Biliary brush cytology for the diagnosis of malignancy: a single center experience [Citološki razmazi brisa četkicom u dijagnostici malignih promjena bilijarnog stabla: naše iskustvo]

Differentiation between benign and malignant biliary strictures is critical to the provision of adequate treatment. Brush cytology during the endoscopic retrograde cholangiopancreatography (ERCP) is the most commonly used method for obtaining tissue confirmation of the nature of biliary strictures. It’s specificity is remarkably high but reported sensitivities for the diagnosis of malignancy are low. Aim of our study was to assess sensitivity and specificity of biliary brush cytology in our institution, to find out main causes of false negative diagnoses and to confirm impression that the team approach has impact on sensitivity. Gold standard for diagnosis was definitive surgical histology or adequate clinical follow up for minimum of six month. Direct smears made by cytotechnician at the endoscopy room, and stained according to Papanicolaou and May-Grünwald Giemsa (MGG) were examined for well-recognized features of malignancy on conventional smears as a part of diagnostic routine. Cytologic diagnoses were benign, atypical/reactive, suspicious for malignancy and malignant. Of 143 brushings with available definitive diagnosis 36 (25%) had malignant cytologic diagnosis and 91(63.6%) were classified as benign, 3 were atypical/reactive and 13 suspicious for malignancy with 20 »false-negative« cases. When specimens with atypical and suspicious cytology were excluded from data analysis sensitivity was 64% and specificity was 100% and when suspicious findings were taken into account as true positives sensitivity rose to 71%. We find that biliary brush cytology, although mainly depending on the skill of endoscopist, as well as the experience of the cytologist, is a valuable method for obtaining accurate tissue diagnosis of biliary strictures, thus solving eternal diagnostic dilemma: benign or malignant

IMMUNOSENESCENCE, INFLAMMAGING AND RESILIENCE: AN EVOLUTIONARY PERSPECTIVE OF ADAPTATION IN THE LIGHT OF COVID-19 PANDEMIC

The evolution of immunology enabled the study of role of innate and adaptive immunity in systems biology network of immunosenescence and inflammaging. Due to global reduction in birth rates and reduced mortality, in year 2025 there will be about 1.2 billion of people over age of sixty, worldwide. The notion that the real age is not chronological, but the biological one led to the concept of "bioage", defining the biologic reactivity and resilience, including the immune competence of an individual. A competent immune network, systemic and mucosal is intrinsic to resilience and homeostasis of the human holobiont as the unit of evolution. In elderly, the immunosenescence could be associated with higher levels of proinflammatory mediators (such as IL-6), frialty and mortality. Proi-inflammatory state in elderly is denoted as inflammaging, characterized with low-grade (sterile) inflammation, as a physiologic response to life-long antigenic stimuli. When under control, inflammaging could be regarded as an efficient defense mechanism, oposed and regulated by anti-inflammatory pathways and molecules. Immunosensecence. The emerging concepts of "individual immunobiography" and "trained immunity" speak in favour that the immunological experience during the life would shape the ability of each individual to respond to various stimuli, strongly influencing the elements of innate and adaptive immunity, including macrophages and innate lymphoid cells. Older age is one of the main risk factors for the severe clinical picture and adverse outcome of COVID-19 infection, due to immunosenscence and chronic low-grade inflammation (inflammaging), both characterizing the immune reactioin in elderly. The senescent immune system, along with the advanc ed process of inflammaging is prone to react with uncontrolled activation of innate immune response that leads to cytokine release syndrome, tissue damage and adverse outcome of infection. Further research is aimed to nutritional and pharmacologic (immunomodulatory) interventions to influence the process of bioaging and immunosenscence, and to modulate the reaction of elderly to infection, including the COVID-19

The Importance of P-glycoprotein Multidrug Transporter Activity Measurement in Patients with Helicobacter pylori Infection

P-glycoprotein is important in local antibiotic resistance. Aim was to evaluate the role of P-glycoprotein in local antibiotic resistance in patients with antral gastritis during antibiotic therapy to Helicobacter pylori infection. In the group of 53 patients with pathohistologically verified gastritis and microbiologically confirmed H. pylori infection (no signs of antimicrobial resistance) we have determined P-glycoprotein activity in gastric mucosa biopsy specimens, and compared them with the P-glycoprotein activity in 12 control subjects with normal endoscopic findings. The H. pylori positive patients were treated according to Maastricht protocol with short-term 7-day therapy consisting of two antibiotics (amoxicillin and azithromycin/metronidazole and clarithromycin) and a proton pump inhibitor. P-glycoprotein activity was determined in rhodamine dye efflux test and quantified by ratio of the mean fluorescence (RMF) in flow cytometry analysis. H. pylori was successfully eradicated in the first cycle in 20 patients, whereas therapy was continued in 33 patients. The mean pre-treatment RMF values were higher in patients with H. pylori infection then in control subjects (p<0.0046). RMF was also higher in patients with multiple therapeutic failure than in those with successful H. pylori eradication (p<0.0001). RMF increased significantly during the antibiotic therapy (p<0.05). P-glycoprotein might be one of the causes of therapy failure in patients with H. pylori. Our study confirms the importance of quantitative evaluation of P-glycoprotein expression during antibiotic treatment response

Isolated Splenic Metastasis from Colorectal Carcinoma in a High Risk Patient: A Case Report

Isolated splenic metastasis arising from a colorectal carcinoma is a rare finding. We report a case of 74-year-old man with a medical history od diabetes type II and paroxysmal atrial fibrillation, who underwent a right hemicolectomy for an adenocarcinoma of caecum in August 2004. In June 2007 the patient was diagnosed with high grade aortic valve stenosis as well as long segment stenosis of the first obtuse marginal branch of left coronary artery. He was suggested aortic valve replacement with coronary artery bypass grafting but he refused the surgery. In October 2007 the patient underwent a 18FDG – PET scanning, due to increasing values of CEA serum level, which showed a 5 cm big isolated hypermetabolic lesion in the spleen. Due to operative risk, splenectomy was refused by surgeons. The patient underwent a chemotherapy with capecitabine in total of 8 cycles before his CEA level began to rise and MSCT showed a progression in size of splenic metastasis. The patients condition was reevaluated by a team of experts and splenectomy was performed in September 2008. In May 2009 during the postoperative follow up, MSCT scanning revealed enlarged lymph nodes in celiac region and hepatic lesion suspicious of metastasis and the patient was addmited for further chemotherapy treatment. There is still no standardized treatment for this condition due to small number of cases reported in literature. Splenectomy followed by chemotherapy seems to be an optimal treatment but still no final conclusions can be made

Biliary Brush Cytology for the Diagnosis of Malignancy: A Single Center Experience

Differentiation between benign and malignant biliary strictures is critical to the provision of adequate treatment. Brush cytology during the endoscopic retrograde cholangiopancreatography (ERCP) is the most commonly used method for obtaining tissue confirmation of the nature of biliary strictures. It’s specificity is remarkably high but reported sensitivities for the diagnosis of malignancy are low. Aim of our study was to assess sensitivity and specificity of biliary brush cytology in our institution, to find out main causes of false negative diagnoses and to confirm impression that the team approach has impact on sensitivity. Gold standard for diagnosis was definitive surgical histology or adequate clinical follow up for minimum of six month. Direct smears made by cytotechnician at the endoscopy room, and stained according to Papanicolaou and May-Grünwald Giemsa (MGG) were examined for well-recognized features of malignancy on conventional smears as a part of diagnostic routine. Cytologic diagnoses were benign, atypical/reactive, suspicious for malignancy and malignant. Of 143 brushings with available definitive diagnosis 36 (25%) had malignant cytologic diagnosis and 91(63.6%) were classified as benign, 3 were atypical/reactive and 13 suspicious for malignancy with 20 »false-negative« cases. When specimens with atypical and suspicious cytology were excluded from data analysis sensitivity was 64% and specificity was 100% and when suspicious findings were taken into account as true positives sensitivity rose to 71%. We find that biliary brush cytology, although mainly depending on the skill of endoscopist, as well as the experience of the cytologist, is a valuable method for obtaining accurate tissue diagnosis of biliary strictures, thus solving eternal diagnostic dilemma: benign or malignant

Isolated Splenic Metastasis from Colorectal Carcinoma in a High Risk Patient: A Case Report

Isolated splenic metastasis arising from a colorectal carcinoma is a rare finding. We report a case of 74-year-old man with a medical history od diabetes type II and paroxysmal atrial fibrillation, who underwent a right hemicolectomy for an adenocarcinoma of caecum in August 2004. In June 2007 the patient was diagnosed with high grade aortic valve stenosis as well as long segment stenosis of the first obtuse marginal branch of left coronary artery. He was suggested aortic valve replacement with coronary artery bypass grafting but he refused the surgery. In October 2007 the patient underwent a 18FDG – PET scanning, due to increasing values of CEA serum level, which showed a 5 cm big isolated hypermetabolic lesion in the spleen. Due to operative risk, splenectomy was refused by surgeons. The patient underwent a chemotherapy with capecitabine in total of 8 cycles before his CEA level began to rise and MSCT showed a progression in size of splenic metastasis. The patients condition was reevaluated by a team of experts and splenectomy was performed in September 2008. In May 2009 during the postoperative follow up, MSCT scanning revealed enlarged lymph nodes in celiac region and hepatic lesion suspicious of metastasis and the patient was addmited for further chemotherapy treatment. There is still no standardized treatment for this condition due to small number of cases reported in literature. Splenectomy followed by chemotherapy seems to be an optimal treatment but still no final conclusions can be made

Aportes desde la gestión integral del recurso hídrico para la determinación de la capacidad de carga turística en destinos insulares. caso de estudio Islas de Providencia y Santa Catalina

Los procesos turísticos que no son adecuadamente planificados generan presión sobre los sistemas ambientales, generando conflictos, problemas y decisiones difíciles de abordar por su complejidad enmarcada en la relación sociedad-naturaleza. Es evidente que estos procesos además de atentar contra el patrimonio natural, representan una gran amenaza para el patrimonio social y cultural. De acuerdo con la Organización Mundial del Turismo, este sector presenta un crecimiento importante en los últimos años y se prevé, que siga creciendo en los próximos. Es necesario entonces, estudiar de qué manera se pueden gestionar los destinos turísticos para ofrecer servicios de calidad garantizando la sostenibilidad. Los Estudios de Capacidad de Carga Turística representan uno de los instrumentos de mayor importancia para lograr estos propósitos, donde a través de un proceso sistemático se analizan variables que tienen influencia directa sobre el territorio y la prestación de servicios turísticos, con el fin de determinar la cantidad de visitantes que puede recibir y/o atender un destino sin alterar de manera significativa sus dinámicas naturales, sociales y culturales

Imunobiologija crijevne suznice: od lokalne imunosti i mikrobioma do zglobne upale

Sagledavajući evolucijski razvoj kralježnjaka i njihovu koevoluciju s vlastitom crijevnom mikrobiotom i okolišem, postaje jasno važno mjesto imunološkog sustava pridruženog sluznicama u razvoju ukupnog imunološkog sustava jedinke i jačanju obrambenog sustava organizma. Koncept limfatičkog tkiva pridruženog sluznici crijeva u širem smislu predstavlja strukturu i funkciju urođene i stečene, humoralne i celularne imunosti pridružene sluznici u procesiranju luminalnih antigena. Taj koncept uključuje integritet sluzničke barijere, sloj sluzi, očuvani epitelni sloj i uske veze između stanica, lučenje antimikrobnih peptida, obrasce prepoznavanja antigena, uključivši mikrobne i one nastale oštećenjem tkiva, obrasce stvaranja signala i puteve prijenosa signala, mehanizme humoralne i celularne imunosti, citokinsku mrežu i lokalni citokinski okoliš, interakciju urođenih limfoidnih stanica s pomagačkim, izvršnim i regulacijskim limfocitima T, interakciju s ostalim stanicama strome te metaboličku i imunološku interakciju s vlastitim mikrobiomom. Rezultati brojnih istraživanja zabilježili su etiopatogenetsku povezanost između crijevne i zglobne upale, tvrdeći kako se u patogenetskom kolopletu isprepliću činitelji naslijeđa, promijenjena imunološka reakcija te činitelji okoliša, onog vanjskog i unutarnjeg pod kojim razumijevamo crijevnu mikrobiotu. Opravdano je ustvrditi kako za sve skupine navedenih reumatoloških bolesti postoji, kako za koji entitet, više ili manje dokaza o povezanosti s crijevnom upalom, odnosno patološkom imunološkom reakcijom i crijevnom disbiozom. Za sada, ne postoji dovoljno dokaza da bi ta povezanost imala kauzalni karakter. Rezultati dobiveni primjenom umjetne inteligencije u obradi velikih količina podataka mogli bi izdvojiti fenotipski različite skupine bolesnika s reumatoidnim artritisom i spondiloartropatijama, uz dijagnostičke i terapijske implikacije. Prvenstveno u svjetlu pretpostavke da gensko naslijeđe, imunološka reakcija i crijevna disbioza na različit način doprinose nastanku bolesti u različitih skupina bolesnika, odnosno u individualnom bolesniku. Primjenom načela translacijske medicine u istraživanju, dijagnostici i terapiji crijevne i zglobne upale činimo značajan korak naprijed ka preciznoj i personaliziranoj medicini

Quantitative Analysis of Troponin I Serum Values in Patients with Acute Cholecystitis

The diagnosis and staging of acute cholecystitis, upon a lot of diagnostic methods and some scoring systems, is still a great clinical problem. The aim of the study was to investigate if serum Troponin I is elevated in patients with acute cholecystitis. Following informed consent, 65 patients with clinical and laboratory signs of acute cholecystitis were enrolled. All patients had measured serum Troponin I level and an abdominal ultrasound was done before definitive treatment was performed. Increased serum Troponin I level was found in most patients with severe form of acute cholecystitis (p6 mm) thickness (r=0.58). Our study confirms that in most patients with severe and acute cholecystitis, serum Troponin I is increased. Troponin I level is in a lower range than it would be in patients with cardiac muscle damage or necrosis. Measuring serum Troponin I is a fast, reliable and widely performed test that could, with other routinely measured parameters, help in early diagnosis of the severe form of acute cholecystitis