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.

[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.

[Iron deficiency anemia and its importance in gastroenterology clinical practise].

Iron deficiency anemia (IDA) is a universal problem involving individuals of all ages and both sexes and is a common cause of referral to medical departments. This anemia is one of the most common types of anemia. IDA impairs growth and intellectual development in children and adolescent. In women IDA is most common in reproductive period because of menstrual and pregnancy iron losses. IDA affects roughly 10-30% of all pregnancies and, among others morbidities, may contribute of developing postpartum depression. Among other adult patient, chronic occult gastrointestinal bleeding is the leading cause of IDA. Approximately, one third of patients with anemia have iron deficiency and up to two thirds of patients with IDA have serious gastrointestinal lesions detected with esophagogastroduodenoscopy and colonoscopy, including 10-15% with malignancy. However, in practice not all anemic patients undergo appropriate diagnostic tests to detect iron deficiency. Furthermore, a substantial proportion of patients with IDA do not undergo endoscopic evaluation. The approach to its investigation and subsequent therapy depends upon a comprehensive understanding of iron metabolism and heme synthesis. Once diagnosis of iron deficiency or IDA is established, evaluation for the cause of anemia must be appropriate performed and treatment must include corrective replenishment of body stores.

[Gastrointestinal stromal tumors (GIST) of the stomach as a cause of upper gastrointestinal bleeding].

Gastrointestinal stromal tumors (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. GIST is currently defined as a gastrointestinal tract mesenchymal tumor containing spindle cells (less commonly epitheloid cells or rarely both) and showing CD 117 (c-kit protein) positivity in more than 95% of cases. Although they may arise throughout the gut, the commonest site are stomach (60-70%), small intestine (20-30%), colorectum (5%) and esophagus (up to 5%). Rarely, GISTs develop in the retroperitoneum, omentum or mesentery. GIST originates from the intestinal cell of Cajal (ICC). ICCs are located in and around the myenteric plexus and are thought to function as intestinal pacemaker cells. Historicaly, GIST were often misclassified as leiomyomas or leiomyosarcomas. Subsequently, it has been determined that GISTs have distinct ultrastructural features and immunophenotypical markers compared with smooth muscle and smooth muscle tumors. GIST predominantly occur in middle aged and older patients, with no significant difference in the sex incidence. Data from the recent population study suggest an incidence of about 10-22 cases per million persons per year. Clinical presentation of GIST varies widely, and depends on tumor size and location. GISTs that caused symptoms tended to be larger with an average size of 6cm versus 2cm for asymptomatic GISTs. Symptoms are most commonly related to mass effect or bleeding. GISTs can grow very large before producing symptoms. Commonest symptom of gastric GIST is manifest or occult bleeding. Abudant, life-threateting bleeding that require urgent surgery is rare. For patient with primary, localized, nonmetastatic GIST, complete surgical resection represents the only chance for cure. Lymhadenectomy is not necessary, because lymph node metastasis is very rare. The 5 year survival rate in patients with resected primary GISTs ranges from 48-65%. Conventional chemotherapy and radiation therapy is ineffective in the treatment of GIST. Imatinib mesilate (a tyrosine kinase inhibitor) was confirmed to be effective against metastatic or unresectable GISTs.

[Less frequent causes of upper gastrointestinal bleeding].

Upper gastrointestinal (GI) bleeding represents emergency which despites modern advances in treatment still carry substantial mortality. Mortality remained relatively constant in the last 50 years at approximately 12%. Peptic ulcers remain the most common cause of upper GI bleeding and account approximately 50% of all cases. Next leading causes are esophageal and gastric varices, and gastroduodenal erosions. Mallory Weiss tears, angiodysplasia and gastric antral vascular ectasia (GAVE)-Watermelon stomach are less frequent but important causes of upper GI bleeding that contribute substantially to the overall morbidity and mortality. Recognition of such lesions is crucial to provide effective hemostasis. In most cases endoscopic therapy is procedure of choice which significantly improved the outcome of patients. In cases where endoscopic hemostasis is not effective, or patients rebleed after initial control surgical therapy may be required. This article will review recent advances in diagnosis and therapy of upper GI bleeding caused by Mallory Weiss tears, angiodysplasia or Watermelon stomach.

[Dieulafoy's lesion: rare cause of massive upper gastrointestinal bleeding].

Dieulafoy's lesion is an unusual and potentially life-threatening cause of massive, recurrent gastrointestinal bleeding. Its reported incidence as a source of upper gastrointestinal bleeding ranges from 0.3-6.7%. Dieulafoy's lesion is most commonly located in the proximal stomach (75% of cases). Lesion typically occur within 6 to 10 cm of the esophagogastric junction, generally along the lesser curvature of the stomach. Similar lesions have been identified in the esophagus, duodenal bulb, jejunum, ileum, colorectum, anal canal, even in bronchus. Detection and identification of the Dieulafoy's lesion as the source of bleeding can often be difficult, especially because most present with massive bleeding. Because of intermittent nature of bleeding, initial endoscopy is diagnostic in 60% of the cases, so repeated endoscopies are often necessary. If the lesion can be endoscopically documented, attempts should be made to achieve hemostasis using one or a combination of several endoscopic modalities. Success has been reported with multipolar electrocoagulation, heater probe, noncontact laser photocoagulation, injection sclerotherapy, endoscopic hemoclipping and band ligation. Surgery is reserved for lesions that cannot be controlled by endoscopic techniques. When localized, a wide wedge resection of entire area traversed by the large submucosal artery is recomended because rebleeding has been described after simple coagulation and ligation.

[Upper gastrointestinal bleeding as a surgical complication of primary gastric lymphoma].

Primary gastric lymphomas are of the extranodal non-Hodgkin type. The gastrointestinal tract is the most common site of extranodal non-Hodgkin lymphomas and accounts 30-45% of all extranodal lymphomas. Gastrointestinal lymphomas occurs in the stomach in 55-70% of cases. Primary gastric lymphoma is relatively rare tumor accounting 1-7%, of all gastric malignancies. An increased incidence has been documented recently. The median age of diagnosis is approximately 60 years old, and disease affects an equal number of men and women. The initial symptoms may be vague and nonspecific leading to delayed establishment of diagnosis up to several years. Many patients came down late with advanced disease and complications such as upper gastrointestinal bleeding. Twenty to thirty percent may present with occult bleeding or hematemesis et melena while gastric obstruction and perforation are less common. Gastric bleeding can also occur as a complication of chemotherapy. The incidence of gastric bleeding in patients receiving chemotherapy is up to 11%. In most cases surgical resection is necessary to achieve hemostasis. Given the rate of surgical complications, especially gastric bleeding, there is still an important role for surgeon in the multimodal treatment of patients with primary gastric lymphoma.

[Systemic hemostatic drugs].

Understanding the haemostatic changes is crucial in developing strategies for the management of haemorrhage syndroma. In recent years, the revised model of coagulation ("cell based" model) provided a much more authentic description of the coagulation process. Pharmacological intervention, especially desmopresin, antifibrinolytics (synthetics and nature) and increasingly recombinant activated factor VII are being used in prevention and therapeutically to control bleeding of variety etiologies. Skillfull surgery combined with blood saving methods and careful management of blood coagulation will all help in sucessfull haemorrhage prevention and treatment, and reduce unnecessary blood loss and transfusion requirements and its attendant risks. Among the all avalaible tests, the use of thromboelastography has allowed for more detailed dynamic assessment of the various steps of hemostasis.

Kinetics of ultrasonic extraction of extractive substances from garden (Salvia officinalis L.) and glutinous (Salvia glutinosa L.) sage.

The kinetics of ultrasonic extraction of extractive substances (ES) from dry herbs of garden (Salvia officinalis L.) and glutinous (Salvia glutinosa L.) sage using petroleum ether, 70% ethanol or water at 40 degrees C, as well as the composition of dry extracts, were studied. The mechanism of ultrasonic extraction is confirmed to occur in two steps: first, dissolution of the ES near the particle surface (washing) and, second, diffusion from the solid particles to the bulk of the liquid extract (slow extraction). The process is described mathematically using three concepts of the unsteady diffusion through plant material, the film theory and the empirical equation of Ponomaryov. The yield of ES increases with increasing solvent polarity, and nearly the maximum concentration of ES in liquid extracts is achieved for about 20 min. The composition of extracts depends on both the extraction conditions applied and the plant material.

The significance of lymphonodal micrometastasis in the patients with gastric adenocarcinoma.

Micrometastasis is defined as microscopical deposit of malignant cells, less than 2mm in diameter, separated from the primary tumor. This does not include discontinous growth in peritumoral region, but include microinolvement of regional lymph nodes. The literature on micrometastases, with special resperct to nodal micrometastasis, and their implications in gastric adenocarcinoma have been reviewed. Immunohistochemical detection offer the best accuracy for detection of nodal micrometastasis. Molecular techniques are more sensitive than method of immunohistochemical detection, but methods are compromised with false positive results caused by various sources of biological contamination. It is more than obvious that there is no definite agreement neither about risk factors, nor definitive clinical significance of micrometastatic node involvement in the patients with gastric adenocarcinoma. At present, the role of occult lymph node involvement proved its significance in two major fields: defining criteria for limited surgical dissection in the patients with early (sm) carcinoma in respect to detection of micrometastatic tissue in sentinel lymph node, and distinguishing the category of pN0 (Mi+) patients with potential benefit of postoperative adjuvant therapy.

[Iatrogenic perforations of the esophagus and hypopharynx--5 year experience at the Center for Esophageal Surgery]. / Jatrogene perforacije jednjaka i hipofarinksa--petogodisnje iskustvo Centra za hirurgiju jednjaka.

Iatrogenic perforations of the esophagus and hypopharynx are important problem, due to diagnostic difficulties, controversies about adequate treatment, and high morbidity and mortality rate. Incidence of iatrogenic perforations is from 50 to 75% of all perforations. In the period from April 1999. to April 2004, 15 patients with iatrogenic perforation of the esophagus and hypopharynx were treated at the Department of esophageal surgery, First University Surgical Hospital in Belgrade. In majority of patients iatrogenic perforation occured during endoscopic interventional procedure (endoscopic removal of ingested foreign body--10 pts, endotracheal intubation--2 pts, intraoperative iatrogenic perforation--2 pts, pneumatic dilatation--1 pt). Surgical treatment was performed in 12 (80%) pts and 3 (20%) pts were treated conservatively. Surgical approach was cervicoabdominal, thoracoabdominal and cervicothoracoabdominal in 9.1 and 2 pts, respectively. Among 12 operated pts, primary repair of the esophagus was performed in 5 pts, and esophageal resection or exclusion in 7 pts. Overall mortality rate was 13.3% (2 pts), in surgical group 8.3% (1 pt) and in conservatively treated group 33.3% (1 pt). Iatrogenic perforations of the esophagus and hypopharynx are diagnostic and therapeutic problem. Awareness of the possibility of esophageal perforation during instrumental manipulations and early diagnosis is essential for successful, individually adapted, and in most cases surgical, treatment.

[The effect of parathormone on arterial blood pressure in patients on hemodialysis]. / Uticaj parathormona na arterijski pritisak krvi kod bolesnika na hemodijalizi.

We evaluated the effect of PTH on blood pressure in haemodialysed patients. The correlation was found between systolic, diastolic pressure and PTH. The results have shown that PTH might have the influence on regulation of arterial blood pressure in these patients.

[Voice frequencies in patients treated with chronic hemodialysis]. / Osnovna frekvencija glasa bolesnika lecenih ponavljanim hemodializama.

Stress effects on respiration and muscle tension are most likely to affect phonation and articulation; the acoustic parameters reflecting vocal indicators of stress are fundamental frequency, duration and intensity. The aim of this study was to explore the link between some psychosomatic states of patients on dialysis and physical parameters of the vowel "e". Fundamental frequency, intensity and duration of the vowel "e" produced before, during and after dialysis were investigated. The results showed that in the period before dialysis the fundamental frequency was greater, duration was longer and intensity was unchanged. This investigation showed that the changes of the parameters of voice were induced with the changes of psychophysiological states of the patients on dialysis. These patients were in the state of chronicle stress, but the period before the treatment was associated with special, anticipatory stress that induced greater fundamental frequency and longer duration of the pronunciation of the vowel "e".