Absolute CT perfusion parameter values after the neoadjuvant chemoradiotherapy of the squamous cell esophageal carcinoma correlate with the histopathologic tumor regression grade.

PURPOSE: To analyze value of the computed tomography (CT) perfusion imaging in response evaluation of the esophageal carcinoma to neoadjuvant chemoradiotherapy (nCRT) using the histopathology as reference standard. METHODS: Forty patients with the squamous cell esophageal carcinoma were re-evaluated after the nCRT by CT examination, which included low-dose CT perfusion study that was analyzed using the deconvolution-based CT perfusion software (Perfusion 3.0, GE). Histopathologic assessment of tumor regression grade (TRG) according to Mandard's criteria served as reference standard of response evaluation. Statistical analysis was performed using Spearman's rank correlation coefficient (r(S)) and Kruskal-Wallis's test. RESULTS: The perfusion CT parameter values, measured after the nCRT in the segment of the esophagus that had been affected by neoplasm prior to therapy, significantly correlated with the TRG: blood flow (BF) (r(S)=0.851; p<0.001), blood volume (BV) (r(S)=0.732; p<0.001) and mean transit time (MTT) (r(S)=-0.386; p=0.014). Median values of BF and BV significantly differed among TRG 1-4 groups (p<0.001), while maximal esophageal wall thickness did not (p=0.102). Median BF and BV were gradually rose and MTT decreased as TRG increased, from 21.4 ml/min/100 g (BF), 1.6 ml/100 g (BV) and 8.6 s (MTT) in TRG 1 group, to 37.3 ml/min/100 g, 3.5 ml/100 g and 7.5 s in TRG 2 group, 81.4 ml/min/100 g, 4.1 ml/100 g and 3.8 s in TRG 3 group, and 121.1 ml/min/100 g, 4.9 ml/100 g and 3.7 s in TRG 4 group. In all 15 patients who achieved complete histopathologic regression (TRG 1), BF was <30.0 ml/min/100 g. CONCLUSIONS: CT perfusion could improve the accuracy in response evaluation of the esophageal carcinoma to nCRT.

Micrometastasis of hypopharyngeal cancer.

PURPOSE: The aim of this study is to estimate the incidence and clinical impact of lymph node micrometastases in hypopharyngeal squamous cell cancer (HSCC). MATERIALS AND METHODS: In this retrospective study, we enrolled 58 patients who have undergone surgery for HSCC (between January 2004 and January 2011). Pharyngolaryngectomy and oesophagectomy with selective bilateral neck dissection was performed in all patients. Based on standard histological examination, 17 patients met N0 and 8 patients met N1 criteria and were further evaluated for the presence of micrometastases and isolated tumour cells (ITC). Following immunohistochemical analysis, the patients were grouped according to the presence of micrometastases and ITCs. RESULTS: In the pN0 group, cytokeratin-positive cells were detected in five patients, and they were marked as N0/CK+. Among these five patients, two were found to harbour micrometastases and ITCs, whilst in three, only ITCs were found. Two patients (11.75 %) were upstaged to pN1. The patients marked as N0/CK+ had a statistically significant worse overall survival rates than pN0 patients with tissue samples read as negative for cytokeratin immunostaining (p = 0.019, p < 0.05). In the pN1 group, cytokeratin-positive cells were detected in two patients, with one patient showing micrometastases and ITC, and the other showing ITC only. One patient was upstaged to pN2. CONCLUSION: Patients with lymph node micrometastases and ITC had worse overall survival rates, which may indicate that more aggressive post-operative treatment regimens should be considered for these HSCC patients.

Comparison between the deconvolution and maximum slope 64-MDCT perfusion analysis of the esophageal cancer: is conversion possible?

PURPOSE: To estimate if CT perfusion parameter values of the esophageal cancer, which were obtained with the deconvolution-based software and maximum slope algorithm are in agreement, or at least interchangeable. METHODS: 278 esophageal tumor ROIs, derived from 35 CT perfusion studies that were performed with a 64-MDCT, were analyzed. "Slice-by-slice" and average "whole-covered-tumor-volume" analysis was performed. Tumor blood flow and blood volume were manually calculated from the arterial tumor-time-density graphs, according to the maximum slope methodology (BF(ms) and BV(ms)), and compared with the corresponding perfusion values, which were automatically computed by commercial deconvolution-based software (BF(deconvolution) and BV(deconvolution)), for the same tumor ROIs. Statistical analysis was performed using Wilcoxon matched-pairs test, paired-samples t-test, Spearman and Pearson correlation coefficients, and Bland-Altman agreement plots. RESULTS: BF(deconvolution) (median: 74.75 ml/min/100g, range, 18.00-230.5) significantly exceeded the BF(ms) (25.39 ml/min/100g, range, 7.13-96.41) (Z=-14.390, p<0.001), while BV(deconvolution) (median: 5.70 ml/100g, range: 2.10-15.90) descended the BV(ms) (9.37 ml/100g, range: 3.44-19.40) (Z=-13.868, p<0.001). Both pairs of perfusion measurements significantly correlated with each other: BF(deconvolution), versus BF(ms) (rS=0.585, p<0.001), and BV(deconvolution), versus BV(ms) (rS=0.602, p<0.001). Geometric mean BF(deconvolution)/BF(ms) ratio was 2.8 (range, 1.1-6.8), while geometric mean BV(deconvolution)/BV(ms) ratio was 0.6 (range, 0.3-1.1), within 95% limits of agreement. CONCLUSIONS: Significantly different CT perfusion values of the esophageal cancer blood flow and blood volume were obtained by deconvolution-based and maximum slope-based algorithms, although they correlated significantly with each other. Two perfusion-measuring algorithms are not interchangeable because too wide ranges of the conversion factors were found.

Is there a correlation between molecular markers and response to neoadjuvant chemoradiotherapy in locally advanced squamous cell esophageal cancer?

PURPOSE: To evaluate the expression of epidermal growth factor receptor (EGFR), p53, p21 and thymidylate synthase (TS) in a pretherapy biopsy specimen of locally advanced squamous cell esophageal cancer and correlate these markers with response to neoadjuvant chemoradiotherapy. METHODS: Sixty-two patients with histopathologically proven locally advanced (T3 or greater) squamous cell esophageal cancer were enrolled. The expression of EGRF, p53, p21 and TS markers was assessed with immunohistochemistry. Semiquantitative assessment of expression of these markers was performed based on the percent of the stained cells. Radiotherapy (45-50.4 Gy) was delivered concomitantly with 5-fluorouracil (5-FU)/leucovorin (LV)/cisplatin (CIS) chemotherapy. Five to 6 weeks after chemoradiation, response to treatment was assessed. Medically fit and operable patients were operated. The resected material underwent histopathological evaluation of tumor expansion, histological classification after initial multimodality treatment (yp TNM), residual status and tumor regression grade (TRG). RESULTS: Out of 62 patients enrolled, 41 (66%) were evaluated for molecular markers. Clinical response rate was 43.9%. Out of 41 patients, 12 (29%) underwent surgery. TRG 1 was noted in 58% of the patients. In a pretherapy tumor specimen, positive expression was noted in 80, 90, 80 and 71% for EGFR, p53, p21 and TS, respectively. We noted no statistically significant difference neither between tumor marker expression and clinical response to chemoradiation, nor between tumor marker expression and TRG. CONCLUSION: We registered no difference in response to treatment between EGFR, TS, p21 and p53 positive and negative staining.

Current concepts in the anatomy and origin of pharyngeal diverticula.

The role of this paper is to present the current concepts in anatomy and etiopathogenesis of pharyngeal diverticula. Precise anatomical considerations highly emphasizing the weak anatomic areas which predispose the pouch formation are discussed. Focus exposed in details will also be given upon the structural and functional characteristics of the upper esophageal sphincter as well as to its physiological states, architecture and dynamic functions. A brief review of historical and current perspectives regarding the origin of pharyngeal diverticula has also been given. Special attention is given to the abnormal cricopharyngeal function in patients with pharyngeal pouches in the terms of altered UES compliance, importance of gastroesophageal reflux and histopathologic changes of cricopharyngeal muscle.

Surgical experience of the national institution in the treatment of Zenker's diverticula.

AIM: To review the 8-year experience of the Department of Esophagogastric Surgery, First Surgical University Hospital in Belgrade in the surgical management of Zenker's diverticula (ZD). METHODS: Between January 2000 and January 2009, 52 patients underwent surgical procedure for the treatment of ZD. Complete preoperative workup including the symptom evaluation and large variety of structural and functional diagnostic procedures were conducted before the surgery. After the operative treatment patients underwent detailed follow-up in regular intervals up to 3 years. RESULTS: Preoperative evaluation marked higher incidence of hiatal hernia and pathologic gastroesophageal reflux (GER) among the patients with ZD then in normal population. According to the preoperative evaluation and size of diverticula, as well as due to the intraopertive findings, a variety of surgical procedures were performed, including myotomy alone (n = 2), diverticulopexy and myotomy (n = 36) and diverticulectomy and myotomy (n = 14). Regardless of the operative treatment no salivary cervical fistulas were observed. Late and early postoperative results revealed low incidence in postoperative transitory dysphagia or regurgitation. CONCLUSION: The results of this study show that the open surgical procedures are safe and effective in the treatment of ZD. Cricopharyngeal myotomy remains the essential focus of treatment, while the choice of resecting or suspending the diverticulum is brought upon its size. Complete preoperative investigation must be conducted in ZD patients, and the role of pathologic GER must be taken into account when we discuss the origin of this disorder.

[Delayed MDCT in preoperative analysis of the hypopharyngeal postcricoid carcinomas].

INTRODUCTION: Determination of borders of the postcricoid tumors is of great significance during preoperative analysis, because it can be of considerable influence on operative treatment and its planning. Therefore, exact demarcation, delineation and opacification of tumor zone on CT analysis is crucial. MATERIAL AND METHOD: Late CT scan delay of 150 sec and slow vein flow of contrast agents of 1 ml/sec is radiological method of choice in preoperative evaluation of carcinoma of the post-cricoid region. For our purposes we used modern MSCT Light Speed GE 64, with slice thick of 2.5 mm (retro recon of 0.625) with software postprocesing. RESULTS AND DISCUSSION: In our study, we have detaily analized 25 patients with clinically proved carcinoma of hypopharynx, of which 8 had the hardest form of tumor. Control group were patients to whom CT scan was done by standard protocol and CT time scan of 50 sec. With all 8 of them, scanned by protocol of delay time of 150 sec, was proved a statistically important validity of interpretation and demarcation of tumors. CONCLUSION: Delay time on CT scanning is proved to be efficient protocol for visualization of neck soft tissues which includes the walls of hypopharynx.

[Preoperative chemoradiotherapy in locally advanced esophageal cancer].

Preoperative or definitive chemoradiotherapy defines today the standard treatment of patients with localized or locally advanced esophageal cancer. Preliminary results of our study are presented. 46 patients with locally advanced squamous cell esophageal cancer (T3-4, N0-1, M0) were enrolled. All patients recieved concomitant chemotherapy (Cisplatin/5FU/LV) and radiotherapy (45-50, 4Gy). Clinical response rate was 59% (3 patients (7%) complete response, 24 patients (52%) partial regression, 13 (28%) stabile disease, 6 patients (13%) disease progression). Out of 46 patients, 12 were operated (26%), all with R0 resection. Complete patohistolgical regression (TRG 1) was noted in 5 patients (42%). TRG 2 i TRG 3 in one (8%) and 3 patients (25%), and TRG 4 in 3 patients (25%). Mean survival time in operated group of patients was 9.3 months, and in nonoperated group 5.5 months. Studies show improved survival rate in patients with complete response to chemoradiotherapy and R0 resection. Individualy tailored therapy is essential.

[Solving of complications arising during and after application self-expandible metallic stents in palliation of malignant dysphagia].

INTRODUCTION: During palliative treatment of malignant disphagia in inoperabile patients various and serious complications may occur and compromite the method of treatment if there were not solved. AIM: Goal is to present the most frequent complications due to esophageal stenting and the way of their solving. MATERIALS AND METHOD: From 1996. to 2009. in 237 patients (164 esophageal carcinoma, 33 carcinoma of the esophagogastric junction, 14 bronchial carcinoma, 7 esophagojejunal anastomosis, 9 esophageal fistulas) 245 stents have been placed (54 uncovered and 191 covered). Mean survival period was 14.7 months (ranged from 1 do 33 months). Esophageal perforation (1), stent migration (9), malignant tissue ingrowth (31) and overgrowth (24) have been revealed by barium contrast study during follow up. Perforation was solved by placing covered stent, migration by removing migrated stent endoscopically or surgically, ingrowth and overgrowth by balon dilating or restenting under the fluoroscopically guidance and control. CONCLUSION: One can expect and recognize complications regarding esophageal stenting because it is the only way for their sucsessfull treatment.

Gastroesophageal reflux in infants and children.

Gastroesophageal reflux disease (GERD) is the most common esophageal disorder and the most frequent reason why infants are referred to the pediatric gastroenterologist, affecting as much as 30% of the pediatric population. Presenting features of GERD in infants and children are quite variable and follow patterns of gastrointestinal and extra-esophageal manifestations that vary between individual patients and may change according to age. Patients may be minimally symptomatic, or may exhibit severe esophagitis, bleeding, nutritional failure, or severe respiratory problems. GERD is also complex for the diagnostic techniques required to assess its repercussions or explain its origin. Although different abnormalities in motility variables, such as lower eso-phageal sphincter (LES) function, esophageal peristalsis and gastric motor activity can contribute to the development of GERD, the degree of esophageal acid exposure represents the key factor in its pathogenesis. Esophageal pH monitoring, based on both the detection of acid reflux episodes and the measurement of their frequency and duration, has been regarded as the most sensitive and specific diagnostic tool for diagnosing reflux disease. The aim of this paper is to give a concise review for the clinicians encountering this specific disease in infants and children.

The accuracy of ultrasonography in classification of groin hernias according to the criteria of the unified classification system.

BACKGROUND: The modern concept of type-related individualized groin hernia surgery imposes a demand for precise and accurate preoperative determination of the type of groin hernia. The aim of this prospective study was to evaluate the accuracy of ultrasonography in classification of groin hernias, according to the criteria of the unified classification system. Unified classification divides groin hernias into nine types (grades): type I (indirect, small), II (indirect, medium), III (indirect, large), IV (direct, small), V (direct, medium), VI (direct, large), VII (combined-pantaloon), VIII (femoral), and O (other). PATIENTS AND METHODS: One hundred and twenty-five adult patients with clinically diagnosed or suspected groin hernias were examined. Ultrasonography of both groins was performed with a 5 to 10-MHz linear-array transducer. Preoperative ultrasonographic findings of type of groin hernia were compared with the intraoperative findings, which were considered the gold standard. RESULTS: Total accuracy of ultrasonography in determination of type of groin hernia was 96% (119 of 124 correct predictions of type of groin hernia compared with surgical explorations). All hernias of types I, IV, V, VII, and VIII were correctly identified with ultrasonography (sensitivity and specificity 100%). In the remaining five cases of the 124 (4%), hernia was incorrectly classified with ultrasonography: type VI (direct, large) was misdiagnosed as type III (indirect, large) in three cases, type III as type VI in one case, and type III as type II (indirect, medium) in one case. The sensitivity and the specificity of ultrasonography in classifying type II were 100 and 99%, respectively, for type III, 85 and 97%, and for type VI, 90 and 99%. CONCLUSION: Ultrasonography of the groin regions could be used with great accuracy for precise classification of groin hernias in adults. Each type of groin hernia, according to the unified classification system that we used for classification, has a characteristic ultrasonographic presentation, which is demonstrated in this study.

Bimonthly 24 h infusion of high-dose 5-fluorouracil vs EAP regimen in patients with advanced gastric cancer. A randomized phase II study.

BACKGROUND: To investigate the activity and toxicity of high dose (HD) infusional 5-FU in comparison to EAP regimen as first-line chemotherapy in patients with advanced gastric cancer. PATIENTS AND METHODS: Histologically confirmed measurable advanced gastric cancer, age < 72 yr, ECOG performance status 0-2, no prior chemo- and radiotherapy, adequate organ functions. TREATMENT: EAP arm: doxorubicin (40 mg/m(2)), etoposide (360 mg/m(2)), and cisplatin (80 mg/m(2)) every 28 d; HD 5-FU arm: 5-FU 2.6 g/m(2) 24 h infusion, biweekly. RESULTS: Sixty patients were randomized. Patient characteristics (arms EAP/HD 5-FU): Median age 57/55 yr, median PS 1/1, LAD (patients) 3/8, M1 (patients) 27/22. Median number of cycles (range): EAP arm 4 (2-8), HD 5-FU arm 2 (1-8). Worst toxicity per cycle (grade 3 and 4 in%): Neutropenia 20/3, thrombocytopenia 9/0, anemia 9/13, diarrhea 3/10, nausea 17/7, vomiting 10/0 for EAP and HD 5-FU arms, respectively. All patients were eligible for response in both arms. Confirmed response rate (95%CI): EAP arm 34% [16-50%]/HD 5-FU arm 10% (0-21%), no change: 46/40%, progression of disease: 20/50, respectively. Overall survival (range): EAP arm A 7 mo [3-27], HD 5-FU arm 6 mo (4-25). CONCLUSIONS: Infusional HD 5-FU showed a low incidence of severe toxicity. But given the low efficacy of 5-FU in the dosage we applied in the study, it cannot be recommended as a single treatment for further studies. Assessment of higher dose intensity and/or dose density of 5-FU, with introduction of other active drugs in combination, could be an option for further studies.

[Treatment of gastrointestinal hemorrhage manifestation induced by nonsteroidal anti-inflammatory agents]].

INTRODUCTION: The risk of upper gastrointestinal tract bleeding in the patients taking NSAID estimates 1% per year. Bleeding stops spontaneously in approximately 80% of all cases. Persistent and repeated bleeding (expecialy during the initial hospitalization) still represent the serious clinical problem. In this group of patients, mortality rate is between 6-10%, which in the USA counts 10-20000 patients per year. AIM OF THE STUDY: The purpose of this review is to update the current knowledge of the use of different therapeutic strategies in patients with NSAID induced upper gastrointestinal bleeding. RESULTS: Proton pump inhibitors (PPI) therapy is effective as a prevention of NSAID induced acidopeptic lesions, and also represents the first and best therapeutic option for the treatment of complications, such as upper gastrointestinal bleeding. In the last three decades use of early flexibile (diagnostic and therapeutic) endoscopy, agressive acidosupression (PPIs), and surgical treatment in restrictive indications, resulted in decreasing of the mortality rates from 25-35% to 6-10%. When PPIs and flexible endoscopy are not sufficient in the control of upper gastrointestinal bleeding, use of systemic hemostatic drugs could be taken into consideration. CONCLUSION: Multidisciplinary approach, precise diagnostic and therapeutic critearia would probably result in better outcome of patients with active upper gastrointestinal bleeding.

[Radiologic palliation of dysphagia--placement of esophageal stents under radiologic control].

As for the gastrointestinal tract, stents are most commonly applied in the esophagus. Majority of the esophageal stents are implanted for the purpose of palliation of the inoperable malignant dysphagias, however they may also be used, although less frequently, for dilatation of the constricted anastomosis, covering of fistulas and least frequently for dilatation of the benign stenoses. Increasingly frequently the stents are used in the prepyloric gastric region, duodenal and rectosigmoid portion of the colon. The paper describes our own six-year experience in application of the gastrointestinal stents for palliation of dysphagia.

Colon interposition in the treatment of esophageal caustic strictures: 40 years of experience.

The objective of this article was to analyze 40 years of experience of colon interposition in the surgical treatment of caustic esophageal strictures from the standpoints of our long-term personal experience. Colon interposition has proved to be the most suitable type of reconstruction for esophageal corrosive strictures. The choice of colon graft is based on the pattern of blood supply, while the type of anastomosis is determined by the stricture level and the part of colon used for reconstruction. In the period between 1964 and 2004, colon interposition was performed in 336 patients with a corrosively scared esophagus, using the left colon in 76.78% of the patients. In 87.5% a colon interposition was performed, while in the remaining patients an additional esophagectomy with colon interposition had to be done. Hypopharyngeal strictures were present in 24.10% of the patients. Long-term follow-up results were obtained in the period between 1 to up to 30 years. Early postoperative complications occurred in 26.48% of patients, among which anastomosic leakage was the most common. The operative mortality rate was 4.16% and late postoperative complications were present in 13.99% of the patients. A long-term follow up obtained in 84.82% of the patients found excellent functional results in 75.89% of them. We conclude that a colon graft is an excellent esophageal substitute for patients with esophageal corrosive strictures, and when used by experienced surgical teams it provides a low rate of postoperative morbidity and mortality, and long-term good and functional quality of life.

[Gastrointestinal hemorrhage--hemorrhage from the upper digestive system].

Upper gastrointestinal (GI) bleeding represents the commonest emergency managed by gastroenterologists utilizing substantial clinical and economic resources. Manifestations of GI bleeding depend uppon its localization, magnitude and co-morbidity. Although endoscopic haemostasis has significantly improved the outcome of patients with upper GI bleeding, in some cases patients continue to bleed or rebleed after initial control requiaring early elective surgery in order to decrease mortality. Despite recent advances in, both, endoscopic and surgical therapy, mortality rates have remained essentialy unchanged at 6-15%.

[The role of wireless capsule endoscopy in the evaluation of patients with suspected small bowel bleeding: a single center experience].

BACKGROUND: Capsule endoscopy (CE) is a new diagnostic tool for the study of patients with suspected small bowel pathology. The aim of the study was to clarify the usefulness of CE in the group of patients with obscure (overt / occult) gastrointestinal (GI) bleeding. PATIENTS AND METHODS: Thirty patients (14 men, 16 women, mean age 50 years, range 9 -79 years) were enrolled in the study. All of them undergone non-diagnostic esophagogastroduodenoscopy, colonoscopy and barium follow-through of the small bowel. All patients underwent capsule endoscopy. Fourteen patients had overt and sixteen occult bleeding. The single senior endoscopist interpreted CE findings in an unblinded manner. RESULTS: CE identified a source of bleeding in 14/30 patients (46.6%). Lesions identified were: tumors in five pts, vascular lesions, Crohnzs disease and Meckelzs diverticulum in two pts and fresh bleeding, segmental celiac disease and colonic diverticulosis in one patient each. CE identified a source of bleeding in 9/14 (64.3%) of patients with ongoing overt bleeding and in only 5/16 (31.3%) of patients with occult bleeding. The positive suspicious findings were seen in 6/30 (20%) of patients (2/14 with overt bleeding and 4/16 with occult bleeding. In 3/14 (21.4%) with overt and 7/16 (43.7%) with occult bleeding findings on CE were negative. All patients with negative findings on follow-up remained asymptomatic for one year. Capsule retention because of unsuspected stenosis occurred in a single patient and required surgery, which resolved the problem. CONCLUSION: CE is an effective diagnostic tool for patients with obscure GI bleeding. It is safe and painless technique which can diagnose the bleeding site beyond the reach of conventional endoscopy. The best candidates for the procedure are those with ongoing and overt bleeding.

[The influence of risk factors in recurrent peptic ulcer haemorrhage].

Gastrointestinal hemorrhage is one of the most frequent complications that occurs in 15 20% patients with peptic ulcer disease. Recurrent ulcer haemorrhage presents in the first 72 hours after initial bleeding: they are the most im portant cause of death. The aim of our study was to show the possibility of ulcer recurrent haemorrhage combined with risk factors: age 60, high risk lesion (active arterial bleeding, visible blood vessel, adherent coagulum), the size, ulcer base and localization (posterior duodenal wall. lesser curvature or high gastric ulcer), commorbidities ( cardiovascular and liver diseases) and haemodynamic instabilities. The combination of these risk-factor, unproportionally increases the risk: presence of two risk factors gives the possibility of recurrent bleeding of 16.67%, three risk factors 58.82%, four 93.33%, while the presence of five risk factors shows 100% posibility. Probability of death is 8.27 times greater if ulcer haemorrhage occurs.