[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.

Frailty and Constellations of Factors in Aging HIV-infected and Uninfected Women--The Women's Interagency HIV Study.

BACKGROUND: Biological similarities are noted between aging and HIV infection. Middle-aged adults with HIV infection may present as elderly due to accelerated aging or having more severe aging phenotypes occurring at younger ages. OBJECTIVES: We explored age-adjusted prevalence of frailty, a geriatric condition, among HIV+ and at risk HIV- women. DESIGN: Cross-sectional. SETTING: The Women's Interagency HIV Study (WIHS). PARTICIPANTS: 2028 middle-aged (average age 39 years) female participants (1449 HIV+; 579 HIV-). MEASUREMENTS: The Fried Frailty Index (FFI), HIV status variables, and constellations of variables representing Demographic/health behaviors and Aging-related chronic diseases. Associations between the FFI and other variables were estimated, followed by stepwise regression models. RESULTS: Overall frailty prevalence was 15.2% (HIV+, 17%; HIV-, 10%). A multivariable model suggested that HIV infection with CD4 count<200; age>40 years; current or former smoking; income ≤$12,000; moderate vs low fibrinogen-4 (FIB-4) levels; and moderate vs high estimated glomerular filtration rate (eGFR) were positively associated with frailty. Low or moderate drinking was protective. CONCLUSIONS: Frailty is a multidimensional aging phenotype observed in mid-life among women with HIV infection. Prevalence of frailty in this sample of HIV-infected women exceeds that for usual elderly populations. This highlights the need for geriatricians and gerontologists to interact with younger 'at risk' populations, and assists in the formulation of best recommendations for frailty interventions to prevent early aging, excess morbidities and early death.

[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.

[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.

[Surgical therapy of pancreatic cancer - 5 years survival]. / Resekabilní karcinom pankreatu 5leté prezití.

INTRODUCTION: The purpose was to identify 5-year survivors among a group of radically resected patients with pancreatic cancer and analyse the characteristics and factors associated with their 5-year survival. Single tertiary centre experience. METHOD: A prospectively maintained database of 155 pancreatic resections from January 2006 to June 2010 was scanned to identify patients after curative radical resections for pancreatic ductal adenocarcinoma. The clinical and pathological data was analysed retrospectively. The outcomes of the PDAC group were evaluated using Kaplan-Meier analysis (survival) with the Log-rank test and Cox regression analysis (evaluation of prognostic factors). Characteristics of the survivors were discussed. Significance level of 0.05 was used. Those factors were used as independent variables for Cox regression analysis whose significant effect on survival was shown based on Kaplan-Meier analysis. RESULTS: Among 155 patients undergoing a curative pancreatic resection, 73 had a pancreatic ductal adenocarcinoma. Fifteen patients (20.5%) after radical surgery survived over 5 years, 13 of whom are still alive. In the group of the survivors, the mean overall survival was 77.1 months (60110) and the median survival was 74 months. The mean relapse-free interval in the group of the survivors was 63.3 months (14110) with the median of 65 months. Factors associated with a longer survival included the absence of lymph node infiltration (p=0.031), uncomplicated postoperative course (p=0.025), absence of vascular invasion (p=0.017), no blood transfusions (p=0.015) and the use of postoperative therapy - predominantly chemotherapy (p=0.009). Significant independent predictors of survival included vascular invasion HR=2.239 (95%CI: 1.0934.590; p=0.028), postoperative chemotherapy HR=2.587 (95%CI: 1.3015.145; p=0.007) and blood transfusion HR=2.080 (95%CI: 1.0274.212; p=0.042). The risk of death was increased 2.2 times in patients with vascular invasion, 2.1 times in patients with transfusions, and finally 2.6 times in those with no chemotherapy. CONCLUSION: Factors associated with an improved overall survival included: the absence of lymph node infiltration, an uncomplicated postoperative course, absence of vascular invasion, no need of blood transfusions, and finally the use of postoperative chemotherapy. Vascular invasion, use of blood transfusions and postoperative adjuvant chemotherapy were significant independent prognostic factors of survival.

[The importance of endosonography in preoperative management of patients with pancreatic head carcinoma]. / Význam endosonografie v predoperacním managementu nemocných s karcinomem hlavy pankreatu.

INTRODUCTION: Pancreatic ductal cancer remains a devastating disease with an urgent need for improved diagnostics and new treatment strategies. It has no early specific symptoms, shows rapid progression and is practically undiagnosable in the early stage. Survival of radically operated patients is rather unsatisfactory. Nonetheless, only radical surgical resection offers potentially curative treatment. MATERIAL AND METHODS: The authors present a set of 70 patients (2009-2011) who underwent radical surgery - pancreatic head resection - for ductal pancreatic head adenocarcinoma. A retrospective study analyzes the accuracy of T-staging using preoperative CT and EUS. RESULTS: In 21 (30%) patients, CT did not prove pathology in the head of the pancreas. Subsequent endosonography revealed a mass in the head of the pancreas in 88% of patients with negative CT scans. The conformity of CT (detection of the mass) with the histopathological finding was detected in 68.2% of cases, 95% CI for compliance: 55.6%-79.1%. The conformity of endosonography (detection of the mass) with the histopathological finding was detected in 96.0% of cases, 95% CI for compliance: 86.3%-99.5%. The conformity between CT and endosonography was found in 68.8% of cases, 95% CI for compliance: 53.8%-81.3%. The conformity of preoperative CT staging and final histopathological staging was observed in 18.2% of cases, 95% CI for compliance: 9.8%-29.6%. The conformity of preoperative endosonography staging and final histopathological staging was seen in 42.0% of cases, 95% CI for compliance: 28.2%-56.8%. The conformity of accuracy of preoperative CT staging and endosonography staging was detected in 37.5% of cases, 95% CI for compliance: 23.9%-52.7%. In 58.3% of cases, endosonography compared with CT findings evaluated higher T stage (p = 0.001). CONCLUSION: Pancreatic head carcinoma presents mostly with obstructive jaundice. CT diagnosis of small tumours often fails. Subsequent endosonography in case of a negative CT usually contributes significantly to the final diagnosis and helps determine the indication for surgery. EUS is more accurate than CT in showing the tumour mass in the pancreatic head. In our group EUS revealed the mass in 96% of patients versus 68% in CT. When evaluating the staging, CT is accurate only in 18.2% of patients, EUS in 42% of patients. Both methods, EUS and particularly CT, underestimate the actual final T-staging of the disease.