Long-term follow-up of two randomized trials comparing laparoscopic Nissen 360° with anterior 90° partial fundoplication.

BACKGROUND: The side-effects of Nissen fundoplication have led to modifications, including partial fundoplications such as an anterior 90° wrap. Five-year follow-up of two randomized trials suggested fewer side-effects following anterior 90° partial fundoplication, but better reflux control after Nissen fundoplication. However, longer-term outcomes have not been reported. This study combined data from previous trials to determine 10-year outcomes. METHODS: From 1999 to 2003, 191 patients were enrolled in two randomized trials comparing anterior 90° partial versus Nissen fundoplication. Trial protocols were similar, and data were combined to determine long-term clinical outcomes. Patients completed annual questionnaires assessing dysphagia, heartburn, medications, satisfaction and other symptoms. Visual analogue scales (0-10), a composite dysphagia score (0-45) and yes/no responses were used. RESULTS: Of the 191 patients, 152 (79·6 per cent) were available for 10-year follow-up. After anterior 90° fundoplication, patients reported less dysphagia to solids (score 2·03 versus 3·18 for the Nissen procedure; P = 0·037). Heartburn scores were lower after Nissen fundoplication (1·90 versus 2·83 for anterior 90° fundoplication; P = 0·035) and fewer patients required proton pump inhibitors (PPIs) (22 versus 39 per cent respectively; P = 0·035). Satisfaction scores were similar for both anterior 90° and Nissen groups (7·45 versus 7·36 respectively; P = 0·566), and the majority considered their original decision for surgery to be correct (86 versus 84 per cent; P = 0·818). CONCLUSION: After 10 years, both procedures achieved similar success as measured by global satisfaction measures. Patients who had a Nissen fundoplication reported more dysphagia, whereas more heartburn and PPI consumption were reported after anterior 90° fundoplication. Registration numbers: ACTRN12607000298415 and ACTRN12607000304437 (http://www.anzctr.org.au/).

ANTECEDENTES: Para evitar los efectos secundarios de la fundoplicatura de Nissen se han propuesto modificaciones técnicas, incluyendo las fundoplicaturas parciales como la plicatura anterior de 90°. El seguimiento a 5 años de dos ensayos aleatorizados sugiere menos efectos secundarios tras la fundoplicatura anterior de 90°, pero mejor control del reflujo con la fundoplicatura de Nissen. Sin embargo, no se han descrito los resultados a largo plazo. Este estudio combinó datos de dos ensayos previos para determinar los resultados a 10 años. MÉTODOS: Entre 1999 y 2003, se reclutaron 191 pacientes en dos ensayos aleatorizados que comparaban la fundoplicatura parcial anterior 90° versus fundoplicatura de Nissen. Los protocolos de ambos ensayos fueron similares, y los datos se combinaron para determinar los resultados clínicos a largo plazo. Los pacientes completaron cuestionarios anuales que evaluaban disfagia, pirosis, medicaciones, satisfacción y otros síntomas. Se utilizaron escalas analógicas visuales (0-10), una variable compuesta para la puntuación de disfagia (0-45) y respuestas sí/no. RESULTADOS: De los 191 pacientes, 152 (79,6%) pudieron seguirse a los 10 años. Tras la fundoplicatura anterior de 90°, los pacientes refirieron menos disfagia a sólidos (2,03 versus 3,18, P = 0,037). Las puntuaciones de pirosis fueron inferiores tras fundoplicatura de Nissen (2,83 versus 1,90, P = 0,035) y menos pacientes tomaban inhibidores de la bomba de protones (proton pump inhibitors, PPIs; 22% versus 39%, P = 0,035). Las puntuaciones de satisfacción fueron similares para ambos grupos de fundoplicatura anterior 90° y Nissen (7,45 versus 7,36, P = 0,566), y la mayoría consideró su decisión original para la cirugía como correcta (86,1% versus. 83,8%, P = 0,818). Las tasas de reoperación fueron similares (10,0% versus 8,8%). CONCLUSIÓN: Después de 10 años, ambos procedimientos lograron un éxito similar medido con medidas de satisfacción global. Los pacientes con fundoplicatura de Nissen referían más disfagia mientras que los pacientes con fundoplicatura anterior 900 describieron más pirosis y consumo de PPIs.

Asymmetrical elevation of esophagogastric junction pressure suggests hiatal repair contributes to antireflux surgery dysphagia.

The radial distribution of esophago-gastric junction (EGJ) pressures with regard to troublesome dysphagia (TDysph) after antireflux surgery is poorly understood. Before and after antireflux surgery, end-expiratory and peak-inspiratory EGJ pressures were measured at eight angles of 45° radial separation in patients with reflux disease. All 34 patients underwent posterior crural repair, then either 90° anterior (N = 13) or 360° fundoplication (N = 21). Dysphagia was assessed prospectively using a validated questionnaire (score range 0-45) and TDysph defined as a dysphagia score that was ≥5 above pre-op baseline. Compared with before surgery, for 90° fundoplication, end-expiratory EGJ pressures were highest in the left-anterolateral sectors, the position of the partial fundoplication. In other sectors, pressures were uniformly elevated. Compared with 90° fundoplication, radial pressures after 360° fundoplication were higher circumferentially (P = 0.004), with a posterior peak. Nine patients developed TDysph after surgery with a greater increase in end-expiratory and peak-inspiratory EGJ pressures (P = 0.03 and 0.03, respectively) and significantly higher inspiratory pressure at the point of maximal radial pressure asymmetry (P = 0.048), compared with 25 patients without TDysph. Circumferential elevation of end-expiratory EGJ pressure after 90° and 360° fundoplication suggests hiatal repair elevates EGJ pressure by extrinsic compression. The highly localized focal point of elevated EGJ pressure upon inspiration in patients with TDysph after surgery is indicative of a restrictive diaphragmatic hiatus in the presence of a fundoplication.

Multicentre factorial randomized clinical trial of perioperative immunonutrition versus standard nutrition for patients undergoing surgical resection of oesophageal cancer.

BACKGROUND: Preoperative immunonutrition has been proposed to reduce the duration of hospital stay and infective complications following major elective surgery in patients with gastrointestinal malignancy. A multicentre 2 × 2 factorial RCT was conducted to determine the impact of preoperative and postoperative immunonutrition versus standard nutrition in patients with oesophageal cancer. METHODS: Patients were randomized before oesophagectomy to immunonutrition (IMPACT® ) versus standard isocaloric/isonitrogenous nutrition, then further randomized after operation to immunonutrition versus standard nutrition. Clinical and quality-of-life outcomes were assessed at 14 and 42 days after operation on an intention-to-treat basis. The primary outcome was the occurrence of infective complications. Secondary outcomes were other complications, duration of hospital stay, mortality, nutritional and quality-of-life outcomes (EuroQol EQ-5D-3 L™, European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and EORTC QLQ-OES18). Patients and investigators were blinded until the completion of data analysis. RESULTS: Some 278 patients from 11 Australian sites were randomized; two were excluded and data from 276 were analysed. The incidence of infective complications was similar for all groups (37 per cent in perioperative standard nutrition group, 51 per cent in perioperative immunonutrition group, 34 per cent in preoperative immunonutrition group and 40 per cent in postoperative immunonutrition group; P = 0·187). There were no significant differences in any other clinical or quality-of-life outcomes. CONCLUSION: Use of immunonutrition before and/or after surgery provided no benefit over standard nutrition in patients undergoing oesophagectomy. Registration number: ACTRN12611000178943 ( https://www.anzctr.org.au).

IGFBP7 is associated with poor prognosis in oesophageal adenocarcinoma and is regulated by promoter DNA methylation.

BACKGROUND: We examined whether silencing of IGFBP7 was associated with survival in patients with oesophageal adenocarcinoma. METHODS: Protein expression of IGFBP7 was determined using immunohistochemistry in a tissue microarray representing tumours from 65 patients with oesophageal adenocarcinoma who had not had neoadjuvant therapy. DNA methylation of the IGFBP7 promoter was determined with the melt curve analysis in cell lines and patient tissues. RESULTS: Expression of IGFBP7 was observed in the oesophageal adenocarcinoma of 34 out of 65 (52%) patients and was associated with significantly reduced median (11 vs 92 months) and 5-year survival (25% vs 52%). Multivariate analysis identified expression as an independent prognostic indicator for survival (hazard ratio=3.24, 95% confidence interval=1.58-6.67, P-value=0.0014). Hypermethylation of IGFBP7 was associated with silencing of gene expression in cell lines and patient tissues (P-value=0.0225). Methylation was observed in the squamous mucosa of 2 out of 15 (13%) patients with Barrett's oesophagus and 3 out of 17 (18%) with oesophageal adenocarcinoma. Methylation was observed in 14 out of 18 (78%) of biopsies of Barrett's mucosa and 23 out of 34 (68%) patients with oesophageal adenocarcinoma. CONCLUSION: Reduced IGFBP7 protein expression was associated with longer survival in patients with oesophageal adenocarcinoma. Methylation of the IGFBP7 promoter was associated with silencing of gene expression and was frequent in Barrett's oesophagus and oesophageal adenocarcinoma.

Impact of participation in randomized trials on outcome following surgery for gastro-oesophageal reflux.

BACKGROUND: Patients may be unwilling to participate in clinical trials if they perceive risks. Outcomes were evaluated following surgery for gastro-oesophageal reflux in patients recruited to randomized trials compared with patients not in trials. METHODS: This study compared outcomes of patients who had surgery for reflux within or outside randomized trials between 1994 and 2009. The choice of procedure outside each trial was according to surgeon or patient preference. Clinical outcomes were determined 1 and 5 years after surgery using a standardized questionnaire, with analogue scales to assess heartburn, dysphagia and overall satisfaction. Subgroup analysis was undertaken for those aged less than 75 years undergoing laparoscopic Nissen fundoplication. RESULTS: Some 417 patients entered six randomized trials evaluating surgery for reflux and 981 underwent surgery outside the trials. The trial group contained a higher proportion of men and younger patients, and patients in trials were more likely to have undergone Nissen fundoplication. At 1 year, patients in the trials had slightly lower heartburn scores and less abdominal bloating, but otherwise similar outcomes to those not in the trials. At 5 years there were no differences, except for a slightly higher dysphagia score for liquids in the trial group. For the subgroup analysis, demographic data were similar for both groups. There were no differences at 1 year, but at 5 years patients enrolled in the trials had higher scores for dysphagia for liquids and heartburn. All of the statistically significant differences were thought unlikely to be clinically relevant. CONCLUSION: Participation in a randomized trial assessing surgery for reflux did not influence outcomes.

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.

Meta-analysis of two randomized controlled trials to identify long-term symptoms after division of the short gastric vessels during Nissen fundoplication.

BACKGROUND: Randomized trials suggest that division of the short gastric vessels during Nissen fundoplication is unnecessary. Some trials report an increased risk of gas bloat symptoms following division of the short gastric vessels. In this study long-term follow-up data from the two largest randomized clinical trials of division versus no division of the short gastric vessels during laparoscopic Nissen fundoplication were combined to determine whether there were differences in late outcome. METHODS: Patients with gastro-oesophageal reflux disease who underwent primary laparoscopic antireflux surgery and were included in two previously reported randomized trials were studied. Of 99 patients enrolled in the Swedish study and 102 in the Australian study, the short gastric vessels were divided in 104 and left intact in 97. Data sets were combined and late clinical outcomes analysed. RESULTS: At 10-12 years' follow-up (mean 11.5 years) clinical data were obtained from 170 patients (86 with vessels divided, 84 undivided). Statistical analysis of the combined data set showed no significant differences in symptoms of heartburn or dysphagia, ability to belch or vomit, and use of antisecretory medications. Division of the short gastric vessels was associated with a higher rate of bloating symptoms (72 versus 48 per cent; P = 0.002). CONCLUSION: Division of the short gastric vessels is followed by a slightly poorer clinical outcome at late follow-up after Nissen fundoplication. Surgeons should avoid dividing these vessels when undertaking a laparoscopic Nissen fundoplication.

Impact of ineffective oesophageal motility and wrap type on dysphagia after laparoscopic fundoplication.

BACKGROUND: Laparoscopic 360° fundoplication is the most common operation for gastro-oesophageal reflux disease, but is associated with postoperative dysphagia in some patients. Patients with ineffective oesophageal motility may have a higher risk of developing postoperative dysphagia, but this remains unclear. METHODS: From 1991 to 2010, 2040 patients underwent primary laparoscopic fundoplication for gastro-oesophageal reflux disease and met the study inclusion criteria; 343 had a 90°, 498 a 180° and 1199 a 360° fundoplication. Primary peristalsis and distal contraction amplitude during oesophageal manometry were determined for 1354 patients. Postoperative dysphagia scores (range 0-45) were recorded at 3 and 12 months, then annually. Oesophageal dilatations and/or reoperations for dysphagia were recorded. RESULTS: Preoperative oesophageal motility did not influence postoperative dysphagia scores, the need for dilatation and/or reoperation up to 6 years. Three-month dysphagia scores were lower after 90° and 180° compared with 360° fundoplication (mean(s.e.m.) 8·0(0·6) and 9·8(0·5) respectively versus 11·9(0·4); P < 0·001 and P = 0·003), but these differences diminished after 6 years of follow-up. The incidence of dilatation and reoperation for dysphagia was lower after 90° (2·6 and 0·6 per cent respectively) and 180° (4·4 and 1·0 per cent) fundoplications than with a 360° wrap (9·8 and 6·8 per cent; both P < 0·001 versus 90° and 180° groups). CONCLUSION: Tailoring the degree of fundoplication according to preoperative oesophageal motility by standard manometric parameters has no long-term impact on postoperative dysphagia. There is, however, a proportionate increase in short-term dysphagia scores with increasing degree of wrap, and a corresponding proportionate increase in dilatations and reoperations for dysphagia. These differences in dysphagia scores diminish with time.

Immunonutrition in patients undergoing esophageal cancer resection.

Specialized nutritional support containing immunonutrients such as arginine, omega-3 fatty acids, and ribonucleic acid significantly reduces the incidence of postoperative infective complications and hospital length of stay in elective surgery patients. However, immunonutrition use is not standard practice in esophago-gastric units internationally. This review provides a clinical update regarding the use of immunonutrition in patients undergoing major gastrointestinal surgery and, in particular, esophageal cancer resection, and provides direction for future collaborative research. A review of MEDLINE and Cochrane Library databases was conducted for randomized controlled trials or meta-analyses. A recent meta-analysis demonstrated that preoperative immunonutrition use significantly reduces hospital length of stay and the incidence of postoperative complications in patients undergoing major elective surgery, particularly for gastrointestinal malignancies. Only three small randomized controlled trials have evaluated immunonutrition use in patients exclusively undergoing esophageal cancer surgery. These were unable to determine whether immune-enhancing formulae positively influence key clinical outcomes such as mortality, hospital and intensive care unit length of stay, and postoperative morbidity in this patient group. Currently, there is insufficient evidence to recommend routine use of immunonutrition in patients undergoing esophageal cancer surgery. Future collaborative research should evaluate whether: (i) immunonutrition use positively influences key clinical outcomes in this population; (ii) these patients benefit from preoperative supplementation with an immune-enhancing formula or whether they require postoperative continuation (perioperative approach) to combat their risk of complications after surgery; and (iii) these formulae can be used safely in those patients who develop sepsis.

Detection of lymph node metastases in oesophageal cancer.

BACKGROUND: The importance of lymph node status in oesophageal cancer cannot be disputed. It is therefore surprising that no standardization exists in either terminology or methodology in lymph node analysis. METHODS: All online databases were searched to identify articles published from 1970 onwards. This was supplemented by hand searching references of retrieved articles. RESULTS AND CONCLUSION: Without accurate identification of lymph node metastases, patients cannot be staged properly, nor can best practice for the treatment of oesophageal cancer be determined. This review outlines the problem and proposes recommendations for standardization in terminology and methodology for the detection of lymph node metastases in oesophageal cancer.

Systematic review of endoscopic treatments for gastro-oesophageal reflux disease.

BACKGROUND: The aim of this review was to assess the safety and efficacy of endoscopic procedures for gastro-oesophageal reflux disease. METHODS: Literature databases including Medline, Embase and PubMed were searched up to May 2006 without language restriction. Randomized controlled trials and non-randomized comparative studies with at least ten patients in each study arm, and case series studies of at least ten patients, were included. RESULTS: A total of 33 studies examining seven endoscopic procedures (Stretta procedure, Bard EndoCinch, Wilson-Cook Endoscopic Suturing Device, NDO Plicator, Enteryx, Gatekeeper Reflux Repair System and Plexiglas) were included in the review. Of the three procedures that were tested against sham controls (Stretta procedure, Bard EndoCinch and Enteryx), patient outcomes in the treatment group were either as good as, or significantly better than, those of control patients in terms of heartburn symptoms, quality of life and medication usage. However, for the two procedures that were tested against laparoscopic fundoplication (Stretta) procedure and Bard EndoCinch), outcomes for patients in the endoscopic group were either as good as, or inferior to, those for the laparoscopic group. CONCLUSION: At present there is insufficient evidence to determine the safety and efficacy of endoscopic procedures for gastro-oesophageal reflux disease, particularly in the long term.

Long-term outcomes of revisional surgery following laparoscopic fundoplication.

BACKGROUND: A small proportion of patients who have laparoscopic antireflux procedures require revisional surgery. This study investigated long-term clinical outcomes. METHODS: Patients requiring late revisional surgery following laparoscopic fundoplication for gastro-oesophageal reflux were identified from a prospective database. Long-term outcomes were determined using a questionnaire evaluating symptom scores for heartburn, dysphagia and satisfaction. RESULTS: The database search found 109 patients, including 98 (5.6 per cent) of 1751 patients who had primary surgery in the authors' unit. Indications for surgical revision were dysphagia (52 patients), recurrent reflux (36), mechanical symptoms related to paraoesophageal herniation (16) and atypical symptoms (five). The median time to revision was 26 months. Outcome data were available for 104 patients (median follow-up 66 months) and satisfaction data for 102, 88 of whom were highly satisfied (62.7 per cent) or satisfied (23.5 per cent) with the outcome. Patients who had revision for dysphagia had a higher incidence of poorly controlled heartburn (20 versus 2 per cent; P = 0.004), troublesome dysphagia (16 versus 6 per cent; P = 0.118) and a lower satisfaction score (P = 0.023) than those with recurrent reflux or paraoesophageal herniation. CONCLUSION: Revisional surgery following laparoscopic fundoplication can produce good long-term results, but revision for dysphagia has less satisfactory outcomes.

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.

Symptoms experienced during 24-h pH monitoring and their relationship to outcome after laparoscopic total fundoplication.

Some patients having a 24-h pH monitoring test prior to laparoscopic fundoplication experience no symptoms at all in spite of having a positive test, and other patients experience only atypical symptoms in spite of having a positive test. This study investigates the postoperative outcome of such patients. All patients underwent esophageal manometry and 24-h esophageal pH monitoring before laparoscopic total fundoplication. Patients were divided into three groups based on their symptom profile recorded during a positive 24-h pH monitoring: those with typical symptoms (n = 104), those with atypical symptoms (n = 28) and those who experienced no symptoms at all (n = 23). The outcomes measured were heartburn score (0-10), dysphagia composite score (0-45) and satisfaction score (0-10) at 12 months after surgery. Outcome analysis reveals the heartburn scores were significantly reduced postoperatively for all groups of patients. At 1 year after surgery, there was no difference among the three groups of patients in terms of heartburn score and dysphagia composite scores, nor the experience of bloating, belching, or their willingness to repeat surgery. Despite one group experiencing no symptoms, and another group atypical symptoms during a positive pH study, the postoperative satisfaction scores for these two groups was good, but significantly less (P = 0.03, P = 0.02, respectively) than the group of patients with a typical symptom index. In conclusion, patients who experience only atypical symptoms or no symptoms at all during their preoperative positive 24-h pH monitoring may still obtain a good result from antireflux surgery. However, these symptom profiles should alert the surgeon that such patients may have an outcome which is not as good as patients who experience only typical symptoms during a pH study.

Patterns of treatment failure and prognostic factors associated with the treatment of esophageal carcinoma with chemotherapy and radiotherapy either as sole treatment or followed by surgery .

PURPOSE: The records of patients with esophageal cancer who were treated with a combined modality therapy were reviewed to determine the effects of simultaneously administered chemotherapy and radiotherapy (RT) at sites of recurrence and the relationship between treatment outcome and clinicopathologic variables. PATIENTS AND METHODS: One hundred seventeen patients were treated with fluorouracil (800 mg/m2) [corrected] and cisplatin (80 mg/m2) combined with either 36 Gy (36 patients) or 54 to 60 Gy (35 patients) of RT as sole therapy. Forty-six patients underwent surgery after they had received chemotherapy and 36 Gy of RT as initial treatment. Patients with either squamous cell cancer (SCC) or adenocarcinoma were included. RESULTS: Complete endoscopic regression after an initial 36 Gy of RT and chemotherapy occurred in more than 50% of patients and in both tumor types. Relief of dysphagia accompanied tumor regression. Forty-two tumors were resected, and 11 showed a complete histologic response. Significant associations were demonstrated between enhanced survival and a diagnosis of SCC, a complete endoscopic response to initial chemotherapy and RT, and a tumor length of less than 5 cm. Multivariate analyses suggested that tumor length and complete endoscopic response were independent prognostic variables. The survival rate of patients treated by resection or radical-dosage RT was not significantly different. CONCLUSIONS: The relief of dysphagia demonstrates the palliative value of chemotherapy and RT in both tumor types. The similar survival rates of patients with SCC or adenocarcinoma treated either surgically or with high-dose combined therapy (54 to 60 Gy) emphasize the need to evaluate the role of surgery and combined treatment in randomized studies.

Combined modality therapy for esophageal carcinoma: preliminary results from a large Australasian multicenter study.

PURPOSE: This report updates local control and survival experience and focuses on treatment toxicity in 294 patients with esophageal cancer who have been treated at six Australasian centers using three prospective unrandomized protocols that used concurrent radiation, cisplatin, and modest dose infusional fluorouracil. METHODS AND MATERIALS: Protocol 1--"definitive" chemoradiation. One hundred and thirty-seven patients have been treated with "definitive" radiation to 60 Gy in 6 weeks plus two courses of cisplatin (80 mg/m2) and infusional fluorouracil (800 mg/m2/day over 4 days) during the first and fourth weeks of radiation. Protocol 2--"preoperative" chemoradiation and surgery. Seventy-eight patients received chemoradiation using the same chemotherapy, but 30-35 Gy in 3-4 weeks prior to surgery. Protocol 3--"palliative" chemoradiation. Seventy-nine patients deemed incurable were treated "palliatively" with the same chemoradiation protocol without surgery. Follow-up ranges from 6 months to 7 years (mean 22 months) in live patients. RESULTS: Durable palliation of dysphagia in all three treatment groups has been reflected by encouraging 3-year survival expectations of 43.2 +/- 5% in definitively treated patients, 40.3 +/- 7.65% in surgically treated patients, and 8.5% +/- 3.9% in the palliatively treated patients. There are early indications that female patients have fared better than males. Toxicity levels were modest in all three groups. Following definitive treatment, severe myelotoxicity (World Health Organization grades 3 and 4) occurred in 19%, severe esophagitis (World Health Organization grade 3) in 11%, and moderate or severe benign stricture in 17%, depending upon age and sex of the patient (being worse in female patients). CONCLUSIONS: These studies demonstrate that the concurrent addition of modest dose cisplatin and infusional dose fluorouracil to radiation in the definitive, preoperative, and palliative settings contribute to high rates of durable dysphagia-free survival, with overall survival comparable to (and possibly better than) the chemoradiation arm of the recently reported Intergroup Study, but at the cost of less morbidity.

Physiologic response to cricopharyngeal myotomy and diverticulum suspension.

Ten patients who had a cricopharyngeal myotomy and diverticulum suspension for pharyngoesophageal diverticulum have been studied clinically, radiologically, and manometrically. There were no deaths or morbidity and all patients have achieved marked improvement of their symptoms. Before operation all patients but one had low resting tone in the upper esophageal sphincter and all patients had normal relaxation of the sphincter upon swallowing. The coordination of pharyngeal contraction and sphincter relaxation was normal in six patients and abnormal in four patients. After operations the only change was an increase in resting tone in seven patients, and there was no change in three patients. We conclude that cricopharyngeal myotomy and diverticulum suspension constitute an effective form of treatment for pharyngoesophageal diverticulum.

Major liver resection without a blood transfusion: is it a realistic objective?

BACKGROUND: Observations from 75 patients undergoing resection of the liver during a recent period have been analyzed with respect to the use of perioperative blood transfusions and operative outcome. METHODS: Twenty-six patients were operated on for benign disease and 49 patients for malignant disease. Twenty-one patients underwent a right or left hepatectomy, 49 patients underwent removal of one or more anatomic segments of the liver, and five patients underwent wedge resection of a lesion in the liver. There was one postoperative death. RESULTS: The median blood loss was 0 units (range, 0 to 15 units). Sixty-three percent of the patients underwent operation without the need for a blood transfusion. The median postoperative stay was 10 days (range, 4 to 88 days). In the group of patients who did not undergo a blood transfusion the median postoperative stay was 9 days (range, 4 to 28 days), and in the patients who had a blood transfusion it was 14 days (range, 6 to 84 days) (p less than 0.0003). CONCLUSIONS: The performance of major liver resection without a blood transfusion is a realistic objective.

Wound metastasis after laparoscopy with different insufflation gases.

BACKGROUND: There is growing evidence that laparoscopy for malignancy is associated with an increased incidence of metastasis to port sites. This study investigated the effect of different insufflation gases on port-site metastasis after laparoscopy in an established animal model. METHODS: Forty-eight Dark Agouti rats with an established adenocarcinoma in the left flank underwent laparoscopic intraperitoneal tumor laceration. The gas used for insufflation was one of the following (12 rats in each group): (1) CO2, (2) N2O, (3) helium, or (4) air. Rats were killed 7 days after the procedure, and the port sites were examined for the presence of tumor metastasis. RESULTS: Tumor involvement of port sites was significantly less likely after helium insufflation than in the other groups (p < 0.0001). There was no significant difference between the air, CO2, and N2O groups. CONCLUSIONS: This study suggests that the development of metastases in port sites after laparoscopy may be influenced in part by the choice of insufflation gas used to create the pneumoperitoneum. In particular, helium was associated with a reduced rate of metastases.