Vladimír Procházka

Serum-based microRNA signatures in early diagnosis and prognosis prediction of colon cancer

Early detection of colorectal cancer is the main prerequisite for successful treatment and reduction of mortality. Circulating microRNAs were previously identified as promising diagnostic, prognostic and predictive biomarkers. The purpose of this study was to identify serum microRNAs enabling early diagnosis and prognosis prediction of colon cancer. In total, serum samples from 427 colon cancer patients and 276 healthy donors were included in three-phase biomarker study. Large-scale microRNA expression profiling was performed using Illumina small RNA sequencing. Diagnostic and prognostic potential of identified microRNAs was validated on independent training and validation sets of samples using RT-qPCR. Fifty-four microRNAs were found to be significantly deregulated in serum of colon cancer patients compared to healthy donors (P < 0.01). A diagnostic four-microRNA signature consisting of miR-23a-3p, miR-27a-3p, miR-142-5p and miR-376c-3p was established (AUC = 0.917), distinguishing colon cancer patients from healthy donors with sensitivity of 89% and specificity of 81% (AUC = 0.922). This panel of microRNAs exhibited high diagnostic performance also when analyzed separately in colon cancer patients in early stages of the disease (T1-4N0M0; AUC = 0.877). Further, a prognostic panel based on the expression of miR-23a-3p and miR-376c-3p independent of TNM stage was established (HR 2.30; 95% CI 1.44-3.66; P < 0.0004). In summary, highly sensitive signatures of circulating microRNAs enabling non-invasive early detection and prognosis prediction of colon cancer were identified.

MiR-21, miR-34a, miR-198 and miR-217 as diagnostic and prognostic biomarkers for chronic pancreatitis and pancreatic ductal adenocarcinoma

BackgroundPancreatic ductal adenocarcinoma is an aggressive malignancy with late presentation, metastatic potential and very poor prognosis. Therefore, there is an urgent need for novel diagnostic and prognostic biomarkers. MicroRNAs are small non-coding RNAs that post-transcriptionally regulate gene expression. Altered expression of microRNAs has been reported in wide range of malignancies, including pancreatic ductal adenocarcinoma. The aim of this study was to analyze the expression of selected microRNAs in normal pancreas, chronic pancreatitis and pancreatic ductal adenocarcinoma tissues and evaluate their diagnostic and prognostic potential.FindingsUsing quantitative real-time PCR, expression levels of 4 microRNAs were examined in 74 tumor tissues, 18 tissues of chronic pancreatitis and 9 adjacent normal tissues and correlated with clinicopathological features of patients. Expression levels of miR-21, miR-34a and miR-198 were significantly higher, whereas levels of miR-217 were significantly lower in pancreatic ductal adenocarcinomas compared to healthy tissues and tissues of chronic pancreatitis. Moreover, increased expression of miR-21 and miR-198 was significantly associated with shorter disease free survival and overall survival.ConclusionsOur data suggest that altered expression of examined microRNAs is related to neoplastic transformation and progression of the disease and these microRNAs could serve as diagnostic and prognostic biomarkers for pancreatic ductal adenocarcinoma.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1373952531543898

Laparoscopic radiofrequency ablation of functioning pancreatic insulinoma: video case report.

Insulinomas are the most common functioning endocrine tumors of the pancreas. Most of them are well-differentiated tumors, with benign or uncertain behavior at the time of diagnosis. Surgery is considered to be the only curative treatment modality. We present the first case report of a 75-year-old woman with functioning insulinoma of the pancreatic body, which was destroyed by laparoscopic-assisted radiofrequency ablation. Hypoglycemic paroxysms disappeared immediately after surgery. The postoperative course was uneventful. The patient was discharged on the eighth postoperative day. There was a new onset of diabetes mellitus, without any further hypoglycemic paroxysm from surgery to the present—4 months. Laparoscopic-assisted radiofrequency ablation is shown to be a feasible and safe method for the treatment of functioning pancreatic insulinoma.

Spontaneous duodenal intramural haematoma imitating pancreatic pseudocyst.

Abstract Spontaneous intramural duodenal haematoma develops mostly as a complication of anticoagulation therapy. Other causes were reported only as case reports. CT diagnostics has some typical features in an intramural haematoma of the small bowel. This is especially hyperdensity of the bowel wall during the first 10 days from the onset of symptoms (30–80 HU), which could contribute to the differentiation from other infiltrative processes. These features are fully expressed only in a certain part of patients. We reported a 54 year-old female treated for epigastric pain. The patient’s history, laboratory data, ultrasonography and CT findings resulted in a mistaken diagnosis of acute pancreatitis, necrosis of the pancreatic body with a subsequent development of pancreatic pseudocyst. The CT guided drainage was performed. The correct diagnosis was made one year later-surgical treatment was indicated for clinical signs of GI obstruction and CT findings of pseudocyst recurrence. During the operation, there was a finding of intramural haematoma in the duodenojejunal border. We performed an evacuation of the haematoma and gastroenteroanastomosis.

Initial data on a novel endovascular radiofrequency catheter when used for arterial occlusion in liver cancer

ZusammenfassungGRUNDLAGEN: Wir untersuchten die Sicherheit und Wirksamkeit eines neuen endovaskulären Radiofrequenzkatheters (VesCoag) für den Arterienverschluss beim Management von Lebertumoren. METHODIK: Die Patienten hatten einen nicht resektablen primären oder sekundären Lebertumor. Der primäre Endpunkt war, ob VesCoag in das Zielgefäß eingebracht werden konnte, der sekundäre Endpunkt, ob es zu einem Angiographie-geprüften Verschluss des Gefäßes kam. ERGEBNISSE: VesCoag wurde bei 13 Patienten angewendet (4 Metastasen, 7 hepatozelluläre Karzinome, 2 intrahepatale Gallenganskarzinome). In allen Fällen konnte VesCoag ohne Komplikation (Ruptur, Dissektion) in die Zielgefäße eingebracht werden. Die Durchleuchtungszeit betrug 12,86 min, die Sondenaktivierung 240 (20–600) sec. Die abgegebene Energie betrug 2 W–120 W. Die bipolare Radiofrequenz konnte in keinem Fall einen adäquaten Gefäßverschluss erzielen, deshalb wurde der monopolare Modus verwendet. 4mal kam es zu Schmerzen, ein angiographisch nachgewiesener Verschluss wurde in 11 Fällen erzielt. 12 der 13 Patienten erhielten eine weiterführende Therapie (10× Chemoembolization, 1× Chemotherapie, 1× Lipiodol). SCHLUSSFOLGERUNGEN: Diese erste Erfahrung mit VesCoag zeigt, dass die Methode sicher ist und einen gezielten Verschluss von Zielgefäßen erlaubt.SummaryBACKGROUND: To assess the safety and effectiveness of a newly designed endovascular radiofrequency (RF) catheter (VesCoag) when used for arterial occlusion in the management of liver cancer. METHODS: Patients considered for the study had either primary or secondary cancer of the liver, which was not suitable for initial surgical resection. The primary endpoint of the study was whether VesCoag could be manipulated into the target blood vessel and the secondary endpoint was whether on angiography the blood vessel had been sealed. RESULTS: VesCoag was used in 13 patients. The indications for treatment were metastatic disease in 4, hepatocellular carcinoma in 7, and intrahepatic cholangiocarcinoma in 2. In all cases, VesCoag was manipulated into the target vessel for activation. There were no technical problems such as vessel dissection or rupture. The average fluoroscopic time was 12.86 min and the mean duration of probe activation was 240 (range 20–600) seconds. The lowest wattage used was 2 W and the highest 120 W. In no cases was bipolar radiofrequency activation sufficient to produce vessel sealing, so monopolar mode was used throughout. There were four minor complications of pain. The angiographic endpoint of target vessel occlusion was achieved in 11 patients. In 12 out of 13 cases an additional endovascular therapeutic maneuver was performed after VesCoag activation. These additional therapies were chemoembolization n = 10, chemotherapy n = 1, and lipiodol n = 1. CONCLUSIONS: This early assessment of VesCoag shows it to be safe and fulfill its design remit of being able to produce precise occlusion of the targeted vessel.

Pre-operative Plasma miR-21-5p Is a Sensitive Biomarker and Independent Prognostic Factor in Patients with Pancreatic Ductal Adenocarcinoma Undergoing Surgical Resection

Blood plasma microRNAs (miRNAs) are emerging as a clinically useful tool for non-invasive detection and prognosis estimation in various cancer types including pancreatic ductal adenocarcinoma (PDAC). The aim of the present study was to provide an independent validation of circulating miRNAs identified in previous studies as diagnostic and/or prognostic biomarkers in PDAC. Based on the literature search, 6 miRNAs were chosen as candidates for independent validation; miR-21-5p, miR-375, miR-155, miR-17-5p, miR-126-5p and miR-1290. Validation of these miRNAs was performed in a cohort of 25 patients with PDAC undergoing surgical resection and 24 healthy donors. Plasma levels of miRNAs were determined using quantitative real-time PCR. We confirmed significantly higher levels of all tested miRNA in blood plasma of PDAC patients in comparison to healthy controls with miR-21-5p showing the highest analytical performance (p<0.001; AUC>0.99). Increased levels of miR-21-5p (p=0.045) and miR-375 (p=0.013) were significantly associated with overall survival. Multivariate analysis demonstrated that miR-21-5p is a significant unfavorable prognostic factor independent on other clinical variables including adjuvant chemotherapy (hazard ratio 2.95; 95% CI 1.06-8.18; p=0.038). Our preliminary data indicate promising diagnostic and prognostic utility of plasma miR-21-5p in PDAC patients.

Achalasia-Which method of treatment to choose for senior patients?

ZusammenfassungAusgangscharakteristik: Achalasie ist eine selten aufkommende Erkrankung, die jährlich 1 Person per 100.000 betrifft. Diese schließt eine rare primäre motorische Störung des distalen Ösophagus ein.Methoden: Im Verlauf der Zeitperiode 1998–2006 wurden 115 Patienten verschieden Heilungsarten der Achalasie unterzogen, eine Teilgruppe der Senioren zählte 26 Patienten. Davon 6 Patienten (Alter 69,7 J.) wurden der modifizierten Heller’schen Kardiomyotomie unterzogen, und zwar als Folge des Mißerfolgs vorhergehender endoskopischer Interventionen. Die Standardmanometrie des Ösophagus, sowie die 24 Stunden dauernden pH-Messungen, wurden prä- und postoperativ durchgeführt.Ergebnisse: Sechs an Achalasie leidende Patienten im Seniorenalter wurden der laparoskopischen Heller’schen Myotomie unterzogen. Der durchschnittliche präoperative LES-Tonus war 55mmHg, der postoperative Tonus ist auf 11mHg gefallen. Bei allen Patienten haben wir die Toupet’sche Teilfundoplikation durchgeführt, durch die präoperative Ösophagoskopie wurde keine Mikroperforierung des Ösophagus gefunden. Wir haben einen minimalen pathologischen gastroösophagischen Reflux in der pH Messung registriert - der durchschnittliche präoperative DeMeester’sche Score war 8, der postoperative dann 10,5. Die prolongierte Dysphagie kam bei keinem Patienten vor - der präoperative GIQLI Score war 94 pts., der postoperative Score dann 106 pts. In der Patientengruppe der Operierten wurde keine Mortalität oder Morbidität beobachtet.Schlußfolgerungen: Unsere Operationsergebnisse und die postoperative Patientenbeobachtung zeigen, dass die laparoskopische Heller’sche Myotomie mit der Toupet’schen Teilfundoplikation eine sichere und effektive Heilungsmethode darstellen und als die Methode der ersten Wahl für die keine Kontraindikationen für die laparoskopische Operation aufweisenden Patienten im Seniorenalter empfohlen werden können.AbstractBackground Achalasia is an uncommon illness affecting 1 per 100,000 patients a year. It encompasses a rare, primary motor disorder of the distal esophagus. Methods Over the period 1998-2006, 115 patients underwent various treatments for achalasia; the subgroup of seniors consisted of 26 patients. Six patients of these (age 69.7 y) underwent a modified Heller cardiomyotomy due to failure of previous endoscopic interventions. Standard esophageal manometry and 24 hour pH metry were performed pre- and postoperatively. Results Six senior patients with achalasia underwent a laparoscopic Heller myotomy. Average preoperative tonus of the LES was 55 mmHg, postoperative tonus of the LES decreased to 11 mmHg. We performed Toupet partial fundoplication in all patients; no microperforation of the esophagus was found in the preoperative esophagoscopy. We recorded minimal pathological gastroesophageal reflux in pH metry – the average preoperative DeMeester score was 8, postoperatively 10.5. Prolonged dysphagia was not present in any patient – preoperative GIQLI score was 94, postoperative score was 106. There was no mortality or morbidity in the group of the operated patients. Conclusion Our operational results and postoperative follow-up show that laparoscopic Heller myotomy with Toupet partial fundoplication is a safe and effective treatment and can be recommended as the method of first choice for senior patients with no contraindication for laparoscopic operation.

Neovascularization after ischemic conditioning of the stomach and the influence of follow-up neoadjuvant chemotherapy thereon

Introduction Esophagectomy and reconstruction remain the optimal treatment for patients with resectable esophageal cancer. Neovascularization after ischemic conditioning of the stomach before esophagectomy is a laparoscopic procedure which may potentially reduce gastric conduit ischemia. Aim To investigate the influence of ischemic conditioning on neovascularization along the greater curvature of the stomach and to explore the effect of neoadjuvant chemotherapy on neovascularization after ischemic conditioning. Material and methods Staging laparoscopy was performed before the main resection procedure; during this procedure ischemic conditioning was performed. Samples taken from the human stomach were divided into 3 groups: group A – patients after ischemic conditioning with a delay of 30–45 days after left gastric artery (LGA) ligation (n = 4); group B – patients who were undergoing neoadjuvant chemotherapy with a delay of 90–140 days after left gastric artery ligation (n = 4); and control group C – patients without ischemic conditioning (n = 7). Results After ischemic conditioning with a delay of 30–45 days, the count of neovessels along the greater curvature of the stomach increased from 5.4 ±0.7 in the control group to 17.5 ±0.9 in a low-power field of view (LPF) in group A and increased still further on average to 19.8 ±10.4 in group B. Conclusions Left gastric artery ligation only is a sufficient procedure for ischemic conditioning of the stomach. Neovascularization along the greater curvature is a continuous process that depends on delay time. Neoadjuvant therapy has no influence on the effect of neovascularization.

Surgical Treatment of Ampullary Adenocarcinoma: Single Center Experience and a Review of Literature

BACKGROUND Adenocarcinomas of ampulla of the Vater are relatively uncommon tumors of the gastrointestinal tract. In premalignant lesions endoscopic treatment predominate. According to some authors even early adenocarcinomas (limited to mucosa) can be solved endoscopically. In malignant lesions affecting deeper layers (including submucosa) surgical therapy is the most important. The article summarises the current view for a surgical treatment of ampullary adenocarcinomas and presents results concerning our group of patients. MATERIALS AND METHODS In 2012-2016 a total number of 17 patients underwent resection for a tumor of ampulla of the Vater. Patients underwent standard staging, were presented before a multidisciplinary committee and referred to a surgical treatment. The main measured parameters were the type of surgical procedure, 30-day morbidity and mortality, histopathologic result and subsequent oncologic treatment. The Leeds Pathology Protocol was used to evaluate the specimens after pancreaticoduodenectomy (PD). RESULTS PD (n = 9) was a more often performed procedure than the transduodenal surgical ampullectomy (TSA) (n = 8). TSA predominated in polymorbid patients. Histological results (n = 17) established adenoma with high-grade dysplasia in 4 patients, the diagnosis of adenocarcinoma was set in 13 patients. Eight patients underwent adjuvant oncologic therapy (2 had adjuvant chemotherapy, 6 had combination of chemoradiotherapy). CONCLUSION Premalignant neoplasias of ampulla of the Vater can be mostly solved by endoscopy. If endoscopic resection is not possible surgical therapy is indicated. PD is preferred procedure in the diagnosis of adenocarcinoma. In high-risk and polymorbid patients, with no suspicion for a metastatic lymph nodes, TSA can be considered. Endoscopic ultrasonography is the imaging modality of choice for local staging of ampulla of the Vater and has important role in deciding between endoscopic, local surgical excision (TSA) or radical resection (PD). Our results confirmed rightfulness to perform TSA especially in elderly or polymorbid patients, where in histopathologic specimens evaluation in TSA procedures early T stage and more favorable grading predominated.Key words: adenocarcinoma of the ampulla of Vater - duodenum - endoscopic resection - ampullectomy - pancreaticoduodenectomy - surgery.

Mucinous cystic neoplasm of the liver or intraductal papillary mucinous neoplasm of the bile duct? A case report and a review of literature

Mucinous cystic neoplasm of the liver (MCN-L) and intraductal papillary mucinous neoplasm of the bile duct (IPMN-B) are diagnoses that were classified by the World Health Organization in 2010 as mucin-producing bile duct tumors of the hepatobiliary system. The preoperative differential diagnosis between these two entities is difficult; the presence of a communication with the bile duct is usually considered as a typical sign of IPMN-B. However, the presence of an ovarian-like stroma (OLS) has been established to define the diagnosis of MCN-L. We present the case of a 33-year-old woman with a rapid progression of a cystic tumor of the liver. In 2 years, the lesion increased from 27 to 64 mm and a dilation of the left hepatic duct appeared. Percutaneous transhepatic drainage with a biopsy was performed. No malignant cells were found on biopsy. Because of the rapid progression of the cystic tumor and unclear malignant potential, left hemihepatectomy was performed. Even though tumor masses were present in the biliary duct, on the basis of the presence of OLS, histology finally confirmed MCN-L with intermediate-grade intraepithelial dysplasia to high-grade intraepithelial dysplasia. The patient is currently under oncologic follow-up with no signs of recurrence of the disease. We present a rare case where MCN-L caused a dilation of the left hepatic duct, a sign that is usually a characteristic of IPMN-B.Mucinous cystic neoplasm of the liver (MCN-L) and intraductal papillary mucinous neoplasm of the bile duct (IPMN-B) are diagnoses that were classified by the World Health Organization in 2010 as mucin-producing bile duct tumors of the hepatobiliary system. The preoperative differential diagnosis between these two entities is difficult; the presence of a communication with the bile duct is usually considered as a typical sign of IPMN-B. However, the presence of an ovarian-like stroma (OLS) has been established to define the diagnosis of MCN-L. We present the case of a 33-year-old woman with a rapid progression of a cystic tumor of the liver. In 2 years, the lesion increased from 27 to 64 mm and a dilation of the left hepatic duct appeared. Percutaneous transhepatic drainage with a biopsy was performed. No malignant cells were found on biopsy. Because of the rapid progression of the cystic tumor and unclear malignant potential, left hemihepatectomy was performed. Even though tumor masses were present in the biliary duct, on the basis of the presence of OLS, histology finally confirmed MCN-L with intermediate-grade intraepithelial dysplasia to high-grade intraepithelial dysplasia. The patient is currently under oncologic follow-up with no signs of recurrence of the disease. We present a rare case where MCN-L caused a dilation of the left hepatic duct, a sign that is usually a characteristic of IPMN-B.