Chemotherapy changes cytotoxic activity of NK-cells in cancer patients

In recent years, it has been shown that under certain conditions cytostatic agents (chemotherapy and radiotherapy) can restore the functioning of the immune system impaired by malignancy burden. The modifications of biological properties by cytostatics acting make cancer cells visible for the immune system recognition and elimination. Eighteen patients diagnosed with primary local breast (8) and gastric (10) cancer between 2014 and 2016 were enrolled in the investigation. The phenotypic features of NK were assessed by flow cytometry using mAb (BD Pharmingen) against CD45 (common leukocyte antigen) and CD56 (NK-marker) for surface staining, CD107a (LAMP-1), Perforin (PF) and Gransime B (GB) for intracellular staining. We examined NK populations in the peripheral blood of cancer patients before treatment and in 5 days after second course of NACT. We found that NK populations produced PF in cancer patents, which were absent before treatment, increased after NACT. Their emergence can be associated with the immunoactivating effects of chemotherapy, realized by the modification of tumor cells or elimination of immunosuppressive cells

Irradiation specifically sensitises solid tumour cell lines to TRAIL mediated apoptosis

BACKGROUND: TRAIL (tumor necrosis factor related apoptosis inducing ligand) is an apoptosis inducing ligand with high specificity for malignant cell systems. Combined treatment modalities using TRAIL and cytotoxic drugs revealed highly additive effects in different tumour cell lines. Little is known about the efficacy and underlying mechanistic effects of a combined therapy using TRAIL and ionising radiation in solid tumour cell systems. Additionally, little is known about the effect of TRAIL combined with radiation on normal tissues. METHODS: Tumour cell systems derived from breast- (MDA MB231), lung--(NCI H460) colorectal--(Colo 205, HCT-15) and head and neck cancer (FaDu, SCC-4) were treated with a combination of TRAIL and irradiation using two different time schedules. Normal tissue cultures from breast, prostate, renal and bronchial epithelia, small muscle cells, endothelial cells, hepatocytes and fibroblasts were tested accordingly. Apoptosis was determined by fluorescence microscopy and western blot determination of PARP processing. Upregulation of death receptors was quantified by flow cytometry. RESULTS: The combined treatment of TRAIL with irradiation strongly increased apoptosis induction in all treated tumour cell lines compared to treatment with TRAIL or irradiation alone. The synergistic effect was most prominent after sequential application of TRAIL after irradiation. Upregulation of TRAIL receptor DR5 after irradiation was observed in four of six tumour cell lines but did not correlate to tumour cell sensitisation to TRAIL. TRAIL did not show toxicity in normal tissue cell systems. In addition, pre-irradiation did not sensitise all nine tested human normal tissue cell cultures to TRAIL. CONCLUSIONS: Based on the in vitro data, TRAIL represents a very promising candidate for combination with radiotherapy. Sequential application of ionising radiation followed by TRAIL is associated with an synergistic induction of cell death in a large panel of solid tumour cell lines. However, TRAIL receptor upregulation may not be the sole mechanism by which sensitation to TRAIL after irradiation is induced

СТРЕСС-ОТВЕТ ПРИ РАДИКАЛЬНЫХ ОПЕРАЦИЯХ ПО ПОВОДУ РАКА ЖЕЛУДКА

The purpose of the study was to evaluate the anesthetic effect of the combination of xenon and dexmedetomidine during surgery for gastric cancer. Material and methods. The prospective randomized study included 53 patients with operable II–III stage gastric cancer. The age range was from 26 to 75 years. The patients underwent gastrectomy (n=21) and subtotal distal gastrectomy (n=32). The study group comprised 27 patients who received anesthesia with xenon and dexmedetomidine combined with epidural analgesia. The control group consisted of 26 patients who received anesthesia with sevoflurane in combination with epidural analgesia. Intraoperative patient monitoring was performed according to Harvard intraoperative monitoring standards. Plasma levels of ACTH, STH cortisole, IL-1β, IL-6, and CRP as well as cytokine profile were used to evaluate the effect of two anesthetic methods. Results. In the perioperative period, the combination of xenon and dexmedetomidine in combination with epidural analgesia was characterized by significant inhibition of systemic inflammatory reactions and a lower release of stress hormones as components of a surgical stress response expressed by a lower level of pro-inflammatory cytokines and somatotropic hormone. The frequency of postoperative inflammatory complications was lower in the xenon group than in the control group. Conclusion. The use of the combination of xenon and dexmedetomidine during surgery for gastric cancer provides a more adequate course of the perioperative period. Цель исследования – оценить эффективность анестезиологического пособия комбинацией ксенона и дексмедетомидина при операциях по поводу рака желудка. Материал и методы. В проспективное рандомизированное исследование включены 53 пациента с операбельным раком желудка II–III стадий, в возрасте 26–75 лет, ASA I–II, которым были выполнены операции в объеме гастрэктомии (n=21), субтотальной дистальной резекции желудка (n=32). В I (основной) группе (n=27) проводилась комбинированная анестезия ксеноном и дексмедетомидином в сочетании с эпидуральной аналгезией. Во II (контрольной) группе (n=26) проводилась анестезия севорфлюраном в сочетании с эпидуральной аналгезией. Проводился стандартный интраоперационный мониторинг по Гарвардскому стандарту. Эффективность сравниваемых методов анестезиологического пособия оценивали по уровеню АКТГ, СТГ, кортизола, IL-1β, IL-6 и СРБ и цитокиновому профилю. Результаты. Комбинация ксенона и дексмедетомидина в сочетании с эпидуральной аналгезией на всех этапах периоперационного периода характеризовалась значимым торможением системных воспалительных реакций и меньшим выбросом гормонов стресса как компонентов хирургической стрессовой реакции, выражающейся более низким уровнем провоспалительных цитокинов и соматотропного гормона. В основной группе отмечена меньшая частота послеоперационных нехирургических осложнений, обусловленных системной воспалительной реакцией. Заключение. Применение комбинированного анестезиологического пособия с использованием ксенона и дексмедетомидина при операциях по поводу рака желудка обеспечивает более адекватное течение периоперационного периода.

A modified surgical approach to women with obstetric anal sphincter tears by separate suturing of external and internal anal sphincter. A modified approach to obstetric anal sphincter injury

<p>Abstract</p> <p>Background</p> <p>Long-term results after obstetric anal sphincter injury (OASI) are poor. We aimed to improve the long-term outcome after OASI by lessening symptoms of anal incontinence.</p> <p>Methods</p> <p>In a prospective study at Malmö University Hospital, twenty-six women with at least grade 3B OASI were classified and sutured in a systematic way, including separate suturing of the internal and external sphincter muscles with monofilament absorbable sutures. The principal outcome assessed by answers given to six questions, was a difference in anal incontinence score, between the study group and two control groups (women with prior OASI [n = 180] and primiparous women delivered vaginally without a diagnose of OASI [n = 100]).</p> <p>Results</p> <p>An anal incontinence score of zero (i.e., no symptoms) was found in 74% of the study group, 47% of the OASI control group, and 66% of the vaginal control group (<it>p </it>= 0.02 and 0.5, as compared to the study group).</p> <p>Conclusions</p> <p>A modified suturing technique was followed by significant improved one-year symptoms of anal incontinence as compared to historical cases.</p

Ten Misconceptions from the History of Analysis and Their Debunking

The widespread idea that infinitesimals were "eliminated" by the "great triumvirate" of Cantor, Dedekind, and Weierstrass is refuted by an uninterrupted chain of work on infinitesimal-enriched number systems. The elimination claim is an oversimplification created by triumvirate followers, who tend to view the history of analysis as a pre-ordained march toward the radiant future of Weierstrassian epsilontics. In the present text, we document distortions of the history of analysis stemming from the triumvirate ideology of ontological minimalism, which identified the continuum with a single number system. Such anachronistic distortions characterize the received interpretation of Stevin, Leibniz, d'Alembert, Cauchy, and others.Comment: 46 pages, 4 figures; Foundations of Science (2012). arXiv admin note: text overlap with arXiv:1108.2885 and arXiv:1110.545

ОЦЕНКА ЭФФЕКТИВНОСТИ ЭПИДУРАЛЬНОЙ АНЕСТЕЗИИ ПРИ КОМБИНИРОВАННОМ И ХИРУРГИЧЕСКОМ ЛЕЧЕНИИ РАКА ПРЯМОЙ КИШКИ

The comparative analysis of the efficacy of anesthetic management in 53 patients with operable rectal cancer was carried out. In the study group patients (n=29), preemptive thoracic epidural analgesia was used. In the control group, (n=24), anesthesia was induced with sevofluorane and fentanyl. Preemptive thoracic epidural analgesia provided a reliable blockade of nociceptors and neural pathways, normalized stress response and decreased the severity of the systemic inflammatory response by stimulating the production of antiinflammatory cytokines.Проведен сравнительный анализ эффективности обеспечения и течения периоперационного периода у 53 больных операбельным раком прямой кишки. В основной группе (n=29)  в качестве интраоперационного обезболивания применялась упреждающая анестезия на основе инфузионной грудной эпидуральной аналгезии. В контрольной группе (n=24) пациентов оперировались в условиях анестезии с использованием севофлюрана и фентанила. Установлено, что в основной группе отмечается более адекватное течение анестезиологического этапа периоперационного периода. Упреждающая анестезия на основе периоперационной инфузионной грудной эпидуральной аналгезии обеспечивает надежную блокаду ноцицептивных и чувствительных рецепторов и проводящих нервных путей и обеспечивает нормализацию стрессового ответа, а также уменьшает выраженность системной воспалительной реакции за счет стимуляции продукции противовоспалительных цитокинов

Непосредственные результаты расширенных и мультивисцеральных резекций при раке прямой кишки

Background. Currently, the indications for multivisceral pelvic resections have increased dramatically. However, short-and long-term outcomes after these resections for locally advanced rectal cancer remain a subject of debate.The purpose of the study was to evaluate short-term surgical and oncological outcomes after multivisceral pelvic resections in patients with locally advanced rectal cancer.Material and methods. We analyzed surgical outcomes in 32 patients (13 men and 19 women) aged 44-69 years, with locally advanced rectal cancer, who were treated between 2010 and 2016. Of the 32 patients, 28 (87.5 %) had rectal cancer with invasion into adjacent organs (posterior wall of the bladder - 13, uterus - 10, ureters - 5, prostate - 4, vagina - 3; simultaneous damage to more than 2 organs - 14, multiple primary malignant tumors: rectal cancer + bladder cancer - 2, rectal cancer + endometrial cancer - 1, rectal cancer + rectal GIST - 1.Results. Total pelvic evisceration was performed in 6 (18.8 %) cases, combined resection of the rectum and adjacent organs was performed in 26 (81.2 %). Urinary tract resection was performed in 24 (75.0 %) patients. Of these patients, 13 (40.6 %) had primary plasty of the bladder and/or ureters. Postoperative surgical complications were observed in 11 (34.4 %) patients, of whom 7 (21.8 %) patients needed re-surgery. In 1 patient (3.1 %), who died in the early postoperative period, the cause of death was thrombosis of the right iliac vessels with subsequent acute renal failure. For patients with locally advanced rectal cancer, long-term outcomes were as follows: the overall and recurrence-free 2-year survival rates were 75 % and 56.3 %, respectively. All patients with multiple primary malignant tumors were alive with no evidence of disease recurrence at a follow-up of &gt;24 months.Conclusion. Multivisceral resection in patients with locally advanced rectal cancer is a complex surgical procedure requiring the multidisciplinary team of surgeons. Despite high operative morbidity, proper perioperative management of the patients helps to achieve satisfactory immediate treatment outcomes. Long-term outcomes allowed us to consider such resections as a method of choice for locally advanced and multiple primary rectal cancers.Введение. В настоящее время значительно расширились показания для мультивисцеральных резекций малого таза, однако непосредственная и отдаленная эффективность подобных операций при местнораспространенном раке прямой кишки остается предметом дискуссий.Цель исследования - оценить непосредственные хирургические и онкологические результаты мультивисцеральных резекций органов малого таза у больных местнораспространенным раком прямой кишки.Материал и методы. Проведен анализ результатов хирургического лечения 32 больных (мужчин - 13, женщин - 19) в возрасте 44-69 лет, с местнораспространенными и первично-множественными опухолями прямой кишки, которые получали лечение в 2010-16 гг. Из них у 28 (87,5 %) пациентов - рак прямой кишки (РПК) с инвазией в смежные органы (задняя стенка мочевого пузыря - 13, матка - 10, мочеточники - 5, простата - 4, влагалище - 3; в 14 случаях - одновременное поражение более 2 органов), у 4 (12,5 %) - первичномножественные злокачественные опухоли органов малого таза (РПК + рак мочевого пузыря - 2, РПК + рак эндометрия - 1, РПК + GIST прямой кишки - 1).Результаты. Объемы выполненных операций: в 6 (18,8 %) случаях - полная эвисцерация малого таза, в 26 (81,2%) - комбинированная резекция прямой кишки с резекцией смежных органов. Чаще всего выполнялась резекция мочевых путей - у 24 (75,0 %) больных, из них у 13 (40,6 %) - первичная пластика мочевого пузыря и/или мочеточников. Послеоперационные хирургические осложнения развились у 11 (34,4 %) пациентов, что потребовало повторных операций в 7 (21,8 %) наблюдениях. В раннем послеоперационном периоде умер 1 (3,1 %) больной, причина - тромбоз правых подвздошных сосудов с последующей острой почечной недостаточностью. Отдаленные результаты: РПК - общая и безрецидивная 2-летняя выживаемость -75 % и 56,3 % соответственно, ПМЗО - все пациенты живы без признаков рецидивов, сроки наблюдения &gt;24 мес.Заключение. Лечение распространенных опухолей органов малого таза требует выполнения обширных операций мультидисциплинарной бригадой хирургов. Несмотря на травматичность побочных вмешательств, при адекватном обеспечении периоперационного периода непосредственные результаты можно расценивать как удовлетворительные. Отдаленные результаты позволяют рассматривать подобные операции в качестве метода выбора при местнораспространенном и первично-множественном раке прямой кишки

A systematic review of non-invasive modalities used to identify women with anal incontinence symptoms after childbirth

© 2018, The International Urogynecological Association. Introduction and hypothesis: Anal incontinence following childbirth is prevalent and has a significant impact upon quality of life (QoL). Currently, there is no standard assessment for women after childbirth to identify these symptoms. This systematic review aimed to identify non-invasive modalities used to identify women with anal incontinence following childbirth and assess response and reporting rates of anal incontinence for these modalities. Methods: Ovid Medline, Allied and Complementary Medicine Database (AMED), Cumulative Index of Nursing and Allied Health Literature (CINAHL), Cochrane Collaboration, EMBASE and Web of Science databases were searched for studies using non-invasive modalities published from January 1966 to May 2018 to identify women with anal incontinence following childbirth. Study data including type of modality, response rates and reported prevalence of anal incontinence were extracted and critically appraised. Results: One hundred and nine studies were included from 1602 screened articles. Three types of non-invasive modalities were identified: validated questionnaires/symptom scales (n = 36 studies using 15 different instruments), non-validated questionnaires (n = 50 studies) and patient interviews (n = 23 studies). Mean response rates were 92% up to 6 weeks after childbirth. Non-personalised assessment modalities (validated and non-validated questionnaires) were associated with reporting of higher rates of anal incontinence compared with patient interview at all periods of follow-up after childbirth, which was statistically significant between 6 weeks and 1 year after childbirth (p < 0.05). Conclusions: This systematic review confirms that questionnaires can be used effectively after childbirth to identify women with anal incontinence. Given the methodological limitations associated with non-validated questionnaires, assessing all women following childbirth for pelvic-floor symptomatology, including anal incontinence, using validated questionnaires should be considered