Significance of preoperative C-reactive protein as a parameter of the perioperative course and long-term prognosis in squamous cell carcinoma and adenocarcinoma of the oesophagus

AIM： C-reactive protein （CRP） is an acute-phase reactant and a known indicator of the malignant potential of the tumour. The aim of this study was to investigate the significance of preoperative CRP as a parameter of the perioperative course and long-term prognosis in patients with squamous cell carcinoma and aclenocarcinoma of the oesophagus. METHODS： Serum CRP was determined preoperatively in 291 of 371 patients undergoing oesophagectomy for cancer from December 1989 to March 2004. Median patient age was 59 （28-79） year, 82.5% of patients were males. Squamous cell carcinoma was diagnosed in 151 （51.9%） and aclenocarcinoma in 122 patients. Transhiatal oesophagectomy was clone in 151 （51.9%） patients and 134 （46.0%） patients underwent the abclominothoracic procedure. RESULTS： In 127 （43.6%） patients the preoperative serum CRP concentration was within the normal range （〈 5 mg/clL）, elevated CRP levels were measured in 164 （56.4%） patients. Tumour extension （P 〈 0.0005） and the number of lymph nodes affected by metastatic spread （P = 0.015） were significantly increased in the group with elevated CRP levels. Among the perioperative parameters both the number of blood transfusions （P = 0.006） and the general complication rate （P = 0.002） were higher in patients with elevated preoperative CRP levels. The long-term survival rate of 13.6 （0-109.8） mo was poorer in the group with elevated CRP levels compared to 18.9 （0-155.4） mo in the group with normal CRP levels （log-rank test： P = 0.107）. Multivariateanalysis with backward variables selection identified preoperative CRP as an independent prognostic factor of the long-term prognosis in patients with oesophageal carcinoma, with a hazard ratio of 1.182 （95% confidence interval： 1.030-1.356）. CONCLUSION： The preoperative serum CRP-level is an easily determined independent prognostic marker in patients with squamous cell carcinoma and adenocarcinoma of the oesophagus.

Risk factors for Barrett’s oesophagus and oesophageal adenocarcinoma:Results from the FINBAR study

AIM:To investigate risk factors associated with Barrett's oesophagus and oesophageal adenocarcinoma.METHODS:This all-Ireland population-based case-control study recruited 224 Barrett's oesophagus patients,227 oesophageal adenocarcinoma patients and 260 controls.All participants underwent a structured interview with information obtained about potential lifestyle and environmental risk factors.RESULTS:Gastro-oesophageal reflux was associated with Barrett's [OR 12.0(95% CI 7.64-18.7)] and oesophageal adenocarcinoma [OR 3.48(95% CI 2.25-5.41)].Oesophageal adenocarcinoma patients were more likely than controls to be ex-or current smokers [OR 1.72(95% CI 1.06-2.81)and OR 4.84(95% CI 2.72-8.61)respectively] and to have a high body mass index [OR 2.69(95% CI 1.62-4.46)].No significant associations were observed between these risk factors and Barrett's oesophagus.Fruit but not vegetables were negatively associated with oesophageal adenocarcinoma [OR 0.50(95% CI 0.30-0.86)].CONCLUSION:A high body mass index,a diet low in fruit and cigarette smoking may be involved in the progression from Barrett's oesophagus to oesophageal adenocarcinoma.

Psychosocial factors and their association with reflux oesophagitis,Barrett's oesophagus and oesophageal adenocarcinoma

AIM:To investigate the role of psychological characteristics as risk factors for oesophageal adenocarcinoma(OAC),as well as the reflux-mediated precursor pathway.METHODS:An all-Ireland population-based case-control study recruited 230 reflux oesophagitis(RO),224 Barrett's oesophagus(BO) and 227 OAC patients and 260 controls.Each case/control group completed measures of stress,depression,self-efficacy,self-esteem,repression and social support.A comparative analysis was undertaken using polytomous logistic regression adjusted for potential confounders.RESULTS:Compared to controls,OAC patients were almost half as likely to report high stress levels over their lifetime(P = 0.010,OR 0.51;95%CI:0.29-0.90)and 36% less likely to report having experienced depression(OR 0.64;95%CI:0.42-0.98).RO patients reported significantly higher stress than controls particularly during middle-and senior-years(P for trends < 0.001).RO patients were 37% less likely to report having been highly emotionally repressed(OR 0.63;95%CI:0.41-0.95).All case groups(OAC,RO and BO) were more likely than controls to report having had substantial amounts of social support(OR 2.84;95%CI:1.63-4.97;OR 1.97;95%CI:1.13-3.44 and OR 1.83;95%CI:1.03-3.24,respectively).CONCLUSION:The improved psychological profile of OAC patients may be explained by response shift.The role of psychological factors in the development of OAC requires further investigation.

Barrett's oesophagus: Current controversies

Oesophageal adenocarcinoma is rapidly increasing in Western countries. This tumour frequently presents late in its course with metastatic disease and has a very poor prognosis. Barrett's oesophagus is an acquired condition whereby the native squamous mucosa of the lower oesophagus is replaced by columnar epithelium following prolonged gastro-oesophageal reflux and is the recognised precursor lesion for oesophageal adenocarcinoma. There are multiple national and society guidelines regarding screening,surveillance and management of Barrett's oesophagus,however all are limited regarding a clear evidence base for a well-demonstrated benefit and cost-effectiveness of surveillance,and robust risk stratification for patients to best use resources. Currently the accepted risk factors upon which surveillance intervals and interventions are based are Barrett's segment length and histological interpretation of the systematic biopsies. Further patient risk factors including other demographic features,smoking,gender,obesity,ethnicity,patient age,biomarkers and endoscopic adjuncts remain under consideration and are discussed in full. Recent evidence has been published to support earlier endoscopic intervention by means of ablation of the metaplastic Barrett's segment when the earliest signs of dysplasia are detected. Further work should concentrate on establishing better risk stratification and primary and secondary preventative strategies to reduce the risk of adenocarcinoma of the oesophagus.

Treatment of dysplastic Barrett's Oesophagus in lower volume centres after structured training

AIM: To investigate whether dysplastic Barrett's Oesophagus can be safely and effectively treated endoscopically in low volume centres after structured training. METHODS: After attending a structured training program in Amsterdam on the endoscopic treatment of dysplastic Barrett's Oesophagus, treatment of these patients was initiated at St Marys Hospital. This is a retrospective case series conducted at a United Kingdom teaching Hospital, of patients referred for endoscopic treatment of Barrett's oesophagus with high grade dysplasia or early cancer, who were diagnosed between January 2008 and February 2012. Data was collected on treatment provided(radiofrequency ablation and endoscopic resection), and success of treatment both at the end of treatment and at follow up. Rates of immediate and long term complications were assessed. RESULTS: Thirty-two patients were referred to St Marys with high grade dysplasia or intramucosal cancer within a segment of Barrett's Oesophagus. Twentyseven met the study inclusion criteria, 16 of these had a visible nodule at initial endoscopy. Treatment was given over a median of 5 mo, and patients received a median of 3 treatment sessions over this time. At the end of treatment dysplasia was successfully eradicated in 96% and intestinal metaplasia in 88%, on per protocol analysis. Patients were followed up for a median of 18 mo. At which time complete eradication of dysplasia was maintained in 86%. Complications were rare: 2 patients suffered from post-procedural bleeding, 4 cases were complicated by oesophageal stenosis. Recurrence of cancer was seen in 1 case. CONCLUSION: With structured training good outcomes can be achieved in low volume centres treating dysplastic Barrett's Oesophagus.

Benign Stenosis of Oesophagus: About 101 Cases in the Digestive Endoscopy Department of the General Idrissa Pouye Hospital (Dakar, Senegal)

Introduction: Benign oesophageal strictures are defined as narrowing of the oesophageal lumen not related to neoplastic pathology. They are frequently encountered during endoscopic practice and are often responsible for a reduction in the quality of life of patients due to the appearance of dysphagia. In sub-Saharan Africa, little data are available on these benign esophageal strictures. The objective of our study was to determine the sociodemographic, diagnostic and therapeutic aspects of benign oesophageal strictures in a digestive endoscopy centre in Senegal. Patients and Methods: This was a retrospective, descriptive study analysing reports of upper GI endoscopies performed between January 2015 and December 2017 in a hospital in Senegal. Reports that concluded to have non-neoplastic oesophageal stenosis were collated. Sociodemographic data, indications for and results of endoscopy, and therapeutic modalities were collected. These data were analysed using the Sphinx version 5 software. Results: We collected 101 cases of benign oesophageal stenosis, representing a prevalence of 2.1% in the endoscopy centre. The mean age of the patients was 34 years (range 2 and 83 years) with a median of 37.9 years. There was a female predominance with a sex ratio of 0.38 (73 females). Dysphagia, the main symptom, was present in 87 patients (86.1% of cases) with a Dysphagia score greater than or equal to 2 in 51 patients (50.5%). The average duration of this dysphagia, excluding caustic stenosis, was 4 years (extremes 1 and 15 years). Endoscopy revealed simple stenosis in 76 cases (75.2% of cases). A membranous ring of the cervical oesophagus, suggestive of the Plummer-Vinson syndrome ring, was found in 60 patients (59.4% of cases) and was the primary cause;other aetiologies were dominated by caustic stenosis (19 cases), Schatzki rings (8 cases) and peptic stenosis (4 cases). Endoscopic dilatation was performed in 90 patients (89.1% of cases) with Savary Gilliard bougies (87 cases) and hydrostatic balloons (3 cases). The average number of dilatation sessions was 1.69. In 10 patients (11.1%), refractory stenosis was observed. This stenosis could be resolved after further dilatation in 8 cases before the 8th session. In 2 patients, dilatation failed. Conclusion: Benign oesophageal strictures in our digestive endoscopy centre in Senegal mainly affect young adults, with a predominance of women. Diagnosis is often late. Cervical oesophageal rings in the context of Plummer-Vinson syndrome are the main cause. Oesophageal dilatation with bougies is of great therapeutic value.

Swallowing of Casson fluid in oesophagus under the influence of peristaltic waves of varying amplitude

The experimentally verified fact that there is a high pressure zone in the lower part of the oesophagus has established that the earlier models fall short of representing the realistic swallowing process in the oesophagus. Since the high pressure is created by gradually increasing amplitudes of peristaltic waves, swallowing of Casson fluid in oesophagus is mathematically remodeled. It is revealed that in the case of exponentially increasing amplitude, pressure is non-uniformly distributed for different cycles. Pressure increases along the entire length of the oesophagus; and finally toward the end of the oesophageal flow, it increases quite significantly, probably to ensure delivery into the stomach. This is a similar observation for Newtonian as well as non-Newtonian fluids but Casson fluids need more pressure; and hence more efforts are required by the oesophagus to transport the fluid forward. When wave amplitude is small, flow rates are small. In such a case, Casson fluid requires higher flow rates for reflux to occur in comparison to Newtonian fluid. This tendency gradually diminishes with increasing amplitude. For a particular value of amplitude, there is no difference; and beyond that the trends are quite opposite. Thus, Casson fluid is found to be less prone to reflux near the wall. It is also concluded that for the Newtonian fluid as well as for the non-Newtonian Casson fluid, reflux is more likely to occur with increasing amplitude and it is further augmented by the addition of amplifying parameter.

Radiotherapy of carcinoma of oesophagus in China

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Squamous cell carcinoma after radiofrequency ablation for Barrett's dysplasia

Barrett’s oesophagus(BO)is a usually indolent condition that occasionally requires endoscopic therapy.Radiofrequency ablation(RFA)is an effective endoscopic treatment for high grade dysplasia(HGD)and intramucosal cancer in BO.It has a good efficacy,durability and safety profile although complications can occur.Here we describe a case of RFA in a patient with high grade dysplasia.Although the response to treatment was initially very good with the development of neosquamous epithelium,the patient very rapidly developed a squamous cell cancer of the oesophagus confirmed on radiology,histology and immunohistochemistry.Sanger sequencing confirmed that the original HGD and the squamous cell cancer(SCC)were derived from separate clonal origins.The report highlights the fact that SCC of the oesophagus has been noted after endoscopic ablation for BO previously and suggest that ablation of BO may encourage the clonal expansion of cells carrying carcinogenic mutations once a dominant clonal population has been eradicated.

Three-field vs two-field lymph node dissection for esophageal cancer:A meta-analysis

AIM: To assess the effects of 3-field lymphadenectomy for esophageal carcinoma.

Overexpression of Slug is associated with malignant progression of esophageal adenocarcinoma

AIM: To characterise expression of known E-cadherin repressors; Snail, Slug and Twist in the development of esophageal adenocarcinoma. METHODS: E-cadherin, Slug, Snail and Twist mRNA expression in Barrett's metaplasia and esophageal adenocarcinoma specimens was examined by real-time reverse transcription-polymerase chain reaction (RT-PCR). Semi-quantitative immunohistochemistry was used to examine cellular localisation and protein levels. The effect of Slug on epithelial mesenchymal transition (EMT) markers was examined by transfection of Slug into an adenocarcinoma line OE33.RESULTS: Cellular localisation of Slug in Barrett's metaplasia was largely cytoplasmic whilst in adenocarcinoma it was nuclear. Semi-quantitative analysis indicated that Slug was more abundant in adenocarcinoma compared to matched Barrett's metaplastic specimens. Snail and Twist were expressed in adenocarcinoma but were cytoplasmic in location and not induced compared to Barrett's mucosa. These observations were supported by mRNA studies where only Slug mRNA was shown to be over-expressed in adenocarcinoma and inversely correlated to E-cadherin expression. Overexpression of Slug in OE33 mediated E-cadherin repression and induced the mesenchymal markers vimentin and fibronectin.CONCLUSION: Progression to adenocarcinoma is associated with increased Slug expression and this may represent a mechanism of E-cadherin silencing.

Upper gastrointestinal tract capsule endoscopy using a nurse-led protocol: First reported experience

AIM To test the feasibility and performance of a novel upper gastrointestinal(GI) capsule endoscope using a nurse-led protocol. METHODS We conducted a prospective cohort analysis of patients who declined gastroscopy(oesophagogastroduodenoscopy, OGD) but who consented to upper GI capsule endoscopy. Patients swallowed the upper GI capsule following ingestion of 1 liter of water(containing simethicone). A series of positional changes were used to exploit the effects of water flow and move the upper GI capsule from one gravity-dependent area to another using a nurse-led protocol. Capsule transit time, video reading time, mucosal visualisation, pathology detection and patient tolerance was evaluated.RESULTS Fifty patients were included in the study. The mean capsule transit times in the oesophagus and stomach were 28 s and 68 min respectively. Visualisation of the following major anatomical landmarks was achieved(graded 1-5: Poor to excellent): Oesophagus, 4.8(± 0.5); gastro-oesophageal junction(GOJ), 4.8(± 0.8); cardia, 4.8(± 0.8); fundus, 3.8(± 1.2); body, 4.5(± 1); antrum, 4.5(± 1); pylorus, 4.7(± 0.8); duodenal bulb, 4.7(± 0.7); second part of the duodenum(D2), 4.7(± 1). The upper GI capsule reached D2 in 64% of patients. The mean video reading time was 48 min with standard playback mode and 20 min using Quickview(P = 0.0001). No pathology was missed using Quickview. Procedural tolerance was excellent. No complications were seen with the upper GI capsule. CONCLUSION The upper GI capsule achieved excellent views of the upper GI tract. Future studies should compare the diagnostic accuracy between upper GI capsule and OGD.

Reduced esophageal cancer incidence in statin users,particularly with cyclo-oxygenase inhibition

AIM:To examine the association between statin use and the development of esophageal cancer METHODS:We performed a systematic review and meta-analysis.Multiple databases(Pubmed,EMBASE,Cochrane Library,Web of Science,Wiley Interscience and Google Scholar) were systematically searched for studies reporting the association of statin use and the development of esophageal cancer.Literature searching and data abstraction were performed independently by two separate researchers.The quality of studies reviewed was evaluated using the Newcastle-Ottawa Quality assessment scale.Meta-analysis on the relationship between statin use and cancer incidence was performed.The effect of the combination of statin plus a cyclo-oxygenase inhibitor was also examined.RESULTS:Eleven studies met eligibility criteria,9 high and 2 medium quality.All were observational studies.Studies examining adenocarcinoma development in Barrett's esophagus included 317 cancers and 1999 controls,population-based studies examining all esophageal cancers included 371203 cancers and 6083150 controls.In the Barrett's population the use of statins(OR = 0.57;95%CI:0.43-0.75) and cyclo-oxygenase inhibitors(OR = 0.59;95%CI:0.45-0.77) were independently associated with a reduced incidence of adenocarcinoma.Combined use of a statin plus cyclooxygenase inhibitor was associated with an even lower adenocarcinoma incidence(OR = 0.26;95%CI:0.1-0.68).There was more heterogeneity in the population-based studies but pooled adjusted data showed that statin use was associated with a lower incidence of all combined esophageal cancers(OR = 0.81;95%CI:0.75-0.88).CONCLUSION:Statin use in patients with Barrett's oesophagus is associated with a significantly lower incidence of adenocarcinoma.The chemopreventive actions of statins,especially combined with cyclooxygenase inhibitors deserve further exploration.

Computation of flow through the oesophagogastric junction

Whilst methods exist to indirectly measure the effects of increased flow or gastro-oesophageal refluxing, they cannot quantitatively measure the amount of acid travelling back up into the oesophagus during reflux, nor can they indicate the flow rate through the oesophagogastric junction (OGJ). Since OGJ dysfunction affects flow it seems most appropriate to describe the geometry of the OGJ and its effect on the flow. A device known as the functional lumen imaging probe (FLIP) has been shown to reliably measure the geometry of and pressure changes in the OGJ. FLIP cannot directly measure flow but the data gathered from the probe can be used to model flow through the junction by using computational flow dynamics (CFD). CFD uses a set of equations known as the Navier-Stokes equations to predict flow patterns and is a technique widely used in engineering. These equations are complex and require appropriate assumptions to provide simplifications before useful data can be obtained. With the assumption that the cross-sectional areas obtained via FLIP are circular, the radii of these circles can be obtained. A cubic interpolation scheme can then be applied to give a high-resolution geometry for the OGJ. In the case of modelling a reflux scenario, it can be seen that at the narrowest section a jet of fluid squirts into the oesophagus at a higher velocity than the fluid surrounding it. This jet has a maximum velocity of almost 2 ms-1 that occurs where the OGJ is at its narrowest. This simple prediction of acid ‘squirting’ into the oesophagusillustrates how the use of numerical methods can be used to develop a better understanding of the OGJ. This initial work using CFD shows some considerable promise for the future.

Unsteady peristaltic transport of Maxwell fluid through finite length tube:application to oesophageal swallowing

This paper analytically investigates the unsteady peristaltic transport of the Maxwell fluid in a finite tube. The walls of the tube are subjected to the contraction waves that do not cross the stationary boundaries. The analysis is carried out by a long wavelength approximation in the non-dimensional form. The expressions for the axial and radial velocities are derived. The pressures across the wavelength and the tubelength are also estimated. The reflux phenomenon is discussed, which culminates into the determination of the reflux limit. Mathematical formulations are physically interpreted for the flow of masticated food materials such as bread and white eggs in the oesophagus. It is revealed that the Maxwell fluids are favorable to flow in the oesophagus as compared with the Newtonian fluids. This endorses the experimental finding of Takahashi et al. （Takahashi, T., Ogoshi, H., Miyamoto, K., and Yao, M. L. Viscoelastic properties of commercial plain yoghurts and trial foods for swallowing disorders. Rheology, 27, 169- 172 （1999））. It is further revealed that the relaxation time does not affect the shear stress and the reflux limit. It is found that the pressure peaks are identical in the integral case while different in the non-integral case.

The oesophageal zero-stress state and mucosal folding from a GIOME perspective

The oesophagus is a cylindrical organ with a collapsed lumen and mucosal folds. The mucosal folding may serve to advance the function of the oesophagus, i.e. the folds have a major influence on the flow of air and bolus through the oesophagus. Experimental studies have demonstrated oesophageal mucosal folds in the no- load state. This indicates that mucosal buckling must be considered in the analysis of the mechanical reference state since the material stiffness drops dramatically after tissue collapse. Most previous work on the oesophageal zero-stress state and mucosal folding has been experimental. However, numerical analysis offers a promising alternative approach, with the additional ability to predict the mucosal buckling behaviour and to calculate the regional stress and strain in complex structures. A numerical model used for describing the mechanical behaviour of the mucosal-folded, three- layered, two-dimensional oesophageal model is reviewed. GIOME models can be used in the future to predict the tissue function physiologically and pathologically.

Role of artificial intelligence in the diagnosis of oesophageal neoplasia:2020 an endoscopic odyssey

The past decade has seen significant advances in endoscopic imaging and optical enhancements to aid early diagnosis.There is still a treatment gap due to the underdiagnosis of lesions of the oesophagus.Computer aided diagnosis may play an important role in the coming years in providing an adjunct to endoscopists in the early detection and diagnosis of early oesophageal cancers,therefore curative endoscopic therapy can be offered.Research in this area of artificial intelligence is expanding and the future looks promising.In this review article we will review current advances in artificial intelligence in the oesophagus and future directions for development.

Endoscopic resection techniques and ablative therapies for Barrett’s neoplasia

Esophageal adenocarcinoma is the most rapidly increas- ing cancer in western countries.High-grade dysplasia (HGD)arising from Barrett’s esophagus(BE)is the most important risk factor for its development,and when it is present the reported incidence is up to 10% per patient-year.Adenocarcinoma in the setting of BE develops through a well known histological sequence,from non-dysplastic Barrett’s to low grade dysplasia and then HGD and cancer.Endoscopic surveillance programs have been established to detect the presence of neo- plasia at a potentially curative stage.Newly developed endoscopic treatments have dramatically changed the therapeutic approach of BE.When neoplasia is confined to the mucosal layer the risk for developing lymph node metastasis is negligible and can be successfully eradi- cated by an endoscopic approach,offering a curative in- tention treatment with minimal invasiveness.Endoscopic therapies include resection techniques,also known as tissue-acquiring modalities,and ablation therapies or non-tissue acquiring modalities.The aim of endoscopic treatment is to eradicate the whole Barrett’s segment,since the risk of developing synchronous and metachro- nous lesions due to the persistence of molecular aberra- tions in the residual epithelium is well established.

Dysphagia lusoria: A late onset presentation

Dysphagia lusoria is a term used to describe dysphagia secondary to vascular compression of the oesophagus. The various embryologic anomalies of the arterial brachial arch system often remain unrecognised and asymptomatic, but in 30%-40% of cases can result in tracheo-oesophageal symptoms, which in the majority of cases manifest as dysphagia. Diagnosis of dysphagia lusoria is via barium swallow and chest Computed tomography scan. Manometric abnormalities are variable, but age-related manometric changes may contribute to clinically relevant dysphagia lusoria in patients who present later in life. Our report describes a case of lateonset dysphagia secondary to a right aortic arch with an aberrant left subclavian artery, which represents a rare variant of dysphagia lusoria. The patient had proven additional oesophageal dysmotility with solid bolus only and a clinical response to dietary modification.

Dysphagia: Thinking outside the box

Dysphagia is a common symptom that is important to recognise and appropriately manage, given that causes include life threatening oesophageal neoplasia, oropharyngeal dysfunction, the risk of aspiration, as well as chronic disabling gastroesophageal reflux(GORD). The predominant causes of dysphagia varies between cohorts depending on the interplay between genetic predisposition and environmental risk factors, and is changing with time. Currently in white Caucasian societies adopting a western lifestyle, obesity is common and thus associated gastroesophageal reflux disease is increasingly diagnosed. Similarly, food allergies are increasing in the west, and eosinophilic oesophagitis is increasingly found as a cause. Other regions where cigarette smoking is still prevalent, or where access to medical care and antisecretory agents such as proton pump inhibitors are less available, benign oesophageal peptic strictures, Barrett's oesophagus, adeno-as well as squamous cell carcinoma are endemic. The evaluation should consider the severity of symptoms, as well as the pretest probability of a given condition. In young white Caucasian males who are atopic or describe heartburn, eosinophilic esophagitis and gastroesophageal reflux disease will predominate and a proton pump inhibitor could be commenced prior to further investigation. Upper gastrointestinal endoscopy remains a valid first line investigation for patients with suspected oesophageal dysphagia. Barium swallow is particularly useful for oropharyngeal dysphagia, and oesophageal manometry mandatory to diagnose motility disorders.