision, appropriate crural closure, also with direct hiatal defect where possible, and routine use of antireflux procedure.

Endoscopic plastic stenting for bile duct stones: stent changing on demand or every 3 months. A prospective comparison study.

BACKGROUND AND STUDY AIMS: Endoscopic biliary sphincterotomy and stone removal is the standard of care for choledocholithiasis, with a success rate of > 90%. For stones ≤ 25 mm diameter, mechanical lithotripsy, extracorporeal shock wave lithotripsy, electrohydraulic lithotripsy, and laser lithotripsy can be used. In the case of failure, the next step is surgery. In elderly patients and in patients with an elevated surgical risk, stenting is the only treatment modality. In these cases the aim is to avoid the onset of acute obstructive cholangitis. The aim of the current study was to evaluate the best management of plastic stents in patients with biliary duct stones who were unfit for surgery and in whom previous endoscopic therapy had failed. METHODS: Patients who were high surgical risks and in whom stone clearance was not possible due to the number and sizes of stones were included. Between March 2008 and September 2010 all patients were treated with endoscopic plastic biliary stenting at four tertiary care referral centers in Italy. Patients were randomly assigned to two groups: in Group A (n=39) plastic stents were changed every 3 months or sooner if symptoms appeared; in Group B plastic stents were changed on demand at the onset of symptoms, and ultrasonography and blood samples were performed every 3 months to check for signs of cholestasis and inflammation. The primary outcome was the rate of cholangitis. The secondary outcome was the rate of stone clearance after a period of stenting. RESULTS: A total of 78 patients were included in the study (43 M/35F; mean age 76 years). Acute cholangitis occurred in 3 patients from Group A and in 14 patients from Group B (P=0.03). Mortality related to cholangitis occurred in one patient from Group A and three patients from Group B (P=n.s.). The mean follow-up was 13.5 months (range 2-23). Stone clearance after long term stenting occurred in 24 patients from Group A (61.5 %) and in 21 patients from group B (53.8%) (P=n.s.). CONCLUSIONS: In patients with bile duct stones who were treated with biliary plastic stents, the best stent management to avoid cholangitis was stent changing at defined intervals (every 3 months in the current study). The data confirmed that plastic biliary stenting may decrease stone size with a high percentage of subsequent total stone clearance.

Sutureless jejuno-jejunal anastomosis in gastric cancer patients: a comparison with handsewn procedure in a single institute.

BACKGROUND: The biofragmentable anastomotic ring has been used to this day for various types of anastomosis in the gastrointestinal tract, but it has not yet achieved widespread acceptance among surgeons. The purpose of this retrospective study is to compare surgical outcomes of sutureless with suture method of Roux-and-Y jejunojejunostomy in patients with gastric cancer. METHODS: Two groups of patients were obtained based on anastomosis technique (sutureless group versus hand sewn group): perioperative outcomes were recorded for every patient. RESULTS: The mean time spent to complete a sutureless anastomosis was 11 ± 4 min, whereas the time spent to perform hand sewn anastomosis was 23 ± 7 min. Estimated intraoperative blood loss was 178 ± 32 ml in the sutureless group and 182 ± 23 ml in the suture-method group with no significant differences. No complications were registered related to enteroanastomosis. Intraoperative mortality was none for both groups. CONCLUSIONS: The Biofragmentable Anastomotic Ring offers a safe and time-saving method for the jejuno-jejunal anastomosis in gastric cancer surgery, and for this purpose the ring has been approved as a standard method in our clinic. Nevertheless currently there are few studies on upper gastrointestinal sutureless anastomoses and this could be the reason for the low uptake of this device.

Laparoscopic Nissen-Rossetti fundoplication is a safe and effective treatment for both Acid and bile gastroesophageal reflux in patients poorly responsive to proton pump inhibitor.

PURPOSE: The aim of this study was to evaluate the effectiveness of laparoscopic Nissen-Rossetti fundoplication in patients with gastroesophageal reflux disease (GERD) poorly responsive to standard dose proton pump inhibitor (PPI) therapy. METHODS: A total of 35 patients (19 women, 16 men, mean age 44.6 ± 14.01 years) were enrolled. All the patients underwent symptom questionnaires, upper gastrointestinal endoscopy, esophageal manometry, and combined 24-hour esophageal pH and bilirubin monitoring. Following this, the patients with persistent pathological esophageal acid and/or bilirubin exposure underwent laparoscopic antireflux surgery, followed by clinical and instrumental 12-month follow-up. RESULTS: One year after surgery, there was a significant improvement of symptom score, compared with standard PPI dose period (3.54 ± 1.67 vs 20.8 ± 10.9, P < .0001; paired t test) and mean percentage total time acid and bile exposure showed a significant decrease (4.9 ± 2.9 vs 2.03 ± 0.74 and 8.3 ± 3.03 vs 0.84 ± 0.56, P < .0001; paired t test). CONCLUSIONS: In patients with GERD poorly responsive to standard PPI dose, laparoscopic Nissen-Rossetti fundoplication appears to be a safe and effective treatment of symptoms, esophageal damage, as well as both acid and bile reflux.

Multifocal gastrointestinal stromal tumor: A case report with CT, surgical, and histopathologic correlation.

Mutifocal gatrointestinal stromal tumors (GISTs) are rare conditions that are usually associated with other syndromes or reported in pediatric cases. The sporadic form represents only 11% of GISTs. The imaging features on a contrast-enhanced computed tomography examination, surgery and histopathology of a rare case of a sporadic multifocal small bowel GISTs in an emergency setting are described. This case highlights how GISTs appearances on an imaging computed tomography may vary. Radiologists can have difficulty in defining the point of origin of large lesions. In our case, laparotomy open surgery was mandatory to figuring out the correct diagnosis.

The calibrated laparoscopic Heller myotomy with fundoplication.

BACKGROUND: Esophageal achalasia is the most common primary esophageal motor disorder. Laparoscopic Heller's myotomy combined with fundoplication represents the treatment of choice for this disease, achieving good results in about 90% of patients. However, about 10% of treated patients refer persistent or recurrent dysphagia. Many Authors showed that this failure rate is related to inadequate myotomy. OBJECTIVE: To verify, from experimental to clinical study, the modifications induced by Heller's myotomy of the esophago- gastric junction on LES pressure (LES-P profile, using a computerized manometric system. METHODS: From 2002 to 2010 105 patients with achalasia underwent laparoscopic calibrated Heller myotomy followed by antireflux surgery. The calibrated Heller myotomy was extended for at least 2.5 cm on the esophagus and for 3 cm on the gastric side. Each step was evaluated by intraoperative manometry. Moreover, intraoperative manometry and endoscopy were used to calibrate the fundoplication. RESULTS: The preoperative mean LES-P was 37.73 ± 12.21. After esophageal and gastric myotomy the mean pressure drop was 21.3% and 91.9%, respectively. No mortality was reported. CONCLUSION: Laparoscopic calibrated Heller myotomy with fundoplication achieves a good outcome in the surgical treatment of achalasia. The use of intraoperative manometry enables an adequate calibration of myotomy, being effective in the evaluation of the complete pressure drop, avoiding too long esophageal myotomy and, especially, too short gastric myotomy, that may be the cause of surgical failure.

Laparoscopic calibrated total vs partial fundoplication following Heller myotomy for oesophageal achalasia.

AIM: To compare the mid-term outcomes of laparoscopic calibrated Nissen-Rossetti fundoplication with Dor fundoplication performed after Heller myotomy for oesophageal achalasia. METHODS: Fifty-six patients (26 men, 30 women; mean age 42.8 ± 14.7 years) presenting for minimally invasive surgery for oesophageal achalasia, were enrolled. All patients underwent laparoscopic Heller myotomy followed by a 180° anterior partial fundoplication in 30 cases (group 1) and calibrated Nissen-Rossetti fundoplication in 26 (group 2). Intraoperative endoscopy and manometry were used to calibrate the myotomy and fundoplication. A 6-mo follow-up period with symptomatic evaluation and barium swallow was undertaken. One and two years after surgery, the patients underwent symptom questionnaires, endoscopy, oesophageal manometry and 24 h oesophago-gastric pH monitoring. RESULTS: At the 2-year follow-up, no significant difference in the median symptom score was observed between the 2 groups (P = 0.66; Mann-Whitney U-test). The median percentage time with oesophageal pH < 4 was significantly higher in the Dor group compared to the Nissen-Rossetti group (2; range 0.8-10 vs 0.35; range 0-2) (P < 0.0001; Mann-Whitney U-test). CONCLUSION: Laparoscopic Dor and calibrated Nissen-Rossetti fundoplication achieved similar results in the resolution of dysphagia. Nissen-Rossetti fundoplication seems to be more effective in suppressing oesophageal acid exposure.

Prevalence of bile reflux in gastroesophageal reflux disease patients not responsive to proton pump inhibitors.

AIM: To determine the prevalence and characteristics of bile reflux in gastroesophageal reflux disease (GERD) patients with persistent symptoms who are non-responsive to medical therapy. METHODS: Sixty-five patients (40 male, 25 female; mean age, 50 +/- 7.8 years) who continued to report symptoms after 8 wk of high-dose proton pump inhibitor (PPI) therapy, as well as 18 patients with Barrett's esophagus, were studied. All patients filled out symptom questionnaires and underwent endoscopy, manometry and combined pH-metry and bilimetry. RESULTS: There were 4 groups of patients: 22 (26.5%) without esophagitis, 24 (28.9%) grade A-B esophagitis, 19 (22.8%) grade C-D and 18 (21.6%) Barrett's esophagus. Heartburn was present in 71 patients (85.5%) and regurgitation in 55 (66.2%), with 44 (53%) reporting simultaneous heartburn and regurgitation. The prevalence of pathologic acid reflux in the groups without esophagitis and with grades A-B and C-D esophagitis was 45.4%, 66.6% and 73.6%, respectively. The prevalence of pathologic bilirubin exposure in these 3 groups was 53.3%, 75% and 78.9%, respectively. The overall prevalence of bile reflux in non-responsive patients was 68.7%. Pathologic acid and bile reflux was observed in 22.7% and 58.1% of non-esophagitic patients and esophagitic patients, respectively. CONCLUSION: The high percentage of patients poorly responsive to PPI therapy may result from poor control of duodenogastroesophageal reflux. Many patients without esophagitis have simultaneous acid and bile reflux, which increases with increasing esophagitis grade.

Report of a rare case of colon cancer complicated by anomalies of intestinal rotation and fixation: a case report.

INTRODUCTION: The Situs viscerum inversus associated with anomalies of intestinal rotation and fixation is an extremely rare condition. To the authors' knowledge, this is the first report of colon cancer associated with intestinal malrotation and mesenterium ileocolicum commune. CASE PRESENTATION: A 34-year-old man with a 2-month history of diarrhea associated with abdominal pain and weight loss underwent abdominal ultrasonography, colonscopy with biopsies and abdominal computed tomography scan with intravenous contrast. A right colonic neoplasm was diagnosed, observed only at surgery, as neither computed tomography or ultrasonography showed the intestinal malrotation. Particularly, the third and the fourth part of the duodenum descended vertically, without Treitz's ligament in support to the duodeno-jejunal flexure. The small bowel and the colon were located in the right and left side of the abdominal cavity, respectively. CONCLUSION: The anomaly of situs viscerum inversus influenced the surgical strategy in this case because of the vascular and lymphatic anomalies. Lymphatic vessels were therefore marked with subserosal injection of patent blue in the proximity of the tumor. Subsequently, right colectomy was performed. Colectomy extended from the distal ileum to the descending colon, by ligature of the right colic artery and vein at the origin from the superior mesenteric vessels. Patent blue guided lymphadenectomy was also performed with curative intent. Finally, a mechanical ileo-colic anastomosis was carried out. After right colectomy and ileo-descending anastomosis, the Ladd's procedure for intestinal malrotation was unnecessary. The authors believe that this strategy, despite the anatomical difficulties, represents an effective procedure for the radical surgical treatment of the right colon cancer associated with anomalies of intestinal rotation and fixation.

Prevalence of pathological duodenogastric reflux and the relationship between duodenogastric and duodenogastrooesophageal reflux in chronic gastrooesophageal reflux disease.

UNLABELLED: The role of duodenogastric reflux in gastrooesophageal reflux disease is still controversial. AIMS: (i) To determine the prevalence of pathological duodenogastric reflux (DGR) in gastrooesophageal reflux disease patients and (ii) to define the relationship between DGR and duodenogastrooesophageal reflux. METHODS: We evaluated 92 patients referred for investigation of recurrent reflux symptoms after proton pump inhibitors (PPI) therapy. All the patients filled out symptom questionnaires and underwent endoscopy, oesophageal manometry and combined oesophagogastric pH and bilirubin monitoring. RESULTS: Endoscopy divided the 92 patients into four groups (group I: 25 nonoesophagitis patients, group II: 26 patients with grade A-B oesophagitis, group III: 21 patients with grade C-D oesophagitis and group IV: 20 patients with Barrett's oesophagus. Twenty-four of the 92 patients (26%) showed pathological DGR. Abnormal oesophageal bilirubin exposure was observed in 62 of the 92 patients (67.4%). Of the 62 patients with abnormal oesophageal bilimetry, 15 (24.2%) patients simultaneously showed pathological DGR. The gastric bilirubin exposure in patients with abnormal oesophageal, Bilitec tests did not differ from that in patients with normal oesophageal bilimetry (P>0.05). A weak correlation between oesophageal and gastric bilirubin exposure, both expressed as a percentage of time, was found (r=0.28; P<0.01). CONCLUSION: Pathological DGR is present in a little more than a quarter of patients with recurrent reflux and dyspeptic symptoms after PPI therapy. Excessive DGR is not a prerequisite for pathological oesophageal exposure to duodenal contents. Gastric bilirubin monitoring may be useful to choose the best surgical treatment for patients with reflux and dyspeptic symptoms refractory to PPI.