Clear cell renal carcinoma metastases to the pancreas.

INTRODUCTION: To date, clear cell renal carcinoma (Grawitz tumour) remains the most frequent malignant tumour of the kidney in adults. It metastasises in more than 25% of cases, most frequently to the bones (osteolytic metastases), lungs, brain, liver, adrenal glands and the contralateral kidney. Metastases to the pancreas are rare and represent 1-4% of all malignant tumours of the pancreas. METHODS: This is a retrospective analysis of patients who were operated at the Department of Surgery in Pilsen between 2010 and 2018 for histologi-cally verified metastasis of clear cell carcinoma (Grawitz tumour) to the pancreas. RESULTS: We operated 12 patients (8 men and 4 women). The metastases appeared on average 8 years and 8 months following the primary urolo-gical surgery. The mean age of the male patients was 66.5 years and that of the female patients was 67.4 years. In our sample, the diagnostic specificity of the CT scan was 50%, the diagnostic specificity of endoscopic ultrasound (EUS) was 75% and subsequent EUS-guided fine needle aspiration biopsy performed in 100% of cases yielded a specificity of 75%. Resectability was 92%. The average length of hospitalisation was 11.5 days. Post-operative complications according to Clavien-Dindo were grade 1 in 66%, grade 2 in 1.25% and grade 5 in 8.3% of the cases. The 30-day post-operative mortality was 8.3% (one patient).  Conclusion: Clear cell renal carcinoma metastases to the pancreas are very rare. However, if radically removed, the patient has a good prognosis with regards to long-term survival.

Madelungs disease - a case report.

INTRODUCTION: Madelungs disease is a rare illness manifested by the uncontrollable proliferation of unencapsulated adipose tissue which accumulates symmetrically in the hypodermis in the area of the neck, shoulders, back and thighs. As part of differential diagnosis it is necessary to investigate tumours in the area of the neck, dysfunction of the thyroid gland, Cushings syndrome and rare lipomatosis. CASE REPORT: In the case report, the authors present the case of a 52-year-old male patient with a large formation on the neck, trunk and the scrotal area. A suspicion of liposarcoma was expressed based on the imaging examinations performed. RESULTS: Excisions of tumorous loci on several occasions were indicated for the patient. Lipomas without abnormalities were proven in all histolo-gical examinations. CONCLUSION: The diagnosis of Madelungs disease is based on the clinical findings, imaging (computed tomography CT, magnetic resonance imaging MRI) and biopsy examination. Laboratory methods tend to focus rather on associated internal diseases. Treatment is only symptomatic and consists in surgical removal of the foci. However, it is often associated with the risk of recurrence.

[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.

Cardiorespiratory fitness attenuates risk for major adverse cardiac events in hyperlipidemic men and women independent of statin therapy: The Henry Ford ExercIse Testing Project.

AIMS: We sought to evaluate the effect of cardiorespiratory fitness (CRF) in predicting mortality, myocardial infarction (MI), and revascularization in patients with hyperlipidemia after stratification by gender and statin therapy. METHODS AND RESULTS: This retrospective cohort study included 33,204 patients with hyperlipidemia (57 ± 12 years old, 56% men, 25% black) who underwent physician-referred treadmill stress testing at the Henry Ford Health System from 1991 to 2009. Patients were stratified by gender, baseline statin therapy, and estimated metabolic equivalents from stress testing. We computed hazard ratios using Cox regression models after adjusting for demographics, cardiac risk factors, comorbidities, pertinent medications, interaction terms, and indication for stress testing. RESULTS: There were 4,851 deaths, 1,962 MIs, and 2,686 revascularizations over a median follow-up of 10.3 years. In men and women not on statin therapy and men and women on statin therapy, each 1-metabolic equivalent increment in CRF was associated with hazard ratios of 0.86 (95% CI 0.85-0.88), 0.83 (95% CI 0.81-0.85), 0.85 (95% CI 0.83-0.87), and 0.84 (95% CI 0.81-0.87) for mortality; 0.93 (95% CI 0.90-0.96), 0.87 (95% CI 0.83-0.91), 0.89 (95% CI 0.86-0.92), and 0.90 (95% CI 0.86-0.95) for MI; and 0.91 (95% CI 0.88-0.93), 0.87 (95% CI 0.83-0.91), 0.89 (95% CI 0.87-0.92), and 0.90 (95% CI 0.86-0.94) for revascularization, respectively. No significant interactions were observed between CRF and statin therapy (P > .23). CONCLUSION: Higher CRF attenuated risk for mortality, MI, and revascularization independent of gender and statin therapy in patients with hyperlipidemia. These results reinforce the prognostic value of CRF and support greater promotion of CRF in this patient population.

Implementation of the integrated management of childhood illness with parasitological diagnosis of malaria in rural Ghana: health worker perceptions.

BACKGROUND: Timely and appropriate management of febrile illness among children under five years of age will contribute to achieving Millennium Development Goal-4. The revised World Health Organization-Global Malaria Programme's policy on test-based management of malaria must integrate effectively into the Integrated Management of Childhood Illness (IMCI). This study reports on perceptions of health workers on the health system factors influencing effective delivery of test-based diagnosis of malaria with IMCI. METHODS: A qualitative study was conducted among a range of health workers at different levels of the health system in the Brong Ahafo Region of Ghana. Interview transcripts were transferred into Nvivo 8 software for data management and analysis. A frame-work approach at two levels was used in the analysis, which included the processes required for implementation of test-based management of malaria and the health systems context. RESULTS: Forty-nine in-depth interviews were conducted. The National Health Insurance Scheme (NHIS) was perceived to have led to an increase in health facility attendance, thereby increasing the workload of health workers. Workload was reported as the main reason that health workers were not able to complete all of the examinations included in the IMCI algorithm. The NHIS financing guidelines were seen to be determining diagnosis and treatment practices by health-care givers. Concern was expressed about the erratic supply of malaria rapid diagnostic test kits (RDTs), the quality of RDTs related to potential false negative results when clinical symptoms were consistent with malaria. IMCI was seen as important but practically impossible to fully implement due to workload. CONCLUSIONS: Implementation of the WHO-revised IMCI guideline is confronted with a myriad of health systems challenges. The perceptions of front-line health workers on the accuracy and need for RDTs together with the capacity of health systems to support implementation plays a crucial role. The NHIS financing guidelines of diagnostics and treatments are influencing clinical decision-making in this setting. Further study is needed to understand the impact of the NHIS on the feasibility of integrating test-based management for malaria into the IMCI guidelines.

[Malignant mesothelioma in the peritoneal cavity - a case report]. / Maligní mezoteliom v peritoneální dutine - kazuistika.

Malignant mesothelioma is a rare tumour with an incidence of 0.53 cases per million inhabitants. Only about 20% of cases occur in the peritoneum. The authors use the case report of a male patient with malignant mesothelioma occurring in the peritoneal cavity to demonstrate the difficulty of preoperative diagnosis: preoperative examinations made the authors consider a primary liver tumour and only definitive histological examination revealed the diagnosis. The discussion deals with the epidemiology, diagnosis and treatment of this rare disease and underlines the unique role of surgical therapy in its management.

[Chronic abdominal pain with a rare cause]. / Chronické bolesti bricha s raritní prícinou.

The authors use a case report of a female patient with chronic abdominal pain progressing postprandially as an example to demonstrate the complexity of the diagnostic process in patients with these complaints, as well as a surprising peroperative finding in which a small neuroendocrine tumour of the small intestine was the cause of the difficulties. The ensuing discussion also deals with other possible causes of chronic abdominal pain associated with eating disorders.

[Quality of life is an important factor in the indication in patients with advanced pancreatic carcinoma--a prospective multicentric study]. / Kvalita zivota je dulezitým faktorem indikacní rozvahy u nemocných s pokrocilým karcinomem pankreatu--multicentrická prospektivní studie.

INTRODUCTION: The aim of this report is to present results of prospective multicentric study on quality of life (QoL) in advanced ductal pancreatic adenocarcinoma patients. MATERIAL AND METHOD: In 426 patients with advanced ductal pancreatic adenocarcinoma, the following parameters were studied: type of treatment, complication rates, 1, 2 and 3-year survival rates. QoL was assessed in 151 patients, using a generic SF-36 questionnaire prior the therapy and then 3 months after the treatment. Arithmetic mean and standard deviation (SD) were used for the QoL pool analysis. The results were evaluated using SF-36 software, t-test for independent samples, ANOVA, paired t-test and SPSS 19.0.1 (IBM Corporation, 2010). The p value < 0.05 was considered as statistically significant. RESULTS: There was a significant difference in the median, 1,2 and 3-year survival rates in the patients with stage III pancreatic cancer who underwent radical resection (RR) compared to the paliative therapy patients (p < 0.001). The highest initial overal QoL value was observed in 39 stage III patients who underwent RR (60.5 +/- 1.84) and no significant decrease in this value was recorded over a 3-month postoperative period (difference--5.1 +/- 16.6, p = 0.064). Paliative therapy resulted in significant reduction in the overall QoL value (p = 0.020). In the paliative therapy group of patients, BDA resulted in significant reduction in the overall QoL value 3 months after the procedure (p = 0.017 vs. ns.). In the group of stage IV patients, nonsignificant increase in the overall QoL value was recorded in 8 patients 3 months after BDA (46.4 +/- 17.0 vs. 51.1 +/- 9.5 p = 0.525). Nonsignificant increase in the overal QoL values was also observed in 18 patients after stent introduction (30.6 +/- 8.3 vs. 31.5 +/- 8.5 p = 0.783). Nonsignificant deterioration in QoL was recorded in patients undergoing exploration, whose initial QoL values corresponded with those in RR patients, while 3 months after the explorative surgery their QoL values were similar to those recorded in the stent group patients (62.0 +/- 16.1 vs. 41.7 +/- 23.6 s rozdílem -20.3 +/- 16.2 p < 0.001). CONCLUSION: Based on the results of the multicentric prospective study in patients with locally advanced stage III and IV ductal pancreatic adenocarcinoma, the following conclusions can be presented: (1) median and 1, 2 and 3-year survival rates in stage III patients were significantly higher in the RR group compared to the paliative therapy patients, (2) initial QoL in stage III patients was significantly the highest in patients who underwent RR. Significant decrease in QoL was recorded in BDA patients. Paliative stent introduction resulted in nonsignificant improvement in the QoL 3 months after the procedure, while the initial QoL values were the lowest in this group, (3) QoL assessment in stage IV patients showed statistically nonsignificant improvement after BDA or stent procedures, the most significant deterioration was observed in the exploration group, (4) no complication which would result in prolongation of the respective hospitalization times was recorded in 67%, (5) early postoperative complications did not result in significant QoL deterioration 3 months after the procedure, (6) absence of chemotherapy results in significant decrease in QoL.

[Pancreatic trauma]. / Poraneni slinivky brisní.

Injuries to the pancreas are relatively rare, occurring in around 10% of case involving serious trauma to the abdominal cavity, with 65% of such injuries resulting trauma occurs only exceptionally, involving only 5% of all injuries. The mortality of this entity is influenced by many factors, especially the age of the injured person, the seriousness of the injury, the duration of the shock, the potentially associated trauma, early diagnosis and correct selection of suitable treatment. The authors present here 4 case reports describing injuries to the pancreas and documenting the diagnostic and therapeutic approaches in cases of this very serious trauma.

Deficiencies of human complement component C4A and C4B and heterozygosity in length variants of RP-C4-CYP21-TNX (RCCX) modules in caucasians. The load of RCCX genetic diversity on major histocompatibility complex-associated disease.

The complement component C4 genes located in the major histocompatibility complex (MHC) class III region exhibit an unusually complex pattern of variations in gene number, gene size, and nucleotide polymorphism. Duplication or deletion of a C4 gene always concurs with its neighboring genes serine/threonine nuclear protein kinase RP, steroid 21-hydroxylase (CYP21), and tenascin (TNX), which together form a genetic unit termed the RCCX module. A detailed molecular genetic analysis of C4A and C4B and RCCX modular arrangements was correlated with immunochemical studies of C4A and C4B protein polymorphism in 150 normal Caucasians. The results show that bimodular RCCX has a frequency of 69%, whereas monomodular and trimodular RCCX structures account for 17.0 and 14.0%, respectively. Three quarters of C4 genes harbor the endogenous retrovirus HERV-K(C4). Partial deficiencies of C4A and C4B, primarily due to gene deletions and homoexpression of C4A proteins, have a combined frequency of 31.6%. This is probably the most common variation of gene dosage and gene size in human genomes. The seven RCCX physical variants create a great repertoire of haplotypes and diploid combinations, and a heterozygosity frequency of 69.4%. This phenomenon promotes the exchange of genetic information among RCCX constituents that is important in homogenizing the structural and functional diversities of C4A and C4B proteins. However, such length variants may cause unequal, interchromosomal crossovers leading to MHC-associated diseases. An analyses of the RCCX structures in 22 salt-losing, congenital adrenal hyperplasia patients revealed a significant increase in the monomodular structure with a long C4 gene linked to the pseudogene CYP21A, and bimodular structures with two CYP21A, which are likely generated by recombinations between heterozygous RCCX length variants.

[Small intestine invagination in an adult]. / Invaginace tenkého streva v dospelosti.

Bowel intussusception in adulthood is relatively rare. It is the cause of bowel movement disorders in around 1-5% of cases. In contrast to intussusception in childhood, where the cause is usually unclear, in adulthood the unequivocal causes are known in 70-90% of cases. These predominantly include benign tumours of the small intestine. The authors describe 2 case reports, where small bowel intussusception was the cause of the bowel movement disorder and non-specific abdominal pain. This clinical entity must be kept in mind as the possible cause of non-specific abdominal pain in adulthood. If a malignancy is suspected, then the rules of oncological surgery should be followed.

Triptorelin 6-month formulation in the management of patients with locally advanced and metastatic prostate cancer: an open-label, non-comparative, multicentre, phase III study.

BACKGROUND AND OBJECTIVES: Triptorelin 6-month formulation was developed to offer greater convenience to both patients and physicians by reducing the injection frequency. The efficacy, pharmacokinetics and safety of a new 6-month formulation of triptorelin were investigated over 12 months (48 weeks). The primary objective was to evaluate the formulation in achieving castrate serum testosterone levels (< or = 1.735 nmol/L or < or = 50 ng/dL) on day 29 and in maintaining castration at months 2-12. Absence of luteinizing hormone (LH) stimulation and change in prostate-specific antigen (PSA) level were also assessed. METHODS: An open-label, non-comparative, phase III study in 120 patients with advanced prostate cancer was conducted from July 2006 to August 2007 in private and public institutions in South Africa. Each patient received two consecutive intramuscular injections of triptorelin embonate (pamoate) 22.5 mg at an interval of 24 weeks. In all patients, testosterone (primary outcome measurement) was measured at baseline and then every 4 weeks; LH was measured before and 2 hours after the two injections. PSA was measured on day 1 and at weeks 12, 24, 36 and 48. Adverse events were recorded at each visit. RESULTS: In the intent-to-treat population, 97.5% (95% CI 92.9, 99.5) of patients achieved castrate serum testosterone levels by day 29, and 93.0% (95% CI 86.8, 97.0) maintained castration at months 2-12. After the second injection, 98.3% of patients showed absence of LH stimulation. The most frequent drug-related adverse events were hot flushes (71.7% of patients). No patient withdrew from the study as a result of an adverse event. CONCLUSIONS: The triptorelin 6-month formulation was well tolerated and was able to achieve and maintain castration for the treatment of locally advanced and metastatic prostate cancer. By reducing the frequency of required injections, this new formulation offers a more convenient treatment regimen. (Clinical Trial Registration,NCT00751790 at www.clinicaltrials.gov).

[Significance of the TPS cytokeratin marker in the postoperative follow up of colorectal carcinoma patients]. / Význam cytokeratinového markeru TPS v pooperacním sledováiní nemocných s kolorektálním karcinomem.

AIM: Examination of tumour markers conducive to follow up of the patients with colorectal carcinoma. MATERIAL AND METHODS: The tumour markers were examined in the population of patients with primarily established and histologically verified colorectal adenocarcinoma. RESULTS: The resection therapy resulted in the decrease in post-operative CEA levels. There were no changes in pre- and post-operative CA 19-9 levels; unlike with post-operative TPS levels having been significantly increased, probably due to reparation processes resulting from the surgery. It can be concluded that pre- and post-operative CEA levels are the most suitable markers to check the effect of surgery. With a 95%-specificity for the establishment of recidives, the highest sensitivity was reached with TPS (83%); the sensitivities of the classical tumour markers CEA and CA 19-9 were significantly lower (41% and 25%, respectively). The results should be interpreted with caution due to a small number of relapses regarding a short follow up and rather local-regional character of the recidives. CONCLUSION: However, TPS seems to be a promising marker for the follow up of the patients with colorectal carcinoma. Thus, an ideal combination seems to be that of CEA and TPS.

Antibody Reactivity to Merozoite Antigens in Ghanaian Adults Correlates With Growth Inhibitory Activity Against Plasmodium falciparum in Culture.

BACKGROUND: Plasmodium falciparum uses a repertoire of merozoite-stage proteins for invasion of erythrocytes. Antibodies against some of these proteins halt the replication cycle of the parasite by preventing erythrocyte invasion and are implicated as contributors to protective immunity against malaria. METHODS: We assayed antibody reactivity against a panel of 9 recombinant antigens based on erythrocyte-binding antigen (EBA) and reticulocyte-like homolog (Rh) proteins in plasma from children with malaria and healthy adults residing in 3 endemic areas in Ghana using enzyme-linked immunosorbent assay. Purified immunoglobulin (Ig)G from adult plasma samples was also tested for invasion inhibition against 7 different P falciparum culture lines, including clinical isolates. RESULTS: Antibodies against the antigens increased in an age-dependent manner in children. Breadth of reactivity to the different antigens was strongly associated with in vitro parasite growth inhibitory activity of IgG purified from the adults. The strongest predictors of breadth of antibody reactivity were age and transmission intensity, and a combination of reactivities to Rh2, Rh4, and Rh5 correlated strongly with invasion inhibition. CONCLUSIONS: Growth inhibitory activity was significantly associated with breadth of antibody reactivity to merozoite antigens, encouraging the prospect of a multicomponent blood-stage vaccine.

Microchimerism of maternal origin persists into adult life.

Recent studies indicate that fetal cells persist in maternal blood for decades after pregnancy. Maternal cells are known to engraft and persist in infants with immunodeficiency, but whether maternal cells persist long-term in immunocompetent offspring has not specifically been investigated. We developed sensitive human leukocyte antigen-specific (HLA-specific) PCR assays and targeted nonshared maternal HLA genes to test for persistent maternal microchimerism in subjects with scleroderma and in healthy normal subjects. Nonshared maternal-specific DNA was found in 6 of 9 scleroderma patients. In situ hybridization with double labeling for X and Y chromosome-specific sequences revealed female cells in peripheral blood samples from 2 male scleroderma patients. HLA-specific PCR also frequently revealed persistent maternal microchimerism in healthy control subjects. The mean age of all subjects with maternal microchimerism was 28 years (range: 9-49 years). With few exceptions, mothers of subjects with persistent maternal microchimerism were HLA incompatible with subjects for class I and class II alleles. These results clearly indicate that HLA-disparate maternal cells can persist in immunocompetent offspring well into adult life. The biological significance of maternal microchimerism and whether it might contribute to autoimmune disease requires further investigation.

Prognostic importance of thymidine kinase in colorectal and breast cancer.

BACKGROUND: Thymidine kinase (TK) plays an essential role in the processing of thymidine within the cell and therefore it is an important marker of proliferation, particularly in tumor cells. The aim of our study was to determine the diagnostic, prognostic and predictive importance of TK measurement in cancer. PATIENTS AND METHODS: TK was measured using radioreceptor analysis (RRA) with Immunotech assay kits. The serum level of TK was measured in 1087 patients with malignant disease (355 patients with hematology malignancies and 732 patients with solid tumors). RESULTS: Serum levels of TK were significantly elevated in inflammatory and immunological diseases in comparison with healthy individuals. Malignant diseases were associated with elevated serum levels of TK only in particular cases (e.g. hematological malignancies, cervical cancer). This marker has a high sensitivity for use as a primary diagnostic tool. It also has a high sensitivity during the follow-up period in breast and colorectal cancer for the prediction of relapse at the time of primary diagnosis and 3 months earlier than the diagnosis of relapse by imaging methods. CONCLUSION: TK represents a secondary tumor marker which is particularly useful for cancer disease monitoring. Interpretation of this marker must be performed only in association with evaluation of clinical status since all other possible non-specific causes (inflammatory or immunological diseases) of elevated serum levels must be excluded.

Clinicopathological assessment and quantitative estimation of the matrix metalloproteinases MMP-2 and MMP-7 and the inhibitors TIMP-1 and TIMP-2 in colorectal carcinoma tissue samples.

BACKGROUND: The matrix metalloproteinases (MMP) are a family of proteolytic enzymes involved in tumor growth and in the process of invasion. The aim of our study was to test the levels of MMP-2, MMP-7, and the MMP inhibitors TIMP-1 and TIMP-2 mRNA in colorectal carcinoma tissue samples with the clinicopathological status of the disease. PATIENTS AND METHODS: Colorectal carcinoma tissue samples were obtained from 38 patients who underwent resection of colorectal carcinoma. The expression levels of mRNA of MMP-2, MMP-7, TIMP-1, TIMP-2 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a housekeeping gene were quantified in these tissue samples using the method of reverse transcription real-time PCR. RESULTS: It was found that the levels of mRNA expression of MMP-2, TIMP-2, MMP-7 and TIMP-1 were significantly higher in tumor tissue samples than in the normal colorectal tissue (p < 0.0020, p < 0.0467, p < 0.0007 and p < 0.0003 respectively). The level of mRNA expression of MMP-2, MMP-7, TIMP-2 and TIMP-1 did not correlate with the stage of the disease, localization of the tumor, metastatic spread or with disease-free survival (DFI). We recorded a statistically significant inverse negative correlation (r = -0.85; p < 0.0001) between the levels of MMP-7 mRNA and TIMP-2 mRNA. Correlations between the values of mRNA MMP-7 vs. TIMP-1, MMP-2 vs. TIMP-2, MMP-2 vs. TIMP-1 and MMP-2 vs. MMP-7 were not statistically significant. CONCLUSION: We found that there were statistically significant differences in the levels of MMP-2, MMP-7, TIMP-1, TIMP-2 mRNA between normal colorectal tissue and tumor tissue, but we did not find any statistically significant correlation between mRNA levels of MMP-2, MMP-7, TIMP-1, TIMP-2 expression and localization of tumor, clinical stage or course of disease. We found an inverse negative statistically significant correlation between mRNA levels of MMP-7 and TIMP-2. On the basis of these results the clinical use of this approach to the determination of a prognosis is ambiguous.