Peroral endoscopic myotomy (POEM) for treating esophageal motility disorders

Review Article on Endoscopic Therapy© Annals of Translational Medicine. All rights reserved. Pneumatic dilatation and Heller myotomy have been thoroughly studied as the most viable treatment options for achalasia. The pendulum, however, is shifting to the minimally invasive approach. Since Inoue et al. published the experience of the first 17 cases of peroral endoscopic myotomy (POEM) in 2010, there have been at least 5,000 cases performed worldwide and the number is increasing exponentially. Experts across the globe have been extending the indications to various esophageal motility disorders, to patients of extremes of age, sigmoidal esophagus and re-operated patients. There are a few variations in technique across different centers in defining the gastroesophageal junction (GEJ) and adequacy of myotomy, the optimal length, site of myotomy and whether the full thickness of the muscle wall should be cut. Large case series demonstrated its promising efficacy & reasonable complication profile. Randomized controlled trial in comparison with the gold standard, Heller myotomy, is ongoing. The future application of submucosal tunnelling technique is thrilling with its extension in tumour resection, antropyloromyotomy and other natural orifice transluminal endoscopic surgery (NOTES).published_or_final_versio

Intraperitoneal chemotherapy for gastric cancer with peritoneal carcinomatosis: is HIPEC the only answer?

Gastric cancer with peritoneal carcinomatosis is notorious for its dismal prognosis. While the pathophysiology of peritoneal dissemination is still controversial, the rapid downhill course is universal. Patients usually suffer abdominal distension, intestinal obstruction and various complications before they succumb after a median of 3 - 6 months. Although not adopted in most international treatment guidelines, intraperitoneal chemotherapy has growing evidence compared with conventional systemic chemotherapy for the treatment of peritoneal carcinomatosis. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy is well-established for clinical benefit but is technically demanding with substantial treatment-related morbidities and mortality. On the other hand, normothermic intraperitoneal chemotherapy in the form of bidirectional neoadjuvant treatment is promising with various newer chemotherapeutic agents. Regardless of the treatment technique applied, the essential element of success is meticulous patient selection and availability of expertise. Future direction is along the line of personalized treatment with the application of translational science.published_or_final_versio

Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma: magnifying endoscopy findings

Gastric mucosaâ associated lymphoid tissue lymphoma is uncommon and most patients have an indolent clinical course. The clinical presentation and endoscopic findings can be subtle and diagnosis can be missed on white light endoscopy. Magnifying endoscopy may help identify the abnormal microstructural and microvascular patterns, and target biopsies can be performed. We describe herein the case of a 64-year-old woman with Helicobacter pyloriâ negative gastric mucosaâ associated lymphoid tissue lymphoma diagnosed by screening magnification endoscopy. Helicobacter pyloriâ eradication therapy was given and she received biological therapy. She is in clinical remission after treatment. The use of magnification endoscopy in gastric mucosaâ associated lymphoid tissue lymphoma and its management are reviewed.published_or_final_versio

Standardized uptake value (SUV) in PET/CT for esophageal cancer correlates with pathological stage and predicts R-category of resection

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Predictive factors in the evaluation of treatment response to neoadjuvant chemoradiotherapy in patients with advanced esophageal squamous cell cancer (Review Article)

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Outcomes after oesophageal perforation: a retrospective cohort study of patients with different aetiologies

Introduction: The mortality rate after oesophageal perforation is high despite advances in operative and non-operative techniques. In this study, we sought to identify risk factors for hospital mortality after oesophageal perforation treatment. Methods: We retrospectively examined patients treated for oesophageal perforation in a university teaching hospital in Hong Kong between January 1997 and December 2013. Their demographic and clinical characteristics, aetiology, management strategies, and outcomes were recorded and analysed. Results: We identified a cohort of 43 patients treated for perforation of the oesophagus (28 men; median age, 66 years; age range, 30-98 years). Perforation was spontaneous in 22 (51.2%) patients (15 with Boerhaaveâ s syndrome and seven with malignant perforation), iatrogenic in 15 (34.9%), and provoked by foreign body ingestion in six (14.0%). Of the patients, 14 (32.6%) had pre-existing oesophageal disease. Perforation occurred in the intrathoracic oesophagus in 30 (69.8%) patients. Emergent surgery was undertaken in 23 patients: 16 underwent primary repair, six surgical drainage or exclusion, and one oesophagectomy. Twenty patients were managed non-operatively, 13 of whom underwent stenting. Two stented patients subsequently required oesophagectomy. Four patients had clinical signs of leak after primary repair: two were treated conservatively and two required oesophagectomy. Overall, six (14.0%) patients required oesophagectomy, one of whom died. Nine other patients also died in hospital; the hospital mortality rate was 23.3%. Pre-existing pulmonary and hepatic disease, and perforation associated with malignancy were significantly associated with hospital mortality (P=0.03, < 0.01, and < 0.01, respectively). Conclusions: Most oesophageal perforations were spontaneous. Mortality was substantial despite modern therapies. Presence of pre-existing pulmonary disease, hepatic disease, and perforation associated with malignancy were significantly associated with hospital mortality. Salvage oesophagectomy was successful in selected patients.published_or_final_versio

Use of flow cytometry in the analysis of stage III squamous cell carcinoma of the oesophagus and its association with MIB-1

Aims - To examine the prognostic and pathobiological importance of DNA content in oesophageal squamous cell carcinomas in Hong Kong Chinese subjects; to evaluate its association with the immunohistochemical proliferative marker MIB-1. Methods - Paraffin wax embedded tumour tissue and adjacent normal tissue (control tissue) samples from 45 resected stage III oesophageal squamous cell carcinomas were studied using flow cytometric analysis. The DNA content and the clinicopathological data of these patients were analysed together with the MIB-1 labelling index. Results - DNA aneuploidy was present in 14 (31%) of the 45 cases. However, the DNA content did not correlate significantly with the age, sex, or survival of the patients, nor the length, location, differentiation and MIB-1 labelling index of the oesophageal carcinomas. The synthetic (S) phase fraction of diploid tumours bore no relation to the patients' survival or MIB-1 score. Conclusions - Flow cytometry was not as useful as the MIB-1 labelling index in predicting the biological characteristics of the tumours and the prognosis of patients with oesophageal squamous cell carcinomas. This study does not support the routine use of DNA flow cytometric analysis in oesophageal cancers.published_or_final_versio

Continuous intraoperative vagus nerve stimulation for monitoring of recurrent laryngeal nerve during minimally invasive esophagectomy

Review Article on Esophageal Surgerypublished_or_final_versio

MicroRNA-375 inhibits tumour growth and metastasis in oesophageal squamous cell carcinoma through repressing insulin-like growth factor 1 receptor

Background: To understand the involvement of micro- RNA (miRNA) in the development and progression of oesophageal squamous cell carcinoma (ESCC), miRNA profiles were compared between tumour and corresponding non-tumour tissues. Methods: miRCURY LNA array was used to generate miRNA expressing profile. Real-time quantitative PCR was applied to detectthe expression of miR-375 in ESCC samples and its correlation with insulin-like growth factor 1 receptor (IGF1R). Methylation-specific PCR was used to study the methylation status in the promoter region of miR-375. The tumour-suppressive effect of miR-375 was determined by both in-vitro and in-vivo assays. Results: The downregulation of miR-375 was frequently detected in primary ESCC, which was significantly correlated with advanced stage (p=0.003), distant metastasis (p<0.0001), poor overall survival (p=0.048) and disease-free survival (p=0.0006). Promoter methylation of miR-375 was detected in 26 of 45 (57.8%) ESCC specimens. Functional assays demonstrated that miR-375 could inhibit clonogenicity, cell motility, cell proliferation, tumour formation and metastasis in mice. Further study showed that miR-375 could interact with the 39-untranslated region of IGF1R and downregulate its expression. In clinical specimens, the expression of IGF1R was also negatively correlated with miR-375 expression (p=0.008). Conclusions: This study demonstrates that miR-375 has a strong tumour-suppressive effect through inhibiting the expression of IGF1R. The downregulation of miR-375, which is mainly caused by promoter methylation, is one of the molecular mechanisms involved in the development and progression of ESCC.published_or_final_versio

A Versatile Orthotopic Nude Mouse Model for Study of Esophageal Squamous Cell Carcinoma

Increasing evidence indicates tumor-stromal interactions play a crucial role in cancer. An in vivo esophageal squamous cell carcinoma (ESCC) orthotopic animal model was developed with bioluminescence imaging established with a real-time monitoring platform for functional and signaling investigation of tumor-stromal interactions. The model was produced by injection of luciferase-labelled ESCC cells into the intraesophageal wall of nude mice. Histological examination indicates this orthotopic model is highly reproducible with 100% tumorigenesis among the four ESCC cell lines tested. This new model recapitulates many clinical and pathological properties of human ESCC, including esophageal luminal stricture by squamous cell carcinoma with nodular tumor growth, adventitia invasion, lymphovascular invasion, and perineural infiltration. It was tested using an AKT shRNA knockdown of ESCC cell lines and the in vivo tumor suppressive effects of AKT knockdown were observed. In conclusion, this ESCC orthotopic mouse model allows investigation of gene functions of cancer cells in a more natural tumor microenvironment and has advantages over previous established models. It provides a versatile platform with potential application for metastasis and therapeutic regimen testing.published_or_final_versio