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A large tumorous mass completely surrounding and compressing the coeliac trunk was identified on computed tomography in a young woman with a six-month history of progressive abdominal pain. The tumor was excised along with the coeliac trunk and the proximal parts of its branches. The hepatic artery was reconstructed with an aorto-hepatic autogenous bypass. Postoperatively the patient had neurogenic diarrhea, which subsided on medical treatment. Seven months after surgery the patient is in a good state of health and living a normal life.

Pancreatic ductal adenocarcinoma represents a disease with increasing incidence. Its prognosis is the worst among all malignancies despite the aggressive combined multimodal treatment across all stages. In metastatic disease, median survival is approximatelly one year. The mainstay of treatment is chemotherapy (neo/adjuvant, palliative) and in selected subgroups of patients even radiotherapy. Nevertheless, nowadays there are very few prognostic and/or predictive biomarkers available that can be used to identify and better stratify patients based on risk to tailored treatment. Potentially, promising areas of research are circulating tumor cells and circulating tumor DNA, which can be easily obtained from peripheral blood – so called liquid biopsy. They may serve as a tool to assess response to applied treatment, and to detect the emergence of treatment-resistant clones or early disease relapse. Moreover, their study may allow identification of potentially tumor-specific alterations, which may serve as target structures for targeted (tailored) therapy. Alternatively, different prognostic indexes/scores calculated by analysis of selected parameters of blood and/or biochemistry can be used to better stratify patients based on risk and better predict prognosis. The aim of this mini-review is to provide a basic overview of the current state of the art in this area and its potential significance for clinical practice.

Receptory velke rodiny HER hraji v připadě karcinomu prsu významnou roli, ktera prochazi postupným rozvojem v souvislosti s biologickým vývojem, a to jak na poli diagnostickem tak terapeutickem. HER2 pozitivita u karcinomu prsu původně sama o sobě představovala nepřiznivý prognostický faktor. To se změnilo diky moderni lecbě pomoci monoklonalnich protilatek. Dalsi meznik pote představuje konecna analýza dat ze studie CLEOPATRA. Tato studie se zaměřila na přinos přidani monoklonalni protilatky pertuzumabu ke standardni terapii trastuzumabem a docetaxelem. Pertuzumab se važe na stejný cil jako trastuzumab, avsak na jinem vazebnem mistě, inhibuje tak heterodimerizaci HER2 a HER3 receptorů. Dimerizace HER2 s dalsimi cleny skupiny HER je přitom největsim hnacim mechanismem růstu a přeživani nadorových buněk. Pertuzumab ma sam o sobě minimalni protinadorovou ucinnost, použiva se proto výhradně v kombinaci s trastuzumabem. Tento kombinovaný přistup tedy zlepsuje blokadu HER2 signalni drahy porusenim dimerizace HER3 a HER2 receptoru. Velice zajimave se ovsem jevi využiti exprese HER3, jako možneho prognostickeho markeru u TNBC převažně ve spojitosti s graviditou a kojenim. Dale se předpoklada, že HER-3 receptor se podili nejen na přežiti a proliferaci buněk, ale take na regulaci exprese PD-L1. Mohlo by se tedy jednat o potencialni cil imunoterapie. Pohled na receptor HER-3 bude vsak daleko složitějsi a jak se zda, nadměrna exprese tohoto receptoru, bude mit jak negativni, tak pozitivni prognostický význam.

The dorsal pancreatic artery is the main artery of the body and tail of the pancreas. Its origin and branching is highly variable. The aim of this study was to perform a meta-analysis to generate pooled prevalence data on the presence and origin of the dorsal pancreatic artery. Clinically important aspects of the dorsal pancreatic artery were summarised during the literature review.Major medical databases were searched. Data on the presence and point of origin of the dorsal pancreatic artery were extracted and quantitatively synthesised. The obtained data of anatomical based studies and computed tomography based studies were statistically analysed.In total, 30 studies, comprising 2322 anatomical and computed tomography based cases were included. The dorsal pancreatic artery was present in 95.8% of cases. It originated from the splenic artery in 37.6% of cases, common hepatic artery in 18.3% of cases, coeliac trunk in 11.9% of cases and the superior mesenteric artery in 23.9% of cases. Other rare origins were present in 2.77% of cases. Multiple dorsal pancreatic arteries were found in 1,7% of cases. There was no significant difference in the presence or origin of the dorsal pancreatic artery between anatomical and computed tomography based studies.The dorsal pancreatic artery is present in the vast majority of cases. Its origin and branching are highly variable. Multiplicity of the dorsal pancreatic artery is infrequent.

Therapy for pancreatic ductal adenocarcinoma remains challenging, and the chances of a complete cure are very limited. As in other types of cancer, the expression and role of miRNAs in controlling the biological properties of this type of tumor have been extensively studied. A better insight into miRNA biology seems critical to refining diagnostics and improving their therapeutic potential. In this study, we focused on the expression of miR-21, -96, -196a, -210, and -217 in normal fibroblasts, cancer-associated fibroblasts prepared from a ductal adenocarcinoma of the pancreas, and pancreatic carcinoma cell lines. We compared these data with miRNAs in homogenates of paraffin-embedded sections from normal pancreatic tissues. In cancer-associated fibroblasts and cancer cell lines, miRNAs differed significantly from the normal tissue. In detail, miR-21 and -210 were significantly upregulated, while miR-217 was downregulated. Similar transcription profiles were earlier reported in cancer-associated fibroblasts exposed to hypoxia. However, the cells in our study were cultured under normoxic conditions. We also noted a relation to IL-6 production. In conclusion, cultured cancer-associated fibroblasts and carcinoma cells reflect miR-21 and -210 expression similarly to the cancer tissue samples harvested from the patients.

Ambulatory pH monitoring of pathological reflux is an opportunity to observe the relationship between symptoms and exposure of the esophagus to acidic or non-acidic refluxate. This paper describes a method for the development, manufacturing, and implantation of a miniature wireless-enabled pH sensor. The sensor is designed to be implanted endoscopically with a single hemostatic clip. A fully passive rectenna-based receiver based on a zero-bias Schottky diode is also constructed and tested. To construct the device, a two-layer printed circuit board and off-the-shelf components were used. A miniature microcontroller with integrated analog peripherals is used as an analog front end for the ion-sensitive field-effect transistor (ISFET) sensor and to generate a digital signal which is transmitted with an amplitude shift keying transmitter chip. The device is powered by two primary alkaline cells. The implantable device has a total volume of 0.6 cm3 and a weight of 1.2 grams, and its performance was verified in an ex vivo model (porcine esophagus and stomach). Next, a small footprint passive rectenna-based receiver which can be easily integrated either into an external receiver or the implantable neurostimulator, was constructed and proven to receive the RF signal from the implant when in proximity (20 cm) to it. The small size of the sensor provides continuous pH monitoring with minimal obstruction of the esophagus. The sensor could be used in routine clinical practice for 24/96 h esophageal pH monitoring without the need to insert a nasal catheter. The "zero-power" nature of the receiver also enables the use of the sensor for automatic in-vivo calibration of miniature lower esophageal sphincter neurostimulation devices. An active sensor-based control enables the development of advanced algorithms to minimize the used energy to achieve a desirable clinical outcome. One of the examples of such an algorithm would be a closed-loop system for on-demand neurostimulation therapy of gastroesophageal reflux disease (GERD).

Head and neck squamous cell carcinomas (HNSCC) are a highly heterogenous disease which can be induced by two main carcinogens - tobacco and/or alcohol, or by HR HPV infection. This work examined 60 paraffin-embedded biopsies of head and neck carcinomas after histological verification. HPV infection, including its specific types in various HNSCC areas, was studied using multiplex qPCR. Expression levels of p16INK4A and p53 were detected by subsequent IHC analysis as being potential diagnostic markers. Based on the assumption that patients with HNSCC could benefit from anti-EGFR therapy (cetuximab), but the predictors are not yet defined, analyses of point mutations of ras genes (Kras, Nras) were carried out using multiplex qPCR and sequence analysis of the Braf gene. All statistical data were processed by Chi-x2 test.HPV infection was detected in 23.34 % of cases with HNSCC, of which 100 % were HPV 16, which is the most frequently infection found in the oropharyngeal region. Using IHC analysis, a positive expression of P16INK4A was detected in 100 % of HPV-positive HNSCC while this expression was discovered to be highly correlated with HPV infection. Furthermore, a correlation between p53 and HPV-negative HNSCC was proved. The mutation incidence was the highest in the Kras gene (codon 12 and codon 146), Nras (codon 12) and Braf. A correlation between tumor location in the oropharyngeal region and Kras mutations was proved. The HPV infection correlated with Kras mutations in case of codon 146 but on the grounds of low amount of output data, these figures could be irrelevant. In one case, c.1808 G>A, protein 603 Arg>Gln mutation was found in the Braf gene but its correlation with head and neck carcinomas has not been described yet (Tab. 2, Fig. 2, Ref. 24). Keywords: head and neck carcinomas, biopsy, HPV types, PCR, p16INK4A, p53, molecular predictors, Kras, Nras, Braf.

Ideal dressings of surgical wounds should provide moist, semi‐permeable, and antiseptic environments for optimal wound healing. To maximise patient comfort, surgical dressings must be hypoallergenic, not restrict movement, and allow patients to manage their personal hygiene. From the aspect of health care personnel, dressings should enable visual monitoring of the wound without the need for removing them, thus reducing the number of dressing changes. The active antimicrobial effect of silver cations has been demonstrated by many studies. StopBac is a unique surgical dressing based on the sol‐gel process. Silver cations are bound in a colloidal solution in an organic‐inorganic hybrid organosilicate oligomer. This gel is deposited on a pad using spray atomisation. The result is a polymer nanolayer matrix with prolonged and controlled release of silver ions. This pad forms part of a waterproof hypoallergenic transparent adhesive bandage. The goal of this study was to prospectively evaluate the ability of StopBac to prevent surgical site infections (SSIs) in patients after abdominal surgery. The secondary goal was to compare costs and determine the properties of this new material. A total of 32 patients were included in the study. The patients were followed up until their surgical wounds healed completely. An SSI occurred only in one patient.

Surgical resection remains the cornerstone for the curative treatment of oncological disease. In a situation when a tumour encases a critical arterial or venous structure, long term oncological control may be achieved only through careful preoperative planning within a multidisciplinary team incorporating oncological and vascular specialists. The present review addresses the principles in planning oncovascular surgery, describes the oncovascular procedure in pancreatic, liver, renal and endometriosis cancer as well as vascular involvement in retroperitoneal soft sarcoma and sarcoma in lower extremity. In conclusion, the present review highlights that major vessel involvement of a tumour mass should not necessarily be considered as a barrier to en bloc resection and hence curative oncosurgery procedure.

We present a case of a 100-year-old polymorbid patient with signs of bowel obstruction. After failure of conservative therapy computed tomography was performed, which revealed the course of the obstruction to be a gallstone in the terminal ileum. The gallstone was removed surgically without complications and the patient recovered well and had an uneventful postoperative course.

Higher incidence of injury in trauma patients older than 65 years is connected with growing morbidity and mortality, first of all in polytrauma. Incidence of preexisting diseases play a great role in development of postinjury reaction. There are risk factors for genesis of postinjury complications and also mortality of victims. Growing number of polytrauma patients older than 65 years admitted to Trauma Centre Faculty Hospital Královské Vinohrady was reason for evaluation of epidemiological data and their comparison with data regarding to victims younger than 65 years. In retrospective study was evaluated 239 injured patients with polytrauma, admitted in Emergency unit Department of anesthesiology and resuscitation. From overall number was 47 victims older than 65 years (29/61 %). 75 years was an average age in victims older than 65 years. Primary admission to Trauma Centre was in case of 42 (85 %) victims older than 65 years. Between causes of injury were most frequent traffic accidents and falls. Most frequent injury in geriatric patients was craniocerebral injury in 36 patients (76 %) and thoracic trauma in 38 patients (80 %). Skeletal fractures of extremities were found in 21 (44 %) victims. From comparison of APACHE II score in both group of patients (19 in group of younger patients vs. 27,2 in group of older victims) is possible to establish higher incidence of preexisting diseases in patients older than 65 years. Average ISS score evaluated serious of trauma was without statistic significant difference (22 vs. 21). Number of deaths was 42 (22 %) in group of victims younger than 65 years and 22 (47 %) in group of victims older than 65 years. Older victims (over 65 years old) were exposed higher mortality in comparison with younger patients. On the result of treatment participate preexisting diseases besides age. Mechanism of injury and from this resulting type of trauma in older population need new strategy in postinjury care. Performance of primary admission of older victims with polytrauma to Trauma Centre is tend to this strategy.

Due to population aging in developed countries, it has become necessary to prepare a functional health care plan for the elderly. One of the possibilities to improve postoperative outcomes and recovery in elderly patients is to perform common surgical procedures in the regime of one-day surgery. We compared elderly patients who underwent surgery in a large university hospital with elderly patients who underwent surgery in a facility dedicated to one-day surgery. The homogeneity and clinical outcomes of the two groups were statistically analyzed. Complications were assessed according to the Clavien-Dindo classification. There were no statistically significant differences in demographic data and pre-operative risk assessment (ASA). The one-day surgery group had fewer complications and a shorter average hospital stay. Advanced age is not the only criterion for assessing the biological state of the patient and therefore does not always necessitate surgical care in a university hospital setting with a high volume of acute and complicated cases. Many elderly patients will benefit from a more individualized approach and healthcare facilities that specialize solely in elective procedures. When indicating elderly patients for one-day surgery, their health status is more important than their calendar age.

As life expectancy increases in economically developed countries, there is an increasing need for medical care for the elderly. In surgical fields, this means that the number and spectrum of surgical interventions in elderly patients is increasing. Because of this special attention should be paid to the preoperative evaluation in these patients. Communication with the patient and relatives is crucial in order to decide on the extent of the surgical intervention and whether to treat these patients with curative or palliative intent. It is imperative that physicians understand the physiology of aging and its associated risks, as traditional perioperative risk assessment tools are insufficient in this patient group.

We present a case of a 93-year-old patient with colorectal carcinoma indicated to right hemicolectomy. Shortly before planned surgery patients condition was complicated by pulmonary embolism, deterioration and protracted bleeding from the tumor. After careful internal and preoperative preparation patient underwent right hemicolectomy with uncomplicated course of hospitalization and transferred back to internal department to internal, rehabilitation and nutritional care. Thanks to intensive perioperative care and despite the patient#39;s high age, the patient#39;s quality of life has not decreased in any way and enjoys good health.

Population aging is one of the most significant health problems of the 21st century and has led to an increased need for surgery in elderly patients. Only chronological age should not be decisive when indicating patients for elective procedures. Other objective findings should be taken into account too. The complex geriatric examination is an optimized, detailed and accurately defined method, which leads to better postoperative outcomes in elderly patients. In everyday practice it is sufficient to evaluate the mental, physical and nutritional state of the patient. The goal of our study was to evaluate the perioperative morbidity and mortality of elderly patients undergoing hepatopancreatobiliary procedures. In our retrospective study we evaluated prospectively collected data of patients who underwent surgical procedures between 2015 and March 2019. In total 245 patients underwent pancreatic procedures and 156 underwent hepatic procedures. Morbidity and mortality were evaluated in the first 75 postoperative days and classified according the Clavien-Dindo classification. Our results show that when surgical procedures are correctly indicated in elderly patients, acceptable postoperative morbidity and mortality can be achieved. Since the year 2018 we have been actively using prerehabilitation in our center and it has led to improved postoperative outcomes in elderly and high-risk patients.

Pancreatic ductal adenocarcinoma (PDAC) remains a disease with extremely poor prognosis and limited effective available treatment. Differential expression of miRNAs isolated from tumor tissue has been proposed as a marker for tumor diagnosis, progression, and prognosis. Nevertheless, the prognostic value of miRNAs expression in PDACs for patient outcome still remains unclear. Expression of 7 selected miRNAs, isolated from FFPE samples of 54 PDAC patients, was quantified using RT-qPCR. The relationship of miRNA expression levels with tumor histology, clinicopathological characteristics, patient overall survival (OS), and progress-free survival (PFS), was subsequently evaluated. Overexpression of miR-21, miR-155, and miR-210 was observed in PDACs (up to 72.62, 232.36, and 181.38-fold, respectively), in comparison with non-neoplastic tissues. On the other hand, miR-96 and miR-217 were significantly downregulated in PDACs (up to one hundred times). No differences were, however, noticed between cancer and normal tissues for the expression levels of miR-148a and miR-196a. On the other hand, expression levels of all 7 miRNAs failed to demonstrate a significant correlation with parameters of tumor progression, such as tumor stage, grade, nodal involvement, perineural, and vascular invasion. The positive correlation of miR-210 levels was, however, observed with patient age (ρ=0.35). Additionally, miR-148a and miR-217 expressions have shown a positive association with tubular tumor growth pattern (ρ=0.39; ρ=0.28). The negative correlation of miR-148a values was also demonstrated with dissociative growth pattern and nuclear atypia (ρ=-0.30; ρ=-0.27). Finally, no statistically significant correlation could be demonstrated with the expression levels of all 7 tested miRNAs and PDAC patient survival; neither for OS nor for PFS (p>0.05). Our data have confirmed abnormal miRNAs expression in PDACs in comparison with adjacent non-neoplastic tissue. On the other hand, no correlation was discovered between miRNA expression and parameters of tumor progression. We have found a significant association between histologic tumor growth patterns and miRNA expression, making this work the first study, which analyses this aspect of PDAC. Finally, in our group of patients, no relationship of miRNA levels and patient prognosis could be demonstrated. Therefore, further investigation is required to evaluate the predictive and prognostic potential of miRNAs in a clinical setting.

INTRODUCTION Analysis and comparison of short-term results of laparoscopic liver resections (LLR) and open liver resections (OLR) for colorectal cancer liver metastases (CRCLM). METHODS Retrospective analysis of patients operated for CRCLM in the time period from May 2007 to May 2019 (12 years) at the department of surgery, University Hospital Hradec Kralove and University Hospital Kralovske Vinohrady. RESULTS 206 liver resections were performed; 167 (81.1%) OLR and 39 (18.9%) LLR procedures. Conversion to open surgery was necessary in 6 cases (15.4%). LLR was associated with a longer operation time (194±107 min) vs (129±58 min) for OLR. The ICU stay, 3.5±4.3 days for OLR and 4.1±8.1 days for LLR, and the hospital stay, 11.9±8.3 days (OLR) vs 12.1±11.3 days (LLR), were comparable. Perioperative blood loss was lower in the LLR group, 189±166 ml vs 360±410 ml. Total transfusion rate was similar, 10.8% (OLR) vs 12.8% (LLR). Oncologic radicality was also comparable in both groups; negative resection margin was achieved in 78% (OLR) and 80% (LLR). Postoperative morbidity and mortality was comparable in both groups; morbidity was 33% (OLR) vs 31% (LLR), while mortality was 1.8% (OLR) vs 2.6% (LLR). CONCLUSION LLR for CRCLM provided comparable short-term results compared to OLR in our group of patients even in the learning curve period. However, it should be noted that the study group is a highly selected group of patients.

Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a rare peripheral T cell lymphoma. BIA-ALCL is a disease of the fibrous capsule surrounding the implant and occurs in patients after both breast reconstruction and augmentation. More than 300 cases have been reported so far, including two in a transgender patient. Here we describe BIA-ALCL presented with a mass in a transgender patient and the first case of BIA-ALCL in the Czech Republic. In 2007, a 33-year-old transgender male to female underwent bilateral breast augmentation as a part of his transformation to female. In June 2014, the patient developed a 5-cm tumorous mass in her left breast. Magnetic resonance imaging of the chest revealed a ruptured implant and a tumorous mass penetrating into the capsule and infiltrating the pectoral muscle. An R0 surgery was indicated-the implant, silicone gel and capsule were removed, and the tumorous mass was resected together with a part of the pectoral muscle. Histology revealed anaplastic large-cell lymphoma. The patient underwent standard staging procedures for lymphoma including a bone marrow trephine biopsy, which confirmed stage IE. The patient was treated with the standard chemotherapy for systemic ALCL-6 cycles of CHOP-21. The patient was tumor-free at the 2-year follow-up. BIA-ALCL has been reported mostly in women who received implants for either reconstructive or aesthetic augmentation. This is the third report of BIA-ALCL in a transgender person, the first in the Czech Republic. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Introduction. The aim of this study was to compare the indications, operative details, and clinical outcomes of nonexposed endoscopic wall-inversion surgery with endoscopic-navigated laparoscopic wedge resection of gastric submucosal tumours. Methods. Medical records were reviewed for patients who underwent nonexposed endoscopic wall-inversion surgery (NEWS) at the Faculty Hospital Kralovske Vinohrady and endoscopic-navigated laparoscopic wedge resection (LWR) at the Kepler University Hospital. Demographic, tumour, surgical, perioperative, and follow-up data were collected and compared. Results. Eleven patients underwent NEWS and twelve patients underwent LWR. NEWS was associated with a longer operating time and more frequent suture line bleeding (3 cases in the NEWS group versus 1 case in the LWR group). Negative resection margins were achieved in all NEWS procedures and in 11 of the LWRs. The difference in size between the tumour and the resected specimen was smaller in the NEWS group. Length of hospitalisation was similar between the two groups (NEWS=6.8 days, LWR=6.5 days). Follow-up gastroscopies at 12 months postoperatively revealed no signs of recurrence in any of the patients. Conclusion. Nonexposed endoscopic wall-inversion surgery is a new technique for the treatment of gastric tumours. It allows for more precise resections with more frequent achievement of negative resection margins than LWRs. Additionally, it may allow for better preservation of gastric function and limit communication between the gastric lumen and peritoneal cavity. The longer operating time and more frequent complications associated with the NEWS reflects the limited experience with these new techniques.

In recent years multidetector computed tomography (MDCT) has been used to investigate vascular anatomy for scientific and diagnostic purposes. These studies allow for much larger sample sizes than traditional cadaveric studies. The aim of this research was to perform a systematic review and meta-analysis on studies investigating the variations of the celiac trunk using MDCT. Major medical databases were used to find studies investigating celiac trunk anatomy using MDCT. Extracted information included demographic details, number of normal celiac trunks, and number of each variant celiac trunk. Using a random effects meta-analysis the pooled prevalence of each variation was calculated. A total of 36 studies from 14 countries and four continents were included in the meta-analysis. The total number of subjects included was 17,391. The total prevalence of variant celiac trunks was 10.85%. The different types of celiac trunk variations with their prevalences were: gastrosplenic trunk (3.46%), hepatosplenic trunk (3.88%), hepatogastric trunk (0.24%), absent celiac trunk (0.28%), celiacomesenteric trunk (0.46%), hepatosplenomesenteric trunk (0.26%), gastrosplenomesenteric trunk (0.07%), and celiacomesenteric anastomosis (0.09%). A total of 61 cases (0.19%) were either not described or not described adequately to be included in our classification. Major variations of the celiac trunk are not uncommon and should be anticipated before radiological and surgical interventions. Knowledge of celiac trunk anatomy is important in hepatopancreatobiliary surgery, transplantology, and interventional radiology.

Cholangiocellular carcinoma (CCC) is a malignant tumor harboring a poor prognosis, occurring in the liver, gallbladder and in extra- or intrahepatic biliary ducts. The article reviews the topic concerning CCC from the point of view of a surgical pathologist. The paper deals with classification of CCC into an intrahepatic/peripheral and hilar/extrahepatic subtype with different morphology, molecular features and prognosis; together with classical gross pathology, histopathology and natural history of CCC. Hilar and extrahepatic CCC share some biological characteristics with pancreatic ductal adenocarcinoma. The review comprises various types of precancerous lesions of biliary tract, summarizes updates in 8th edition of TNM classification and describes the routine issues concerning histopathological diagnostics of CCC, including immunohistochemistry and frozen section methods.

Cholangiocarcinoma is a relatively rare, highly fatal neoplasm originating from the biliary epithelium. Its only potentially curative treatment option is a radical surgical resection. The aim of our work was to evaluate the feasibility and the safety of intraoperative ERCP and direct cholangioscopy (SpyGlass) to assess the intraductal border of cholangiocarcinoma proliferation. The study ran from November 2015 to January 2018. The group included patients with histologically verified cholangiocarcinoma and, based on available examinations, the resectability of the tumor was assessed by a multidisciplinary team. In cases of indicated surgical resection we peroperatively performed ERCP with cholangioscopy SpyGlass and "diaphanoscopy" in all patients. The resectability was assessed on the basis of these examinations and the peroperative surgical findings. The resection procedure itself was performed only in 2 out of the total of 14 patients, as other patients were indicated for the implantation of metallic SEMS within the ERCP procedure in the operating room instead. To validate the cholangioscopic findings, we used our own criteria based on both the Monaco and other criteria. We divided the findings according to the presence or absence of ulceration, prominent polyposis, pathological vascularization (4 types), pressure defect with a coagulum in the presence of previous stent implantation, papillomatous changes or discolorations of the mucosa. Out of the total number of 14 patients only two patients were indicated for resection and in both cases R0 resection was achieved. The remaining patients were intraoperatively indicated for palliative implantation of SEMS based on the same unresectable finding during cholangioscopy and laparotomy. We demonstrated the technical feasibility and safety of direct peroperative cholangioscopy. Our results show that direct perioperative cholangioscopy is one of the methods which can contribute to a more accurate determination of tumor spread margins.

Cholangiocarcinoma is a cancer with very poor prognosis. The only potentially curative approach is surgical resection of tumor. However, the rate of local and distant recurrence after radical surgery is still high. Benefit of adjuvant therapy is not clearly defined, nevertheless patients at high risk of recurrence are indicated to chemotherapy or chemoradiotherapy. Locally advanced, unresectable disease can also be treated with chemotherapy alone, or with her combination with radiotherapy. Required radiation doses are relatively high, therefore it is necessary to use highly conformal radiation therapy. Treatment of metastatic disease is currently based on systemic therapy, combination of gemcitabine and cisplatin as standard of care. Benefit of targeted molecular therapy is not clear at present, but ongoing research in genetic profiling of tumor may help to improve current clinical practice. Patients with cholangiocarcinoma have to be discussed during multidisciplinary team meetings.

Cholangiocellular carcinoma is a relatively rare malignant tumor, originating from cholangiocytes, with poor prognosis and late diagnosis. It is a malignancy with a variable biological etiology, numerous genetic and epigenetic changes. Its incidence in the Czech Republic is about 1.4 per 100,000 people per year. For good prognosis and long-term survival, early diagnosis with surgical treatment is important. In these cases, a 5-year survival rate is about 20-40 %. In the early diagnosis imaging methods and histopathological verification play an essential role, whereas laboratory oncomarkers are not yet sufficiently accurate. The same applies for genetic markers. This leads to the search of new molecular targets and the high effort in the introduction of cytological and molecular-biological methods with high specificity and sensitivity into routine practice. Current early diagnosis is based on the use of efficient imaging methods. The use of genetic testing, and especially knowledge of the molecular basis of this disease, will be of a great benefit. The observation of the association between the genetic pathways, IDH1, RAS-MAPK etc., and genetic mutations of genes, such as TP53, KRAS, SMAD4, BRAF, IDH1/2, may be significant. From the molecular point of view, it is also interesting to monitor oncogenic potential in HBV/HCV infection.

Cholangiocarcinoma represents the second most common primary liver malignancy. Despite it comprises only 3 % of all gastrointestinal malignancies, its incidence has been increasing recently. Cholangiocarcinomas are hepatobiliary cancers with features of cholangiocyte differentiation and from clinical point of view they are classified anatomically as intrahepatic or extrahepatic form. The only curative treatment with aim of long term and disease-free survival is surgery - liver resection or liver transplantation. Current progress in perioperative treatment and increased surgical skills has changed old treatment algorithms and widen number of patients suitable for curative treatment. On the other hand, surgical intervention is connected with not negligible morbidity and mortality. A rigorous knowledge of the disease extent and all prognostic factors is main condition for proper treatment decision.

Introduction The incidence of colorectal cancer in young patients is increasing. The goal of this study was to investigate whether clinicopathological features and survival differed between young, middle-aged and elderly patients. Methods The Czech National Cancer Registry was searched to identify all cases of colorectal cancer between 1982 and 2014. Three subgroups of patients were created: young patients, defined as being between 18 and 40 years of age, middle-aged patients, defined as being between 41 and 74 years of age, and elderly patients, defined as being over the age of 75 years. Results A total of 192,241 patients diagnosed with colorectal cancer between the years 1982 and 2014 were included in the study. Out of these, 3,287 patients (1.7%) were between 18 and 40 years of age, 134,139 patients (69.8%) were between 41 and 74 years of age and 54,815 patients (28.5%) were 75 years of age or older. The young patients had a higher incidence of mucinous adenocarcinoma and signet ring cell carcinoma, more advanced disease and more rectal tumours than elderly patients. Nonetheless, young patients received treatment more frequently and had better cancer-specific survival than the older patients. Conclusion The better prognosis in young patients is presumably due to their better physiological reserve and lower incidence of comorbidities. Efforts should be made in younger patients to diagnose early and treat aggressively.

Surgical treatment is not commonly recommended in the management of autoimmune pancreatitis. The article describes a dilemma in diagnostics and treatment of a 68-year old man with the mass in the head of the pancreas that mimicked pancreatic cancer and that was diagnosed as a type 1 autoimmune pancreatitis (IgG4-related pancreatitis) after a surgical resection. Diagnosis of the autoimmune pancreatitis is a real clinical challenge, as in the current diagnostic criteria exists some degree of overlap in the findings between autoimmune pancreatitis and pancreatic cancer (indicated by the similarity in radiologic findings, elevation of IgG4, sampling errors in pancreatic biopsy, and the possibility of synchronous autoimmune pancreatitis and pancreatic cancer). Despite the generally accepted corticosteroids as the primary treatment modality in autoimmune pancreatitis, we believe that surgical resection remains necessary in a specific subgroup of patients with autoimmune pancreatitis (Fig. 4, Ref. 37).

Circulating tumor cells (CTCs) are important targets for treatment and critical surrogate markers when evaluating cancer prognosis and therapeutic response. A sensitive methodology for detecting CTCs in gastric cancer (GC) patients is needed. In this study we demonstrate a device for enrichment and cultivation of CTCs. In total, 22 patients with GC, all candidates for surgery, were enrolled in the study. Peripheral blood samples were collected before surgery, and patients were re-evaluated within operation and divided into two groups: resectable and non-resectable GC. A new size-based separation test for enrichment and cultivation of CTCs was used (MetaCell®). In addition to cytomorphological analysis, gene expression of tumor associated genes (Cytokeratin-18, Cytokeratin-19, Cytokeratin-20, Cytokeratin-7, EPCAM, MUC1, HER2, EGFR) and of leukocyte markers (e.g. CD45, CD68) was tested in enriched CTC fractions. CTCs were detected in 59 % of the patients studied (n = 13/22). CTCs were detected in seven patients of the resection group (7/10, 70 %) and six of the non-resectable group (6/12, 50 %). Enrichment of the viable CTCs allowed subsequent successful cultivation in vitro. The cytomorphological characterization of the CTCs was a prerequisite of random gene expression testing in CTC-positive samples. In CTC-positive samples gene expression of cytokeratin 18 and 19 was elevated in comparison to the whole blood gene expression analysis. CTCs were found to be present in both resectable and non-resectable gastric cancer patients. The size-based separation platform for CTCs may be used for in vitro cultivation, as well as in subsequent molecular analysis if desired. The sensitivity of CTC-detection could be enhanced by the combination of cytomorphological and molecular analysis. Electronic supplementary material The online version of this article (doi:10.1007/s10616-015-9866-9) contains supplementary material, which is available to authorized users.

The presence of circulating tumor cells (CTCs) in patients with metastatic carcinoma is generally associated with poor clinical outcome. There have been many investigations showing a possible use of CTCs as minimally invasive predictive and prognostic biomarker in cancer medicine. In this report a size-based method (MetaCell ® ) for quick and easy enrichment and cultivation of CTCs is presented to enable possible CTCs use in esophageal cancer (EC) management. In total, 43 patients with diagnosed EC, 20 with adenocarcinoma (Adeno Ca) and 23 with squamous cell carcinoma (SCC), were enrolled into the adaptive prospective-like study. All the patients were candidates for surgery. The CTCs were detected in 27 patients (62.8%), with a higher rate in adenocarcinoma (75%) than SCC (52%). Finally, there were 26 patients with resectable tumors exhibiting CTCs-positivity in 69.2% and 17 patients with non-resectable tumors with 41.7% CTCs-positivity. Interestingly, in the patients undergoing neoadjuvant therapy, the CTCs were detected at time of surgery in 55.5% (10/18). The overall size-based filtration approach enabled to isolate viable CTCs and evaluate to their cytomorphological features by means of vital fluorescent staining. The CTCs were cultured in vitro for further downstream appli- cations including immunohistochemical analysis. This is the first report of the successful culturing of esophageal cancer CTCs. The detection of CTCs presence could help in the future to guide timing of surgical treatment in EC patients. (Folia Histochemica et Cytobiologica 2014, Vol. 52, No. 3, 171-177)

e15784 Background: Pancreatic cancer is the second leading cause of death in tumor diseases worldwide. Neuropilin-1 (NRP1) is overexpressed in many tumors including the pancreatic cancer. The main goal is to reveal the role of NRP1 in the process of tumorigenesis. The expression of NRP1 and the presence of KRAS point mutation lead to the cell survival by lowering the SMAD2 phosphorylation. On the other hand, the NRP1 inactivation and the wild-type KRAS in tumor cells lead to the tumor growth inhibition. Our aim is to prove correlation between NRP1 level, SMAD2 and the mutational status of KRAS, NRAS in prognosis of patients with pancreatic cancer. Methods: Retrospective study is based on analysis of 50 FFPE bioptical samples (40 resections, 8 punctures, 2 thin-needle biopsies); histology verified all as adenocarcinomas. The expression level of NRP1 and SMAD2 is measured by Imunohistochemistry by mice monoclonal antibodies Anti-Neuropilin 1 and Anti-SMAD2 (Abcan) on the device BenchMark ULTRA (Ventana Medical Systems), Roche. DNA isolation is executed by QIAamp DNA Mini Kit. We used Codon Specific Mutation Detection Kit (Diatech pharmacogenetics) for detection of somatic point mutations in codons 12, 13, 61 and 146 of KRAS and NRAS genes. BRAF mutational status was revealed by direct sequencing on ABI Prism 3130. We monitor the level of expression of NRP1 and SMAD2 and correlate it to the mutational status of RAS and BRAF, and disease prognosis. Results: NRP1 expression was detected in 24 out of 50 cases, SMAD2 expression was detected in 13 of 50 cases, other cases without expression. KRAS gene mutation was detected in 8 cases out of 60, other cases of WT. Mutation in the NRAS gene was detected in 3 of 50 cases. BRAF gene mutation was detected in 1 case out of 50, other WT. NRP1 expression correlated with KRAS gene mutation status in 9 cases and a strong correlation (p = < 0.001) was recorded. One case of mutation in the BRAF gene correlated with KRAS mutation status and NRP1 expression. Due to the small number of samples tested, without statistical significance. Inactivation of NRP1 was detected in 15 cases and was confirmed by the WT status of the KRAS gene. Conclusions: Was demonstrated that causal relationship exists between inactive NRP1 and wild-type KRAS, and that these should cause decrease of the rate of tumor growth. These characteristics, which are achievable simultaneously during the histological verification, may serve as a potential prognostic marker for subsequent decision of how radical surgical resection should be.

Contains fulltext : 202265.pdf (Publisher’s version ) (Closed access) Cancer cells without mitochondrial DNA (mtDNA) do not form tumors unless they reconstitute oxidative phosphorylation (OXPHOS) by mitochondria acquired from host stroma. To understand why functional respiration is crucial for tumorigenesis, we used time-resolved analysis of tumor formation by mtDNA-depleted cells and genetic manipulations of OXPHOS. We show that pyrimidine biosynthesis dependent on respiration-linked dihydroorotate dehydrogenase (DHODH) is required to overcome cell-cycle arrest, while mitochondrial ATP generation is dispensable for tumorigenesis. Latent DHODH in mtDNA-deficient cells is fully activated with restoration of complex III/IV activity and coenzyme Q redox-cycling after mitochondrial transfer, or by introduction of an alternative oxidase. Further, deletion of DHODH interferes with tumor formation in cells with fully functional OXPHOS, while disruption of mitochondrial ATP synthase has little effect. Our results show that DHODH-driven pyrimidine biosynthesis is an essential pathway linking respiration to tumorigenesis, pointing to inhibitors of DHODH as potential anti-cancer agents.

Objective The diagnosis of sepsis is difficult in immunocompromised patients owing to their modified response to infection. Our experiment in minipigs was designed to compare responses to sepsis between experimental groups of septic minipigs with and without immunosuppression. Methods Minipigs with identical baseline parameters were randomized into 3 groups: Sepsis (n = 10); immunosuppression (n = 11), including cyclosporine, methylprednisolone, and mycophenolate mofetil treatment before surgery, and a sham group (n = 6). Sepsis was induced by cecal ligation and puncture (CLP). We recorded selected clinical and laboratory parameters up to 24 hours postoperatively. Results All CLP animals developed septic shock with a febrile response, tachycardia, and hypotension requiring noradrenaline administration. The hemodynamic responses to sepsis in septic groups with and without immunosuppression were similar. Noradrenaline infusion was started on average later in the immunosuppression than in the group without immunosuppression; however, the difference was not significant. The kinetics of the plasma levels of most selected cytokines and C-reactive protein were similar in both septic groups. At 10 hours after surgery, the immunosuppression group showed significantly lower interleukin (IL)-6 levels compared with the sepsis group. At 19, 22, and 25 hours after surgery immunosuppressed animals displayed significantly greater increases in IL-10 levels compared with the cohort without immunosuppression. Conclusions CLP is a simple, reproducible model of sepsis in minipigs. All CLP animals developed sepsis within 24 hours on average. Significant differences in IL-6 and IL-10 plasma levels were recorded between septic animals with versus without immunosuppression.

Introduction. Liquid biopsies are noninvasive tests using blood or body fluids to detect circulating tumor cells (CTCs) or the products of tumor cells, such as fragments of nucleic acids or proteins that are shed into biological fluids from primary tumor or its metastates. The analysis of published clinical studies provides coherent evidence that the presence of CTCs detected in peripheral blood is a strong prognostic factor in patients with colorectal carcinoma (CRC). The aim of the study was to implement size-based separation protocol of CTCs in CRC patients. Material and methods. Patients diagnosed with different stages of CRC (n = 98) were included in the study. All patients have been diagnosed for colorectal adenocarcinoma by pathology examination, 45 patients with colon carcinoma and 53 with rectosigmoid cancer. A size-based separation method (MetaCell®) for viable CTC enrichment from peripheral blood was used to assess the presence of CTCs by cytomorphological evaluation using vital fluorescence microscopy. Results. Cytomorphological analysis revealed that 81 (83%) tested samples were CTC-positive and 17 (17%) were CTC-negative. We report a successful isolation of CTCs with proliferation potential in patients with CRC. The CTCs were cultured in vitro for further downstream applications. Some of the isolated CTCs were able to grow in vitro for 6 months as a standard cell culture. Conclusions. We established a reliable, inexpensive and relatively fast protocol for CTCs enrichment in CRC patients by means of vital fluorescence staining which enables their further analysis in vitro .

Background Pancreatic cancer is recognized as one of the most fatal tumors due to its aggressiveness and resistance to therapy. Statins were previously shown to inhibit the proliferation of cancer cells via various signaling pathways. In healthy tissues, statins activate the heme oxygenase pathway, nevertheless the role of heme oxygenase in pancreatic cancer is still controversial. The aim of this study was to evaluate, whether anti-proliferative effects of statins in pancreatic cancer cells are mediated via the heme oxygenase pathway. Methods In vitro effects of various statins and hemin, a heme oxygenase inducer, on cell proliferation were evaluated in PA-TU-8902, MiaPaCa-2 and BxPC-3 human pancreatic cancer cell lines. The effect of statins on heme oxygenase activity was assessed and heme oxygenase-silenced cells were used for pancreatic cancer cell proliferation studies. Cell death rate and reactive oxygen species production were measured in PA-TU-8902 cells, followed by evaluation of the effect of cerivastatin on GFP-K-Ras trafficking and expression of markers of invasiveness, osteopontin (SPP1) and SOX2. Results While simvastatin and cerivastatin displayed major anti-proliferative properties in all cell lines tested, pravastatin did not affect the cell growth at all. Strong anti-proliferative effect was observed also for hemin. Co-treatment of cerivastatin and hemin increased anti-proliferative potential of these agents, via increased production of reactive oxygen species and cell death compared to individual treatment. Heme oxygenase silencing did not prevent pancreatic cancer cells from the tumor-suppressive effect of cerivastatin or hemin. Cerivastatin, but not pravastatin, protected Ras protein from trafficking to the cell membrane and significantly reduced expressions of SPP1 (p

Background: Pulmonary endarterectomy (PEA) is an effective treatment for chronic thromboembolic pulmonary hypertension (CTEPH). The present study tested the hypothesis that inflammation, as determined by circulating cytokine levels, may contribute to the difficulty in controlling arterial blood pressure after PEA. Materials and Methods: Thirty-six patients with CTEPH (22 males and 14 females) underwent PEA using cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest. Plasma concentrations of tumor necrosis factor α, interleukin (IL)-1β, IL-6 and IL-8 were measured repeatedly in arterial blood samples. Results: A significant correlation between norepinephrine support and IL-6 plasma concentrations was shown at the separation from CPB (k = 0.742) and 12 h after it (k = 0.801) as well as between norepinephrine support and IL-8 concentrations 12 h after the separation from CPB. Furthermore, a significant correlation was found between the cardiac index (CI) and both IL-6 and IL-8 at the separation from CPB. Conclusions: Hemodynamic instability after PEA has been associated with higher postoperative plasma concentrations of IL-6 and IL-8. The positive relation between inflammatory cytokines and CI, or cytokines and vasopressor support, is in accordance with the hypothesis that cytokine activation may be among the neurohumoral factors responsible for cardiodepression and systemic vasoplegia in CTEPH patients undergoing PEA.

Background: The aim of the prospective study was to characterize the disturbance of gastric electrical control activity in different types of ileus and to correlate surface electrogastrography (EGG) findings with a set of inflammatory markers. Patients and Methods: Fifty-four adult patients with mechanic, vascular and paralytic ileus proven on clinical and radiological exams and 14 age- and sex-matched controls were examined. Gastric myoelectrical activity was recorded using 3 Ag-AgCl disposable skin electrodes connected in pseudo-unipolar mode by Microdigitrapper device. The captured signal was amplified and digitalized. The dominant frequency was calculated using computerized algorithms (Fast Fourier transform and running spectrum analysis). The results were correlated with the known pathological diagnoses and 4 inflammatory parameters – interleukin (IL)-1β, IL-6, procalcitonin (PCT) and C-reactive protein. Results: Irregular EGG activity without a dominant frequency or bradygastria (electrical control activity frequency Conclusions: EGG examination confirmed a high sensitivity in the evaluation of gastric electrical control activity in both vascular and paralytic ileus. Significant correlation of EGG findings and both IL-6 and PCT plasma levels supports a role of the inflammatory milieu in the pathogenesis of impaired gastric electrical activity in patients with ileus.

Background: Both ghrelin and leptin are important signals in the regulation of food intake and energy balance. Leptin concentrations are elevated in the majority of obese individuals, and its levels usually correlate with adiposity and body mass index. Ghrelin as a new growth hormone (GH)-releasing peptide was discovered in 1999. Ghrelin stimulates food intake and exhibits gastroprotective properties. Many other regulatory effects of both ghrelin and leptin involving cardiovascular, gastrointestinal, renal, and endocrine systems were revealed. New experimental studies show both hormones as new acute phase reactants in animal models of inflammatory reaction. The aim of this study was to characterize the levels of circulating ghrelin and leptin in relation to systemic inflammatory response. We used a postoperative bacterial sepsis after large abdominal surgery as a model of cytokine network hyperstimulation. Patients and Methods:The prospective study was performed on 25 surgical patients with proven postoperative intra-abdominal sepsis after large abdominal surgery. Plasma levels of ghrelin (RIA), leptin, TNF-α, IL-1β, sIL-2R, IL-6 (ELISA analysis), CRP and α1-antitrypsin (nephelometric analysis) were analyzed. Results: Authors demonstrate statistically significant elevation of plasma ghrelin (492.3 ± 70.6 ng/l) and leptin (31.6 ± 12.2 µg/l) compared with the control group (336.5 ± 46,1, p < 0.01 for ghrelin, 3.5 ± 1.2 µg/l, p < 0.001 for leptin). The regression coefficient was the highest for ghrelin and IL-6 (r = 0,44, p < 0.05), and for ghrelin and TNF (r = 0.43, p < 0.05) in the sepsis group. In regard to leptin, the regression coefficient was the highest for IL-6 and leptin (r = 0.53, p < 0.05) and for leptin and CRP (r = 0.51, p < 0.05). There was no significant correlation between ghrelin and IL-1β, ghrelin and sIL-2R, and leptin and IL-1β. Conclusions: During postoperative intra-abdominal sepsis, both ghrelin and leptin plasma levels are elevated and positively correlate with both inflammatory cytokines (TNF-α, IL-6) and main APP member (CRP). It supports experimental finding that TNF-α and IL-6 can be important regulatory factors of their synthesis. This hormonal reaction is not specific to sepsis – the significant increase of both ghrelin and leptin occurs during an uncomplicated postoperative response, although in a lesser extent than was shown in sepsis.

Background . Postoperative ileus is a distressing and frequent adverse effect after laparoscopic cholecystectomy (LCE). The goal of this prospective study was to evaluate if the new