Acute gastric outlet obstruction secondary to exclusive paraoesophageal small bowel herniation: a case report.

INTRODUCTION: Herniation of abdominal viscera into the thorax may occur as a consequence of abnormal defects in the diaphragm. In adults, the most common condition relates to herniations through a weakened crural orifice via which the oesophagus normally traverses. These hiatus hernias are classified as types I-IV depending on the extent of visceral involvement. CASE REPORT: We present here a case of type IV hiatus hernia with massive mediastinal herniation of the small bowel, yet remarkable in that the stomach itself remained completely intra-abdominal. Gastric outlet obstruction occurred as a consequence of extrinsic proximal small bowel compression. DISCUSSION: To our knowledge this is the first reported case of paraoesophageal hernia exclusively involving small bowel, without involving any part of the stomach, and yet causing gastric outlet obstruction.

The role of adjuvant platinum-based chemotherapy in esophagogastric cancer patients who received neoadjuvant chemotherapy prior to definitive surgery.

BACKGROUND AND OBJECTIVES: For patients with operable esophagogastric cancer, peri-operative chemotherapy confers a significant overall survival benefit compared to surgery alone, however only 30-40% of patients demonstrate histopathological response. It is unclear whether those with no neoadjuvant chemotherapy response should go onto receive adjuvant chemotherapy, as no further benefit may be conferred. METHODS: Esophagogastric cancers were prospectively captured with associated histopathological tumor regression grades following neoadjuvant chemotherapy. This cohort was then interrogated for clinico-pathological and survival outcomes. RESULTS: Following neoadjuvant chemotherapy and surgery, patients with chemotherapy responsive cancers, who were administered adjuvant chemotherapy gained a significant overall survival benefit. Multivariate Cox analysis, demonstrated a final adjusted hazard ratio for adjuvant therapy of 0.509; (95%CI 0.28-0.93); P = 0.028. In contrast, patients with non-responsive tumors, who underwent adjuvant chemotherapy, did not show any survival benefit. Chemotherapy toxicity was prevalent and contributed to only half of patients receiving adjuvant chemotherapy. CONCLUSIONS: These results suggest the benefit of the adjuvant portion of chemotherapy is limited to those who demonstrate a histopathological response to neoadjuvant chemotherapy. The administration of the adjuvant portion of chemotherapy to patients without a response to neoadjuvant chemotherapy may not provide any survival benefit, while potentially causing increased morbidity.

Individual patient oesophageal cancer 3D models for tailored treatment.

BACKGROUND: A model to predict chemotherapy response would provide a marked clinical benefit, enabling tailored treatment of oesophageal cancer, where less than half of patients respond to the routinely administered chemotherapy. METHODS: Cancer cells were established from tumour biopsies taken from individual patients about to undergo neoadjuvant chemotherapy. A 3D-tumour growth assay (3D-TGA) was developed, in which cancer cells were grown with or without supporting mesenchymal cells, then subjected to chemo-sensitivity testing using the standard chemotherapy administered in clinic, and a novel emerging HDAC inhibitor, Panobinostat. RESULTS: Individual patient's cancer cells could be expanded and screened within a clinically applicable timescale of 3 weeks. Incorporating mesenchymal support within the 3D-TGA significantly enhanced both the growth and drug resistance profiles of the patient's cancer cells. The ex vivo drug response in the presence, but not absence, of mesenchymal cells accurately reflected clinical chemo-sensitivity, as measured by tumour regression grade. Combination with Panobinostat enhanced response and proved efficacious in otherwise chemo-resistant tumours. CONCLUSIONS: This novel method of establishing individual patient oesophageal cancers in the laboratory, from small endoscopic biopsies, enables clinically-relevant chemo-sensitivity testing, and reduces use of animals by providing more refined in vitro models for pre-screening of drugs. The 3D-TGA accurately predicted chemo-sensitivity in patients, and could be developed to guide tailored patient treatment. The incorporation of mesenchymal cells as the stromal cell component of the tumour micro-environment had a significant effect upon enhancing chemotherapy drug resistance in oesophageal cancer, and could prove a useful target for future drug development.

Expression of the calpain system is associated with poor clinical outcome in gastro-oesophageal adenocarcinomas.

BACKGROUND: Surgery is critical in the management of gastro-oesophageal cancer, and the addition of neo-adjuvant chemotherapy has proved to be of benefit. The calpain system has been implicated in tumour progression and response to various anti-cancer therapies, and therefore expression of the system was determined in this tumour type. METHODS: Two cohorts of gastro-oesophageal adenocarcinomas were investigated for calpain-1, calpain-2, calpain-9 and calpastatin expression using conventional immunohistochemistry. 88 patients who received neo-adjuvant chemotherapy and 140 patients who received surgery alone were investigated using a tissue microarray approach. RESULTS: Calpain-1, calpain-2 and calpastatin expression was associated with adverse cancer-specific survival in the neo-adjuvant cohort (P = 0.004, P = 0.001 and P = 0.012 respectively); which remained significant in multivariate analysis (Hazard ratio (HR) = 0.337; 95% confidence interval (CI) = 0.140-0.81; P = 0.015, HR = 0.375; 95% CI = 0.165-0.858; P = 0.020 and HR = 0.481; 95% CI = 0.257-0.900; P = 0.022 respectively). Calpain-1 and calpastatin expression was also associated with adverse cancer specific survival in the primary surgery cohort (P = 0.001 and P = 0.013 respectively); which remained significant in multivariate analysis (HR = 0.309; 95% CI = 0.159-0.601; P = 0.001 and HR = 0.418; 95% CI = 0.205-0.850; P = 0.016 respectively). Calpain-9 expression was not associated with cancer-specific survival in the neo-adjuvant and primary surgery cohorts. CONCLUSION: Determining the expression levels of calpain-1, calpain-2 and calpastatin may provide clinically relevant prognostic information for gastro-oesophageal adenocarcinomas; these findings warrant further studies in larger cohorts of patients.

Early laparoscopy versus active observation in acute abdominal pain: systematic review and meta-analysis.

INTRODUCTION: Patients with acute abdominal pain account for half of acute general surgical admissions. About one-third have no clear diagnosis at the time of presentation. Traditionally, such patients were managed by active observation and repeated clinical assessment over a period of time. More recently, the use of early laparoscopy has been advocated. METHODS: The Medline and PubMed databases, trial registries and conference proceedings were searched to identify randomised controlled trials comparing early laparoscopy to active observation in patients with undifferentiated acute abdominal pain. RESULTS: The systematic review identified four eligible trials (811 patients). Early laparoscopy reduced the number of patients discharged without a final diagnosis (pooled odds ratio: 0.13; 95% CI: 0.03-0.51; p=0.003). There were no statistically significant effects on complications, readmission rates or hospital stay. There was evidence of significant heterogeneity between the trials. CONCLUSION: There is insufficient evidence to recommend routine use of early laparoscopy as the gold standard in patients with undifferentiated acute abdominal pain. Conversely, there is no evidence of harm. Further large clinical trials are required to determine the role of laparoscopy in this clinical situation.