Possible Predictive Markers of Response to Therapy in Esophageal Squamous Cell Cancer.

The aim of the present study was to investigate the relationship between the intensity of biomarker expression and the response to radiochemotherapy in patients with advanced esophageal squamous cell cancer (ESCC). Ninety-two patients with locally advanced ESCC were examined retrospectively. Pre-treatment tumor samples were stained for proteins SOUL, Hsp 16.2, Growth Hormone-Releasing Hormone Receptor (GHRH-R) and p-Akt using immunhistochemistry methods. Kaplan-Meier curves were used to show the relationship between intensity of expression of biomarkers and clinical parameters and 3-year OS. A significant correlation was found between high intensity staining for Hsp 16.2, p-Akt and SOUL and poor response to NRCT. Application of a higher dose of radiation and higher dose of cisplatin resulted in better clinical and histopathological responses, respectively. Among the clinical parameters, the localization of the tumor in the upper-third of the esophagus and less than 10% weight loss were independent prognostic factors for increased 3-year OS. Hsp16.2, p-Akt and SOUL are predictors of negative response to NRCT, therefore these biomarkers may become promising targets for therapy. Furthermore, level of expression of p-Akt, weight loss and the localization of the tumor are significant factors in the prediction of OS in ESCC.

Prognostic role of HPV infection in esophageal squamous cell carcinoma.

BACKGROUND: The aims of this study were to evaluate whether HPV infection has a prognostic role in patients with esophageal squamous cell carcinoma who underwent oncological treatment and also to compare the heat shock proteins (Hsp) 90, 27 and 16.2 and growth hormone-releasing hormone receptor (GHRH-R) expression patterns of the pre-treatment tumor biopsies with the HPV status and with the oncological response. METHODS: Pre-treatment tumor biopsies of 74 patients with locally advanced esophageal squamous cell carcinoma were processed retrospectively. The presence of HPV was detected by chromogenic in situ hybridization. Hsp and GHRH-R expressions were determined using immunohistochemistry. Following neoadjuvant or definitive radiochemotherapy, the patients were restaged according to the Response Evaluation Criteria in Solid Tumors. The correlation between the HPV status, response to treatment and Hsp and GHRH-R expressions were evaluated. RESULTS: Fourteen (19%) patients were HPV-positive. These patients were more likely to respond poorly to multimodal therapy (71.4% were non-responders vs. 28.6% responders) and had shorter survival compared to HPV-negative patients (mean survival of 8 months vs. 11 months), although the difference was not significant. A significantly higher number of HPV-positive patients expressed Hsp 90 and 16.2 at high levels (93 and 79%, respectively) than at low levels (Chi-Square p = 0.019 and p = 0.031). Higher levels of Hsp expressions were associated with poorer response to therapy and worse overall survival. No correlation was found between GHRH-R expression and the HPV status, nor between GHRH-R expression and the treatment response of the examined samples. CONCLUSIONS: We found that HPV infection was associated with poor response to oncological treatment and decreased overall survival, and therefore proved to be a negative prognostic factor in patients with esophageal squamous cell carcinoma. There was a linear correlation between levels of Hsp 90 and 16.2 expression and HPV positivity.

Gastroesophageal Reflux Disease Might Induce Certain-Supposedly Adaptive-Changes in the Esophagus: A Hypothesis.

BACKGROUND: The increasing prevalence of GERD has become a major concern due to its major health and economic impacts. Beyond the typical unpleasant symptoms, reflux can also be the source of severe, potentially life-threatening complications, such as aspiration. AIM: Our aim was to support our hypothesis that the human body may in some cases develop various protective mechanisms to prevent these conditions. METHODS: Based on our experiences and review of the literature, we investigated the potential adaptive nature of seven reflux complications (hypertensive lower esophageal sphincter, achalasia, hypertensive upper esophageal sphincter, Zenker's diverticulum, Schatzki's ring, esophageal web, and Barrett's esophagus). RESULTS: Patients with progressive GERD may develop diverse structural and functional esophageal changes that narrow the lumen of the esophagus and therefore reduce the risk of regurgitation and protect the upper aerodigestive tract from aspiration. The functional changes (hypertensive lower esophageal sphincter, achalasia, hypertensive upper esophageal sphincter) seem to be adaptive reactions aimed at easing the unpleasant symptoms and reducing acid regurgitation. The structural changes (Schatzki's ring, esophageal web) result in very similar outcomes, but we consider these are rather secondary consequences and not real adaptive mechanisms. Barrett's esophagus is a special form of adaptive protection. In these cases, patients report significant relief of their previous heartburn as Barrett's esophagus develops because of the replacement of the normal squamous epithelium of the esophagus by acid-resistant metaplastic epithelium. CONCLUSION: We believe that GERD may induce different self-protective reactions in the esophagus that result in reduced acid regurgitation or decreased reflux symptoms.

The effect of trimetazidine in reducing the ischemia-reperfusion injury in rat epigastric skin flaps.

BACKGROUND: Ischemia-reperfusion injury may lead to insufficient microcirculation and results in partial flap loss during the free flap surgeries. OBJECTIVE: This study aimed to investigate the effect of trimetazidine (TMZ) on oxidative stress, inflammation and histopathological changes, using the epigastric skin flap model in rats. METHODS: 40 male Wistar rats were used, that were divided into four groups. Control group, non-treated ischemic (I/R)-group and two trimetazidine treated groups (preischemically, postischemically) were established. To create ischemia in the skin flap, the superficial epigastric vessels were clamped for six hours, followed by twenty-four hours of reperfusion. Blood samples and biopsies from skin flaps were collected at the end of the reperfusion period. The inflammatory response, the degree of oxidative stress (by measuring the plasma level of malondialdehyde (MDA), reduced glutathione (GSH); sulfhydryl (-SH) groups) and histopathological changes were evaluated. RESULTS: Inflammatory response, and oxidative stress were significantly attenuated in the trimetazidine treated groups, compared to the non-treated ischemic group. Histopathological findings were also correlated with the biochemical results. CONCLUSION: In our study trimetazidine could reduce the ischaemia-reperfusion injury, even after an unexpected ischemic period, so it is a promising drug during free tissue transfer, replantation or during revascularization procedures in the future.

Achalasia following reflux disease: coincidence, consequence, or accommodation? An experience-based literature review.

Achalasia is a motility disorder of the esophagus characterized by the defective peristaltic activity of the esophageal body and impaired relaxation of the lower esophageal sphincter due to the degeneration of the inhibitory neurons in the myenteric plexus of the esophageal wall. The histopathological and pathophysiological changes in achalasia have been well described. However, the exact etiological factors leading to the disease still remain unclear. Currently, achalasia is believed to be a multifactorial disease, involving both extrinsic and intrinsic factors. Based on our experience and the review of literature, we believe that gastroesophageal reflux disease (GERD) might be one of the triggering factors leading to the development of achalasia. However, it is also stated that the two diseases can simultaneously appear independently from each other. Considering the large number and routine treatment of patients with GERD and achalasia, the rare combination of the two may even remain unnoticed; thus, the analysis of larger patient groups with this entity is not feasible. In this context, we report four cases where long-standing reflux symptoms preceded the development of achalasia. A literature review of the available data is also given. We hypothesize that achalasia following the chronic acid exposure of the esophagus is not accidental but either a consequence of a chronic inflammation or a protective reaction of the organism in order to prevent aspiration and lessen reflux-related symptoms. This hypothesis awaits further clinical confirmation.

[Esophageal complications of gastroesophageal reflux disease: consequences or defensive reactions?] / A gastrooesophagealis refluxbetegség nyelocsoszövodményei: következmények vagy védekezoreakciók?

Gastroesophageal reflux disease affects more than 10% of the adult population. Most patients can be effectively treated with lifestyle changes and adequate acid-reducing therapy. However, about 10% of the patients remain symptomatic despite treatment and severe complications may develop. Interestingly, some of these complications seem to be a sort of defensive mechanism that may either alleviate the patient's symptoms or prevent developing further complications. In Barrett's esophagus, which can be unambigously considered as a complication of gastroesophageal reflux disease, reflux symptoms ruining the quality of life may significantly improve, since the metaplastic Barrett epithelium is much more resistent to gastric acid, than the normal epithelial lining of the esophagus. Furthermore, the motility disorders (hypertensive lower esophageal sphincter, achalasia, cricopharyngeal achalasia) and structural changes (Schatzki's ring, esophageal stricture, subglottic trachea stenosis), which develop as a complication of reflux may help to prevent aspiration that can cause new complaints and may lead to further complications. Orv Hetil. 2017; 158(20): 763-769.

[Complications and reoperations following laparoscopic antireflux surgery]. / Szövodmények és reoperációk laparoszkópos antirefluxmutétek után.

Laparoscopic antireflux surgery is an effective treatment for patients with gastro-esophageal reflux disease, when it is refractory to conservative management. In experienced centers the procedure is safe, although complications may develop either during surgery or in the early or late postoperative period, which may necessitate revisional surgery. Between 1998 and 2015 a total of 407 patients underwent laparoscopic antireflux surgery at the Department of Surgery, University of Pécs. This interval was divided into two periods. In the first one, between 1998 and 2006, we operated on 241 patients who were all enrolled in a prospective study. All the diagnostic examinations were carried out at our institution. In the second period 166 patients were treated with minimal invasive surgery and the data were analyzed retrospectively. The 407 patients comprised 161 men and 246 women with a median age of 53,1 years. Hiatoplasty was reinforced with teres ligament in 27 cases, a prosthetic mesh was used in 28 cases and fascia lata in a four cases, when hiatal closures were not considered reliable. In 16 cases (4%) the operation was converted to open procedure, and our mortality rate was 0,5%. Revisional surgery was performed laparoscopically in 39 patients, and thoraco-laparotomy was done in six cases (12%). 5 additional reoperations were performed in patients, who had their primary antireflux surgery in another institution. Our 4% conversion, 12% reoperation and 0,5% mortality rates correspond to the figures published in the literature. In conclusion, this study confirms that laparoscopic antireflux surgery is a safe procedure with very good clinical outcomes. Late complications, such as recurrent reflux disease and reherniation, as well as revisional surgery occured almost exclusively after surgical treatment of the large hiatal hernias.

Laparoszkópos hiatushernia-rekonstrukciót követo intraoesophagealis hálómigráció.

CASE PRESENTATION: The authors report the case of a 68-year-old patient who presented with dysphagia 4 months after a mesh-reinforced antireflux surgery. Examinations revealed partial penetration of the mesh into the esophagus. During an expedited surgery, the mesh was removed through thoraco-laparotomy. Distal esophagus and proximal gastric resections were carried out due to longitudinal perforation site and esophageal stricture, and the continuity of the alimentary tract was restored with jejunal interposition. At the 3-month follow-up visit the patient was asymptomatic and a swallow examination showed normal conditions after the surgery. DISCUSSION: Several studies have shown that primary closure of large hiatal hernias is associated with high recurrence rate. In order to reduce this ratio, mesh reinforcement of the crural repair was introduced to prevent reherniation. Therefore, the incidence of recurrence has indeed decreased, however, mesh-related complications have increased. Because of the special anatomical site, the mesh around the gastroesophageal junction is in continuous movement and this can potentially lead to complications such as esophageal erosion, perforation or extensive fibrosis and stenosis. These complications may cause severe, even life-threatening conditions that could only be treated with difficult surgeries. Based on the experience of our case and the review of the literature, we would like to highlight one of the potential, serious complications of mesh-reinforced hiatal repair.