Determination of the Primary Molecular Target of 1,2,4-Triazole-Ciprofloxacin Hybrids

We have synthesized and examined the antibacterial activity, toxicity and affinity towards bacterial type II topoisomerases of a series of 1,2,4-triazole-ciprofloxacin hybrids. A number of these compounds displayed enhanced activity against Gram-positive and Gram-negative bacteria when compared to ciprofloxacin. The toxic concentrations of the obtained derivatives, evaluated on HEK-293 cells using MTT assay, were much higher than concentrations required to produce antibacterial effect. Finally, the results of enzymatic studies showed that the analyzed compounds demonstrated other preferences as regards primary and secondary molecular targets than ciprofloxacin.This research was supported by the Ministry of Science and Higher Education under Iuventus Plus grant No. IP2014 037473. Tomasz Plech is a recipient of the Fellowship for Young Researchers with Outstanding Scientific Achievements from the Medical University of Lublin (Lublin, Poland)

Zniszczenia mikrobiologiczne zbiorów na tle warunków przechowywania w wybranych bibliotekach i archiwach w Polsce

The aims of this work were to assess the biodeterioration of library and archive collections as well as to identify the causes of the destructive processes. The investigation was carried out in five selected storerooms with particular attention being paid to the accumulation of moisture on wall barriers. The measurements of air relative humidity (RH) and temperature as well as the assessment of the biodeterioration of the collections were performed. The samples taken from the objects attacked by microorganisms were microbiologically tested. A direct dependency between the defects of buildings and the accumulation of moisture on wall barriers was confirmed. The source of moisture accumulation in some storerooms were rainwater penetrating the interior of the rooms through a leaky emergency door, through cracks in roof or terrace coverings or water from the overfilled manholes. The floodings resulted in the water stains on walls and ceilings, flaking of paint coatings, or sometimes colourful deposits of moulds or salts. The average values of the air RH in the examined storerooms ranged between 46.0% and 47.4%. However, it was noted that this parameter highly fluctuated up to 30% RH during a year. The average temperatures were between 19.5 and 21.0ºC, which means they were around 1.5 to 3ºC higher than temperatures recommended for library and archive collections. The temperature values were also variable and, to a large extent, dependent on the outdoor conditions. Around a quarter of collections in all examined storerooms was, to a larger or lesser degree, damaged by living organisms (fungi, insects and rodents). Some of the threats were still up-to-date, e.g. the attack of insects in one of the storerooms. However, a great number of other damage, in particular caused by microorganisms, has its beginnings in the past and the microorganisms responsible for the damage may have been inactive for a long time now. Hence, it is very difficult to find a correlation between the results of microscope examinations of deposits taken from the attacked places and the results of cultivation of microorganisms from the same spots. The collections had been stored in the examined storerooms for a relatively short period of time between 10 and 30 years. Their condition of preservation was, to a larger degree, affected by violent conditions (storing in basements, storing in attics, moving places, wars) and moisture, which had accumulated for decades before the collections were placed in the examined storerooms.

Badania nad zastosowaniem celulozy bakteryjnej w konserwacji i restauracji dzieł sztuki

Bacterial cellulose (BC) obtained in the bacterial biosynthesis by Acetobacter xylinum is considered one of the most interesting materials tested and used in different areas of the human activity. Successful its applications in medicine and food industry launched a study of this material on a large scale. Many characteristic and unique properties of bacterial cellulose are used already in the paper industry Research and application of bacterial cellulose nano fibers made up of cellulose, its non-toxic, biocompatibility and biodegradability fit perfectly into the world of interest and progress in nanotechnology. Plant cellulose and bacterial cellulose have the same chemical structure, but different chemical and physical properties. Bacterial Cellulose is biopolymer not soluble, more elastic and demonstrate a high tensile strength. The study was performed in collaboration with the Institute of Technical Biochemistry, Technical University of Łódź. Planned and carried out the study covered a wide range of experience of testing the applicability of bacterial cellulose as well as its modification in the work of restoration. So far, studies and practical adaptation of bacterial cellulose in our research are the first tests in the conservation area. The exceptions were the addition of bacterial cellulose sample during the manufacture of paper hand-derived, which as noted have a positive impact on the properties of paper produced and lead to the conclusion that the paper with the participation of bacterial cellulose can be used for archival and preservation purposes. Research undertaken in this study are the first extensive experience seeking to use the unique properties of this material such as high strength and elasticity, content of pure cellulose with a high degree of polymerization and the ability of these material to modification. Microscopic analysis (SEM, ESEM, AFM) showed significant differences in the structural construction of the test paper and bacterial cellulose (BC). BC is a product of a multi-layered as opposed to a paper test. It consists of a large number of very fine mesh of layers made of the microfibrils, whose thickness is usually tens of nanometers (usually less than 100 nm). Preliminary studies of bacterial cellulose membranes indicated the need to modify the native membrane by drying them to form sheets, and further grinding in the presence of water. Suspensions of bacterial cellulose known in our work hygrogels were modified with the addition of fillers, dyes, methyl cellulose, fibers of paper, fabric and dry shredded leather and parchment. The obtained hydrogels were characterized by low density and high water content, which allowed the formation of thin coats or seams. Additive methylcellulose had a positive influence on the properties of suspensions and coats. Structure of the sheets turned out by use the hydrogels was in contrast to the less dense sheets of BC a more flexible and bibulous. These suspensions were poured on the low-pressure suction table create flexible, durable sheets with similar appearance to the materials, which were the source fiber supplements. Hydrogels blended well with the fibers of fabrics, leather and parchment response for good and flexible materials. A significant advantage of bacterial cellulose is easy given to maintaining its forms such as impress of the sieve or cloth texture and others. Sheets of bacterial cellulose, its suspension were used as a bonding agent to reinforcing by coating and lining of test paper. Adhesive properties of hydrogels demonstrated that they can be used as a bonding mediums. Suspensions of bacterial cellulose fibers made from various materials were used for filling the holes in paper, textiles, leather and parchment. Lining samples of Bacterial cellulose sheets did not show any tendency to cracking and tearing. The test paper lining on sheet of BC strengthened the mechanical properties of the test paper. Suspensions of bacterial cellulose fibers used for coating the test paper and tissue samples delicate reinforcing them. Positive effect of application dried sheets to restoration of old photos, application of modified hydrogels to filling and reinforcing the paper and others tested treatment indicate necessary to continue of the evaluation on these field. Study were performed a wide range of experience. By microscopy examination (SEM, ESEM, OTC) was identified the morphology and structure of the membranes, any modified sheets and products. Colorimetrically determined by the brightness and colors of tested materials. PH and mechanical properties of the membranes, modified sheets and adhesive bonded joints to conservation materials was tested according to Polish standards. Determined mass, thickness, basis weight of the bio-cellulose materials and their changes under influence of the modification applied. Researched the optimal methods of membranes and modified sheets drying. Determined the rate of water vapour transmission according to Polish standards. It was made also evaluation of hygro-stability of the biocellulosic sheets. Biocellulose and test paper changes were studied under the influence of accelerated ageing. The results of investigation indicated that Bacterial Cellulose was more sensitive to microbial attack than the test paper. This characteristic can be improved by application of biocides.

Survivin expression at the mRNA level in tumors and the protein concentration in the serum and peritoneal fluid in patients with serous ovarian tumors

Objectives: Ovarian cancer is one of the gynecological cancers that have the worst prognosis. The expression of the proteins from the IAP family (inhibitor of apoptosis protein), including survivin, is observed in many types of cancer. The aim of the study was to evaluate survivin at the mRNA level in tumors and the protein concentration in the serum and peritoneal fluid of patients with serous ovarian cancer in order to assess the relationship between the concentration of survivin and the histological subtypes of cancer. Material and methods: The study group consisted of 55 women, including patients with serous ovarian cancer (n = 30, nine low-grade serous carcinoma LGSC, 21 high-grade serous carcinoma HGSC), serous cysts (n = 10) and the control group (n = 15). The concentration of protein in the peritoneal fluid and serum was assessed using ELISA tests. The expression of survivin gene BIRC5 in the tumors was assessed using the RT-qPCR method. Results: The data that was obtained indicated that the concentration of survivin was higher in the serum of the women with serous ovarian cancer compared those that had benign tumors (p < 0.05) and the control group (p < 0.001). The survivin concentration was also higher in both the serum and peritoneal fluid in the HGSC group compared to the LGSC group (p < 0.001). The mRNA level was highest in the HGSC group, and there was a statistically significant difference compared to those in the benign tumor group and HGSC group ( p < 0.05). Conclusions: The observed changes prove that the expression level increases significantly in HGSC in both the protein and mRNA levels. Based on these findings, it can be assumed that assessing this parameter could be a useful additional indicator of the progression and differentiation of this type of cancer. However, this requires further research in a larger group of patients and possibly in other types of ovarian cancer

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

W ostatnim czasie obserwuje się większe zainteresowanie rzadkimi nowotworami neuroendokrynnymi żołądkowo-jelitowo-trzustkowymi (GEP NEN). Wykrywalność nowotworów neuroendokrynnych w ostatnich latach wzrosła. Ponad 50% GEP NEN stanowią rakowiaki, które najczęściej są znajdowane przypadkowo podczas zabiegu operacyjnego w jelicie cienkim i w wyrostku robaczkowym oraz w momencie rozpoznania przerzutów odległych, głównie do wątroby. Istnieje konieczność współdziałania specjalistów różnych dziedzin medycyny w celu opracowania właściwych zasad postępowania diagnostyczno-leczniczego w tej grupie chorych. W niniejszej publikacji przedstawiono ogólne zalecenia Polskiej Sieci Guzów Neuroendokrynnych dotyczące postępowania u chorych z GEP NEN, opracowane podczas Konferencji, która odbyła się w Kamieniu Śląskim w kwietniu w 2013 roku. Członkowie grup roboczych zaktualizowali rekomendacje z 2008 roku.W kolejnych częściach tego opracowania przedstawiono zasady postępowania w:— nowotworach neuroendokrynnych żołądka i dwunastnicy (z uwzględnieniem gastrinoma);— nowotworach neuroendokrynnych trzustki; — nowotworach neuroendokrynnych jelita cienkiego i wyrostka robaczkowego;— nowotworach neuroendokrynnych jelita grubego.Zaproponowane rekomendacje przez ekspertów polskich i zagranicznych reprezentujących różne dziedziny medycyny (endokrynologię, gastroenterologię, chirurgię, onkologię, medycynę nuklearną i patomorfologię) powinny być pomocne w diagnostyce i leczeniu tych chorych. (Endokrynol Pol 2013; 64 (6): 418–443)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. (Endokrynol Pol 2013; 64 (6): 418–443

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

W pracy przedstawiono uaktualnione polskie zalecenia postępowania z chorymi na nowotwory neuroendokrynne (NEN) jelita cienkiego i wyrostka robaczkowego. Jelito cienkie, a przede wszystkim jelito kręte jest miejscem najczęstszego występowania tych nowotworów. Większość z nich to nowotwory wysokozróżnicowane i wolno rosnące. Rzadko są to nowotwory niskozróżnicowane, szybko rosnące o niekorzystnym rokowaniu. Ich objawy mogą być nietypowe, a rozpoznanie przypadkowe. Typowe objawy zespołu rakowiaka występują w mniej niż 10% przypadków. W diagnostyce laboratoryjnej najbardziej przydatne jest oznaczenie stężenia chromograniny A, badanie stężenia kwasu 5-hydroksyindolooctowego jest pomocne w monitorowaniu zespołu rakowiaka. W obrazowaniu stosuje się ultrasonografię, tomografię komputerową, rezonans magnetyczny, kolonoskopię, wideoendoskopię kapsułkową, enteroskopię dwubalonową, scyntygrafię receptorów somatostatynowych. Szczegółowe badanie histologiczne jest kluczowym dla właściwego rozpoznania i leczenia chorych z NEN jelita cienkiego i wyrostka robaczkowego. Leczeniem z wyboru jest postępowanie chirurgiczne, radykalne lub paliatywne. W leczeniu farmakologicznym czynnych i nieczynnych hormonalnie NEN jelita cienkiego i wyrostka robaczkowego podstawowe znaczenie mają analogi somatostatyny. Terapia radioizotopowa u chorych z dobrą ekspresją receptorów somatostatynowych stanowi kolejną opcję terapeutyczną. Chemioterapia jest na ogół nieskuteczna. U pacjentów z rozsianym NEN jelita cienkiego i progresją choroby oraz nieskutecznością innych metod terapii można zastosować ewerolimus. Przedstawiono także zalecenia odnośnie monitorowania chorych z NEN jelita cienkiego i wyrostka robaczkowego. (Endokrynol Pol 2013; 64 (6): 444–493)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. (Endokrynol Pol 2013; 64 (6): 480–493

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

W niniejszej publikacji przedstawiono zaktualizowane zalecenia dotyczące diagnostyczno-terapeutycznego postępowania w nowo­tworach neuroendokrynnych trzustki (PNEN) zaproponowane przez Polską Sieć Guzów Neuroendokrynnych. Zawierają one nowe dane uzyskane w latach 2013–2016, które albo potwierdziły wcześniejsze wytyczne, albo doprowadziły do zmian lub utworzenia dodatkowych zaleceń. W diagnostyce duże znaczenie mają badania biochemiczne, obrazowe (anatomiczne i czynnościowe), jak również rozpoznanie histopatologiczne, które determinuje postępowanie z chorymi na PNEN i musi być potwierdzone badaniem immunohistochemicznym. Terapia PNEN wymaga współpracy wielodyscyplinarnej grupy doświadczonych specjalistów zajmujących się nowotworami neuroendokrynnymi. Leczenie chirurgiczne jest podstawową metodą postępowania w wielu przypadkach. Dalsza terapia wymaga wielokierunkowego działania, dlatego omówiono zasady bioterapii, leczenia radioizotopowego, celowanego leczenia molekularnego oraz chemioterapii.This article presents updated diagnostic and therapeutic guidelines for the management of pancreatic neuroendocrine tumours (PNEN), proposed by the Polish Network of Neuroendocrine Tumours. The guidelines contain new data received in the years 2013–2016, which confirm previous recommendations, and have led to modification of previous guidelines or have resulted in the formulation of new guidelines. Biochemical and imaging (anatomical and functional) tests are of great importance in diagnostics, as well as histopathological diagnosis to determine the management of PNEN patients, but they must be confirmed by an immunohistochemical examination. PNEN therapy requires collaboration among the members a multidisciplinary team of specialists experienced in the management of these neoplasms. Surgery is the basic form of treatment in many cases. Further therapy requires a multidirectional procedure; therefore, the rules of biotherapy, peptide receptor radionuclide therapy, molecular targeted therapy, and chemotherapy are discussed

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

W niniejszej pracy przedstawiono uaktualnione zalecenia grupy ekspertów Polskiej Sieci Guzów Neuroendokrynnych dotyczące zasad postępowania w nowotworach neuroendokrynnych żołądka i dwunastnicy z uwzględnieniem gastrinoma. Omówiono epidemiologię, patogenezę i obraz kliniczny tych nowotworów. Przedstawiono zalecenia dotyczące zasad postępowania diagnostycznego, z uwzględ­nieniem diagnostyki biochemicznej, histopatologicznej oraz lokalizacyjnej. Przedstawiono także zasady postępowania terapeutycznego, w tym leczenie endoskopowe i chirurgiczne, oraz omówiono możliwości leczenia farmakologicznego i radioizotopowego. Przedstawiono także zalecenia odnośnie do monitorowania chorych z NEN żołądka, dwunastnicy z uwzględnieniem gastrinoma.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 diagnoses. The principles of treatment are discussed, including endoscopic, surgical, pharmacological, and radionuclide treatments. Finally, there are also recommendations on patient monitoring

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

W pracy przedstawiono uaktualnione polskie zalecenia postępowania z chorymi na nowotwory neuroendokrynne (NEN) jelita cienkiego i wyrostka robaczkowego. Jelito cienkie, a w szczególności jelito kręte, należą do najczęstszych lokalizacji tych nowotworów. Większość z nich to nowotwory wysokozróżnicowane i wolno rosnące; rzadko są to raki neuroendokrynne. Ich objawy mogą być nietypowe, a rozpoznanie opóźnione albo przypadkowe. Zapalenie wyrostka robaczkowego jest najczęściej pierwszą manifestacją NEN o tym umiej­scowieniu. Typowe objawy zespołu rakowiaka występują u około 20–30% pacjentów z NEN jelita cienkiego z przerzutami odległymi. Jedną z głównych przyczyn zgonu u pacjentów z zespołem rakowiaka są choroby serca — rakowiakowa choroba serca. W diagnostyce laboratoryjnej najbardziej przydatne jest oznaczenie stężenia chromograniny A, badanie stężenia kwasu 5-hydroksyindolooctowego jest pomocne w diagnostyce zespołu rakowiaka. W obrazowaniu stosuje się ultrasonografię, tomografię komputerową, rezonans magnetyczny, kolonoskopię, wideoendoskopię kapsułkową, enteroskopię dwubalonową, scyntygrafię receptorów somatostatynowych. Szczegółowe badanie histologiczne jest kluczowe dla właściwego rozpoznania i leczenia chorych z NEN jelita cienkiego i wyrostka robaczkowego. Leczeniem z wyboru jest postępowanie chirurgiczne, radykalne lub paliatywne. W leczeniu farmakologicznym czynnych i nieczyn­nych hormonalnie NEN jelita cienkiego i wyrostka robaczkowego podstawowe znaczenie mają długodziałające analogi somatostatyny. U chorych z NET jelita cienkiego w okresie uogólnienia z progresją w trakcie leczenia SSA, z wysoką ekspresją receptorów somatostatynowych należy rozważyć w pierwszej kolejności leczenie radioizotopowe, a następnie terapie celowane — ewerolimus. Po wyczerpaniu powyższych dostępnych terapii w wybranych przypadkach można rozważyć chemioterapię. Przedstawiono także zalecenia odnośnie do monitorowania chorych.This study presents the revised Polish guidelines regarding the management of patients suffering from neuroendocrine neoplasms (NENs) of the small intestine and appendix. The small intestine, especially the ileum, is the most common location for these neoplasms. Most are well differentiated and slow growing. Their symptoms may be atypical, which can result in delayed or accidental diagnosis. Appendicitis is usually the first manifestation of NEN in this location. Typical symptoms of carcinoid syndrome occur in approximately 20–30% of patients suffering from small intestinal NENs with distant metastases. The main cause of death in patients with carcinoid syndrome is carcinoid heart disease. The most useful laboratory test is the determination of chromogranin A, while concentration of 5-hydroxyindoleacetic acid is helpful in the diagnostics of carcinoid syndrome. For visualisation, ultrasound, computed tomography, magnetic resonance imaging, colonoscopy, video capsule endoscopy, double-balloon enteroscopy, and somatostatin receptor scintigraphy may be used. A detailed his­tological report is crucial for the proper diagnostics and therapy of NENs of the small intestine and appendix. The treatment of choice is surgical management, either radical or palliative. The pharmacological treatment of the hormonally active and non-active small intestinal NENs as well as NENs of the appendix is based on long-acting somatostatin analogues. In patients with generalised NENs of the small intestine in progress during the SSA treatment, with good expression of somatostatin receptors, the first-line treatment should be radio­isotope therapy, while targeted therapies, such as everolimus, should be considered afterwards. When the above therapies are exhausted, in certain cases chemotherapy may be considered

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

Nowotwory/guzy neuroendokrynne (NEN/NET) jelita grubego są rozpoznawane coraz częściej, szczególnie guzy odbytnicy. To zjawisko jest najprawdopodobniej związane z powszechnym wykonywaniem kolonoskopii przesiewowych. Coraz więcej przemawia za tym, że NEN odbytnicy i okrężnicy to dwie odrębne choroby. Nowotwory neuroendokrynne odbytnicy są najczęściej zmianami niewielkich roz­miarów, cechują się niskim lub umiarkowanym stopniem złośliwości histologicznej, dobrym rokowaniem i większość z nich kwalifikuje się do leczenia endoskopowego. Natomiast NEN okrężnicy to często nowotwory agresywne, niskozróżnicowane, o złej lub niepewnej prognozie, wymagające operacji. Zasady postępowania z tymi chorymi stale się zmieniają. Opierając się na najnowszym piśmiennictwie oraz ustaleniach wypracowanych na spotkaniu roboczym Polskiej Sieci Guzów Neuroendokrynnych (grudzień 2016 r.) w pracy uzupełniono i uaktualniono dane i wytyczne postępowania dotyczące NEN jelita grubego, opublikowane w Endokrynologii Polskiej 2013; 64: 494–504.Neuroendocrine neoplasms/tumours (NENs/NETs) of the large intestine are detected increasingly often, especially rectal tumours, which is probably associated with the widespread use of screening colonoscopy. There is a growing body of evidence supporting the thesis that the NENs of the rectum and the NENs of the colon are two different diseases. Rectal NENs are usually small lesions, of low to moderate histological malignancy, associated with good prognosis, and most may be treated endoscopically. NENs of the colon, however, are often aggressive, poorly differentiated, associated with a poor or uncer­tain prognosis, and require surgical treatment. The management guidelines regarding these groups of patients are constantly changing. On the basis of the recent literature data and conclusions reached by the working meeting of the Polish Network of Neuroendocrine Tumours (December 2016), this study completes and updates the data and management guidelines regarding colorectal NENs published in Endokrynologia Polska 2013; 64: 358–368.