Adjuvant statin therapy for oesophageal adenocarcinoma: the STAT-ROC feasibility study.

BACKGROUND: Statins inhibit proliferative signalling in oesophageal adenocarcinoma (OAC) and their use is associated with better survival in observational studies. The present study was undertaken to examine the feasibility of assessing adjuvant statin therapy in patients with operable OAC in a phase III RCT. METHODS: For this multicentre, double-blind, parallel-group, randomized, placebo-controlled feasibility trial, adults with OAC (including Siewert I-II lesions) who had undergone oesophagectomy were centrally allocated (1 : 1) to simvastatin 40 mg or matching placebo by block randomization, stratified by centre. Participants, clinicians and investigators were blinded to treatment allocation. Patients received treatment for up to 1 year. Feasibility outcomes were recruitment, retention, drug absorption, adherence, safety, quality of life, generalizability and survival. RESULTS: A total of 120 patients were assessed for eligibility at four centres, of whom 32 (26·7 per cent) were randomized, 16 in each group. Seven patients withdrew. Participants allocated to simvastatin had lower low-density lipoprotein cholesterol levels by 3 months (adjusted mean difference -0·83 (95 per cent c.i. -1·4 to -0·22) mmol/l; P = 0·009). Median adherence to medication was greater than 90 per cent between 3 and 12 months' follow-up. Adverse events were similar between the groups. Quality-of-life data were complete for 98·3 per cent of questionnaire items. Cardiovascular disease, diabetes and aspirin use were more prevalent in the non-randomized group, whereas tumour site, stage and grade were similar between groups. Survival estimates were imprecise. CONCLUSION: This RCT supports the conduct and informs the design considerations for a future phase III trial of adjuvant statin therapy in patients with OAC. Registration number: ISRCTN98060456 (www.isrctn/com).

ANTECEDENTES: Las estatinas inhiben las señalizaciones proliferativas en el adenocarcinoma de esófago (oesophageal adenocarcinoma, OAC) y su uso se asocia con mejor supervivencia en estudios observacionales. El presente estudio se llevó a cabo para examinar la viabilidad de evaluar el tratamiento adyuvante con estatinas en pacientes con OAC operable en un ensayo aleatorizado y controlado de fase III. MÉTODOS: En este ensayo de viabilidad controlado por placebo, aleatorizado, de grupos paralelos, doble ciego y multicéntrico, los pacientes adultos con OAC (incluyendo lesiones Siewert I/II) que fueron sometidos a esofaguectomía se asignaron de forma centralizada (1:1) a tratamiento con simvastatina 40 mg o placebo equivalente mediante aleatorización en bloques, estratificados por centro. Los participantes, los clínicos y los investigadores desconocían la asignación del tratamiento. Los pacientes recibieron el tratamiento hasta un año. Los resultados de viabilidad fueron reclutamiento, retención, absorción del fármaco, adherencia, seguridad, calidad de vida, generalización, y supervivencia. RESULTADOS: Un total de 120 pacientes fueron evaluados para elegibilidad en 4 centros, de los cuales 32 (26,7%) fueron aleatorizados, 16 en cada grupo. Siete pacientes abandonaron el ensayo. Los pacientes asignados a tratamiento con simvastatina tenían niveles de colesterol LDL más bajos a los 3 meses (diferencia media ajustada, −0,83 mmol/L, i.c. del 95% −1,4 a −0,22, P = 0,009). La mediana de la adherencia a la medicación fue mayor del 90% entre los 3-12 meses de seguimiento. Los eventos adversos fueron similares entre los grupos. Los datos de calidad de vida estaban completos en el 98,3% de las preguntas del cuestionario. Enfermedad cardiovascular, diabetes y uso de aspirina eran más prevalentes en el grupo no aleatorizado, mientras que la localización del tumor, el estadio y el grado fueron similares entre los grupos. Las estimaciones de supervivencia fueron imprecisas. CONCLUSIÓN: Este RCT apoya la realización e informa de las consideraciones de diseño para un futuro ensayo de fase III de tratamiento adyuvante con estatinas en pacientes con OAC.

Annual computed tomography scans do not improve outcomes following esophagectomy for cancer: a 10-year UK experience.

Evidence for the best approach to follow-up patients after esophagectomy for cancer is scant and conflicting, and has led to a wide variety in practice. The aim of this study was to evaluate whether our annual routine computed tomography (aCT) scan program changes outcomes. A retrospective review of 169 patients who underwent esophagectomy for cancer in our unit between 2001 and 2010 was performed. aCT scan was part of follow-up in all patients to 5 years. Minimum follow-up was 37 months. The primary outcome measure was survival. Recurrence was detected in 61 cases (36%). aCT scan diagnosed recurrence in only a minority of cases (17 cases, 28%). In the majority of patients, clinical evidence prompted an unplanned CT scan (uCT; 44 cases, 72%). There was no difference in unadjusted survival between the two groups (hazard ratio = 0.61, 95% confidence interval 0.34-1.08, P = 0.090), nor was one more likely to receive secondary oncological treatment (aCT 41% vs. uCT 44%, P = 1.000). When we adjusted survival patterns for confounding covariates, the uCT cohort showed a protective effect (hazard ratio = 0.54, 95% confidence interval 0.28-0.98, P = 0.042). These data suggest that aCT scans do not influence management or survival after esophagectomy. A consensus follow-up protocol for patients treated for esophageal cancer remains to be established.

Relationship between symptom response and oesophageal acid exposure after medical and surgical treatment for gastro-oesophageal reflux disease.

BACKGROUND: The relationship between symptom severity and objective evidence of gastro-oesophageal reflux disease (GORD) after medical and surgical treatment has recently been questioned. This study aimed to compare the symptomatic and physiological response (as measured by pHmetry) to the treatment of GORD by proton pump inhibitors (PPIs) and by laparoscopic antireflux surgery, and to examine the relationship between the patient's subjective and objective response to treatment of GORD. METHODS: Seventy patients underwent 24-h oesophageal pH measurement and DeMeester symptom assessment (for heartburn and regurgitation, grade 0-3) while off medical treatment, while taking PPIs and after laparoscopic fundoplication. RESULTS: The median percentage total time with oesophageal pH < 4 off treatment, during medical treatment and after fundoplication was 9.5, 4.3 and 0.5 per cent respectively. After medical treatment 30 patients became asymptomatic although 18 of these still had pathological reflux on pH testing. Of the 19 patients who remained symptomatic after surgery only two had pathological acid reflux. CONCLUSION: The symptomatic response of patients to either PPIs or antireflux surgery is a poor indicator of successful treatment in terms of reduced lower oesophageal acid exposure. A high proportion of patients whose symptoms are improved by PPIs still have pathological levels of acid reflux. Conversely, most patients who complain of reflux symptoms after antireflux surgery have no evidence of residual reflux on pHmetry.

Minimally invasive surgery for ileo-colic Crohn's disease.

OBJECTIVE: Patients requiring surgery for Crohn's disease are likely to undergo further surgery due to recurrent disease. A prospective study of laparoscopic-assisted surgery for ileo-colic Crohn's disease is reported. METHOD: Forty-one patients (26 female; median age 35 years) with ileo-colic Crohn's disease, without evidence of either fistula or abscess formation underwent laparoscopic-assisted surgery. All had medical therapy, including steroids, but had failed to respond or relapsed. Sixteen patients (39%) had previous surgery for Crohn's disease and 26 (63.4%) had previous abdominal surgery. Laparoscopic procedures (n=42) included ileocaecal/ileocolic resection (n=39), small bowel resection (n=1) and strictureplasty (n=2). RESULTS: The median operating time was 90 min (range 60-180). There were 6 conversions (14.6%). Of the 35 patients whose operation was completed laparoscopically, the median postoperative stay was 5 days (3-9) and the median time to full activity was 20 days (7-49). No major complications or death were recorded. The median follow up (34 out of 35) after surgery is 15.3 months (1-55). Twenty-four patients remain symptom free and 4 have minimal symptoms with no clinical or radiological evidence of recurrence of Crohn's disease. Six have however, developed recurrence requiring medical (n=5) and surgical (n=1) treatment. CONCLUSION: Laparoscopic-assisted surgery for Crohn's disease is feasible. It has the advantage of minimizing hospital stay and promoting early recovery in a group of patients who are likely to have further surgery due to the nature of the disease.

Synchronous perforation of a Meckel's diverticulum and a duodenal ulcer.

Dual perforation of the gastrointestinal tract is rare. We present a case of a patient who presented with a simultaneous perforation of a Meckel's diverticulum and a duodenal ulcer.

Compliance measurement of lower esophageal sphincter and esophageal body in achalasia and gastroesophageal reflux disease.

Little is known about the effect of achalasia and gastroesophageal reflux disease (GERD) on compliance of the esophageal body and the lower esophageal sphincter (LES). Twenty-two patients with achalasia, 14 with GERD, and 14 asymptomatic volunteers were assessed. Recording apparatus consisted of a specially developed PVC bag tied to a compliance catheter, a barostat, and a polygraph. Intrabag pressures were increased incrementally while the bag volume was recorded. In each subject, pressure-volume graphs were constructed for both the esophageal body and LES and the compliance calculated. In achalasia, compliance of the esophageal body was significantly higher (P < 0.01) than in controls, whereas LES compliance was similar. Patients with GERD had a highly compliant LES in comparison to both controls and to patients with achalasia (P < 0.01 and P < 0.001, respectively); however there was no difference in their esophageal body compliance. In conclusion, foregut motility disorders can cause changes in organ compliance that are detectable using a barostat and a suitably designed compliance bag. Further measurement of compliance may provide clues to the pathogenesis of these disorders.

Electrical stimulation for propelling endoscopes.

BACKGROUND: Methods are needed for propulsion of endoscopes and wireless video capsules along the small intestine. This work aims to test the hypothesis that electrical stimulation could propel an endoscope by stimulating muscular contraction. METHODS: Prototype acrylic ovoid-shaped devices were constructed with 2 stainless steel electrodes mounted on the tapered section. Five devices 15 to 23 mm diameter with a taper of 28 degrees to 40 degrees (included angle) were tested. When these devices were in contact with the bowel wall, electrostimulation was applied causing circular muscle contraction, which when applied to the taper of the ovoid resulted in forward propulsion of the device. The method does not induce peristalsis but works by stimulating local contraction. The device was tested in the small intestine and esophagus of anesthetized pigs. RESULTS: Electrostimulation caused the ovoid to advance rapidly (6 mm/sec) up and down the esophagus by inducing circular esophageal muscle contraction. When stimulated at 15 Hz with 30-ms pulses, the threshold for movement in the small intestine was 12 mA; at 20 mA the device moved reliably in either direction in the small intestine at speeds of up to 4.5 mm/sec and negotiated tight curves. CONCLUSION: Electrostimulation can move endoscopes in the small intestine.

An ambulant porcine model of acid reflux used to evaluate endoscopic gastroplasty.

BACKGROUND: There is a lack of suitable models for testing of therapeutic procedures for gastro-oesophageal reflux disease. Endoscopic sewing methods might allow the development of a new less invasive surgical approach to treatment of gastrointestinal disorders. AIMS: To develop an animal model of gastro-oesophageal reflux for testing the efficacy of a new antireflux procedure, endoscopic gastroplasty, performed at flexible endoscopy without laparotomy or laparoscopy. METHODS: At endoscopy a pH sensitive radiotelemetry capsule was sewn to the oesophageal wall, 5 cm above the lower oesophageal sphincter, in six large white pigs. Ambulant pH recordings (48-96 hours; total 447 hours) were obtained. The median distal oesophageal pH was 6.8 (range 6.4-7.3); pH was less than 4 for 9.3% of the time. After one week, endoscopic gastroplasty was performed by placing sutures below the gastro-oesophageal junction, forming a neo-oesophagus of 1-2 cm in length. Postoperative manometry and pH recordings (24-96 hours; total 344 hours) were carried out. RESULTS: Following gastroplasty, the median sphincter pressure increased significantly from 3 to 6 mm Hg and in length from 3 to 3.75 cm. The median time pH was less than 4 decreased significantly from 9.3% to 0.2%. CONCLUSIONS: These are the first long term measurements of oesophageal pH in ambulant pigs. The finding of spontaneous reflux suggested a model for studying treatments of reflux. Endoscopic gastroplasty increased sphincter pressure and length and decreased acid reflux.

A randomised controlled comparison of injection, thermal, and mechanical endoscopic methods of haemostasis on mesenteric vessels.

BACKGROUND AND AIMS: A randomised controlled comparison of haemostatic efficacy of mechanical, injection, and thermal methods of haemostasis was undertaken using canine mesenteric vessels to test the hypothesis that mechanical methods of haemostasis are more effective in controlling haemorrhage than injection or thermal methods. The diameter of arteries in human bleeding ulcers measures up to 3.45 mm; mesenteric vessels up to 5 mm were therefore studied. METHODS: Mesenteric vessels were randomised to treatment with injection sclerotherapy (adrenaline and ethanolamine), bipolar diathermy, or mechanical methods (band, clips, sewing machine, endoloops). The vessels were severed and haemostasis recorded. RESULTS: Injection sclerotherapy and clips failed to stop bleeding from vessels of 1 mm (n = 20) and 2 mm (n = 20). Bipolar diathermy was effective on 8/10 vessels of 2 mm but failed on 3 mm vessels (n = 5). Unstretched elastic bands succeeded on 13/15 vessels of 2 mm but on only 3/10 vessels of 3 mm. The sewing machine achieved haemostasis on 8/10 vessels of 4 mm but failed on 5 mm vessels (n = 5); endoloops were effective on all 5 mm vessels (n = 5). CONCLUSIONS: Only mechanical methods were effective on vessels greater than 2 mm in diameter. Some mechanical methods (banding and clips) were less effective than expected and need modification. Thermal and (effective) mechanical methods were significantly (p < 0.01) more effective than injection sclerotherapy. The most effective mechanical methods were significantly more effective (p < 0.01) than thermal or injection on vessels greater than 2 mm.

Antireflux operations at flexible endoscopy using endoluminal stitching techniques: an experimental study.

BACKGROUND: Three antireflux operations-gastroplasty, fundoplication, and anterior gastropexy-were developed for performance at flexible endoscopy without laparotomy or laparoscopy. METHODS: An endoscopic sewing machine mounted on a standard gastroscope, endoscopic knotting devices, overtube, and nylon thread were used to perform these operations in adult beagle dogs. RESULTS: Gastroplasty (n = 10) was accomplished by suturing the anterior and posterior wall of the stomach to create a gastric tube (neoesophagus) along the lesser curve. An anatomic arrangement similar to fundoplication (n = 6) was achieved by invaginating the esophagus and fixing it to the stomach 2 cm distal to the cardioesophageal junction. Anterior gastropexy (n = 6) was performed using a technique similar to that used in creating percutaneous gastrostomies. There was no mortality. Ninety percent of sutures were seen at repeat endoscopy at 4 to 8 week intervals. The gastroplasty group was selected for more extensive evaluation. Manometry using a three-channel perfused catheter system before and after the procedures showed an increase in the lower esophageal sphincter pressure (preoperative median 4.6 mm Hg; post-operative median 13.33 mm Hg, p = 0.008) and cardiac yield pressures (preoperative median 10 mm Hg; postoperative median 19 mm Hg, p = 0.007). CONCLUSIONS: This study demonstrates the feasibility of performing antireflux operations at flexible endoscopy, without laparoscopy or laparotomy, by use of endoluminal suturing techniques.

A comparison of the strength of knots tied by hand and at laparoscopy.

BACKGROUND: The strength of knots tied at laparoscopy was compared with that of hand-tied knots. STUDY DESIGN: The force needed to undo or break eight types of knots that were tied in fresh postmortem human stomachs was measured. The knotting performance of nylon, polyglactin 910, braided silk, polytetrafluoroethylene, braided polyester fiber, braided polyester suture, polyamide 66, and polydiaxone was also compared. RESULTS: Measurements of knot strength of two to six half hitches (hand tied) showed that four half hitches were necessary to tie a secure nonslipping knot with most monofilament threads (nylon, polytetrafluoroethylene, braided polyester suture, and polyamide 66), while three half hitches were adequate to secure a knot when polyglactin 910, braided polyester fiber, silk, and polydiaxone were used. Additional throws did not increase knot strength once the knot no longer slipped (p = NS). Some commonly tied knots, three half hitches and surgical knots at laparoscopy were weaker than the same hand-tied knots (p < 0.05) but an additional throw increased knot security (p < 0.01). Differences between laparoscopic and hand-tied knot strengths were greater for monofilament than multifilament threads. There was a wider distribution of strengths for laparoscopically tied than hand-tied knots. Four half hitches were the most secure configuration for laparoscopically tied knots and were significantly stronger than three half hitches and surgical knots (p < 0.01). The extracorporeally tied slipknot (Roeder loop) was significantly less secure than four half hitches (p < 0.05). CONCLUSIONS: This study demonstrates that laparoscopically formed knots may be weaker than those tied by hand and shows that improvements in knot strength at laparoscopy can be achieved by choice of optimal knot configuration for different suture materials.

Physiological and symptomatic outcome after laparoscopic gastric fundoplication.

The complications of open antireflux operations may be reduced by laparoscopic techniques. Fifteen patients of median age 42 (range 16-79) years with gastro-oesophageal reflux underwent laparoscopic fundoplication. Preoperative and postoperative assessment was by clinical scoring, oesophageal pH measurement and manometry. Median (range) operating time was 115 (60-210) min and hospital stay 3 (1-6) days, with no conversions to open operation and only one minor wound infection. Four patients had occasional reflux symptoms on postoperative assessment at a median of 7 weeks and nine had occasional dysphagia. Median DeMeester symptom scores improved from 4 to 1.5 (P = 0.001). There were significant increases in both lower oesophageal sphincter pressure and length. The nocturnal proportion of time at pH < 4 decreased from 9.6 to 0.05 per cent (P = 0.02), although the drop in total proportion of time at pH < 4 (10.4 to 2.2 per cent) was not statistically significant (P = 0.08). Early objective results of laparoscopic fundoplication show improved symptoms, decreased acid reflux and altered lower sphincter function. The procedure combines the benefits of early mobilization and reduced morbidity with the efficacy of the traditional open operation.

Knot tying at flexible endoscopy.

Four new knotting techniques were developed for use at flexible endoscopy: (1) half hitches tied with knot-pusher, (2) thread-locking device, (3) self-tightening slip-knot, and (4) externally releasable knot. Remoteness from site of action, access through small-diameter orifice, and difficulty in applying lateral traction to tighten knots are problems met in knot tying at endoscopy. All four knotting techniques were studied in experiments on postmortem human stomachs and used for radio-telemetry studies and anti-reflux operations in survival studies in dogs using endoscopic sewing techniques. Half hitches tied at endoscopy with a knot-pusher were also used in human studies to treat esophageal reflux and secure pH radio-telemetry capsules for long-term measurements. Externally releasable knots were used to secure nasogastric tubes to the stomach of five patients for long-term nutrition. Knot tying is feasible at flexible endoscopy by a variety of new techniques. Endoscopically tied knots can be as secure as surgically hand-tied knots and have been used successfully in man.