A pleiotropy scan to discover new susceptibility loci for pancreatic ductal adenocarcinoma.

Pleiotropic variants (i.e., genetic polymorphisms influencing more than one phenotype) are often associated with cancer risk. A scan of pleiotropic variants was successfully conducted ten years ago in relation to pancreatic ductal adenocarcinoma susceptibility. However, in the last decade, genetic association studies performed on several human traits have greatly increased the number of known pleiotropic variants. Based on the hypothesis that variants already associated with a least one trait have a higher probability of association with other traits, 61,052 variants reported to be associated by at least one genome wide association study (GWAS) with at least one human trait were tested in the present study consisting of two phases (discovery and validation), comprising a total of 16,055 pancreatic ductal adenocarcinoma (PDAC) cases and 212,149 controls. The meta-analysis of the two phases showed two loci (10q21.1-rs4948550 (P=6.52×10-5) and 7q36.3-rs288762 (P=3.03×10-5) potentially associated with PDAC risk. 10q21.1-rs4948550 shows a high degree of pleiotropy and it is also associated with colorectal cancer risk while 7q36.3-rs288762 is situated 28,558 base pairs upstream of the Sonic Hedgehog (SHH) gene, which is involved in the cell differentiation process and PDAC etiopathogenesis. In conclusion, none of the single nucleotide polymorphisms (SNPs) showed a formally statistically significant association after correction for multiple testing. However, given their pleiotropic nature and association with various human traits including colorectal cancer, the two SNPs showing the best associations with PDAC risk merit further investigation through fine mapping and ad hoc functional studies.

Pancreaticoduodenectomy in patients with an unusual course of the hepatic artery.

INTRODUCTION: Variations in hepatic artery anatomy are very common in the population. The aim of this study is to evaluate the rates of individual types of hepatic artery variants in the population of patients undergoing pancreaticoduodenectomy (PD), assess the accuracy of preoperative staging CT imaging to identify hepatic artery variants, and evaluate the impact of the hepatic artery variants on perioperative and postoperative morbidity of PD patients. METHODS: A prospective observation study of 147 patients undergoing PD for a pancreatic head pathology at the 1st Department of Surgery, University Hospital Olomouc between 1/2015-12/2018. Preoperative diagnosis of the course of the hepatic artery was made based on staging CT imaging analysis of the abdomen. The result was classified according to the Michels' scale and correlated with the final perioperative finding. Demographic, histopathological and clinicopathological data were included in a prospectively maintained database. RESULTS: A total of 147 patients were included in the study, 83 (56.5%) males and 64 (43.5%) females, median age 65.0 (37-83) years. A variant course of the hepatic artery was found in 37 (25.2%) patients. The accuracy of preoperative CT imaging in determining the variant was 100%. The presence of a hepatic artery variant was not statistically significant as a factor in terms of postoperative complications - CD I-II (50.0% vs 47.2%), CD III-IV (8.3% vs 13.8%). Similarly, the 30-day (4.2% vs 2.4%) and 90-day mortality rates (4.2% vs 3.3%) were comparable in both groups. CONCLUSION: Preoperative diagnosis of vascular variants based on multidetector CT imaging of the abdomen is routinely available and shows high detection accuracy. There was no difference in postoperative morbidity and mortality in patients with and without a variant hepatic artery undergoing PD.

Appendiceal tumors and pseudomyxoma peritonei: current recommendations for clinical practice.

Appendiceal tumors and pseudomyxoma peritonei (PMP) are rare tumors. Perforated epithelial tumors of the appendix are the most common source of PMP. This disease is characterized by the presence of mucin of varying degrees of consistency, partially adherent to the surfaces. Appendiceal mucoceles themselves are also very rare and usually their treatment involves only a simple appendectomy. The aim of this study was to provide an up-to-date review of the recommendations for the diagnosis and treatment of these malignancies according to the current guidelines of The Peritoneal Surface Oncology Group International (PSOGI) and the Blue Book of the Czech Society for Oncology of the Czech Medical Association of J. E. Purkyne (COS CLS JEP).

Minimally-invasive pancreatic surgery in high volume centers in the Czech Republic - current status and possible implementations.

INTRODUCTION: Minimally-invasive surgical methods have been becoming ever more common also in the segment of pancreatic surgery. The aim of this paper was to analyze the current state of minimally-invasive surgery in the Czech Republic and the justification and potential of implementing such procedures. METHODS: Analysis of high volume centers using healthcare providers´ and payers´ data. RESULTS: Thirteen pancreatic surgical centers meet the proposed criteria for being called a high volume center - a center of highly specialized care in pancreatic surgery based on the annual number of at least 17 major resections of the pancreas. According to data from healthcare payers, laparoscopy was used in 0.6%-65.7% of procedures in individual centers. However, these are not resection procedures. The centers themselves report a significantly smaller number of minimally-invasive pancreatic resection procedures. The actual numbers of minimally-invasive resection procedures in the current system are practically impossible to verify. The potential for implementing minimally-invasive pancreatic surgery in the Czech Republic can be estimated based on the identification of candidate patients. CONCLUSION: Due to the fragmentation of this operative segment, its costs and small numbers of patients suitable for minimally-invasive pancreatic surgery even among high volume centers, the implementation rate of these methods is very slow. The need to centralize this segment of care appears to be very urgent from all points of view.

Middle and distal bile duct carcinoma, retrospective analysis & short-term and long-term outcomes of surgical therapy.

INTRODUCTION: The prognosis of extrahepatic cholangiocarcinoma is dismal and the only way to achieve long-term survival is surgical resection. While pancreatoduodenectomy (PD) is the standard procedure for distal cholangiocarcinoma (distal bile duct cancer; DBDC), bile duct segmental resection (BDR) can be used as an alternative approach for middle bile duct cholangiocarcinoma (middle bile duct cancer; MBDC). The aim of the study was to calculate the short-term and long-term outcomes of curative-intent surgery in distal bile duct cholangiocarcinoma patients. METHODS: A retrospective cohort study of consecutive patients treated for MBDC and DBDC with PD or BDR between 1/2009-12/2019. The patients were divided according to the type of surgical resection (PD and BDR group). Demographic, clinicopathological and histopathological data and overall survival (OS) were evaluated in both groups. OS was estimated using the Kaplan-Meier analysis. RESULTS: The study comprised a total of 62 patients - 45 patients (72.6%) in the PD group and 17 (27.4%) in the BDR group. Patients undergoing BDR were significantly older than those receiving PD (p=0.048). Men predominated in the PD group (N=34/45; 75.6%) while more women were included in the BDR group (N=10/17; 58.8%). Median age was higher in the BDR group (p=0.048). Serious morbidity (Clavien-Dindo III-V) (33.3% vs 11.8%), 30-day and 90-day mortality (4.4% vs 0.0% and 8.9% vs 5.9%, respectively) predominated in the PD group although the differences were not statistically significant, as well as a longer hospital stay (16.0 days vs 11.0 days; p=0.002). Pathological assessments revealed comparable numbers of positive lymph nodes in both groups, but a significantly higher number of total resected lymph nodes in the PD group (p.

Enzyme replacement following total pancreatectomy; population analysis

Introduction: Total pancreatectomy (TPE) inevitably leads to absolute exocrine pancreatic insufficiency (EPI). No specific recommendations are available for enzyme replacement in such cases. The aim of our analysis was to explore the actual EPI replacement rates among patients following TPE after a certain period of time from the surgery. Methods: This retrospective analysis of living patients who had undergone TPE more than 2 years ago was done using a simple questionnaire to investigate the following: BMI prior to TPE, 3 months after TPE and at the time of data collection (in 2022), together with the actual number of daily bowel movements; and the replacement characteristics ­ the daily dose, its scheme and subjective satisfaction evaluation. Results: In total, we obtained data from 26 living patients with the history of TPE with their median follow up of 56 months (30­157). Malignant disease was confirmed in 69% patients based on histology; a benign tumor was present in the rest, although malignancy had been suspected preoperatively. Median BMI decreased from preoperative 27.4 (19.1­41.1) to 24.1 (19.8­33.7) 3 months following TPE, and median BMI value of 25.5 (21.2­34.5) was established at 30­157 months from TPE. The mean number of daily bowel movements was 2.2 (median 2, range 1­8) and the mean daily replacement dose was 182,000 units of lipase (median 175,000 u., range 0­250,000 u.) at the time of our investigation. Subjective satisfaction was reported by 85% responders and a lack of satisfaction despite maximum EPI replacement was expressed by 15% responders. Conclusion: BMI decreased shortly after TPE. In the long term, up to 80% of the patients achieved preoperative BMI values ±10% after TPE. Due to persistent steatorrhea and more frequent bowel movements despite enzyme replacement, 15% of the patients remained subjectively dissatisfied after TPE, but 85% of the patients did not perceive even more frequent bowel movements as unpleasant and were satisfied with their condition. The need of individualized enzyme replacement therapy of EPI following TPE is evident.

Pancreatic cancer in chronic pancreatitis ­ the diagnostic and therapeutic dilemma; an overview of cases

Introduction: Any mass in chronic pancreatitis (CP) is a difficult diagnostic and therapeutic problem. The aim of the study is a) to use our own group to determine the actual incidence of non-malignant masses in CP where any mass is highly suspected of being malignant; and b) to determine the actual incidence of malignant tumors in CP. Methods: We present a retrospective analysis of our group of patients operated in 2015­2019 for CP, a mass in CP and suspected malignancy in the mass in CP. Additionally, we present difficult cases in terms of preoperative diagnosis. Results: Thirty-three of 340 (9.7%) pancreatic resection were done due to any form of chronic pancreatitis in 2015­2019. A mass in the pancreatic head was present in 16 (48%) patients; of these, pancreatic ductal adenocarcinoma (PDAC) was suspected in 10 (62%) patients based on EUS, CT or PETCT, and also based on positive tissue diagnosis using EUS-FNA in 6 cases. Bypass or Frey procedure were done in 59 patients (HJA, PJA, Frey). Preoperative tissue sampling was done in 8 (13%) patients and malignancy was suspected in 25%. Intraoperatively, malignancy was confirmed only in one patient assessed as non-malignant in the preoperative period. The clinical course in 3 other patients undergoing HJA, although tumor-free at the time of the surgery, indicated PDAC in CP. Conclusion: The ability to detect malignant cells in a mass in CP remains poor even using all of the available sophisticated methods and the success depends on many variable factors. The rate of "unnecessary" right-sided resections of a mass in CP reached 48% in our patient group, while the rate of resections which should have been performed instead of bypass procedures was 7%. A certain percentage of the so-called excessive pancreatic resections, as well as the failure to perform a resection due to an undetected/unrecognized pancreatic tumor in CP should continue to be expected.

Inferior pancreaticoduodenal artery aneurysm rupture as a cause of haemoperitoneum - case report and review of the literature.

INTRODUCTION: Arterial aneurysms of the pancreaticoduodenal arcade (PDA) represent approximately 2% of all aneurysms of visceral arteries. Despite a low incidence, this group of aneurysms is clinically significant due to its high risk of rupture. CASE REPORT: A 45 years old patient presented with a pancreaticoduodenal arcade aneurysm rupture along with a tight stenosis at the origin of the coeliac trunk. Retrograde blood flow from the superior mesenteric artery (SMA) to the hepatic artery (HA) via PDA limited our therapeutic options due to the necessity to maintain liver perfusion. The patient was indicated for an interventional radiology procedure, which consisted of percutaneous transluminal angioplasty (PTA) with stent placement at the origin of the coeliac trunk and subsequent transarterial embolisation (TAE) - trapping of the aneurysm using coils. Due to clinical signs of the intra-abdominal compartment syndrome, within 24 hours of the radiological treatment, the patient was indicated for surgical revision (laparotomy). During the surgery, no signs of active bleeding were found; coagula were evacuated from the abdominal cavity (800 ml) and laparostomy was performed with a temporary closure using a grid. Final closure of the abdominal cavity was performed on postoperative day 20 from the initial procedure. Follow-up abdominal CT performed 22 months after TAE showed no recurrence of the aneurysm. CONCLUSION: Aneurysm rupture represents a serious case of acute abdomen which requires urgent treatment. The preferred method of treatment for ruptured PDA aneurysms is the endovascular intervention using TAE, which is associated with lower morbidity and mortality than the surgical intervention. Concurrent coeliac trunk stenosis requires consideration given the need to maintain sufficient liver perfusion after TAE of the PDA aneurysm, acting up to this point as a collateral circulation of the liver. The choice of the therapeutic approach should be individualised taking into account the above mentioned recommendations.

Fistuloclysis as a method of nutritional management in a patient with high output enteroatmospheric fistula - a case report.

Enteric fistula is a pathological communication between the small intestine and surrounding tissue. In case of communication with body surface it is called an enterocutaneous or enteroatmospheric fistula. There are many causes of enterocutaneous/enteroatmospheric fistula occurrence. A common result is malnutrition and organ dysfunction which leads to increased morbidity and mortality of the patients. Adequate nutritional support is a very important element in the management of patients with enterocutaneous/enteroatmospheric fistulas. One of the options of nutritional support is fistuloclysis which means administration of enteral nutrition formula to the distal fistula. We present the case of 76-year-old patient with a high-localized and high output enteroatmospheric fistula in whom we were able to reach adequate nutritional status using fistuloclysis, followed by closure of the fistula.

Tumor grade as significant prognostic factor in pancreatic cancer: validation of a novel TNMG staging system.

Aim of the study was to asses the tumor grade prognostic value in the Czech pancreatic cancer patients and to evaluate the accuracy of TNMG prognostic model. Retrospective analysis of 431 pancreatic cancer patients undergoing pancreatic resection in seven Czech oncological centers between 2003 and 2013 was performed. The impact of tumor grade and the accuracy of TNMG prognostic model were evaluated. Lymph node status, tumor size, tumor stage and grade were proved as statistically significant survival predictors. The lower tumor differentiation (grade 3 and 4) was associated with poorer prognosis in all stages (stage I: HR 2.23 [1.14; 4.36, CI 95%] p=0.019, stage II: HR 3.09 [2.01; 4.77, CI 95%] p=0.001, stage III and IV: HR 3.52 [1.73; 7.18, CI 95%] p=0.001). Kaplan-Meier analysis verified statistically significant impact of new TNMG stages on survival after resection for pancreatic cancer (p=0.001). In conclusion, we can state that the tumor grade was confirmed as statistically significant prognostic factor in pancreatic cancer. Its incorporation into the current TNM classification enables more accurate prognosis prediction within particular clinical stages. That is why an inclusion of the grade to the standard TNM classification should be discussed.

[The effect of circulating tumor cells on the survival of patients with pancreatic cancer 5-year results]. / Vliv prukazu cirkulujících nádorových bunek na prezívání pacientu s karcinomem pankreatu - petileté výsledky.

INTRODUCTION: Pancreatic cancer (PDAC) is one of the most aggressive malignancies. Its incidence increases worldwide and, despite the developments in cancer research, mortality rates have not decreased. Poor prognosis of the disease is due to many factors, mainly late diagnosis. Distant metastases and peritoneal carcinomatosis are caused by hematogenous and lymphogenous spreading of the tumorous cells. One of the factors that may influence patient survival are so-called circulating tumor cells (CTCs). The aim of our work was to evaluate the possible influence of CTCs on the survival of patients with PDAC. METHOD: We included patients who underwent a radical or palliative surgical intervention at the First Department of Surgery of Medical Faculty and University Hospital in Olomouc between 1 January 2008 and 31 December 2012. The required samples for CTCs detection were taken from each patient. The detection of the CTCs was performed using real-time RT-PCR. The results were statistically processed and evaluated. RESULTS: We included 126 patients in total, of which 88 were treated radically and 38 received palliative treatment. Mean age was 63 years in patients with radical and 64 years in patients with palliative surgery. Mean survival time in radically treated patients was 29.6 months, in patients with palliative treatment the mean survival time was 8.5 months. The survival time of radically treated patients with CTCs was 27.2 months, without CTCs it was 33.8 months. CONCLUSION: We did not prove a statistically significant difference in survival between radically treated PDAC patients with and without detected CTCs in our work.Key words: pancreatic cancer - circulating tumor cells survival.

[Solid pseudopapillary neoplasms of the pancreas]. / Solidní pseudopapilární tumor pankreatu.

INTRODUCTION: Solid pseudopapillary neoplasm (SPN) is a very rare neoplasm that occurs in girls and young women in 90% of cases; the range is 779 years of age, and the median is 28 years of age. This tumour was first described by Virginia Frantz in 1959 as a papillary cystic tumour of the pancreas. METHODS: The aim of this retrospective study was to analyse the incidence of SPN in all patients with a pancreatic tumour operated at the 1st Dept. of Surgery, University Hospital Olomouc between years 2006 and 2015. Clinical symptoms, imaging methods used, tumour marker positivity, histological findings, postoperative complications and disease-free interval were all evaluated. RESULTS: Of the 454 patients operated on between 20062015, the diagnosis of SPN was made in five female patients. The following imaging methods were used in the preoperative diagnostic process: CT, MRI, PET/CT and endosonography. In four patients the tumour was localised in the tail of the pancreas; these women underwent left-sided pancreatectomy. In one patient, the tumour was located in the pancreatic head and a pylorus-preserving pancreaticoduodenectomy was performed. Complications were seen only in one patient who underwent revision on the first postoperative day for bleeding from the pancreatic cut surface. Pancreatic fistula was not observed in any of the patients. The procedures were considered as sufficient from the oncological viewpoint due to the radical resection procedure and negative resection margin, and therefore no adjuvant oncological treatment was indicated in any of the patients. During the follow-up period, recurrence was not observed in any one of the patients. CONCLUSION: Solid pseudopapillary neoplasm of the pancreas is a rare disorder with a low malignant potential occurring primarily in young women. Generally, SPN has a good prognosis; however, advanced stages of the disease with distant metastases may be encountered in rare cases. The only curative treatment is radical surgical resection.Key words: solid pseudopapillary neoplasm Frantzs tumour pancreas.

[Postpancreatectomy haemorrhage (PPH), prevalence, diagnosis and management]. / Krvácení po pankreatektomii (PPH), prevalence, diagnostika a resení.

INTRODUCTION: Postpancreatectomy haemorrhage (PPH) is considered to be the most severe specific postoperative complication following pancreatic resections and its treatment is difficult and requires coordinated interdisciplinary collaboration. PPH causes 11-38% of all post-pancreatectomy deaths. The aim of this study was to determine the prevalence of PPH in a set of patients operated on within the last 10 years, and to analyze the diagnostic methods, treatment modalities and the outcomes. METHODS: A retrospective analysis of patients undergoing pancreatic resections between 2006 and 2015. Clinically relevant PPH (types B and C) were the subject of interest. The onset, location and severity of PPH were analysed. Other factors analysed included operation diagnosis of PPH, diagnostic methods along with signs of sentinel bleeding, treatment options undertaken including the number of transfusions. 30-day, 90-day and in-hospital mortality, as well as the length of hospital stay and readmission rate were calculated. A descriptive statistical method was used. RESULTS: A total of 449 patients were operated on. Pancreatoduodenectomy (DPE) or pylorus-preserving pancreatoduodenectomy (PPPD) was done in 76.4%, left sided pancreatectomy (LPE) in 19.8% and total pancreatectomy (TPE) in 3.8%. 190 of the patients (42.3%) were women and 259 (57.7%) men, with the mean age of 61.5±11.1 years. A total of 23 (5.1%) PPH cases were identified, 21 (4.7%) were clinically relevant. Eight patients (35%) developed early PPH with direct reoperation, late PPH was seen in 14 patients after DPE and in one after LPE. Sentinel bleeding was present in 53.3% of late PPH cases. CT/CTA was performed in four patients with subsequent DSA performed in three. DSA identified a gastroduodenal artery stump pseudoaneurysm in one patient, which was resolved using a stent. Surgical intervention for late PPH was required in 10 patients in total, six of whom needed direct surgery due to the rapid development of circulatory instability and 3 due to inconclusive radiological management. One patient needed surgical drainage of both an abscess and haematoma. In two patients the origin of bleeding was due to a gastric ulcer, which was proven and solved endoscopically and 2 patients required conservative treatment only. The specific mortality for PPH was 17.4%. In the group of patients that suffered with any PPH following DPE and PPDPE the mortality rate was 22.2%, and 28.6% for late PPH. If late PPH developed coincidentally with postoperative pancreatic fistula (POPF), the mortality was 44%. In the early PPH group, an average of 10.1±2.5 transfusion units (TUs) were used with an average length of hospital stay 17.5±4.8 days and zero mortality in comparison to an average of 11.7±10 TUs and 29.9±14.6 days in hospital and 26.6% mortality in the late PPH group. CONCLUSION: PPH is a severe complication, which has a high mortality rate. It also often coincidentally develops with POPFs. Early clinical diagnosis with identification of its cause plays a key role in management. The use of interventional radiology in the treatment of PPH has begun to dominate other treatment modalities due to a very high success rate, and close collaboration with interventional radiologists is necessary in order to reduce the rate of surgical intervention required in PPH. KEY WORDS: haemorrhage - pancreas - resection - complications - mortality.

[The survival of patients with radically non-resectable pancreatic cancer]. / Prezívání pacientu s radikálne neresekabilním karcinomem pankreatu.

INTRODUCTION: Pancreatic cancer (PDAC) is one of the most aggressive malignancies. Its poor prognosis is due to a combination of various factors, mainly aggressive biology of the tumour, non-specific symptoms in early stages, their underestimation, prolonged time to diagnosis and late onset of treatment. The majority of patients are diagnosed in an advanced stage of the disease. Median survival of these patients ranges from 211 months. The most common consequences of locally advanced disease that require intervention include obstruction of the duodenum and biliary obstruction. The purpose of our study was to analyze the survival of patients with radically inoperable PDAC undergoing palliative surgery or exploration with biopsy, and to evaluate the influence of patient and tumour factors and treatment modalities on survival. METHODS: In our retrospective study we included all patients with radically inoperable PDAC undergoing a non-radical surgical intervention between 01 January 2006 and 31 December 2014. Patient age, histopathological findings, surgical and oncological treatment and survival were included in the analysis. The results were statistically processed and evaluated using IBM SPSS Statistics software version 22 (USA). RESULTS: 184 patients with radically inoperable PDAC, 105 males and 79 females, were included in our study. Mean age of the patients was 64 years and most patients presented with stage IV of the disease. Mean survival time was 7.04 months and median 4.7 months. CONCLUSION: We determined a statistically significant influence of the following factors on patient survival: sex, stage, presence of distant metastases at the time of surgery and oncological treatment administration. Mean and median survival of patients with radically inoperable tumours matches global statistics. KEY WORDS: pancreatic cancer - radically non-resectable - palliative surgery - survival.

[Current status regarding surgical treatment of pancreatic cancer in the Czech Republic]. / Aktuální stav chirurgické lécby karcinomu pankreatu v Ceské republice.

INTRODUCTION: The aim is to map the current situation in the surgical treatment of pancreatic cancer in the Czech Republic. This information has been obtained from surgical treatment providers using a simple questionnaire and by identifying the so called high volume centres. The information has been collected in the interest of organizing and planning research projects in the field of pancreatic cancer treatment. METHOD: We addressed centres known to provide surgical treatment of pancreatic cancer. A simple questionnaire formulated one question about the total number of pancreatic resections, also separately for the diagnoses PDAC - C25, in the last two years (2014 and 2015). Other questions focused on the use of diagnostic methods, neoadjuvant therapy, preoperative assessment of risks, the possibility of rapid intraoperative histopathology examination, Leeds protocol, monitoring of morbidity and mortality including long-term results, and the method of postoperative follow-up and treatment. ÚZIS (Institute of Health Information and Statistics of the Czech Republic) was addressed with a request to analyze the frequency of reported total numbers for DPE, LPE, TPE and to do the same with respect to diagnosis C 25 for the last two years, available for the entire Czech Republic (2013, 2014). RESULTS: Altogether 19 institutions were identified by the preceding audit, which reported more than 10 pancreatic resections annually; these institutions were addressed with the questionnaire. Sixteen institutions responded to the questions, 13 of them completely. CONCLUSION: The majority of potentially radical surgeries for PDAC in the Czech Republic are carried out at 6 institutions. All of the institutions that participated in the survey collect data about morbidity and mortality and monitor their results. KEY WORDS: pancreas cancer outcomes surgery.

[Tumor cells transfer between the patient and laboratory animal as a basic methodological approach to the study of cancerogenesis and identification of biomarkers]. / Transfer nádorových bunek mezi pacientem a laboratorním zvíretem jako základní metodický prístup ke studiu kancerogeneze a identifikace biomarkeru.

INTRODUCTION: The investigation of prognostic and predictive factors for early diagnosis of tumors, their surveillance and monitoring of the impact of therapeutic modalities using hybrid laboratory models in vitro/in vivo is an experimental approach with a significant potential. It is preconditioned by the preparation of in vivo tumor models, which may face a number of potential technical difficulties. The assessment of technical success of grafting and xenotransplantation based on the type of the tumor or cell line is important for the preparation of these models and their further use for proteomic and genomic analyses. METHODS: Surgically harvested gastrointestinal tract tumor tissue was processed or stable cancer cell lines were cultivated; the viability was assessed, and subsequently the cells were inoculated subcutaneously to SCID mice with an individual duration of tumor growth, followed by its extraction. RESULTS: We analysed 140 specimens of tumor tissue including 17 specimens of esophageal cancer (viability 13/successful inoculations 0), 13 tumors of the cardia (11/0), 39 gastric tumors (24/4), 47 pancreatic tumors (34/1) and 24 specimens of colorectal cancer (22/9). 3 specimens were excluded due to histological absence of the tumor (complete remission after neoadjuvant therapy in 2 cases of esophageal carcinoma, 1 case of chronic pancreatitis). We observed successful inoculation in 17 of 28 tumor cell lines. CONCLUSION: The probability of successful grafting to the mice model in tumors of the esophagus, stomach and pancreas is significantly lower in comparison with colorectal carcinoma and cell lines generated tumors. The success rate is enhanced upon preservation of viability of the harvested tumor tissue, which depends on the sequence of clinical and laboratory algorithms with a high level of cooperation.Key words: proteomic analysis - xenotransplantation - prognostic and predictive factors - gastrointestinal tract tumors.

[Proximal gastrectomy for adenocarcinoma of the gastroesophageal junction in a selected set of patients immediate and long-term results]. / Proximální gastrektomie u selektovaných pacientu s adenokarcinomem gastroezofageální junkce, bezprostrední a dlouhodobé výsledky operacní terapie.

INTRODUCTION: The authors present the results of surgical resection in the form of proximal gastrectomy in a selected set of patients with adenocarcinoma of the gastroesophageal junction. The selection criteria included: ASA III-IV, internal comorbidities and elderly patients. METHODS: Between 2007 and 2015, 28 patients with adenocarcinoma of the gastroesophageal junction underwent proximal gastrectomy at the 1st Department of Surgery. The patient set consisted of 19 (67.8%) men and 9 (32.3%) women aged 5289 years with the median age of 72.5 years. Endoscopic examination revealed a tumour of the gastroesophageal junction, which was evaluated according to the Siewert classification: type I was present in 4 (16.7%) cases, type II in 12 (42.3%), and type III in 12 (42.3%). Histological analysis revealed adenocarcinoma in all cases. Proximal gastrectomy with lymphadenectomy was performed in all patients. Splenectomy was performed in eleven patients. The continuity of the gastrointestinal tract was ensured by esophagogastroanastomosis, and pyloromyotomy was performed as a standard procedure. Cryostatic examination revealed positive resection margins in the esophagus in five patients, which led to the resection of the distal esophagus from the right-sided thoracotomy. RESULTS: Injury to the biliary tract was observed in one case in the perioperative period, which was treated by hepaticojejunoanastomosis onto an excluded jejunal loop. The following complications were observed postoperatively: bleeding, respiratory complications, anastomotic dehiscence, laparotomy wound dehiscence, and inflammatory infiltration in the abdominal cavity. Thirty-day mortality was 10.7% in our patient set. CONCLUSION: Proximal gastrectomy with lymphadenectomy is an appropriate alternative for polymorbid patients with adenocarcinoma of the gastroesophageal junction and provides good short- and long-term results.Key words: cancer of gastroesophageal junction proximal gastrectomy complications of therapy.

[Synchronous cancer duplicities of pancreas and stomach/kidney and their surgical treatment]. / Synchronní nádorové duplicity pankreatu a zaludku/ledviny a jejich lécba.

INTRODUCTION: The occurence of synchronous pancreatic cancer and other primary cancer is not frequent and reaches about 5.6% as reported in autoptic studies. Double resections of the pancreas with another organ due to synchronous malignancies have been published only in quite sporadic sets of cases or individual case reports. The authors present three cases of synchronous pancreatic malignancies and stomach or renal cancers treated with surgery, including results and survival. CASES: Three patients with synchronous double cancer were identified in a series of 400 pancreatic resections (20062014). Two patients presented with symptoms of pancreatic periampullary tumors (bile duct obstruction, weight loss and abdominal pain). The second malignancies were identified as incidental during diagnostic work-up (asymptomatic cancer of the stomach, kidney). Pancreatoduodenectomies (PDE) with lymphadenectomies were performed due to ductal adenocarcinomas (pT2N1M0 G3 and pT3N1M0 G2). The second procedures included subtotal gastrectomy with lymphadenectomy (gastric adenocarcinoma pT1N1M0, G2) and nephrectomy (renal papillary carcinoma pT1bN0M0, G3). Postoperative adjuvant chemotherapy with gemcitabine was given in both patients. Survival rates were 12 and 19 months, respectively. The third patient suffered from abdominal pain and weight loss. Diagnostic work-up revealed stomach carcinoma and early pancreatic adenocarcinoma. Double resection - subtotal gastrectomy with lymphadenectomy and pancreatoduodenectomy with lymphadenectomy - was performed. Gastric adenocarcinoma pT2N2M0, G3 and pancreatic ductal papillary-mucinous adenocarcinoma pT2N0M0, G1 were found in the specimens. Adjuvant radiochemotherapy with 5-fluorouracil and leukovorine was given postoperatively. This patient is still alive nearly 5 years after the surgery, without any reccurence. CONCLUSION: The survival of patients with double synchronous pancreatic malignancies and other primary tumors in our set seems to be influenced by the stage and biology of pancreatic cancer. The survival was worse when the duplicity was presented with symptoms of pancreatic cancer. Pancreatic cancer found incidentally when another malignancy is presented has more favourable results.

[Pancreatic metastases--diagnosis, radical surgery, complications and survival]. / Metastázy do pankreatu--diagnostika a moznosti radikální lécby, komplikace, prezívání.

INTRODUCTION: Although generally uncommon, pancreatic metastases are increasingly encountered in clinical practice. The benefit of pancreatic resections in this setting is unclear and still being discussed. Renal cell carcinoma is the most frequent primary tumour metastasing to the pancreas--R0 resections in cases of solitary metastases can be performed. Resections in malignant melanoma and ovarian cancer are rather considered as palliative. The aim of this study is to analyse our own set of patients operated on for metastases into the pancreas and evaluate the results of their surgical treatment. METHODS: We identified the patients operated on for metastases to the pancreas. Patient and tumour characteristics were summarized using descriptive statistics. RESULTS: A total of 9 patients (out of 312 patients undergoing resection for malignancy in the period of 2006-2014) with pancreatic metastases were analysed. All but one were asymptomatic; the symptomatic patient suffered from GI bleeding. All patients had a metachronous lesion with a median length of 12 years (421 years) between the initial operation and pancreatic resection. The most common metastasing tumour was renal cell carcinoma (77%) with the highest incidence occurring at the head of the pancreas (44%). The most frequent procedure used was the pylorus-preserving pancreatic head resection (44%). The median operating time was 247 min, (126375 min). Six patients were complication free, the median of their hospital stay was 9.5 days (812 days). Complications included PPH type C and PF type B both of which required surgical intervention; however, PF type A required no intervention. No postoperative deaths occurred, multiple metastases were found in 4 patients with renal cell carcinoma metastases. The median of follow-up has been 11.5 months, (334 months). CONCLUSION: Survival after pancreatic resections due to renal cell carcinoma is favourable. Mortality is low and morbidity is similar to that associated with pancreatic resections due to other aetiologies, making surgery a valid and safe treatment option. Lifelong follow-up of patients after nephrectomy is advised. Resections in pancreatic metastases of malignant melanoma or ovarian carcinoma are considered as palliative, their indication being individual following interdisciplinary consultation.

[Determination of CEA, EGFR and hTERT expression in peritoneal lavage in patients with pancreatic adenocarcinoma using RT - PCR method]. / Stanovení exprese CEA, EGFR a hTERT v peritoneální lavázi u pacientu s adenokarcinomem pankreatu metodou RT-PCR.

INTRODUCTION: The aim of this study is to assess the significance of CEA, EGFR and hTERT as markers of occult tumor cells for predicting treatment outcomes in pancreatic cancers, as well as determining the cut-off values of these markers individually in peritoneal lavage. METHOD: The study compared 87 patients undergoing palliative operations (bypass surgery, biological sampling for subsequent oncological treatment) for either stage III or IV (UICC) pancreatic ductal adenocarcinomas with a control group of 24 healthy patients. Abdominal cavity lavage was performed at the beginning of the surgery in both groups, using 100 ml of physiological solution (phosphate buffered saline, pH 7.2). The samples were transported in bottles containing 1.5 ml 0.5 M EDTA and 10 ml of fetal bovine serum. Total RNA samples were all processed and purified by reverse transcription. Occult tumor cells in the peritoneal lavage were detected by the real-time RT-PCR method using CEA, EGFR and hTERT as markers of tumor cells. Another aim was to calculate the cut-off values of these markers. Statistical analysis was done using software R (www.r-project.org) and Statistica (StatSoft, Inc. USA). RESULTS: Mean expression of CEA, EGFR and hTERT in peritoneal lavage in the control group was 2501, 716749 and 104 copies of mRNA / mg RNA. Threshold, cut-off values were determined as the "mean + 2 times standard deviation". Absolute expression values were further normalized to expression of the house-keeping gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH). After normalization, cut-off values of the tested markers were 4.89, 115.88 and 0.02 copies of mRNA/GAPDH mRNA. As regards absolute expression of the markers tested, only hTERT was able to statistically significantly (p<0.001) distinguish the analysed groups, where patients with advanced pancreatic adenocarcinoma had a higher expression of hTERT. Absolute expression of CEA or EGFR was not able to discriminate between the two groups. The more accurate normalized expression values of the test markers demonstrated a statistically significantly higher expression of hTERT (p<0.005) and CEA (p<0.001) in patients with advanced adenocarcinoma compared to the control group. CONCLUSION: Absolute hTERT expression in peritoneal lavage of patients with advanced pancreatic cancer was significantly higher compared to the control group.