Session 2: Extramural vascular invasion and extranodal deposits: should they be treated the same?

Professor Nagtegaal has already highlighted that lymph nodes are probably not responsible for the development of liver metastases. If they are not, then is there another mechanism? Professor Haboubi addresses the question of extranodal deposits - their frequency and their importance in the development of metastatic disease. The experts review the evidence and discuss whether this information will alter treatment decisions and staging systems in the future

Anal cancer with large metastases into the perirectal fat: differential diagnosis and treatment policy

Selected squamous-cell anal carcinoma (SCAC) patients are initially presented with large pararectal lymph node metastases.The aim of this study was to investigate safety, efficacy and long-term outcome of chemoradiotherapy in this patient group.Materials and methods. SCAC patients, initially referred with gastrointestinal stromal tumors, rectal cancer diagnosis or patients with regional metastatic lymph nodes more than twice the size of the primary tumour were included in this retrospective analysis. Previous treatment, diagnostic and clinical mistakes of primary care specialists, short- and long-term outcome of chemoradiotherapy were analyzed.Results. 6 patients were included. Primary tumour size varied between 0.5 and 6.5 cm (median – 1.7 cm), metastatic lymph node size varied between 4.2 and 7.4 cm (median – 6.4 cm). All patients received radical doses of chemoradiation. All patients developed grade 3 toxicities, 2 patients developed grade 4 toxicities. Median followup was 15.5 months. 5 out of 6 patients had persistent complete clinical response. 1 patient died of disease progression (incomplete response and metachronous distant metastases).Conclusion. SCAC patients with large regional lymph node metastases have equal prognosis with the rest of the patient group of adequate treatment was carried out

Polybrene Inhibits Human Mesenchymal Stem Cell Proliferation during Lentiviral Transduction

Human mesenchymal stem cells (hMSCs) can be engineered to express specific genes, either for their use in cell-based therapies or to track them in vivo over long periods of time. To obtain long-term expression of these genes, a lentivirus- or retrovirus-mediated cell transduction is often used. However, given that the efficiency with these viruses is typically low in primary cells, additives such as polybrene are always used for efficient viral transduction. Unfortunately, as presented here, exposure to polybrene alone at commonly used concentratons (1–8 µg/mL) negatively impacts hMSC proliferation in a dose-dependent manner as measured by CyQUANT, EdU incorporation, and cell cycle analysis. This inhibition of proliferation was observable in culture even 3 weeks after exposure. Culturing the cells in the presence of FGF-2, a potent mitogen, did not abrogate this negative effect of polybrene. In fact, the normally sharp increase in hMSC proliferation that occurs during the first days of exposure to FGF-2 was absent at 4 µg/mL or higher concentrations of polybrene. Similarly, the effect of stimulating cell proliferation under simulated hypoxic conditions was also decreased when cells were exposed to polybrene, though overall proliferation rates were higher. The negative influence of polybrene was, however, reduced when the cells were exposed to polybrene for a shorter period of time (6 hr vs 24 hr). Thus, careful evaluation should be done when using polybrene to aid in lentiviral transduction of human MSCs or other primary cells, especially when cell number is critical

Рак анального канала с крупными метастазами в параректальную клетчатку: дифференциальная диагностика и лечебная тактика

Selected squamous-cell anal carcinoma (SCAC) patients are initially presented with large pararectal lymph node metastases.The aim of this study was to investigate safety, efficacy and long-term outcome of chemoradiotherapy in this patient group.Materials and methods. SCAC patients, initially referred with gastrointestinal stromal tumors, rectal cancer diagnosis or patients with regional metastatic lymph nodes more than twice the size of the primary tumour were included in this retrospective analysis. Previous treatment, diagnostic and clinical mistakes of primary care specialists, short- and long-term outcome of chemoradiotherapy were analyzed.Results. 6 patients were included. Primary tumour size varied between 0.5 and 6.5 cm (median – 1.7 cm), metastatic lymph node size varied between 4.2 and 7.4 cm (median – 6.4 cm). All patients received radical doses of chemoradiation. All patients developed grade 3 toxicities, 2 patients developed grade 4 toxicities. Median followup was 15.5 months. 5 out of 6 patients had persistent complete clinical response. 1 patient died of disease progression (incomplete response and metachronous distant metastases).Conclusion. SCAC patients with large regional lymph node metastases have equal prognosis with the rest of the patient group of adequate treatment was carried out.У отдельных групп пациентов доминирующим проявлением плоскоклеточного рака анального канала являются метастазы в па­ раректальную клетчатку.Целью данного исследования было оценить безопасность и эффективность химиолучевой терапии, прогноз заболевания у данной категории пациентов.Материалы и методы. В данное ретроспективное исследование включались больные с гистологически верифицированным плоско­ клеточным раком анального канала, которые направлялись на лечение с исходным диагнозом «гастроинтестинальная стромаль­ная опухоль» или «рак прямой кишки», а также пациенты, у которых размеры пораженных регионарных лимфатических узлов превышали размеры первичной опухоли более чем в 2 раза. Мы анализировали: предшествующее лечение, диагностические и ле­чебные ошибки, осложнения, непосредственные и отдаленные результаты химиолучевой терапии.Результаты. В исследование были включены 6 пациенток. Размеры первичной опухоли составили от 0,5 до 6,5 см (медиана 1,7 см), размеры наиболее крупного метастаза – от 4,2 до 7,4 см (медиана 6,4 см). Всем пациенткам была проведена химиолучевая те­рапия по радикальной программе. Осложнения III степени развились у 6 больных, осложнения IV степени – у 2. Медиана наблю­дения составила 15,5 мес. У 5 из 6 пациенток удалось добиться стойкой полной резорбции опухоли. Одна пациентка погибла от прогрессирования заболевания (неполная резорбция первичной опухоли, множественные метастазы в печень и легкие).Заключение. При правильном построении лечебной тактики прогноз больных с крупными метастазами плоскоклеточного рака в параректальную клетчатку не отличается от такового в общей лечебной группе

ИНТЕРСФИНКТЕРНЫЕ РЕЗЕКЦИИ ПО ПОВОДУ РАКА НИЖНЕАМПУЛЯРНОГО ОТДЕЛА ПРЯМОЙ КИШКИ С ПОРАЖЕНИЕМ АНОРЕКТАЛЬНОЙ ЗОНЫ АНАЛЬНОГО КАНАЛА

Preoperative chemoradiotherapy and surgery for low rectal cancer involving anorectal region are discussed in this article.Subjects .and .methods . 42 patients were included in this study, 18 received neoadjuvant chemoradiotherapy 5 × 5 Gy and 24 had chemo-radiotherapy up to 40 Gy in 4 Gy fractions.Results . Treatment had acceptable toxicity levels with grade III toxicity of 11.1 % and 8.3 % accordingly. 20.8 % had pathological complete response following 40 Gy chemoradiotherapy. 22.2 % patients in 5 × 5 Gy group had intershinctering resections comparing to 75 % patients in 40 Gy group. No local or distant recurrences were observed with a median followup of 42.9 months and 18.1 months accordingly.Conclusions . Developed treatment scheme have high efficacy, improving surgery ablastics and leading to good long-term outcome, improving sphincter preservation rate and patients quality of life.В данной статье рассматриваются вопросы предоперационной химиолучевой терапии (ХЛТ) и хирургического лечения пациентов с локализацией аденокарциномы в нижнеампулярном отделе прямой кишки с переходом на аноректальную зону.Материалы и методы . Работа основана на анализе результатов лечения 42 пациентов, 18 из которых проведен курс неоадъювантной термоХЛТ с локальным подведением электронакцепторного соединения с метронидазолом 5 × 5 Гр и 24 больным с целью достижения максимальной регрессии опухоли проведена термоХЛТ также с локальным подведением электронакцепторного соединения с метронидазолом до суммарной очаговой дозы 40 Гр.Результаты . Проведенный анализ безопасности используемых схем лечения показал, что данные программы обладают приемлемым профилем токсичности в пределах 11,1 и 8,3 % соответственно. Полный лечебный патоморфоз первичной опухоли достигнут у 20,8 % после предоперационной термоХЛТ 40 Гр. При использовании предоперационной термоХЛТ 5 × 5 Гр интерсфинктерные резекции выполнены у 22,2 % больных, а при использовании ХЛТ 40 Гр – у 75 %. Отдаленные результаты по степени возникновения локальных рецидивов и метастазов   показали, что до настоящего времени рецидивов и метастазов не зарегистрировано ни в одной группе пациентов при медиане наблюдения 42,9 и 18,1 мес соответственно.Заключение . Разработанные неоадъювантные программы лечения являются безопасным высокоэффективным методом лечения, позволяющим повысить абластичность хирургического вмешательства, улучшить отдаленные результаты лечения, увеличить частоту выполнения сфинктеросохраняющих операций, снизить процент инвалидизации пациентов и тем самым сохранить качество жизни у данной категории больных

ВОЗМОЖНОСТИ СТАНДАРТНЫХ РЕЖИМОВ МАГНИТНО-РЕЗОНАНСНОЙ ТОМОГРАФИИ СОВМЕСТНО С ДИФФУЗИОННО-ВЗВЕШЕННОЙ МАГНИТНО-РЕЗОНАНСНОЙ ТОМОГРАФИЕЙ В ОЦЕНКЕ МЕСТНОЙ РАСПРОСТРАНЕННОСТИ РАКА ПРЯМОЙ КИШКИ

In this article we present up-to-date views on rectal cancer imaging. Accurate initial and follow-up staging of rectal cancer is vitally important and provides information essential for treatment decision making, preoperative therapy and surgery planning. Almost worldwide magnetic resonance imaging (MRI) is currently considered as the most advanced staging modality for rectal cancer; however conventional MRI sequences have some diagnostic limits and not always allow to differentiate fibrotic tissue (present either desmoplastic reaction or fibrotic changes due to preoperative radiotherapy) from tumor. On the basis of our own experience and published data we tried to demonstrate imaging possibilities of conventional and diffusion-weighted (DW) MRI in local staging of rectal cancer.Статья посвящена актуальным вопросам диагностики рака прямой кишки (РПК). Корректное первичное и предоперационное стадирование РПК позволяет выбирать необходимую тактику лечения, планировать предоперационную терапию и само хирургическое вмешательство. На сегодняшний момент во многих странах магнитно-резонансная томография (МРТ) является диагностическим методом выбора для стадирования РПК, но стандартные режимы МРТ имеют свои пределы и не всегда позволяют дифференцировать фиброзную ткань (которая может представлять десмопластическую реакцию или постлучевой фиброз) от опухолевой ткани.На основе литературных данных и собственного накопленного опыта мы попытались продемонстрировать возможности не только стандартных режимов МРТ, но и диффузионно-взвешенной МРТ ((ДВ)-МРТ) в оценке местной распространенности РПК

Mechanisms of bone-marrow stem cell-mediated delayed ischemic neuroprotection in rat retina

The abstract can be viewed at http://www.asaabstracts.com/strands/asaabstracts/abstract.htm;jsessionid=8B0404AE3FDBF0AB9EAE20152CF76D98?year=2011&index=10&absnum=5635Poster Session: Experimental Neurosciences: abstract no. A130

Functional single-cell hybridoma screening using droplet-based microfluidics

Monoclonal antibodies can specifically bind or even inhibit drug targets and have hence become the fastest growing class of human therapeutics. Although they can be screened for binding affinities at very high throughput using systems such as phage display, screening for functional properties (e.g., the inhibition of a drug target) is much more challenging. Typically these screens require the generation of immortalized hybridoma cells, as well as clonal expansion in microtiter plates over several weeks, and the number of clones that can be assayed is typically no more than a few thousand. We present here a microfluidic platform allowing the functional screening of up to 300,000 individual hybridoma cell clones within less than a day. This approach should also be applicable to nonimmortalized primary B-cells, as no cell proliferation is required: Individual cells are encapsulated into aqueous microdroplets and assayed directly for the release of antibodies inhibiting a drug target based on fluorescence. We used this system to perform a model screen for antibodies that inhibit angiotensin converting enzyme 1, a target for hypertension and congestive heart failure drugs. When cells expressing these antibodies were spiked into an unrelated hybridoma cell population in a ratio of 1∶10,000 we observed a 9,400-fold enrichment after fluorescence activated droplet sorting. A wide variance in antibody expression levels at the single-cell level within a single hybridoma line was observed and high expressors could be successfully sorted and recultivated

Radiological Biomarkers in MRI directed Rectal Cancer Radiotherapy Volume Delineation.

Our study evaluated whether an MRI reporting system highlighting areas of contiguous and discontinuous extramural venous invasion (EMVI) can improve the accuracy of gross tumour volume (GTV) delineation. Initially, 27 consecutive patients with locally advanced rectal cancer treated between 2012 and 2014 were evaluated. We used an MRI reporting proforma that documented the position of the primary tumour, lymph nodes and EMVI. The new GTVs delineated were compared with historical radiotherapy treatment volumes to identify the frequency of GTV geographical miss. We observed that the delineation of involved nodes and areas of EMVI was more likely to represent sources of uncertainty wherein nodal GTV geographical miss was evident in 5 out of 27 patients (19%). Complete EMVI GTV geographical miss occurred in two patients (7%). We re-evaluated our radiotherapy practice in a further 27 patients after the implementation of a modified MRI reporting system. An improvement was seen; nodal miss was observed in two patients (7%) and partial EMVI miss in one patient (4%), although these areas were encompassed in the planning target volume (PTV). Our study shows that extramural venous invasion and involved nodes need to be highlighted on MRI to improve the accuracy of rectal cancer GTV delineation