Publications by authors named "Anna Sowa-Staszczak"

69 Publications

Heterogeneity of the Clinical Presentation of the MEN1 LRG_509 c.781C>T (p.Leu261Phe) Variant Within a Three-Generation Family.

Genes (Basel) 2021 Mar 31;12(4). Epub 2021 Mar 31.

Department of Endocrinology, Jagiellonian University Medical College, 31-008 Cracow, Poland.

Multiple neuroendocrine neoplasia type 1 (MEN1) is a rare genetic disorder with an autosomal dominant inheritance, predisposing carriers to benign and malignant tumors. The phenotype of MEN1 syndrome varies between patients in terms of tumor localization, age of onset, and clinical aggressiveness, even between affected members within the same family. We describe a heterogenic phenotype of the variant c.781C>T (LRG_509t1), which was previously reported only once in a family with isolated hyperparathyroidism. A heterozygous missense variant in exon 4 of the gene was identified in the sequence of the gene, i.e., c.781C>T, leading to the amino acid change p.Leu261Phe in a three-generation family. In the screened family, 5/6 affected members had already developed hyperparathyroidism. In the index patient and two other family members, an aggressive course of pancreatic neuroendocrine tumor (insulinoma and non-functioning neuroendocrine tumors) with dissemination was diagnosed. In the index patient, late diagnosis and slow progression of the disseminated neuroendocrine tumor have been observed (24 years of follow-up). The very rare variant of , LRG_509t1 c.781C>T /p.Leu261Phe (LRG_509p1), diagnosed within a three-generation family has a heterogenic clinical presentation. Further follow-up of the family members should be carried out to confirm the spectrum and exact time of clinical presentation.
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http://dx.doi.org/10.3390/genes12040512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067145PMC
March 2021

Efficacy of multimodal anticancer therapy in the course of pancreatic neuroendocrine carcinoma.

Endokrynol Pol 2021 Feb 23. Epub 2021 Feb 23.

Jagiellonian University Medical College, Krakow, Poland.

Neuroendocrine neoplasms are a heterogeneous group, comprising of well-differentiated neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas, which show major differences regarding histology, genetics, biological behaviour and clinical manifestations. Neuroendocrine carcinomas are relatively rare, therefore little data on long-term management are available. The present study shows a 10-year follow-up of a patient diagnosed with a disseminated pancreatic neuroendocrine carcinoma (pNEC) in young age. On CT examination, a cyst in the tail of the pancreas was described and the subsequent magnetic resonance revealed the pancreatic tail tumor, suspected to be adenocarcinoma infiltrating splenic vessels and adipose tissue with metastatic lymph nodes and liver metastases. The biopsyof liver confirmed NEN with chromogranin expression, while pancreatic biopsy was non-diagnostic. Surgical approach with the use of PRRT with subsequent chemotherapy and treatment with long-acting somatostatin analogue proved to be effective in the presented case, confirming benefit from multimodal anticancer therapy. There is a need to use all diagnostic methods to select the optimal therapy in patients with pNECs to provide them with better care and the longest possible survival.
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http://dx.doi.org/10.5603/EP.a2021.0005DOI Listing
February 2021

The Usefulness of [F]F-Fluorodeoxyglucose and [F]F-Sodium Fluoride Positron Emission Tomography Imaging in the Assessment of Early-Stage Aortic Valve Degeneration after Transcatheter Aortic Valve Implantation (TAVI)-Protocol Description and Preliminary Results.

J Clin Med 2021 Jan 22;10(3). Epub 2021 Jan 22.

Department of Cardiology and Cardiovascular Interventions, University Hospital, 30-688 Kraków, Poland.

Transcatheter aortic valve implantation (TAVI) is now a well-established treatment for severe aortic stenosis. As the number of procedures and indications increase, the age of patients decreases. However, their durability and factors accelerating the process of degeneration are not well-known. The aim of the study was to verify the possibility of using [F]F-sodium fluoride ([F]F-NaF) and [F]F-fluorodeoxyglucose ([F]F-FDG) positron emission tomography/computed tomography (PET/CT) in assessing the intensity of TAVI valve degenerative processes. In 73 TAVI patients, transthoracic echocardiography (TTE) at initial (before TAVI), baseline (after TAVI), and during follow-up, as well as transesophageal echocardiography (TEE) and PET/CT, were performed using [F]F-NaF and [F]F-FDG at the six-month follow-up (FU) visit as a part of a two-year FU period. The morphology of TAVI valve leaflets were assessed in TEE, transvalvular gradients and effective orifice area (EOA) in TTE. Calcium scores and PET tracer activity were counted. We assessed the relationship between [F]F-NaF and [F]F-FDG PET/CT uptake at the 6 = month FU with selected indices e.g.,: transvalvular gradient, valve type, EOA and insufficiency grade at following time points after the TAVI procedure. We present the preliminary PET/CT ([F]F-NaF, [F]F-FDG) results at the six-month follow-up period as are part of an ongoing study, which will last two years FU. We enrolled 73 TAVI patients with the mean age of 82.49 ± 7.11 years. A significant decrease in transvalvular gradient and increase of effective orifice area and left ventricle ejection fraction were observed. At six months, FU valve thrombosis was diagnosed in four patients, while 7.6% of patients refused planned controls due to the COVID-19 pandemic. We noticed significant correlations between valve types, EOA and transaortic valve gradients, as well as [F]F-NaF and [F]F-FDG uptake in PET/CT. PET/CT imaging with the use of [F]F-FDG and [F]F-NaF is intended to be feasible, and it practically allows the standardized uptake value (SUV) to differentiate the area containing the TAVI leaflets from the SUV directly adjacent to the ring calcifications and the calcified native leaflets. This could become the seed for future detection and evaluation capabilities regarding the progression of even early degenerative lesions to the TAVI valve, expressed as local leaflet inflammation and microcalcifications.
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http://dx.doi.org/10.3390/jcm10030431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866182PMC
January 2021

Ectopic ACTH syndrome of different origin-Diagnostic approach and clinical outcome. Experience of one Clinical Centre.

PLoS One 2020 25;15(11):e0242679. Epub 2020 Nov 25.

Department of Endocrinology, Jagiellonian University, Krakow, Poland.

Purpose: Ectopic Cushing Syndrome (EAS) is a rare condition responsible for about 5-20% of all Cushing syndrome cases. It increases the mortality of affected patients thus finding and removal of the ACTH-producing source allows for curing or reduction of symptoms and serum cortisol levels. The aim of this study is to present a 20-year experience in the diagnosis and clinical course of patients with EAS in a single Clinical Centre in Southern Poland as well as a comparison of clinical course and outcomes depending on the source of ectopic ACTH production-especially neuroendocrine tumors with other neoplasms.

Methods: Twenty-four patients were involved in the clinical study with EAS diagnosed at the Department of Endocrinology between years 2000 and 2018. The diagnosis of EAS was based on the clinical presentation, hypercortisolemia with high ACTH levels, high dose dexamethasone suppression test and/or corticotropin-releasing hormone tests. To find the source of ACTH various imaging studies were performed.

Results: Half of the patients were diagnosed with neuroendocrine tumors, whereby muscle weakness was the leading symptom. Typical cushingoid appearance was seen in merely a few patients, and weight loss was more common than weight gain. Patients with neuroendocrine tumors had significantly higher midnight cortisol levels than the rest of the group. Among patients with infections, we observed a significantly higher concentrations of cortisol 2400 levels in gastroenteropancreatic neuroendocrine tumors. Chromogranin A correlated significantly with potassium in patients with neuroendocrine tumors and there was a significant correlation between ACTH level and severity of hypokalemia.

Conclusion: EAS is not common, but if it occurs it increases the mortality of patients; therefore, it should be taken into consideration in the case of coexistence of severe hypokalemia with hypertension and muscle weakness, especially when weight loss occurs. Because the diagnosis of gastroenteropancreatic neuroendocrine tumor worsens the prognosis-special attention should be paid to these patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242679PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688153PMC
January 2021

Acromegaly and late-onset primary hyperparathyroidism in a female with a rare MEN1 gene variant of yet undetermined clinical significance (p.Val167Ala).

Endokrynol Pol 2020 30;71(6):579-580. Epub 2020 Oct 30.

Department of Endocrinology, Jagiellonian University Medical College, Cracow, Poland.

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http://dx.doi.org/10.5603/EP.a2020.0063DOI Listing
October 2020

Difficulties in the diagnosis and treatment of malignant paraganglioma of the urinary bladder.

Endokrynol Pol 2020 15;71(2):196-197. Epub 2020 Apr 15.

Clinical Department of Endocrinology, University Hospital, Jagiellonian University, Medical College, Krakow, Poland.

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http://dx.doi.org/10.5603/EP.a2019.0068DOI Listing
January 2021

Diagnostic imaging of gastrointestinal neuroendocrine neoplasms with a focus on ultrasound.

J Ultrason 2019 Nov 30;19(78):228-235. Epub 2019 Sep 30.

Clinical Department of Endocrinology, University Hospital in Kraków, Kraków, Poland.

The diagnosis of gastrointestinal neuroendocrine neoplasms represents a significant diagnostic challenge since these tumours have a various, often non-specific clinical presentation. Currently, more than half of gastroenteropancreatic neuroendocrine neoplasms are detected incidentally, usually during surgery, diagnostic imaging studies or endoscopic procedures performed for other indications. Sometimes the first symptom of the disease is the presence of metastatic lesions in the liver. A neuroendocrine tumour is diagnosed based on the clinical presentation, assessment of specific and non-specific biochemical markers, imaging studies and histopathological examination. Focal lesions, both primary and metastatic may be small and often have an atypical location. Diagnostic imaging of neuroendocrine tumours is of fundamental importance for determining the location of the primary lesion, staging of the disease, selection of treatment and monitoring of its effects. In addition, diagnostic imaging make it possible not only to detect tumours, but also to perform therapeutic procedures based on the result. Transabdominal ultrasound is one of the first diagnostic imaging method for neuroendocrine neoplasms. New ultrasound techniques such as ultrasound elastography, contrast-enhanced ultrasound, endoscopic ultrasound, intraductal and intraoperative ultrasound improve the efficacy of ultrasound examination. Endoscopic ultrasound is a fundamental diagnostic tool for the detection of neuroendocrine tumours of the pancreas and the distal part of the colon. Due to the large variety of neuroendocrine tumours and differences in tumour biology, clinical stage and expression of somatostatin receptors, no single imaging method is sufficient; therefore, in order to determine the right diagnosis and select the best treatment, it is recommended that a combined morphological and functional assessment be used.
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http://dx.doi.org/10.15557/JoU.2019.0034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856780PMC
November 2019

Consolidation with Y ibritumomab tiuxetan radioimmunotherapy in mantle cell lymphoma patients ineligible for high dose therapy: results of the phase II multicentre Polish Lymphoma Research Group trial, after 8-year long follow-up.

Leuk Lymphoma 2019 11 9;60(11):2689-2696. Epub 2019 Apr 9.

Policlinico "Sant'Orsola-Malpighi" - University of Bologna Institute of Hematology "Seràgnoli", Bologna, Italy.

Polish Lymphoma Research Group performed a phase-II trial to test whether Y ibritumomab tiuxetan radioimmunotherapy (Y90) may constitute an alternative consolidation for mantle cell lymphoma patients unfit for high-dose therapy. Forty-six patients were consolidated with Y90 following response to the 1st ( = 34) or 2nd line ( = 12) (immuno)chemotherapy. Majority of the patients had advanced disease (stage IV and presence of B-symptoms in 85% and 70%, respectively) and high MIPI (5.8, range 4-7). Consolidation with Y90 increased the complete remission (CR) rate obtained by the 1st line therapy from 41% to 91% and allowed for median PFS of 3.3 and OS of 6.5 years. In the first relapse, CR rate increased from 16% to 75%, while median PFS and OS totaled 2.2 and 6.5 years, respectively. At 8 years, 30% of patients, consolidated in the 1st line CR were alive, without relapse. Toxicity associated with Y90 is manageable, more severe after fludarabine-based regimens.
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http://dx.doi.org/10.1080/10428194.2019.1602261DOI Listing
November 2019

Early chemotherapy de-escalation strategy in patients with advanced-stage Hodgkin lymphoma with negative positron emission tomography scan after 2 escalated BEACOPP cycles.

Pol Arch Intern Med 2019 04 4;129(4):259-266. Epub 2019 Apr 4.

Department of Hematology, Jagiellonian University Medical College, Kraków, Poland

INTRODUCTION Escalated BEACOPP (escBEACOPP: bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) significantly improves overall response rates (ORRs) and prolongs progression‑free survival (PFS) in patients with advanced‑stage Hodgkin lymphoma (HL). However, 6 to 8 cycles of escBEACOPP are associated with increased acute toxicity and late complications. OBJECTIVES We aimed to determine the role of early positron emission tomography-computed tomography (PET‑CT) response assessment in a de‑escalation strategy. PATIENTS AND METHODS We retrospectively analyzed 188 consecutive patients with advanced‑stage HL treated at diagnosis. Patients received 2 cycles of escBEACOPP followed by an early PET‑CT response assessment performed after 2 cycles of chemotherapy (PET2). Patients with an active disease continued therapy with escBEACOPP, while those with negative PET2 were de‑escalated to ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine). Radiotherapy was allowed in patients with stage IIBX. RESULTS PET2 allowed for de‑escalation of therapy in 141 patients (75%). Their ORR was 92.2%, with a complete remission (CR) rate of 91.5%; 10‑year PFS and overall survival (OS) were 87.2% and 95%, respectively. In the whole cohort, ORR was 87.8% (CR, 85.6%), while the 10‑year PFS and OS were 79.3% and 89.4%, respectively. Hematological and thromboembolic complications were significantly more frequent in patients treated with 6 escBEACOPP cycles, including febrile neutropenia (25 patients, [53.2%] vs 7 [5%]), serious anemia (35 [74.5%] vs 11 [7.8%]), or thrombocytopenia (16 [34%] vs 7 [5%]) (P <0.001 for all comparisons with de‑escalation strategy) as well as pulmonary embolism (3 [6.4%] vs 0) (P = 0.02). CONCLUSIONS The early de‑escalation strategy allows for effective treatment of advanced HL, with a comparable efficacy to that of 6 to 8 cycles of escBEACOPP, but with significantly reduced toxicity.
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http://dx.doi.org/10.20452/pamw.14786DOI Listing
April 2019

Coexistence of neurofibromatosis type 1 with multiple malignant neoplasia.

Neuro Endocrinol Lett 2018 Sep;39(3):149-155

Clinical Department of Endocrinology, Jagiellonian University in Krakow, Poland.

Neurofibromatosis type 1 (NF1, von Recklinghausen disease) is inherited in autosomal dominant way genetic disorder, with an incidence at birth 1:3000. It is one of the most common congenital disorders. It is characterized by café-au-lait spots, neurofibromas, and less common MPTST and gliomas of the optic nerve. It is caused by germline mutations of the NF1 gene, which acts as tumor suppressor. Inactivation of the gene leads to increased activation of the kinase pathways, and in consequence, uncontrolled proliferation of cells. The disease predisposes to the development of both benign and malignant tumors. Malignant tumors, but not related to the nervous system occur in neurofibromatosis quite rare. The aim of the study is a literature review of NF1, with presentation of a patient with NF1 and coexisting numerous tumors: synchronous somatostatinoma and gastrointestinal stromal tumor with metachronous prostate adenocarcinoma and non-small cell lung carcinoma. And attempt to answer the question if there is a common pathway for oncogenesis of these four tumors.
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September 2018

Temozolomide therapy for aggressive pituitary Crooke's cell corticotropinoma causing Cushing's Disease - a case report with literature review.

Endokrynol Pol 2018 10;69(3):306-312. Epub 2018 Jan 10.

Klinika Endokrynologii, Uniwersytet Jagielloński, Kraków, Poland.

Context: Aggressive pituitary tumours causing Cushing's Disease are very rare, difficult to treat, and usually resistant to conventional therapy. There is growing evidence for the use of temozolomide (TZM), an alkylating chemotherapeutic agent, as first line chemotherapy in tumours resistant to repeated neurosurgery, radiotherapy and adrenalectomy.

Objective: To present the response to TMZ in a rare case of an aggressive pituitary tumour in the course of Cushing's Disease and to review the literature referring to similar cases.

Patient: In this report, we present the case of a 61 year old male patient who was diagnosed with Cushing's Disease in the course of a pituitary invasive macroadenoma in 2011. The patient underwent 4 transphenoidal non-radical neurosurgeries (2012,2013) with rapid tumour progression, repeated non-radical bilateral adrenalectomy (2012, 2013) and stereotactic radiotherapy, and gamma knife surgery (2013, 2015). Histopathological examination revealed macroadenoma with high cell polymorphism and the presence of Crooke's cells, Ki- < 2%. Since 2015 the patient has been treated with 6 cycles of TMZ (320 mg per day for 5 consecutive days, 28-day cycle) with clinical and biochemical improvement and stabilized tumour size and no side effects. TMZ was continued for up to 9 cycles with a stable serum level of cortisol and ACTH being observed. However, clinical symptoms like headaches, visual field impairment, and finally hearing loss started to progress from the eighth cycle. After the ninth cycle of TMZ, there was a sudden increase in the size of the tumour, impairment of the cortisol and ACTH level, marked deterioration of the clinical status with the recurrence of severe headaches, narrowing of the visual field and hearing loss. At the beginning of 2016, a sudden clinical status and sight deterioration, strong headaches, drop of the right eyelid with widening of the pupil were observed. The patient died in February 2016.

Lessons: The case of our patient suggests that the response to the TMZ treatment monotherapy in aggressive pituitary tumour causing Cushing's Disease could be partial and restricted to 7-8 cycles followed by rapid progression of the tumor mass. Therefore, further research should be carried out with regard to new methods to extend the responsiveness and duration of TMZ treatment and to investigate predictors of responsiveness. < p > < /p >.
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http://dx.doi.org/10.5603/EP.a2018.0011DOI Listing
October 2018

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

Endokrynol Pol 2017 ;68(2):79-110

Klinika Endokrynologii i Nowotworów Neuroendokrynnych, Katedra Patofizjologii i Endokrynologii, Śląski Uniwersytet Medyczny.

Progress in the diagnostics and therapy of gastro-entero-pancreatic (GEP) neuroendocrine neoplasms (NEN), the published results of new randomised clinical trials, and the new guidelines issued by the European Neuroendocrine Tumour Society (ENETS) have led the Polish Network of Neuroendocrine Tumours to update the 2013 guidelines regarding management of these neoplasms. We present the general recommendations for the management of NENs, developed by experts during the Third Round Table Conference - Diagnostics and therapy of gastro-entero-pancreatic neuroendocrine neoplasms: Polish recommendations in view of current European recommenda-tions, which took place in December 2016 in Żelechów near Warsaw. Drawing from the extensive experience of centres dealing with this type of neoplasms, we hope that we have managed to develop the optimal management system, applying the most recent achievements in the field of medicine, for these patients, and that it can be implemented effectively in Poland. These management guidelines have been arranged in the following order: gastric and duodenal NENs (including gastrinoma); pancreatic NENs; NENs of the small intestine and appendix, and colorectal NENs.
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http://dx.doi.org/10.5603/EP.2017.0015DOI Listing
July 2017

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

Endokrynol Pol 2017 ;68(2):250-260

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 uncer-tain 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.
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http://dx.doi.org/10.5603/EP.2017.0019DOI Listing
July 2017

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

Endokrynol Pol 2017 ;68(2):223-236

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 his-tological 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 radio-isotope therapy, while targeted therapies, such as everolimus, should be considered afterwards. When the above therapies are exhausted, in certain cases chemotherapy may be considered.
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http://dx.doi.org/10.5603/EP.2017.0018DOI Listing
July 2017

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

Endokrynol Pol 2017 ;68(2):169-197

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.
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http://dx.doi.org/10.5603/EP.2017.2016DOI Listing
July 2017

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

Endokrynol Pol 2017 ;68(2):138-153

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.
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http://dx.doi.org/10.5603/EP.2017.0016DOI Listing
July 2017

Radiolabeled peptides: current and new perspectives.

Q J Nucl Med Mol Imaging 2017 Jun;61(2):153-167

Department of Endocrinology, Jagiellonian University, Medical College, Krakow, Poland.

Radiolabeled peptides have been the subject of research for over 20 years and during that time possibility/variety of peptide receptor imaging and later targeted radiotherapy increased significantly. The targeted receptors belong to the large family of G-protein-coupled receptors or tyrosine kinases receptors partially connected with them. They both regulate large signaling networks, control multiple cell functions and are implicated in many diseases including cancers. The essential feature of peptides used in nuclear medicine involves their ability to binding with high affinity and specify to their receptors overexpressed on tumor cells. Currently most important peptide radiotracers are somatostatin, GLP-1, bombesin, gastrin/cholecystokinin-2, neurokinin type 1, CXCR4, EGF, VEGF and integrins. These tracers are mainly based on nuclides which are radiometals or on 18F and may be used in both SPECT or PET techniques as well as for hybrid imaging. Using of chelators suitable for peptide labeling with diagnostic and therapeutic radionuclids enables the theranostic approach. In this review we will provide a brief overview over currently available radiopharmaceuticals based on different groups of peptides.
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http://dx.doi.org/10.23736/S1824-4785.17.02971-5DOI Listing
June 2017

Epidemiology of gastroenteropancreatic neuroendocrine neoplasms in Krakow and Krakow district in 2007-2011.

Endokrynol Pol 2017 ;68(1):42-46

Department of Endocrinology, University Hospital in Krakow, Krakow, Poland.

Introduction: Gastroenteropancreatic neuroendocrine neoplasms (GEPNEN) are rare and heterogeneous tumours with variable biology. The aim of this study was to evaluate the epidemiology of GEPNEN in the population of Krakow and Krakow district in 2007-2011.

Material And Methods: The Database of the Chair and Department of Endocrinology, Jagiellonian University Medical College, comprising the data on NEN cases collected from the Endocrinology Department, University Hospital in Krakow and from independent sources: surgery, pathology, and endocrinology departments located in the Krakow area, was searched for cases of GEPNEN patients living in Krakow and Krakow district, diagnosed between 2007 and 2011. Eighty-eight such patients (39 males, 49 females, median age at diagnosis 59 ± 17 years) were identified and characterised.

Results: The mean follow-up time was 2.67 ± 1.6 years. The most frequent primary location of GEPNEN was small intestine (20%), followed by the appendix (18%), stomach (16%), pancreas (16%), rectum (15%), and colon (15%). NENG1 predominated (64%) in the analysed group. Most well-differentiated GEPNEN (63%) were diagnosed at stage I; however, 18% of them were diagnosed at stage IV. Metastases at diagnosis were found in 31% of patients. The GEPNEN incidence rate in 2007-2011 was 2.1/100000 inhabitants/year, without significant increase during the studied period.

Conclusions: GEPNEN incidence and epidemiology in the population of Krakow and Krakow district is similar to the incidence observed in most European countries. Registers are important tools to evaluate GEPNEN epidemiology. (Endokrynol Pol 2017; 68 (1): 42-46).
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http://dx.doi.org/10.5603/EP.2017.0006DOI Listing
May 2017

Does combination of "cold" and "hot" somatostatin analogs prolong survival of patients with neuroendocrine neoplasms?

Endocr J 2017 Feb 17;64(2):171-177. Epub 2016 Nov 17.

Department of Endocrinology, University Hospital, Krakow, Poland.

A number of detected neuroendocrine neoplasms (NENs) has been on the increase due to our awareness of the NENs risk and the development of different imaging techniques. Therapy of NENs involves surgery, chemotherapy, "cold" somatostatin analogs (SSA), peptide receptor radionuclide therapy (PRRT) and kinase inhibitors in pancreatic NENs. The aim of this study is to assess the efficacy of SSA in combination with "hot" somatostatin analogs, and the survival rate of our patients with advanced NENs. Seventy nine patients with metastatic NEN and positive somatostatin receptor scintigraphy (SRS) were enrolled in the study. Every patient was supposed to receive a dose of 7.4 GBq/m PRRT in 4-5 cycles every 4-9 weeks. Response to the therapy was assessed according to Response Evaluation Criteria In Solid Tumors (RECIST). SSA were administered one month after the last cycle of PRRT and have been continued during the whole follow up period. Median observation time was 33 months (IQR 13.6-55.6), median time to progression was 28 months (IQR 12.1-39.2) and median time to event was 28 months (IQR 12.1-39.2). Overall survival for this group of patients was 60 months. PFS was 39 months and EFS was equal to 33 months. In our group of patients not many serious adverse events were observed. PRRT using radiolabelled somatostatin analogs followed by therapy with "cold" somatostatin analogs is a promising treatment option for patients with metastatic or inoperable somatostatin receptor-positive NENs with the possibility of survival prolongation.
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http://dx.doi.org/10.1507/endocrj.EJ16-0219DOI Listing
February 2017

99mTc Labeled Glucagon-Like Peptide-1-Analogue (99mTc-GLP1) Scintigraphy in the Management of Patients with Occult Insulinoma.

PLoS One 2016 15;11(8):e0160714. Epub 2016 Aug 15.

Department of Endocrinology, Jagiellonian University Medical College, Kraków, Poland.

Introduction: The aim of this study was to assess the utility of [Lys40(Ahx-HYNIC-99mTc/EDDA)NH2]-exendin-4 scintigraphy in the management of patients with hypoglycemia, particularly in the detection of occult insulinoma.

Materials And Methods: Forty patients with hypoglycemia and increased/confusing results of serum insulin and C-peptide concentration and negative/inconclusive results of other imaging examinations were enrolled in the study. In all patients GLP-1 receptor imaging was performed to localise potential pancreatic lesions.

Results: Positive results of GLP-1 scintigraphy were observed in 28 patients. In 18 patients postsurgical histopathological examination confirmed diagnosis of insulinoma. Two patients had contraindications to the surgery, one patient did not want to be operated. One patient, who presented with postprandial hypoglycemia, with positive result of GLP-1 imaging was not qualified for surgery and is in the observational group. Eight patients were lost for follow up, among them 6 patients with positive GLP-1 scintigraphy result. One patient with negative scintigraphy was diagnosed with malignant insulinoma. In two patients with negative scintigraphy Munchausen syndrome was diagnosed (patients were taking insulin). Other seven patients with negative results of 99mTcGLP-1 scintigraphy and postprandial hypoglycemia with C-peptide and insulin levels within the limits of normal ranges are in the observational group. We would like to mention that 99mTc-GLP1-SPECT/CT was also performed in 3 pts with nesidioblastosis (revealing diffuse tracer uptake in two and a focal lesion in one case) and in two patients with malignant insulinoma (with the a focal uptake in the localization of a removed pancreatic headin one case and negative GLP-1 1 scintigraphy in the other patient).

Conclusions: 99mTc-GLP1-SPECT/CT could be helpful examination in the management of patients with hypoglycemia enabling proper localization of the pancreatic lesion and effective surgical treatment. This imaging technique may eliminate the need to perform invasive procedures in case of occult insulinoma.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0160714PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4985165PMC
July 2017

NEN - the role of somatostatin receptor scintigraphy in clinical setting.

Nucl Med Rev Cent East Eur 2016 ;19(2):118-25

Nuclear Medicine Unit, Endocrinology Department, University Hospital, Krakow, Poland.

Detection of neuroendocrine neoplasms (NENs) and monitoring of their response to therapy is still challenging due to huge heterogeneity of that group of tumors. Actually, NENs visualization is mainly based on molecular imaging while in the past it was relied on less effective structural imaging including CT and MRI. Molecular imaging techniques in combination with structural imaging (hybrid imaging), especially in patients with well-differentiated NENs, in addition to morphological provide the functional information about tumor which benefits in a more accurate patient management, including more sensitive visualization of primary tumors, more precise staging and better therapy follow-up. Overexpression of somatostatin receptors (SSTR) on NENs' cell membrane was a basis for development of somatostatin receptor scintigraphy (SRS) using single photon emission tomography SPECT, which is today a well-established standard in molecular imaging of NENs, and further imaging improvement in the field of positron emission tomography (PET). Use of hybrid imaging (SPECT/CT, PET/CT) increased sensitivity of examination, mainly resulting in better detection of small lesions. Generally, somatostatin receptor imaging with PET/CT is an emerging technique, although still with limited access, but due to several advantages over SSTR SPECT/CT, should be used if available. It is worth mentioning, that both SSTR PET/CT and SSTR SPECT/CT have some limitations, such as relatively low detection rate of benign insulinomas, poorly differentiated GEP-NETs and liver metastases. For that reason further improvement of NETs imaging is necessary. The most promising new tracers' families are based on SSTR antagonists, 64Cu-radiolabeled ligands and glucagon-like peptide-1 receptor (GLP-1R) imaging. Finally, in case of poor-differentiated neuroendocrine cancers 18F-FDG PET/CT may be beneficial in comparison with molecular imaging based on somatostatin receptor modalities.
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http://dx.doi.org/10.5603/NMR.2016.0023DOI Listing
March 2017

Noninsulinoma pancreatogenous hypoglycaemia in adults--a spotlight on its genetics.

Endokrynol Pol 2015 ;66(4):344-54

Chair and Department of Endocrinology Jagiellonian University, Medical College.

Hyperinsulinaemic hypoglycaemia (HH) is also classically referred to as "nesidioblastosis". Heterogeneous clinical manifestation of the disease causes risk of late diagnosis or even misdiagnosis. In infants and children, it can lead to serious and permanent damage to the central nervous system, which leads to the manifesting mental retardation. HH is characterised by unregulated insulin secretion from pancreatic β-cells. This effect has been correlated with nine genes: ABCC8, KCNJ11, GCK, GLUD-1, HADH1, SLC16A1, HNF4A, HNF1A, and UCP2. Mutations in these genes were found in approximately 48% of cases. The genetic background of the remaining cases is unknown. Understanding the genetic basis of familial hyperinsulinism has changed the early look at the disease. It has allowed for the differentiation of specific types of the disease. Depending on which of the nine disease-associated loci bears a pathogenic mutation, they differ in phenotype and pattern of inheritance. This review provides a brief overview of the genetic mechanisms of HH and its possible clinical presentations.
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http://dx.doi.org/10.5603/EP.2015.0044DOI Listing
February 2017

Gastroenteropancreatic neuroendocrine neoplasms: a 10-year experience of a single center.

Pol Arch Med Wewn 2015 29;125(5):337-46. Epub 2015 Apr 29.

Introduction: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) constitute a rare and heterogeneous group of tumors with varied biology.

Objectives: The aim of this study was to establish the clinical characteristics of patients with GEP-NEN and identify factors influencing their 5-year survival.

Patients And Methods: The study included 122 patients living in Kraków or its administrative region, who were diagnosed with GEP-NEN between 2002 and 2011.

Results: The mean follow-up period was 4.9 ±2.8 years. The most frequent primary site of the tumor was the small intestine (n = 25; 20%), followed by pancreas (n = 23; 19%), rectum (n = 23; 19%), stomach (n = 21; 17%), appendix (n = 19; 16%), and colon (n = 11; 9%). There were 84 tumors classified as NEN G1; 31, as NEN G2; 5, as neuroendocrine carcinoma; and 1, as mixed adenoneuroendocrine carcinoma. Most well-differentiated GEP-NENs (n = 57; 57%) were diagnosed at stage I according to the American Joint Committee on Cancer / Union for International Cancer Control (AJCC/UICC) classification; 77% of NEN G1 (n = 64) were diagnosed at stage I, but the majority of NEN G2—at stage IV (n = 18; 58%). Metastases at diagnosis were found in 38 patients (34%). In 90% of the cases (n = 101), tumors were hormonally nonfunctional. The overall 5-year survival was 85%. In the univariate analysis, NEN G2 (P = 0.003), higher stage according to the AJCC/UICC classification (P <0.001), and metastases at diagnosis (P <0.001) were associated with poorer prognosis. In standardized multivariate models, higher stage (P = 0.02) and metastases at diagnosis (P = 0.02) were independent risk factors for death.

Conclusions: The most important factors affecting survival of patients with GEP-NENs are tumor stage and the presence of metastases at diagnosis. The analysis of single-center data improves identification of patients with poorer prognosis requiring a more aggressive approach.
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http://dx.doi.org/10.20452/pamw.2832DOI Listing
January 2017

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

Endokrynol Pol 2013 ;64(6):459-79

Division of Endocrinology, Department of Pathophysiology and Endocrinology, Medical University of Silesia, Katowice, Poland.

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.
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http://dx.doi.org/10.5603/EP.2013.0031DOI Listing
September 2015

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

Endokrynol Pol 2013 ;64(6):444-58

Division of Endocrinology, Department of Pathophysiology and Endocrinology, Medical University of Silesia, Katowice, Poland.

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.
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http://dx.doi.org/10.5603/EP.2013.0030DOI Listing
September 2015

Optimization of image reconstruction method for SPECT studies performed using [⁹⁹mTc-EDDA/HYNIC] octreotate in patients with neuroendocrine tumors.

Nucl Med Rev Cent East Eur 2013 ;16(1):9-16

Department of Endocrinology, Jagiellonian University Medical College, Krakow, Poland.

Background: Somatostatin receptor scintigraphy (SRS) is a useful tool in the assessment of GEP-NET (gastroenteropancreatic neuroendocrine tumor) patients. The choice of appropriate settings of image reconstruction parameters is crucial in interpretation of these images. The aim of the study was to investigate how the GEP NET lesion signal to noise ratio (TCS/TCB) depends on different reconstruction settings for Flash 3D software (Siemens).

Methods: SRS results of 76 randomly selected patients with confirmed GEP-NET were analyzed. For SPECT studies the data were acquired using standard clinical settings 3-4 h after the injection of 740 MBq 99mTc-[EDDA/HYNIC] octreotate. To obtain final images the OSEM 3D Flash reconstruction with different settings and FBP reconstruction were used. First, the TCS/TCB ratio in voxels was analyzed for different combinations of the number of subsets and the number of iterations of the OSEM 3D Flash reconstruction. Secondly, the same ratio was analyzed for different parameters of the Gaussian filter (with FWHM = 2-4 times greater from the pixel size). Also the influence of scatter correction on the TCS/TCB ratio was investigated.

Results: With increasing number of subsets and iterations, the increase of TCS/TCB ratio was observed. With increasing settings of Gauss [FWHM coefficient] filter, the decrease of TCS/TCB ratio was reported. The use of scatter correction slightly decreases the values of this ratio.

Conclusions: OSEM algorithm provides a meaningfully better reconstruction of the SRS SPECT study as compared to the FBP technique. A high number of subsets improves image quality (images are smoother). Increasing number of iterations gives a better contrast and the shapes of lesions and organs are sharper. The choice of reconstruction parameters is a compromise between image qualitative appearance and its quantitative accuracy and should not be modified when comparing multiple studies of the same patient.
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http://dx.doi.org/10.5603/NMR.2013.0003DOI Listing
January 2014

Nephrotoxicity after PRRT - still a serious clinical problem? Renal toxicity after peptide receptor radionuclide therapy with 90Y-DOTATATE and 90Y/177Lu-DOTATATE.

Endokrynol Pol 2013 ;64(1):13-20

Nuclear Medicine Department, Medical University of Warsaw, Banacha St. 1a,Warsaw, Poland.

Introduction: The kidneys play an essential role in PRRT. The infusion of amino acids could reduce uptake in the kidney of radiolabelled peptides. The purpose of this study was to determine the extent of kidney damage post PRRT.

Material And Methods: 53 patients, with disseminated neuroendocrine tumours (NET), received 3-5 cycles of up to a maximum 7.4 GBq/m2 calculated dose of 90Y-DOTATATE (n = 25) and 90Y/177Lu-DOTATATE (n = 28). Creatinine levels were measured and glomerular filtration rates (GFR) were calculated. A mixed amino acid infusion was used for nephroprotection.

Results: Patients treated with 90Y-DOTATATE had a mean creatinine level of 0.77 ± 0.19 mg/dL and a mean GFR (mL/min/1.73 m2) of 103.6 ± 30.8. Patients treated with 90Y/177Lu-DOTATATE had a mean creatinine level of 0.92 ± 0.33 mg/dL and a mean GFR of 84.7 ± 26.3. In the follow up, among patients treated with 90Y-DOTATATE and 90Y/177Lu-DOTATATE, the mean GFR level at 12 months was 101.2 ± 31.3 v. 83.9 ± 25.2, at 24 months 80.2 ± 32.7 v. 77.2 ± 31.1, at 36 months 78.9 ± 42.1 v. 67.5 ± 9.7, and 48 months 59.7 ± 15.2 v. 72.6 ± 11.2. The mean yearly decrease in GFR was 4.5 mL in all treated patients; for patients treated with 90Y-DOTATATE and 90Y/177Lu-DOTATATE it was 6.8 v. 3.0, respectively.

Conclusions: 90Y/177Lu-DOTATATE treatment induced statistically significantly less change in kidney function compared to 90Y-DOTATATE.
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May 2013