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luigi bonavina

luigi.bonavina@fastwebnet.it

Journal articles

2008
 
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R Cardani, E Mancinelli, G Saino, L Bonavina, G Meola (2008)  A putative role of ribonuclear inclusions and MBNL1 in the impairment of gallbladder smooth muscle contractility with cholelithiasis in myotonic dystrophy type 1.   Neuromuscul Disord 18: 8. 641-645 Aug  
Abstract: Myotonic dystrophy type 1 (DM1) is an autosomal dominant multisystemic disorder caused by expansion of unstable trinucleotide (CTG) repeats at 3' untranslated region of the DMPK gene on chromosome 19q13.3. Mutant transcripts are retained in muscle nuclei as ribonuclear inclusions and interact with RNA-binding proteins, such as muscleblind-like protein 1 (MBNL1), leading to a reduction in their activity. The reduced MBNL1 activity has been associated to skeletal and cardiac muscle dysfunction. However, other organs and systems may be involved. It has been reported that 25-50% of DM1 patients have abdominal symptoms due to cholelithiasis or gallstones. Since impaired gallbladder motility plays an important role in gallstones formation, we have analyzed by FISH combined with MBNL1-immunofluorescence, the gallbladder obtained from a woman affected by DM1 who required a cholecystectomy at the age of 30. Gallbladders obtained from two no-DM1 subjects have been used as controls. Ribonuclear inclusions and MBNL1 foci accumulate and colocalize in nuclei of DM1 gallbladder smooth muscle cells. On the contrary, no ribonuclear inclusions are detectable in cell nuclei of control gallbladders and MBNL1 is uniformly distributed in smooth muscle cell nuclei. These results suggest that nuclear accumulation of MBNL1 and ribonuclear inclusions may have a direct adverse effect on gallbladder smooth muscle contractility and thus contribute to gallstones formation in DM1 patients.
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Davide Bona, Luigi Stefano Schipani, Marco Nencioni, Barbara Rubino, Luigi Bonavina (2008)  Laparoscopic resection for incidentally detected Meckel diverticulum.   World J Gastroenterol 14: 31. 4961-4963 Aug  
Abstract: The management of Meckel diverticulum found unexpectedly during an abdominal operation remains controversial. Most published reports have included only patients undergoing diverticulectomy or bowel resection through laparotomy. We report a case of a carcinoid tumor in a Meckel's diverticulum which was incidentally detected and removed during laparoscopic inguinal hernia repair. Although there is no compelling evidence in the literature to recommend prophylactic diverticulectomy, laparoscopic stapled resection represents a viable and safe approach in healthy individuals undergoing elective surgery for other purposes.
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Luigi Bonavina, Greta I Saino, Davide Bona, John Lipham, Robert A Ganz, Daniel Dunn, Tom DeMeester (2008)  Magnetic augmentation of the lower esophageal sphincter: results of a feasibility clinical trial.   J Gastrointest Surg 12: 12. 2133-2140 Dec  
Abstract: BACKGROUND: The high prevalence of gastroesophageal reflux disease continues to encourage the development of treatment modalities to fill the gap between acid-suppression therapy and the laparoscopic Nissen fundoplication. The Magnetic Sphincter Augmentation device has been designed to augment the lower esophageal sphincter barrier using magnetic force. A multi-center feasibility trial was done to evaluate safety and efficacy. METHODS: Patients with typical heartburn (at least partially responding to proton-pump inhibitors), abnormal esophageal acid exposure, and normal esophageal peristalsis were enrolled. Patients with hiatal hernia >3 cm were excluded from the study. The device was implanted laparoscopically around the distal esophagus. RESULTS: Over a 1-year period, 38 out of 41 enrolled patients underwent this procedure in 3 hospitals. No operative complications were recorded. A free diet was allowed since post-operative day one, and 97% of patients were discharged within 48 h. The mean follow-up was 209 days (range 12-434 days). The GERD-HRQL score decreased from 26.0 to 1.0 (p < 0.005). At 3 months post-operatively, 89% of patients were off anti-reflux medications, and 79% of patients had a normal 24-h pH test. All patients preserved the ability to belch. Mild dysphagia occurred in 45% of patients. No migrations or erosions of the device occurred. CONCLUSIONS: Laparoscopic implant of the MSA device is safe and well tolerated. It requires minimal surgical dissection and a short learning curve compared to the conventional Nissen fundoplication.
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2007
 
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Luigi Bonavina, Davide Bona, Medhanie Abraham, Greta Saino, Emmanuele Abate (2007)  Long-term results of endosurgical and open surgical approach for Zenker diverticulum.   World J Gastroenterol 13: 18. 2586-2589 May  
Abstract: AIM: To assess the effectiveness of minimally invasive versus traditional open surgical approach in the treatment of Zenker diverticulum. METHODS: Between 1976 and 2006, 297 patients underwent transoral stapling (n = 181) or stapled diverticulectomy and cricopharyngeal myotomy (n = 116). Subjective and objective evaluations of the outcome of the two procedures were made at 1 and 6 mo after operation, and then every year. Long-term follow-up data were available for a subgroup of patients at a minimum of 5 and 10 years. RESULTS: The operative time and hospital stay were markedly reduced in patients undergoing the endosurgical approach. Overall, 92% of patients undergoing the endosurgical approach and 94% of those undergoing the open approach were symptom-free or were significantly improved after a median follow-up of 27 and 48 mo, respectively. At a minimum follow-up of 5 and 10 years, most patients were asymptomatic after both procedures, except for those individuals undergoing an endosurgical procedure for a small diverticulum (< 3 cm). CONCLUSION: Both operations relieve the outflow obstruction at the pharyngoesophageal junction, indicating that cricopharyngeal myotomy has an important therapeutic role in this disease independent of the resection of the pouch and of the surgical approach. Diverticula smaller than 3 cm represent a formal contraindication to the endosurgical approach because the common wall is too short to accommodate one cartridge of staples and to allow complete division of the sphincter.
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Luigi Bonavina, Davide Bona, Greta Saino, Claudio Clemente (2007)  Pseudoachalasia occurring after laparoscopic Nissen fundoplication and crural mesh repair.   Langenbecks Arch Surg 392: 5. 653-656 Sep  
Abstract: BACKGROUND: Benign esophageal pseudoachalasia is a rare condition. DISCUSSION: We report the case of a 70-year-old man who complained of severe dysphagia after laparoscopic Nissen fundoplication and crural mesh repair performed for long-standing gastroesophageal reflux disease. Severe dysphagia and nocturnal aspiration developed soon after the operation. A marked dilatation of the esophageal body and a manometric pattern resembling achalasia was documented. RESULTS: Endoscopic balloon dilatation was ineffective. Five months after the initial operation, the patient underwent revisional laparoscopic surgery that consisted of Nissen's wrap takedown, enlargement of the hiatus with partial resection of the mesh, Heller myotomy, and Dor fundoplication. After a 2-year follow-up, the patient is doing well and is free of symptoms.
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Davide Bona, Dario Sarli, Greta Saino, Matteo Quarenghi, Luigi Bonavina (2007)  Successful conservative management of benign gastro-bronchial fistula after intrathoracic esophagogastrostomy.   Ann Thorac Surg 84: 3. 1036-1038 Sep  
Abstract: Benign gastro-bronchial fistula is a rare and devastating complication of esophagectomy with gastric replacement. The most likely cause is a leak from the esophagogastric anastomosis with subsequent mediastinal abscess and rupture into the posterior wall of the tracheobronchial tree. The clinical presentation includes cough upon swallowing, fever, and recurrent pneumonia. Early surgical treatment is the standard of care. A unique case of chronic gastro-bronchial fistula is reported in this article. The patient, a 57-year-old woman, was referred from another hospital after 6 months of symptomatic therapy and total enteral nutrition. A self-expanding esophageal metal stent allowed exclusion of the fistula with symptom relief and return to oral alimentation.
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2006
 
PMID 
Luigi Bonavina (2006)  Minimally invasive surgery for esophageal achalasia.   World J Gastroenterol 12: 37. 5921-5925 Oct  
Abstract: Esophageal achalasia is the most commonly diagnosed primary esophageal motor disorder and the second most common functional esophageal disorder. Current therapy of achalasia is directed toward elimination of the outflow resistance caused by failure of the lower esophageal sphincter to relax completely upon swallowing. The advent of minimally invasive surgery has nearly replaced endoscopic pneumatic dilation as the first-line therapeutic approach. In this editorial, the rationale and the evidence supporting the use of laparoscopic Heller myotomy combined with fundoplication as a primary treatment of achalasia are reviewed.
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Dario Sarli, Davide Bona, Medhanie Abraham, Luigi Bonavina (2006)  Conservative and surgical treatment of esophago-gastric anastomotic leaks   Ann Ital Chir 77: 5. 391-396 Sep/Oct  
Abstract: OBJECTIVE: To evaluate the results of conservative and surgical management of esophago-gastric anastomotic leaks after esophagectomy for carcinoma. MATERIALS AND METHODS: A retrospective analysis of 510 patients subjected to esophagectomy and gastric pull-up with intra-thoracic or cervical anastomosis was performed. RESULTS: Twenty four cases (6.1%) of intra-thoracic anastomotic leaks and 17 (13.9%) cervical leaks were observed and treated. The conservative treatment was adopted in 19 intra-thoracic leakages (79%) and in 10 cervical leakages (59%). The leak-related mortality rate was 16.6% in patients with intra-thoracic leaks and 11.7% in those with cervical leaks. DISCUSSION: The introduction of staplers has dramatically decreased, but not eliminated, the risk of intra-thoracic and cervical anastomotic leaks. In our series the choice of the therapeutic approach was based on clinical and endoscopic findings. Patients with anastomotic dehiscence and gastric graft ischemia required reoperation, whereas conservative treatment was possible in the majority of cases. CONCLUSION: The treatment of esophago-gastric anastomotic leaks must be tailored to the individual patient. Early endoscopy is crucial for recognition of ischemia of the transposed stomach.
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2005
 
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D Bona, R Incarbone, B Chella, M Vecchi, L Bonavina (2005)  Heartburn and multiple-site foregut perforations as primary manifestation of Crohn's disease.   Dis Esophagus 18: 3. 199-201  
Abstract: SUMMARY: Crohn's disease may affect any segment of the digestive tract, more commonly the distal ileum, colon and/or perianal region. There is an increasing number of reports dealing with foregut Crohn's disease. We present the case of a patient with a history of heartburn and multiple spontaneous perforations of the esophagus, duodenum and jejunum as a primary manifestation of Crohn's disease who required emergency surgical and endoscopic procedures. Early detection of Crohn's disease may decrease the incidence of acute life-threatening complications provided that appropriate medical treatment is administered and a multidisciplinary approach is offered to these patients.
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Elena Bernardin, Stefano Boati, Davide Bona, Medhanie Abraham, Greta Saino, Luigi Bonavina (2005)  Bouveret's syndrome: a rare clinical variant of gallstone ileus   Chir Ital 57: 2. 267-270 Mar/Apr  
Abstract: Bouveret's syndrome is a rare complication of gallstone disease characterized by gastric outlet obstruction due to impaction of single or multiple gallstones which have migrated through a bilio-enteric fistula. The main symptoms are nausea, vomiting and epigastric pain. The diagnosis is achieved by plain film of the abdomen, ultrasonography and CT scan, which reveal aerobilia (an indirect sign of bilio-enteric fistula), and the obstructing gallstone. The treatment of this condition requires removal of the stone through an endoscopic or surgical approach, and possible cholecystectomy with closure of the fistula. The Authors report a case of Bouveret's syndrome in an 86-year-old female patient who underwent successful surgical treatment.
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Luigi Bonavina, Tommaso Lupattelli, Davide Bona, Santi Trimarchi, Giovanni Nano, Vincenzo Rampoldi, Luigi Inglese (2005)  Bronchoesophageal fistula after endovascular repair of ruptured aneurysm of the descending thoracic aorta.   J Vasc Surg 41: 4. 712-714 Apr  
Abstract: Aortoesophageal fistula secondary to thoracic aneurysm is rare and is usually fatal without prompt surgical intervention. A 79-year-old man with significant comorbidities and previous cancer surgery was admitted on an emergency basis because of the suspicion of a ruptured thoracic aortic aneurysm. Computed tomographic scan followed by angiography demonstrated a ruptured thoracic aneurysm with aortoesophageal fistula. An endovascular stent graft repair was performed with successful exclusion of both aneurysm and fistula. On postoperative day 6, dyspnea and an isolated episode of hemoptysis occurred. Endoscopy revealed the presence of a bronchoesophageal fistula, which necessitated double exclusion of the esophagus and feeding jejunostomy. At 6 months, clinical, bronchoscopic, and computed tomographic scan follow-up showed complete sealing of the aneurysm and resolution of the bronchoesophageal fistula. At 9 months, the patient was still alive but refused to undergo substernal gastric bypass in an attempt to restore oral feeding. Endovascular repair seems promising as an emergent and palliative treatment of aortoesophageal fistula. To the best of our knowledge, this is the first case in which a bronchoesophageal fistula developed after successful endovascular repair of aortoesophageal fistula. The pathogenesis of this complications remains unclear.
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2004
 
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Luigi Bonavina, Davide Bona, Pierre René Binyom, Alberto Peracchia (2004)  A laparoscopy-assisted surgical approach to esophageal carcinoma.   J Surg Res 117: 1. 52-57 Mar  
Abstract: BACKGROUND: Surgical resection is the treatment of choice for esophageal carcinoma. Over the past decade, laparoscopy has proven an accurate staging modality for detecting peritoneal carcinosis and small metastatic liver deposits unsuspected at preoperative investigation. This has led to a change in surgical strategy in up to 20% of patients. In addition, by means of laparoscopic techniques, it is possible to mobilize the stomach and perform a safe transhiatal mediastinal dissection at least up to the level of the inferior pulmonary veins. PATIENTS AND METHODS: Laparoscopy-assisted esophagectomy was attempted in 43 patients over the past 3 years. The esophagectomy was performed via laparoscopy combined with right thoracotomy (group A) or with left cervicotomy and transmediastinal endodissection (group B). RESULTS: The overall conversion rate to laparotomy was 11.6%. No hospital deaths occurred. The morbidity rate was 20% in group A and 30.7% in group B. The mean hospital stay was 11 in group A and 10 days in group B. Five patients died between 11 and 19 months after surgery with recurrent disease. No port-site metastases were recorded during follow-up. CONCLUSIONS: This approach has proven feasible and safe in the medium-term follow-up. Further experience and a longer follow-up are needed to assess the impact of these procedures on long-term survival.
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Luigi Bonavina, Medhanie Abraham, Stefano Boati, Davide Bona (2004)  Laparoscopic treatment of incisional hernia with Parietex mesh. Preliminary results and review of the literature   Chir Ital 56: 4. 545-549 Jul/Aug  
Abstract: Conventional surgery for incisional hernia carries a postoperative morbidity and recurrence rate of more than 12%. The aim of this study was to report our experience with the laparoscopic treatment of incisional hernia with the use of a composite mesh (Parietex, Sofradim, Celbio). The median duration of the operation was 135 minutes. In one patient peritonitis from small bowel perforation occurred on postoperative day 2 and required emergency surgery. The median postoperative hospital stay was 3 days. No complications were observed over a median follow-up period of 12 months. The goal of the laparoscopic treatment of incisional hernia is to decrease the incidence of local complications and the recurrence rate which are seen with traditional open surgery. To this should be added all the advantages of minimally invasive surgery in terms of decreased postoperative pain, length of hospital stay, and sick leave.
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Chiara Dall'Asta, Medhanie Abraham, Davide Bona, Bruno Ambrosi, Luigi Bonavina (2004)  Cushing disease resistent to conventional therapy: role of bilateral laparoscopic adrenalectomy   Chir Ital 56: 6. 801-804 Nov/Dec  
Abstract: Cushing's disease is the most frequent form of endogenous hypercortisolism in the adult. It is a rare disease, whose natural history is not well known, and has a tremendous impact on patients' quality of life. Trans-sphenoidal surgery is the first therapeutic option in the management of these patients, but it is associated with a 25% long-term recurrence rate. Based on the observation of two patients, the Authors discuss the multidisciplinary approach, the indications and the timing of treatment by bilateral adrenalectomy. Also, the peculiar aspects of the laparoscopic surgical technique are outlined.
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Chiara Dall'asta, Laura Barbetta, Luigi Bonavina, Paolo Beck-Peccoz, Bruno Ambrosi (2004)  Recurrence of Cushing's disease preceded by the reappearance of ACTH and cortisol responses to desmopressin test.   Pituitary 7: 3. 183-188  
Abstract: At present no single test is considered of absolute value in identifying patients successfully operated for Cushing's disease who are at risk for recurrence. The present report describes the first two patients in whom ACTH/cortisol abnormal responses to desmopressin disappeared after cure and then clearly reappeared during long-term follow-up several months before the clinical and hormonal features of hypercortisolism became manifest.The case histories of 2 young women are reported. The diagnosis of Cushing's disease was made on the basis of clinical features and standard hormonal criteria. Both patients, showing abnormal ACTH/cortisol rises after desmopressin test, underwent pituitary adenomectomy by transsphenoidal surgery and after operation plasma ACTH and serum cortisol levels were 0.2 and 0.4 pmol/l and 56 and 32 nmol/l, respectively. During the follow-up both patients underwent desmopressin (10 microg iv), ovine CRH (1 microg/kg iv) and 1 mg dexamethasone tests at 1, 6, 12, 24 months after surgery.In these two cases the ACTH/cortisol response to desmopressin normalized following pituitary adenomectomy, concomitantly with the normalization of all the other clinical and hormonal parameters. Subsequently abnormal rises after the synthetic AVP analogue administration appeared: paradoxical ACTH/cortisol increments after desmopressin occurred 24 and 6 months before any other hormonal or clinical sign of recurrence of hypercortisolism.As desmopressin may be able to stimulate ACTH/cortisol release in Cushing's disease, but not in normal subjects, we suggest that it can have a role in early identifying successfully operated Cushing's patients at risk for recurrence.
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Barbara Chella, Davide Bona, Giacomo Gazzano, Nadia Bellaviti, Luigi Bonavina (2004)  Abdominal cystic lymphangioma: a case report   Chir Ital 56: 3. 463-466 May/Jun  
Abstract: Intra-abdominal cystic lymphangioma is a rare dysembryogenetic tumour. Although laparoscopic treatment may be feasible and has been reported in the literature, the extension of the mass to the retroperitoneum can make a minimally invasive surgical approach difficult or impossible. We describe the case of a patient with lymphangioma with retroperitoneal extension who underwent successful surgical therapy.
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Alberto Peracchia, Luigi Bonavina, Davide Bona, Marco Pagani, Stefano Bona (2004)  Evolution of anastomotic techniques in oesophageal surgery: experience at the Milan University Department of Surgery   Chir Ital 56: 3. 307-312 May/Jun  
Abstract: Despite the fact that the incidence and severity of postoperative complications after oesophagectomy have substantially decreased over the past two decades, anastomotic leakage is still a potentially catastrophic event. In this article, the experience of a single surgical unit is analysed. Over the period from 1992 to 2003, 435 oesophagectomies with oesophagogastroplasty were performed at the Milan University Department of Surgery. The overall mortality rate was 1.6%. The incidence of anastomotic leakage was 8.5% (6.5% for intrathoracic anastomoses and 14% for cervical anastomoses), and the mortality rate due to leakage was 13.5%. The authors discuss the factors associated with anastomotic leakage by comparing their personal experience with data from the international literature.
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Luigi Bonavina, Raffaello Incarbone, Valeria Midolo, Davide Bona, Stefano Ferrero, Chiara Dall'Asta (2004)  Prognostic significance of lymphatic micrometastasis of esophageal adenocarcinoma   Chir Ital 56: 2. 189-196 Mar/Apr  
Abstract: The aim of the study was to test the hypothesis that a subgroup of patients considered N0 at standard single-section pathological examination may have occult lymph-node metastases (micrometastases) associated with a poor prognosis. Fifty-nine patients with oesophageal adenocarcinoma undergoing resection were studied by standard histological examinations, serial sections and immunohistochemistry, and their long-term prognoses were compared. Eight (26%) out of 31 patients previously staged as pN0 at standard histological examination were staged as pN1 or Pn2 by serial sections and/or immunohistochemistry and had a prognosis which was significantly worse than that of true pN0 patients (5-year survival: 38% vs 76%, respectively; P < 0.05) and similar to that of pN1 patients. More than a quarter of those patients classified as pN0 at standard histological examination may have occult lymph node metastases at serial sections and/or immunohistochemistry and have a prognosis similar to that of pN1 patients.
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Davide Bona, Riccardo Enrini, Luigi Bonavina (2004)  Intestinal obstruction caused by migration of intragastric device used for the treatment of obesity   Chir Ital 56: 2. 285-288 Mar/Apr  
Abstract: The authors report a case of intestinal obstruction caused by the rupture of an intragastric balloon for the treatment of obesity and requiring surgical treatment. This unusual case shows that careful patient selection and follow-up are of paramount importance for successful endoscopic treatment of obesity.
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Luigi Bonavina, Raffaello Incarbone, Davide Bona, Alberto Peracchia (2004)  Esophagectomy via laparoscopy and transmediastinal endodissection.   J Laparoendosc Adv Surg Tech A 14: 1. 13-16 Feb  
Abstract: An original technique for minimally invasive transmediastinal esophagectomy is described. A combined laparoscopic and video-mediastinoscopic approach was attempted in a series of patients with high-grade dysplasia or carcinoma of the esophagus. Laparoscopy allowed mobilization of the stomach and dissection of the distal esophagus at least up to the level of the inferior pulmonary veins. Through a left cervicotomy, endodissection of the upper thoracic esophagus was accomplished with an operating video-mediastinoscope. After complete upward and downward mobilization from the mediastinal bed, the specimen was retrieved through the cervical incision and the stomach was guided laparoscopically into the posterior mediastinum. Compared to the laparoscopic total esophagectomy, this approach provides a more controlled and safer dissection of the upper mediastinum.
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2003
 
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Luigi Bonavina, Albert Via, Raffaello Incarbone, Greta Saino, Alberto Peracchia (2003)  Results of surgical therapy in patients with Barrett's adenocarcinoma.   World J Surg 27: 9. 1062-1066 Sep  
Abstract: The incidence of adenocarcinoma arising from Barrett's esophagus is dramatically increasing in Western countries. The purpose of this study was to report our experience in the surgical management of these patients. Between November 1992 and December 2000, 330 consecutive patients with adenocarcinoma of the esophagogastric junction were observed in our institution. Of these, 105 (31.8%) had Barrett's carcinoma. In 12 individuals (11.4%) adenocarcinoma was discovered during endoscopic surveillance for Barrett's esophagus. Twelve patients with doubtful cleavage planes at preoperative investigation were treated with neoadjuvant chemotherapy. Overall, 80 patients (76.2%) underwent esophagectomy without operative mortality. The Ivor Lewis approach was used in 70 patients; of these, 31 underwent extended mediastinal lymph node dissection. Seventy-four patients (92.5%) had R0 resection. The overall 5-year survival rate was 48%. Survival was significantly associated with stage, lymph node status, and completeness of resection. Early diagnosis remains the prerequisite for curative treatment of esophageal carcinoma. An extended mediastinal lymphadenectomy does not increase morbidity, allows precise tumor staging, and may prove effective in preventing local recurrences. Neoadjuvant therapy requires major improvement before it can be unconditionally recommended outside clinical trials.
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L Bonavina, R Incarbone, M Reitano, A Tortorano, M Viviani, A Peracchia (2003)  Candida colonization in patients with esophageal disease: a prospective clinical study.   Dis Esophagus 16: 2. 70-72  
Abstract: The incidence of Candida infection has significantly increased over the recent years, becoming the fourth most common pathogens isolated in patients admitted to intensive care units (ICU). Mortality rates ranging between 6 and 38% have been reported to be associated with candidemia. Esophageal surgery may increase the risk of systemic Candida infection in critical patients requiring postoperative ICU admission. The aim of the present study was to assess the prevalence of Candida colonization in patients with esophageal disease undergoing surgery. Between April 1999 and April 2001, 131 patients with esophageal disease and 40 healthy volunteers were prospectively tested for Candida colonization by oral and pharyngeal swab. Candida colonization was significantly more frequent in patients with esophageal disease than in control subjects (38.9 vs 7.5%, P < 0.01); the prevalence was higher in individuals with carcinoma than in those with benign disease (51.8 vs 24%, P < 0.02), and in patients undergoing neoadjuvant chemoradiation therapy compared to those having primary surgery (55.5 vs 34.4%, P < 0.01). These data suggest that Candida colonization of the gastrointestinal tract is common in patients with esophageal disease. Pharmacological attempts to prevent or reduce the magnitude of this event may be worthwhile before surgery. However, the hypothesis that antifungal oral prophylaxis with nonabsorbable drugs may lower the incidence of candidemia in patients with gastrointestinal Candida colonization, especially in those candidates to postoperative ICU admission, should be tested by randomized double-blinded studies.
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L Bonavina, R Incarbone, G Saino, P Clesi, A Peracchia (2003)  Clinical outcome and survival after esophagectomy for carcinoma in elderly patients.   Dis Esophagus 16: 2. 90-93  
Abstract: Advances in perioperative management have allowed more and more elderly patients to undergo major surgery with postoperative morbidity and mortality rates comparable to those of younger individuals. The aim of this study was to evaluate the impact of age on the clinical outcome and long-term survival of patients with esophageal carcinoma undergoing esophagectomy. Nine-hundred patients with esophageal carcinoma were divided into two groups: A (n = 403) with age > or = 65 years, and B (n = 497) with age < 65 years. One-hundred and fifty three (38%) patients of group A underwent surgery compared to 272 (55%) of group B (P < 0.01). Postoperative mortality, and the prevalence of anastomotic leak and respiratory complications were similar in both groups; conversely, there was a higher prevalence of cardiovascular complications in group A (13% vs 3%, P < 0.01). Five-year survival was about 35% in both groups. In conclusion, advanced age should no longer be considered an absolute contraindication to esophagectomy for carcinoma in selected patients. In fact, the postoperative mortality and long-term survival rates of elderly patients undergoing resection are comparable to that of younger individuals.
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D Perego, G Casella, L Bonavina, U Pozzetti, D Soligo, R Incarbone, C A Buda, V Baldini (2003)  Esophageal involvement as an uncommon modality of relapse of Hodgkin lymphoma.   Dis Esophagus 16: 3. 270-272  
Abstract: We present a case of systemic Hodgkin's lymphoma, relapsed with esophageal involvement after 3 years of complete remission. The importance of an accurate diagnostic work-up is emphasized. Esophagectomy and chemotherapy followed by bone marrow transplantation allowed a complete response and the long-term survival of the patient.
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M Pagani, P Granelli, B Chella, L Antoniazzi, L Bonavina, A Peracchia (2003)  Barrett's esophagus: combined treatment using argon plasma coagulation and laparoscopic antireflux surgery.   Dis Esophagus 16: 4. 279-283  
Abstract: The treatment of Barrett's esophagus is still controversial. Actually, the only method to prevent the development to cancer is endoscopic surveillance, which ensures good results in terms of long-term survival. An ideal treatment capable of destroying columnar metaplasia, followed by squamous epithelium regeneration could potentially result in a decrease of the incidence of adenocarcinoma. Recently most ablative techniques were used, such as photodynamic therapy, ablation therapy with Nd-YAG laser or argon plasma coagulation and endoscopic mucosal resection. We started a prospective study in January 1998, enrolling 94 patients affected by Barrett's esophagus and candidates for antireflux repair in order to assess the effectiveness and the results of endoscopic coagulation with argon plasma combined with surgery in the treatment of uncomplicated Barrett's esophagus. All patients underwent endoscopic treatment with argon plasma; we observed complete response in 68 patients (72.34%), 27 of them (39.7%) underwent antireflux surgery and the other 41 continued medical therapy. Post-operatively 19 patients (70%) underwent regular surveillance endoscopies and in two cases metaplasia recurred. The final objective of these combined treatments should be the complete eradication of metaplastic mucosa. Our experience was that argon plasma coagulation combined with antireflux surgery or proton pump inhibitor therapy gave satisfactory results, even if follow-up is too short to evaluate the potential evolution of metaplasia to cancer. For this reason, we recommend that this technique should be done only in specialized centres and that these patients continue their endoscopic surveillance program.
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Luigi Bonavina, Enrico Mozzi, Alberto Peracchia (2003)  Virtual surgical education: experience with medicine and surgery students   Chir Ital 55: 6. 829-833 Nov/Dec  
Abstract: The use of virtual reality simulation is currently being proposed within programs of postgraduate surgical education. The simple tasks that make up an operative procedure can be repeatedly performed until satisfactory execution is achieved, and the errors can be corrected by means of objective assessment. The aim of this study was to evaluate the applicability and the results of structured practice with the LapSim laparoscopic simulator used by undergraduate medical students. A significant reduction in operative time and errors was noted in several tasks (navigation, clipping, etc.). Although the transfer of technical skills to the operating room environment remains to be demonstrated, our research shows that this type of teaching is applicable to undergraduate medical students and in future may become a useful tool for selecting individuals for surgical residency programs.
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Luigi Bonavina, Davide Bona, Alberto Luporini, Nicoletta Navoni, Roberto Zucali (2003)  Surgery for esophageal carcinoma and the role of neoadjuvant therapy.   Acta Biomed 74 Suppl 2: 15-20  
Abstract: Esophagectomy is a major surgical procedure. Due to the related morbidity and mortality, this operation should be carried out in high-volume referral centers by expert surgeons. Only patients in whom a complete resection is predictable at preoperative staging can consistently benefit from the operation. Chemoradiation therapy should be the first-line approach in patients with locally advanced tumors. A pathological complete response to neoadjuvant therapy is associated with a significantly improved long-term survival.
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2002
 
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Raffaello Incarbone, Luigi Bonavina, Fabio Bassi, Alberto Peracchia (2002)  Impact of endoscopic surveillance of Barrett's esophagus on survival of patients with esophageal adenocarcinoma   Chir Ital 54: 5. 591-596 Sep/Oct  
Abstract: In an attempt to reduce mortality from oesophageal adenocarcinoma, it has been recommended to enroll patients with Barrett's oesophagus in endoscopic surveillance programs in order to detect malignant degeneration at an early and possibly curable stage. The aim of this study was to assess the impact of endoscopic biopsy surveillance on the outcome of Barrett's adenocarcinoma. From November 1992 to December 2000, 328 patients with histologically proven oesophageal adenocarcinoma were referred to our department. One hundred of these patients had Barrett's adenocarcinoma. In 12 (12%) patients, cancer was discovered during endoscopic surveillance for Barrett's metaplasia. The prevalence of gastro-oesophatgeal reflux disease in the Barrett's group was 38.8% versus 8.1% (P < 0.01) of non-Barrett's patients. In the surveyed group, there were 9 (75%) early stage tumours (Tis-1N0), versus 10 (11.4%, P < 0.01) in the non-surveyed patients. Three out of five surveyed patients operated on for high grade dysplasia proved to have invasive carcinoma in the oesophagectomy specimen. All surveyed patients were alive after a median follow-up period of 50 months; the median survival in the non-surveyed group was 24 +/- 3 months (P < 0.01). Endoscopic surveillance of Barrett's oesophagus allows early detection of malignant degeneration and better long-term survival than in non-surveyed patients.
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PMID 
Luigi Bonavina, Raffaello Incarbone, Greta Saino, Alberto Peracchia (2002)  Esophagectomy for carcinoma: impact of age on clinical results and survival   Chir Ital 54: 5. 587-590 Sep/Oct  
Abstract: Advances in perioperative management have allowed more and more elderly patients to undergo major surgery with postoperative morbidity and mortality rates similar to those of younger individuals. The aim of this study was to evaluate the impact of age on the clinical outcome and long-term survival of patients with oesophageal cancer undergoing oesophagectomy. Eight hundred and seventy-five patients with oesophageal carcinoma were divided into two groups: A (n = 393) aged > or = 65 years, and B (n = 482) aged < 65 years. One hundred and forty-nine (38%) patients in group A underwent surgery compared to 263 (55%) in group B (P < 0.01). Postoperative mortality and the prevalence of anastomotic leak and respiratory complications were similar in both groups. There was, however, a higher prevalence of cardiovascular complications in group A (13% versus 3%, P < 0.01). Five-year survival was about 35% in both groups. In conclusion, advanced age should not be considered a contra-indication to oesophagectomy for carcinoma, since the long-term survival of elderly patients undergoing resection is similar to that of younger ones.
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PMID 
Luigi Bonavina, Davide Bona, Medhanie Abraham, Fabio Bassi, Alberto Peracchia (2002)  Esophagectomy by video-assisted laparoscopic and trans-mediastinal approach   Chir Ital 54: 3. 285-288 May/Jun  
Abstract: The aim of study was to report our experience with an original technique of oesophagectomy without thoracotomy. The operation consists of two complementary approaches. Laparoscopic access enables the surgeon to mobilize the stomach and dissect the distal oesophagus. Cervical access allows dissection of the upper thoracic oesophagus under vision using a special videomediastinoscope. Six patients with oesophageal carcinoma or high-grade dysplasia in Barrett's oesophagus were selected for this operation over the period from October 2000 to December 2001. The operation was completed by minimally invasive access in 4 of the 6 patients. The mean duration of the operation was 240 minutes, and the postoperative hospital stay 9.5 days. One patient required endoscopic pneumatic dilatation of the pylorus 2 weeks after surgery. This technique enhances the safety of conventional oesophagectomy without thoracotomy by avoiding the "blind" dissection of the upper mediastinum. The advantages of laparoscopy include superior staging of the disease, gastric mobilization, and lymphadenectomy of the lower mediastinum. The ideal candidates for this operation are patients with high-grade dysplasia or T1-N0 adenocarcinoma arising from Barrett's oesophagus.
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DOI   
PMID 
R Incarbone, L Bonavina, G Saino, D Bona, A Peracchia (2002)  Outcome of esophageal adenocarcinoma detected during endoscopic biopsy surveillance for Barrett's esophagus.   Surg Endosc 16: 2. 263-266 Feb  
Abstract: BACKGROUND: In an attempt to reduce mortality from esophageal adenocarcinoma, it has been recommended to enroll patients with Barrett's esophagus in endoscopic surveillance programs in order to detect malignant degeneration at an early and possibly curable stage. The aim of this study was to assess the impact of endoscopic biopsy surveillance on outcome of Barrett's adenocarcinoma. METHODS: Between November 1992 and June 2000, 312 patients with histologically proven esophageal adenocarcinoma were referred to our department. Ninety-seven of these patients had Barrett's adenocarcinoma. In 12 (12.2%) patients, cancer was discovered during endoscopic surveillance for Barrett's metaplasia. RESULTS: The prevalence of gastroesophageal reflux disease in the Barrett's group was 38.8% versus 8% (p < 0.01) in non-Barrett's patients. In the surveyed group, there were 9 (75%) early stage tumors (Tis-1/N0) versus 9 (10.6%, p < 0.01) in the nonsurveyed patients. Three of 5 surveyed patients operated on for high-grade dysplasia proved to have invasive carcinoma in the esophagectomy specimen. All surveyed patients were alive at a median follow-up of 48 months; the median survival in the nonsurveyed group was 24 +/- 3 months (p < 0.01). CONCLUSION: Endoscopic surveillance of Barrett's esophagus provides early detection of malignant degeneration and a better long-term survival than in nonsurveyed patients.
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2001
 
PMID 
A Peracchia, L Bonavina, M Botturi, M Pagani, A Via, G Saino (2001)  Current status of surgery for carcinoma of the hypopharynx and cervical esophagus.   Dis Esophagus 14: 2. 95-97  
Abstract: Hypopharynx and cervical esophagus represent a critical location for a squamous cell carcinoma, a neoplasm that usually requires extensive surgery. Although morbidity and mortality of resection have markedly decreased over the past decade, the major issue in these patients remains quality of life owing to the need for combination with a laryngectomy to provide radical treatment. Chemoradiation therapy has the potential to downstage and even cure the disease without altering quality of life dramatically. Today, in the absence of randomized trials, the choice between surgery and definitive chemoradiotherapy should be based on clear information and the patient's preference. Salvage surgery is feasible and effective in selected patients.
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DOI   
PMID 
L Bonavina, G Saino, D Bona, M Abraham, A Peracchia (2001)  Thoracoscopic management of chylothorax complicating esophagectomy.   J Laparoendosc Adv Surg Tech A 11: 6. 367-369 Dec  
Abstract: BACKGROUND: Chylothorax is a relatively uncommon complication of esophageal surgery that may lead to severe respiratory, nutritional, and immunologic deficiencies. PATIENTS AND METHODS: Between 1992 and 2000, 3 of 316 patients (0.9%) undergoing transthoracic esophagectomy for carcinoma developed postoperative chylothorax. Two of them had previously been treated with neoadjuvant chemoradiation, and one had been submitted to esophagogastric resection through a left thoracotomy. After a 2-week trial of total parenteral nutrition and drainage, two patients underwent thoracic duct ligation via thoracotomy. In the last patient, the operation was completed by thoracoscopy. The azygos vein and the periaortic tissue above the diaphragm were encircled en bloc by a right-angled clamp, and a roticulating endostapler was applied. RESULTS: Reoperation was successful in all patients. The postoperative hospital stay was 4 days. CONCLUSION: Thoracoscopy is a safe and effective procedure for the treatment of chylothorax complicating esophagectomy. Given the minimal trauma to the patient, early thoracoscopic reoperation can be advocated in patients with high-output chyle loss in order to reduce the hospital stay.
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PMID 
E Ancona, A Ruol, S Santi, S Merigliano, V C Sileni, H Koussis, G Zaninotto, L Bonavina, A Peracchia (2001)  Only pathologic complete response to neoadjuvant chemotherapy improves significantly the long term survival of patients with resectable esophageal squamous cell carcinoma: final report of a randomized, controlled trial of preoperative chemotherapy versus surgery alone.   Cancer 91: 11. 2165-2174 Jun  
Abstract: BACKGROUND: Surgery is the standard treatment for patients with resectable esophageal carcinoma, but the long term prognosis of these patients is unsatisfactory. Some randomized trials of preoperative chemotherapy suggest that the prognosis of patients who respond may be improved. METHODS: This randomized, controlled trial compared patients with clinically resectable esophageal epidermoid carcinoma who underwent surgery alone (Arm A) with those who received preoperative chemotherapy (Arm B). Overall survival and the prognostic impact of major response to chemotherapy were analyzed. Forty-eight patients were enrolled in each arm. Chemotherapy consisted of two or three cycles of cisplatin (100 mg/m2 on Day 1) and 5- fluorouracil (1000 mg/m2 per day continuous infusion on Days 1-5). In both study arms, transthoracic esophagectomy plus two-field lymphadenectomy was performed. The two groups were comparable in terms of patient characteristics. RESULTS: Forty-seven patients were evaluable in each arm. The curative resection rate was 74.4% (35 of 47 patients) in Arm A and 78.7% (37 of 47 patients) in Arm B. Treatment-related mortality was 4.2% in both arms. The response rate to preoperative chemotherapy was 40% (19 of 47 patients), including 6 patients (12.8%) who achieved a pathologic complete responses. Overall survival was not improved significantly. The 19 patients in Arm B who responded to chemotherapy and underwent curative resection had significantly better 3-year and 5-year survival rates (74% and 60%, respectively) compared with both nonresponders (24% and 12%, respectively; P = 0.0002) and patients in Arm A who underwent complete resection (46% and 26%, respectively; P = 0.01): Patients who achieved a pathologic complete response (P = 0.01), but not those who achieved a partial response (P = 0.2), had significantly improved survival. CONCLUSIONS: Patients with resectable esophageal carcinoma who underwent preoperative chemotherapy and obtained a pathologic complete response had a significantly improved long term survival. Major efforts should be undertaken to identify patients before neoadjuvant treatments who are likely to respond.
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PMID 
M Montorsi, R Santambrogio, P Bianchi, E Opocher, G P Cornalba, G Dapri, L Bonavina, M Zuin, M Podda (2001)  Laparoscopy with laparoscopic ultrasound for pretreatment staging of hepatocellular carcinoma: a prospective study.   J Gastrointest Surg 5: 3. 312-315 May/Jun  
Abstract: Laparoscopy with laparoscopic ultrasound (L-LUS) has proved to be superior to conventional CT imaging in the staging of hepatocellular carcinoma (HCC). The aim of our prospective study was to evaluate the efficacy of L-LUS as compared with currently available imaging techniques (spiral CT or Lipiodol CT) in patients with HCC and liver cirrhosis. From January 1998 to May 2000, 70 consecutive patients (50 men and 20 women; mean age 67 +/- 7 years) were enrolled. Liver cirrhosis was related to chronic hepatitis C virus infection in 55, hepatitis B virus infection in seven, and alcohol abuse in eight patients. Preoperative diagnostic workup included the following: 70 ultrasound examinations of the liver, 23 CT scans after Lipiodol arteriography, and 53 spiral CT scans. A single lesion was found in 39 patients, two lesions in 20 patients, and three lesions in 11 patients. L-LUS was performed in all patients under general anesthesia using a two- to three-trocar technique. The examination was completed in 68 patients (97%); in two cases extensive adhesions prevented the L-LUS examination. L-LUS yielded additional information in 39 patients (57%). New histologically proved HCC lesions were detected in 14 patients (in the same liver segment in 4 cases and in different liver segments in 10 cases), and an adrenal metastasis was seen in one patient. In 23 patients, benign nodules were identified as regenerative macronodules, low-grade dysplastic nodules, or small hemangiomas. In 10 patients, correct localization of the primary lesion was detected by L-LUS in comparison with the preoperative liver location. In our experience, L-LUS is a safe and reliable procedure. It provides superior information (intraoperative histologic confirmation) for the diagnosis and pretreatment staging of HCC in patients with cirrhosis when compared with current radiologic imaging techniques.
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PMID 
S Romagnoli, M Roncalli, D Graziani, B Cassani, E Roz, L Bonavina, A Peracchia, S Bosari, G Coggi (2001)  Molecular alterations of Barrett's esophagus on microdissected endoscopic biopsies.   Lab Invest 81: 2. 241-247 Feb  
Abstract: Alterations in proto-oncogenes and tumor suppressor genes play a role in the sequence from Barrett's metaplasia to esophageal adenocarcinoma. The present study aims to ascertain whether molecular abnormalities take place in Barrett's metaplasia and low-grade dysplasia and to correlate them with the histological features of the esophageal mucosa. Forty-one formalin-fixed, paraffin-embedded endoscopic esophageal biopsies were classified according to the type of metaplastic changes (noncolumnar fundic and cardial metaplasia; columnar metaplasia, with and without intestinal features). After microdissection samples were examined for loss of heterozygosity (LOH) using polymorphic markers on 5q (D5S82), corresponding to APC (adenomatous polyposis coli) gene, 13q (CA repeat in intron 2 position 14815 to 14998 of the retinoblastoma gene), 17p (D17S513) corresponding to p53 locus, and for p53 mutations. Molecular alterations including LOH, allelic imbalance, and microsatellite instability could be detected in all types of metaplastic changes and sporadically in the squamous epithelium adjacent to the metaplastic tissue. Molecular alterations involving microsatellites D5S82 and the CA repeat inside the retinoblastoma gene were more frequent in nonintestinal metaplasia whereas those involving the p53 locus took place in columnar intestinal metaplasia and in low-grade dysplasia. Clonal changes were demonstrated in different metaplastic areas in three patients. Genetic alterations comprising LOH and microsatellite instability characterize Barrett's mucosa and appear related to the type of metaplastic change. Some of them precede the development of intestinal metaplasia, suggesting that genetic alterations take place earlier than previously thought.
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2000
 
PMID 
R Incarbone, L Bonavina, S Szachnowicz, G Saino, A Peracchia (2000)  Rising incidence of esophageal adenocarcinoma in Western countries: is it possible to identify a population at risk?   Dis Esophagus 13: 4. 275-278  
Abstract: Symptomatic gastroesophageal reflux disease (GERD) and Barrett's mucosa are risk factors for esophageal adenocarcinoma (ADC). The aim of this study was to analyze the anthropometric features and prevalence of GERD in patients with ADC compared with patients with squamous cell carcinoma (SCC) and control subjects. A total of 262 patients with ADC and 302 with SCC were enrolled consecutively. A control group of 262 individuals, sex and age matched to the ADC group, and an additional group of 138 patients with GERD confirmed by 24-h pH monitoring were used for comparison. The prevalence of symptomatic GERD was 32.4% in the subgroup of patients with Barrett's ADC (male-female=6.4:1; mean age=62 years) vs. 8% in those with gastric cardia carcinoma (P< 0.01), 3% in the SCC group (P< 0.01), and 10% in the control group (P< 0.01). ADC patients, controls and refluxers had similar body mass index (BMI) that was significantly higher than in the SCC group (P< 0.05). Whether surveillance endoscopy is indicated in men over 50 years with a long-lasting history of GERD and a BMI >25 remains to be determined.
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PMID 
H Feussner, L Bonavina, J M Collard, J Holste, S Freys, O P Horváth, T Rüdiger, H J Stein, K H Fuchs (2000)  Experimental evaluation of the safety and biocompatibility of a new antireflux prosthesis.   Dis Esophagus 13: 3. 234-239  
Abstract: Previous studies have shown that encircling of the esophagogastric junction by a semiabsorbable scarf effectively prevents gastroesophageal reflux. The present study was performed to assess the long-term safety and biocompatibility of this type of scarf. The semiabsorbable scarf was implanted into 20 dogs either laparoscopically or via laparotomy. Pre- and post-operatively, contrast radiography, esophageal manometry, and upper gastrointestinal endoscopy were performed. No cases of perforation, stricture formation or other adverse effects were found after 1 and 2 years. It is concluded that the new type of scarf is without any adverse side-effects. Functional evaluation in reflux patients appears to be warranted.
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1999
 
PMID 
R Incarbone, L Bonavina, M Reitano, A Peracchia (1999)  Esophageal function studies in the management of gastroesophageal reflux disease.   Int J Surg Investig 1: 4. 351-356  
Abstract: BACKGROUND: Esophageal function testing, i.e. esophageal manometry and 24-h pH monitoring, are usually carried out to diagnose gastroesophageal reflux disease (GERD) in patients with atypical symptoms, when there is no evidence of esophagitis at endoscopy, or following previous unsuccessful surgery. Additionally, these studies should be considered mandatory before surgery to confirm the diagnosis and to tailor the procedure to the motility pattern of the individual patient. AIM: The aim of this study was to assess the role of esophageal function studies in the management of patients with GERD. METHODS: Patients with a mechanically defective lower esophageal sphincter (LES) and abnormal esophageal acid exposure proven at 24-h pH monitoring were considered for surgery. A 360 degrees fundoplication (Nissen) was performed in patients with good esophageal motility, whereas a partial 180 degrees fundoplication (Toupet) in patients with a defective motility. Five hundred and eighty-six patients were referred to our laboratory for symptoms suggestive of GERD between November 1992 and April 1999. RESULTS: Twenty-four hour esophageal pH monitoring was positive in 65.5% of these patients; manometry showed a defective lower esophageal sphincter and a defective esophageal body motility in 57.8% and 21.7% respectively. One hundred and two patients underwent a total fundoplication, and 43 patients a partial wrap. At a mean follow-up of 36 months (range 5-69) the actuarial success rate in the control of reflux was 90%. Three (2.9%) patients undergoing a Nissen fundoplication complained of persistent dysphagia; two of them had preoperative esophageal body dysfunction. CONCLUSION: Esophageal function studies allow proper selection of patients for surgery and guide in the choice of the antireflux operation.
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DOI   
PMID 
Peracchia, Bonavina, Incarbone, Floridi (1999)  Results of surgical therapy in patients with adenocarcinoma of the esophagus and cardia.   Gastric Cancer 2: 2. 89-94 Aug  
Abstract: BACKGROUND: Adenocarcinoma of the esophagus and cardia is a challenging disease for the surgeon. Delay in diagnosis, nodal involvement, and incompleteness of resection have an adverse effect on long-term prognosis. Efforts are currently oriented to identify patients who may benefit from extensive resection.METHODS: Between November 1992 and May 1998, 218 patients with histologically proven adenocarcinoma of the distal esophagus or cardia were referred to our Department. In 6 patients (10.2%) cancer was discovered during endoscopic surveillance for Barrett's metaplasia. Overall, 147 patients (67%) underwent resection. An Ivor-Lewis approach was used in 121 patients; of these, 51 underwent an extended mediastinal lymph node dissection.RESULTS: Median cumulative survival was 25.9 +/- 3.1 months in patients undergoing resection, and 7 +/- 1.3 months in patients having palliation ( P < 0.01). Survival was significantly higher in patients with negative nodes than in those with lymph node metastases (54 +/- 12.9 versus 17 +/- 2.8 months; P < 0.01). Six of the 51 patients (11.8%) undergoing extended lym-phadenectomy had metastatic upper mediastinal nodes. Additional serial sections and immunohistochemistry were performed in 46 patients. In 6 of 18 patients (33.3%) with negative nodes at conventional hematoxylin-eosin examination, immunohistochemistry demonstrated micrometastases in the lesser curvature, paracardial, peripancreatic, or lower mediastinal nodes. Three of these patients had recurrent disease within the first year of follow-up.CONCLUSIONS: Early diagnosis remains the prerequisite for curative treatment of adenocarcinoma of the esophagus and cardia. Endoscopic surveillance appears to be warranted in patients with Barrett's metaplasia. When a curative resection is attempted, extended lymphadenectomy improves tumor staging and may prevent local recurrences. Serial sections and immunohistochemistry provide additional accuracy in the staging of the disease and may prove useful to select patients for adjuvant therapy.
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