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.

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.

[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.

Surgical treatment and clinical course of patients with hypopharyngeal carcinoma.

In the period between 1 January 1978 and 1 January 2004, 85 patients with hypopharyngeal squamocellular carcinoma were admitted at the Department of Esophagogastric Surgery in Belgrade. Among them, only 46 patients (54.1%) had radical surgical en-block resection and functional neck dissection, and they were included into an historical cohort study. In 40 patients a pharyngolaryngoesophagectomy was performed using for reconstruction, stomach tissue in 29 and colon tissue in 11 patients. Since 1996, in six patients with localized hypopharyngeal carcinoma pharyngolaryngectomy was performed with resection of cervical esophagus and free jejunal graft interposition. The overall incidence of morbidity was 50.0% and the overall mortality rate was 13.0% (6 patients). Mean hospital stay was 35 days (range, 18-78 days). The median survival of patients was 26 months, and overall 5-year survival rate was 26.5%. At present, surgery seems to be the appropriate therapeutic choice for patients with advanced hypopharyngeal carcinoma, providing a definitive palliation of dysphagia and relatively good long-term survival. At our Institution, after pharyngolaryngoesophagectomy, reconstructive method of choice is gastric 'pull-up', and the colon is used only when stomach tissue is not available, that is, previous gastric resections, inappropriate blood supply, synchronous gastric carcinoma and so on. Recently, pharyngolaryngectomy and free jejunal transfer has become the standard technique in patients with small carcinomas (up to 3 cm) confined to the hypopharynx in the absence of synchronous esophageal and/or gastric carcinoma.

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.

[Strategy in the treatment of hypopharyngeal and cervical esophageal carcinoma]. / Strategija u lecenju karcinoma hipofarinksa i cervikalnog jednjaka.

In the period between January 1st, 1978 and January 1st, 2003, 82 unselected patients with hypopharyngeal and cervical esophageal squamocellular carcinoma were treated at the Department of Esophagogastric Surgery, First University Surgical Hospital, Clinical Center of Serbia. In 43 (52.4%) patients operated with curative intent, radical surgical en-block resection and functional neck dissection has been performed. In 26 (60.5%) patient reconstruction was performed with stomach, in 11 (25.6%) left colon, and 6 (14%) free jejunal transfer. The overall 2-year and 5-year survival rate were 55.88% (19 patients) and 26.47% (9 patients), respectively. No patient undergoing nutritive gastrostomy and radiotherapy was alive after two years. At present surgery looks like the treatment of choice for hypopharyngeal and cervical esophageal carcinoma, providing a definitive palliation of dysphagia and better long-term survival. Free jejunal transfer has become the standard technique for reconstruction of the pharynx and hypopharynx especially with proximal lesions, whereas, gastric tube interposition is the technique of choice for reconstruction of the hypopharynx and cervical esophagus when the resection extends below the thoracic inlet or when there is a presence of synchronous carcinoma of theesophageal.

[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.

[History of surgery of stomach and cardial carcinoma]. / Istorijat hirurgije karcinoma zeluca i kardije.

Despite the marked decline in incidence during last 50 years, gastric cancer remains significant cause of mortality and morbidity worldwide. According to data in 1984. incidence in Yugoslavia was 35 per 100,000. In the United States, where incidence is not high, 24,000 new cases and 13,300 deaths had been estimated for the year 1992. Despite fact that modern diagnostic and surgical concept changed perspective for significant number of the patients with gastric carcinoma, most authors agree that Gastric cancer may be the most seriously mismanaged malignancy from a surgical perspective in the USA ... (Paul H. Sugarbaker, M.D, April 1999.) Analyzing medical literature, with special respect to domestic literature, authors analyzed historical data of gastric cancer surgery.

Modified stapling technique of esophagojejunal anastomosis.

The most dangerous complication of total gastrectomy, often causing postoperative death, is dehiscence of esophagojejunal anastomosis. After analyzing more then 300 patients undergoing surgery for gastric and/or cardiac carcinoma at our department in the period 1992-96, we concluded that the main cause of anastomotic dehiscence was a technically insufficient anastomosis, and the main risk factor was hypertrophied muscular layer of the esophagus (predominantly in advanced cardiac carcinoma). In this paper we discuss indications for, and the surgical technique of, our own modification of mechanical esophagojejunal anastomosis. In the period between 1 January 1997 and 1 March 2001, 148 procedures were performed using the modified anastomotic technique. In only two patients (1.35%) were radiological signs of small anastomotic leakage observed. The described modification of mechanical esophagojejunal anastomosis is safe and is not a time-consuming procedure. It is highly recommended in the treatment of the obstructive cardiac carcinoma with a compensatory hypertrophied muscular layer of the esophagus.

[Correction of failed primary surgical interventions in benign lesions of the esophagus]. / Korekcija neuspelih primarnih hirurskih intervencija kod benignih lezija jednjaka.

In an retrospective analysis of documentation and printed paper in period between 1964-1998 168 patients required reoperations in benign esophageal lesions. Failed initial interventions were found in 66 (39.28%) pts. operated in our clinic and 102 (60.71%) pts operated in other institutions in our country. The corrective procedure was possible in 140 (83.33%) pts and impossible in 11 (6.54%). Post-operative mortality was 7.73% so the definitive failed corrections were 14.27%. The main cause of failure were: Defective operative technique, wrong preoperative diagnosis and indications including inadequate initial procedure. Among the 168 pts undergoing corrective surgery, more than a half of pts had obstructive lesions requiring resections and reconstructions. Dilatation of the stricture was possible in 16% followed by total diversion, particularly in previous gastric surgery. Malignant degeneration of benign lesions were found in 10.71%. Only 4 pts (2.3%) refused suggested operations. Satisfactory long-term results especially in patients undergoing esophageal corrective reconstructions for benign diseases were good to excellent in regular yearly postoperative routine control examination.

[Surgical treatment of cardial carcinoma]. / Hirursko lecenje karcinoma kardije.

In the period from 1970 to 1996, in the Departmenf of Esophagogastric Surgery, Belgrade, Yugoslavia 562 have been operated with curative intent due to cardiac carcinoma. Since 1970 until 1985, in 182 patients a distal esophagectomy and proximal gastrectomy followed by eosphagogastro anastomosis had been performed. In the period between 1982 and 1996, a distal esophagectomy with total gastrectomy and radical or extended radical dissection and intrathoracic esophagojejuno anastomosis in 380 patients (192 hand sewn 3/0 interrupted sutures and 188 spapled anastomosis) had been performed. In our opinion for the majority of patients with advanced cardiac carcinoma distal esophagectomy and total gastrectomy, via the left thoracoabdominal approach, with D2 pancreas preserving splenectomy and dissection of lymph nodes in stations 16a1 and 16a2 is a surgical therapy of choice. Overall complications of such a procedure not differ in type and number from those after standard total gastrectomy and D2 dissection.

[Surgical strategy in the treatment of primary lymphoma of the stomach]. / Hirurska strategija u lecenju primarnog limfoma zeluca.

Primary gastric lymphoma has been traditionally accounted for only 1-7% of all malignancies of the stomach. During the period 1980-1996 in Department of Esophagogastric Surgery of University Surgical Hospital in Belgrade 41 patients have been operated due to primary gastric lymphoma. Radical surgery is the only therapeutic procedure in more then 45% of patients. It is also a safe procedure with specific complication rate less then 22%, and specific mortality rate less then 5%. In our experience, total gastrectomy with systematic lymphadenectomy is a therapy of choice in most patients with primary gastric lymphoma.