Robert Król

NBL1 and anillin (ANLN) genes over-expression in pancreatic carcinoma

The aim of the study was to analyze the gene expression profile of pancreatic cancer to derive novel molecular markers of this malignancy. The snap-frozen or RNA-later preserved samples of 18 pancreatic adenocarcinomas, 5 chronic pancreatitis cases and 6 specimens of grossly normal pancreas were used for microarray analysis by HG-U133 Plus 2.0 oligonucleotide Affymetrix arrays. Validation was carried out by real-time quantitative PCR (Q-PCR) in the set of 66 samples: 31 of pancreatic cancer, 14 of chronic pancreatitis and 21 of macroscopically unchanged pancreas. By Principal Component Analysis of the microarray data we found a very consistent expression pattern of normal samples and a less homogenous one in chronic pancreatitis. By supervised comparison (corrected p-value 0.001) we observed 11094 probesets differentiating between cancer and normal samples, while only seventy six probesets were significant for difference between cancer and chronic pancreatitis. The only gene occurring within the best 10 genes in both comparisons was S100 calcium binding protein P (S100P), already indicated for its utility as pancreatic cancer marker by earlier microarray-based studies. For validation we selected two genes which appeared as valuable candidates for molecular markers of pancreatic cancer: neuroblastoma, suppression of tumorigenicity 1 (NBL1) and anillin (ANLN). By Q-PCR, we confirmed statistically significant differences in these genes with a 9.5 fold-change difference between NBL1 expression in cancer/normal comparison and a relatively modest difference between cancer and pancreatitis. For ANLN even more distinct differences were observed (cancer/normal 19.8-fold, cancer/pancreatitis 4.0-fold). NBL1 and anillin are promising markers for pancreatic carcinoma molecular diagnostics.

Neuroendocrine neoplasms of the small intestine and the appendix — management guidelines (recommended by the Polish Network of Neuroendocrine Tumours)

We present revised Polish guidelines regarding the management of patients harbouring neuroendocrine neoplasms (NENs) of the small intestine and appendix. The small intestine, especially the ileum, is the most common origin of these neoplasms. Most of them are well differentiated with slow growth. Rarely, they are less differentiated, growing fast with a poor prognosis. Since symptoms can be atypical, the diagnosis is often accidental. Typical symptoms of carcinoid syndrome occur in less than 10% of patients. The most useful laboratory marker is chromogranin A; 5-hydroxyindoleacetic acid is helpful in the monitoring of carcinoid syndrome. Ultrasound, computed tomography, magnetic resonance imaging, colonoscopy, video capsule endoscopy, balloon enteroscopy and somatostatin receptors scintigraphy are used in the visualisation. A histological report is crucial for the proper diagnostics and therapy of NENs, and it has been extensively described. The treatment of choice is surgery, either radical or palliative. Somatostatin analogues are crucial in the pharmacological treatment of the hormonally active and non-active small intestine NENs and NENs of the appendix. Radioisotope therapy is possible in patients with a good expression of somatostatin receptors. Chemotherapy is not effective in general. Everolimus therapy can be applied in patients with generalised NENs of the small intestine in progression and where there has been a failure or an inability to use other treatment options. Finally, we make recommendations regarding the monitoring of patients with NENs of the small intestine and appendix.

Impact of Pancreas Transplantation on the Quality of Life of Diabetic Renal Transplant Recipients

UNLABELLED Simultaneous pancreas and kidney transplantation (SPKT) is considered to be the best method of treatment for patients with chronic renal failure (CRF) resulting from insulin-dependent diabetes mellitus (IDDM). The aim of the study was to compare the quality of life (QOL) of patients with IDDM and CRF subjected to SPK or kidney transplantation alone (KTA). MATERIALS AND METHODS We analyzed 21 patients after SPKT with good function of both grafts. The results were compared with 17 patients with functioning kidney grafts. Minimal observation time was 6 months. QOL was evaluated using Kidney Disease and Quality of Life Short Form (KDQOL-SF), which was sent to recipients by post. Results were presented as medians and interquartile ranges of calculated scored KDQOL-SF points. RESULTS Observation time was 30 months (range, 6-85). Analyzed groups did not differ as regards patient age at transplantation or duration of diabetes and dialysis treatment before transplantation. After SPKT patients reported higher QOL compared with KTA as regards symptom/problem list, 90.91 (86.36-95.46) versus 84.09 (75.00-90.91; P = .04), effects of kidney disease, 90.63 (84.38-93.75) versus 81.25 (68.75-82.14; P = .001); cognitive function, 93.33 (86.67-100.00) versus 80.00 (73.33-93.33; P = .03); overall health, 80.00 (70.00-90.00) versus 50.00 (50.00-70.00; P = .001); physical functioning, 90.00 (75.00-100.00) versus 80.00 (55.00-85.00; P = .03); and pain, 100.00 (90.00-100.00) versus 67.50 (45.00-90.00; P = .005), respectively. CONCLUSION SPKT had a positive impact on selected parameters of QOL among patients with IDDM and CRF compared to KTA.

Risk Factors for Early Hemorrhagic and Thrombotic Complications After Kidney Transplantation

INTRODUCTION Clotting disturbances resulting from chronic renal failure do not remit immediately after successful kidney transplantation (KTx). Hemorrhagic and thrombotic complications after KTx increase the risk of transplanted kidney loss. The aim of the study was to analyze the influence of clotting system disturbances and applied antithrombotic prophylaxis on the development of hemorrhagic and thrombotic complications among KTx patients in the early postoperative period. MATERIALS AND METHODS Sixty seven KTx patients underwent measurement of plasma activated partial thromboplastin time (APTT); international normalized ratio; fibrinogen and D-dimer concentration; activity of antitrombin III; protein C and S, VIII, IX; and von Willebrand factors, as well as platelet counts. RESULTS A perigraft hematoma developed in 25.4% patients, of whom 4.5% required reoperation. Lower antithrombin III activity (96.2±27.6 vs 112.3±17.4, P=.02) on postoperative day (POD) 7 and higher fibrinogen concentration (4.41±2.03 vs 3.35±0.87, P=.01) and platelet count (269.8±117.5 vs 215.8±64.8, P=.03) on POD 14 were noted in recipients with a hematoma compared to those free of this complication. A perigraft hematoma developed in 57.9% patients undergoing antithrombotic prophylaxis and in 12.5% without this treatment (P=.0002). Among patients receiving unfractionated heparin, we observed extension of APTT on POD 1 (45.9±53.2 vs 30.9±7.5 seconds, P=.04), higher von Willebrand factor activity on POD 7 (348.8±122.2 vs 218.5±125.5, P=.02), and higher D-dimer concentrations POD 7 and 14 (1662±894 vs 757±708, P=.002 and 1614±1372 vs 672±532, P=.003, respectively). No significant differences were observed as regards to analyzed parameters between patients receiving low-molecular-weight heparin versus those not receiving antithrombotic prophylaxis. CONCLUSIONS Disturbances in analyzed parameters of hemostasis did not increase the risk of hemorrhagic and thrombotic complications in the early period after KTx. Antithrombotic prophylaxis increases the risk of hemorrhagic complications and should be introduced only for selected renal transplant recipients.

Diagnostic and therapeutic guidelines for gastro-entero-pancreatic neuroendocrine neoplasms (recommended by the Polish Network of Neuroendocrine Tumours)

An increased interest in gastro-entero-pancreatic neuroendocrine neoplasms (GEP NENs) has recently been observed. These are rare neoplasms and their detection in recent years has improved. Over 50% of GEP NENs are carcinoids, and they are usually found incidentally during surgery in the small intestine and appendix and at diagnosis in distant metastases, mainly to the liver. There is a need for co-operation between specialists in various disciplines of medicine in order to work out the diagnostic and therapeutic guidelines. In this publication, we present general recommendations of the Polish Network of Neuroendocrine Tumours for the management of patients with GEP NENs, developed at the Consensus Conference which took place in Kamień Śląski in April 2013. Members of the guidelines working groups were assigned sections of the 2008 guidance to update. In the subsequent parts of this publication, we present the rules of diagnostic and therapeutic management of: - neuroendocrine neoplasms of the stomach and duodenum (including gastrinoma); - pancreatic neuroendocrine neoplasms; - neuroendocrine neoplasms of the small intestine and the appendix; - colorectal neuroendocrine neoplasms. The proposed recommendations by Polish and foreign experts representing different fields of medicine (endocrinology, gastroenterology, surgery, oncology, nuclear medicine and pathology) will be helpful in the diagnosis and treatment of GEP NENs patients.

Donor-Dependent Risk Factors for Early Surgical Complications After Simultaneous Pancreas-Kidney Transplantation

INTRODUCTION The success of simultaneous pancreas-kidney transplantation (SPK) depends in a large degree on avoidance of surgical complications in the early postoperative period. The aim of the study was to analyze the Pre-procurement Pancreas Allocation Suitability Score (P-PASS) and the deceased donor parameters included within it as risk factors for early surgical complications after SPK. MATERIAL AND METHODS Forty-six consecutive donors whose kidney and pancreas were simultaneously transplanted were included in the study. RESULTS Donor age was older among recipients who lost their pancreatic grafts: 30.4±6.9 versus 24.1±6.9 years. Donor age was also older among recipients who lost their pancreatic grafts or died compared with those discharged with a functioning graft: 29.3±5.7 versus 24.0±6.9 years. Donor body mass index (BMI) was higher among patients who died compared with those who were discharged: 25.3±1.1 versus 23.2±2.5 kg/m2. P-PASS was higher in patients who lost their pancreatic grafts (17.6±2.1 vs 15.2±1.8) or died (15.3±1.9 vs 17.2±1.9), or lost pancreatic graft or died (15.2±1.8 vs 17.0±2.2) or with intra-abdominal infections (IAI; 17.1±1.7 vs 15.0±1.8). The incidence of donors≥30 years old was higher among recipients with IAI (45.4% vs 14.3%; P=.04). An higher rate of donors with P-PASS>16 was revealed among patients who lost their pancreatic grafts (26.7% vs 3.2%), died (26.7% vs 3.2%), lost the pancreatic graft or died (33.3% vs 6.4%), or experienced IAI (46.7% vs 9.7%). Multivariate logistic regression analysis revealed P-PASS (odds ratio 2.57; P=.014) and serum sodium (odds ration, 0.91; P=.048) to be important predictors of IAI development. CONCLUSION Older age and higher BMI among deceased donors increased the risk of IAI, pancreatic graft loss, or recipient death after SPK. Transplantation of a pancreas from a donor with a low P-PASS score was associated with a lower risk of surgical complications after SPK.

Pancreatic neuroendocrine neoplasms — management guidelines (recommended by the Polish Network of Neuroendocrine Tumours)

We present revised diagnostic and therapeutic guidelines for the management of pancreatic neuroendocrine neoplasms (PNENs) proposed by the Polish Network of Neuroendocrine Tumours.These guidelines refer to biochemical (determination of specific and nonspecific neuroendocrine markers) and imaging diagnostics (EUS, CT, MR, and radioisotope examination with a 68Ga or 99Tc labelled somatostatin analogue).A histopathological diagnostic, which determines the further management of patients with PNENs, must be necessarily confirmed by immunohistochemical tests. PNENs therapy requires collaboration between a multidisciplinary team of specialists experienced in the management of these neoplasms. Surgery is the basic form of treatment. Medical therapy requires a multidirectional procedure, and therefore the rules of biotherapy, peptide receptor radionuclide therapy, chemotherapy and molecular targeted therapy are discussed.

Gastroduodenal neuroendocrine neoplasms including gastrinoma — management guidelines (recommended by the Polish Network of Neuroendocrine Tumours)

This paper presents the updated Polish Neuroendocrine Tumour Network expert panel recommendations on the management of neuroendocrine neoplasms (NENs) of the stomach and duodenum, including gastrinoma. The recommendations discuss the epidemiology, pathogenesis and clinical presentation of these tumours as well as their diagnosis, including biochemical, histopathological and localisation diagnosis. The principles of treatment are discussed, including endoscopic, surgical, pharmacological and radionuclide treatment. Finally, recommendations on patient monitoring are given.

Colorectal neuroendocrine neoplasms — management guidelines (recommended by the Polish Network of Neuroendocrine Tumours)

Neuroendocrine neoplasms of the large intestine account for 20% of all neuroendocrine neoplasms (NENs) and are most commonly found in the rectum. The rate of detection of colorectal NENs is increasing, and this tendency will continue due to the widespread use of colonoscopy as a screening tool and the removal of all diagnosed lesions. This paper provides updated guidelines for the management of patients with colorectal NENs. Recent data on epidemiology, clinical characteristics, biochemical, and pathomorphological diagnosis as well as useful imaging techniques are presented. We look in detail at novel methods of treatment including endoscopic and surgical management, pharmacological and radioisotope therapy. We summarise monitoring of the treatment.

Simultaneous liver mucinous cystic and intraductal papillary mucinous neoplasms of the bile duct: a case report.

Cystic hepatic neoplasms are rare tumors, and are classified into two separate entities: mucinous cystic neoplasms (MCNs) and intraductal papillary mucinous neoplasms of the bile duct (IPMN-B). We report the case of a 56-year-old woman who presented with abdominal pain and jaundice due to the presence of a large hepatic multilocular cystic tumor associated with an intraductal tumor. Partial hepatectomy with resection of extrahepatic bile ducts demonstrated an intrahepatic MCN and an intraductal IPMN-B. This is the first report of the simultaneous occurrence of these two histologically distinct entities in the liver.