Long-term survival and nearly asymptomatic course of carcinoid tumour with multiple metastases (treated by surgery, chemotherapy, 90Y-DOTATATE, and LAR octreotide analogue): a case report

Carcinoids are the most common neuroendocrine tumours. They are usually slowly growing, located in the small intestine, secrete serotonin, and are characterized by long survival of patients, so prognosis is generally good. The most frequently encountered clinical presentations of carcinoids are intermittent abdominal pain and carcinoid syndrome (diarrhoea and flushing). Metastases worsen the prognosis and limit the survival of the patients. We report a case of carcinoid tumour with primary focus in the ileum, with an appendix infiltration, in a thirty-two-year-old woman with acute appendicitis symptoms only. Carcinoid was diagnosed postoperatively by histopathological examination. Nowadays, twenty-five years after the surgery, there is evidence of nearly asymptomatic numerous metastases. Only intermittent abdominal pain for about 1-2 years was reported. Partial metastases resection was performed, followed by chemotherapy, 90Y-DOTATATE and then long-acting release octreotide analogue therapy. In the meantime, severe chronic heart failure (NYHA IV) due to tricuspid combined valvular heart disease and pulmonary hypertension was diagnosed. Combined therapy, typical for chronic heart failure, together with long-acting octreotide analogue highly improved the patient’s heart sufficiency and reduced carcinoid syndrome symptoms. The only adverse events of octreotide therapy were hyperbilirubinaemia and itching. Long-term survival is typical for carcinoids, but 30-years survival has not been described in the literature yet.Rakowiak jest jednym z najczęstszych guzów neuroendokrynnych. Umiejscawia się w obrębie jelita cienkiego, zazwyczaj jako wolno rosnący guz wydzielający serotoninę. Pacjentów chorych na rakowiaka charakteryzuje długie przeżycie i dobre w większości przypadków rokowanie. Najczęstszymi objawami tego nowotworu są nawracające bóle w jamie brzusznej i objawy zespołu rakowiaka (biegunka i napadowe zaczerwienienia skóry - "flush"). Pojawienie się przerzutów pogarsza rokowanie oraz skraca czas przeżycia chorych. Opisany przypadek dotyczy 32-letniej kobiety z pierwotnym ogniskiem rakowiaka zlokalizowanym w jelicie krętym, naciekajacym wyrostek robaczkowy z objawami ostrego zapalenia wyrostka robaczkowego. Rakowiak został zdiagnozowany pooperacyjnie na podstawie oceny histopatologicznej. Dwadzieścia pięć lat po zabiegu operacyjnym wykryto prawie bezobjawowe liczne ogniska przerzutowe. Chora w wywiadzie wymieniła jedynie nawracające bóle w jamie brzusznej w okresie 1-2 lat przed rozpoznaniem przerzutów. W trakcie zabiegu operacyjnego usunięto część guzów przerzutowych, a następnie poddano pacjentkę chemioterapii, leczeniu 90Y-DOTATATE, a następnie preparatami oktreotydu LAR. W międzyczasie rozpoznano przewlekłą, ciężką niewydolność serca (NYHA IV) w przebiegu złożonej wady zastawki trójdzielnej serca oraz nadciśnienia płucnego. Złożona terapia, typowa dla przewlekłej niewydolności serca razem z długodziałającym analogiem oktreotydu znacznie poprawiły wydolność serca oraz zredukowały objawy zespołu rakowiaka. Jedynym działaniem niepożądanym terapii oktreotydem były hiperbilirubinemia oraz świąd. Długi okres przeżycia jest typowy dla rakowiaka, jednak 30-letnie przeżycie nie było dotychczas opisywane w literaturze

Charakterystyka modeli in vitro do badań nad rakiem jajnika

W leczeniu onkologicznym coraz większą rolę odgrywają leki celowane molekularnie. W terapii raka jajnika najbardziej obiecujące wyniki daje zastosowanie leków z grupy inhibitorów polimerazy poliADP-rybozy (PARP). Badania kliniczne ostatnich lat wykazały, że inhibitory PARP stosowane w terapii podtrzymującej wydłużają czas wolny od progresji o wiele miesięcy. To zachęca do poszukiwania kolejnych leków celowanych i stwarza nadzieję, że rak jajnika może się stać chorobą przewlekłą, o wieloletnim przebiegu.Problemem w badaniach nad rakiem jajnika jest heterogenność choroby. Ostatnie badania wskazują, że różne typy histologiczne mogą mieć odrębne pochodzenie tkankowe. Według współczesnej wiedzy określenie „rak jajnika” jest sztucznym pojęciem, obejmującym różne inwazyjne raki zlokalizowane w obrębie miednicy. Badania genetyczne i immunofenotypowe wskazują, że niskozróżnicowany rak surowiczy, najczęstszy i najgorzej rokujący typ histologiczny, w większości przypadków wywodzi się z nabłonka jajowodu, raki endometrioidalne i jasnokomórkowe wywodzą się zaś prawdopodobnie z endometrium. Dlatego w badaniach podstawowych i przedklinicznych nad rakiem jajnika potrzebne są dobrze scharakteryzowane modele odpowiadające poszczególnym typom histologicznym.W niniejszej pracy omówiono najczęściej wykorzystywane linie komórkowe stosowane w badaniach in vitro. Opracowanie ma na celu podsumowanie zalet i ograniczeń różnych modeli, obejmujących hodowle pierwotne i stabilne linie komórkowe, model hodowli dwu- i trójwymiarowej itp. W szczególności autorzy chcą zwrócić uwagę badaczy, że najczęściej stosowane linie komórkowe SKOV3 i A2780 nie są właściwym modelem do badań nad niskozróżnicowanym rakiem surowiczym

Characteristic of cells isolated from human Abdominal Aortic Aneurysm samples cultured in vitro

Abstract Background: This study aimed to standardize cell culture methods for major cell types isolated from three layers of human AAA. We also aimed to determine cell types in each layer of each AAA segment and compare them with cell types in layers of control, unchanged segments. Material and methods We divided AAAs into three segments along the AAA and control segments flanking the aneurysm. Isolated cells following expansion were analyzed by flow cytometry, immunochemistry and microscopic methods. Fluorochrome-conjugated antibodies were used to detect the three major cell types (endothelial cells, smooth muscle cells, and fibroblasts) in each layer of every AAA segment. Results: Culture of cells from the three AAA segments was successfully established in 21% of patients. In all of the layers, only a small proportion of cells showed layer- specific markers of cell types. The majority of cells from every layer were positive for CD90, which is considered specific marker of fibroblasts in the aorta. Conclusions: We describe methodology for isolation of cells, their culture conditions, and phenotypic characterization for AAA. The wall of AAA loses its specific types of cells in all of the layers compared with the normal abdominal aortic wall

Impact of the putative cancer stem cell markers and growth factor receptor expression on the sensitivity of ovarian cancer cells to treatment with various forms of the HER inhibitors and cytotoxic drugs

Increased expression and activation of human epidermal growth factor receptor (EGFR) and HER-2 have been reported in numerous cancers. The aim of this study was to determine the sensitivity of a large panel of human ovarian cancer cell lines (OCCLs) to treatment with various forms of small molecule tyrosine kinase inhibitors (TKIs) and cytotoxic drugs. The aim was to see if there was any association between the protein expression of various biomarkers including three putative ovarian cancer stem cell (CSC) markers (CD24, CD44, CD117/c-Kit), P-glycoprotein (P-gp), and HER family members and response to treatment with these agents. The sensitivity of 10 ovarian tumour cell lines to the treatment with various forms of HER TKIs (gefitinib, erlotinib, lapatinib, sapitinib, afatinib, canertinib, neratinib), as well as other TKIs (dasatinib, imatinib, NVP-AEW541, crizotinib) and cytotoxic agents (paclitaxel, cisplatin and doxorubicin), as single agents or in combination, was determined by SRB assay. The effect on these agents on the cell cycle distribution, and downstream signaling molecules and tumour migration were determined using flow cytometry, western blotting, and the IncuCyte Clear View cell migration assay respectively. Of the HER inhibitors, the irreversible pan-TKIs (canertinib, neratinib and afatinib) were the most effective TKIs for inhibiting the growth of all ovarian cancer cells, and for blocking the phosphorylation of EGFR, HER-2, AKT and MAPK in SKOV3 cells. Interestingly, while the majority of cancer cells were highly sensitive to treatment with dasatinib, they were relatively resistant to treatment with imatinib (i.e., IC50 >10 µM). Of the cytotoxic agents, paclitaxel was the most effective for inhibiting the growth of OCCLs, and of various combinations of these drugs, only treatment with a combination of NVP-AEW541 and paclitaxel produced a synergistic or additive anti-proliferative effect in all three cell lines examined (i.e., SKOV3, Caov3, ES2). Finally, of the TKIs, only treatment with afatinib, neratinib and dasatinib were able to reduce the migration of HER-2 overexpressing SKOV3 cells. We did not find any significant association between the expression of putative ovarian CSC marker, HER family members, c-MET, ALK, and IGF-IR and the response to the irreversible HER TKIs. Our results support the need for further investigations of the therapeutic potential of these irreversible HER family blockers in ovarian cancer, and the therapeutic potential of dasatinib when used in combination with the inhibitors of the HER family members in ovarian cancer

The relationship between the circadian type and work-family spillover.

Celem niniejszej pracy było zbadanie w jaki sposób typ okołodobowy wiąże się z występowaniem pozytywnego lub negatywnego wpływu między pracą a rodziną. Badaniami objęto grupę 42 mężczyzn w wieku od 24 do 52 lat pracujących w przedsiębiorstwie FAKRO sp. z o. o. w Nowym Sączu zajmującym się produkcją i dystrybucją okien. Badani pracowali w systemie dwuzmianowym z turnusem zmianowym trwającym 5 dni, rotującym do przodu. W badaniu wykorzystano takie narzędzia jak: Kwestionariusz Typu Okołodobowego Folkarda (2011) i Skala Wzajemnego Oddziaływania Pracy i Rodziny autorstwa Grzywacza i Marks (2000). Analiza wyników wykazała związek między małymi możliwościami opanowania senności a wyższym natężeniem konfliktu praca – rodzina. Znaczy to, że osoby o ospałym typie okołodobowym spostrzegają więcej negatywnego wpływu pracy na rodzinę. Hipotezy dotyczące związku elastyczności nawyków snu z którymkolwiek wymiarem relacji praca - rodzina nie zostały potwierdzone. Nie potwierdziły się też hipotezy mówiące o korelacji wymiaru zdolności – niezdolności opanowania senności z konfliktem rodzina – praca oraz facylitacją praca – rodzina i rodzina – praca.The aim of the study presented in this thesis was to examine relationship between circadian type and work-family spillover seen as positive or negative interface between work and family. Research was conducted in FAKRO company, producing and distributing windows, among male shiftworkers at the age of 24 to 52. Variables were measured with: Circadian Type Inventory by Folkard (2011) and Work – Family Spillover Scale by Grzywacz & Marks (2000). The results show relationship between high level of inability to overcome drowsiness and high level of work – family conflict. The study showed no significant correlation between people of flexible circadian type and work – family spillover, both positive and negative. Also there was no significant correlation between languid type and family – work conflict and both types of facilitation

Neurogenic muscle hypertrophy as an uncommon case of the calf enlargement — a case report and literature review

Unilateral limb edema is a common diagnostic problem. Apart from the most common pathologies, i.e. chronicvenous insufficiency and lymphedema, differential diagnosis should include unusual causes of asymmetric extremityedema. We presented a case of 41-year-old man with suspicion of lymphedema of the left calf, who reportedto a lymphology clinic. We discuss subsequent steps of the diagnostic procedure in case of the calf edema.In our patient, neurogenic muscle hypertrophy was found to be the cause of the calf enlargement. The diagnosiswas confirmed by results of ultrasound, magnetic resonance, computed tomography, lymphoscintigraphy andelectromyography examinations. Neurogenic muscle hypertrophy is a very rare and unusual cause of the calfenlargement. Nevertheless, it should be taken into account in the differential diagnosis

Different Patterns of Bacterial Species and Antibiotic Susceptibility in Diabetic Foot Syndrome with and without Coexistent Ischemia

Aims. Infection in diabetic foot syndrome (DFS) represents serious medical problem, and the annual risk of DFS in diabetic patients is 2.5%. More than half of the patients with DFS have symptoms of extremity ischemia (peripheral arterial disease (PAD)). The aim of the present study was to analyze the frequency of particular bacterial strains in people with DFS, analyze the impact of arterial ischemia on the occurrence of a given pathogen, and evaluate the antibacterial treatment based on the results of bacterial culture. Methods. The analysis included 844 bacterial strains obtained from 291 patients with DFS hospitalized in the Department of Angiology in years 2016–2019. Results. The most common isolates were Staphylococcus aureus, Enterococcus faecalis, Enterobacter cloacae, Pseudomonas aeruginosa, and Acinetobacter baumannii. Nearly 20% of the species were found to have at least one resistance mechanism. In patients with PAD, Gram-negative species were isolated more commonly than in people without PAD. The most useful drugs in DFS in hospitalized patients are penicillins with beta-lactamase inhibitors, 3rd- to 5th-generation cephalosporins (with many exceptions), carbapenems, aminoglycosides, and tigecycline. Conclusions. Bacterial strains isolated from ischemic DFS are more resistant to commonly used antibacterial agents, i.e., penicillins (including penicillins with beta-lactamase inhibitors), cephalosporins (except for the 4th and 5th generations), glycopeptides, and linezolid. When planning treatment of hospitalized patients with DFS, the presence of ischemia in DFS should always be taken into consideration. It determines the occurrence of particular bacterial species and the choice of antibacterial agent and may determine the rate of treatment success

Comparison of TLS and SLAM technologies for 3D reconstruction of objects with different geometries

Technological advances have made the 3D mapping process easily available and simpler. However, there are still aspects that need to be improved and enhanced. The efficient acquisition of 3D data and reconstruction of objects with high accuracy continues to be a challenge for the scientific community. One of the most frequently used 3D mapping methods is Terrestrial Laser Scanning (TLS), which allows the collection of high-resolution and precise data. Another method gaining popularity among researchers and professionals is mobile scanning technology, which enables real-time data capture. Its mobility and speed make it an effective alternative to traditional scanning technologies. This article compares two mapping technologies: SLAM (Simultaneous Localization and Mapping) and TLS taking into account the technical aspects of the instruments, processing methods, time and cost, and concluding with an assessment of the final accuracy. The geometry of several selected objects was analyzed. The resulting root mean square error (RMSE) for the compared distances on the two point clouds was 5 cm, which proves that the SLAM technology can be successfully applied for scenarios requiring centimeter-level accuracy

Fibronectin and Periostin as Prognostic Markers in Ovarian Cancer

Previously, based on a DNA microarray experiment, we identified a 96-gene prognostic signature associated with the shorter survival of ovarian cancer patients. We hypothesized that some differentially expressed protein-coding genes from this signature could potentially serve as prognostic markers. The present study was aimed to validate two proteins, namely fibronectin (FN1) and periostin (POSTN), in the independent set of ovarian cancer samples. Both proteins are mainly known as extracellular matrix proteins with many important functions in physiology. However, there are also indications that they are implicated in cancer, including ovarian cancer. The expression of these proteins was immunohistochemically analyzed in 108 surgical samples of advanced ovarian cancer (majority: high-grade serous) and additionally on tissue arrays representing different stages of the progression of ovarian and fallopian tube epithelial tumors, from normal epithelia, through benign tumors, to adenocarcinomas of different stages. The correlation with clinical, pathological, and molecular features was evaluated. Kaplan–Meier survival analysis and Cox-proportional hazards models were used to estimate the correlation of the expression levels these proteins with survival. We observed that the higher expression of fibronectin in the tumor stroma was highly associated with shorter overall survival (OS) (Kaplan–Meier analysis, log-rank test p = 0.003). Periostin was also associated with shorter OS (p = 0.04). When we analyzed the combined score, calculated by adding together individual scores for stromal fibronectin and periostin expression, Cox regression demonstrated that this joint FN1&POSTN score was an independent prognostic factor for OS (HR = 2.16; 95% CI: 1.02–4.60; p = 0.044). The expression of fibronectin and periostin was also associated with the source of ovarian tumor sample: metastases showed higher expression of these proteins than primary tumor samples (χ2 test, p = 0.024 and p = 0.032). Elevated expression of fibronectin and periostin was also more common in fallopian cancers than in ovarian cancers. Our results support some previous observations that fibronectin and periostin have a prognostic significance in ovarian cancer. In addition, we propose the joint FN1&POSTN score as an independent prognostic factor for OS. Based on our results, it may also be speculated that these proteins are related to tumor progression and/or may indicate fallopian–epithelial origin of the tumor

Charakterystyka modeli in vitro do badań nad rakiem jajnika

Nowadays, targeted therapy plays a growing role in oncological treatment. In ovarian cancer, particularly promising results are achieved with poly (ADP-ribose) polymerase (PARP) inhibitors. Recent clinical trials have shown that PARP inhibitors can result in significantly longer progression-free survival. These results encourage the search for other targeted therapies and bring hope that ovarian cancer can soon become a manageable chronic disease. The main problem in ovarian cancer research is the heterogeneity of this disease. Recent studies have shown that different histological types of ovarian cancer can originate from distinct tissues. According to the recent knowledge, “ovarian cancer” is an artificial term for distinct invasive malignancies localised within the pelvis. Genetic and immunophenotype analyses have shown that high-grade serous ovarian cancer, the most frequent histological type and the one with the worst prognosis, originates mainly from fallopian tube epithelium, while endometrioid and clear-cell cancers originate from the endometrium. For these reasons, in basic and preclinical studies on ovarian cancer, one has to carefully choose a well-defined model system, corresponding to the histological type of interest. In this article, we discuss ovarian cancer cell lines most frequently used in in vitro studies. Our aim is to indicate the advantages and disadvantages of different models, encompassing primary and established cell cultures, two- and three-dimensional models, etc. In particular, we would like to alert researchers to the fact that the most popular cell lines SKOV3 and A2780 do not represent a suitable model for studies on high-grade serous ovarian cancer.Coraz większą rolę w leczeniu onkologicznym odgrywają leki celowane molekularnie. W terapii raka jajnika najbardziej obiecujące wyniki daje zastosowanie leków z grupy inhibitorów polimerazy poliADP-rybozy (PARP). Badania kliniczne ostatnich lat wykazały, że inhibitory PARP stosowane w terapii podtrzymującej wydłużają czas wolny od progresji o wiele miesięcy. To zachęca do poszukiwania kolejnych leków celowanych i stwarza nadzieję, że rak jajnika może się stać chorobą przewlekłą, o wieloletnim przebiegu. Problemem w badaniach nad rakiem jajnika jest heterogenność choroby. Ostatnie badania wskazują, że różne typy histologiczne mogą mieć odrębne pochodzenie tkankowe. Według współczesnej wiedzy, określenie „rak jajnika” jest sztucznym pojęciem obejmującym różne inwazyjne raki zlokalizowane w obrębie miednicy. Badania genetyczne i immunofenotypowe wskazują, że niskozróżnicowany rak surowiczy, najczęstszy i najgorzej rokujący typ histologiczny, w większości przypadków wywodzi się z nabłonka jajowodu, zaś raki endometrioidalne i jasnokomórkowe wywodzą się prawdopodobnie z endometrium. Dlatego, w badaniach podstawowych i przedklinicznych nad rakiem jajnika potrzebne są dobrze scharakteryzowane modele odpowiadające poszczególnym typom histologicznym. W niniejszej pracy omówiono najczęściej wykorzystywane linie komórkowe stosowane w badaniach in vitro. Nasze opracowanie ma na celu podsumowanie zalet i ograniczeń różnych modeli, obejmujących hodowle pierwotne i stabilne linie komórkowe, model hodowli dwu- i trójwymiarowej. W szczególności pragniemy zwrócić uwagę badaczy, że najczęściej stosowane linie komórkowe SKOV3 i A2780, nie są właściwym modelem do badań nad niskozróżnicowanym rakiem surowiczym