Clinicopathological and molecular characterization of gastroesophageal junction (GEJ) adenocarcinoma before age of 40 years

Gastroesophageal junction (GEJ) adenocarcinoma are uncommon before age of 40 years. While certain clinical, pathological and molecular features of GEJ adenocarcinoma in older patients have been extensively studied, these characteristics in the younger population remain to be determined. In the recent literature, a high sensitivity and specificity for the detection of dysplasia and esophageal adenocarcinoma was demonstrated by using multicolor fluorescence in situ hybridization (FISH) DNA probe set specific for the locus specific regions 9p21 (p16), 20q13.2 and Y chromosome. We evaluated 663 patients with GEJ adenocarcinoma and further divided them into 2 age-groups of or= 50 years, rispectively. FISH with selected DNA probe for Y chromosome, locus 9p21 (p16), and locus 20q13.2 was investigated with formalin fixed and parassin embedded tissue from surgical resections of 17 younger and 11 older patients. Signals were counted in > 100 cells with each given histopathological category. The chromosomal aberrations were then compared in the 2 age-groups with the focus on uninvolved squamous and columnar epithelium, intestinal metaplasia (Barrett's mucosa), glandular dysplasia, and adenocarcinoma. Comparisons were performed by the X2 test, Fisher's exact test, Student's t-test and Mann-Whitney U-test as appropriate. Survival was estimated by the Kaplan-Meier method with univariate analysis by the log-rank. Significance was taken at the 5% level. There was no difference in the surgical technique applied in both age groups and most patients underwent Ivor Lewis esophagectomy. Among clinical variables there was a higher incidence of smocking history in older patient group. We identified a progressive loss of Y chromosome from benign squamos epithelium to Barrett's mucosa and glandular dysplasia, and, ultimately, to a near complete loss in adenocarcinoma in both age groups. The young group revealed significantly more losses of 9p21 in both benign and neoplastic cells when compared to the older patients group. In addition, we demonstrated an increase in the percentage of cells showing gain of locus 20q13.2 with progression from benign epithelium through dysplasia to adenocarcinoma with almost the same trend in both the young and the older patients. When compared with the older age-group, younger patients with GEJ adenocarcinoma possess similar known demographics, environmental factors, clinical, and pathologic characteristics. The most commonly detected genetic aberrations of progressive Y chromosomal loss, 9p21 locus loss, and 20q13 gains were similar in the younger and older patients. However the rate of loss of 9p21 is significantly higher in young patients, in both the benign and the neoplastic cells. The loss of 9p21, and possibly, the subsequent inactivation of p16 gene may be one of the molecular mechanisms responsible for the accelerated neoplastic process in young patients

Laparoscopic Dor Fundoplication and oesophageal Myotomy

The laparoscopic approach to the Heller myotomy has become widely accepted. With the exception of rare situations, e.g. complications requiring conversion and complex redo surgery, laparoscopic myotomy, supplemented by the Dor fundoplication, is considered the standard technique. The general principles of the procedure are the same as that for the open technique. In this chapter, elements of the operation specific to the laparoscopic approach are presented

Technique of preservation of vagus nerves at the lower esophagus and cardia during minimally invasive surgery for functional esophageal diseases.

Background: To show in a video the technical passages for the preservation of vagus nerves during benign esophageal surgery. Methods: 76 consecutive minimally invasive procedures were reviewed. Results: The position of the vagus nerves from the cardiac level where the left vagus becomes anterior to the lesser curvature at the level of the branch of the nerves for the gallbladder is not variable; 2) the left vagus becomes anterior and adherent to the esophagus between 6 and 9 cm above the apex of the hiatus; 3) vaguses can be visualized; their position is also assessed while passing over the cord with an endodissect device; 4) the safest way to manage the vaguses is to know exactly where they are during each step of the surgery; 5) the dangerous steps of the minimally invasive surgery are: a) the isolation of the left nerve where it becomes anterior, b) at the lesser curvature especially when resecting the fat pad or the sac of a II-IV hiatus hernia, c) when dissecting posteriorly the esophagus, in case of panmural esophagitis. The following cases are presented:1 case of normal ge-junction during GERD surgery, 2 cases of short esophagus, 2 cases of type III-IV hiatus hernias, 2 Heller-Dor operation for achalasia. 2 cases of redo surgery for recurrent hiatus hernia. Discussion: The video demonstrates several examples of booby traps for the vagus nerves integrity. When it is essential to mobilize adequately the lower esophagus, the surgeon must know in every moment where the vagus nerves are, particularly in diffi cult situations. Disclosure: All authors have declared no confl icts of interest

One hundred percent Follow up of a case series of patients operated upon for type II-IV Hiatus Hernia(II-IV HH) in the arch of 30 years..

Background: Medical and surgical literature often points out the risk of bias in interpreting results of GERD-HH surgery because of the frequent incompleteness and relatively short time of post operative follow up. Because of the peculiarity of the Italian NHS and society (low % of migration), we have the opportunity to report on a case series totally followed up according to a protocol for an unusually long time. Methods: 66 patients (median age 67.5 years) (41 women, 25 men) with II-IV HH underwent surgery from 1980 to 1994 with the “open” surgical approach and 34 (median age 69 years) (26 women, 8 men) in the period 1995–2010 with minimally invasive techniques. Patients at given time underwent interview, barium swallow and endoscopy. Results were considered poor in case of relapse of symptoms, endoscopic esophagitis any grade, hiatus hernia, post operative antirefl ux medical therapy. Follow up time was calculated from surgery to the last complete follow up. Results: The cumulative post-operative mortality was 3/100, 97 patients were followed up for a median period of 96 months (IQR 25.5–201) : 12 months, 11 patients; 13–36 months, 8 patients; 37–60 months, 17 patients; 61–120 months, 22 patients; 121–216 months, 22 patients; and 217–440 months, 17 patients. Hiatal hernia (HH) relapse occurred in 6/97 (6.2%). Satisfactory results were obtained in 92.8%, excellent in 39.2%, good in 43.2%, fair in 10.4%, and poor in 7.2% (6 HH relapse, 1 esophagitis without HH relapse). Discussion: Surgery for type II-IV hiatal hernia may be objectively satisfactory after years decades. Disclosure: All authors have declared no confl icts of interest

Effectivenes of Antireflux Surgery(Fundoplication) for the cure of Chronic Cough with or without GERD Symptoms.

Background: The outcome of surgical therapy for atypical extra-esophageal symptoms allegedly secondary to GERD is controversial. Aim of this study was to assess the results of antirefl ux surgery in patients affected by 1) typical, 2) typical atypical, (chronic cough), in whom a dedicated preoperative work up was performed. Methods: Between 1995 and 2010, 151 patients with GERD-related typical and/or atypical symptoms were submitted to antirefl ux surgery. One hundred percent preoperatively underwent semi-quantitative evaluation of typical/atypical symptoms, chronic cough and esophagitis, barium swallow, endoscopy and histology and esophageal manometry (24 h pH-recording or intraluminal impedance/pH monitoring system in the absence of gross esophagitis). In addition, patients with chronic cough underwent chest HRCT scan, methacholine challenge test and spirometry. Surgery was performed exclusively on patients positive for GERD and negative for pulmonary diseases. Preoperative tests for GERD were repeated at follow-up. Results: Patients were ordered into two groups: A) 83 patients with typical symptoms only, B) 68 patients with typical symptoms and chronic cough. In both groups, antirefl ux surgery demonstrated to signifi cantly improve typical symptoms. The global score for outcome showed no signifi cant differences between group A and B. In group B, antirefl ux surgery signifi cantly improved chronic cough as well. Discussion: The preoperative work up was highly effective in selecting patients for antirefl ux surgery which achieved very satisfactory results in the treatment of GERD and GERD-related chronic cough. Disclosure: All authors have declared no confl icts of interest

Surgical repair of Type II-IV Hiatal Hernia: frequency of True Short Esophagus and Results.

Surgical repair of type II-IV hiatal hernia: frequency of true short esophagus and results.Background: The surgical management of type II-IV hiatal hernia is controversial. Failure to recognize the condition of short esophagus may concur to the high rate of hernia’s recurrence. We measured intraoperatively the distance between the gastro-esophageal junction (GEJ) and the hiatus (length of the abdominal esophagus) in patients undergoing surgery for type II-IV hiatus hernias. Methods: 34 patients underwent minimally invasive surgery. After isolation of the GEJ and resection of the sac, the position of the gastric folds was localized endoscopically and two clips were applied. The distance between the clips and the diaphragm (abdominal esophagus) was measured with a dedicated ruler after mediastinal dissection. In case of abdominal esophagus 1.5 cm a Collis-Nissen was performed. Results: 17 (50%) fl oppy Nissen and 17 (50%) thoracoscopic Collislaparotomic Nissen were performed. In the latter group, (all type III-IV hernia), after mediastinal mobilization the length of the abdominal esophagus was ≤1.5 cm. Post-operative mortality was 5.8% and morbility 17.6%. Global results (median follow up 48 months) were excellent in 43.8%, good in 50%, fair in 3.1%, and poor in 3.1%. Hiatal hernia relapse occurred in 3.1% of patients. Discussion: True short esophagus is present in 50% of type III-IV and in none of type II hiatus hernia. The intraoperative measurement of the length of the abdominal esophagus is an objective method for recognizing these patients. Disclosure: All authors have declared no confl icts of interest

Roux en Y Gastrojejunostomy for the treatment of complex Esophago-Gastric problems.

Roux en Y gastrojejunostomy for the treatment of complex esophago-gastric problems.Background: Roux en Y gastrojejunostomy has been proposed for the treatment: a) of complex benign esophageal problems generally in alternative to distal esophagus resection; b) of complex redo antirefl ux surgery; c) of associated gastric antrum and gastro-esophagel junction diseases, to avoid acidalkaline esophageal refl ux, common after Billroth II gastrojejunostomy. The Roux Stasis Syndrome (RSS) may impair results in 10% to 50% of cases. Aim of the study is to evaluate the incidence of RSS after Roux en Y gastrojejunostomy performed avoiding division of the jejunal mesentery, the gastrojejunal terminolateral anastomosis being vertical to optimize emptying. Methods: Of 38 patients, 27 were followed up in long term. Patients were consecutively submitted to distal gastric resection for neoplastic or functional disease of the esophageal and/or gastric tract and reconstruction with Roux en Y jejunostomy. Patients were followed up with clinical interview, barium swallow, endoscopy. Results: Mortality was 2.6% and morbility was 16.2%. Median follow-up was 113.6 months (range 6–192 months). RSS were found in 2 on 27 patients (7.4%). Two patients (with caustic injury) were then subjected to esophagocolo- gastroplasty for esophageal stenosis not otherwise treatable, one patient (already undergone two redo surgery for esophageal achalasia) complained of signifi cant dysphagia. In the remaining patients the functional result is satisfactory. Discussion: Roux en Y gastrojejunostomy is an effective option for the treatment of complex esophago-gastric problems. The Roux Stasis Syndrome may be minimized with few technical details. Disclosure: All authors have declared no confl icts of interest

Long-term results of the Thoracoscopic Collis-Laparoscopic Nissen for the treatment of severe Gastro-Oesophageal reflux with Acquired Short Esophagus.

Objectives: The purpose of this study is to present the long-term results of thoracoscopic Collis and laparoscopic Nissen performed for the treatment of severe GERD associated with short oesophagus. Methods: GERD patients were assessed before surgery with interview based on semi-quantitative scales for grading of symptoms and oesophagitis from 0 (no symptoms and oesophagitis) to 3 (severe symptoms and oesophagitis), global evaluation (excellent, good, fair, insufficient), endoscopy + histology, barium swallow, manometry; after surgery every year, alternating interview and tests (same questionnaires as above) except routine manometry, according to a protocol. Intraoperatively the length of the abdominal oesophagus after maximal mediastinal mobilization of the oesophagus was measured with a validated technique; true short oesophagus was diagnosed when the submerged segment was <1.5 cm. After surgery, result in patients receiving medical therapy or with recurrent hernia, although asymptomatic, was classified as insufficient. Results: From 1996 to 2011, 299 minimally invasive procedures for GERD were performed. In 62/299 (20.7%) short oesophagus was assessed. The left thoracoscopic Collis gastroplasty was associated with 1 Toupet and 1 Dor (motility disorders), with the Nissen floppy fundoplication in 60 patients (24 women, 36 men, mean age 55.2±13.7 years, range 20–77). Five procedures were converted at the beginning of the experience. Mortality was 1.7% (1/60), morbidity 11.7% (7/60). The mean follow-up was 58.6±32.1 months (range 12–108). Conclusions: With the thoracoscopic Collis-laparoscopic Nissen in patients affected by severe GERD and true short oesophagus, satisfactory long-term results were achieved in 93.4% of cases. Disclosure: All authors have declared no conflicts of interest

Long-term results of the Heller\u2013Dor operation with intraoperative manometry for the treatment of esophageal achalasia

Objective: In the last 10 years, the Heller-Dor operation has by far been the most reported technique in the English literature for treating esophageal achalasia. Quality of outcome is sometimes different between studies, which is likely due to technical reasons. The aim of this study was to analyze the details of myotomy and fundoplication in relation to curing dysphagia and the occurrence of post-operative reflux esophagitis (RE) achieved over 30 years of a single center\u2019s experience. Methods: This study examined the period between January 1979 and December 2008 in which the same technique was performed by five staff surgeons and several residents. Intraoperative manometry was used in 100% of the 262 patients to abolish the high pressure zone (HPZ) with a long esophagogastric myotomy and to protect the surface of the myotomy with a long but soft anterior fundoplication (six to eight sutures on each side of the myotomy, trimmed to avoid RE without impairing esophageal emptying). A total of 202 patients [97 men, median age 55.5 years; interquartile range (IQR) = 43.7-71] underwent laparotomy, and another 60 patients (24 men, median age 46 years; IQR = 36.2-63) underwent laparoscopy. The follow up consisted of a clinical interview, an endoscopy, barium swallow at given intervals and manometry when needed. We then used a semiquantitative scale to grade the results. Results: Death occurred in 1/202 patients in the laparotomy group (severe portal hypertension in congenital cardiopathy) and 0/60 in the laparoscopy group, with three conversions. All patients received follow-up care. The median follow ups in the laparotomy and laparoscopy groups were 96 months (IQR = 48-190.5) and 48 months (IQR = 27-69.5), respectively. At intraoperative manometry, myotomy resulted in a complete abolition of the HPZ in 100% of the patients. The Dor-related HPZ length and mean pressure were 4.5 (\ub1 0.4) cm and 13.3 (\ub1 2.2) mmHg in the laparotomy group and 4.5 (\ub1 0.5) cm and 13.2 (\ub1 2.2) mmHg in the laparoscopy group (p = 0.75;). In the laparotomy group, poor results [19/201 (9.5%)] were secondary to RE in 15/201 (7.5%) of the patients. In two patients, RE was diagnosed after 184 and 252 months, and recurrent dysphagia was diagnosed in 4/201 patients (2%), all resulting in end-stage sigmoid achalasia. In the laparoscopy group, 2/60 patients (3.3%) had RE and none had recurrent dysphagia. Conclusions: A long esophagogastric myotomy protected by means of Dor fundoplication cures or substantially reduces dysphagia in the great majority of patients affected by esophageal achalasia and effectively controls postoperative esophagitis. Intraoperative manometry is likely the key factor for achieving the reported results