David I. Watson

A learning curve for laparoscopic fundoplication. Definable, avoidable, or a waste of time?

OBJECTIVE The objective of this study was to determine whether a learning curve for laparoscopic fundoplication can be defined, and whether steps can be taken to avoid any difficulties associated with it. SUMMARY BACKGROUND DATA Although early outcomes after laparoscopic fundoplication have been promising, complications unique to the procedure have been described. Learning curve problems may contribute to these difficulties. Although training recommendations have been published by some professional bodies, there is disagreement about what constitutes adequate supervised experience before the solo performance of laparoscopic antireflux surgery, and the true length of the learning curve. METHODS The outcome of 280 laparoscopic fundoplications undertaken by 11 surgeons during a 46-month period was assessed prospectively. The experience was analyzed in three different ways: 1) by an assessment of the overall learning experience within chronologically arranged groups, 2) by an assessment of all individual experiences grouped according to the experience of individual surgeons, and 3) by a comparison of early outcomes of operations performed by the surgeons who initiated laparoscopic fundoplication with the early experience of surgeons beginning laparoscopic fundoplication later in the overall institutional experience. RESULTS The complication, reoperation, and laparoscopic to open conversion rates all were higher in the first 50 cases performed by the overall group, and in the first 20 cases performed by each individual surgeon. These rates were even higher in the initial first 20 cases, and the first 5 individual cases. However, adverse outcomes were less likely when surgeons began fundoplication later in the overall experience, when experienced supervision could be provided. CONCLUSIONS A learning curve for laparoscopic fundoplication can be defined. Experienced supervision should be sought by surgeons beginning laparoscopic fundoplication during their first 20 procedures. This should minimize adverse outcomes associated with an individuals learning curve.

Prospective double-blind randomized trial of laparoscopic Nissen fundoplication with division and without division of short gastric vessels.

OBJECTIVE To determine whether division of the short gastric vessels (SGVs) and full mobilization of the gastric fundus is necessary to reduce the incidence of postoperative dysphagia and other adverse sequelae of laparoscopic Nissen fundoplication. SUMMARY BACKGROUND DATA Based on historical and uncontrolled studies, division of the SGVs has been advocated during laparoscopic Nissen fundoplication to improve postoperative clinical outcomes. However, this modification has not been evaluated in a large prospective randomized trial. METHODS One hundred two patients with proven gastroesophageal reflux disease presenting for laparoscopic Nissen fundoplication were prospectively randomized to undergo fundoplication with (52 patients) or without (50 patients) division of the SGVs. Patients with esophageal motility disorders, patients requiring a concurrent abdominal procedure, and patients who had undergone previous antireflux surgery were excluded. Patients were blinded to the postoperative status of their SGVs. Clinical assessment was performed by a blinded independent investigator who used multiple standardized clinical grading systems to assess dysphagia, heartburn, and patient satisfaction 1, 3, and 6 months after surgery. Objective measurement of lower esophageal sphincter pressure, esophageal emptying time, and distal esophageal acid exposure and radiologic assessment of postoperative anatomy were also performed. RESULTS Operating time was increased by 40 minutes (median 65 vs. 105) by vessel division. Perioperative outcomes and complications, postoperative dysphagia, relief of heartburn, and overall satisfaction were not improved by dividing the SGVs. Lower esophageal sphincter pressure, acid exposure, and esophageal emptying times were similar for the two groups. CONCLUSION Division of the SGVs during laparoscopic Nissen fundoplication did not improve any clinical or objective postoperative outcome.

An evaluation of prognostic factors and tumor staging of resected carcinoma of the esophagus

Objective:To evaluate prognostic factors and tumor staging in patients after esophagectomy for cancer. Summary Background Data:Several reports have questioned the appropriateness of the sixth edition of the International Union Against Cancer (UICC) TNM guidelines for staging esophageal cancer. Additional pathologic characteristics, besides the 3 basic facets of anatomic spread (tumor, node, metastases), might also have prognostic value. Methods:All patients who underwent resection of the esophagus for carcinoma between January 1995 and March 2003 were extracted from a prospective database. Univariate and multivariate analysis was performed to identify prognostic factors for survival. The goodness of fit and accuracy of 3 staging models (UICC-TNM, Korst classification, Rice classification) predicting survival were assessed. Results:A total of 292 patients (mean age, 63 years) underwent esophagectomy. The 5-year overall survival rate was 29% (median, 21 months). pT-, pN-, pm-stage, and radicality of the resection were independent prognostic factors. Subdivision of T1 tumors into mucosal and submucosal showed significant differences in 5-year survival between both groups: 90% versus 47%, respectively (P = 0.01). Subdivision of pN-stage into 3 groups based on the number of positive nodes (0, 1–2, and >3 nodes positive) or the lymph node ratio (0, 0.01–0.2, and >0.2) also refined staging (P = 0.001 and P < 0.001, respectively). The current subclassification of M1 (M1a and M1b) is not warranted (P = 0.41). The staging model of Rice was more accurate than the UICC-TNM classification in predicting survival. Conclusion:This study supports the view that the current (6th edition) UICC-TNM staging model for esophageal cancer needs to be revised.

Division of Short Gastric Vessels at Laparoscopic Nissen Fundoplication: A Prospective Double-Blind Randomized Trial With 5-Year Follow-Up

ObjectiveTo determine whether division of the short gastric vessels at laparoscopic fundoplication confers long-term clinical benefit to patients. Summary Background DataDividing the short gastric vessels during surgery for gastroesophageal reflux is controversial. This prospective randomized study was designed to determine whether there is a benefit in terms of patient outcome at a minimum of 5 years after primary surgery. MethodsBetween May 1994 and October 1995, 102 patients undergoing a laparoscopic Nissen fundoplication were randomized to have their short gastric vessels either divided or left intact. By September 2000, 99 (50 no division, 49 division) patients were available for follow-up, and they all underwent a detailed telephone interview by an independent and masked investigator. ResultsThere were no significant differences between the groups at 5 years of follow-up in terms of the incidence of epigastric pain, regurgitation, odynophagia, early satiety, inability to belch, anorexia, nausea, vomiting, nocturnal coughing, and nocturnal wheezing. There was also no difference between the groups in the incidence of heartburn when determined by either yes/no questioning or a 0-to-10 visual analog scale. There was no difference between the groups in terms of the incidence and severity of dysphagia determined by yes/no questioning, 0-to-10 visual analog scales, or a composite dysphagia score. There was a significantly increased incidence of flatus production and epigastric bloating and a decreased incidence of ability to relieve bloating in patients who underwent division of the short gastric vessels. ConclusionsDivision of the short gastric vessels during laparoscopic Nissen fundoplication does not improve any measured clinical outcome at 5 years of follow-up and is associated with an increased incidence of “wind-related” problems.

Laparoscopic anterior 180-degree versus Nissen fundoplication for gastroesophageal reflux disease: systematic review and meta-analysis of randomized clinical trials

Objective:To compare short- and long-term outcome after 180-degree laparoscopic anterior fundoplication (180-degree LAF) with laparoscopic Nissen fundoplication (LNF). Summary of Background Data:LNF is currently the most frequently performed surgical therapy for gastroesophageal reflux disease. Alternatively, 180-degree LAF has been alleged to reduce troublesome dysphagia and gas-related symptoms, with similar reflux control. Methods:MEDLINE, EMBASE, Cochrane Library, and web of Knowledge CPCI-S were searched for randomized clinical trials comparing primary 180-degree LAF with LNF. The methodological quality was evaluated to assess bias risk. Primary outcomes were esophageal acid exposure, esophagitis, heartburn score, dilatation for dysphagia, modified Dakkak dysphagia score (0–45), and reoperation rate. Meta-analysis was conducted at 1 and 5 years. Results:Five distinct randomized clinical trials comparing 180-degree LAF (n = 227) with LNF (n = 231) were identified. At 1 year, the Dakkak dysphagia score [2.8 vs 4.8; weighted mean difference: −2.25; 95% confidence interval (CI): −2.66 to −1.83; P < 0.001], gas bloating [11% vs 18%; relative risk (RR) 0.59; 95% CI: 0.36–0.97; P = 0.04], flatulence (14% vs 25%; RR: 0.57; 95% CI: 0.35–0.91; P = 0.02), inability to belch (19% vs 31%; RR: 0.63; 95% CI: 0.40–0.99; P = 0.05), and inability to relieve bloating (34% vs 44%; RR: 0.74; 95% CI: 0.55–0.99; P = 0.04) were lower after 180-degree LAF. Esophageal acid exposure (standardized mean difference: 0.19; 95% CI: −0.07 to 0.46; P = 0.15), esophagitis (19% vs 13%; RR: 1.42; 95% CI: 0.69–2.91; P = 0.34), heartburn score (standardized mean difference: 1.27; 95% CI:−0.36 to 2.90; P = 0.13), dilatation rate (1.4% vs 2.8%; RR: 0.60; 95% CI: 0.19–1.91; P = 0.39), reoperation rate (5.7% vs 2.8%; RR: 2.08; 95% CI: 0.80–5.41; P = 0.13), perioperative outcome, regurgitation, proton pump inhibitor (PPI) use, lower esophageal sphincter pressure, and patient satisfaction were similar after 180-degree LAF and LNF. At 5 years, the Dakkak dysphagia score, flatulence, inability to belch, and inability to relieve bloating remained lower after 180-degree LAF. The 5-year heartburn score, dilatation rate, reoperation rate, PPI use, and patient satisfaction were similar. Conclusions:At 1 and 5 years, dysphagia and gas-related symptoms are lower after 180-degree LAF than after LNF, and esophageal acid exposure and esophagitis are similar, with no differences in heartburn scores, patient satisfaction, dilatations, and reoperation rate. These results lend level 1a support for the use of 180-degree LAF for the surgical treatment of gastroesophageal reflux disease.

Minimally Invasive Versus Open Esophagectomy for Patients With Esophageal Cancer

BACKGROUND Minimally invasive esophagectomy (MIE) compared with open esophagectomy (OE) has been shown to have clinical advantages, but selection bias is present. METHODS All patients undergoing MIE or OE for cancer between 1999 and 2007 were eligible for analysis. To minimize selection bias, only patients who also met the selection criteria for the thoracoscopic approach were included in the open esophagectomy group. RESULTS Fifty-six patients underwent MIE and 98 OE. No significant differences in demographics or pathologic data between groups occurred, with the exception of thoracic epidural analgesia (OE 98%, MIE 71.1%, p < 0.001), and neoadjuvant treatment (OE 50.5%, MIE 71.4%, p = 0.016). Morbidity and in-hospital death were not significantly different. Duration of surgery was longer in MIE (250 vs 209 minutes, p < 0.001) and blood loss less (320 mL vs 857 mL, p < 0.001). Intensive care unit stay was shorter in MIE (3.0 vs 6.8 days, p = 0.022). The relative risk (RR) for in-hospital death was 0.57 (p = 0.475) if the patients underwent MIE. After adjusting for thoracic epidural analgesia, the RR was 0.29 (p = 0.213) for the MIE group. The RR for surgical morbidity was 1.47 (p = 0.154) for patients undergoing MIE. Neoadjuvant treatment increased the RR for surgical morbidity to 1.78 (p = 0.028). No difference between the two groups concerning survival occurred. CONCLUSIONS The MIE is comparable with the OE. In MIE, neoadjuvant treatment increased the risk of surgical morbidity. Thoracic epidural analgesia in MIE reduced the risk of in-hospital death and should be considered for all patients undergoing esophagectomy.

MicroRNA profiling of Barrett's oesophagus and oesophageal adenocarcinoma

The genetic changes that drive metaplastic progression from squamous oesophageal mucosa toward intestinal metaplasia and adenocarcinoma are unclear. The aberrant expression of microRNAs (miRNAs) is involved in the development of cancer. This study examined whether miRNAs play a role in the development of oesophageal adenocarcinoma.

Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis

Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n = 40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC.

Ten‐year clinical outcome of a prospective randomized clinical trial of laparoscopic Nissen versus anterior 180° partial fundoplication

A randomized trial of laparoscopic Nissen fundoplication and anterior 180° partial fundoplication was undertaken to determine whether the anterior procedure might reduce the incidence of dysphagia and other adverse outcomes following surgery for gastro‐oesophageal reflux disease. This study evaluated clinical outcomes after 10 years.

Outcome of laparoscopic Nissen fundoplication in patients with disordered preoperative peristalsis.

BACKGROUND: A 360 degrees or Nissen fundoplication remains controversial in patients with disordered peristalsis, some surgeons preferring a partial wrap to minimise postoperative dysphagia. AIM: To evaluate symptoms and manometric outcome in patients with disordered peristalsis after Nissen fundoplication. PATIENTS: In an initial series of 345 patients studied prospectively, 31 patients who had undergone a Nissen fundoplication had disordered peristalsis. Using preoperative manometry, patients were classified as: equivocal primary peristalsis (eight patients); abnormal primary peristalsis (four patients); abnormal maximal contraction pressure (13 patients); abnormal primary peristalsis and maximal contraction pressure (six patients). METHODS: Postoperatively, patients underwent a barium meal, oesophageal manometry and standardised clinical review by a blinded scientific officer. RESULTS: Twenty eight (90%) patients had satisfaction scores of at least 8 out of a maximum of 10 and all would undergo surgery again. Whereas 15 (48%) patients had dysphagia scores greater than 4/10 preoperatively, only two (6%) had these scores at one year. Improved peristalsis was seen in 78% of postoperative manometric studies, and mean preoperative lower oesophageal sphincter pressure increased from 6.6 (range 0-21) mm Hg to 19 (4-50) mm Hg. CONCLUSIONS: These results are similar to the overall group of 345 patients and suggest that disordered peristalsis, and possibly even absent peristalsis, is not a contraindication to Nissen fundoplication as performed in these patients.