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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Opposite effects of recombinant human transforming growth factor-beta 1 on bone regeneration in vivo: effects of exclusion of periosteal cells by microporous membrane.

The efficacy of local delivery of recombinant human transforming growth factor-beta 1 (rhTGF-beta 1) to promote bone regeneration, with or without cellular contribution from the periosteum, was evaluated in transosseous defects. Implantation of rhTGF-beta 1 into 5 mm in diameter "critical size defects" in the rat mandible resulted in a dose-dependent (0.1-20 micrograms/defect) bone bridging at both 12 and 24 days, independent of the type of delivery system [3% methyl cellulose gel, porous CaCO3 particles, or poly(lactide-co-glycolide) beads]. The bridging, however, never exceeded 24% at 12 days or 34% after 24 days. In contrast, when access of cells from the periosteum to the defect was prevented by means of microporous expanded polytetrafluoroethylene barrier membranes (GORE-TEX membrane), rhTGF-beta 1 caused a dose-dependent inhibition of bone regeneration. The bioactivity of the growth factor was confirmed by implantation of 5 or 10 micrograms rhTGF-beta 1 in 12 mm in diameter bicortical defects in rabbit calvaria, which resulted in complete bone healing within 28 days, whereas control defects displayed a bridging of 40%-50%. The findings support the concept, based on in vitro experiments by others, that TGF-beta 1 primarily has a proliferative effect on cells already committed to the osteoblastic lineage, but also imply that TGF-beta 1 may be inhibitory to induction of osteogenic cells in vivo.

Mosaic rearrangement of chromosome 18: characterization by FISH mapping and DNA studies shows trisomy 18p and monosomy 18p both of paternal origin.

Structural abnormalities of chromosome 18p mainly consist of isochromosomes of the short arm, which result in tetrasomy 18p. Trisomy 18p is much rarer, and less well characterized. We report on a 12-year-old girl with minor facial anomalies, delayed development, abnormal hands, atopic dermatitis, and hearing loss. She was mosaic for two abnormal cell lines in peripheral blood. In 90% of cells, a dicentric chromosome with duplication of the whole short arm of chromosome 18 resulted in trisomy 18p; 10% of cells had monosomy 18p, arising from a t(14;18)(p11;q11). FISH mapping, with multiple region specific and locus specific probes from the short and long arm of chromosome 18, showed that the structure of the dicentric chromosome 18 was 18pter-->18q23::18q11-->18pter. DNA polymorphisms for chromosome 18 showed that the abnormalities of chromosome 18 were paternal in origin. Combining all results, we could link the trisomy 18p and monosomy 18p to a common origin via a complex series of events in an early mitosis.

c-erbB-2 overexpression in the dysplasia/carcinoma sequence of Barrett's oesophagus.

AIMS--To investigate overexpression of the oncoprotein c-erbB-2 in the dysplasia/carcinoma sequence of Barrett's columnar-lined oesophagus (CLO). METHODS--Immunohistochemical staining was performed using the monoclonal antibody NCL-CB-11 on formalin fixed tissue from 31 cases of Barrett's carcinoma, 20 cases of cancer associated dysplastic CLO, seven cases of dysplastic CLO without cancer, and 20 cases of non-dysplastic CLO. Membranous staining was regarded as positive for c-erbB-2 overexpression; cytoplasmic staining was recorded separately as its significance is uncertain. RESULTS--Membranous c-erbB-2 overexpression was observed in eight of 31 (26%) carcinomas and in none of the cases of dysplastic CLO. Variable cytoplasmic staining was seen in four of 31 (13%) tumours and seven of 27 (26%) cases of dysplastic CLO. No staining was observed in non-dysplastic CLO. CONCLUSIONS--C-erbB-2 overexpression is a relatively late event in the development of some Barrett's carcinomas and is unlikely to be involved in the early stages of neoplastic transformation of CLO.

Amplification of cyclin D1 and MDM-2 in oesophageal carcinoma.

AIMS: This study investigated amplification of the cyclin D1 and MDM-2 genes, and overexpression of the cyclin D1 gene product, in oesophageal carcinoma. METHODS: Paired tumour and normal DNA samples from 26 oesophageal adenocarcinomas and 19 squamous cell carcinomas were analysed by Southern blotting with specific DNA probes for cyclin D1 and MDM-2, and for a control gene (alpha-lactalbumin). The cyclin D1 and MDM-2 gene copy numbers were calculated for each tumour. Expression of the cyclin D1 gene was assessed by immunohistochemical analysis of its protein product. RESULTS: Cyclin D1 gene amplification (by a factor of between two and six) was identified in seven tumours (16%). MDM-2 gene amplification (by a factor of between two and 11) was identified in 10 tumours (22%). Overexpression of cyclin D1 protein was identified in eight tumours and was significantly associated with gene amplification (P=0.04; Fisher's exact test), and with early T stage (P=0.01; Fisher's exact test). CONCLUSIONS: Cyclin D1 and MDM-2 amplification and cyclin D1 overexpression occur, although infrequently, in the development of oesophageal carcinoma. Cyclin D1 overexpression may influence tumour behaviour, causing the disease to present at an earlier T stage. The mechanism for this effect is unclear, and warrants further investigation.

Human papillomavirus and oesophageal squamous cell carcinoma in the UK.

Human papillomavirus (HPV) has previously been identified in up to 67% of squamous cell carcinomas of the oesophagus. In particular, HPV types of 16 and 18 are believed to play an important role in neoplastic transformation, by means of their oncoproteins E6 and E7. Most of these studies, however, pertain to areas of high incidence of squamous cell carcinoma of the oesophagus (the Far East and South Africa). It is not known if HPV plays any role in the development of oesophageal squamous cell carcinoma in the UK, where the tumour is relatively uncommon. The polymerase chain reaction was used to examine frozen tissue from 22 oesophageal squamous cell carcinomas for the presence of specific DNA sequences from oncogenic strains of HPV. PCR products were further analysed by Southern blot hybridization. No HPV sequences were detected in any tumours. These results suggest that these types of HPV are not associated with oesophageal squamous cell carcinoma in this country. It is unlikely, therefore, that HPV plays a significant role in the pathogenesis of squamous cell carcinoma of the oesophagus in the UK.