Milan Kujundzic

Role of Repeated Endoscopic Ultrasound-Guided Fine Needle Aspiration in Small Solid Pancreatic Masses with Previous Indeterminate and Negative Cytological Findings

Introduction: Despite advances in imaging techniques, the differentiation between pancreatic cancer and benign lesions remains difficult. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is an effective method for providing tissue diagnosis, but problems occur when lesions are small or the cytological diagnosis is indeterminate. Aim: To prospectively evaluate the utility of EUS-FNA in patients with small solid pancreatic lesions and those with initial indeterminate or negative cytological diagnosis. Methods: During the study period we performed a total of 119 EUS-FNA procedures on 46 patients (mean age 56.3 years) for 47 small solid pancreatic lesions (range 7–30 mm, mean 17.2 mm in diameter). FNAs were performed in the presence of a cytopathologist. If cytological diagnoses were indeterminate, EUS-FNA was repeated within 3 weeks. Diagnoses were confirmed histologically or by follow-up (clinical and imaging: EUS +/– FNA and CT). Results: Localization of the lesions: head 28 (60%), uncinate process 4 (9%), body 11 (23%) and tail 4 (9%). On average, 3.7 passes were performed. We observed no complications. Initial cytological findings were: malignant 17 (36%), benign 21 (45%), and indeterminate 9 (19%). 8 (78%) of the indeterminate findings were confirmed to be malignant on repeated procedures. A diagnosis of pancreatic cancer was subsequently confirmed in 1 patient who had a benign cytological finding. 19 patients underwent surgery. Histology confirmed a neoplasm in all cases. Sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy were 68, 100, 100, 73 and 83%, respectively. After repeated EUS-FNAs of indeterminate findings sensitivity, negative predictive value and diagnostic accuracy rose to 92, 77 and 96%, respectively. Conclusion: EUS-FNA is a highly effective method for providing tissue diagnosis in patients with small solid pancreatic masses. Repeated procedures enhanced diagnostic accuracy in indeterminate findings, among which was high percentage of malignancies. EUS-FNA reduced the number of operations in patients with pancreatic solid masses.

Activity of serum angiotensin-converting enzyme as a tumour marker of hepatocellular carcinoma.

OBJECTIVE Previous studies have pointed to the changes of serum angiotensin-converting enzyme (SACE) values in patients with liver disease and cancer located in different sites. The aim of this study was to determine the changes in SACE values in patients with hepatocellular carcinoma (HCC) and liver cirrhosis. METHODS The study comprised 30 patients with HCC (22 men and eight women) of average age 48.6 +/- 9.0 years and 30 patients with liver cirrhosis (21 men, nine women) of average age 49.1 +/- 9.5 years. The control group consisted of 30 healthy volunteers with matching anthropometric characteristics. SACE activity was determined by a spectrophotometric method using synthetic hippuryl-glycyl-glycine as substrate. RESULTS The mean SACE value was considerably lower in patients with HCC, 22.8 U/ml (95% CI, 22.5-23.9), both those in whom HCC developed in cirrhotic liver (n = 23), 23.7 (22.9-24.5) as well as those with HCC without cirrhosis (n = 7), 21.8 (21.0-22.6), with regard to patients with liver cirrhosis, 37.2 (36.6-37.8) (P < 0.001). There was also a statistically significant difference between healthy, 29.9 (29.4-30.3), and both groups of HCC patients (P < 0.001). No significant differences could be found between the group of HCC patients with and without liver cirrhosis (P < 0.05). In patients with liver cirrhosis SACE value was increased in accordance with the severity of the disease expressed by Childs classification; however, at each stage SACE values were considerably lower in patients with HCC in cirrhotic liver (Child A, 35.8 vs 22.1; Child B, 38.7 vs 24.2; Child C, 40.0 vs 28.3) (P < 0.001). Alfa-fetoprotein (AFP) values did not correlate with the SACE activity. The SACE value was also significantly decreased in patients with HCC whose AFP were not altered. CONCLUSION The study has shown that SACE values are low in patients with advanced HCC. It may be helpful in detecting HCC in patients with cirrhosis, where it can be difficult to differentiate between small HCC tumours and regeneration nodules.

Historical Impact to Drive Research in Peptic Ulcer Disease

The story of gastric acid secretion began with early ideas on gastric secretion (Spallanzani and de Réaumur, 17th century) and with first descriptions of food digestion (Dupuytren and Bichat, Beaumont, early 18th century), followed by proof that gastric juice contained acid (Prout, early 18th century). The research continued with first descriptions of gastric glands as the source of gastric acid and its changes upon digestive stimulus (Purkinje and Golgi, mid and late 19th century). The theory of ‘nervism’ – the neuro-reflex stimulation of gastric secretion by vagal nerve (Pavlov, early 20th century) was contrasted by a histamine-mediated concept of gastric secretion (Popielski and Code, mid 20th century). Thus, gastric acid and pepsin (Schwann, early 19th century) were found to be essential for food digestion and studies also pointed to histamine, being the most potent final common chemostimulator of oxyntic cells. The discoveries in etiopathogenesis of mucosal injury were marked by the famous dictum: ‘No acid, no ulcer’ (‘Ohne saueren Magensaft kein peptisches Geschwür’, Schwarz, 1910) that later induced the term of ‘mucosal defense’ and the notion that the breaking of ‘gastric mucosal barrier’ represents the initial step in the process of mucosal injury (Davenport, Code and Scholer, mid 20th century). The prostaglandins were shown to influence all major components of gastric mucosal barrier, described with the term ‘cytoprotection’ (Vane, Robert and Jacobson, 1970s). Beginning in the latter half of 19th century, the studies on gastric bacteriology that followed enabled the discovery of association between Campylobacter (Helicobacter) pylori and peptic ulcers (Warren and Marshall, 1980s) that led to worldwide major interventions in treating peptic ulcer disease. The surgical approach to peptic ulcer had been outlined by resection procedures (Billroth, Pean, Moynihan, late 19 century) and vagotomy, with or without drainage procedures (Jaboulay, Latarjet, Dragstedt, mid 20th century). Antacids, protective agents, anticholinergics, and later gastrin antagonists and prostaglandins were used for decades in the treatment of peptic ulcer, with differing effects. The advent of the concept of H2-receptor antagonists (Black, 1970s) and the discovery of acid (proton) pumps in parietal cells (Ganser, Forte and Sachs, late 1970s) paved the way for potent (H2 antagonists) and profound acid inhibition (proton pump inhibitors) that revolutionized the treatment of acid-related disorders, including peptic ulcer disease. Worldwide, peptic ulcer and its complications remain the cause of significant morbidity, especially in older age groups, representing a major burden for ambulatory and hospital healthcare resources.

EUS-Guided Vascular Procedures: A Literature Review

Endoscopic ultrasound (EUS) is continuously stepping into the therapeutic arena, simultaneously evolving in different directions, such as the management of pancreatic and biliary diseases, celiac neurolysis, delivering local intratumoral therapy, and EUS-guided endosurgery. EUS-guided vascular procedures are also challenging, considering the variety of vascular pathology, proximity of the vascular structures to the GI tract wall, high resolution, and real-time guidance offering an attractive access route and precise delivery of the intervention. The literature on vascular therapeutic EUS demonstrates techniques for the management of upper GI variceal and nonvariceal bleeding, pseudoaneurysms, and coiling and embolization procedures, as well as the creation of intrahepatic portosystemic shunts. The paucity of studies, diversity of study designs, and the number of animal model studies hamper a systematic approach to the conclusion and decision making important to clinicians and healthcare policy makers. Nevertheless, theoretical benefits and findings up to date concerning technical feasibility, efficacy, and safety of the procedures drive further research and development in this rather young therapeutic arena.

Leptomeninges as the first and only dissemination site of colorectal cancer

Dear Editor, Colorectal cancer (CRC) is one of the most common cancer types in the world, ranked second in developed countries for both genders, with the incidence of around 70–80 per population of 100,000. CRC disseminates most frequently to liver, lung, and bones, whereas it is rather rare in other organs. The incidence of colorectal adenocarcinoma dissemination to the leptomeninges is not estimated and seems to be quite rare. We report a case of a woman with CRC and the disease dissemination to the leptomeninges as the first and only dissemination site. A 61-year-old woman presented to the infectious diseases emergency room with a one-month history of fatigue, fever, photophobia, and mild headache that progressed to severe headache and vertigo. All of these symptoms appeared shortly after a mild conjunctivitis on both eyes that was treated with tobramycin eye-drops. The patient also emphasized a 1-year history of strabismus of the right eye and substantial weight loss of about 12 kg in a period of several months. She had no history of malignancies or any other serious diseases. Fifteen years ago, she had cataract surgery with a plastic lens implemented in her left eye. Physical examination, except for nonparalytic convergent strabismus of the right eye, was unremarkable with no clinical signs of meningitis. Body temperature was 38.0°C. Upon admission to the infectious diseases ward, a lumbar puncture was performed. The cerebrospinal fluid (CSF) analysis showed hypercellular sterile CSF with predominantly adenocarcinoma cells of unknown origin with elevated total protein level (64.5 g/dL) and low glucose level (1.9 mmol/L—33% of the blood level). The contrast-enhanced computed tomography (CECT) of the brain, made in order to enlighten this finding, did not find any pathological substrate except mild maxillary sinusitis on the left. Computed tomography (CT) of the abdomen was performed thereafter, and a large tumor mass in the ascending colon was found, though the patient had no symptoms or clinical signs of gastrointestinal obstruction. No lesions elsewhere in the abdomen were detected. Chest X-ray examination was normal. Thereafter, the patient was referred to the gastroenterology ward. Physical examination on admission to the gastroenterology ward showed moderate pain on deep palpation in the right iliac region and nonparalytic convergent strabismus of the right eye with hypermature cataract of the same eye. Neurological examination revealed no evidence of motor dysfunction or sensory changes including pathologic reflexes, except the aforementioned convergent strabismus, photophobia, and vertigo. The complete blood count revealed mild anemia with hemoglobin concentration of 114 g/L. Laboratory serum examination results showed high cholesterol (7.56 mmol/L) and triglyceride (2.84 mmol/L) level, increased gamma glutamyl-transpeptidase (90 U/L) and low concentration of iron (2.5 μmol/L). Blood coagulation was also slightly impaired with prothrombin time of 0.93 INR, fibrinogen of 5.8 g/L, and prolonged fibrinolysis. Additionally, C-reactive protein of 31.1 mg/L was detected. Tumor marker carbohydrate antigen 19-9 was highly increased (>1,000 kIU/L) with carcinoembryonic Int J Colorectal Dis (2009) 24:355–356 DOI 10.1007/s00384-008-0560-7

Informed Consent for Gastrointestinal Endoscopy: A View of Endoscopists in Croatia

Background/Aim: There are many differences and deficiencies in the process of informed consent. The aim of this study was to get the view of gastrointestinal endoscopists in Croatia on obtaining patients’ consent before endoscopic procedures. Methods: During the 2004 annual meeting of the Croatian Society of Gastroenterology, endoscopists were asked to answer a questionnaire according to common clinical practice in affiliated institutions. It included questions on endoscopists’ experience and education in medical ethics, as well as on the nature and quality of information given to patients and their opinion on proposed measures for improvement of the informed consent process. Results: The questionnaire was distributed to 96 endoscopists attending the meeting and the response rate was 54% (52/96). In only 50% of institutions was the obtained consent written and potential complications of endoscopic procedures are occasionally given to the patient. In the minority of cases the patient is provided with information about alternative diagnostic tests and/or treatment options, and the information about mortality rate was almost never discussed. Conclusions: In Croatia, the process of informed consent for endoscopy needs improvement and should be regarded against the background of education in medical ethics, regional burden in endoscopic practice and appropriateness of by-laws and local guidelines.