Pulmonary embolism : an experimental and clinical study

Thesis (M.S.) -- University of Adelaide, Department of Surgery, 198

A Selective Approach to Bleeding Esophageal Varices

It is possible that the best results of treatment for bleeding esophageal varices will come when a selective approach is used. In patients bleeding acutely and in patients with poor liver function shunt operations should be avoided, and a direct attack on the varices with either sclerosant therapy, percutaneous obliteration, or staple gun gastro-esophageal transsection should be carried out. In patients who have stopped bleeding, or those in whom elective treatment is being undertaken, the best operation at present appears to be selective distal splenorenal shunt

Five-year outcome after laparoscopic anterior partial versus Nissen fundoplication: four randomized trials

Author version made available in accordance with the publisher's policy.Objective: To compare longer term (5-year) outcomes for reflux control and post-surgery side effects following laparoscopic anterior (90˚ and 180˚) partial vs. Nissen fundoplication for gastroesophageal reflux. Summary Background Data: Laparoscopic Nissen fundoplication is the most frequently performed surgical procedure for gastroesophageal reflux. It achieves excellent control of reflux, but in some patients is followed by troublesome side effects. To reduce the risk of side effects laparoscopic anterior partial fundoplication variants have been advocated, although some studies suggest poorer reflux control. Methods: From 1995 to 2003, 461 patients with gastroesophageal reflux were enrolled in 4 randomized controlled trials comparing anterior partial vs. Nissen fundoplication. Two trials evaluated anterior 180˚, and 2 anterior 90˚ partial fundoplication. The original trial data were combined and a re-analysis from original data was undertaken to determine outcomes at 5-years follow-up. Reflux symptom control and side effects were evaluated in a blinded fashion using standardized questionnaires, including 0-10 analog scores (0=no symptoms, 10=severe symptoms). Results: At 5 years, patients who underwent an anterior 90˚ or 180˚ partial fundoplication had less side effects compared with Nissen fundoplication and were equally satisfied with the overall outcome. Reflux control, measured by heartburn scores and antisecretory medication use, was similar for anterior 180˚ partial vs. Nissen fundoplication, but inferior after anterior 90˚ partial vs. Nissen fundoplication. Conclusions: Anterior 180˚ partial fundoplication achieves durable control of reflux symptoms and less side effects compared with Nissen fundoplication. Although reflux control following anterior 90˚ partial fundoplication appears less effective than after Nissen fundoplication. This data supports the use of anterior 180˚ partial fundoplication for the surgical treatment of gastroesophageal reflux

Randomized controlled trial of laparoscopic anterior 180° partial versus posterior 270° partial fundoplication.

Article first published online: 28 NOV 2013. This item is under embargo for a period of 12 months from the date of publication, in accordance with the publisher's policy.BACKGROUND: Previous trials show good outcomes following anterior and posterior partial versus Nissen fundoplication for gastro-oesophageal reflux. However, it is unclear which partial fundoplication performs best. This study compared anterior 180° versus posterior 270° fundoplication. METHODS: At three hospitals, patients were randomized to anterior 180° versus posterior 270° partial fundoplication, and clinical outcomes were determined using a structured questionnaire at 3, 6 and 12 months. Heartburn, dysphagia and satisfaction were assessed using 0-10 analoue scales, and adverse outcomes and side effects were determined. Endoscopy, manometry and pH monitoring were performed 6 months after surgery. RESULTS: Forty-seven patients were randomized to anterior (n = 23) versus posterior (n = 24) fundoplication. Clinical outcomes for 93-98% of patients were available at each follow-up point. At 12 months, the mean heartburn score was higher following anterior fundoplication (2.7 versus 0.8, P = 0.045), although differences were not significant at earlier follow-up. Conversely, following posterior fundoplication, patients were less able to belch at 3 (56% versus 16%, P = 0.013) and 6 months (43% versus 9%, P = 0.017). No significant differences were demonstrated for dysphagia. Both groups had high rates of satisfaction with the outcome - 85% versus 86% satisfied at 12 months follow-up. CONCLUSION: Both partial fundoplications are effective treatments for gastro-oesophageal reflux. Posterior partial fundoplication is associated with less reflux symptoms offset by more side effects.Australian National Health & Medical Research Council

Laparoscopic repair of very large hiatus hernia with sutures versus absorbable mesh versus nonabsorbable mesh a randomized controlled trial

Author version made available in accordance with pubilsher policy. 12 month embargo applies from the date of publication (1 Feb 2015).Objective: Determine whether absorbable or non-absorbable mesh in repair of large hiatus hernias reduces the risk of recurrence, compared to suture repair. Summary Background Data: Repair of large hiatus hernia is associated with radiological recurrence rates of up to 30%, and to improve outcomes mesh repair has been recommended. Previous trials have shown less short term recurrence with mesh, but adverse outcomes limit mesh use. Methods: Multicentre prospective double blind randomized controlled trial of 3 methods of repair; sutures vs. absorbable mesh vs. non-absorbable mesh. Primary outcome - hernia recurrence assessed by barium meal X-ray and endoscopy at 6 months. Secondary outcomes - clinical symptom scores at 1, 3, 6 and 12 months. Results: 126 patients enrolled - 43 sutures, 41 absorbable mesh and 42 non-absorbable mesh. 96.0% were followed to 12 months, with objective follow-up data in 92.9%. A recurrent hernia (any size) was identified in 23.1% following suture repair, 30.8% - absorbable mesh, and 12.8% - non-absorbable mesh (p=0.161). Clinical outcomes were similar, except less heartburn at 3 & 6 months and less bloating at 12 months with non-absorbable mesh, and more heartburn at 3 months, odynophagia at 1 month, nausea at 3 & 12 months, wheezing at 6 months, and inability to belch at 12 months following absorbable mesh. The magnitude of the clinical differences were small. Conclusions: No significant differences were seen for recurrent hiatus hernia, and the clinical differences were unlikely to be clinically significant. Overall outcomes following sutured repair were similar to mesh repair

Metallothionien 3 expression is frequently down-regulated in oesophageal squamous cell carcinoma by DNA methylation

BACKGROUND: Metallothionein 3 (MT3) inhibits growth in a variety of cell types. We measured MT3 gene expression by RT-PCR, and DNA methylation in the MT3 promoter by combined bisulphite restriction analysis, in four oesophageal cancer cell lines and the resected oesophagus from 64 patients with oesophageal squamous cell carcinoma (SCC). RESULTS: MT3 expression was not detected in one of the four oesophageal cell lines. The MT3 promoter was methylated in all of the oesophageal cell lines, but the degree of methylation was greater in the non-expressing cell line. After treatment with 5-aza-2'-deoxycytidine there was a reduction in the degree of methylation, and an increase in MT3 expression, in each of the cell lines (p < 0.01). Methylation was detected in 52% (33 of 64) of primary SCC and 3% (2 of 62) of histologically normal resection margins. MT3 expression was measured in 29 tumours, 17 of which had methylation of MT3. The expression of MT3 was significantly less in the methylated tumours compared to either the unmethylated tumours (p = 0.03), or the matched margin (p = 0.0005). There was not a significant difference in MT3 expression between the tumour and the margin from patients with unmethylated tumour. No correlations were observed between methylation of MT3 and survival time, patient age, gender, smoking or drinking history, tumour stage, volume, or lymph node involvement. CONCLUSION: We conclude that MT3 expression is frequently down-regulated in oesophageal SCC, by DNA methylation, but that this is not a prognostic indicator

Similarity of aberrant DNA methylation in Barrett's esophagus and esophageal adenocarcinoma

Background Barrett's esophagus (BE) is the metaplastic replacement of squamous with columnar epithelium in the esophagus, as a result of reflux. It is the major risk factor for the development of esophageal adenocarcinoma (EAC). Methylation of CpG dinucleotides of normally unmethylated genes is associated with silencing of their expression, and is common in EAC. This study was designed to determine at what stage, in the progression from BE to EAC, methylation of key genes occurs. Results We examined nine genes (APC, CDKN2A, ID4, MGMT, RBP1, RUNX3, SFRP1, TIMP3, and TMEFF2), frequently methylated in multiple cancer types, in a panel of squamous (19 biopsies from patients without BE or EAC, 16 from patients with BE, 21 from patients with EAC), BE (40 metaplastic, seven high grade dysplastic) and 37 EAC tissues. The methylation frequency, the percentage of samples that had any extent of methylation, for each of the nine genes in the EAC (95%, 59%, 76%, 57%, 70%, 73%, 95%, 74% and 83% respectively) was significantly higher than in any of the squamous groups. The methylation frequency for each of the nine genes in the metaplastic BE (95%, 28%, 78%, 48%, 58%, 48%, 93%, 88% and 75% respectively) was significantly higher than in the squamous samples except for CDKN2A and RBP1. The methylation frequency did not differ between BE and EAC samples, except for CDKN2A and RUNX3 which were significantly higher in EAC. The methylation extent was an estimate of both the number of methylated alleles and the density of methylation on these alleles. This was significantly greater in EAC than in metaplastic BE for all genes except APC, MGMT and TIMP3. There was no significant difference in methylation extent for any gene between high grade dysplastic BE and EAC. Conclusion We found significant methylation in metaplastic BE, which for seven of the nine genes studied did not differ in frequency from that found in EAC. This is also the first report of gene silencing by methylation of ID4 in BE or EAC. This study suggests that metaplastic BE is a highly abnormal tissue, more similar to cancer tissue than to normal epithelium.Eric Smith, Neville J De Young, Sandra J Pavey, Nicholas K Hayward, Derek J Nancarrow, David C Whiteman, B Mark Smithers, Andrew R Ruszkiewicz, Andrew D Clouston, David C Gotley, Peter G Devitt, Glyn G Jamieson and Paul A Dre

Quality of Life Following Repair of Large Hiatal Hernia is Improved but not Influenced by Use of Mesh: Results From a Randomized Controlled Trial

Author version made available following 12 month embargo from date of publication (5 Feb 2015) in accordance with Publisher copyright policy.Introduction Laparoscopic surgery is the treatment of choice for repair of large hiatus hernia, but can be followed by recurrence. Repair with prosthetic mesh has been recommended to prevent recurrence, although complications following mesh repair have generated disagreement about whether or not mesh should be used. The early objective and clinical results of a randomized trial of repair with mesh vs. sutures have been reported, and revealed few differences. In the current study we evaluated quality of life outcomes within this trial at follow-up to 2 years. Methods In a multicenter prospective double-blind randomized trial three methods for repair of large hiatus hernia were compared: sutures vs. repair with absorbable mesh (Surgisis) vs. nonabsorbable (Timesh). Quality of life assessment using the Short-Form 36 (SF-36) questionnaire was undertaken at 3, 6, 12 and 24 months after surgery. SF-36 outcomes (8 individual scales and 2 composite scales) were determined for each group, and compared between groups, and across different follow-up points. Results 126 patients were enrolled - 43 sutures, 41 absorbable mesh and 42 non-absorbable mesh. 115 (91.3%) completed a preoperative questionnaire, and 113 (89.7%) completed the postoperative questionnaire at 3 months, 116 (92.1%) at 6 months, 114 (90.5%) at 12 months, and 91 (72.2%) at 24 months. The SF-36 Physical and Mental Component scores (PCS & MCS) improved significantly following surgery, and this improvement was sustained across 24 months follow-up (p<0.001 for PCS and MCS at each follow-up point). There were no significant differences between the groups for the component scores or the eight SF-36 subscale scores at each follow-up time. 29 individuals had a recurrence at 6 months follow-up, of which 9 were symptomatic. The PCS were higher in patients with recurrence vs. without (p<0.01), and in patients with a symptomatic recurrence vs. asymptomatic recurrence vs. no recurrence (p=0.001). Conclusion SF-36 measured quality of life improved significantly after repair of large hiatal hernia at up to 2 years follow-up, and there were no differences in outcome for the different repair techniques. The use of mesh vs. no mesh in repair of large hiatal hernia did not influence quality of life