Metastatic seminoma with isolated gastric metastases: a case report.

Gastric metastases are a rare occurrence in patients with malignancy. In case reports of these arising from germ cell tumours, the majority were non-seminomatous germ cell tumours and had evidence of retroperitoneal involvement. We present a unique case of a 67-year-old man with metastatic testicular pure seminoma. He presented with dyspepsia and investigation found isolated metastases to the gastric mucosa and sub-mucosa from a right testicular primary. No lymph node involvement was identified. The patient was managed with curative intent with total gastrectomy and inguinal orchidectomy. To date, there is no evidence of disease recurrence.

Routine pre- and post-neoadjuvant chemotherapy fitness testing is not indicated for oesophagogastric cancer surgery.

Introduction There is a known correlation between anaerobic threshold (AT) during cardiopulmonary exercise testing and development of cardiopulmonary complications in high-risk patients undergoing oesophagogastric cancer surgery. This study aimed to assess the value of routine retesting following neoadjuvant chemotherapy. Methods Patients undergoing neoadjuvant chemotherapy with subsequent oesophagogastric cancer surgery with pre- and post-neoadjuvant chemotherapy cardiopulmonary exercise data were identified from a prospectively maintained database. Measured cardiopulmonary exercise variables included AT and maximum oxygen uptake at peak exercise (VO2 peak). Anaerobic threshold values within 1 ml/kg/minute were considered static. Patients were grouped into AT ranges of less than 9 ml/kg/minute, 9-11 ml/kg/minute and greater than 11 ml/kg/minute. Outcome measures were unplanned intensive care stay, postoperative cardiovascular morbidity and mortality. Results Between May 2008 and August 2017, 42 patients from 675 total resections were identified, with a mean age of 65 years (range 49-84 years). Mean pre-neoadjuvant chemotherapy AT was 11.07 ml/kg/minute (standard deviation, SD, 3.24 ml/kg/minute, range 4.6-19.3 ml/kg/minute) while post-neoadjuvant chemotherapy AT was 11.19 ml/kg/minute (SD 3.05 ml/kg/minute, range 5.2-18.1 ml/kg/minute). Mean pre-neoadjuvant chemotherapy VO2 peak was 17.13 ml/kg/minute, while post-chemotherapy this mean fell to 16.59 ml/kg/minute. Some 44.4% of patients with a pre-chemotherapy AT less than 9 ml/kg/minute developed cardiorespiratory complications compared with 42.2% of those whose AT was greater than 9 ml/kg/minute (P = 0.914); 63.6% of patients in the post-neoadjuvant chemotherapy group with an AT less than 9 ml/kg/minute developed cardiorespiratory complications. There was no correlation between direction of change in AT and outcome. Conclusion In our patient population, neoadjuvant chemotherapy does not appear to result in a significant mean reduction in cardiorespiratory fitness. Routine pre- and post-neoadjuvant chemotherapy cardiopulmonary exercise testing is currently not indicated; however, larger studies are required to demonstrate this conclusively.

The cost-effectiveness of radiofrequency ablation for Barrett's esophagus with low-grade dysplasia: results from a randomized controlled trial (SURF trial).

BACKGROUND AND AIMS: The Surveillance versus Radiofrequency Ablation (SURF) trial randomized 136 patients with Barrett's esophagus (BE) containing low-grade dysplasia (LGD), to receive radiofrequency ablation (ablation, n = 68) or endoscopic surveillance (control, n = 68). Ablation reduced the risk of neoplastic progression to high-grade dysplasia and esophageal adenocarcinoma (EAC) by 25% over 3 years (1.5% for ablation vs 26.5% for control). We performed a cost-effectiveness analysis from a provider perspective alongside this trial. METHODS: Patients were followed for 3 years to quantify their use of health care services, including therapeutic and surveillance endoscopies, treatment of adverse events, and medication. Costs for treatment of progression were analyzed separately. Incremental cost-effectiveness ratios (ICER) were calculated by dividing the difference in costs (excluding and including the downstream costs for treatment of progression) by the difference in prevented events of progression. Bootstrap analysis (1000 samples) was used to construct 95% confidence intervals (CIs). RESULTS: Patients who underwent ablation generated mean costs of U.S.$13,503 during the trial versus $2236 for controls (difference $11,267; 95% CI, $9996-$12,378), with an ICER per prevented event of progression of $45,066. Including the costs for treatment of progression, ablation patients generated mean costs of $13,523 versus $4,930 for controls (difference $8593; 95% CI, $6881-$10,153) with an ICER of $34,373. Based on the various ICER estimates derived from the bootstrap analysis, one can be reasonably certain (>75%) that ablation is efficient at a willingness to pay of $51,664 per prevented event of progression or $40,915 including downstream costs of progression. CONCLUSIONS: Ablation for patients with confirmed BE-LGD is more effective and more expensive than endoscopic surveillance in reducing the risk of progression to high-grade dysplasia/EAC. The increase in costs of ablation can be justified to avoid a serious event such as neoplastic progression. At a willingness to pay of $40,915 per prevented event of progression, one can be reasonably certain that ablation is efficient. (www.trialregister.nl number: NTR 1198.).

Improvement over time in outcomes for patients undergoing endoscopic therapy for Barrett's oesophagus-related neoplasia: 6-year experience from the first 500 patients treated in the UK patient registry.

BACKGROUND: Barrett's oesophagus (BE) is a pre-malignant condition leading to oesophageal adenocarcinoma (OAC). Treatment of neoplasia at an early stage is desirable. Combined endoscopic mucosal resection (EMR) followed by radiofrequency ablation (RFA) is an alternative to surgery for patients with BE-related neoplasia. METHODS: We examined prospective data from the UK registry of patients undergoing RFA/EMR for BE-related neoplasia from 2008 to 2013. Before RFA, visible lesions were removed by EMR. Thereafter, patients had RFA 3-monthly until all BE was ablated or cancer developed (endpoints). End of treatment biopsies were recommended at around 12 months from first RFA treatment or when endpoints were reached. Outcomes for clearance of dysplasia (CR-D) and BE (CR-IM) at end of treatment were assessed over two time periods (2008-2010 and 2011-2013). Durability of successful treatment and progression to OAC were also evaluated. RESULTS: 508 patients have completed treatment. CR-D and CR-IM improved significantly between the former and later time periods, from 77% and 56% to 92% and 83%, respectively (p<0.0001). EMR for visible lesions prior to RFA increased from 48% to 60% (p=0.013). Rescue EMR after RFA decreased from 13% to 2% (p<0.0001). Progression to OAC at 12 months is not significantly different (3.6% vs 2.1%, p=0.51). CONCLUSIONS: Clinical outcomes for BE neoplasia have improved significantly over the past 6 years with improved lesion recognition and aggressive resection of visible lesions before RFA. Despite advances in technique, the rate of cancer progression remains 2-4% at 1 year in these high-risk patients. TRIAL REGISTRATION NUMBER: ISRCTN93069556.

Long term efficacy of Photodynamic Therapy (PDT) as an ablative therapy of high grade dysplasia in Barrett's oesophagus.

BACKGROUND: Barrett's high grade dysplasia (HGD) is a pre-malignant condition which requires treatment with either oesophagectomy or ablative endoscopic therapy. Endoscopic ablative techniques have evolved through Photodynamic Therapy (PDT) to more recently radiofrequency ablation (RFA). Although RFA has superseded PDT due to improved efficacy and safety profile there remains a significant cohort of patients previously treated by PDT where the long term outcome is unclear. This study's aim was to assess the long term efficacy of PDT in patients with Barrett's HGD. METHODS: Between June 2002 and 2007 21 patients (16 male, median age 70) underwent PDT for HGD in Barrett's oesophagus. Patients received intravenous photosensitiser Photofrin (Porfimer sodium) forty eight hours prior to endoscopic light activation by laser light at 630 nm. The patients returned at 6-12 weekly intervals for repeat endoscopy and biopsy. RESULTS: Sixteen patients remained free of HGD at median 62 (range 36-114) months. Three patients developed adenocarcinoma at 47, 48 and 54 months (15%). Two patients were treated endoscopically with RFA and YAG laser, while one patient had surgical resection. Four patients developed recurrent HGD treated with repeat PDT. There was a significant reduction in length of Barrett's segment (from 5 cm to 3 cm) post PDT. The stricture rate requiring endoscopic therapy was 37% and 10% of patients developed photosensitivity reactions. CONCLUSION: PDT successfully ablated HGD in 84% of patients and could therefore still be considered an effective salvage treatment for this condition in patients with co-morbidities precluding them for surgical resection.

Cardiopulmonary exercise testing as a predictor of complications in oesophagogastric cancer surgery.

INTRODUCTION: An anaerobic threshold (AT) of <11 ml/min/kg can identify patients at high risk of cardiopulmonary complications after major surgery. The aim of this study was to assess the value of cardiopulmonary exercise testing (CPET) in predicting cardiopulmonary complications in high risk patients undergoing oesophagogastric cancer resection. METHODS: Between March 2008 and October 2010, 108 patients (83 men, 25 women) with a median age of 66 years (range: 38-84 years) underwent CPET before potentially curative resections for oesophagogastric cancers. Measured CPET variables included AT and maximum oxygen uptake at peak exercise (VO2 peak). Outcome measures were length of high dependency unit stay, length of hospital stay, unplanned intensive care unit (ICU) admission, and postoperative morbidity and mortality. RESULTS: The mean AT and VO2 peak were 10.8 ml/min/kg (standard deviation [SD]: 2.8 ml/min/kg, range: 4.6-19.3 ml/min/kg) and 15.2 ml/min/kg (SD: 5.3 ml/min/kg, range: 5.4-33.3 ml/min/kg) respectively; 57 patients (55%) had an AT of <11 ml/min/kg and 26 (12%) had an AT of <9 ml/min/kg. Postoperative complications occurred in 57 patients (29 cardiopulmonary [28%] and 28 non-cardiopulmonary [27%]). Four patients (4%) died in hospital and 21 (20%) required an unplanned ICU admission. Cardiopulmonary complications occurred in 42% of patients with an AT of <9 ml/min/kg compared with 29% of patients with an AT of ≥9 ml/min/kg but <11 ml/min/kg and 20% of patients with an AT of ≥11 ml/min/kg (p = 0.04). There was a trend that those with an AT of <11 ml/min/kg and a low VO2 peak had a higher rate of unplanned ICU admission. CONCLUSIONS: This study has shown a correlation between AT and the development of cardiopulmonary complications although the discriminatory ability was low.

Endoscopic ablation of Barrett's neoplasia with a new focal radiofrequency device: initial experience with the Halo60.

Radiofrequency ablation (RFA) is an accepted treatment for the eradication of dysplastic Barrett's esophagus (DBE) and residual Barrett's esophagus after endoscopic resection of intramucosal adenocarcinoma. Circumferential balloon-based and focal catheter-based RFA devices are currently used (the Halo360 and Halo90). However, a new smaller focal ablation device (the Halo60) has been developed, which may be of benefit in patients with short tongues of Barrett's neoplasia, small residual islands, difficult anatomy, or strictures. We report the first use of this device in 17 patients with either DBE or residual Barrett's esophagus after endoscopic resection of intramucosal adenocarcinoma.

The relationship between tumour necrosis, tumour proliferation, local and systemic inflammation, microvessel density and survival in patients undergoing potentially curative resection of oesophageal adenocarcinoma.

BACKGROUND: There is increasing evidence that the local and systemic inflammatory responses are associated with survival in oesophageal cancer. The aim of this study was to examine the relationship between tumour necrosis, tumour proliferation, local and systemic inflammation and microvessel density and survival in patients undergoing potentially curative resection of oesophageal adenocarcinoma. METHODS: The interrelationship between tumour necrosis, tumour proliferation, local inflammatory response (Klintrup-Makinen criteria, intra-tumoural CD8+ lymphocyte and macrophage infiltration), systemic inflammatory response (modified Glasgow Prognostic score (mGPS)), and microvessel density was examined in 121 patients undergoing potentially curative resection for oesophageal adenocarcinoma (including type I and II tumours of the gastro-oesophageal junction). RESULTS: Tumour necrosis was not significantly associated with any tumour measure other than the degree of differentiation. On multivariate analysis, only age (HR 1.93, 95% CI 1.23-3.04, P=0.004), mGPS (HR 2.91, 95% CI 1.51-5.62, P=0.001), positive to total lymph node ratio (HR 2.38, 95% CI 1.60-3.52, P<0.001) and macrophage infiltration (HR 1.49, 95% CI 1.02-2.18, P=0.041) were independently associated with cancer-specific survival in oesophageal adenocarcinoma. Intra-tumoural macrophages were associated with tumour proliferation (P<0.001) and CD8+ lymphocytes infiltration (P<0.01). CONCLUSION: The results of this study suggest that tumour necrosis does not link local and systemic inflammatory responses and is not significantly associated with survival. In contrast, tumour macrophage infiltration appears to have a central role in the proliferative activity and the coordination of the inflammatory cell infiltrate and is independently associated with poorer survival in patients with oesophageal adenocarcinoma.

The pharmacokinetics and safety of porfimer after repeated administration 30-45 days apart to patients undergoing photodynamic therapy.

BACKGROUND: Porfimer is an intravenous (i.v.) injectable photosensitizing agent used in the photodynamic treatment of tumours and of high-grade dysplasia in Barrett's oesophagus. AIM: To assess the pharmacokinetics as well as the safety profiles of porfimer after a first and a second dose administered 30-45 days apart in patients undergoing photodynamic therapy. METHODS: Nineteen patients (16 with cholangiocarcinoma) were enrolled. Porfimer sodium was administered by i.v. injection over 3-5 min. Blood samples were collected prior to starting i.v. drug injection and postdose at different time points after the first and second administrations. RESULTS: Porfimer exposure values after the second administration were statistically higher than those observed after the first administration, suggesting a slight accumulation of porfimer following repeated administration. The apparent mean elimination half-life of porfimer increased from 410 h after the first administration to 725 h after the second administration. The safety profiles of porfimer after a first and a second administration were similar and did not raise additional concern. Eight patients experienced nine serious adverse events. Only photosensitivity was deemed study-drug related. CONCLUSION: Porfimer appears to display a safe and tolerable profile when used in patients requiring a second photodynamic therapy within 45 days.

A cost comparison of photodynamic therapy and metallic stents in the palliation of oesophageal cancer.

BACKGROUND: There is currently little information on the cost effectiveness of photodynamic laser therapy (PDT) compared with other palliative treatments for oesophageal cancer. AIM: To compare the cost of oesophageal cancer palliation associated with PDT with those of another standard option, self-expanding metallic stents. METHODS: A cost comparison study using prospectively and retrospectively collected data was conducted. Data was collected from 25 patients who had received PDT between 1999 and 2003. Costs were compared with data from patients who received a metallic stent between 1998 and 2000. Costs were estimated using routine costs for the year 2002-2003. RESULTS: Patients receiving PDT or oesophageal stents were similar in terms of age, gender and tumour presentation. Patients receiving PDT had slightly shorter duration of symptoms, less metastatic spread but similar dysphagia scores to those in the oesophageal stent group. Costs of initial PDT treatment were significantly higher than those associated with stent placement (PDT mean costs £2068.48 versus stent mean costs £1086.76; cost difference £981.72 (95% CI: £844.47-1118.96)). This higher cost persisted throughout future re-interventions and hospital episodes. Patients receiving PDT survived longer however (132.5 (70.5-250 days) (medium IQR)) than those receiving a stent 105 (31-172.5 days), thus the mean cost per day's survival was equivalent between the two treatments. There was no impact of PDT on patients' quality of life at 6 weeks post-treatment. CONCLUSIONS: Although initially more expensive than metallic stents, a longer survival results in PDT being as cost effective as stenting in oesophageal palliation. A larger, randomised controlled trial is required combining both economic evaluation and quality of life measurement to fully establish the best palliative treatment in this disease.

A randomized trial comparing heater probe plus thrombin with heater probe plus placebo for bleeding peptic ulcer.

BACKGROUND & AIMS: This multicenter, double-blind, controlled trial compared the efficacy of combined endoscopic hemostatic treatment using the heater probe plus thrombin injection with that of the heater probe plus placebo injection as treatment for peptic ulcers with active bleeding or nonbleeding visible vessels. Efficacy was defined in terms of primary hemostasis, prevention of rebleeding, and need for urgent surgery. METHODS: Two hundred forty-seven patients presenting with major peptic ulcer bleeding were randomized to heater probe plus thrombin or to heater probe plus placebo. The groups were well matched for all risk categories including age, endoscopic stigmata, shock, and severity of comorbid diseases. Endoscopic therapy was applied using the heater probe followed by injection of thrombin or placebo. RESULTS: Successful primary hemostasis was achieved in 97% of patients. Rebleeding developed in 19 (15%) of thrombin plus heater probe patients and 17 (15%) of placebo plus heater probe patients. Emergency surgery was necessary in 16 and 13 patients, respectively. Eight patients in the thrombin group had adverse events compared with 4 in the placebo group. Eight (6%) of thrombin plus heater probe patients and 14 (12%) of placebo plus heater probe patients died (P = 0.21). CONCLUSIONS: The combination of thrombin and the heater probe does not confer an additional benefit over heater probe and placebo as endoscopic treatment for bleeding peptic ulcer. Our trial does not support the use of this combination of hemostatic therapy.

A phase I and pharmacokinetic study of capecitabine in combination with epirubicin and cisplatin in patients with inoperable oesophago-gastric adenocarcinoma.

BACKGROUND: The purpose of this study was to evaluate the dose-limiting toxicity (DLT) and maximum tolerated dose of capecitabine when used in combination with epirubicin and cisplatin (ECC) in patients with oesophageal or gastric adenocarcinoma. Response rate, progression-free survival (PFS) and overall survival were also determined, and the effect of previous oesophago-gastric surgery or concurrent oesophago-gastric cancer on the absorption and metabolism of capecitabine was evaluated. PATIENTS AND METHODS: Patients with inoperable oesophago-gastric adenocarcinoma received up to six cycles of epirubicin (50 mg/m(2) i.v., 3-weekly), cisplatin (60 mg/m(2) i.v., 3-weekly) and capecitabine, the latter administered orally in an intermittent schedule (14 days treatment; 7-day rest period) at 3-weekly intervals. Patients were recruited into one of four escalating dose cohorts (500, 825, 1000 and 1250 mg/m(2) bd). Dose escalation occurred after six patients had completed at least one cycle of chemotherapy at the previous dose level, with DLT assessed on the toxicity of the first cycle only. Blood sampling for pharmacokinetic analyses was performed over the first 10 h of day 1 of cycle 1. RESULTS: Thirty-two patients, median age 63 years (range 32-76 years), ECOG performance status < or =2 with locally advanced (10) or metastatic (22) disease were recruited and were evaluable for toxicity. Two of five patients experienced DLT at 1250 mg/m(2) bd with grade II stomatitis (one patient) and grade III diarrhoea with febrile neutropenia (one patient). Cumulative toxicity for all cycles (n = 140) (worst grade per patient) includes grade IV oesophagitis (one patient), grade III diarrhoea (five), grade IV neutropenia with infection (seven), grade II stomatitis (four) and grade IV thrombocytopenia (one). Of 29 patients with evaluable disease, there was one complete response and six partial responses [24% response rate [95% confidence interval (CI) 10% to 44%]], a median PFS of 22 weeks (95% CI 17-27 weeks) and median overall survival of 34 weeks (95% CI 19-49 weeks). Capecitabine was rapidly absorbed after oral administration, with a t(max) of 1-2 h for capecitabine, DFCR (5'-deoxy-5-fluorocytidine) and DFUR (5'-deoxy-5-fluorouridine). The C(max) and AUC(0-)( infinity ) for capecitabine, DFCR and DFUR were similar to those observed in previous monotherapy studies of capecitabine taken after food. CONCLUSION: A dose of 1000 mg/m(2) bd of capecitabine is recommended for use on an intermittent schedule in combination with these doses and schedule of epirubicin and cisplatin. This regimen is tolerable and active in oesophago-gastric adenocarcinoma. A randomised phase III comparison with ECF is justified.

Randomized clinical trial comparing self-expanding metallic stents with plastic endoprostheses in the palliation of oesophageal cancer.

BACKGROUND: There is little evidence of the clinical and cost effectiveness of self-expanding metallic stents in the palliation of oesophageal cancer. The aims of this randomized trial were to evaluate the immediate and medium-term clinical outcomes following palliative intubation, examine patient quality of life, and evaluate costs and benefits from the perspective of the health service. METHODS: Fifty patients with inoperable oesophageal cancer were randomly allocated a metallic stent (n = 25) or plastic endoprosthesis (n = 25). Patients were followed up monthly until death. RESULTS: There was no significant difference in procedure-related complications or mortality rate between the two groups. There was a trend towards significance in favour of metallic stents with respect to quality of life and survival (median survival 62 versus 107 days for plastic prosthesis and metallic stent respectively). The cost of the initial placement of metallic stents was significantly higher than that of plastic endoprostheses ( pound 983 versus pound 296). After 4 weeks, cost differences were no longer significant. CONCLUSION: Metallic stents may contribute to improved survival and quality of life in patients with oesophageal cancer. Although initially more expensive, this cost difference does not last beyond 4 weeks. A larger trial involving approximately 300 patients would be required to detect a quality of life benefit of the magnitude observed in this trial.

Brush cytology in the assessment of pancreatico-biliary strictures: a review of 406 cases.

AIMS: To assess the accuracy of brush cytology in patients investigated for pancreatico-biliary strictures. METHODS: All pancreatico-biliary brush cytology specimens submitted from two major teaching hospitals over a 6.5 year period were reviewed. Four hundred and forty eight satisfactory specimens from 406 patients with adequate clinical and/or pathological follow up data were examined in the study period. RESULTS: Two hundred and forty six patients (60.6%) were shown to have neoplastic strictures. One hundred and forty seven tumours were identified cytologically, including 87 of 146 pancreatic carcinomas, 29 of 47 cholangiocarcinomas, one of one bile duct adenoma, four of seven carcinomas of the gallbladder, eight of 13 ampullary carcinomas, two of three ampullary adenomas, 10 of 16 malignancies of undetermined origin, none of two islet cell tumours, one of three hepatocellular carcinomas, and five of eight metastatic tumours. The three adenomas identified on brush cytology could not be distinguished from adenocarcinoma morphologically. One hundred and sixty patients (39.4%) had benign strictures, most often as a result of chronic pancreatitis and bile duct stones. There were three false positive cytological diagnoses mainly as a result of the misinterpretation of cases with relatively scant and/or degenerative atypical epithelial cells. Forty one cases were reported as atypical or suspicious of malignancy on brush cytology, of which 29 were ultimately shown to have carcinoma. The overall diagnostic sensitivity and specificity were 59.8% and 98.1%, respectively. The sensitivity increased from 44.3% in the initial third of cases to 70.7% in the final third of cases examined in the series. CONCLUSIONS: Brush cytology, in conjunction with other clinical and radiological investigations, is a useful technique in the assessment of patients with suspected pancreatico-biliary neoplasia.

A phase II study of epirubicin, cisplatin and raltitrexed combination chemotherapy (ECT) in patients with advanced oesophageal and gastric adenocarcinoma.

BACKGROUND: The aim of this study was to evaluate the efficacy of the combination of epirubicin, cisplatin and ralitrexed (Tomudex). ECT, in patients with advanced oesophageal or gastric adenocarcinoma. Efficacy was assessed primarily as response rate and secondarily in terms of toxicity, time to progression and survival. PATIENTS AND METHODS: Twenty-one patients with histologically and/or cytologically proven unresectable (7) or metastatic (14) gastro-oesophageal adenocarcinoma, who had bi-dimensionally measurable disease, with ECOG performance status < or = 2. with adequate haematological, hepatic and renal function received first-line chemotherapy with epirubicin (50 mg/m2). cisplatin (60 mg/m2) and Tomudex (2.5 mg/m2), ECT, at three-weekly intervals. Treatment consisted of three cycles of chemotherapy, with a further three cycles if there was disease response or stabilisation. RESULTS: ECT is an active regimen in the treatment of advanced gastro-oesophageal adenocarcinoma with an overall intention-to-treat response rate of 29% (95% confidence intervals (CI): 11%-52%). In addition, 4 (19%) patients had stable disease. Median time to progression was 19 weeks (95% CI: 7-31 weeks). Median overall survival was 18 weeks (95% CI: 11-24 weeks). Seventeen patients failed to complete the six cycles of treatment due to disease progression (5). toxicity (3), non-toxic death (1 pulmonary embolism, 1 cardiac), severe allergy to epirubicin (1), patient decision (1) and five patients after the study was discontinued early due to toxicity. There were three toxic deaths: two due to sepsis complicating neutropaenia and one due to cardiorespiratory failure following drug induced enteritis. Nine patients experienced grade 3 or 4 neutropaenia, two patients experienced grade 3 or 4 nausea and vomiting and one patient had grade 4 diarrhoea. CONCLUSIONS: The combination of epirubicin, cisplatin and tomudex is active against advanced gastro-oesophageal adenocarcinoma but the toxicity suggests that further evaluation in a randomised comparison to ECF is not appropriate.

Increased prevalence of precancerous changes in relatives of gastric cancer patients: critical role of H. pylori.

BACKGROUND & AIMS: Helicobacter pylori is believed to predispose to gastric cancer by inducing gastric atrophy and hypochlorhydria. First-degree relatives of patients with gastric cancer have an increased risk of developing gastric cancer. The aim of this study was to determine the prevalence of atrophy and hypochlorhydria and their association with H. pylori infection in first-degree relatives of patients with gastric cancer. METHODS: H. pylori status, gastric secretory function, and gastric histology were studied in 100 first-degree relatives of patients with noncardia gastric cancer and compared with those of controls with no family history of this cancer. RESULTS: Compared with healthy controls, relatives of patients with gastric cancer had a higher prevalence of hypochlorhydria (27% vs. 3%) but a similar prevalence of H. pylori infection (63% vs. 64%). Relatives of cancer patients also had a higher prevalence of atrophy (34%) than patients with nonulcer dyspepsia (5%) matched for H. pylori prevalence. Among the relatives of cancer patients, the prevalence of atrophy and hypochlorhydria was increased only in those with evidence of H. pylori infection, was greater in relatives of patients with familial cancer than in relatives of sporadic cancer index patients, and increased with age. Eradication of H. pylori infection produced resolution of the gastric inflammation in each subject and resolution of hypochlorhydria and atrophy in 50% of the subjects. CONCLUSIONS: Relatives of patients with gastric cancer have an increased prevalence of precancerous gastric abnormalities, but this increase is confined to those with H. pylori infection. Consequently, prophylactic eradication of the infection should be offered to such subjects.

Incidence and nature of bile duct injuries following laparoscopic cholecystectomy: an audit of 5913 cases. West of Scotland Laparoscopic Cholecystectomy Audit Group.

The rapid introduction of laparoscopic cholecystectomy has been associated with an apparently increased incidence of bile duct injury which has provoked worldwide concern. The true incidence and mechanism of iatrogenic ductal injury during the development of this procedure remain unclear. To assess this, the introduction of laparoscopic cholecystectomy in the West of Scotland has been audited prospectively over a 5-year period. All cases of biliary ductal injury have been independently reviewed. Some 48 surgeons undertaking laparoscopic cholecystectomy in 19 hospitals submitted prospective data between September 1990 and September 1995. A total of 5913 laparoscopic cholecystectomies were attempted with 98.3 per cent completion of data collection. During this period 37 laparoscopic bile duct injuries occurred. The annual incidence peaked at 0.8 per cent and has fallen to 0.4 per cent in the final year of audit. Injuries occurred after a median personal experience of 51 (range 3-247) laparoscopic cholecystectomies in 22 surgeons. Major bile duct injuries occurred in 20 of 37 patients, giving an incidence of 0.3 per cent. Five mechanisms for laparoscopic ductal injury were identified, including tenting, confluence and diathermy injuries as well as the classical and variant classical types. Ductal injuries were discovered at operation in 18 patients with consequent repair giving a good clinical outcome in 17. Contributory factors (severe inflammation, aberrant anatomy and poor visualization) were present in only 13 of 37 cases. This audit suggests that, at least in the introductory period, laparoscopic cholecystectomy is associated with an overall bile duct injury rate higher than that reported previously after open cholecystectomy, although the incidence of major ductal injury is similar. The late downward trend in bile duct injury, however, suggests there may be a prolonged learning curve for this procedure. Improved understanding of the mechanism of injury may lead to yet further reductions in this complication.

Early outcome after open versus extraperitoneal endoscopic tension-free hernioplasty: a randomized clinical trial.

BACKGROUND: The use of minimal access surgery for repair of groin hernias is controversial. The aim of this study was to compare endoscopic tension-free hernia repair with open tension-free hernia repair within a randomized clinical trial. METHODS: One hundred twenty patients were randomized by four surgeons during a 1-year period. Early outcome measures were then analyzed by intention to treat. RESULTS: Median postoperative pain scores (63 [interquartile range (IQR), 23 to 81] versus 35 [IQR, 17 to 62]; p = 0.004) and analgesia requirements (2.5 [IQR, 2 to 4] doses verus 2.0 [IQR, 1 to 3] doses; p = 0.0008) were significantly less for patients undergoing endoscopic hernia repair. Hospital stay (1 [IQR, 0 to 1] day versus 2 [IQR, 1 to 2] days; p < 0.0001) was also significantly reduced for the endoscopic group. Wound complications occurred significantly more frequently in the open group. No difference in pulmonary function or metabolic response to trauma (interleukin-6, C-reactive protein, glucose, albumin) was observed between the groups. CONCLUSIONS: This study shows significant short-term advantages for endoscopic tension-free repair over open tension-free repair. However, larger studies with a longer follow-up period are required to establish the relative merits of both procedures in the management of patients with groin hernias.