Nuclear antigen Ki-67 – a high-risk index for the development of gastric cancer in patients with chronic gastric diseases

Departamentul Gastropulmonologie, Institutul Oncologic, Catedra Oncologie, Hematologie şi Radioterapie, USMF „Nicolae Testemiţanu”, Chişinău, Republica Moldova, Al XII-lea Congres al Asociației Chirurgilor „Nicolae Anestiadi” din Republica Moldova cu participare internațională 23-25 septembrie 2015Introducere: Tipul intestinal de cancer gastric se dezvoltă pe fundalul maladiilor gastrice cronice, prin proliferarea necontrolată a epiteliului mucoasei gastrice. Scopul: Evidenţierea gradului de expresie a Ki-67 în carcinoamele gastrice şi în mucoasa gastrică nemalignizată cu modificări inflamatorii, induse de infecţia cu Helicobacter pylori. Material şi metode: Studiul imunohistochimic a fost realizat pe materialul tisular postoperator la bolnavi de cancer gastric tip difuz şi intestinal din formaţiunea tumorală şi din mucoasa gastrică non-neoplazică. Preoperator a fost efectuată analiza imunologică la anticorpii IgG Hp, ce a fost pozitivă la toţi pacienţii cu cancer gastric de tip intestinal. Rezultate: Expresia Ki-67 în mucoasa gastrică a variat în funcţie de severitatea schimbărilor produse de infecţia cu Helicobacter pylori. Schimbări ale mucoasei peritumorale – de tipul gastrită cronică, severitatea căreia a fost apreciată conform criteriilor histologice ale sistemului Sydney. Expresia Ki-67 în carcinoamele gastrice a fost foarte variabilă comparativ cu imunopozitivitatea din mucoasa gastrică peritumorală. În adenocarcinoamele de tip intestinal imunopozitivitatea celulelor neoplazice a fost mult mai sporită decît în mucoasa nemalignizată. Concluzii: Infecţia cu Helicobacter pylori induce în mucoasa gastrică un proces inflamator, instalîndu-se condiţii de proliferare locală, ceea ce crează condiţii de promoţie a cancerului gastric de tip intestinal. S-a observat o rată mai mare de proliferare a celulelor epiteliale în adenocarcinoamele de tip intestinal şi o rată mai mare de proliferare a celulelor limfoide în mucoasa peritumorală cu infiltrat inflamator, faţă de stroma carcinoamelor.Introduction: Gastric cancer of intestinal-type can appear on the background of chronic gastric diseases with uncontrolled proliferation of gastric mucosal epithelium. Aim: To study the degree of Ki-67 expression in gastric carcinomas and in non-malignant gastric mucosa with inflammatory changes due to Helicobacter pylori. Material and methods: Immunohistochemistry was applied on postoperative tissue specimens from patiens with gastric cancer of diffuse and intestinal type, from the tumor and non-affected gastric mucosa. Preoperative, all patients with intestinal-type gastric cancer tested positive for IgG Hp antibodies. Results: Ki-67 expression varied dependently on the severity of changes produced by H.pylori. The changes in the peritumoral mucosa like chronic gastritis, were appreciated by the Sydney classification. Ki-67 expression in gastric carcinomas varied significantly compared to the one from peritumoral gastric mucosa. In intestinal-type adenocarcinomas immunopositivity of tumoral cells was higher than in non-malignant mucosa. Conclusions: Helicobacter pylori infection induces gastric mucosal inflammation leading to local proliferation that creates conditions for gastric cancer of intestinal-type development. It can be observed a higher proliferation rate of epithelial cells in intestinal-type adenocarcinomas and that of lymphoid cells in peritumoral mucosa with inflammatory infiltrate

Insulinoma – a rare neuroendocrine tumor: clinical case and review of literature

Laboratorul Științific Tumorile Toracelui, Sistemului Digestiv și Urogenital, Secția Gastrologie, IMSP Institutul Oncologic, Universitatea de Stat de Medicină și Farmacie ”Nicolae Testemițanu”, Chișinău, Republica Moldova, Al XIII-lea Congres al Asociației Chirurgilor „Nicolae Anestiadi” și al III-lea Congres al Societății de Endoscopie, Chirurgie miniminvazivă și Ultrasonografie ”V.M.Guțu” din Republica MoldovaIntroducere: Insulinomul este o tumoare neuroendocrină rară, provenită din celulele ß ale pancreasului. Incidența insulinoamelor este de 1 la 1 milion de populație pe an, 90-95% dintre acestea sunt tumori benigne, 90% sunt localizate intrapancreatic și 90% sunt solitare. Insulinoamele se pot întâlni sporadic sau în asociere cu sindromul MEN-1. Manifestările clinice includ simptome ale hipoglicemiei, clasificate în neuroglicopenice și adrenergice. Material și metode: Pacient de 23 de ani, s-a prezentat cu un tablou clinic de hipoglicemie, manifestat prin: simptome neuroglicopenice (stări convulsive periodice) și adrenergice (slăbiciune generală pronunțată, tremor, palpitații și transpirații profuze), cu debutul acestora timp de aproximativ 1 an. Examenul fizic a fost fără particularități. Hipoglicemia ajungea până la 0,8-1,1 mmol/l cu corijarea acesteia la administrarea glucozei. RMN abdominal a relevat o formațiune de volum a cozii pancreasului de 25*37*27 mm, cu contur clar, omogenă, hipervasculară, fără semne de invadare a structurilor adiacente. S-a intervenit chirurgical, intraoperator depistându-se o formațiune tumorală de culoare brună, incapsulată, localizată la nivelul cozii pancreasului, fără date de metastazare la distanță; s-a efectuat enucleerea tumorii. Rezultate: Înlăturarea chirurgicală a tumorii a dus la dispariția simptomelor și la normalizarea glicemiei. Rezultatul histologic a relevat o tumoare neuroendocrină bine diferențiată G1 (Pancitokeratina +, Sinaptofizina +, Cromogranina A +, Ki67-10%). Concluzii: Diagnosticul precoce și tratamentul chirurgical sunt cruciale în menajarea insulinoamelor. Procedura de elecție este enucleerea tumorii, însă în unele cazuri este necesară o rezecție mai extinsă. Simptomele hipoglicemice dispar odată cu înlăturarea tumorii.Introduction: Insulinoma is a rare neuroendocrine tumor originating from ß-cells of the pancreas. The incidence of insulinoma is 1 to 1 million population per year, 90-95% of these are benign tumors, 90% have intrapancreatic localization and 90% are solitary. Insulinomas can occur sporadically or in association with MEN-1 syndrome. Clinical manifestations include symptoms of hypoglycemia classified as neuroglycopenic and adrenergic. Material and methods: 23-year old male patient presented with a clinical picture of hypoglycemia manifested by: neuroglycopenic symptoms (periodic seizures) and adrenergic symptoms (severe fatigue, tremors, palpitations and profuse sweating) for approximately 1 year. Physical exam was normal. Hypoglycemia was down to 0,8-1,1 mmol/l, with return to normal range after glucose administration. Abdominal MRI revealed a homogenous, hypervascular tumor mass in the pancreatic tail of 25*37*27 mm in size, with regular contour and without signs of invasion in adjacent structures. Surgical intervention was made and an encapsulated tumor of brown color, localized in the tail of the pancreas was found intraoperatively, with no signs of distant metastases; tumor enucleation was performed. Results: Surgical removal of the tumor led to the disappearance of symptoms and a normalized glucose level. Histologic report revealed a well differentiated G1 neuroendocrine tumor (Pancytokeratin +, Synaptophysin +, Chromogranin A+, Ki67-10%). Conclusions: Early diagnosis and surgical treatment are crucial in the management of insulinomas. The elective procedure is tumor enucleation, however, in certain a cases a more extended resection is necessary. Hypoglycemic symptoms disappear after tumor removal

Clinical case: gastrointestinal stromal tumor (GIST) of duodenum

Secția Gastrologie, Laboratorul de chirurgie gastrică și toracică, Institutul Oncologic, Chișinău, Republica Moldova, Conferința stiințifică „Nicolae Anestiadi – nume etern al chirurgiei basarabene” consacrată centenarului de la nașterea profesorului Nicolae Anestiadi 26 august 2016Introducere. Morbiditatea GIST reprezintă 0,65-1,45 la 100000 populație; tumorile GIST se întâlnesc cel mai frecvent în stomac (50%), urmate de intestinul subțire (25%), colon (10%), oment/mezou (7%) și esofag (5%). Mazur și Clark pentru prima dată au folosit termenul “tumoră gastrointestinală stromală” în 1983. Prezentarea cazului. Pacienta T., 53 de ani; debutul bolii s-a manifestat prin hemoragie gastrointestinală activă care s-a rezolvat prin tratament conservativ în spitalul de circumscripție. Peste o lună se prezintă în stare extrem de gravă (29.08.2014), la IMSP IO cu hemoragie TDS activă și sindrom anemic sever. FEGDS: Neoplasm al papilei Vater, forma protruzivă (Histologie: leiomiom). CT abdomen: Tumoare solidă masivă în cavitatea abdominală din dreapta, ce reiese din duoden. Formațiuni secundare (Nr. 5) în parenchimul hepatic. S-a intervenit chirurgical (01.09.2014), din considerente vitale (hemoragia continua) prin rezecția duodenului și jejunului cu aplicarea gastrojejunoanastomozei posterioare. Histologie postoperator: tumoră gastrointestinală stromală a duodenului, din celule fusiforme. A facut un postoperator obișnuit. Pacienta ulterior a urmat tratament cu Imatinib mesilat (Glivec®) 400mg/zi timp de 6 luni după care se constată avansarea procesului din contul creșterii metastazelor hepatice. A fost mărită doza de Glivec® până la 800mg/zi pe fondul căreia a avut loc stabilizarea procesului care se menține până în prezent. Concluzii. Principala și unica metodă de tratament radical este excizia tumorii cu capsula integră. Pozitivitatea markerului c-KIT(CD117) confirmă diagnosticul de GIST. În cazul rezecțiilor R1/R2, prezenței metastazelor sau deteriorării capsulei este indicat tratamentul cu imatinib mesilat, în cazul respectiv demonstrând o supraviețuire și calitate a vieții satisfăcătoare.Introduction. GIST morbidity represents 0,65-1,45 to 100000 population; GIST tumors are encountered more frequently in the stomach (50%), followed by the small intestine (25%), colon (10%), omentum/mesentery (7%) and esophagus (5%). Mazur and Clark first used the term ”gastrointestinal stromal tumor” in 1983. Case presentation. Female patient T., 53 y/o; the disease started with active gastrointestinal hemorrhage that resolved through conservative treatment in the local hospital. After 1 month, she presented in critical state (29.08.2014) at IMSP IO with active upper GI bleeding, severe anemic syndrome. Endoscopy: protrusive neoplasm of the ampulla of Vater (Histology–leiomyoma). Abdominal CT: Massive solid tumour in right side of the abdomen originating from the duodenum. Secondary foci (Nr. 5) in liver parenchyma. Surgery was performed (01.09.2014) by vital considerations (persistent hemorrhage) – resection of the duodenum and jejunum with posterior gastro-jejunoanastomosis. Postoperative histology: GIST of the duodenum, spindle cell type. The postoperative course was uneventful. The patient was further treated with Imatinib mesylate (Glivec®) 400mg/daily. After 6 months the liver metastases progressed. The dose of Glivec® was increased to 800mg/daily and by the last follow-up stabilization of the disease was obtained. Conclusions. The main and single method of radical treatment consists of tumor excision with intact capsule. The positivity of c-KIT (CD117) confirms the diagnosis of GIST. In case of R1/R2 resections, presence of metastases or loss of capsule integrity, treatment with Imatinib mesylate is indicated, in our case proving a satisfactory survival and quality of life

Results of target-therapy treatment in gastrointestinal stromal tumors (GIST)

Laboratorul de chirurgie gastrică și toracică, Secția Gastrologie, Institutul Oncologic, Catedra de oncologie, hematologie și radioterapie, Laboratorul de chirurgie hepato-pancreato-biliară, USMF „Nicolae Testemițanu”, Chișinău, Republica Moldova, Conferința stiințifică „Nicolae Anestiadi – nume etern al chirurgiei basarabene” consacrată centenarului de la nașterea profesorului Nicolae Anestiadi 26 august 2016Introducere. Imatinib mesilat (IM) este utilizat în tratamentul combinat al GIST ca remediu adjuvant sau în combaterea bolii recidivante/metastatice, însă criteriile de selectare a pacienților și a eficacității tratamentului nu sunt clar stabilite. Scop. Evaluarea comparativă a eficacității tratamentului cu IM. Material și metode. Tratament cu IM 400 mg/zi au primit 30/73 (41,1%) pacienți, dintre care tratament adjuvant – 12/30 (40%) (grup I), iar tratament pentru boală recidivantă/metastatică – 18/30 (60%) (grup II). În grupul I, conform clasificării riscului (Miettinen, 2006), 10/12 (83,3%) tumori – cu risc înalt, iar 2/12 (16,7%) – cu risc intermediar. Eficacitatea tratamentului a fost apreciată în baza criteriilor tomodensitometrice Choi (Choi, 2007): răspuns complet (RC); răspuns parțial (RP); stabilizarea bolii (SB); boală progresivă (BP). Rezultate. În grupul I, după administrarea IM în medie 23,4±4,7 luni – nu s-a înregistrat recidiva bolii. În grupul II – RC s-a înregistrat la 3 (16,7%) pacienți, RP la 8 (44,4%), SB ≥6 luni – la 3 (16,7%) și BP la 4 (22,2%) pacienți. Răspuns obiectiv la tratament (RC+RP) – 11 (61,1%) pacienți, control asupra bolii GIST (RC+RP+SB) – la 14 (77,8%), iar progresarea bolii (BP) pe fond de tratament medicamentos – la 4 (22,4%) pacienți. Urmărirea în dinamică – 34,6±3,64 luni. Intervalul de timp până la constatarea progresării bolii GIST în medie – 24,07±2,97 luni. Supraviețuirea ”de facto” la un an a constituit 94,4%, la 2-ani – 83,3% iar la 3-ani – 72,2%. Concluzii. Criteriul major pentru eficiența ”de facto” a terapiei cu IM este lipsa progresării GIST, iar obținerea unui răspuns complet la tratament poate fi indicator indirect al pronosticului favorabil.Introduction. Imatinib mesylate (IM) is used as adjuvant treatment in GIST or as therapy of recurrent/metastatic disease, but the criteria for patient selection and efficacy of treatment are not clearly established. Purpose. Comparative evaluation of efficacy of IM. Material and methods. Treatment with IM 400mg/day received 30/73 (41.1%) patients, including adjuvant therapy 12/30 (40%) (Ist group), and treatment of recurrent/metastatic disease – 18/30 (60%) (IInd group). According to Miettinen risk classification (Miettinen, 2006) – 10/12 (83.3%) tumors were of high risk and 2/12 (16.7%) – of intermediate risk. Efficacy of the treatment was assessed using CT Choi criteria (Choi, 2007): complete response (CR), partial response (PR), stable disease (SD), progression of disease (PD). Results. In the Ist group, after administration of IM for a median period of 23.4±4.7 months – no recurrence of the disease was recorded. In the IInd group – CR was assessed in 3 (16.7%) patients, PR – in 8 (44.4%), SD ≥6 months – in 3 (16.7%) and PD in 4 (22.2%) patients. Objective response to treatment (CR+PR) was recorded in 11 (61.1%) patients, control of the disease (CR+PR+SD) – in 14 (77.8%), and progression of the disease – in 4 (22.4%) patients. Median follow-up time was 34.6±3.64 months. Median time to progression of the disease was 24.07±2.97 months. 1-year survival rate was 94.4%, 2-year survival rate – 83.3% and 3-year survival rate – 72.2%. Conclusion. The major criteria for effectiveness of IM therapy is the lack of GIST progression and achieving a complete response to treatment may be an indirect indicator of favorable prognosis

Detection and molecular characterisation of Cryptosporidium parvum in British European hedgehogs (Erinaceus europaeus)

Surveillance was conducted for the occurrence of protozoan parasites of the genus Cryptosporidium in European hedgehogs (Erinaceus europaeus) in Great Britain. In total, 108 voided faecal samples were collected from hedgehogs newly admitted to eight wildlife casualty treatment and rehabilitation centres. Terminal large intestinal (LI) contents from three hedgehog carcasses were also analysed. Information on host and location variables, including faecal appearance, body weight, and apparent health status, was compiled. Polymerase Chain Reaction (PCR) targeting the 18S ribosomal RNA gene, confirmed by sequencing, revealed an 8% (9/111) occurrence of Cryptosporidium parvum in faeces or LI contents, with no significant association between the host or location variables and infection. Archived small intestinal (SI) tissue from a hedgehog with histological evidence of cryptosporidiosis was also positive for C. parvum by PCR and sequence analysis of the 18S rRNA gene. No other Cryptosporidium species were detected. PCR and sequencing of the glycoprotein 60 gene identified three known zoonotic C. parvum subtypes not previously found in hedgehogs: IIdA17G1 (n=4), IIdA19G1 (n=1) and IIdA24G1 (n=1). These subtypes are also known to infect livestock. Another faecal sample contained C. parvum IIcA5G3j which has been found previously in hedgehogs, and for which there is one published report in a human, but is not known to affect livestock. The presence of zoonotic subtypes of C. parvum in British hedgehogs highlights a potential public health concern. Further research is needed to better understand the epidemiology and potential impacts of Cryptosporidium infection in hedgehogs

Interferometry with Bose-Einstein Condensates in Microgravity

Atom interferometers covering macroscopic domains of space-time are a spectacular manifestation of the wave nature of matter. Due to their unique coherence properties, Bose-Einstein condensates are ideal sources for an atom interferometer in extended free fall. In this paper we report on the realization of an asymmetric Mach-Zehnder interferometer operated with a Bose-Einstein condensate in microgravity. The resulting interference pattern is similar to the one in the far-field of a double-slit and shows a linear scaling with the time the wave packets expand. We employ delta-kick cooling in order to enhance the signal and extend our atom interferometer. Our experiments demonstrate the high potential of interferometers operated with quantum gases for probing the fundamental concepts of quantum mechanics and general relativity.Comment: 8 pages, 3 figures; 8 pages of supporting materia

Organ-specific allergen challenges in airway allergy: Current utilities and future directions

Atopy has been long used as the screening method for airway allergy. Nevertheless, aeroallergens can trigger respiratory symptoms not only in atopic patients (atopic res piratory allergy, ARA), but also in non-atopic subjects (local respiratory allergy, LRA). Moreover, ARA and LRA can coexist in the same patient, and this clinical scenario has been called dual respiratory allergy (DRA). When the clinical history cannot determine the relevance of sensitizations in ARA patients, nasal, conjunctival or bronchial aller gen challenges (NAC, CAC, and BAC, respectively) should be conducted. Moreover, these tests are required to identify patients with LRA and DRA. The clarification of the allergic triggers of airway diseases has a profound impact on the management strategies the patients can be offered. Importantly, allergen immunotherapy (AIT) remains as the only disease-modifying intervention for ARA. Recent data indicate that AIT might have a similar effect on LRA patients. Nevertheless, AIT success relies largely on the correct phenotyping of allergic individuals, and NAC, CAC, and BAC are very helpful tools in this regard. In this review, we will summarize the main indications and methodology of CAC, NAC, and BAC. Importantly, the clinical implementation of these tests might translate into precision medicine approaches and better health outcomes for patients with airway allergy.Consejería de Salud, Junta de Andalucía, Grant/Award Number: P20_00405; Instituto de Salud Carlos III, Grant/Award Number: PI20/01715, RD21/0002/0008, CM21/00262, CM20/00160, JR22/00048 and JR19/00029. Funding for open access charge: Universidad de Málaga / CBUA

Elastic modeling and steep dips: unraveling the reflected wavefield

As part of a larger elastic numerical modeling project, we have been investigating how energy reflected from steeply dipping interfaces is recorded using typical multicomponent acquisition geometries. Specifically, we have been interpreting how rcflection events from the flanks of salt dome structures are distributed on 3C and 4C phones for vertical seismic profiles (VSPs) and ocean bottom seismic (OBS) or land surface surveys. The ultimate goal of this investigation is to improve the structural imaging of steeply dipping interfaces and eventually to evaluate the usc of the recorded elastic wavefield for fluid description near these interfaces. In the current work, we focus on a common assumption used when processing converted wave reflection seismic data that most PP energy is recorded on the vertical geophone and/or the hydrophone and that most PS energy is recorded on the horizontal geophones. This is a useful assumption when it is valid, because it eliminates the need for separation of the recorded wavefield into P and S wavetypes. Using two elastic models and different acquisition geometries, we examine the validity of this assumption in the presence of steeply dipping interfaces and discuss the implications for converted-wave and vector imaging of salt flanks