Klinička važnost VEGF-A i mikrožilne gustoće u difuznom limfomu velikih B-stanica i folikularnom limfomu niskog stupnja

Angiogenesis is essential for the development, growth and progression of tumors. Although vascular endothelial growth factor (VEGF) is a well-known proangiogenic factor, its impact on lymphoma has not yet been fully clarified. The aim of this study was to evaluate VEGF-A ­expression and microvessel density (MVD) in aggressive lymphoma such as diffuse large B-cell lymphoma (DLBCL), in indolent lymphomas such as low-grade follicular lymphoma (FL), and in lymph node reactive follicular hyperplasia (FH). In 80 prospective and retrospective cases (30 DLBCL, 30 FL and 20 FH), CD31 was analyzed by immunohistochemical staining assessing density of blood vessels, as well as the total number of CD31 positive endothelial cells. The results were compared with relevant clinical data. MVD was 85% in FH, followed by 60% in DLBCL and 43% in low-grade FL. VEGF-A was significantly higher in DLBCL than in low-grade FL and FH. A statistically significant association of MVD and VEGF-A with the International Prognostic Index (IPI) was found in DLBCL. High MVD and VEGF-A expression was observed in DLBCL patients with high IPI, while there was no statistically significant association between MVD and VEGF-A with the Follicular Lymphoma International Prognostic Index in low-grade FL. Our results suggested an important relationship between angiogenesis and high-grade lymphoma.Angiogeneza je bitna za razvoj, rast i progresiju tumora. Iako je vaskularni endotelni faktor rasta (VEGF) dobro poznati proangiogeni čimbenik, njegov utjecaj na limform nije u potpunosti razjašnjen. Cilj ovoga istraživanja bio je procijeniti izraženost VEGF-A i mikrožilnu gustoću (MVD) kod agresivnog limfoma kao što je difuzni limfom velikih B-stanica (DLBCL), kod indolentnih limfoma kao što je folikularni limfom niskog stupnja (FL) i kod reaktivne folikularne hiperplazije limfnih čvorova (FH). Analiza CD31 provedena je u 80 prospektivnih i retrospektivnih slučajeva (30 DLBCL, 30 FL i 20 FH) imunohistokemijskim bojenjem za procjenu gustoće krvnih žila, kao i ukupnog broja endotelnih stanica pozitivnih na CD31. Rezultati su uspoređeni s relevantnim kliničkim podacima. MVD je bila 85% kod FH, 60% kod DLBCL i 43% kod FL niskog stupnja. VEGF-A je bio značajno viši u DLBCL u odnosu na FL niskog stupnja i FH. Statistički značajna udruženost MVD i VEGF-A s Internacionalnim prognostičkim indeksom (IPI) utvrđena je kod DLBCL. Visoka izraženost MVD i VEGF-A zabilježena je u bolesnika s DLBCL s visokim IPI, dok nije bilo statistički značajne udruženosti MVD i VEGF-A s Internacionalnim prognostičkim indeksom za folikularni limfom kod FL niskog stupnja. Rezultati ovog istraživanja ukazuju na važan odnos između angiogeneze i limfoma visokog stupnja

Hepatobiliary neuroendocrine carcinoma: a case report

<p>Abstract</p> <p>Introduction</p> <p>Neuroendocrine carcinoma of the gallbladder is a rather uncommon disease. We report a case of a neuroendocrine tumor that was located in the wall of the gallbladder and that extended into the liver.</p> <p>Case presentation</p> <p>A 52-year-old Caucasian woman presented with right-sided abdominal pain, ascites and jaundice. An MRI scan revealed a tumor mass located in the gallbladder wall and involving the liver. A partial hepatectomy and cholecystectomy were performed. Histology revealed a neuroendocrine tumor, which showed scattered Grimelius positive cells and immuno-expressed epithelial and endocrine markers. Our patient is undergoing chemotherapy treatment.</p> <p>Conclusion</p> <p>Gastroenteropancreatic neuroendocrine tumors need a multidisciplinary approach, involving immunohistochemistry and molecular-genetic techniques.</p

Clear cell variant of diffuse large B-cell lymphoma: a case report

<p>Abstract</p> <p>Introduction</p> <p>Diffuse large B-cell lymphoma is a diffuse proliferation of large neoplastic B lymphoid cells with a nuclear size equal to or exceeding the normal macrophage nuclei. We report a case of a clear cell variant of diffuse large B-cell lymphoma involving a lymph node in the neck, which was clinically suspected of being metastatic carcinoma.</p> <p>Case presentation</p> <p>A 39-year-old Caucasian ethnic Albanian man from Kosovo presented with a rapidly enlarging lymph node in his neck, but he also disclosed B symptoms and fatigue. A cytological aspirate of the lymph node revealed pleomorphic features. Our patient underwent a cervical lymph node biopsy (large excision). The mass was homogeneously fish-flesh, pale white tissue replacing almost the whole structure of the lymph node. The lymph node biopsy showed a partial alveolar growth pattern, which raised clinical suspicion that it was an epithelial neoplasm. With regard to morphological and phenotypic features, we discovered large nodules in diffuse areas, comprising large cells with slightly irregular nuclei and clear cytoplasm admixed with a few mononuclear cells. In these areas, there was high mitotic activity, and in some areas there were macrophages with tangible bodies. Staining for cytokeratins was negative. These areas had the following phenotypes: cluster designation marker 20 (CD20) positive, B-cell lymphoma (Bcl)-2-positive, Bcl-6^-, CD5^-, CD3^-, CD21⁺(in alveolar patterns), prostate-specific antigen-negative, human melanoma black marker 45-negative, melanoma marker-negative, cytokeratin-7-negative and multiple myeloma marker 1-positive in about 30% of cells, and exhibited a high proliferation index marker (Ki-67, 80%).</p> <p>Conclusion</p> <p>According to the immunohistochemical findings, we concluded that this patient has a clear cell variant of diffuse large B-cell lymphoma of activated cell type, post-germinal center cell origin. Our patient is undergoing R-CHOP chemotherapy treatment.</p

Expression of VEGF-A and HIF1 alpha in diffuse large B-cell lymphoma and low grade follicular lymphoma

Angiogenesis is essential for the development, growth and progression of tumors. It is induced by hypoxia through mechanism that include the angiogenic transcription factor, hypoxia-inducible factor (HIF). Vascular endothelial growth factor (VEGF) is a well-known proangiogenic factor whose impact on tumor biology is widely studied. The aim of this study was to evaluate VEGF-A, HIF-1α expression and microvessel density (MVD) in diffuse large B-cell lymphoma (DLBCL), the most frequent aggressive lymphoma type, low grade follicular lymphoma (FL), the most frequent indolent lymphoma type, and reactive follicular hyperplasia (FH), a benign condition with lymphadenopathy. These factors were analyzed in 80 patients (30 DLBCL, 30 FL and 20 FH) diagnosed at the Institutes of Pathology, Faculty of Medicine, University of Pristina and Faculty of Medicine, Cyril & Methodius University of Skopje. VEGF-A and HIF-1α expression was determined using immunohistochemistry, percentage of positive tumor cells and staining intensity were analyzed. MVD was determined by counting the number of blood vessels identified by antiCD31 immunohistochemistry in hot-spots as well as the total number of CD31 positive endothelial cells. The results were compared with Follicular Lymphoma International Prognostic Index – FLIPI (for FL) and International Prognostic Index – IPI (for DLBCL) scores. Our results confirm that angiogenesis and hypoxia correlate with aggressiveness of lymphoma. DLBCL had higher expression of VEGF-A, HIF-α and higher MVD than FL. Also, VEGF-A expression and MVD correlated with IPI and VEGF-A and HIF-1α expression with FLIPI.Angiogeneza je ključna za razvoj, rast i progresiju solidnih tumora. Potaknuta je hipoksijom kroz mehanizam koji uključuje angiogenetski transkripcijski faktor hypoxia-inducible factor (HIF). Vaskularni enodotelijalni faktor rasta (VEGF) dobro je poznat proangiogeni faktor, čija se uloga u biologiji tumora široko istražuje. Cilj ovog istraživanja je procijeniti ekspresiju VEGF-A, HIF-α i CD31 (MVD) u difuznom B-velikostaničnom non-Hodgkin limfomu (DLBCL) kao najčešćem agresivnom tipu limfoma, folikularnom limfomu niskog gradusa (FL) kao najčešćem indolentnom tipu limfoma, i u benignom povećanju limfnog čvora - reaktivnoj folikularnoj hiperplaziji (FH). Nabrojeni faktori analizirani su u 80 slučajeva (30 DLBCL, 30 FL i 20 FH) dijagnosticiranih u Zavodu za patologiju Medicinskog fakulteta Sveučilišta u Prištini i Medicinskom fakultetu Sveučilišta Čirila i Metoda u Skopju. Ekspresija VEGF-A i HIF-α je analizirana nakon imunohistokemijskog bojanja preparata, procjenom postotka pozitivnih tumorskih stanica i intenziteta bojenja. Protutijelom CD31 je procjenjivana gustoća (broj) krvnih žila unutar tumora, kao i ukupni broj CD31 pozitivnih endotelnih stanica. Dobiveni rezultati su uspoređivani s Internacionalnim prognostičkim indeksom za folikularni limfom – FLIPI i Internationalnim prognostičkim indeksom - IPI za DLBCL. Provedeno istraživanje dokazalo je povezanost hipoksije i angiogeneze s agresivnošću limfoma. DLBCL karakterizira viša razina ekspresije VEGF-A, HIF-α i viši MDV u odnosu na folikularni limfom niskog gradusa. Visoka razina ekspresije VEGF-A, HIF-α i viši MVD također su u korelaciji s visokim IPI (u DLBCL-u) dok su VEGF-A i HIF-α u korelaciji s FLIPI (u FL)

Expression of VEGF-A and HIF1 alpha in diffuse large B-cell lymphoma and low grade follicular lymphoma

Angiogenesis is essential for the development, growth and progression of tumors. It is induced by hypoxia through mechanism that include the angiogenic transcription factor, hypoxia-inducible factor (HIF). Vascular endothelial growth factor (VEGF) is a well-known proangiogenic factor whose impact on tumor biology is widely studied. The aim of this study was to evaluate VEGF-A, HIF-1α expression and microvessel density (MVD) in diffuse large B-cell lymphoma (DLBCL), the most frequent aggressive lymphoma type, low grade follicular lymphoma (FL), the most frequent indolent lymphoma type, and reactive follicular hyperplasia (FH), a benign condition with lymphadenopathy. These factors were analyzed in 80 patients (30 DLBCL, 30 FL and 20 FH) diagnosed at the Institutes of Pathology, Faculty of Medicine, University of Pristina and Faculty of Medicine, Cyril & Methodius University of Skopje. VEGF-A and HIF-1α expression was determined using immunohistochemistry, percentage of positive tumor cells and staining intensity were analyzed. MVD was determined by counting the number of blood vessels identified by antiCD31 immunohistochemistry in hot-spots as well as the total number of CD31 positive endothelial cells. The results were compared with Follicular Lymphoma International Prognostic Index – FLIPI (for FL) and International Prognostic Index – IPI (for DLBCL) scores. Our results confirm that angiogenesis and hypoxia correlate with aggressiveness of lymphoma. DLBCL had higher expression of VEGF-A, HIF-α and higher MVD than FL. Also, VEGF-A expression and MVD correlated with IPI and VEGF-A and HIF-1α expression with FLIPI.Angiogeneza je ključna za razvoj, rast i progresiju solidnih tumora. Potaknuta je hipoksijom kroz mehanizam koji uključuje angiogenetski transkripcijski faktor hypoxia-inducible factor (HIF). Vaskularni enodotelijalni faktor rasta (VEGF) dobro je poznat proangiogeni faktor, čija se uloga u biologiji tumora široko istražuje. Cilj ovog istraživanja je procijeniti ekspresiju VEGF-A, HIF-α i CD31 (MVD) u difuznom B-velikostaničnom non-Hodgkin limfomu (DLBCL) kao najčešćem agresivnom tipu limfoma, folikularnom limfomu niskog gradusa (FL) kao najčešćem indolentnom tipu limfoma, i u benignom povećanju limfnog čvora - reaktivnoj folikularnoj hiperplaziji (FH). Nabrojeni faktori analizirani su u 80 slučajeva (30 DLBCL, 30 FL i 20 FH) dijagnosticiranih u Zavodu za patologiju Medicinskog fakulteta Sveučilišta u Prištini i Medicinskom fakultetu Sveučilišta Čirila i Metoda u Skopju. Ekspresija VEGF-A i HIF-α je analizirana nakon imunohistokemijskog bojanja preparata, procjenom postotka pozitivnih tumorskih stanica i intenziteta bojenja. Protutijelom CD31 je procjenjivana gustoća (broj) krvnih žila unutar tumora, kao i ukupni broj CD31 pozitivnih endotelnih stanica. Dobiveni rezultati su uspoređivani s Internacionalnim prognostičkim indeksom za folikularni limfom – FLIPI i Internationalnim prognostičkim indeksom - IPI za DLBCL. Provedeno istraživanje dokazalo je povezanost hipoksije i angiogeneze s agresivnošću limfoma. DLBCL karakterizira viša razina ekspresije VEGF-A, HIF-α i viši MDV u odnosu na folikularni limfom niskog gradusa. Visoka razina ekspresije VEGF-A, HIF-α i viši MVD također su u korelaciji s visokim IPI (u DLBCL-u) dok su VEGF-A i HIF-α u korelaciji s FLIPI (u FL)

Expression of VEGF-A and HIF1 alpha in diffuse large B-cell lymphoma and low grade follicular lymphoma

Angiogenesis is essential for the development, growth and progression of tumors. It is induced by hypoxia through mechanism that include the angiogenic transcription factor, hypoxia-inducible factor (HIF). Vascular endothelial growth factor (VEGF) is a well-known proangiogenic factor whose impact on tumor biology is widely studied. The aim of this study was to evaluate VEGF-A, HIF-1α expression and microvessel density (MVD) in diffuse large B-cell lymphoma (DLBCL), the most frequent aggressive lymphoma type, low grade follicular lymphoma (FL), the most frequent indolent lymphoma type, and reactive follicular hyperplasia (FH), a benign condition with lymphadenopathy. These factors were analyzed in 80 patients (30 DLBCL, 30 FL and 20 FH) diagnosed at the Institutes of Pathology, Faculty of Medicine, University of Pristina and Faculty of Medicine, Cyril & Methodius University of Skopje. VEGF-A and HIF-1α expression was determined using immunohistochemistry, percentage of positive tumor cells and staining intensity were analyzed. MVD was determined by counting the number of blood vessels identified by antiCD31 immunohistochemistry in hot-spots as well as the total number of CD31 positive endothelial cells. The results were compared with Follicular Lymphoma International Prognostic Index – FLIPI (for FL) and International Prognostic Index – IPI (for DLBCL) scores. Our results confirm that angiogenesis and hypoxia correlate with aggressiveness of lymphoma. DLBCL had higher expression of VEGF-A, HIF-α and higher MVD than FL. Also, VEGF-A expression and MVD correlated with IPI and VEGF-A and HIF-1α expression with FLIPI.Angiogeneza je ključna za razvoj, rast i progresiju solidnih tumora. Potaknuta je hipoksijom kroz mehanizam koji uključuje angiogenetski transkripcijski faktor hypoxia-inducible factor (HIF). Vaskularni enodotelijalni faktor rasta (VEGF) dobro je poznat proangiogeni faktor, čija se uloga u biologiji tumora široko istražuje. Cilj ovog istraživanja je procijeniti ekspresiju VEGF-A, HIF-α i CD31 (MVD) u difuznom B-velikostaničnom non-Hodgkin limfomu (DLBCL) kao najčešćem agresivnom tipu limfoma, folikularnom limfomu niskog gradusa (FL) kao najčešćem indolentnom tipu limfoma, i u benignom povećanju limfnog čvora - reaktivnoj folikularnoj hiperplaziji (FH). Nabrojeni faktori analizirani su u 80 slučajeva (30 DLBCL, 30 FL i 20 FH) dijagnosticiranih u Zavodu za patologiju Medicinskog fakulteta Sveučilišta u Prištini i Medicinskom fakultetu Sveučilišta Čirila i Metoda u Skopju. Ekspresija VEGF-A i HIF-α je analizirana nakon imunohistokemijskog bojanja preparata, procjenom postotka pozitivnih tumorskih stanica i intenziteta bojenja. Protutijelom CD31 je procjenjivana gustoća (broj) krvnih žila unutar tumora, kao i ukupni broj CD31 pozitivnih endotelnih stanica. Dobiveni rezultati su uspoređivani s Internacionalnim prognostičkim indeksom za folikularni limfom – FLIPI i Internationalnim prognostičkim indeksom - IPI za DLBCL. Provedeno istraživanje dokazalo je povezanost hipoksije i angiogeneze s agresivnošću limfoma. DLBCL karakterizira viša razina ekspresije VEGF-A, HIF-α i viši MDV u odnosu na folikularni limfom niskog gradusa. Visoka razina ekspresije VEGF-A, HIF-α i viši MVD također su u korelaciji s visokim IPI (u DLBCL-u) dok su VEGF-A i HIF-α u korelaciji s FLIPI (u FL)

The Study of Volume Density of Tracheal Ganglions In Vitro in New Born Babies with Respiratory Distress Syndrome

Volume density of respiratory organs was studied in vitro in newborn babies at different age of gestation (abort, immature, premature and mature) using stereometric method. The total of 23 cases was subject to this study. The respiratory organs (trachea, lungs) were taken from autopsies of newborn babies exited from different causes. For this purpose the tissues were fixed in formalin (10%) solution, cut serially in 7μ and 10μ slabs. Volume density of the respiratory system was assessed stereometricaly using Universal testing system Weibel M 42. We observed that volume density of epithelia, musculature and glands were proportionally present in the tracheal tissue. Cellular interstitial tissue is consistently increasing and corresponds to the developmental stages of the newborn babies. The density of tracheal ganglions is greater in premature ages of immature and premature newborns (p<0,05). Decreased number of ganglion cells is observed in mature ages (p<0,05). This is caused by intensive ramification of ganglions from serosa to deeper layers of trachea right to epithelium. Medium diameter of tracheal ganglions is greater in mature newborn babies and corresponds to developmental ages of babies

Biomechanical and Macroscopic Evaluations of the Effects of 5-Fluorouracil on Partially Divided Flexor Tendon Injuries in Rabbits

Background: The main goals of flexor tendon surgery are to restore digital motion by providing tendon healing and to preserve tendon gliding. Our purpose was to investigate the effects of 5-fluorouracil (5-FU) on tendon adhesions in partially divided profundus flexor tendons (flexor digitorum profundus [FDPs]) following surgical repair and in partially divided FDPs without surgical repair, and to compare the results of the repair versus the nonrepair of zone two injuries via macroscopic and biomechanical evaluations of tendon adhesions. Methods: We used 32 adult male European rabbits (Oryctolagus cunniculus) weighing from 2.5 to 3.5 kg. The study was performed on the deep flexor tendons of the second and third digits of the right hind paws of the rabbits; thus, a total of 64 tendons were examined in this study. Results: Based on the results achieved in our experimental study, the load (N) significantly increased in subgroup 1a in which the tendons were surgically repaired and were not treated with 5-FU compared with subgroup 2a in which tendons were surgically repaired and treated with 5-FU. Conclusions: The load (N) significantly increased in subgroup 1a in which the tendons were surgically repaired and were not treated with 5-FU compared to subgroup 2a in which the tendons were surgically repaired and treated with 5-FU. Therefore, these results revealed a decrease in adhesion formation in the subgroup that was treated with 5-FU due to increased resistance to tendon adhesions during their excursion through the tendon sheath, which in this case required greater traction force