User:Anthonyhcole/Esophageal cancer1

Esophageal cancer: A Review of epidemiology, pathogenesis, staging workup and treatment modalities (Not systematic. Seems clumsey and shallow.)

British Society of Gastroenterology guidelines on the diagnosis and management of Barrett's oesophagus

(UK/Ireland) Guidelines for the management of oesophageal and gastric cancer

Esophageal cancer: staging system and guidelines for staging and treatment

Current management of esophageal cancer

Definition
Should Howel–Evans syndrome ("focal non-epidermolytic palmoplantar keratoderma with carcinoma of the esophagus") be listed, or is it covered by the above?

Surgery

 * Perioperative optimisation

(UK/Ireland) (UK/Ireland) Historically, the majority of trials and meta-analyses evaluating combined modality treatment regimens in the treatment of oesophageal cancer have included squamous cell, adeno- and undifferentiated carcinomas, and tumours located in the proximal, mid and lower oesophagus as well as oesophago-gastric junctional tumours. These recommendations describe the current rationale for treatment strategies based on the main histological subtypes and tumour location. Preoperative radiotherapy A meta-analysis of preoperative radiotherapy for patients with resectable oesophageal carcinoma (any histological subtype) demonstrated that there was a 3—4% absolute improvement in OS (HR 0.89; 95% CI 0.78 to 1.01; p=0.062). Preoperative radiotherapy is therefore not recommended for potentially resectable oesophageal squamous cell or adenocarcinoma. Preoperative chemoradiation Preoperative chemoradiation followed by surgery is superior to surgery alone, as demonstrated in a meta-analysis of 10 RCTs comparing the two strategies. The HR for all-cause mortality was 0.81 (95% CI 0.70 to 0.93; p=0.002), corresponding to a 13% absolute difference in survival at 2 years. A significant benefit favouring preoperative chemoradiation over surgery alone was observed in oesophageal cancer of both squamous cell carcinoma and adenocarcinoma histological subtypes. There have been two further phase III trials comparing chemoradiation with surgery alone in patients with resectable oesophageal or oesophago-gastric junctional cancer. In the Dutch trial, paclitaxel and carboplatin were given with radiotherapy. The median survival for the combined therapy group was 49 months compared with 26 months for the surgery-alone arm. The majority of patients (74%) had distal oesophageal tumours and ~12% had oesophago-gastric junctional tumours. In the subgroup analysis, the beneficial effect was more pronounced in patients with squamous cell carcinoma (HR 0.34; 95% CI 0.17 to 0.65) compared with adenocarcinoma (HR 0.82; 95% CI 0.58 to 1.16). In the FFCD 9901 trial, patients were randomised to combination 5-FU/cisplatin and radiotherapy. The trial included 195 patients with localised stage I and II oesophageal squamous cell carcinoma (70%) and adenocarcinoma (29%). It was stopped early as there was no advantage to the combination regimen. In addition the operative mortality was significantly greater at 7.3% in those treated with chemoradiotherapy. The authors concluded that triple modality therapy was not indicated for such early stage oesophageal cancers. Preoperative chemoradiation alone and preoperative chemotherapy have not been directly compared in the context of a phase III RCT. A phase III RCT has been conducted comparing preoperative chemotherapy with preoperative chemotherapy and chemoradiation in locally advanced lower oesophageal and gastric cardia adenocarcinoma. This study closed early due to poor accrual. A trend towards improved survival in the chemotherapy plus chemoradiation arm was reported; however, this was associated with higher perioperative morbidity. There is a lack of assessment of HRQL in the RCTs comparing preoperative chemoradiation followed by surgery with surgery alone. Prospective series evaluating HRQL during chemoradiation and surgery show a deterioration of HRQL during preoperative treatment that recovers before surgery. After oesophagectomy there is a dramatic reduction in all aspects of HRQL, but no evidence that undergoing preoperative chemoradiation delays postoperative recovery of HRQL. Definitive chemoradiation Chemoradiation results in superior disease control and survival outcomes compared with radiation alone, but is associated with greater toxicity as seen in a review of 19 RCTs. There are few trials directly comparing definitive chemoradiation with surgery alone. A Chinese study of 80 patients with squamous cell carcinoma randomised to surgery or chemoradiation failed to show superiority of either strategy in terms of early DFS or OS. This trial was powered to show superiority of one treatment over another, but failed to report what magnitude of difference was considered superior. There is also a small Swedish study of 91 patients with either squamous cell carcinoma or adenocarcinoma of the oesophagus (50/50) that did not find any differences in treatment outcomes and equivalent survival. Adding surgery to chemoradiation for squamous cell carcinoma can improve local control rates compared with chemoradiation alone, but combined-modality therapy has not been shown to improve survival. A European study of 172 patients with squamous cell carcinoma randomised to induction chemotherapy followed by chemoradiotherapy (40 Gy) and surgery, or induction chemotherapy followed by chemoradiotherapy (at least 65 Gy) reported equivalent OS, but better local progression-free survival in the surgery arm. The addition of surgery also significantly increased treatment-related morbidity (12.8% vs 3.5%; p=0.03). A second European study, the French FFCD 9102 trial, recruited 444 patients with potentially resectable oesophageal cancer of predominantly squamous cell carcinoma subtype (90%). After induction chemoradiation, responding patients were randomised to further chemoradiation or surgery. Median OS was 19.3 months for patients randomised to further chemoradiation and 17.7 months for those randomised to surgery. Again toxicity was higher with combined-modality therapy. The study met its primary end point of non-inferiority for 2 year survival (p=0.03). Both the European studies were equivalence studies powered to determine whether the two treatments could be considered equivalent in terms of survival at 2 years. Equivalence was defined as a difference of <10% and 15%. It is questionable for a cancer with such a low survival rate that such differences would be deemed clinically important. The French trial included an observer-assessed measure of HRQL. Participants randomised to surgery reported worse HRQL 3 months after treatment, but similar scores in both arms were reported at 2 years. In this trial the HRQL assessment was performed by a non-blinded observer, introducing the possibility of bias. One non-randomised prospective series comparing HRQL between patients selected for definitive chemoradiation versus chemoradiation and surgery showed a similar pattern. In the first few months after treatment, HRQL was more severely comprised following a surgical than a non-surgical approach, but at 1 year scores were similar in both groups. In localised squamous cell carcinoma of the oesophagus, although definitive chemoradiation is a current recommended standard of care, there is a lack of evidence to support either a surgical or a non-surgical approach. The recent UK National Audit shows that the disease is treated by both approaches. Surgery should be considered in those treated with chemoradiation who at the end of treatment have histologically confirmed residual disease. A feasibility RCT is being set up to examine whether it is possible to effectively recruit into a trial comparing these treatment options. Ongoing clinical trials, such as SCOPE-1, are evaluating the additional effect of biological agents to treatment regimens, but trials with both clinical and HRQL outcomes comparing chemoradiation with combination treatments including surgery are still needed. For patients with localised oesophageal adenocarcinoma deemed unsuitable for surgery, definitive chemoradiation is a valid treatment option, with consideration given to participation in relevant clinical trials. Guidelines for the management of oesophageal and gastric cancer (2011)
 * Neoadjuvant, perioperative (neoadjuvant and adjuvant) and adjuvant therapy

Esophageal resection

 * Oesophageal surgery

First-line palliative chemotherapy for oesophageal, oesophago-gastric junctional and gastric cancer
The benefits of palliative chemotherapy over Best Supportive Care (BSC) in the treatment of advanced gastric cancer have been demonstrated in four RCTs. For patients considered suitable for systemic treatment, palliative chemotherapy improves median survival from 3 to 4 months with BSC alone to 7 to 10 months. Patients with advanced oesophageal cancer appear to derive the same benefits from systemic chemotherapy as those with gastric or oesophago-gastric junctional tumours, and those of good performance status should be offered combination chemotherapy. Several multicentre studies conducted in the UK that have defined the current standards of care in the treatment of advanced gastric or oesophago-gastric cancer have included patients with oesophageal tumours of squamous cell, adenocarcinoma and undifferentiated carcinoma histological subtypes. Many chemotherapy agents have efficacy in the treatment of advanced gastric cancer, and it is recognised that combination therapy is superior to single-agent therapy. There is, however, no international consensus regarding which combination chemo- therapy regimen should be used first line. Until recently, combination therapy with ECF has been the preferred regimen in the UK. In an RCT ECF was shown to have superior response rates (45% vs 21%, p=0.0002), median OS (8.9 vs 5.7 months, p=0.0009) and 2-year survival (13.5% vs 5.4%, p=0.03) over FAMTX (5-FU, adriamycin and metho-trexate). When compared with MCF (mitomycin C, cisplatin and infused 5-FU) in the treatment of oesophageal, oesophago-gastric junctional and gastric carcinomas, ECF had similar response rates and survival, but was preferable according to HRQL measures. Cisplatin combined with infused 5-FU (CF) is another commonly used regimen. Although ECF and CF have not been directly compared in a phase III randomised trial, a meta-analysis has demonstrated that three-drug regimens containing anthracyclines, cisplatin and 5-FU are superior to two-drug regimens containing either cisplatin/5-FU or anthracyclines/5-FU in terms of OS. The REAL-2 trial is the largest RCT evaluating first-line chemotherapy regimens for advanced oesophago-gastric cancer.

In a 2 3 2 factorial design, 1002 patients were randomised to ECF, ECX, EOF (epirubicin, oxaliplatin and infused 5-FU) or EOX (epirubicin, oxaliplatin and capecitabine). The study met its primary end points demonstrating non-inferiority in OS for capecitabine compared with infused 5-FU (HR for death, 0.86; 95% CI 0.80 to 0.99) and for oxaliplatin compared with cisplatin (HR for death, 0.92; 95% CI 0.80 to 1.10). There was no significant difference in HRQL between the four arms. EOX resulted in longer OS than ECF (HR for death 0.80; 95% CI 0.66 to 0.97; p=0.02). The combination of EOX is therefore at least as efficacious as ECF, with the additional advantages of a more convenient mode of administration (no requirement for hydration or central venous catheter insertion) and an acceptable toxicity profile. Further trials indicate that it is reasonable to substitute capecitabine for infused 5-FU, and oxaliplatin for cisplatin, in the treatment of advanced oesophagogastric cancer. In July 2010, the NICE appraisal of capecitabine determined that use of capecitabine in combination with plat- inum chemotherapy represented a cost-saving to the NHS over infused 5-FU. The V325 study is a randomised phase III trial comparing docetaxel in combination with cisplatin and infused 5-FU (DCF) with the doublet CF. A statistically significant improvement in OS (9.2 vs 8.6 months; p=0.020) was observed; however, this was at the cost of significantly more toxicity, including febrile neutropenia. In a phase II Swiss trial comparing DCF with ECF, DCF resulted in a much higher rate of complicated neutropenia (41% vs 18%). Docetaxel-containing regimens are not currently approved in the UK for this indication. Patients with adequate performance status with inoperable oesophago-gastric cancer should be considered for combination chemotherapy with EOX or ECX. (UK/Ireland) Guidelines for the management of oesophageal and gastric cancer (2011)

First-line palliative targeted agents in combination with chemotherapy
For patients with advanced HER-2-positive oesophago-gastric junctional or gastric cancer, the addition of trastuzumab to a cisplatin and fluoropyrimidine (5-FU or capecitabine) chemotherapy doublet resulted in a statistically significant improvement in response rate (47.3% vs 34.5%; p=0.0017), progression-free survival (6.7 vs 5.5 months; p=0.0002) and median OS (13.8 vs 11.1 months; p=0.0048). Tumours were considered HER-2 positive if the immunohistochemistry score was 3+ or if fluorescent in situ hybridisation (FISH) was positive for HER-2 overexpression. Trastuzumab is now licensed in the UK for patients with previously untreated metastatic HER-2-positive (defined as IHC 3+) gastric or oesophago-gastric junctional adenocarcinoma. This regimen is a valid first-line treatment option for HER-2-positive advanced gastric and oesophago-gastric junctional cancers. How this regimen compares with chemotherapy-only triplet regimens is unknown. The use of other targeted agents, including cetuximab, panitumumab and bevacizumab, in combination with chemotherapy should remain restricted to the context of clinical trials. (UK/Ireland) Guidelines for the management of oesophageal and gastric cancer (2011)

Second-line palliative chemotherapy for oesophago-gastric junctional and gastric cancer
The standard treatment option for patients with advanced gastric or gastro-oesophageal junction tumours is uncertain, and wherever possible it is recommended that patients are enrolled into a RCT. Data from phase II trials have demonstrated activity in the second-line setting for the following agents/combination regimes: irinotecan in combination with cisplatin or fluoropyrimidines, FOLFOX (folinic acid, 5-FU, oxaliplatin), docetaxel monotherapy, docetaxel in combination with oxaliplatin, and paclitaxel alone or in combination with platinum agents. (UK/Ireland) Guidelines for the management of oesophageal and gastric cancer (2011)

Chemotherapy to downstage initially inoperable locally advanced disease for surgery
There is anecdotal evidence that in selected cases, palliative chemotherapy may result in sufficient downstaging of initially. inoperable locally advanced disease to allow surgical resection. For instance, in the randomised trial comparing ECF with FAMTX in patients with locally advanced disease, 12 out of 43 patients treated with ECF (nine complete resections) and five out of 51 patients treated with FAMTX (four complete resections) proceeded to surgery. Of these 17 patients, nine survived for ≥2 years from randomisation. There have not been any randomised controlled studies to compare the addition of surgery to palliative chemotherapy with palliative chemotherapy alone. Such studies may become possible and worthwhile if minimal access surgery can be achieved with reduced complications and better recovery of HRQL than standard open surgery. (UK/Ireland) Guidelines for the management of oesophageal and gastric cancer (2011)

Palliative radiotherapy for oesophageal cancer
Dysphagia and pain are common symptoms associated with unresectable oesophageal cancer. External beam radiotherapy is a local palliative measure that can improve symptoms and is associated with minimal toxicity, but relief from dysphagia is often slow in onset compared with stent insertion. Differences in outcome in terms of HRQL, dysphagia-free survival and OS between different 'locoregional' palliative treatments, particularly in the era of more effective chemotherapy, requires further investigation. (UK/Ireland) Guidelines for the management of oesophageal and gastric cancer (2011)

Endoscopic methods
Oesophageal intubation is an effective means of relieving dysphagia in a single procedure, and stents are now widely used. A Health Technology Assessment (HTA)-sponsored pragmatic RCT of the cost-effectiveness of palliative treatments for patients with inoperable oesophageal cancer studied different types of oesophageal tubes and compared these with non-stent alternatives. This study confirmed the observations made previously that although the older rigid plastic tubes (Atkinson and Celestin) were cheap, they were also associated with a worse quality of swallowing and increased late morbidity. Small (18 mm) diameter self-expanding metal stents (SEMS) were as effective as large (24 mm) stents but induced less pain.
 * Oesophageal intubation

Two-thirds of patients treated with a metal stent can eat solids initially, and there appears to be little difference between the effectiveness of different types of metal stents, although one small RCT suggested that covered metal stents are more effective than non-covered stents as they are complicated by less tumour ingrowth. In the HTA trial, dysphagia was actually worse in 10% of patients 6 weeks after stent insertion. In addition, although initial hospital stay was brief, the total number of inpatient days was in the order of 2—3 weeks, with a median survival of 4 months. There was no difference in cost or effectiveness between SEMS and non-SEMS treatments. It was concluded that an RCT of 18 mm SEMS versus non-stent treatments with survival and HRQL end points would be helpful, as would an audit of palliative patient admissions to determine the reasons and need for inpatient hospital care.

Patients can suffer acid reflux after stent insertion. A series of antireflux stents have been developed to overcome this. Several small RCTs have been performed, but results are inconclusive. Another new development has been the introduction of plastic (Polyflex) stents. A number of small RCTs have shown that these seem to be more difficult to place and have a higher risk of late complications, particularly migration, than metal stents. In addition, some aspects of HRQL were poorer with plastic stents.

Early complications after stent insertion are unusual and, in all RCTs, procedural mortality was acceptable at ≤2%. Late complications are, however, common and occur in up to 25% of patients. These include recurrent dysphagia due to tumour overgrowth for covered or ingrowth for uncovered stents, bolus obstruction and stent migration. In one retrospective study, membrane degradation of covered stents occurred in 8% of cases, leading to tumour ingrowth or reopening of a tracheo-oesophageal fistula which had initially been successfully covered by a stent.

The combination of radiotherapy and stents can be complicated. In patients who have had a stent placed before palliative external radiotherapy it is important to realise that stents appear to increase the radiotherapy dose delivered to the oesophageal mucosa.

Patients who have been previously treated with radiotherapy who later have stents inserted are at increased risk of complications. These may include increased risk of chest pain or severe complications such as fever, bleeding, perforation and fistula formation, which rose in one study from 3% to 23%. In another study, these findings were not confirmed. Other small studies suggest that these complications are relevant only in patients with T4 disease. (UK/Ireland) Guidelines for the management of oesophageal and gastric cancer (2011)

As increasing numbers of patients are now treated with palliative radiotherapy, postradiotherapy strictures are increasingly common. Dilatation for these can be effective in ~80% of treatment sessions, with fewer complications than stent insertion.
 * Oesophageal dilatation

The SIREC multicentre RCT of 12 Gy brachytherapy versus stent insertion included 209 patients in The Netherlands with inoperable oesophageal cancer. The primary outcome was relief of dysphagia during follow-up, and secondary outcomes were complications, treatment for persistent or recurrent dysphagia, HRQL and cost. Analysis was by intention to treat. Dysphagia improved more rapidly after stent placement (n=108) than after brachytherapy (n=101), but long-term relief of dysphagia was better after brachytherapy. Stent placement had more complications than brachytherapy (33% vs 21%; p=0.02), which was mainly due to an increased incidence of late haemorrhage (13% vs 5%; p=0.05). Groups did not differ for persistent or recurrent dysphagia (p=0.81), or for median survival (p=0.23). Patients undergoing brachytherapy reported significantly better role, emotional, cognitive and social function than those undergoing stent placement. Total medical costs were also much the same for stent placement and brachytherapy. The authors concluded that despite slow improvement, single-dose brachytherapy gave better long-term relief of dysphagia than metal stent placement. Since brachytherapy was also associated with fewer complications than stent placement, they recommended it as the primary treatment for palliation of dysphagia from oesophageal cancer. Unsurprisingly, physical and role function and other generic aspects of HRQL deteriorated over time before death, but the decline was more pronounced in the stent group. Given the delay to onset of benefit after brachytherapy, patient data from this study and a consecutive series (n=396) were analysed to create a prognostic model to help inform which patients should be offered stents and which should receive single-dose brachytherapy. Significant prognostic factors for survival included tumour length, WHO performance score and the presence of metastases (multivariable p <0.001) together with age and gender. This model could satisfactorily separate patients with a poor, intermediate and relatively good prognosis within the SIREC trial. For the poor prognosis group, the difference in dysphagia-adjusted survival was 23 days in favour of stent placement compared with brachytherapy (77 vs 54 days, p=0.16). For the other prognostic groups, brachytherapy resulted in a better dysphagia-adjusted survival. The costs of both treatments were very similar.
 * Brachytherapy and stents

In another prospective study, the palliative effect of self-expandable stent placement was compared with that of endoluminal brachytherapy regarding the effect on HRQL and specific symptoms. Sixty-five patients with advanced cancer of the oesophagus or oesophago-gastric junction were randomised to treatment with either an Ultraflex expandable stent or high dose rate endoluminal brachytherapy with three doses of 7 Gy given in 2—4 weeks. This study was small and differences in baseline HRQL scores were observed between the two groups, but results were similar to the larger SIREC trial. In a related study by the same group, stenting was considered more cost-effective than brachytherapy.

Small retrospective case series have shown that covered metal stents can be used successfully to cover iatrogenic oesophageal perforation and tracheo-oesophageal fistulae with minimal procedural morbidity and almost zero mortality. A small number of patients with high oesophageal tumours involving the trachea or major bronchi may benefit from tracheal stenting. This may be combined with oesophageal stenting, but tracheal stenting should always be done first to minimise the risk of causing stridor.
 * Iatrogenic perforation and tracheo-oesophageal fistulae

Various small retrospective cost-effective analyses have compared oesophageal stenting with laser therapy. The mean survival and the cost were similar. In a small prospective randomised trial comparing stents with laser followed by palliative radiotherapy, there was no difference in survival but the costs of laser and radiotherapy were higher than stents. An RCT of 65 patients compared thermal laser ablation with stents. HRQL deteriorated in the stent group but not in the laser-treated group. Patients treated by laser lived longer than patients treated by stent insertion, but the cost of laser therapy was higher.
 * Laser therapy and stents

Fifty-three patients were entered into an RCT comparing treatment response with a self-expandable oesophageal stent loaded with [125I] iodine seeds for intraluminal brachytherapy versus treatment response with a conventional self-expandable covered stent in patients with advanced oesophageal cancer. Dysphagia improved in both groups within the first month after stent placement, but was better in the irradiation—stent group than in the control group after 2 months (p<0.05). The median and mean survival times were better in the irradiation—stent group than in the control group, and the differences were significant (p<0.001). Haemorrhage occurred in a large number of patients in both groups in this study (30%).
 * Novel combinations of stents with other therapies

PDT using Photofrin is a relatively new technique which remains unproven. PDT was successful in relieving dysphagia for ~9 weeks in 85% of 215 patients treated in one retrospective analysis. Patients living >2 months required re-intervention to maintain palliation of malignant dysphagia, and a multimodality treatment approach was common in this study. In another study, almost half the patients required a second treatment with PDT and 10% were later stented. Given that skin photosensitivity after Photofrin administration lasts for 3 months, and mean survival is <6 months, this approach has a significant side effect profile. PDT has been suggested as a salvage treatment for local recurrence after chemoradiotherapy. Compared with using it as a primary therapy, the risk of complications for PDT after chemoradiotherapy is eight times higher.
 * Photodynamic therapy

APC has been evaluated as palliation in a few studies. A retrospective study of 31 patients described complications and tolerance. These patients underwent a median of five treatments per patient (range 1—18). Recanalisation enabling passage of the scope was achieved in 89% of treatments. The dysphagia-free interval was 25 days (range 1—175 days). Perforation was seen in three patients (10%); procedure-related mortality was 1.2%. The median hospital stay for every treatment was 2 days (range 1—27 days). APC was well tolerated, safe and effective, and is an easy and cheap technique with no further restrictions than conventional monopolar electrocoagulation. A study to prospectively evaluate a new high-power system (hp-APC) evaluated palliative treatment of oesophageal cancer as one indication. The mean number of treatment sessions required was 2.3 (range 1—5). Minor complications (pain, dysphagia, neuromuscular irritation or asymptomatic gas accumulation in the intestinal wall) were observed in 13%. Major complications (perforation or stenosis) occurred in two patients (0.9%). Because of the low number of treatment sessions required, it was suggested that hp-APC could be used as an alternative to Nd:YAG laser treatment in tumour debulking. APC also has value in haemorrhage and in recanalisation of blocked stents, particularly with proximal or distal luminal overgrowth. This modality, nevertheless, remains experimental.
 * Argon plasma coagulation

In a prospective RCT comparing ethanol injection with laser therapy, both resulted in similar long-term outcomes, but patients treated with ethanol had a much higher use of analgesia, at 78% compared with 5% with laser. In the HTA study, a small number had primary treatment with ethanol. All developed complete dysphagia, leading the authors to recommend that it should not be used as primary treatment. (UK/Ireland) Guidelines for the management of oesophageal and gastric cancer (2011)
 * Injection therapy

Monitoring
Regular review of patients following treatment of oesophago-gastric cancer can fulfil a number of roles including aftercare and rehabilitation following therapeutic intervention: symptom management, supportive care and surveillance. The complexity of oesophago-gastric cancer treatment frequently induces symptoms which adversely affect HRQL. Specific post-treatment side effects including dysphagia from anastomotic stricture, diarrhoea related to vagotomy and post-thoracotomy pain need appropriate management. Disorders of physiology are not uncommon and may require careful assessment and treatment by a specialist gastroenterologist. These are often insidious, and change in fat and bile salt absorption as well as bacterial overgrowth may be unrecognised by the inexperienced.
 * Follow-up

Although regular review may identify early recurrence, there is no evidence for specific investigations nor that such an approach can affect OS. Endoscopy, cross-sectional imaging and tumour markers have all been evaluated, but lack specificity or sensitivity. It is accepted that patients may gain psychological support from regular review, although few studies have formally evaluated this, and patients may feel more anxious prior to a planned hospital visit. Regular access to CNS support may obviate this effect. Evidence from The Netherlands shows that nurse follow-up after oesophagectomy is both cost-effective and provides equal if not better patient experience.

The concept of survivorship or living beyond cancer is evolving, and experience of patient-led self-referral rather than clinic review at regular intervals is developing. This requires careful discussion and explanation of potential problems with each patient, taking into account individual risk and prognosis in the context of underlying stage of disease.

Clinical nurse specialists
The number of CNSs in the UK has increased to 1800, of which 10% are UGI CNSs. However recent evidence from the NHS peer review programme show that CNS provision for UGI cancer particularly at cancer units is among the lowest for all cancer sites. The role of the nurse includes clinical education, psychological support, research and consultation. The extent of the CNS role is difficult to measure because of the multifaceted nature of the work, complexity of the patient pathway and the more specific requirement to respond to individual patient needs.

Leary and colleagues have studied the work patterns of 463 CNSs (including gastrointestinal nurses) from the UK. Data demonstrate that 68% of time is spent on clinical matters. of which 48% is physical care and 32% psychological care. Not surprisingly, 33% of the nurses' time is given to telephone advice and 34% spent in an outpatient setting. The remaining time is spent on administration (24%), research (2%) and education (3%). CNSs use 'brokering' skills, provide 'clinical rescue work', advice on symptom control and support, and negotiate care pathways, all of which are intended to prevent adverse events, particularly readmission. The impact of psychological care and tailored information given in a supportive environment improves the patients' experience and HRQL. The results from the National Oesophago-Gastric Cancer Audit provide further support from patient experience surveys: 'the CNS role is the pillar in the system'.

The MDT is central to patient care, with CNSs having an integral role; consulting with medical, surgical and allied healthcare professionals in order to provide a co-ordinated approach to care, enhancing quality of care and patients' wellbeing. Nurses also have access to important information particularly acting as the patient's advocate that may influence clinical decisions, and it is therefore essential that MDTs listen to their views.

Prognosis
Prognostic factors