Current endoscopic methods of radical therapy in early esophageal cancer.

During the last three decades, there has been an increasing incidence of the esophageal cancer at the global level, approx. 400,000 new esophageal cancers being currently diagnosed annually. This is the eighth leading cause of cancer incidence and the sixth leading cause of cancer death overall. If we refer to the countries of Western Europe and North America, we could see an increase in the esophageal adenocarcinoma in detriment of squamous cancer. As for the Asian region, referring in particular to China and Japan, 9 out of 10 esophageal cancers are squamous cell carcinomas. Considering that the incidence of gastric cancer in Japan is very high, the endoscopic screenings performed inevitably led to an increased rate of early detection of esophageal cancer, reaching approximately 20% of all esophageal cancers detected. This has led to the possibility of developing therapeutic endoscopic techniques with radical visa that we will describe while presenting comparative data from literature. Currently, however, there are not enough data on the effectiveness of these types of therapies, compared to surgery, in order to be transformed into standard therapeutic endoscopic treatment for early esophageal cancer. However, the combined therapy, resection/ endoscopic ablation + chemoradiotherapy, appears as an alternative to be taken into account. Abbreviations EEC = esophageal early cancer, BE = Barrett's esophagus, HGD = High-grade dysphagia, EUS = Ultra sound endoscopy, CT = Computer tomograph, UGE = Upper gastro endoscopy, PET-CT = Positron Emission Tomography, FNAB = Fine needle aspiration biopsy, EMR = Esophageal mucosal resection, ESD = Esophageal submucosal dissection, SCC = Squamous cellular cancer, PCT = Poli-chemotherapy, RT- Radio-therapy.

Endoscopic palliation of advanced esophageal cancer.

Esophageal cancer represents one of the most aggressive digestive tumors, with a survival rate at 5 years of only 10%. Globally, during the last three decades, there has been an increasing incidence of the esophageal cancer, approx. 400,000 new esophageal cancers being currently diagnosed annually. This represents the eighth leading cause of cancer incidence and the sixth leading cause of cancer death overall. Taking into account the population's global aging and thus, the increase in the number of patients who will not bear surgery, PCT and radiation, or the fact that they do not want it especially because of deficiencies and associated pathology, the endoscopic ablative techniques with palliation purposes represent the alternative. If we refer to the Western Europe countries and North America, we notice an increase of esophageal adenocarcinoma rate versus squamous cancer. As for the Asian region, referring in particular to China and Japan, 9 out of 10 esophageal cancers are squamous cell carcinomas. For at least half of the patients with EC (esophageal cancer) there is no hope of healing because of the advanced regional malignant invasion (T3-4, N+, M+) with no chemo and radiotherapy response, poor preoperative patients' conditions or systemic metastasis. The low life expectancy does not justify the risky medical procedures, the goal of the therapy consisting in the improvement of the quality of life by eliminating dysphagia (reestablishing oral feeding) which represents the most common complication of EC, the respiratory tract complication caused by eso-tracheal fistulas or by eliminating chest pain. To treat dysphagia, which is the main target of palliation, combined methods like endoscopic, chemo and radio-therapy, can be used, each one with indications, benefits and risks.

Prognostic significance of KRAS gene mutations in colorectal cancer--preliminary study.

OBJECTIVE: The prognostic significance of KRAS gene mutations, evaluated by using two methods in patients with colorectal cancer (CRC). MATERIAL AND METHODS: Retrospective study involving 58 patients diagnosed with CRC and treated between 2003 and 2010 in the General and Esophageal Surgery Clinic of "Sf. Maria" Hospital, Bucharest. The macroscopic and microscopic examination of the resected specimens was also processed for genetic analysis in NIRDPBS, where KRAS status was determined by using two methods: PCR-RFLP and pyrosequencing. RESULTS: The clinical and biological parameters of the patients were assessed for 72 months in average. A relapse in 21 patients and a 5-year survival rate of 79.3% was discovered. The genetic analyses of KRAS gene found mutations in 22 cases (45.3%): 17 cases had mutations in codon 12, 5 cases in codon 13. The survival rate analyses of patients with wild KRAS gene compared with the patients carrying the mutation on codon 12 /13 revealed a superposition of the survival curve. The statistical analysis based on the TNM stage revealed different survival curves in stage I and II, shorter survival period in patients with KRAS mutation on codon 13 than in those with wild type gene (stage I--p_value=0.015; stage II--p_value=0.000). CONCLUSIONS: It was not found that KRAS gene status had any prognostic significance. Nevertheless, for stage I and II patients, the mutation found on codon 13 determined a statistic significant shorter survival rate than for those with wild type. The results obtained by using the pyrosequencing method for the determination of KRAS gene status proved that it represented a reliable and reproducible method.

Barrett esophagus: history, definition and etiopathogeny.

The injury of the esophageal epithelium may be determined by the reflux of the gastric acid in the esophagus. Barrett's esophagus (BE) is characterized by the replacement of the normal squamous epithelium with the columnar epithelium, when the healing of the lesion occurs. According to some studies, the incidence of the esophageal adenocarcinoma in patients with BE is of about 0,5% per year. The term Barrett's esophagus is subjected to interpretation nowadays, so it lacks the clarity needed for the clinical and scientific communication on the subject of columnar metaplasia of the esophageal mucosa. The major pathogenetic factor in the development of BE is represented by the reflux disease. The cellular origin of BE is controversial and it represents an issue that needs to be resolved because it will have implications in the putative molecular mechanisms underlying the metaplastic process. The epigenetic or genetic changes, which alter protein expression, function, and/ or activity, in post-mitotic cells to drive transdifferentiation or in stem/ progenitor cells such that they are reprogrammed to differentiate into columnar rather than squamous cells, are driven by the inflammatory environment created by chronic reflux. In order to be able to develop better therapeutic strategies for the patients with this disease, an increasing interest in understanding the pathogenesis of BE at the cellular and molecular level presents these days.

Surveillance in Barrett esophagus.

The only known precursor of the esophageal adenocarcinoma (EAC) is represented by the Barrett's esophagus (BE). EAC incidence has increased sharply in the last 4 decades. The annual conversion rate of BE to cancer is small but significant; therefore the identification of patients at a higher risk of cancer represents a dilemma. The endoscopic surveillance of BE aims to detect dysplasia and in particular high-grade dysplasia and intramucosal cancers that can be endoscopically treated before progressing to invasive cancer with lymph node metastases. Using standard white light endoscopy (WLE), these high-risk lesions are often subtle and hard to detect. In addition to high-definition standard endoscopy, chromoendoscopy (CE), virtual chromoendoscopy (e.g. narrow band imaging), and confocal laser endomicroscopy might increase the diagnostic efficiency for the detection of dysplastic lesions and can also increase the diagnostic efficiency for the detection of BE dysplasia or cancer. This ability to detect subtle mucosal abnormalities that harbor high-grade dysplasia (HGD) or intramucosal carcinoma might enable endoscopists skilled in the assessment of BE to perform targeted rather than random biopsies. The standard protocol will remain the careful examination by using conventional high-resolution endoscopes, combined with a longer inspection time, which is associated with an increased detection of dysplasia until these modalities have been demonstrated to enhance efficiency or be cost effective. Many of the limitations of the current clinical standard may be overcome in the future by the use of multi-modal imaging combined with molecular information.

Paraneoplastic syndrome in primitive retroperitoneal tumours.

INTRODUCTION: Retroperitoneal tumours represent a particular oncological pathology. No other human pathology is so deceiving and scarce in specific clinical symptoms as these tumours. Usually borrowing the symptoms of nearby organs they are discovered in advanced or incurable stages. MATERIAL AND METHOD: We have tried to present to you the challenge of diagnosing some retroperitoneal tumours. One of the rarest signs was by far the paraneoplastic syndrome or the secretion of active biological substances. The study group is composed of histopatologically diagnosed patients. The vast majority were selected from urology and general surgery wards, but there were cases from gynaecology, neurosurgery and even from endocrinology and gastroenterology. RESULTS: Paraneroplastic syndrome represents the secretion of various substances by the tumour, substances that make changes at bioumoral level. In our study we found 3 cases of 32 patients (9,37%) with paraneoplastic syndrome. What is to be noticed is that because of this syndrome the diagnosis was more difficult and was indirectly referred to a retroperitoneal tumour. We would like to present these cases and their particularities. CONCLUSIONS: Every case was a surgical and diagnostic challenge. Biologic active substance secretion or the paraneoplastic syndrome makes the clinical picture even more complicated for primitive retroperitoneal tumours. The clinical symptoms of these tumours require a more careful approach of these patients. Close co-operation with other medical specialties in cases such as ours is mandatory.

Principles of surgical treatment of Zenker diverticulum.

BACKGROUND: Pharyngo-esophageal diverticula are most frequently described in elderly patients, having symptoms such as dysphagia, regurgitation, chronic cough, aspiration and weight loss. The etiology remains controversial, although most of the theories are linked to structural or functional abnormalities of the crico-pharyngeal muscle. With the therapeutic attitude varying from conservative to surgical (with associated morbidity and mortality), the importance of knowing the etiopathology and clinical implications of the disease for establishing the management of the case is mandatory. The aim of the study is the reevaluation of the methods and therapeutic principles in pharyngo-esophageal diverticular disease, starting from the etio pathogeny. MATERIALS AND METHODS: Our study group is made up of 11 patients with surgical indication for Zenker diverticulum, operated between 2001 and 2011. RESULTS: During that period, more patients were diagnosed with this pathology, but the surgical indication was carefully established, in conformity with the actual practice guides, which involve the evaluation of the clinical manifestations determined by the diverticulum, as well as the identification and interception of the pathological mechanisms by the therapeutic gesture. CONCLUSION: Although it has a "benign" pathology, the esophageal diverticulum requires complex surgical procedure that implies significant morbidity.

[Surgical treatment of esophageal diverticula]. / Tratamentul chirurgical al diverticulilor esofagieni.

The aim of this paper is to evaluate the methods and therapeutic principles of esophageal diverticula pathology. We analyze the main pathological mechanisms which establish the therapeutic attitude linked with a complex pretherapeutic evaluation. In our study we enrolled 12 patients operated between 2001-2009 for esophageal diverticula with different topography. In this period of time there were much more patients diagnosed with this pathology, but the need for surgery was establish very tight regarding the actual practical guide which impose the identification and interception of physiological mechanisms by the surgical procedure. We highlight the particular technical details, as well as the important differences of postoperatory complications according to the topography of the diverticula pouch.

[The importance of the timing of surgery in infected severe acute pancreatitis]. / Importanta momentului operator în pancreatita acuta severa infectata.

The management in severe acute pancreatitis evolved in the last two decades. Consulting the literature and the accumulated clinical experience manage to the release of this study based on the comparison of the treatment in PAS between two distinct periods: 1994-1999 (retrospective) and 2000-2007 (prospective). Among the 285 patients whit PAS admitted and treated in the two departments, 224 (78.6%) was submitted to the surgical intervention with various surgical indications. There is an obvious difference between the retrospective and prospective studies concerning the indication of surgery and mostly the timing for surgery. The lots were analyzed concerning the etiology, management of treatments and specific treatments, and the timing of the surgical intervention was analyzed based on the specific etiologic treatment and the period of time between the admission and the first surgical intervention, the mark being the 21 day according with the recommendations of the International Association of Pancreatology. There were analyzed: the period of time between the onset of the disease and the surgical intervention, the status of the patients at the surgical moment, the global mortality based on the timing of surgery, the evolution of the management of PAS along the period of the research, comparisons whit the literature. The registered data were statistically processed using the SPSS test version 17 for Windows.

[Cholangiocarcinoma of the distal bile duct--case presentation]. / Adenocarcinom de coledoc distal--prezentare de caz.

Cholangiocarcinoma is a rare disease (0.15-0.16% in the general population). We present the case of a man, 64 years old, who was admitted to our clinic for emergency with intense jaundice, abdominal pain in the supra-umbilical region. Laboratory analysis revealed elevated total bilirubin (23.5 mg/dl), with predominant direct bilirubin and an increased serum level of alkaline phosphatase and GGT, AST, ALT. The abdominal CT shows an tumor infiltrating distal bile duct, with important dilatation of proximal biliary tree and enlarged retro pancreatic lymph node (8 mm). The first therapeutic procedure was an surgical exploration of the abdomen to asses the resectability of the tumor and an internal biliary drainage colecisto-gastrostomy to allow improving of patient's biological and clinical state and a latter radical operation, after remission of jaundice. After a month we performed cephalic duodenopancreatectomy. Pathology result: moderately differentiated adenocarcinoma of intestinal type (G2) pT2NOMO (stage II). The postoperative evolution was favorable encumbered by a small pancreatic fistula healed by conservative method.

[Principles of treatment in locally advanced esophageal squamous cancer]. / Principii de tratament in cancerul esofagian scuamos avansat local.

The diagnosis established in the symptomatic phase of this disease, most often occurs at advanced stage neoplasia. The purpose of this article is to establish the place and method of surgical and radio-chemo therapy in advanced loco-regional squamous esophageal neoplasm (stage IIB-III). Surgical treatment establishes the best results over long periods of time, however, this is done keeping in mind acceptable morbidity and mortality conditions. Multimodal treatment is encompassed in general efforts to achieve optimal results along with increasing the quantity and quality of life. Neoadjuvant radiochemotherapy (CRT) increases practitioners' possibility of resecting tumors, decreasing their size, and establishing proper means of local (radiotherapy) and systemic (chemotherapy) control. Great efforts are made in finding markers which lead to correct diagnosis and treatment options that will further permit nonresponsive radio and chemo therapy treated patients from experiencing unwanted toxicity. The role of adjuvant therapy is that of decreasing recurrence in patients with residual mediastinal disease after palliative surgical resection. Palliative treatment consists of improving dysphagia, and the quality of life using surgical, endoscopic, photodynamic, laser, radio and chemotherapy as alternatives.

[Difficulties in diagnosis and surgical treatment of a giant retroperitoneal lipoma]. / Probleme de diagnostic si de tactica chirurgicaa ridicate de un lipom retroperitoneal gigant.

Primary retroperitoneal tumors are relatively rare and the histological characters vary. We present the case of a retroperitoneal lipoma in a 51-year-old male patient, whose main complain was enlarging of the abdomen in the last 2 months. The CT of the abdomen and pelvis revealed a giant retroperitoneal tumor. The patient suffered a surgical intervention that revealed a giant retroperitoneal tumor, 40/35 cm, weighting 14 Kg. The pathology exam established the diagnosis: retroperitoneal lipoma with areas of necrosis and lipogranulomatosis. The postoperative evolution was simple.

[The role of esophageal manometry in the management of the patients with gastro-esophageal reflux disease and Barrett's esophagus]. / Rolul manometriei in managementul pacientilor cu boala de reflux gastro-esofagian si esofag Barrett.

AIM: To analyze the correlation between the failure of medical treatment in patients with reflux esophagitis or Barrett esophagus and LES function, manometrically measured. METHODOLOGY: This is a prospective study of 24 patients admitted in our clinic for reflux disease symptoms, who were investigated by endoscopy (combined with biopsy), esophageal manometry and 24 h pH monitoring. The including criteria for the patients was abnormal esophageal exposure to acid reflux, each patient having abnormal 24 h pH monitoring (pH < 4 in the esophagus more then 4.4% in 24 h). Each patient received medical treatment with clinic and endoscopic reevaluation after 3 months. RESULTS: From the 24 patients that were included: 4 patients having Barrett esophagus, 13 patients with esophagitis (3 patients associated complications such as ulcer or esophageal stenosis) and 7 patients without visible lesions on endoscopy. From the 24 patients, 11 patients presented an incompetent LES, characterized by the following values obtained by manometry: total length < or = 2 cm, abdominal length < or = 1 cm, mean pressure: < 6 mmHg. There were 2 patients from the 4 having Barrett esophagus that presented an incompetent LES, and also the 3 patients having esophagitis associated with complications. All patients were reevaluated clinically and endoscopically after 3 months of medical treatment with PPI 40 mg/day. From the 11 patients with incompetent LES, 5 patients had symptoms or modifications on endoscopy, whereas from 13 patients with a competent LES only one patient presented with symptoms of reflux disease. CONCLUSION: The presence of an incompetent LES may be a cause of a poor response to medical treatment and may also be an element for taking into consideration surgical treatment.

[Features of Krukenberg-type tumors--clinical study and review]. / Particularitati ale tumorilor de tip Krukenberg--studiu clinic si review.

Krukenberg-type tumors (KT) are rare among ovarian metastases, but responsible for the most frequent diagnostic confusions with ovarian cancer. They are peculiar: uncertain pathogenesis, challenging etiological diagnosis, poorer prognosis for the primary. We studied 9 cases, with a mean age of 52 years, operated since 2001; no case was discovered as a result of prophylactic oophorectomy. Timing of TK diagnosis: 3--metachronous, 4--synchronous, as incidental discovery and 2--retrospective pathological diagnosis. Site of primary: 3--gastric, 5--colonic or appendiceal, 1--breast. Imaging appearance was useful only if interpreted in clinical conditions. Morphology: 7/9 bilateral, solid or mixed gross appearance, oval, mean diameters 9.4/7.8 cm. Microscopy: in 8 KT of digestive origin, 3--signet-ring cell carcinoma, 3--mucinous adenocarcinoma, 2--mixed pattern; 1 KT or breast origin was diagnosed by immunohistochemistry; 6/9 presented microscopic peritoneal despite a lack of strong correlation with the appearance of carcinomatosis or cytology of ascites. Survival: 3--no evidence, 5--disease-free after 4-13 months, 1--survived 2 years after debulking (4 years after colectomy). Clinical, evolutive and prognostic features of KT are determined by the biologically behavior of the primary (rapid lymphatic and hematogenous spread to the ovary), so the benefit of surgery is limited. Bilateral ovarian tumors, particularly in premenopausal women, must raise a high index of suspicion for KT, before or during surgery; diagnosis is a team challenge.

[Treatment of the esophago-gastric junction adenocarcinoma]. / Tratamentul adenocarcinomului de jonctiune esogastrica.

The aim of the work paper is to present the treatment methods of the esophago-gastric junction adenocarcinoma, (AC) based on our experience and literature data. The later reveal many novelties about AC prophylaxis through Barrett's esophagus (BE) treatment, using proton pomp inhibitors or antireflux surgical procedures, the progress of the endoluminal ablative methods for intestinal metaplasia, as well as a new surgical approach for advances tumors based on Siewert classification. Surgical procedure selection at patients with resectable tumours should be based on the tendency of esophago-gastric junction adenocarcinomas to extend on longitudinal axis, at the submucosa level and the possibility of abdomino-mediastinal lymph nodes metastasis. In located disease, tumoral resection R0 with abdominal and mediastinal lymph nodes dissection represents the optimal therapy, because it confers the best chance of cure. Preoperative radio-chemotherapy appears to increase the chance for a curative resection at the patients with advanced tumors. The main therapeutical purpose in non-responding patients is the palliation of dysphagia and malnutrition.

Pseudo-achalasic behaviour of a middle thoracic esophageal squamous cell carcinoma.

Pseudo-achalasia is a rare pathologic entity that mimics idiopathic achalasia, usually secondary to malignant infiltration of the cardia. Its significance is related to the fact that it may be difficult to distinguish from primary achalasia; the outcome and therapeutic course are different. In fact, a large variety of processes may be responsible for the development of a secondary achalasia syndrome; we present a case with pseudo-achalasia due to a middle thoracic esophageal squamous cell carcinoma.

[Long-term survival after eso-gastrectomy for esophagogastric junction adenocarcinoma--prospective study]. / Supravietuirea la distanta dupa esogastrectomie pentru adenocarcinom de jonctiune esogastrica--studiu prospectiv.

Detection of the esophagogastric junction adenocarcinoma in symptomatic stage determine a low survival. The aim of the study was to identify the prognostic factors after eso-gastrectomy for esophagogastric junction adenocarcinoma. There was done a prospective study of a 43 patients with esophago-gastric resections and abdomino-mediastinal lymph nodes dissection between 2001 and 2006 at the General and Esophageal Surgery "St. Mary" Clinical Hospital: 25 patients with transhiatal total gastrectomy, 6 patients with total gastrectomy and distal esophagectomy by separated incisions, abdominal and thoracic, 3 patients with total gastrectomy and subtotal esophagectomy by abdomino-cervical approach, 9 patients with subtotal esophagectomy by abdomino-cervical approach with cu small gastric curvature resection, radical resections in 22 patients. The patients were followed by clinic, endoscopic, TC exam and tumoral markers. There were done complex statistic analysis using SPSS 16.0. The mean interval of the surveillance was 24 months (6 - 60 months). 1 year survival was 77,74%. Long-term survival was influenced by age (p_value = 0.0129), tumoral grading (p_value = 0.0297), the number of lymph nodes metastasis (p_value = 0.0029) and pT stage (p_value = 0.0139), and was not dependent on Siewert type, ASA class, surgical approach, resection type, the number of the dissected lymph nodes, abdominal or mediastinal. In locally advanced esophagogastric junction adenocarcinoma, the frequency of lymph nodes metastasis (81%) especially in patients with tumoral type III and unfavorable results of surgical treatment as unique therapeutically method show the necessity of a multimodal approach pre and post-operatory by using selection methods with a good prediction of neoadjuvant treatment.

Subphrenic abscess through esophageal leakage after laparoscopic initiated nissen fundoplication--case presentation.

A 56-year-old man with a large paraesophageal hiatus hernia, treated in a tforeign clinic with a Nissen fimdoplication (when a lesion of the gastric fornix during laparoscopic dissection has determined conversion to open technique) is admitted 3 weeks after surgery, being diagnosed with an esophageal leekage witch maintains a large subphrenic abscess with sepsis. The patient was cured by draining the leakage, excluding the esophagus by an "à minima" alimentary jejunostomy, under broad spectrum antibiotherapy.

[Clinical diagnosis of adenocarcinoma of the esophago-gastric junction]. / Diagnosticul clinico-paraclinic al adenocarcinomului de jonctiune eso-gastrica.

The aim of the work paper is to present the diagnosis methods of the esophago-gastric junction adenocarcinoma, based on our experience and literature data. The later reveal many novelties about diagnosis means in Barrett's esophagus (BE), the definition and classification of BE, as well as the progress of the endoscopical, immunohistochemical and molecular methods in surveillance of the dysplasia arising in BE and in detection of intraepithelial neoplasia. Early esophago-gastric junction (EGJ) adenocarcinoma (AC) is asymptomatic and its detection may be possible only through endoscopical surveillance. Although endoscopical surveillance is widely practiced, early AC represents only 20% from AC arising in BE. For this reason is necessary to use some more precise methods for identifying intestinal metaplasia on distal esophagus, in patients with gastro-esophageal reflux disease, as well as for risk stratification in patients with dysplasia and for detection of intraepithelial neoplasia. Applying modern methods of immunohistochemical and molecular diagnosis on endoscopical biopsy or esophageal brushing samples, the diagnosis rate for BE, dysplasia and early AC is improved and using the imaging means permits to obtain preoperative TNM staging and tumoral type (Siewert), with implications in therapeutical management.