Detection Rate of Helicobacter Pylori Infection and Atrophic Gastritis Using Serological Markers “GastroPanel®” Among Employees of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation

Aim: to evaluate, using the “GastroPanel®”, the frequency of detection of H. pylori infection and associated gastric diseases among doctors and medical staff of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, Moscow.Materials and methods. Employees of three branches of the National Medical Research Radiological Centre (n = 434, mean age — 48.5 ± 0.6 years) were examined using laboratory tests “GastroPanel®” (Biohit Oyj, Finland). The test results make it possible to identify infection of the stomach with H. pylori, hypo- and hyperacid conditions, as well as atrophic gastritis of the antrum and body of the stomach, as its precancerous conditions. Esophagogastroduodenoscopy (EGDS) for suspected atrophic gastritis was performed with an Olympus GIF-HQ190 video endoscope (Japan) in a narrow-spectrum mode with close focus (NBI Dual Focus).Results. The absence of pathological signs detected by “GastroPanel®” was established in 23.3 % of cases, hyperacid state — in 18.4 %, and hypoacid state — in 5.2 %. These disorders are classified as functional. Consequently, the conditional norm in total was identified in 46.9 % of observations. An increased level of antibodies to H. pylori was found in 43.3 % of those examined. Atrophic gastritis in the body of the stomach according to the results of the “GastroPanel®” was detected in 4.8 % of cases (median age — 59 years), in the antrum (or increased secretion of hydrochloric acid) — also in 4.8 % of cases (median age — 52 years). Within two months after laboratory diagnostics, EGDS was performed for 10 out of 15 patients examined at the P. Hertsen Moscow Oncology Research Institute in whom, based on the results of the “GastroPanel®”, the presence of atrophic gastritis in the antrum (or increased secretion of hydrochloric acid) was suspected. In 6 out of 10 cases, atrophic gastritis of the antrum was confirmed (in two of them, the atrophy extended to the body of the stomach and was assessed as severe). Of the 11 people with the “GastroPanel®” conclusion “Atrophic gastritis of the body of the stomach,” an endoscopic examination was carried out in 7 persons, and in all these cases the diagnosis was confirmed, and in two people the conclusion was made of severe atrophic pangastritis.Conclusion. “GastroPanel®” confirmed its high significance in identifying H. pylori infection and precancerous atrophic changes in the gastric mucosa. Regarding the occupational risks of infection among medical workers, we consider it advisable to conduct such screening without selecting an asymptomatic population

ПСА И ЕГО ИЗОФОРМЫ В СЫВОРОТКЕ КРОВИ ЖЕНЩИН В НОРМЕ И ПРИ ПАТОЛОГИЧЕСКИХ ПРОЦЕССАХ В МОЛОЧНОЙ ЖЕЛЕЗЕ

The purpose of the study was to provide data on the sources of prostate-specific antigen (Psa) in women, as well as on serum Psa levels in healthy women and in women with benign and malignant breast cancer. Material and methods. We analyzed 50 publications available from PubMed, Medline, Google scholar concerning non-prostatic sources of Psa and its use as a serum tumor-associated marker for benign and malignant breast tumors. Results. In our study, we focus on the recent findings on non-prostatic sources and regulation of Psa synthesis in women as well as on changes in serum concentrations of this marker in patients with benign and malignant breast tumors. Various Psa isoforms (total Psa and free Psa) and free/total ratio for the detection of breast cancer and the assessment of treatment response and early detection of breast cancer recurrence were analyzed. Conclusion. the results obtained highlight the value of the assessment of Psa isoforms for early detection, prediction of therapy response and detection of breast cancer relapse. However, further studies are needed to identify the role of Psa isoforms in the diagnosis and monitoring of breast cancer patients.Цель исследования – представить современные данные об источниках простатического специфического антигена у женщин, а также о сывороточных уровнях этого маркера у женщин в норме, при доброкачественных и злокачественных заболеваниях молочной железы. Материал и методы. Выполнен поиск литературных источников, доступных в базах данных PubMed, Medline, Google scholar. Было отобрано 50 публикаций, посвященных изучению непростатических источников ПСА, использованию данного антигена как серологического опухолеассоциированного маркера при доброкачественных заболеваниях молочной железы (ДЗМЖ) и раке молочной железы. Результаты. Изложены сведения о непростатических источниках и регуляции синтеза простатического специфического антигена (ПСА) у женщин, изменениях сывороточных концентраций этого маркера при различных гормональных нарушениях, у пациенток с доброкачественными заболеваниями и раком молочной железы (РМЖ). Рассмотрена значимость различных изоформ ПСА (общей – общПСА и свободной – свПСА) и их соотношения (свПСА/общПСА) для диагностики РМЖ, а также для оценки эффективности лечения и доклинического выявления рецидивов РМЖ. Заключение. Оценка изоформ ПСА имеет перспективы для раннего выявления, прогноза эффективности лечения и выявления рецидивов РМЖ. Тем не менее делать  окончательные выводы о месте ПСА в диагностике РМЖ преждевременно. Дальнейшие исследования в этой области помогут установить роль изоформ ПСА в диагностике и мониторинге больных РМЖ

КЛИНИЧЕСКАЯ ЗНАЧИМОСТЬ ПРОСТАТИЧЕСКОГО СПЕЦИФИЧЕСКОГО АНТИГЕНА У БОЛЬНЫХ РАКОМ МОЛОЧНОЙ ЖЕЛЕЗЫ

Background. Prostate-specific antigen (PSA ) is predominantly produced by prostate epithelium, however, other tissues can serve as its minor sources in both men and women, including breast tissue. In women, elevated serum PSA levels have been described in different physiological and pathological conditions, including benign breast diseases and breast cancer (BC). PSA is considered as a potential serum tumor marker for BC, but evidences of its possible clinical significance are insufficiently convincing.Aim of the study: investigation of PSA levels in female BC patients and assessment of perspectives of its study as a diagnostic tool for early detection of BC.Material and methods. Serum PSA levels were measured by chemiluminescence immunoassay (ARCHITECT , Abbott) in 99 female patients with histologically confirmed BC (carcinoma in situ – 11, stage I – 56, stage IIA – 32) and 25 conditionally healthy female donors.Results. In the donor group, serum PSA was revealed in 22/25 (88,0 %) cases, and its mean level was 4.0 ± 0.9 ng/l. In the group of BC patients, detectable PSA level was revealed in 68/99 (68.7 %) cases, and its mean level was 2.8 ± 0.9 ng/l. Differences between groups of BC patients and donors in mean marker values were not statistically significant (p>0,05). Serum PSA levels were higher in young women: in the group of BC patients under 40 years old, percentage of PSA -positive cases was 89 %, in the group of patients over 50 years old – 60 %; in groups of donors under 40 and over 50 years old – 100 % and 80 %, respectively. In cases of in situ carcinoma, the mean serum PSA was higher than in cases with stages I and II (3.0 ± 1.2 ng/l vs 1.9 ± 0.3 ng/l and 1.6 ± 0.3 ng/l, respectively; p>0,05). In the group of BC patients, no PSA levels were found to be dependent on the histological type, grade and molecular subtype of the tumor.Conclusion. The PSA level has no clinical significance in early stages of BC, since the proportion of cases with elevated PSA levels and it’s mean value in patients with early stages of BC don’t differ from those in the group of healthy women. Простатический специфический антиген (ПСА) преимущественно продуцируется клетками предстательной железы, однако его минорными источниками могут служить и другие ткани организма как у мужчин, так и у женщин, включая ткани молочных желез. У женщин повышенные сывороточные уровни ПСА описаны при ряде физиологических и патологических состояний, в том числе при доброкачественных заболеваниях молочной  железы и при раке молочной железы (РМЖ). ПСА рассматривают как потенциальный  серологический опухолеассоцированный маркер РМЖ, однако сведения о его возможной клинической значимости недостаточно убедительны. Цель исследования – оценка уровней ПСА у женщин с РМЖ и оценка перспективности его изучения как диагностического показателя при начальных стадиях заболевания. Материал и методы. Сывороточные уровни ПСА измерены иммунохемилюминесцентным методом (aRcHitect, abbott) у 99 пациенток с гистологически верифицированным РМЖ  (карцинома in situ – 11, iА стадия – 56, iiА стадия – 32) и у 25 условно здоровых женщин-доноров. Результаты. В группе здоровых женщин ПСА был выявлен в 22/25 (88,0 %) образцах крови, среднее значение составило 4,0 ± 0,9 нг/л. В группе больных РМЖ  детектируемый уровень ПСА обнаружен в 68/99 (68,7 %) случаях, его средний уровень – 2,8 ± 0,9 нг/л. Отличия между группами больных РМЖ и доноров по среднему уровню маркера статистически недостоверны (p>0,05). Значения ПСА были выше у молодых женщин: у больных РМЖ моложе 40 лет доля ПСА-положительных случаев составила 89  %, у пациенток старше 50 лет – 60 %; в группах доноров моложе 40 лет и старше 50 лет – 100 % и 80 % соответственно. При карциноме in situ средний уровень ПСА оказался выше, чем при i и ii стадии заболевания (3,0 ± 1,2 нг/л против 1,9 ± 0,3 нг/л и 1,6 ± 0,3 нг/л соответственно; p>0,05). У больных РМЖ не выявлено зависимости концентраций ПСА от гистотипа, степени дифференцировки и молекулярного подтипа опухоли. Заключение. Уровень ПСА не обладает клинической значимостью при ранних стадиях РМЖ, так как доля случаев с повышенным уровнем ПСА и среднее значение показателя у больных РМЖ на начальных этапах заболевания не отличаются от таковых в группе здоровых женщин

Современные представления о серологических опухолеассоциированных маркерах и их месте в онкологии

The paper reviews modern concepts of serological tumor markers and their place in oncology: using for differential diagnostics, in the prognosis of the tumor, follow-up and for preclinical revealing of relapses, as well as in the screening aimed at early detection of malignant neoplasms. Biochemical characteristics and functions of most informative tumor markers (CA125, PSA etc.) were described. Currently diagnostic indexes, obtained by the in vitro diagnostic multivariate index assay (IVDMIA), and algorithms using several serological markers begin to apply in laboratory practice to increase diagnostic accuracy. Also some promising new serological tumor markers were described in this review.Обзор посвящен современным представлениям о серологических опухолеассоциированных маркерах (ОМ) и их месте в онкологии: использовании для дифференциальной диагностики, в прогнозе течения опухолевого процесса, мониторинге и для доклинического выявления рецидивов болезни, а также в скрининге, направленном на раннее выявление злокачественных новообразований. Описаны биохимические характеристики и функции наиболее информативных ОМ (СА125, ПСА и др). В настоящее время с целью повышения диагностической точности в лабораторной практике начинают применяться диагностические индексы, полученные путем многопараметрического анализа in vitro (in vitro diagnostic multivariate index assay, IVDMIA), и алгоритмы с использованием нескольких серологических маркеров. Также в обзоре описаны некоторые новые перспективные серологические ОМ

Динамика уровня маркера острого повреждения почек KIM-1 в моче онкологических больных, получающих химиотерапию с цисплатином

Platinum is the main component of the most chemotherapy (CT) regimens, but their use may be limited because of nephrotoxicity. Kidney injury molecule 1 (KIM-1) is considered as an early marker of cisplatininduced acute kidney injury (AKI). The aim of our study was to evaluate the changes in the burinary levels of KIM-1 (uKIM-1) in cancer patients receiving nephrotoxic CT throughout the entire course of the treatment. Material and Methods. The level of uKIM-1 was determined by enzyme immunoassay in untreated 19 patients with solid malignancies before each CT cycle (regimens with cisplatin or oxaliplatin) and every next day after cytostatic drugs administration. uKIM-1 values were normalized to urinary creatinine concentration (uKIM-1). The kidneys function was assessed by the serum creatinine (sCr) and glomerular fltration rate (GFR) value. Results. According to laboratory parameters, renal function in patients before treatment corresponded to normal ranges. During CT, an increase in sCr by more than 50 % (decrease in GFR to 68 ml/min/1.73 m2 ), which corresponded to stage I AKI (KDIGO) was revealed in one patient (5.3 %) only. uKIM-1 levels before CT were above the upper limit of normal range (3.4 ng/mguCr) in 3 patients (15.8 %; median 2.1 ng/mguCr); at the beginning of the 2nd cycle of CT they were increased in 9 patients (47.4 %; median 3.2 ng/mguCr; p=0.0025, Mann-Whitney test); at the beginning of the 3rd cycle of CT uKIM-1 levels were increased in 12 patients (63.2 %; median 4.9 ng/mguCr; p=0.00007). During CT with cisplatin the average level of uKIM-1 increased with each subsequent cycle, in most cases it increased already the day after the administration of cytostatic drugs. No increase in uKIM-1 levels was observed during treatment with oxaliplatin-based regimens. The achievement of the threshold uKIM-1 level of 6.0 ng/mguCr at the beginning of the next cycle of CT was signifcantly associated with a high risk of its further increase (RR=18.8; p=0.0051). Conclusion. An increase in the level of uKIM-1 after cisplatin administration can be regarded as a marker of subclinical kidney damage. In the future, the increase in uKIM-1 level at the beginning of the cycle of CT may be a reason for enhanced preventive measures or the appointment of less nephrotoxic treatment regimens.Препараты платины – основной компонент большинства схем химиотерапии (ХТ) онкологических больных, однако возможность их применения может быть лимитирована нефротоксичностью. На роль раннего маркера острого повреждения почек (ОПП), индуцированного цисплатином, претендует KIM-1 (kidney injury molecule 1). Цель исследования – оценить динамику содержания KIM-1 в моче (uKIM-1) у пациентов, получающих ХТ с высоким риском нефротоксического действия на протяжении всего курса противоопухолевого лекарственного лечения. Материал и методы. В исследование включено 19 первичных больных солидными злокачественными новообразованиями. Уровень uKIM-1 определяли методом иммуноферментного анализа перед каждым циклом ХТ (режимы, включающие цисплатин или оксалиплатин) и через сутки после введения цитостатиков. Величины uKIM-1 нормировали на концентрацию в моче креатинина (uKIM-1). Состояние почек оценивали по содержанию в крови креатинина (sCr) и скорости клубочковой фильтрации (СКФ). Результаты. До начала лечения лабораторные показатели функционального состояния почек у пациентов находились в пределах нормальных значений. На фоне ХТ только у 1 (5,3 %) больного наблюдалось увеличение sCr более чем на 50 % и снижение СКФ до 68 мл/мин/1,73 м2 , что соответствует I стадии ОПП (KDIGO). uKIM-1 до начала лечения превышал верхнюю границу нормы (3,4 нг/мгuCr) у 3 больных (15,8 %; медиана 2,1 нг/мгuCr); к началу 2-го курса ХТ – у 9 больных (47,4 %; медиана 3,2 нг/мгuCr; р=0,0025, критерий Манна–Уитни); к началу 3-го курса – у 12 больных (63,2 %; медиана 4,9 нг/мгuCr; р=0,00007). На фоне ХТ с цисплатином средний уровень uKIM-1 нарастал с каждым последующим циклом, в большинстве случаев – уже через 1 сут после введения цитостатиков. При использовании схем ХТ, не включающих цисплатин, но содержащих оксалиплатин, увеличения uKIM-1 на фоне лечения не наблюдалось. Достижение показателем uKIM-1 порогового уровня 6,0 нг/мгuCr к началу очередного цикла ХТ было ассоциировано с высокой вероятностью дальнейшего его увеличения (RR=18,8; p=0,0051). Заключение. Возрастание уровня uKIM-1 после введения цисплатина может расцениваться как проявление субклинического повреждения почек. Увеличение uKIM-1 в начале очередного цикла ХТ в перспективе может быть основанием для усиленных профилактических мероприятий или назначения менее нефротоксичных схем лечения

CLINICAL SIGNIFICANCE OF BIOMARKERS IN OVARIAN CANCER, PROSTATE CANCER, COLORECTAL CANCER

The review is devoted to modern notions about serum tumor markers and their place in oncology: using for differential diagnosis, in prognosis of course of tumor process, during follow-up, for preclinical detection of disease recurrences, as well as in screening aimed at early detection of malignant neoplasms. Algorithms of using of most informative tumor markers: CA125, HE4 (in ovarian cancer), PSA and its isoforms (in prostate cancer), iFOBT (in colorectal cancer) were described

Autoantibodies against tumor-associated antigens as one class of serological markers

This review is devoted to modern notions about autoantibodies (AAb) as one of classes of tumor biomarkers. Principles of humoral response by way of autoantibodies to different tumor-associated proteins in the process of malignant tumor progression are considered. During carcinogenesis self-proteins may become overexpressed, mutant, undergo posttranslational modification, localize abnormally, degrade aberrantly, becoming immunogenic and, as a result, be recognized by immune system as allogeneic. Advantages of AAb as biomarkers over its ligands – tumor antigens – are discussed.Data regarding a diagnostic value of some AAb are given, modern methods of its assessment are considered. Possibilities of AAb using in screening, aimed at active diagnostics of cancer on early stages as well a

CLINICAL SIGNIFICANSE OF PROSTATE-SPECIFIC ANTIGEN IN BREAST CANCER PATIENTS

Background. Prostate-specific antigen (PSA ) is predominantly produced by prostate epithelium, however, other tissues can serve as its minor sources in both men and women, including breast tissue. In women, elevated serum PSA levels have been described in different physiological and pathological conditions, including benign breast diseases and breast cancer (BC). PSA is considered as a potential serum tumor marker for BC, but evidences of its possible clinical significance are insufficiently convincing.Aim of the study: investigation of PSA levels in female BC patients and assessment of perspectives of its study as a diagnostic tool for early detection of BC.Material and methods. Serum PSA levels were measured by chemiluminescence immunoassay (ARCHITECT , Abbott) in 99 female patients with histologically confirmed BC (carcinoma in situ – 11, stage I – 56, stage IIA – 32) and 25 conditionally healthy female donors.Results. In the donor group, serum PSA was revealed in 22/25 (88,0 %) cases, and its mean level was 4.0 ± 0.9 ng/l. In the group of BC patients, detectable PSA level was revealed in 68/99 (68.7 %) cases, and its mean level was 2.8 ± 0.9 ng/l. Differences between groups of BC patients and donors in mean marker values were not statistically significant (p>0,05). Serum PSA levels were higher in young women: in the group of BC patients under 40 years old, percentage of PSA -positive cases was 89 %, in the group of patients over 50 years old – 60 %; in groups of donors under 40 and over 50 years old – 100 % and 80 %, respectively. In cases of in situ carcinoma, the mean serum PSA was higher than in cases with stages I and II (3.0 ± 1.2 ng/l vs 1.9 ± 0.3 ng/l and 1.6 ± 0.3 ng/l, respectively; p>0,05). In the group of BC patients, no PSA levels were found to be dependent on the histological type, grade and molecular subtype of the tumor.Conclusion. The PSA level has no clinical significance in early stages of BC, since the proportion of cases with elevated PSA levels and it’s mean value in patients with early stages of BC don’t differ from those in the group of healthy women

PROSTATE-SPECIFIC ANTIGEN AND ITS MOLECULAR FORMS IN BLOOD SERUM OF HEALTHY WOMEN AND WOMEN WITH BREAST DISEASE

The purpose of the study was to provide data on the sources of prostate-specific antigen (Psa) in women, as well as on serum Psa levels in healthy women and in women with benign and malignant breast cancer. Material and methods. We analyzed 50 publications available from PubMed, Medline, Google scholar concerning non-prostatic sources of Psa and its use as a serum tumor-associated marker for benign and malignant breast tumors. Results. In our study, we focus on the recent findings on non-prostatic sources and regulation of Psa synthesis in women as well as on changes in serum concentrations of this marker in patients with benign and malignant breast tumors. Various Psa isoforms (total Psa and free Psa) and free/total ratio for the detection of breast cancer and the assessment of treatment response and early detection of breast cancer recurrence were analyzed. Conclusion. the results obtained highlight the value of the assessment of Psa isoforms for early detection, prediction of therapy response and detection of breast cancer relapse. However, further studies are needed to identify the role of Psa isoforms in the diagnosis and monitoring of breast cancer patients

KIM-1 as a potential serological/urinological tumor-associated marker of renal cell carcinoma and chemotherapy nephrotoxicity

The last decades are characterized by an active search for highly sensitive and specific urinological and serological tumor-associated markers of renal cell carcinoma. This review analyses the results of studies of traditional serological tumor-associated markers and a potential new tumor-associated marker of renal cell carcinoma: kidney injury molecule-1, or KIM-1. The structure, sources and functions of KIM-1 in normal conditions and in damaged renal tubules, its potential role in carcinogenesis are described. The experience of using KIM-1 for specifying diagnosis of the most common histological types of renal cell carcinoma is analyzed. Data on KIM-1 expression in malignant tumors in other locations and non-oncological kidney disorders are presented. The role of KIM-1 in early diagnosis of nephrotoxic effect of antitumor drugs is described. The accumulated data is promising in regards to using KIM-1 in clinical oncology as a urinological and serological marker of renal cell carcinoma and chemotherapy nephrotoxicity