ADENOID CYSTIC CARCINOMA OF DISTAL TRACHEA: A CASE REPORT.

Primary malignant tumors of the trachea are very rare with the incidence of less than two per million people per year, and only ten percent of them are adenoid cystic carcinomas. Eighty percent of all tracheal tumors are malignant. Diagnosis is usually late because the symptoms mimic other conditions such as asthma. Clinical picture may sometimes be dramatic when airway is almost closed and emergency recanalization is necessary. Diagnosis is made by chest computed tomography scan or magnetic resonance imaging. Definitive treatment is surgical resection alone or followed by radiation therapy or radiation therapy alone. Radical resection is only accomplished in about half of all cases because of the submucosal tumor growth and limited length of tracheal resection. The role of adjuvant radiation therapy in negative resection margin cases is not clear but all patients with positive resection margin benefit from radiation therapy. We present a case of a 43-year-old patient with primary adenoid cystic carcinoma of distal trachea treated by emergency bronchoscopic recanalization and resection of the tracheal tumor with end-to-end anastomosis.

Postoperative Atrial Fibrillation Prophylaxis and Lung Resection ­ Our Experience with 608 Consecutive Patients

Postoperative atrial fibrillation is a common complication after lung resection. It is burdened by increased mortality and morbidity, prolonged hospitalization, and higher resource utilization in thoracic surgery patients. Therefore, some kind of pharmacological prophylaxis is recommended. In our patients, diltiazem, a calcium antagonist, is administered. We collected data on all 608 patients having undergone lung resection (no less than lobectomy) between November 2012 and May 2015. This period included patients having received diltiazem during their postoperative stay in our Intensive Care Unit and surgical ward, and those that did not receive it. Patients having had atrial fibrillation before the surgery and patients with cardiac pacemaker were excluded from the trial. Other patients were divided into three groups: patients with some kind of antiarrhythmic therapy before and continued after the surgery; patients with diltiazem prophylaxis; and patients without any antiarrhythmic prophylaxis. The data collected were statistically analyzed. We found no statistically significant difference in the incidence of postoperative atrial fibrillation among the groups (p<0.05).

[CLINICAL RECOMMENDATIONS FOR DIAGNOSIS, TREATMENT AND MONITORING OF PATIENTS WITH ESOPHAGEAL AND ESOPHAGOGASTRIC JUNCTION CANCERS].

Esophageal and esophagogastric junction cancers comprise histologically and biologically different malignant tumors in which the progress in the understanding of the disease has not been followed by the improvement in the survival. Diagnosis is set by tumor biopsy during endoscopy. Multimodal approaches containing surgery, radiotherapy and chemotherapy are frequently applied in the treatment of locoregionally advanced disease. However, the optimal sequence of the treatment options is still the issue of numerous clinical trials and meta-analyzes. Metastatic disease is treated with palliative chemotherapy and best supportive care. Treatment decisions should be individualized according to patients' characteristics and made after multidisciplinary team discussion. The following text presents the clinical guidelines in order to standardize the diagnostic procedures, treatment and monitoring of patients with esophageal and esophagogastric junction cancers in the Republic of Croatia.

Intraoperative volume restriction in esophageal cancer surgery: an exploratory randomized clinical trial.

AIM: To investigate whether the fluid volume administered during esophageal cancer surgery affects pulmonary gas exchange and tissue perfusion. METHODS: An exploratory single-center randomized clinical trial was performed. Patients with esophageal cancer who underwent Lewis-Tanner procedure between June 2011 and August 2012 at the Department of Thoracic surgery "Jordanovac", Zagreb were analyzed. Patients were randomized (1:1) to receive a restrictive volume of intraoperative fluid (≤8 mL/kg/h) or a liberal volume (>8 mL/kg/h). Changes in oxygen partial pressure (Pao2), inspired oxygen fraction (FiO2), creatinine, and lactate were measured during and after surgery. RESULTS: Overall 16 patients were randomized and they all were analyzed (restrictive group n=8, liberal group n=8). The baseline value Pao2/FiO2 ratio (restrictive) was 345.01±35.31 and the value six hours after extubation was 315.51±32.91; the baseline Pao2/FiO2 ratio (liberal) was 330.11±34.71 and the value six hours after extubation was 307.11±30.31. The baseline creatinine value (restrictive) was 91.91±12.67 and the value six hours after extubation was 100.88±18.33; the baseline creatinine value (liberal) was 90.88±14.99 and the value six hours after extubation was 93.51±16.37. The baseline lactate value (restrictive) was 3.93±1.33 and the value six hours after extubation was 2.69±0.91. The baseline lactate value (liberal) was 3.26±1.25 and the value six hours after extubation was 2.40±1.08. The two groups showed no significant differences in Pao2/FiO2 ratio (P=0.410), creatinine (P=0.410), or lactate (P=0.574). CONCLUSIONS: Restriction of intraoperative applied volume does not significantly affect pulmonary exchange function or tissue perfusion in patients undergoing surgical treatment for esophageal cancer.

[Clinical recommendations for diagnosis, treatment and monitoring of patients with cancer of unknown primary site]. / Klinicke preporuke za dijagnozu, lijecenje i pracenje bolesnika oboljelih od raka nepoznata primarnog podrijetla.

Cancer of unknown primary (CUP) site comprises very heterogeneous group of various malignant tumors presented in metastatic phase of the disease. Diagnosis is set when primary site remains unidentified after a thorough diagnostic evaluation in patients with histologically proven malignant metastatic disease. Despite poor prognosis in most patients, favorable prognostic clinical entities have been recognized constituting the most important group of patients for oncological treatment. The following text presents the clinical guidelines in order to standardize the diagnosis, treatment and follow-up of patients with cancer of unknown primary site in the Republic of Croatia.

Gastric tube ulcer perforating the pericardium after subtotal esophagectomy.

Subtotal esophagectomy with retrosternal transposition of the gastric tube to the neck was performed in a 62-year-old patient with squamous cell carcinoma of the proximal third of the esophagus. He developed a salivatory fistula in the early postoperative period that healed spontaneously. Five months later, the patient developed partial stenosis of the esophagogastric anastomosis which required recervicotomy and excision, after numerous failed dilatation attempts. Eighteen months later, the patient presented to the hospital for severe pain in the upper abdomen. Clinical work-up revealed pericardial perforation by the gastric tube ulcer necessitating emergent surgery and gastric tube removal. We present a patient who developed both early and late complications of subtotal esophagectomy with gastric tube transposition as well as a review of the literature.

Intraluminal brachytherapy in the management of squamous carcinoma of the esophagus.

Intraluminal high dose rate brachytherapy (ILHDR BT) is one of several effective modalities for palliation of advanced esophageal cancer. Thirty patients with endoscopic-proven, mostly locally advanced, squamous cell carcinoma of the esophagus, not involving the gastroesophageal junction and without distant metastases, were included in this analysis. Twenty-nine patients received two ILHDR BT sessions of 8 Gy within a week and one patient received only one session. All patients were followed monthly. Outcomes included quality of life (QOL), symptoms control: dysphagia, regurgitation, odynophagia, and chest or back pain, as well as, overall survival. Through 4 months of follow-up, QOL was statistically improved (having lowered scores) in regards to feelings (P= 0.013), sleeping (P= 0.032), eating (P= 0.020), and social life (P= 0.002). The most significantly improved symptom was dysphagia (P < 0.006), with a reduction of 0.52 units or one-half grade. Regurgitation, odynophagia, and pain were lower during follow-up but were not statistically significant. The median overall survival from death of any cause was 165 days (with a 95% confidence interval of 128-195 days). In conclusion, ILHDR BT of advanced squamous esophageal cancer consisting of two out-patient procedures is very successful in achieving the primary objectives of the patients to reduce dysphagia and improve QOL.

Promoter methylation status of ASC/TMS1/PYCARD is associated with decreased overall survival and TNM status in patients with early stage non-small cell lung cancer (NSCLC).

BACKGROUND: Lung cancer is the leading cause of cancer-related death worldwide, with 5-year overall survival less than 15%. Therefore, it is essential to find biomarkers for early detection and prognosis. Aberrant DNA methylation is a common feature of human cancers and its utility is already recognized in cancer management. The aim of this study was to explore the diagnostic and prognostic value of the promoter methylation status of the ASC/TMS1/PYCARD and MyD88 genes, key adaptor molecules in the activation of the innate immune response and apoptosis pathways. METHODS: A total of 50 non-small cell lung cancer (NSCLC) patients were enrolled in the study. Methylation of bisulphite converted DNA was quantified by pyrosequencing in fresh frozen malignant tissues and adjacent non-malignant tissues. Associations between methylation and lung function, tumor grade and overall survival were evaluated using receiver-operating characteristics (ROC) analysis and statistical tests of hypothesis. RESULTS: Methylation level of tested genes is generally low but significantly decreased in tumor tissues (ASC/TMS1/PYCARD, P<0.0001; MyD88, P<0.0002), which correlates with increased protein expression. Three CpG sites were identified as promising diagnostic marker candidates; CpG11 (-63 position) in ASC/TMS1/PYCARD and CpG1 (-253 position) and 2 (-265 position) in MyD88. The association study showed that the methylation status of the ASC/TMS1 CpG4 site (-34 position) in malignant and non-malignant tissues is associated with the overall survival (P=0.019) and the methylation status of CpG8 site (-92 position) is associated with TNM-stage (P=0.011). CONCLUSIONS: The methylation status of the ASC/TMS1/PYCARD and MyD88 promoters are promising prognostic biomarker candidates. However, presented results should be considered as a preliminary and should be confirmed on the larger number of the samples.

CYFRA 21-1 in non-small cell lung cancer--standardisation and application during diagnosis.

There is no ideal tumour marker at present. The clinical application of CYFRA 21-1 is possible once a thorough standardisation process is carried out. Standardisation is achieved by determining the reference range in asymptomatic population, benign and malignant lung diseases, and benign and malignant diseases of other organs. Furthermore, it depends on knowledge of research population characteristics, patient medical histories and individual diagnostic procedure results, the size of research target samples and the clinically defined control groups. The cut-off level of CYFRA 21-1 for non-small cell lung cancer (NSCLC) is 1.72 ng/mL in the Croatian population. It is based on the clinically applicable sensitivity of 78% and specificity of 95% in benign lung diseases. The cut-off value is verified by clinical findings. For clinicians the level of CYFRA 21-1 is an early sign of NSCLC in relation to all the benign lung diseases and all the benign diseases of other organs, of which it was confirmed that they can influence the above level, provided that NSCLC is verified using standard diagnostic methods. The level of CYFRA 21-1 is also influenced by the time of sampling in relation to other diagnostic invasive procedures. The marker is clinically applicable if clinical findings verify it; otherwise, it is useless. This research has involved 343 healthy persons, 474 patients with a benign disease and 4440 patients with a malignant disease, 2453 of whom suffer from NSCLC. The sensitivity of CYFRA 21-1 in NSCLC is 78%, in squamous cell lung cancer (SQC) 84.6%, in adenocarcinomas (AD) 74.3% and in large cell lung cancer (LCC) 75.3%. The level of CYFRA 21-1 differs significantly between healthy persons, benign and malignant diseases (p<10(-3)). There are differences between the three histological types of NSCLC (p<10(-6)) and according to T and N (p<10(-3)). The level of CYFRA 21-1 prompts clinicians to repeat the clinical procedure during diagnosis, and helps to detect the disease earlier and implement treatment in NSCLC. We have achieved high concordance between marker findings and clinical diagnostic.

Expression of plakophilin 3 in diffuse malignant pleural mesothelioma.

Diffuse malignant pleural mesothelioma (DMPM) is the most common primary malignant pleural neoplasm still posing major diagnostic, prognostic and therapeutic challenges. Plakophilins are structural proteins considered to be important for cell stability and adhesion in both tumor and normal tissues. Plakophilin 3 is a protein present in desmosomes of stratified and simple epithelia of normal tissues with presence in malignant cells of various tumors where it participates in the process of tumorigenesis. The aim of this study was to investigate the expression of plakophilin 3 protein in DMPM, but also to study its prognostic significance and relation to histologically accessible parameters of aggressive growth. Archival samples of tissue with established diagnosis of DMPM and samples of normal pleural tissue were used. Tumor samples were classified into three histological types of DMPM (epithelioid, sarcomatoid and biphasic). Additional subclassification of epithelioid mesotheliomas into nine patterns based on the prevalent histological component of the tumor was then performed. After immunohistochemical staining, cytoplasmic and membrane immunopositivity of tumor cells was assesed by scoring the intensity of the staining from 0 (no staining) to 4 (very strong staining). Prognostic value and expression of plakophilin 3 with consideration to histologically estimated aggression in tumor growth were then statistically analyzed using non- parametric tests. The results demonstrated higher level of plakophilin 3 expression in tumor samples with histologically more aggressive tumor growth, but no significant prognostic value. According to our study, plakophilin 3 appears to be involved in tumor invasion in malignant mesothelioma.

Esophagogastric anastomosis in rats: Improved healing by BPC 157 and L-arginine, aggravated by L-NAME.

AIM: To cure typically life-threatening esophagogastric anastomosis in rats, lacking anastomosis healing and sphincter function rescue, in particular. METHODS: Because we assume esophagogastric fistulas represent a particular NO-system disability, we attempt to identify the benefits of anti-ulcer stable gastric pentadecapeptide BPC 157, which was in trials for ulcerative colitis and currently for multiple sclerosis, in rats with esophagocutaneous fistulas. Previously, BPC 157 therapies have promoted the healing of intestinal anastomosis and fistulas, and esophagitis and gastric lesions, along with rescued sphincter function. Additionally, BPC 157 particularly interacts with the NO-system. In the 4 d after esophagogastric anastomosis creation, rats received medication (/kg intraperitoneally once daily: BPC 157 (10 µg, 10 ng), L-NAME (5 mg), or L-arginine (100 mg) alone and/or combined or BPC 157 (10 µg, 10 ng) in drinking water). For rats underwent esophagogastric anastomosis, daily assessment included progressive stomach damage (sum of the longest diameters, mm), esophagitis (scored 0-5), weak anastomosis (mL H2O before leak), low pressure in esophagus at anastomosis and in the pyloric sphincter (cm H2O), progressive weight loss (g) and mortality. Immediate effect assessed blood vessels disappearance (scored 0-5) at the stomach surface immediately after anastomosis creation. RESULTS: BPC 157 (all regimens) fully counteracted the perilous disease course from the very beginning (i.e., with the BPC 157 bath, blood vessels remained present at the gastric surface after anastomosis creation) and eliminated mortality. Additionally, BPC 157 treatment in combination with L-NAME nullified any effect of L-NAME that otherwise intensified the regular course. Consistently, with worsening (with L-NAME administration) and amelioration (with L-arginine), either L-arginine amelioration prevails (attenuated esophageal and gastric lesions) or they counteract each other (L-NAME + L-arginine); with the addition of BPC 157 (L-NAME + L-arginine + BPC 157), there was a marked beneficial effect. BPC 157 treatment for esophagogastric anastomosis, along with NOS-blocker L-NAME and/or NOS substrate L-arginine, demonstrated an innate NO-system disability (as observed with L-arginine effectiveness). BPC 157 distinctively affected corresponding events: worsening (obtained with L-NAME administration that was counteracted); or amelioration (L-arginine + BPC 157-rats correspond to BPC 157-rats). CONCLUSION: Innate NO-system disability for esophagogastric anastomoses, including L-NAME-worsening, suggests that these effects could be corrected by L-arginine and almost completely eliminated by BPC 157 therapy.

[Anesthesia and perioperative management of patients with resection for esophageal carcinoma]. / Anestezija i perioperacijski postupak u resekcijskoj kirurgiji karcinoma jednjaka.

The current approach to the anesthetic procedure and postoperative intensive therapy after esophageal resection for esophageal carcinoma, as well as characteristic perioperative pathophysiological events are presented. The contributory factors of severe postsurgical morbidity are considered too. Esophagectomy is an extented procedure which includes laparotomy, thoracotomy and often cervicotomy, and carries a great surgical stress with a huge fluid shift. It is mostly performed in the aged population with a certain co-morbidity: malnutrition, compromized immune status, respiratory and cardiovascular diseases. Standardization of esophageal resection and reconstructive techniques together with the optimal perioperative management significantly reduce operative mortality. Preoperatively, the patients' nutritive, respiratory and cardiac status should be improved. Intraoperatively, beside adequate depth of anesthesia which enables the optimal metabolic response to surgical stress, the invasive hemodynamic monitoring with insertion of pulmonary artery catheter is of great importance. The aim is to ensure adequate tissue perfusion and oxygenation avoiding pulmonary overhydration at the same time. Postoperatively, important role has epidural analgesia, allowing proper breathing and coughing and routine usage of fiberbronchoscopy for clearance of pulmonary secretion. After resection there are several conditions which contribute to cough and swallow disturbances: bilateral vagotomy, the absence of upper and lower esophageal sphincters, transient aperistalsis of the substitute, sometimes a transient vocal cord paresis. All of these make patients prone to regurgitation and aspiration of duodenal and gastric juice. Currently, the pulmonary complications are the leading problems after this procedure, so their prevention and early treatment are the key tasks for the clinicians.