30 research outputs found
Old versus New – Tumor Ablation versus Tumor Nanoablation with Particular Emphasis on Liver Tumors
Loco-regional treatments play a key role in the management of hepatocellular carcinoma (HCC). Image-guided tumor ablation is recommended in patients with early-stage HCC when surgical options are precluded. Radiofrequency ablation is currently established as the standard method for local tumor treatment. Despite major advances in tumor ablation techniques the disease recurs in a high proportion of cases. A major limitation in its overall effectiveness is due to the difficulties of heating large tumors. Small regions of viable tumor may still remain even after apparently good tumor ablation by perfusion-mediated tissue cooling, preventing the whole tumor reaching a sufficient temperature for coagulation and necrosis. Moreover simple heating techniques have trouble discriminating between tumors and surrounding healthy tissues leading to many side effects. In order to overcome these major limitations numerous groups are investigating the use of energy-absorbing agents localized within tumor tissues to facilitate localized heating. A personal answer based on the review of the literature will be offered to the following questions: NIR photothermal therapy, RFA with nanoparticles, or magnetic fluid hyperthermia for the long term management of HCC? How should we deliver nanoparticles: systemically or directly intratumoral? Ablation versus mild hyperthermia: Pros and Cons in the majority of cases, hyperthermia is applied in one of two ways: a) high temperature for short time periods commonly referred to as ablation, or b) lower temperatures for long time periods, often called mild hyperthermia. The former is used to kill cells directly with heat and consequently can be used to thermally ablate tumor. The second method is just above physiological temperature, and these temperatures are more often used to trigger release from thermosensitive drug carriers. Both approaches can be combined with heat-sensitive drug targeting. There are many ways to induce nanoparticle mediated thermal therapy in solid tumors including absorption of infrared light, radiofrequency ablation and magnetically induced heating. These approaches have demonstrated high efficacy in preclinical models of HCC and are already tested in human clinical trials
Особенности диагностики и лечения муцинозных опухолей яичников
Introduction: Ovarian tumors occupy a special place in gynecological pathology due to their great diversity, diagnostic difficulties, specifying their evolutionary nature, establishing the prognosis and treatment. Ovarian mucinous tumors are a group of rare formations, with a cell of as yet undefined origin, but with an apparent progression from benign to borderline and carcinoma. The treatment of a benign ovarian tumor is surgical. Material and methods. The research in question was performed on a group of 50 patients, who were treated in the gynecology department of the IMSP Oncological Institute of the Republic of Moldova, with the diagnosis of mucinous ovarian tumors. Results. The study analyzed data on the diagnosis and treatment of mucinous ovarian tumors. The clinical diagnosis showed a unilateral ovarian involvement in 41 cases (82%) compared to the bilateral one registered in 9 patients (18%). All tumors were large and irregularly shaped. In the case of laboratory diagnosis in assessing the benign or malignant tumor potential, the tumor marker CA-125 was performed, in 41 patients the index was within the norm range from 0-35U / ml and only in 9 cases were there insignificant increases of 50-100U / ml. Ultrasonographic diagnosis is an important method in detecting mucinous ovarian tumors. The treatment of patients is surgical and, depending on the appearance of the tumor intraoperatively and age, they had a radical or less radical character. Conclusions. The most common clinical signs were fullness in the pelvis, dysuria, pain in the lumbar or sacral region. As usual, the mucous ovarian tumors are large. The CA-125 tumor marker was in most cases within the normal range. Imaging investigations are informative and some of them applied to all patients in the study. Endoscopic diagnostic methods are less informative in mucinous ovarian tumors due to bulky formations and the risk of effusion of the mucin into the abdominal cavityIntroducere. Tumorile ovariene ocupă un loc aparte în patologia ginecologică prin marea lor diversitate, prin dificultățile de diagnostic, precizarea caracterului lor evolutiv, stabilirea prognosticului și a tratamentului. Tumorile mucinoase ovariene reprezintă un grup de formațiuni rare, cu o celulă de origine încă nedefinită, dar cu o progresie aparentă de la benignă la limită și la carcinom. Tratamentul unei tumori ovariene benigne este chirurgical. Material și metode. Cercetarea în cauză a fost efectuată pe un lot de 50 paciente, care au fost tratate în secția Ginecologie a IMSP Institutul Oncologic din Republica Moldova, cu diagnosticul de tumori ovariene mucinoase. Rezultate. În studiu au fost analizate date referitoare la diagnosticul și tratamentul tumorilor ovariene mucinoase. Diagnosticul clinic a evidențiat o afectare ovariană unilaterală în 41 de cazuri (82%) față de cea bilaterală înregistrată la 9 paciente (18%). Toate tumorile au fost de dimensiuni mari și cu forme neregulate. În cazul diagnosticului de laborator în aprecierea potențialului tumoral de tip benign sau malign s-a efectuat markerul tumoral CA-125, la 41 paciente indicele a fost în limitele normei de la 0-35U/ml și numai în 9 cazuri s-au evidențiat majorări nesemnificative de la 50-100U/ml. Diagnosticul ultrasonografic este o metodă importantă în depistarea tumorilor ovariene mucinoase. Tratamentul pacientelor este chirurgical și, în dependență de aspectul tumorii intraoperator și vârstă, au avut un caracter radical sau mai puțin radical. Concluzii. Cele mai frecvente semne clinice apărute au fost senzație de plenitudine în pelvis, disurie, dureri în regiunea lombară sau sacrală. Ca de obicei tumorile ovariene mucinoase sunt de dimensiuni mari. Markerul tumoral CA-125 în majoritatea cazurilor a fost în limitele normei. Investigațiile imagistice sunt informative și unele din ele aplicate la toate pacientele din studiu. Metodele endoscopice de diagnostic sunt mai puțin informative în tumorile ovariene mucinoase din cauza formațiunilor voluminoase și riscului de revărsare în cavitatea abdominală a mucinei. Tratamentul tumorilor ovariene mucinoase este exclusiv chirurgical unde vârsta a dictat volumul operatorВведение. Опухоли яичников занимают особое место в гинекологической патологии из-за их большого разнообразия, трудностей диагностики, уточнения их эволюционного характера, установления прогноза и лечения. Муцинозные опухоли яичников представляют собой группу редких образований с клетками, происхождение которых еще не определено, но с очевидным прогрессированием от доброкачественных к пограничным и карциномам. Лечение доброкачественной опухоли яичника хирургическое. Материал и методы. Данное исследование проводилось на группе из 50 пациентов, которые лечились в гинекологическом отделении Института онкологии IMSP Республики Молдова, с диагнозом муцинозные опухоли яичников. Результаты. В исследовании проанализированы данные по диагностике и лечению муцинозных опухолей яичников. При клиническом диагнозе выявлено что одностороннее поражение яичников чаще в 41 случае, что составило 82% по сравнению с двусторонним поражением у 9 пациентами в 18%. Все опухоли большие и неправильной формы. В случае лабораторной диагностики при оценке возможности доброкачественной или злокачественной опухоли онкомаркер СА-125 был в пределах нормы от 0-35 Ед / мл у 41 пациенток (82%), и только в 9 случаях был повышен с 50 -100 Ед/мл. УЗИ диагностика важный метод выявления муцинозных опухолей яичников. Лечение больных хирургическое и в зависимости от возраста и опухоли во время операции решается вопрос об радикальности. Выводы. Наиболее частыми клиническими признаками были ощущение полноты в тазу, дизурия, боли в поясничной или крестцовой области. Как правило, муцинозные опухоли яичников имеют большие размеры. Онкомаркер СА-125 в большинстве случаев был в пределах нормы. Рентгенологические исследования информативны, и некоторые из них применимы ко всем пациентам в исследовании. Эндоскопические методы диагностики менее информативны при муцинозных опухолях яичников из-за объемных образований и риска попадания муцина в брюшную полость. Лечение муцинозных опухолей яичников является исключительно хирургическим и возраст имеет значение в определение объема операци
Intersubunit ionic interactions stabilize the nucleoside diphosphate kinase of <i>Mycobacterium tuberculosis</i>
Most nucleoside diphosphate kinases (NDPKs) are hexamers. The C-terminal tail interacting with the neighboring subunits is crucial for hexamer stability. In the NDPK from Mycobacterium tuberculosis (Mt) this tail is missing. The quaternary structure of Mt-NDPK is essential for full enzymatic activity and for protein stability to thermal and chemical denaturation. We identified the intersubunit salt bridge Arg(80)-Asp(93) as essential for hexamer stability, compensating for the decreased intersubunit contact area. Breaking the salt bridge by the mutation D93N dramatically decreased protein thermal stability. The mutation also decreased stability to denaturation by urea and guanidinium. The D93N mutant was still hexameric and retained full activity. When exposed to low concentrations of urea it dissociated into folded monomers followed by unfolding while dissociation and unfolding of the wild type simultaneously occur at higher urea concentrations. The dissociation step was not observed in guanidine hydrochloride, suggesting that low concentration of salt may stabilize the hexamer. Indeed, guanidinium and many other salts stabilized the hexamer with a half maximum effect of about 0.1 M, increasing protein thermostability. The crystal structure of the D93N mutant has been solved
Comparing Survival of Perihilar Cholangiocarcinoma After R1 Resection Versus Palliative Chemotherapy for Unresected Localized Disease
Background: Resection of perihilar cholangiocarcinoma (pCCA) is a complex procedure with a high risk of postoperative mortality and early disease recurrence. The objective of this study was to compare patient characteristics and overall survival (OS) between pCCA patients who underwent an R1 resection and patients with localized pCCA who received palliative systemic chemotherapy. Methods: Patients with a diagnosis of pCCA between 1997–2021 were identified from the European Network for the Study of Cholangiocarcinoma (ENS-CCA) registry. pCCA patients who underwent an R1 resection were compared with patients with localized pCCA (i.e., nonmetastatic) who were ineligible for surgical resection and received palliative systemic chemotherapy. The primary outcome was OS.Results:Overall, 146 patients in the R1 resection group and 92 patients in the palliative chemotherapy group were included. The palliative chemotherapy group more often underwent biliary drainage (95% vs. 66%, p < 0.001) and had more vascular encasement on imaging (70% vs. 49%, p = 0.012) and CA 19.9 was more frequently >200 IU/L (64 vs. 45%, p = 0.046). Median OS was comparable between both groups (17.1 vs. 16 months, p = 0.06). Overall survival at 5 years after diagnosis was 20.0% with R1 resection and 2.2% with chemotherapy. Type of treatment (i.e., R1 resection or palliative chemotherapy) was not an independent predictor of OS (hazard ratio 0.76, 95% confidence interval 0.55–1.07). Conclusions: Palliative systemic chemotherapy should be considered instead of resection in patients with a high risk of both R1 resection and postoperative mortality.</p
Assessing the impact of COVID-19 on liver cancer management (CERO-19)
Background & Aims: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems and it may have heavily impacted patients with liver cancer (LC). Herein, we evaluated whether the schedule of LC screening or procedures has been interrupted or delayed because of the COVID-19 pandemic. Methods: An international survey evaluated the impact of the COVID-19 pandemic on clinical practice and clinical trials from March 2020 to June 2020, as the first phase of a multicentre, international, and observational project. The focus was on patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma, cared for around the world during the first COVID-19 pandemic wave. Results: Ninety-one centres expressed interest to participate and 76 were included in the analysis, from Europe, South America, North America, Asia, and Africa (73.7%,17.1%, 5.3%, 2.6%, and 1.3% per continent, respectively). Eighty-seven percent of the centres modified their clinical practice: 40.8% the diagnostic procedures, 80.9% the screening programme, 50% cancelled curative and/or palliative treatments for LC, and 41.7% modified the liver transplantation programme. Forty-five out of 69 (65.2%) centres in which clinical trials were running modified their treatments in that setting, but 58.1% were able to recruit new patients. The phone call service was modified in 51.4% of centres which had this service before the COVID-19 pandemic (n = 19/37). Conclusions: The first wave of the COVID-19 pandemic had a tremendous impact on the routine care of patients with liver cancer. Modifications in screening, diagnostic, and treatment algorithms may have significantly impaired the outcome of patients. Ongoing data collection and future analyses will report the benefits and disadvantages of the strategies implemented, aiding future decision-making. Lay summary: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems globally. Herein, we assessed the impact of the first wave pandemic on patients with liver cancer and found that routine care for these patients has been majorly disrupted, which could have a significant impact on outcomes. (C) 2021 The Authors. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL)
Assessing the impact of COVID-19 on liver cancer management (CERO-19).
BACKGROUND & AIMS: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems and it may have heavily impacted patients with liver cancer (LC). Herein, we evaluated whether the schedule of LC screening or procedures has been interrupted or delayed because of the COVID-19 pandemic. METHODS: An international survey evaluated the impact of the COVID-19 pandemic on clinical practice and clinical trials from March 2020 to June 2020, as the first phase of a multicentre, international, and observational project. The focus was on patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma, cared for around the world during the first COVID-19 pandemic wave. RESULTS: Ninety-one centres expressed interest to participate and 76 were included in the analysis, from Europe, South America, North America, Asia, and Africa (73.7%, 17.1%, 5.3%, 2.6%, and 1.3% per continent, respectively). Eighty-seven percent of the centres modified their clinical practice: 40.8% the diagnostic procedures, 80.9% the screening programme, 50% cancelled curative and/or palliative treatments for LC, and 41.7% modified the liver transplantation programme. Forty-five out of 69 (65.2%) centres in which clinical trials were running modified their treatments in that setting, but 58.1% were able to recruit new patients. The phone call service was modified in 51.4% of centres which had this service before the COVID-19 pandemic (n = 19/37). CONCLUSIONS: The first wave of the COVID-19 pandemic had a tremendous impact on the routine care of patients with liver cancer. Modifications in screening, diagnostic, and treatment algorithms may have significantly impaired the outcome of patients. Ongoing data collection and future analyses will report the benefits and disadvantages of the strategies implemented, aiding future decision-making. LAY SUMMARY: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems globally. Herein, we assessed the impact of the first wave pandemic on patients with liver cancer and found that routine care for these patients has been majorly disrupted, which could have a significant impact on outcomes
Contrast enhancement for ultrasound-guided interventions:when to use it and what to expect?
The use of contrast-enhanced ultrasonography (CEUS) has recently become synonymous with high-standard ultrasonography (US). From expanding the reach of US diagnostics to improving the precision of various invasive procedures, CEUS is rapidly becoming a standard in numerous niches. However, proficiency in CEUS comes with a cost, both from a learning curve and material standpoint, and as every growing field, lacks firm evidence and standardization. Therefore, in the current paper, we aim to provide an evidence-based review of available methods and to discuss the advantages and pitfalls of CEUS in interventional procedures, trying to provide strong evidence whenever available, or at least an educated expert opinion if data are lacking
Combined treatments in hepatocellular carcinoma: Time to put them in the guidelines?
The time for battling cancer has never been more suitable than nowadays and fortunately against hepatocellular carcinoma (HCC) we do have a far-reaching arsenal. Moreover, because liver cancer comprises a plethora of stages-from very early to advanced disease and with many treatment options–from surgery to immunotherapy trials–it leaves the clinician a wide range of options. The scope of our review is to throw light on combination treatments that seem to be beyond guidelines and to highlight these using evidence-based analysis of the most frequently used combination therapies, discussing their advantages and flaws in comparison to the current standard of care. One particular combination therapy seems to be in the forefront: Transarterial chemoembolization plus ablation for medium-size non-resectable HCC (3-5 cm), which is currently at the frontier between Barcelona Clinic Liver Cancer classification A and B. Not only does it improve the outcome in contrast to each individual therapy, but it also seems to have similar results to surgery. Also, the abundance of immune checkpoint inhibitors that have appeared lately in clinical trials are bringing promising results against HCC. Although the path of combination therapies in HCC is still filled with uncertainty and caveats, in the following years the hepatology and oncology fields could witness an HCC guideline revolution
The Role of Immunohistochemistry in the Differential Diagnosis between Intrahepatic Cholangiocarcinoma, Hepatocellular Carcinoma and Liver Metastasis, as Well as Its Prognostic Value
Intrahepatic cholangiocarcinoma (iCCA) is the second most frequent primary hepatic malignant tumor, after hepatocellular carcinoma (HCC). Its incidence has risen worldwide, yet the only potentially curative treatment, surgical resection, is seldom applicable, and the median overall survival remains extremely low. So far, there are no personalized therapy regimens. This study investigated whether routine immunohistochemical stains have diagnostic and/or prognostic value in iCCA. Clinical, imaging, and pathology data were retrospectively gathered for patients diagnosed with iCCA, HCC, or liver metastases assessed using liver needle biopsies. Three study groups with an equal number of cases (n = 65) were formed. In the iCCA group, CK19, CA19-9, CK7, and CEA demonstrated the highest sensitivities (100%, 100%, 93.7%, and 82.6%, respectively). The most relevant stains used for diagnosing HCCs were Glypican 3, CD34 (sinusoidal pattern), and Hep Par 1, with corresponding sensitivities of 100%, 100%, and 98.2%. The immunohistochemical panels for diagnosing metastatic tumors were chosen after correlating the clinical data and morphologic H&E aspects. Moderate/intensely positive CK7 expression and absent/low amount of intratumoral immune cells were favorable prognostic factors and correlated with increased overall survival in both the univariate analysis and the multivariate regression adjusted for age, existence of cirrhosis, number of tumors, and tumor differentiation