Enhancing the emergency general surgical service: an example of the aggregation of marginal gains.

INTRODUCTION: We aimed to enhance the emergency general surgical service in our high-volume centre in order to reduce four-hour target breaches, to expedite senior decision making and to avoid unnecessary admissions. MATERIALS AND METHODS: The aggregation of marginal gains theory was applied. A dual consultant on-call system was established by the incremental employment of five emergency general surgeons with a specialist interest in colorectal or oesophagogastric surgery. A surgical ambulatory care unit, which combines consultant-led clinical review with dedicated next-day radiology slots, and a dedicated working week half-day gastrointestinal urgent theatre session were instituted to facilitate ambulatory care pathways. RESULTS: The presence of two consultant surgeons being on call during weekday working hours decreased the four-hour target breaches and allowed consultant presence in the surgical ambulatory care clinic and the gastrointestinal urgent theatre list. Of 1371 surgical ambulatory care clinic appointments within 30 months, 1135 (82.7%) avoided a hospital admission, corresponding to savings of £309,752 . The coordinated functioning of the surgical ambulatory care clinic and the gastrointestinal urgent theatre list resulted in statistically significantly reduced hospital stays for patients operated for abscess drainage (gastrointestinal urgent theatre median 11 hours (interquartile range 3, 38) compared with emergency median 31 hours (interquartile range 24, 53), P < 0.001) or diagnostic laparoscopy/appendicectomy (gastrointestinal urgent theatre median 52 hours (interquartile range 41, 71) compared with emergency median 61 hours (interquartile range 43, 99), P = 0.005). Overnight surgery was reduced with only surgery that was absolutely necessary occurring out of hours. CONCLUSION: The expansion of the 'traditional' on-call surgical team, the establishment of the surgical ambulatory care clinic and the gastrointestinal urgent theatre list led to marginal gains with a reduction in unnecessary inpatient stays, expedited decision making and improved financial efficiency.

Changes in volume, clinical practice and outcome after reorganisation of oesophago-gastric cancer care in England: A longitudinal observational study.

AIM: The centralisation of oesophago-gastric (O-G) cancer services in England was recommended in 2001, partly because of evidence for a volume-outcome effect for patients having surgery. This study investigated the changes in surgical services for O-G cancer and postoperative mortality since centralisation. METHODS: Patients with O-G cancer who had an oesophageal or gastric resection between April 2003 and March 2014 were identified in the national Hospital Episodes Statistics database. We derived information on the number of NHS trusts performing surgery, their surgical volume, and the number of consultants operating. Postoperative mortality was measured at 30 days, 90 days and 1 year. Logistic regression was used to examine how surgical outcomes were related to patient characteristics and organisational variables. RESULTS: During this period, 29 205 patients underwent an oesophagectomy or gastrectomy. The number of NHS trusts performing surgery decreased from 113 in 2003-04 to 43 in 2013-14, and the median annual surgical volume in NHS trusts rose from 21 to 55 patients. The annual 30 day, 90 day and 1 year mortality decreased from 7.4%, 11.3% and 29.7% in 2003-04 to 2.5%, 4.6% and 19.8% in 2013-14, respectively. There was no evidence that high-risk patients were not undergoing surgery. Changes in NHS trust volume explained only a small proportion of the observed fall in mortality. CONCLUSION: Centralisation of surgical services for O-G cancer in England has resulted in lower postoperative mortality. This cannot be explained by increased volume alone.

Endoluminal Vacuum Therapy (E-Vac): A Treatment Option in Oesophagogastric Surgery.

BACKGROUND: Leaks from the upper gastrointestinal tract often pose a management challenge, particularly when surgical treatment has failed or is impossible. Vacuum therapy has revolutionised the treatment of wounds, and its role in enabling and accelerating healing is now explored in oesophagogastric surgery. METHODS: A piece of open cell foam is sutured around the distal end of a nasogastric tube using a silk suture. Under general anaesthetic, the foam covered tip is placed endoscopically through the perforation and into any extra-luminal cavity. Continuous negative pressure (125 mmHg) is then applied. Re-evaluation with change of the negative pressure system is performed every 48-72 h depending on the clinical condition. Patients are fed enterally and treated with broad-spectrum antibiotics and anti-fungal medication until healing, assessed endoscopically and/or radiologically, is complete. RESULTS: Since April 2011, twenty one patients have been treated. The cause of the leak was postoperative/iatrogenic complications (14 patients) and ischaemic/spontaneous perforation (seven patients). Twenty patients (95%) completed treatment successfully with healing of the defect and/or resolution of the cavity and were subsequently discharged from our care. One patient died from sepsis related to an oesophageal leak after withdrawing consent for further intervention following a single endoluminal vacuum (E-Vac) treatment. In addition, two patients who were successfully treated with E-Vac for their leak subsequently died within 90 days of E-Vac treatment from complications that were not associated with the E-Vac procedure. In two patients, E-Vac treatment was complicated by bleeding. The median number of E-Vac changes was 7 (range 3-12), and the median length of hospital stay was 35 days (range 23-152). CONCLUSIONS: E-Vac therapy is a safe and effective treatment for upper gastrointestinal leaks and should be considered alongside more established therapies. Further research is now needed to understand the mechanism of action and to improve the ease with which E-Vac therapy can be delivered.

3D bioengineered tissues: From advancements in in vitro safety to new horizons in disease modeling.

Research aimed at more fully emulating human biology in vitro has rapidly progressed in recent years with advancements in 3D tissue engineering and microphysiological systems. The initial target of such systems has been directed towards drug and chemical safety assessment, with the goal of improving sensitivity and predictive capabilities. Here we discuss recent developments of in vitro organ culture systems, and their future applications in modeling human disease.

Population-based cohort study of the management and survival of patients with early-stage oesophageal adenocarcinoma in England.

BACKGROUND: Until recently, oesophagectomy was the treatment of choice for early oesophageal cancer. Endoscopic treatment has been introduced relatively recently. This observational national database study aimed to describe how endoscopic therapy has been introduced in England and to examine the safety of this approach. METHODS: A population-based cohort study was undertaken of patients diagnosed with oesophageal adenocarcinoma between October 2007 and June 2009 using three linked national databases. Patients with early-stage disease (T1 tumours with no evidence of spread) were identified, along with the primary treatment modality where treatment intent was curative. Short-term outcomes after treatment and 5-year survival were evaluated. RESULTS: Of 5192 patients diagnosed with oesophageal adenocarcinoma, 306 (5·9 per cent) were considered to have early-stage disease before any treatment, of whom 239 (79·9 per cent of 299 patients with data on treatment intent) were managed with curative intent. Of 175 patients who had an oesophagectomy, 114 (65·1 (95 per cent c.i. 57·6 to 72·7) per cent) survived for 5 years. Among these, 47 (30·3 per cent of 155 patients with tissue results available) had their disease upstaged after pathological staging; this occurred more often in patients who did not have staging endoscopic ultrasonography before surgery. Of 41 patients who had an endoscopic resection, 27 (66 (95 per cent c.i. 49 to 80) per cent) survived for 5 years. Repeat endoscopic therapy was required by 23 (56 per cent) of these 41 patients. CONCLUSION: Between 2007 and 2009, oesophagectomy remained the initial treatment of choice (73·2 per cent) among patients with early-stage oesophageal cancer treated with curative intent; one in five patients were managed endoscopically, and this treatment was more common in elderly patients. Although the groups had different patient characteristics, 5-year survival rates were similar.

Risk adjustment models for short-term outcomes after surgical resection for oesophagogastric cancer.

BACKGROUND: Outcomes for oesophagogastric cancer surgery are compared with the aim of benchmarking quality of care. Adjusting for patient characteristics is crucial to avoid biased comparisons between providers. The study objective was to develop a case-mix adjustment model for comparing 30- and 90-day mortality and anastomotic leakage rates after oesophagogastric cancer resections. METHODS: The study reviewed existing models, considered expert opinion and examined audit data in order to select predictors that were consequently used to develop a case-mix adjustment model for the National Oesophago-Gastric Cancer Audit, covering England and Wales. Models were developed on patients undergoing surgical resection between April 2011 and March 2013 using logistic regression. Model calibration and discrimination was quantified using a bootstrap procedure. RESULTS: Most existing risk models for oesophagogastric resections were methodologically weak, outdated or based on detailed laboratory data that are not generally available. In 4882 patients with oesophagogastric cancer used for model development, 30- and 90-day mortality rates were 2·3 and 4·4 per cent respectively, and 6·2 per cent of patients developed an anastomotic leak. The internally validated models, based on predictors selected from the literature, showed moderate discrimination (area under the receiver operating characteristic (ROC) curve 0·646 for 30-day mortality, 0·664 for 90-day mortality and 0·587 for anastomotic leakage) and good calibration. CONCLUSION: Based on available data, three case-mix adjustment models for postoperative outcomes in patients undergoing curative surgery for oesophagogastric cancer were developed. These models should be used for risk adjustment when assessing hospital performance in the National Health Service, and tested in other large health systems.

Variations among 5 European countries for curative treatment of resectable oesophageal and gastric cancer: A survey from the EURECCA Upper GI Group (EUropean REgistration of Cancer CAre).

INTRODUCTION: EURECCA (EUropean REgistration of Cancer CAre) is a network aiming to improve cancer care by auditing outcome. EURECCA initiated an international survey to share and compare patient outcome for oesophagogastric cancer. The present study assessed how a uniform dataset could be introduced for oesophagogastric cancer in Europe. METHODS: Participating countries presented data using common data items describing patients', disease, strategies, and outcome characteristics. Patients treated with curative surgery for squamous cell carcinoma (SCC) or adenocarcinoma (ACA) were included. RESULTS: United Kingdom, the Netherlands, France, Spain and Ireland participated. There were differences in data source ranging from national registries to large collaborative groups. 4668 oesophagogastric cancer cases over a 12 months period were included. The predominant histological type was ACA. Disease stage tended to be earlier in France and Ireland. In oesophageal and junctional cancers neoadjuvant chemoradiotherapy was preferred in the Netherlands and Ireland contrasting with chemotherapy in the UK and France. All countries used perioperative chemotherapy in gastric cancer but 1/3 of patients received this treatment. The mean R0 resection rate was 86% for oesophageal and junctional resections and 88% for gastric resections. Postoperative mortality varied from 1% to 7%. CONCLUSION: This European survey shown that implementing a uniform treatment and outcome data format of oesophagogastric cancer is feasible. It identified differences in disease presentation, treatment approaches and outcome, which need to be investigated, especially by increasing the number of participating countries. Future comparisons will facilitate developments in treatment for the benefit of patient outcomes.

Common data items in seven European oesophagogastric cancer surgery registries: towards a European upper GI cancer audit (EURECCA Upper GI).

AIMS: Seven countries (Denmark, France, Ireland, the Netherlands, Poland, Sweden, United Kingdom) collaborated to initiate a EURECCA (European Registration of Cancer Care) Upper GI project. The aim of this study was to identify a core dataset of shared items in the different data registries which can be used for future collaboration between countries. METHODS: Item lists from all participating Upper GI cancer registries were collected. Items were scored 'present' when included in the registry, or when the items could be deducted from other items in the registry. The definition of a common item was that it was present in at least six of the seven participating countries. RESULTS: The number of registered items varied between 40 (Poland) and 650 (Ireland). Among the 46 shared items were data on patient characteristics, staging and diagnostics, neoadjuvant treatment, surgery, postoperative course, pathology, and adjuvant treatment. Information on non-surgical treatment was available in only 4 registries. CONCLUSIONS: A list of 46 shared items from seven participating Upper GI cancer registries was created, providing a basis for future quality assurance and research in Upper GI cancer treatment on a European level.

Ethnicity in relation to incidence of oesophageal and gastric cancer in England.

BACKGROUND: This study investigated the variation in incidence of all, and six subgroups of, oesophageal and gastric cancer between ethnic groups. METHODS: Data on all oesophageal and gastric cancer patients diagnosed between 2001 and 2007 in England were analysed. Self-assigned ethnicity from the Hospital Episode Statistics dataset was used. Male and female age-standardised incidence rate ratios (IRRs) were calculated for each ethnic group, using White groups as the references. RESULTS: Ethnicity information was available for 83% of patients (76 130/92 205). White men had a higher incidence of oesophageal cancer, with IRR for the other ethnic groups ranging from 0.17 95% confidence interval (CI) (0.15-0.20) (Pakistani men) to 0.58 95% CI (0.50-0.67) (Black Caribbean men). Compared with White women, Bangladeshi women (IRR 2.02 (1.24-3.29)) had a higher incidence of oesophageal cancer. For gastric cancer, Black Caribbean men (1.39 (1.22-1.60)) and women (1.57 (1.28-1.92)) had a higher incidence compared with their White counterparts. In the subgroup analysis, White men had a higher incidence of lower oesophageal and gastric cardia cancer compared with the other ethnic groups studied. Bangladeshi women (3.10 (1.60-6.00)) had a higher incidence of upper and middle oesophageal cancer compared with White women. CONCLUSION: Substantial ethnic differences in the incidence of oesophageal and gastric cancer were found. Further research into differences in exposures to risk factors between ethnic groups could elucidate why the observed variation in incidence exists.

Venous thromboembolism in oesophago-gastric carcinoma: incidence of symptomatic and asymptomatic events following chemotherapy and surgery.

Venous thromboembolism (VTE) is a frequent cause of morbidity and mortality in patients with cancer and those having chemotherapy. However, the incidence of VTE during radical treatment for patients with oesophago-gastric cancer is poorly documented. The incidence of VTE was assessed in 200 consecutive patients with oesophago-gastric cancer having surgery with curative intent; 132 (66%) had neo-adjuvant chemotherapy, 37 (18.5%) had adjuvant chemotherapy and 64 (32%) had no chemotherapy. Patients received 40 mg of Enoxaparin subcutaneously daily during the peri-operative hospital stay. Asymptomatic VTE were detected by routine chest computed tomography (CT) pre and post surgery. Symptomatic patients with suspected VTE were investigated and treated as clinically appropriate. Twenty six patients (13%) developed VTE of which 14 (54%) were symptomatic; 12/26 (46%) VTE were detected pre-operatively, all during or after neo-adjuvant chemotherapy, and 14/26 (54%) post-operatively. There were two post-operative deaths caused by pulmonary emboli occurring at days 24 and 56 respectively despite peri-operative VTE prophylaxis. Multivariate analysis demonstrated that neo-adjuvant chemotherapy was the only factor that predicted pre-operative VTE (p = 0.073) and any VTE (p = 0.045). This study found a 13% incidence of VTE in patients undergoing therapy with curative intent for oesophago-gastric cancer and a statistically significant association between neo-adjuvant chemotherapy and VTE. Half of the patients with VTE were asymptomatic but two had fatal PE's. Current VTE prophylaxis regimens for this patient group may be inadequate.

Can culture confirmation of gonococcal infection be improved in female subjects found to be positive by nucleic acid amplification tests in community clinics?

BACKGROUND: Use of nucleic acid amplification tests (NAATs), such as strand displacement assay (SDA, BD ProbeTec C trachomatis/N gonorrhoeae Amplified DNA Assay), for the detection of gonococcal infection in the community is controversial because of the possibility of false-positive results in low prevalence populations. AIM: To evaluate if culture confirmation of gonococcal infection can be improved for subjects found to be positive by BD ProbeTec in community clinics. METHODS: Two cervical swabs were collected for culture to confirm NAAT positive results in women aged over 16 years-a majority of whom were <25 years and asymptomatic. One swab was urgently transported (UTP) and processed in the laboratory within 2 hours whereas the other swab (RTP) was stored at 4 degrees C, transported at room temperature and processed 4-72 hours after collection depending on the time and day of collection. RESULTS: Altogether, 56 subjects with NAAT positive results were recruited into the study. Nine (16.1%) subjects who were culture negative were excluded from final analysis due to prior antibiotic treatment (4/9) or the culture having been taken more than 1 month after the NAAT was positive (4/9) or an incorrect specimen being received (1/9). Overall, 41/47 (87.2%) NAAT positive subjects were confirmed by culture. In total, 40/47 (85.1%) UTP swabs and 27/47 (57.4%) RTP swabs were positive (p<0.05). CONCLUSION: This study shows that culture confirmation in NAAT positive subjects in a community gonococcus screening programme can be significantly improved by urgent transportation to and processing of specimens in the laboratory.

Generation and validation of a revised classification for oesophageal and junctional adenocarcinoma.

BACKGROUND: Oesophageal adenocarcinoma is the commonest oesophageal malignancy in the West, but is staged using a system designed for squamous cell carcinoma. The aim was to develop and validate a staging system for oesophageal and junctional adenocarcinoma. METHODS: Patients with oesophageal adenocarcinoma (Siewert types I and II) undergoing oesophagectomy with curative intent were randomly assigned to generation (313 patients) and validation (131) data sets. Outcome in the generation data set was associated with histopathological features; a revised node (N) classification was derived using recursive partitioning and tested on the validation data set. RESULTS: A revised N classification based on number of involved lymph nodes (N0, none; N1, one to five; N2, six or more) was prognostically significant (P < 0.001). Patients with involved nodes on both sides of the diaphragm, regardless of number, had the same outcome as the N2 group. When applied to the validation data set, the revised classification (including nodal number and location) provided greater discrimination between node-positive patients than the existing system (P < 0.001). CONCLUSION: A revised N classification based on number and location of involved lymph nodes provides improved prognostic power and incorporates features that may be useful before surgery in clinical management decisions.

Confirmation of BD ProbeTec Neisseria gonorrhoeae reactive samples by Gen-Probe APTIMA assays and culture.

BACKGROUND: Use of nucleic acid amplification tests (NAATs), such as strand displacement assay (SDA), for the detection of gonococcal infection in low prevalence populations is controversial because of the likelihood of false positive results. Use of supplementary NAATs with alternative target sites has been recommended for confirmation of primary NAAT results. AIM: To evaluate if SDA reactive specimens for Neisseria gonorrhoeae, which were either culture positive or negative, can be confirmed by alternative target NAATs such as transcription-mediated assays (TMA). METHODS: SDA reactive specimens were retested by TMA using APTIMA Combo 2 (AC2) and APTIMA GC (AGC) assays. Two different methods of specimen preparation were used to test the specimens. In method A, residual extract after SDA was retested and in method B, the original clinical specimen was re-extracted in TMA medium and then retested. Cervical or urethral swabs were requested to confirm the SDA results by culture. RESULTS: By method A, 26/49 (53.1%) of SDA positive specimens were positive by AC2 and/or AGC; 14/27 (51.8%) culture confirmed SDA positive tests were positive by AC2 and/or AGC. By method B, 38/39 (97.3%) SDA positive results were confirmed by both AC2 and AGC. All the 25 culture confirmed SDA positive tests were confirmed by both AC2 and AGC; 5/6 SDA positive tests that were culture negative were confirmed by both AC2 and/AGC. CONCLUSION: Alternative target site NAATs, such as AC2 and AGC, can be used to confirm SDA positive results using the same clinical specimen. There is high concordance between the three NAATs.

Histopathological and molecular analysis of gastrectomy specimens from hereditary diffuse gastric cancer patients has implications for endoscopic surveillance of individuals at risk.

Hereditary diffuse gastric cancer (HDGC) is caused by germline E-cadherin (CDH1) mutations in 25-40% of tested families. Management options for asymptomatic mutation carriers are fraught, since endoscopic surveillance can miss cancer foci and prophylactic gastrectomy has profound clinical sequelae. The aims of this study were to evaluate the impact of current surveillance practices on pre-operative diagnosis and to characterize the microscopic lesions in gastrectomy specimens to better inform clinical practice. Histological assessment and mapping of endoscopic surveillance and gastrectomy specimens were performed for eight asymptomatic CDH1 mutation carriers. E-cadherin expression and proliferation were analysed and evidence of epithelial-mesenchymal transition (EMT) was sought by immunohistochemistry for vimentin and cytokeratin 8/18. Four of eight patients had lesions detected at endoscopic surveillance. A median of 20.5 (range 0-66) signet ring foci were identified per gastrectomy (including in situ lesions and pagetoid spread). Foci were predominantly identified in the fundus and body (90% endoscopic biopsies and 85% in gastrectomy). The likelihood of detecting foci pre-operatively was positively correlated with the number of biopsies taken and the number of lesions in the gastrectomy specimen. E-cadherin expression in gastrectomy specimens was reduced or absent in all of the foci compared with the intervening gastric tissue, suggesting that these lesions are polyclonal. The foci had a low proliferative index (<2%) and there was no evidence for EMT. Multiple endoscopic biopsy sampling of the gastric mucosa increases the yield of microscopic cancer foci. The low proliferative index and lack of EMT suggests that these foci may represent an indolent stage of HDGC.

Salvage oesophagectomy after local failure of definitive chemoradiotherapy.

BACKGROUND: Definitive chemoradiotherapy (CRT) is one treatment option for locally advanced oesophageal carcinoma. CRT typically consists of high-dose (50-66 Gy) external beam radiotherapy concurrent with 5-fluorouracil and cisplatin. When definitive CRT fails to achieve local control, salvage oesophagectomy is frequently the only treatment available that can offer a chance of long-term survival. METHODS: Online databases were searched for publications relating to salvage oesophagectomy and definitive CRT. Nine series containing a total of 105 patients were reviewed. Demographics, indications for surgery, type of resection, complications and outcome data were extracted. RESULTS: Each centre performed one to three salvage resections per year comprising 1.7-4.1 per cent of the oesophagectomy workload. The overall anastomotic leak rate was 17.1 per cent. The in-hospital mortality rate was 11.4 per cent. Five-year survival rates of 25-35 per cent were achieved. Prognostic factors for increased survival were R0 resection (P = 0.006) and longer interval between CRT and recurrence (P = 0.002). CONCLUSION: Salvage resection after CRT is feasible for selected patients but is a formidable undertaking. Restaging investigations after CRT for potentially resectable tumours in fit candidates should include endoscopy and positron emission tomography-computed tomography. Salvage oesophagectomy is carried out with the goal of cure and it should be attempted only if an R0 resection is technically possible.

Adult duodenal intussusception associated with congenital malrotation.

Enteroenteric intussusception is a condition in which full-thickness bowel wall becomes telescoped into the lumen of distal bowel. In adults, there is usually an abnormality acting as a lead point, usually a Meckels' diverticulum, a hamartoma or a tumour. Duodeno-duodenal intussusception is exceptionally rare because the retroperitoneal situation fixes the duodenal wall. The aim of this report is to describe the first published case of this condition. A patient with duodeno-duodenal intussusception secondary to an ampullary lesion is reported. A 66 year-old lady presented with intermittent abdominal pain, weight loss and anaemia. Ultrasound scanning showed dilated bile and pancreatic ducts. CT scanning revealed intussusception involving the full-thickness duodenal wall. The lead point was an ampullary villous adenoma. Congenital partial (type II) malrotation was found at operation and this abnormality permitted excessive mobility of the duodenal wall such that intussusception was possible. This condition can be diagnosed using enhanced CT. Intussusception can be complicated by bowel obstruction, ischaemia or bleeding, and therefore the underlying cause should be treated as soon as possible.

A prospective comparison of multidisciplinary treatment of oesophageal cancer with curative intent in a UK cancer network.

AIMS: Combined modality therapy (with chemotherapy+/-radiotherapy) has become a standard treatment for locally advanced oesophageal cancer. However, there appears to be no compelling evidence for one treatment type or combination to suit all and at this time the clinical multi-disciplinary team (MDT) forms an important role in selecting optimal therapies for the individual. This prospective comparison in one cancer network, looks at the outcomes of this decision making process. METHODS: Over a five year period 1998-2003, data were prospectively collected on all 330 consecutive patients, referred to a tertiary specialised MDT for whom curative treatment was the planned intent. Patients were managed according to an agreed local protocol and allocated to receive one of 5 treatments: surgery alone (S), pre-operative chemotherapy (C+S), pre-operative chemo-radiotherapy (CRT+S), definitive chemo-radiotherapy (CRT) and radiotherapy alone (RT). RESULTS: The 2 and 5 year survival for all patients receiving potentially curative treatment were 49% and 26% respectively. With 2 and 5 year survival for S, CRT+S, C+S, CRT and RT being 53,21; 57,40; 37,27; 50,27; 23,0 months respectively. Of the surgical therapies, mortality was highest in the CRT+S group, versus C+S and S; 12.5%, 1.6%, 4.5% respectively (p=0.025). Non-surgical based therapies had more than double the incidence of local relapses compared to surgical based therapies; however the CRT group had an overall survival comparable with S alone. The commonest sites of distant relapse were liver (56%), lung (38%), bone (32%) and non-regional lymph nodes (24%). CONCLUSION: The results suggest that in patients who are deemed unfit for surgical intervention, definitive chemoradiotherapy remains a viable alternative; they also lend further support to selected case triple modality therapy. These areas should be further examined in the context of randomised controlled phase III trials.

Pilot study of preoperative combined modality treatment for locally advanced operable oesophageal carcinoma: toxicities and long-term outcome.

AIMS: Paclitaxel, a radiosensitiser, has significant activity in oesophageal cancer. We aimed to conduct a feasibility study of preoperative chemoradiation using paclitaxel, cisplatin and 5-fluorouracil (5-FU). MATERIALS AND METHODS: Sixteen eligible patients were enrolled. Infusional 5-FU, paclitaxel and cisplatin were given for 6 weeks before and concurrent with radiation. Conformal radiotherapy was delivered in two phases (45 Gy in 25 fractions). RESULTS: A total of 62.5% of the patients experienced Grade 3-4 toxicities, 50% required admission; one patient died during the neo-adjuvant phase. Twelve (75%) patients had oesophagectomy, and two (12.5%) died after surgery. Pathological complete remission (PCR) and minimal residual disease were observed in 25% (95% CI 0.5-49.5%) and 18% (95% CI 0-38%) of patients, respectively, who underwent surgery. The median survival was 39.7 months (95% CI 15, not reached); 1-, 2-, 3-, and 4-year survivals were 75% (95% CI 56.5-99.5), 56.3% (36.5-86.7), 50% (30.6-81.6), and 50% (30.6-81.6), respectively. CONCLUSION: Paclitaxel, cisplatin and 5-FU (TCF)-chemoradiation is an active regimen; the current dose schedule tested is associated with unacceptable toxicity, and cannot be recommended for routine clinical use.

A review of the surgical management of metastatic gastrointestinal stromal tumours (GISTs) on imatinib mesylate (Glivec).

Gastrointestinal stromal tumours (GISTs) are defined as a group of C-KIT positive mesenchymal tumours of the gastrointestinal tract. Although they may arise throughout the gut, the commonest sites are stomach and small intestine. Over 80% of metastases are to the liver and omentum. Targeted therapy (imatinib) can inhibit C-KIT and thereby aberrant tumoural proliferation. Imatinib may induce shrinkage of lesions and cystic change. Such physical changes often correspond with reduced metabolic activity demonstrated by (18-FDG)PET scans. These changes may enable metastatectomy reducing tumour pain and the risk of haemorrhage and rupture in the short term. In the long term, resection may lessen the risk of recurrence by removing potentially resistant clones. The precise role of palliative resection for GIST metastases on imatinib remains unclear. Imatinib has changed the natural history of metastatic GISTs, with increased survival times. Surgery remains an important management strategy in the metastatic setting because complete pathological responses are rare with imatinib. Surgery is likely to provide the best palliation, greatest reduction in tumour burden and eliminate resistant clones. A multidisciplinary team approach with expertise concentrated in a few centres specialising in the management of these rare tumours is vital to the successful outcome. Future issues regarding the management of differential response of the metastases to imatinib are highlighted. With the emergence of techniques enabling identification of the precise mutational status of the C-KIT oncogene, the imatinib/surgery sequence could be tailored to the type of C-KIT mutation.