Pre-therapy mRNA expression of TNF is associated with regimen-related gastrointestinal toxicity in patients with esophageal cancer: a pilot study.

PURPOSE: Esophageal cancer has a high mortality rate, and its multimodality treatment is often associated with significant rates of severe toxicity. Effort is needed to uncover ways to maximize effectiveness of therapy through identification of predictive markers of response and toxicity. As such, the aim of this study was to identify genes predictive of chemoradiotherapy-induced gastrointestinal toxicity using an immune pathway-targeted approach. METHODS: Adults with esophageal cancer treated with chemotherapy consisting of 5-fluorouracil and cisplatin and 45-50 Gy radiation were recruited to the study. Pre-therapy-collected whole blood was analyzed for relative expression of immune genes using real-time polymerase chain reaction (RT-PCR). Gene expression was compared between patients who experienced severe regimen-related gastrointestinal toxicity vs. those experiencing mild to moderate toxicity. RESULTS: Blood from 31 patients were analyzed by RT-PCR. Out of 84 immune genes investigated, TNF was significantly elevated (2.05-fold, p = 0.025) in the toxic group (n = 12) compared to the non-toxic group (n = 19). Nausea and vomiting was the most commonly documented severe toxicity. No associations between toxicity and response, age, sex, histology, or treatment were evident. CONCLUSIONS: This study supports evidence of TNF as a predictive biomarker in regimen-related gastrointestinal toxicity. Confirming these findings in a larger cohort is warranted.

Twenty years of experience with laparoscopic antireflux surgery.

BACKGROUND: There are few reports of large patient cohorts with long-term follow-up after laparoscopic antireflux surgery. This study was undertaken to evaluate changes in surgical practice and outcomes for laparoscopic antireflux surgery over a 20-year period. METHODS: A standardized questionnaire, prospectively applied annually, was used to determine outcome for all patients undergoing laparoscopic fundoplication in two centres since commencing this procedure in 1991. Visual analogue scales ranging from 0 to 10 were used to assess symptoms of heartburn, dysphagia and satisfaction with overall outcome. Data were analysed to determine outcome across 20 years. RESULTS: From 1991 to 2010, 2261 consecutive patients underwent laparoscopic fundoplication at the authors' institutions. Follow-up ranged from 1 to 19 (mean 7.6) years. Conversion to open surgery occurred in 73 operations (3.2 per cent). Revisional surgery was performed in 216 patients (9.6 per cent), within 12 months of the original operation in 116. There was a shift from Nissen to partial fundoplication across 20 years, and a recent decline in operations for reflux, offset by an increase in surgery for large hiatus hernia. Dysphagia and satisfaction scores were stable, and heartburn scores rose slightly across 15 years of follow-up. Heartburn scores were slightly higher and reoperation for reflux was more common after anterior partial fundoplication (P = 0.005), whereas dysphagia scores were lower and reoperation for dysphagia was less common (P < 0.001). At 10 years, satisfaction with outcome was similar for all fundoplication types. CONCLUSION: Laparoscopic Nissen and partial fundoplications proved to be durable and achieved good long-term outcomes. At earlier follow-up, dysphagia was less common but reflux more common after anterior partial fundoplication, although differences had largely disappeared by 10 years.

Ten-year clinical outcome of a prospective randomized clinical trial of laparoscopic Nissen versus anterior 180( degrees ) partial fundoplication.

BACKGROUND: A randomized trial of laparoscopic Nissen fundoplication and anterior 180 degrees 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. METHODS: Some 107 patients were randomized to undergo laparoscopic Nissen or anterior 180 degrees partial fundoplication. Ten-year data were not available for 18 patients. Information was obtained from 89 patients (48 Nissen, 41 anterior fundoplication) using a standard clinical questionnaire that focused on symptoms of reflux, potential postoperative side-effects and overall satisfaction with the outcome of surgery. RESULTS: There were no significant differences between the two groups with regard to reflux symptoms, dysphagia, abdominal bloating, ability to belch and overall satisfaction. Between 5 and 10 years after surgery, revisional surgery was required for reflux in two patients after anterior fundoplication. Two patients had revision after Nissen fundoplication, for reflux and recurrent hiatus hernia. CONCLUSION: Both laparoscopic anterior 180 degrees partial and Nissen fundoplication are safe, effective and durable at 10 years' follow-up. Most patients are satisfied with the clinical outcome.

Laparoscopic antireflux surgery in the treatment of gastroesophageal reflux in patients with Barrett esophagus.

BACKGROUND: Patients with gastroesophageal reflux and Barrett esophagus may represent a group of patients with poorer postoperative outcomes. It has been suggested that such patients should undergo open rather than laparoscopic antireflux surgery. HYPOTHESIS: The laparoscopic approach to antireflux surgery is appropriate treatment for patients with Barrett esophagus who have symptomatic gastroesophageal reflux disease. METHODS: The outcome of 757 patients undergoing laparoscopic surgery for gastroesophageal reflux disease from January 1, 1992, through December 31, 1998, was prospectively examined. Barrett esophagus was present in 81 (10.7%) of these patients (58 men and 23 women). The outcome for this group of patients was compared with that of patients undergoing surgery who did not have Barrett esophagus. RESULTS: The types of operation performed were similar for the 2 patient groups. The mean +/- SD length of columnar mucosa was 47.4 +/- 43.6 mm. The average +/- SD operation time was 79.0 +/- 33.4 minutes. Conversion to open surgery occurred in 6 patients. Postoperative outcomes were as follows. Esophageal manometry and 24-hour pH studies before and after laparoscopic fundoplication demonstrated a significant increase in lower esophageal sphincter resting and residual relaxation pressures and a significant decrease in distal esophageal acid exposure. Four patients have developed high-grade dysplasia or invasive cancer within 4 years of their antireflux surgery, and all of these have subsequently undergone esophageal resection. CONCLUSIONS: The outcome of laparoscopic antireflux surgery is similar for patients with Barrett esophagus compared with other patients with gastroesophageal reflux disease. This suggests that laparoscopic surgery is appropriate treatment for this patient group.

Laparoscopic Nissen fundoplication: five-year results and beyond.

HYPOTHESIS: Laparoscopic Nissen fundoplication provides long-term relief of symptoms of gastroesophageal reflux disease. DESIGN: Prospectively evaluated case series. SETTING: University teaching hospital. PATIENTS: From September 1991 to December 1999, we performed more than 900 laparoscopic antireflux procedures. The outcome for patients who underwent surgery between September 1991 and June 1994 (178 cases) was determined. This included all patients having laparoscopic Nissen fundoplication, from the first procedure onward. INTERVENTIONS: Long-term follow-up for 5 or more years after laparoscopic Nissen fundoplication was obtained by an independent investigator who interviewed patients using a structured questionnaire. MAIN OUTCOME MEASURES: Prospective evaluation of clinical symptoms using a structured questionnaire. RESULTS: Outcome data covering a period of 5 or more years after surgery was available for 176 patients (99%), with 2 patients lost to follow-up. Nine patients died (8 of unrelated causes) at some stage following surgery, and the outcome was difficult to determine in 1 patient with cerebral palsy. Hence, questionnaire data were available for 166 patients at a median follow-up of 6 years (range, 5-8 years). Three patients (1.7%) underwent revision surgery for recurrent reflux; 87% of the 176 patients remained free of significant reflux. Reoperation was required for dysphagia in 7 patients (3.9%), 2 for a tight wrap and 5 for a tight diaphragmatic hiatus. In addition, reoperation was necessary for a paraesophageal hiatus hernia in 13 patients (7.3%). Of the reoperations, 56% were performed within 12 months of the original procedure, and 22% during the second year of follow-up. Further surgery was uncommon after 2 years. The long-term outcome was considered "good or excellent" by 90% of patients. CONCLUSIONS: The long-term outcome of laparoscopic Nissen fundoplication is similar to that following open fundoplication. Good results are obtained in most patients.

A prospective randomized trial of laparoscopic Nissen fundoplication with anterior vs posterior hiatal repair.

HYPOTHESIS: The technique used for repair of the esophageal hiatus during laparoscopic Nissen fundoplication can influence the likelihood of postoperative dysphagia. DESIGN: A prospective double-blind randomized control trial. SETTING: A university teaching hospital. PARTICIPANTS: A total of 102 patients with proven gastroesophageal reflux disease, undergoing a laparoscopic Nissen fundoplication were randomized to undergo fundoplication with either anterior (47 patients) or posterior (55 patients) repair of the diaphragmatic hiatus. Patients were excluded for the following reasons: they had esophageal motility disorders, required a concurrent abdominal procedure, had undergone previous antireflux surgery, or had very large hiatus hernias. INTERVENTIONS: Laparoscopic Nissen fundoplication with anterior vs posterior hiatal repair. MAIN OUTCOME MEASURES: Independent assessment of dysphagia, heartburn, patient satisfaction, and other symptoms 1, 3, and 6 months following surgery, using multiple standardized clinical grading systems. Objective measurement of lower esophageal sphincter pressure, esophageal emptying time, distal esophageal acid exposure, and endoscopic assessment of postoperative anatomy and esophageal mucosa. RESULTS: Symptoms of postoperative dysphagia, relief of heartburn, and overall satisfaction 6 months after surgery were not influenced by the hiatal repair technique. However, to achieve a similar incidence of dysphagia, more patients who initially underwent posterior hiatal repair required a second surgical procedure (6 vs 0 patients). The hiatal repair technique did not affect the likelihood of early postoperative paraesophageal herniation. CONCLUSION: Anterior suturing of the hiatus appears to be at least as good in the short-term as posterior suturing as a method of narrowing the hiatus during laparoscopic Nissen fundoplication.

Outcome of laparoscopic anterior 180-degree partial fundoplication for gastroesophageal reflux disease.

Although Nissen fundoplication controls gastroesophageal reflux disease effectively, it is associated with an incidence of side effects. For this reason we have investigated the use of a laparoscopic 180-degree anterior fundoplication as a technique that has the potential to control reflux, but with less associated postoperative dysphagia and fewer gas-related side effects. Good short-term (6-month) outcomes have been previously reported within the content of a randomized trial. This report details the technique we used and describes the outcome of this procedure with longer follow-up in a much larger group of patients. The outcome for patients with gastroesophageal reflux disease who underwent a laparoscopic anterior 180-hemifundoplication was determined. Clinical follow-up was carried out prospectively by an independent scientist who applied a standardized questionnaire yearly following surgery. This questionnaire evaluated symptoms of reflux, postoperative problems including dysphagia, gas bloat, ability to belch, and overall satisfaction with clinical outcome. From July 1995 to May 1999, a total ofc107 patients underwent a laparoscopic anterior hemifundoplication. Four patients underwent further surgery for recurrent heartburn, and persistent troublesome dysphagia occurred in one. At 1 year 89% of patients remained free of reflux symptoms, and at 3 years 84% remained symptom free. Of those with symptoms of reflux, approximately half of them had only mild symptoms. The overall incidence and severity of dysphagia for liquids and solids was not altered by partial fundoplication. Epigastric bloating that could not be relieved by belching was uncommon, and only 11% of the patients at 1 year and 10% at 3 years following surgery were unable to belch normally. Overall satisfaction with the outcome of surgery remained high at 3 years' follow-up. Laparoscopic anterior partial fundoplication is an effective operation for gastroesophageal reflux, with a low incidence of side effects and a good overall outcome.

Early reoperation following laparoscopic antireflux surgery.

PURPOSE: To assess the outcome for patients undergoing early reoperation following laparoscopic antireflux surgery. METHODS: The outcome was prospectively determined for 28 patients who underwent 30 reoperative procedures within 4 weeks of their initial laparoscopic fundoplication between 1992 and 1998. Follow-up ranged from 3 months to 4 years (median 2 years). Before mid 1994, patients were assessed and managed based on clinical findings (first 192 patients in overall series), whereas subsequently (for the most recent 530 patients) all patients underwent routine early postoperative barium swallow radiography, and laparoscopic exploration during the first postoperative week if problems were suspected. RESULTS: The reoperations were performed for acute paraoesophageal hiatus hernia (8 patients), tight oesophageal hiatus (7), postoperative haemorrhage (3), tight Nissen fundoplication (8), early recurrent reflux (1), and coeliac/superior mesenteric artery thrombosis (1). Two patients required a second operation for persistent dysphagia due to a tight hiatus. Both patients initially underwent loosening of their fundoplication. Before mid 1994, reoperations were usually undertaken by an open approach, whereas subsequently a laparoscopic approach has usually been successful. Laparoscopic reintervention was easily achieved within 7 days of the first procedure whereas subsequent surgery was more difficult and often required open surgery. The change in protocol was associated with an improvement in overall patient satisfaction and dysphagia in the latter part of this experience. CONCLUSIONS: Routine early contrast radiology following laparoscopic fundoplication and a low threshold for laparoscopic reexploration facilitates early identification of postoperative problems at a time when laparoscopic correction is easily achieved. This may result in an improved overall outcome for patients requiring early reintervention following laparoscopic antireflux surgery.

Five-year follow-up of a randomized clinical trial of laparoscopic total versus anterior 180 degrees fundoplication.

BACKGROUND: Total fundoplication for gastro-oesophageal reflux disease may be followed by unwanted side-effects. A randomized trial demonstrated that an anterior 180 degrees partial fundoplication achieved effective reflux control and was associated with fewer side-effects in the short term than total fundoplication. This paper reports longer-term (5 year) outcomes from that trial. METHODS: Between December 1995 and June 1997, 107 patients were randomized to undergo either laparoscopic total fundoplication or a laparoscopic anterior 180 degrees fundoplication. After 5 years, 101 of 103 eligible patients (51 total, 50 anterior) were available for follow-up. Each patient was interviewed by a single blinded investigator and a standardized questionnaire was completed. The questionnaire focused on symptoms and overall satisfaction with the results of fundoplication. RESULTS: There were no significant differences between the two groups with regard to control of heartburn or patient satisfaction with the overall outcome. Dysphagia, measured by a visual analogue score for solid food and a composite dysphagia score, was worse at 5 years after total fundoplication. Symptoms of bloating, inability to belch and flatulence were also more common after total fundoplication. Reoperation was required for dysphagia in three patients after total fundoplication and for recurrent reflux in three patients after anterior fundoplication. CONCLUSION: Anterior 180 degrees partial fundoplication was as effective as total fundoplication for managing the symptoms of gastro-oesophageal reflux in the longer term. It was associated with a lower incidence of side-effects, although this was offset by a slightly higher risk of recurrent reflux symptoms.

Hand-assisted laparoscopic vertical banded gastroplasty. Initial report.

Laparoscopic approaches to surgery for morbid obesity offer to reduce the morbidity associated with conventional weight reduction surgery. This paper describes a hand-assisted laparoscopic technique for vertical banded gastroplasty, a method which shortens and simplifies the laparoscopic approach to this established open surgical procedure.

Eversion extraction of the oesophagus.

The technique of eversion extraction of the oesophagus has been used in Japan and China, but is little used in the Western world. This is a report of the technique of the procedure as undertaken in 10 cases of oesophageal disease.

Palliative venting gastrostomy in malignant intestinal obstruction.

This retrospective clinical study reports on the experience of palliative venting gastrostomy (PVG) in an integrated acute teaching hospital and hospice-based palliative care service over a seven-year period (1989-97). PVG was performed for 51 patients with refractory nausea and vomiting resulting from varying degrees and levels of persisting or intermittent malignant bowel obstruction. There were 32 females and 19 males; the mean age was 61 years (range 25-86 years). All patients had advanced and incurable cancer with intra-abdominal spread, originating from the following primary sites: colon and rectum (27), ovary (16), breast (2), pancreas (2), and other (4). The venting gastrostomy tube was inserted endoscopically by a railroading technique in 46 patients (using a 16- to 20-French Dobhoff PEG tube), at open laparotomy in four cases and under radiological (abdominal computerized tomography) control in one case. Endoscopic insertion was attempted and abandoned for technical reasons in a further two cases. The median survival of all 51 patients from the time of gastrostomy insertion was 17 days (range 1-190). In 47/51 (92%), the symptoms of nausea and vomiting were relieved by the procedure, and these patients experienced restoration of some level of oral soft food and fluid intake. Twenty patients were discharged home, and six died at home. In a small group of highly selected patients, for whom pharmacological measures failed to palliate the effects of malignant bowel obstruction, PVG was shown to be a safe and effective means of abolishing or substantially improving vomiting. Provided that the intervention is appropriate to the given clinical situation and acceptable to the patient, it should be considered.

Laparoscopic resection of benign tumors of the posterior gastric wall.

Laparoscopic wedge excision of benign gastric tumors using stapling instruments alone is not feasible for distal lesions and some tumors arising from the posterior gastric wall. An alternative transgastric approach to distal posterior wall lesions utilizing an anterior gastrotomy for access has been successfully applied in two reported cases.

Surgical bypass for palliation of malignant oesophageal obstruction.

It is possible to achieve satisfactory palliation for most patients with malignant oesophageal obstruction by endoscopic means, surgical resection or radiotherapy. Despite these options, a small group of patients remains for whom another alternative should be considered. Fifteen patients presenting with extensive tumour, a non-dilatable stricture, or a tracheo-oesophageal fistula, not suitable for any of the standard methods of palliation, underwent palliative surgical bypass using stomach or colon. The hospital mortality was 33% and the median survival 6 months. Anastomotic leakage occurred in six patients and the median postoperative stay was 28 days (range 20-42 days). All patients who survived surgery, except one, achieved satisfactory palliation. The nature of these patients is such that whatever is done, mortality will almost inevitably be high. The authors believe that all patients in this series were better off than they would have been if left untreated, and oesophageal bypass should be considered for patients with distressing dysphagia due to disease not amenable to standard palliative methods.

The expression and localisation of the angiotensin-converting enzyme mRNA in human adipose tissue.

Recent evidence in rats has indicated that angiotensinogen may be synthesised in adipose tissue surrounding blood vessels and that a local renin-angiotensin system may regulate adipose tissue blood supply and the efflux of fatty acids from fat in that species. This hypothesis is critically dependent on the local expression of the angiotensin converting enzyme gene in adipocytes. Thus the current study set out to examine whether the angiotensin converting enzyme gene was expressed in human adipose tissue and, if it was present, to localise the individual sites of that expression. Northern analysis indicated the presence of mRNA for angiotensin converting enzyme in both subcutaneous and extraperitoneal adipose tissue. In situ hybridisation showed that the gene was expressed in adipocytes. The foregoing results therefore suggest that components of the renin-angiotensin cascade are also present in human adipose tissue and support the hypothesis that adipose tissue may play a role in the local production of Angiotensin II and hence participate in vascular function and blood pressure control in the human.

Pneumothorax during laparoscopic mobilization of the oesophagus.

During laparoscopic dissection of the oesophagus, the left pleura is easily breached, resulting in pneumothorax. This complication has not been widely reported, although it is likely to be common. Management depends on subsequent cardiorespiratory effects, which are variable. Five cases are reported from an initial experience of 190 laparoscopic Nissen fundoplications, illustrating a variety of presentations and management options.

Paraoesophageal hiatus hernia: an important complication of laparoscopic Nissen fundoplication.

Postoperative paraoesophageal hiatus hernia occurred in 17 of 253 patients who underwent laparoscopic fundoplication at five different hospitals. Ten patients have undergone subsequent surgical revision, eight by an open technique and two by laparoscopy. This complication may have important implications for the technique of laparoscopic fundoplication, as it is possible that routine posterior repair of the diaphragmatic hiatus may greatly reduce the risk. Early postoperative contrast radiology may also achieve earlier diagnosis, enabling correction to be undertaken by laparoscopy.

Laparoscopic reoperation following failed antireflux surgery.

BACKGROUND: The aim was to determine the feasibility of laparoscopic revision surgery following previous open and laparoscopic antireflux operations. METHODS: The outcome was determined for 27 patients (14 men, 13 women) who had undergone attempted laparoscopic revision between 3 months and 25 years after a previous antireflux operation. Median follow-up was 12 (range 3-48) months. RESULTS: Thirteen patients had previously had an open antireflux procedure (Nissen fundoplication, seven; transthoracic anatomical repair, five; Belsey procedure, one) and 14 a laparoscopic procedure (Nissen, 12; anterior partial fundoplication, two). The indications for revision were: recurrent reflux, 15; paraoesophageal hiatus hernia, six; troublesome dysphagia, six. Fifteen procedures comprised construction of a new Nissen fundoplication, six conversion from a Nissen to a partial wrap, three repair of a paraoesophageal hernia and three widening of the oesophageal hiatus. Revision was successfully completed laparoscopically in 12 patients following a previous laparoscopic procedure and in nine following a previous open operation. Median operating time was 105 min after previous open surgery and 80 min after laparoscopic surgery. No perioperative complications occurred in either group and a good outcome was achieved in 25 of the 27 patients. CONCLUSION: Laparoscopic reoperative antireflux surgery is feasible. Reoperation is likely to be more difficult following failure of an open procedure than a laparoscopic one.

Laparoscopic surgery for gastro-oesophageal reflux: beyond the learning curve.

From September 1991 to October 1995, 320 Nissen fundoplications were undertaken laparoscopically by 12 surgeons at a single institution. To assess the performance of the procedure in the hands of five 'experienced' surgeons, the first 20 procedures performed by each surgeon or surgical trainee were excluded, providing a group of 174 patients for review. A short loose 360 degrees fundoplication was performed in all instances, with short gastric vessel division performed in 35.0 per cent of patients and hiatal repair in 66.7 per cent. Median operating time was 80 (range 30-210) min and median postoperative stay was 3 (range 1-19) days. Sixteen procedures (9.2 per cent) could not be completed laparoscopically and required conversion to open surgery. Some 144 patients were reviewed by a scientific officer 3 months after surgery, 85 at 12 months, and 32 at 2 years, using a standard clinical questionnaire. All but one were free from reflux symptoms, although 20.1 per cent reported some dysphagia at 3 months' follow-up; this figure declined to 11 per cent at 12 months and 6 per cent (two of 34 patients) at 2 years. At each follow-up interval, 91 per cent of patients were satisfied with the outcome of the surgery. Objective testing with oesophageal motility (75 patients) and barium swallow (113) studies 3-6 months after surgery confirmed the clinical outcome. Complications occurred in nine patients (5.2 per cent); four (2.3 per cent) of these required a subsequent operation within 30 days of surgery for bleeding (one patient), paraoesophageal herniation (one) and dysphagia (two). A further procedure was necessary in six other patients (3.4 per cent) for late problems, including paraoesophageal herniation (two), hiatal stenosis (three) and gastric obstruction (one). Revision was performed laparoscopically in two patients. The clinical results of laparoscopic Nissen fundoplication by 'experienced' laparoscopic surgeons were comparable with those of open surgery.

Changing strategies in the performance of laparoscopic Nissen fundoplication as a result of experience with 230 operations.

From September 1991 to January 1995 we performed 230 Nissen fundoplications by a laparoscopic technique. Whilst a loose 360 degree fundoplication secured by 3 or 4 sutures was performed in all instances, there was variation between surgeons regarding the performance of hiatal repair and division of short gastric vessels; 207 operations were completed laparoscopically and 23 were converted to an open operation when a satisfactory wrap could not be achieved. Operating time ranged from 30 to 260 min (median 95) and the median postoperative stay was 3 days (1-19). Twenty-three patients (10%) underwent a subsequent operation (14 within 3 months of the original surgery), 2 for recurrent reflux, 10 for para-esophageal herniation, 2 for a misplaced fundoplication resulting in gastric obstruction, 7 for persistent dysphagia (4 due to stenosis of the esophageal hiatus), 1 for bleeding, and 1 for mesenteric thrombosis. (This patient died.) Five other patients were readmitted to hospital subsequent to their discharge--four because of pulmonary emboli and one because of gastric obstruction. Some 226 patients (98%) are free of reflux symptoms with follow-up ranging up to 40 months (median 16). Absence of reflux and the integrity of the fundoplication has been confirmed by postoperative esophageal manometry and pH monitoring in 90 patients, and by barium meal in 126. Postoperative recovery has been quick and wound-related morbidity minimal. Although the rate of surgical revision was significant in this series, the likelihood of complications or further surgery, as well as incidence of conversion to open surgery, decreased in the second half of the experience.(ABSTRACT TRUNCATED AT 250 WORDS)