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Biomedical subjects

Christian Rizzetto

Publications and source records attributed to Christian Rizzetto.

6 recordsLinked to original sources

Clinical biology and surgical therapy of intramucosal adenocarcinoma of the esophagus.

BACKGROUND: Mucosal ablation and endoscopic mucosal resection have been proposed as alternatives to surgical resection as therapy for intramucosal adenocarcinoma (IMC) of the esophagus. Acceptance of these alternative therapies requires an understanding of the clinical biology of IMC and the results of surgical resection modified for treatment of early disease. STUDY DESIGN: Retrospective review of 78 patients (65 men, 13 women; median age 66 years) with IMC who were treated with progressively less-extensive surgical resections (ie, en bloc, transhiatal, and vagal-sparing esophagectomy) from 1987 to 2005. RESULTS: The tumor was located in a visible segment of Barrett's esophagus in 65 (83%) and in cardia intestinal metaplasia in 13 (17%). A visible lesion was present in 53 (68%) and in all but 4 the lesion was cancer. In those patients with visible Barrett's, the tumor was within 3 cm of the gastroesophageal junction in 66% and within 1 cm in 37%. Esophagectomy was en bloc in 23, transhiatal in 31, vagal-sparing in 20, and transthoracic in 4. Operative mortality was 2.6%. Vagal-sparing esophagectomy had less morbidity, a shorter hospital stay, and no mortality. Of the patients who had en bloc resection, a median of 41 nodes were removed. One patient had one lymph node metastasis on hematoxylin and eosin staining and two others, normal on hematoxylin and eosin staining, had micrometastases on immunohistochemistry. Actuarial survival at 5 years was 88% and was similar for all types of resections. Two patients died from systemic metastases and seven from noncancer causes. CONCLUSIONS: IMC occurred in cardia intestinal metaplasia and in Barrett's esophagus. Two-thirds of patients with IMC had a visible lesion. Most tumors occurred near the gastroesophageal junction. Node metastases were uncommon, questioning the need for lymphadenectomy. A vagal-sparing technique had less morbidity than other forms of resection and no mortality. Survival after all types of resection was similar. Outcomes of endoscopic techniques should be compared with this benchmark.

Adenocarcinoma↗

Barrett's epithelium after antireflux surgery.

Barrett's epithelium (BE), defined as endoscopically visible, histologically proved intestinal-type epithelium in the esophagus, is considered the ultimate consequence of long-standing gastro(duodeno)esophageal reflux disease (GERD). Recent reports suggest that effective antireflux therapy may promote the regression of this metaplastic process. This study aimed to establish whether antireflux surgery (laparoscopic fundoplication) can induce any endoscopic and/or histologic changes in BE. Thirty-five consecutive cases of BE (11 short-segment [SBE] and 24 long-segment [LBE]) were considered. All patients underwent extensive biopsy sampling before and after surgery (mean follow-up, 28 months; range, 12-99 mo). In all cases, (a) intestinal metaplasia (IM) extension (H&E), (b) IM phenotype (high-iron diamine [HID]), and (c) Cdx2 immunohistochemical expression were histologically scored in the biopsy material obtained before and after fundoplication. After surgery, a significant decrease in IM extension and a shift from incomplete- to complete-type IM were documented in SBE. No significant changes occurred in the LBE group in terms of IM extension or histochemical phenotype. A drop in the immunohistochemical expression of Cdx2 protein was also only documented in the SBE group. Antireflux surgery significantly modifies the histologic phenotype of SBE, but not of LBE.

Adult↗

Long-term outcome of laparoscopic Heller-Dor surgery for esophageal achalasia: possible detrimental role of previous endoscopic treatment.

Laparoscopic Heller myotomy has recently emerged as the treatment of choice for esophageal achalasia. Previous unsuccessful treatments (pneumatic dilations or botulinum toxin [BT] injections) can make surgery more difficult, causing a higher risk of mucosal perforation and jeopardizing the outcome. The study goal was to evaluate the effects of prior endoscopic treatments on laparoscopic Heller myotomy. Between January 1992 and February 2005, 248 patients (130 males and 118 females; median age, 43 years) underwent a laparoscopic Heller-Dor operation for achalasia: 203 underwent primary surgery (group A), 19 had been previously treated with pneumatic dilations (group B), and 26 had BT injections (alone [22] or with dilations [4] (group C)). Median duration of the operation and rate of intraoperative mucosal lesions were not different in the three groups. Median follow-up was 41 months. The 5-year actuarial of control of dysphagia was similar in groups A (86%) and B (94%), whereas only 75% of group C patients were symptom free at 5 years (P = 0.02). On logistic regression analysis, prior treatment with two BT injections or BT combined with dilation was associated with poor outcome of surgery. Further, dilations for surgical failure patients were effective in 80% of group A but in only 33% of group B or C patients. Heller-Dor surgery is safe and effective as a primary or a second-line treatment (after pneumatic dilations or BT injections) for achalasia. However, long-term results seem less satisfactory in patients previously treated with BT.

Adolescent↗

Esophageal achalasia: is the herpes simplex virus really innocent?

This study was designed to test the hypothesis that mononuclear cells in the myenteric plexus of patients with achalasia may be activated by herpes simplex virus type 1 (HSV-1). Strips of esophageal muscle were obtained from patients with achalasia and multiorgan transplant donors who served as control subjects. After muscle digestion, mononuclear cells were purified through a Percoll gradient and cultured in medium, either alone or containing ultraviolet-inactivated HSV-1 or poliovirus (multiplicity of infection 1:1.5). As an indicator of HSV-1-induced lymphocyte activation, we determined T-cell proliferation by means of 3H-thymidine incorporation and interferon gamma release. DNA was extracted from esophageal muscle of achalasia patients and control subjects, and used as a template for PCR analysis using primer pairs specific for HSV-1. Circulating anti-HSV-1 and HSV-2 antibodies were detected by enzyme-linked immunosorbent assay on serum samples. Fifteen patients with naive achalasia and eight control subjects were studied. The prevalence of circulating anti-HSV-1 and HSV-2 antibodies proved similar in the two groups, and no HSV-1 DNA was detected by polyermase chain reaction in the esophageal muscle samples. The proliferative index in mononuclear cells from achalasia patients stimulated with HSV-1 showed a 3.4-fold increase in comparison with control subjects (P<0.01). In addition, a 1.4-fold increase in interferon gamma release after incubation with HSV-1 was observed in cells from achalasia patients but not control subjects. The results of this study indicate that HSV-1-reactive immune cells are present in lower esophageal sphincter muscles of patients with achalasia. We hypothesize that the HSV-1-reactive lymphocytes in lower esophageal sphincter muscles of achalasia patients may contribute to damage of the neurons in the myenteric plexus and lead to the motor dysfunction.

Adult↗

The role of botulinum toxin injection and upper esophageal sphincter myotomy in treating oropharyngeal dysphagia.

The aims of this study were to assess the efficacy and safety of botulinum toxin (BoTox) injection in the cricopharyngeus muscle (CP) and CP myotomy in patients with oropharyngeal dysphagia (OPD) and to identify factors predicting the outcome of these treatments. The study involved patients with persistent OPD despite 2-6 months of rehabilitation, who all underwent clinical evaluation, esophageal manometry, upper gastrointestinal endoscopy, and videofluoroscopy (VFS). Patients received 5-10 BoTox units injections in the CP, identified by electromyography. Surgical myotomy of the upper esophageal sphincter was performed when dysphagia persisted after two BoTox injections. After treatment, patients were reevaluated with clinical interviews and VFS. The study population included 21 patients (15 mean and 6 women; median age, 68 years), classified into three groups, based on the etiology of their OPD: eight (38%) had central nervous system abnormalities, five (24%) had peripheral nerve disease, and eight (38%) were classified as idiopathic. The median time since the onset of dysphagia was 18 months. Thirteen of 21 patients (62%) needed supplemental/total gastrostomy feeding, and 5 of 21 (24%) had tracheostomy. One patient died, on posttreatment day 7, due to massive aspiration. No other BoTox-related complications were observed. After BoTox injection, dysphagia improved in 9 of 21 (43%) patients. Severely altered VFS findings and CP incoordination or low activity predicted BoTox failure at multivariate analysis. Dysphagia improved in 8 of 11 (72.7%) patients who failed to respond to BoTox and underwent myotomy. A mild impairment of VFS findings and a higher pressure of pharyngeal contractions best predicted response to BoTox with or without myotomy. BoTox injection can be used as the first therapeutic option in patients with OPD: it is safe and simple and relieves dysphagia in 43% of cases. If BoTox fails, CP myotomy can be offered to patients with preserved oral and tongue activity at VFS and an intact bolus propulsion ability on manometry.

Aged↗

Oesophageal diverticula.

Oesophageal diverticula are rare. They are most commonly seen at the pharyngo-oesophageal junction (Zenker's diverticula) or at the distal oesophagus (epiphrenic diverticula). In both cases they are caused by altered motility which results in abnormal intraluminal pressure and the pushing of the oesophageal mucosa through focal weaknesses of the muscular wall (pulsion diverticula). The established surgical treatment for these diverticula therefore consists of eliminating the functional obstruction causing the disease (myotomy), associated with resection of the diverticulum (diverticulectomy) or its suspension (diverticulopexy). Recently, the spread of minimally invasive surgery has also led the application of such techniques to the treatment of oesophageal diverticula. Endoscopic diverticulostomy with stapler, laser or coagulation, through a rigid or flexible endoscope, has been demonstrated to be a valid treatment for Zenker's diverticula-as an alternative to surgery-especially in high-risk patients. On the other hand, laparoscopic treatment of epiphrenic diverticula has recently been introduced with encouraging results. However, because the disease is rare, more experience is required in order to allow definitive conclusions.

Diverticulum, Esophageal↗