Curative Therapy Option Research Articles

Progress towards permanent respiratory support.

Although lung transplantation stands as the gold standard curative therapy option for end-stage lung disease, the scarcity of available organs poses a significant challenge in meeting the escalating demand. This review provides an overview of recent advancements in ambulatory respiratory assist systems, selective anticoagulation therapies that target the intrinsic pathway, and innovative surface coatings to enable permanent respiratory support as a viable alternative to lung transplantation. Several emerging ambulatory respiratory assist systems have shown promise in both preclinical and clinical trials. These systems aim to create more biocompatible, compact, and portable forms of extracorporeal membrane oxygenation that can provide long-term respiratory support. Additionally, innovative selective anticoagulation strategies, currently in various stages of preclinical or clinical development, present a promising alternative to currently utilized nonselective anticoagulants. Moreover, novel surface coatings hold the potential to locally prevent artificial surface-induced thrombosis and minimize bleeding risks. This review of recent advancements toward permanent respiratory support summarizes the development of ambulatory respiratory assist systems, selective anticoagulation therapies, and novel surface coatings. The integration of these evolving device technologies with targeted anticoagulation strategies may allow a safe and effective mode of permanent respiratory support for patients with chronic lung disease.

Blinatumomab as a Curative Therapy Option for Relapsed/Refractory Infant Acute Lymphoblastic Leukemia Post-Hematopoietic Stem Cell Transplantation - Case Report

Blinatumomab as a Curative Therapy Option for Relapsed/Refractory Infant Acute Lymphoblastic Leukemia Post-Hematopoietic Stem Cell Transplantation - Case Report

Going Going Gonad: Assessing Iron Staining Impact on Fertility for Patients with Sickle Cell Disease

Introduction: Medical advances in the care of patients with sickle cell disease (SCD) and other hemoglobinopathies have allowed for the focus of care to shift and incorporate long-term quality of life metrics, such as fertility. Concerns for reproductive health in patients with SCD stem from the underlying disease itself as well as from medical therapies that are offered such as hydroxyurea, chronic red blood cell transfusions, and stem cell transplant (SCT). Iron deposition from chronic transfusions in other tissues is known to result in end organ damage and lifelong consequences. While little is known about iron overload and fertility, one study noted testicular iron deposition on MRI in pubertal males with transfusion-dependent beta-thalassemia; results were notable for lower sperm concentrations and a lower percentage of sperm with normal morphology, indicating that iron overload likely has an impact on fertility for patients. Iron deposition has not been studied in the pre-pubertal hemoglobinopathy population. Fertility counseling in this patient population does not often occur until patients are considering SCT as a curative therapy option, as the conditioning regimens for SCT are gonadotoxic. Without a good understanding of the impact of chronic transfusions on fertility for patients with hemoglobinopathies, it is difficult to determine the optimal time to offer fertility preservation to families. We aim to assess iron overload on testicular tissue to gain a better understanding of the impact that medical management and chronic transfusions can have on fertility for a patient with SCD. Methods: Our study is a cross-sectional evaluation of patients with SCD who underwent testicular tissue cryopreservation (TTC) as a part of a multicenter research protocol through the University of Pittsburgh Medical Center (UPMC) prior to SCT. As part of the TTC protocol, each patient provided a small piece of tissue for research, with the remaining cryopreserved for patient use. All samples were evaluated for the presence of germ cells. For this study, demographics, treatment data, imaging results, and labs pertinent to hormonal profile and iron status were obtained. All samples from patients with SCD and thalassemia will undergo additional pathology review to evaluate for the presence of germ cells and iron. At the time of this abstract, the tissue for two patients had been analyzed. Results: Banked research tissue from UPMC includes 77 patients with SCD and 21 patients with beta thalassemia major. Of the 77 SCD patient samples, 42 were found to have germ cells, 34 have not yet been analyzed and 1 had no germ cells present. Of the 21 samples from patients with beta thalassemia major, 17 were found to have germ cells, 3 were not yet analyzed and 1 had no germ cells present. To date, we have obtained pathology review on two patients, both with Hb SS genotype and were on the maximum tolerated dose of hydroxyurea prior to TTC. Patient 1 had been on hydroxyurea for 7 years and had 13 units of blood transfusions, and Patient 2 on hydroxyurea for 4 years and 6units of blood transfusions prior to TTC. Both patients were found to have normal testicular tissue histopathology with presence of germ cells and without evidence of iron on staining (Table 1). Conclusions: Based on our preliminary data it can be noted that patients without significant iron burden, based on low ferritin and a limited transfusion history may not have a significant impact on their testicular histopathology with their iron staining being negative. We will expand our patient cohort to include patients who have a severe disease course requiring more blood transfusions to determine whether this is associated with increased iron deposition in their testicular tissue and/or reduced germ cell numbers. This information will allow teams to optimize the timing of fertility discussions and possible preservation in this patient population, even outside of curative treatment.

Towards Biohybrid Lung Development: Establishment of a Porcine In Vitro Model.

Lung transplantation (LTx) is the only curative therapy option for patients with end-stage lung diseases, though only available for chosen patients. To provide an alternative treatment option to LTx, we aim for the development of an implantable biohybrid lung (BHL) based on hollow fiber membrane (HFM) technology used in extracorporeal membrane oxygenators. Crucial for long-lasting BHL durability is complete hemocompatibility of all blood contacting surfaces, which can be achieved by their endothelialization. In continuation to successful in vitro investigations using human endothelial cells (ECs), indicating general feasibility, the appropriate porcine in vivo model needs to be prepared and established to fill the translational data gap prior to patient’s application. Therefore, isolation of porcine ECs from carotid arteries (pCECs) was established. Following, pCECs were used for HFM endothelialization and examined under static and dynamic conditions using cell medium or heparinized blood, to assess their proliferation capacity, flow resistance and activation state, especially under clinically relevant conditions. Additionally, comparative hemocompatibility tests between native and endothelialized HFMs were performed. Overall, pure pCECs formed a viable and confluent monolayer, which resisted applied flow conditions, in particular due to physiological extracellular matrix synthesis. Additionally, pCECs remained the non-inflammatory and anti-thrombogenic status, significantly improving the hemocompatibility of endothelialized HFMs. Finally, as relevant for reliable porcine to human translation, pCECs behaved in the same way as human ECs. Concluding, generated in vitro data justify further steps towards pre-clinical BHL examination, in particular BHL application to porcine lung injury models, reflecting the clinical scenario with end-stage lung-diseased patients.

S230: HUMAN ΒETA-DEFENSIN 2 TREATMENT MODULATES THE INTESTINAL MICROBIOME AND THE ALLOGENEIC T CELL RESPONSE TO LIMIT ACUTE GRAFT-VERSUS-HOST DISEASE

Background: Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative therapy option for patients with hematological malignancies. Acute graft-versus-host disease (GVHD) is primarily driven by allogeneic donor T cells and remains a serious cause of morbidity and mortality post allo-HCT. In particular, acute GVHD of the gastrointestinal tract (GI GVHD) is associated with a high mortality rate and treatment options are limited. Human β-defensin 2 (hBD-2) is an endogenous epithelial cell-derived host-defense peptide, which is induced by inflammatory stimuli and possesses both antimicrobial and immunomodulatory functions. Aims: In this study, we aimed to investigate the expression of beta defensins in human and murine GI GVHD and the therapeutic effect of recombinant hBD-2 on acute GVHD development in mouse models. Methods: To investigate the functional role of hBD-2 post allo-HCT, we employed established murine GVHD and graft-versus-leukemia (GVL) models and analyzed the allogeneic T cell response using transcriptome and kinome profiling. Shotgun metagenomic sequencing was used to examine the effect of hBD-2 on the intestinal microbiome. Furthermore, we studied beta-defensin expression in two independent acute GVHD patient cohorts and in mice with acute GVHD. Results: We found that expression of murine beta-defensin 4 (mBD-4), the murine orthologue for hBD-2, was reduced in the colon and ileum of mice developing acute GVHD. Oral treatment of mice with recombinant hBD-2 post allo-HCT reduced weight loss and acute GVHD severity and mortality. Furthermore, hBD-2 treatment affected the intestinal microbial composition, including a shift towards higher abundance of Bacteroides species in hBD-2 treated compared to vehicle treated mice. The changes in the microbiome resulted in reduced neutrophil infiltration of the ileum during acute GVHD induction in hBD-2 treated mice. Additionally, hBD-2 dampened pro-inflammatory Th1 cytokine production (TNF, IFN-gamma) by allogeneic T cells in vivo, while preserving the beneficial GVL effect in two different leukemia models. Mechanistically, oral hBD-2 treatment decreased alloreactive T cell infiltration and the expression of genes involved in T cell receptor (TCR) signaling in the ileum of mice with acute GVHD. Using transcriptome and kinome profiling, we found that hBD-2 directly dampened primary murine and human allogeneic T cell proliferation, activation and metabolism by reducing proximal TCR signaling. In patients with acute GI GVHD, intestinal hBD-2 expression was inadequately induced in response to inflammation at the mRNA and protein level when compared to healthy subjects and patients with ulcerative colitis. Summary/Conclusion: In conclusion, our study demonstrates that hBD-2 reduces acute GVHD severity, likely through its effects in shaping the intestinal microbiota, reducing neutrophil infiltration in the ileum and dampening allogeneic T cell responses. Both human and murine acute GVHD are characterized by a lack of intestinal beta-defensin induction and recombinant hBD-2 represents a potential novel therapeutic strategy to counterbalance endogenous hBD-2 deficiency.

Intraoperative Injection of Coloring Dye in the Surgical Treatment of Hidradenitis Suppurativa: A Case Report

Hidradenitis suppurativa (HS) is a recurring and chronic inflammatory skin disease. Various medical and surgical treatments, with varying degrees of efficacy, have been applied based on the Hurley staging system. Since medical treatment cannot change the natural course of the disease and relapse is inevitable in the long-term, radical excision to reduce recurrences is considered as the only curative therapy option for patients with severe II and III stage HS. However, such methods may require intensive reconstructive surgeries and are often accompanied by intraoperative or postoperative problems, resulting in extended treatments. Several methods to detect the degree of the disease and define the resection area have been employed; coloring agents have also been recommended as an option. In this case, we focused on the use of a coloring dye to determine the precise resection margin for a patient with severe HS, as there have been no conclusive reports on the use of a coloring dye in intraoperative operations or follow-up findings. This method could help preserve more viable tissue to reduce the possibility of complications and the duration of hospitalization.

The use of immuno-oncologic therapy in hepatocellular carcinoma in the context of liver transplantation. An interdisciplinary benefit/risk assessment

Multiple systemic therapy options have been recently approved for the treatment of hepatocellular carcinoma (HCC). In particular, immuno-oncology combination therapies can now achieve impressive response rates and significantly prolonged survival with good tolerability. These immuno-oncology (IO)-based combinations are currently not only evaluated for the therapy of advanced HCC, but increasingly also in earlier stages in terms of peri-interventional therapy concepts and also for down-sizing to local therapies. In the context of liver transplantation (LTx), a particularly critical benefit/risk assessment must be made before the use of immunotherapeutics in the context of multimodal concepts, since the risk of a potentially lethal rejection can be significantly increased by immunotherapy. This review is based on a selective literature search performed between December 2020 and April 2021 in the PubMed and Cochrane Library databases. Guidelines, expert opinions, and recommendations from professional societies were given special consideration. Nearly one in five LTx in Germany are performed due to HCCs. In this context, LTx is a curative therapy option not only for the underlying liver disease but also for the malignant tumor. Individual case reports indicate that IO therapy prior to LTx may increase the risk of rejection or liver failure after subsequent liver transplantation. Since 2015, immunotherapeutics have also been widely used for tumor therapy in patients after LTx. In small case series, rejection rates of 36%, associated with rejection-related mortality of 20% of treated patients, have been described. A similar incidence of rejection has also been described following the use of immunotherapeutics in patients after other organ transplantations. In the context of organ transplantation, IO therapy carries the risk of graft rejection, which can lead to graft loss and also patient death. However, from today's point of view, IO-based therapy can be considered in the context of organ transplantation with a careful benefit/risk assessment.

Is Metformin Use Associated With Decreased Thyroid Cancer Risk in Patients With Acromegaly?

Context: Acromegaly has long been blamed to portend an increased risk for benign and malignant thyroid neoplasia. Growth hormone (GH) and consequent insulin-like growth factor 1 (IGF-1) hypersecretion are implicated in cancer promotion. Metformin, a biguanide derived from the French lilac, is gaining considerable interest because of its plausible anti-tumor properties. Besides, metformin has been shown to inhibit somatotroph proliferation and decrease GH secretion in in vivo studies. Patients with acromegaly have high incidence of diabetes and were thereof treated with metformin. We hypothesized metformin use may be linked to decreased thyroid cancer incidence in patients with acromegaly. Study Design and Methods: The medical records of 508 patients with acromegaly followed at our tertiary referral center between 1969 and 2019 were retrospectively reviewed. The inclusion criteria were having a follow-up duration for at least 12 months and being regularly screened for nodular thyroid disease and thyroid cancer by ultrasonography as indicated in respective guidelines. Patients with acromegaly were evaluated based on ongoing or prior history of metformin use or thyroid cancer diagnosis. Metformin exposure was defined as use of metformin for at least 12 months on a regular basis between initial date of acromegaly and time prior to cancer diagnosis date. Considering the long patency period of cancer of interest, we excluded exposures in the year immediately prior to index cancer date. We evaluated the effect of metformin exposure on risk of thyroid cancer using Kaplan-Meier analysis. Results: Final analysis included 377 patients with acromegaly. Mean age at acromegaly diagnosis was 41.6 ± 11.7 and 60.5% of the patients were female. Three hundred twenty-two patients (85.4%) had undergone transsphenoidal surgery as primary therapy, 73 patients (19.4%) needed radiotherapy and 178 patients (46%) received post-operative medical therapy. Median follow-up duration was 73.5 months (IQR [31.0-137.7]). One hundred twenty patients (31.9%) had an ongoing or prior use of metformin, and total of 19 patients (5%) had thyroidcancer. Age at acromegaly diagnosis, gender distribution, baseline GH and IGF-1 levels, pituitary tumor size and invasiveness, biological aggressiveness, curative therapy options, treatment responses didn’t differ between metformin users and non-users, as well as between those having and not having thyroid cancer. Kaplan-Meier estimates for 1 year, 3 years and 5 years of metformin exposure showed decreased probability of thyroid cancer incidence (p<0.05 for all). Conclusion: Although our results imply decreased thyroid cancer risk upon metformin exposure, prospective study designs with larger cohorts are obliged in order to fully elucidate the effect of metformin use on thyroid cancer.

Prognostic biomarkers for cholangiocarcinoma (CCA): state of the art

ABSTRACT Introduction:Although advances in understanding the molecular basis of cholangiocarcinoma (CCA) have been made, surgery is the only curative therapy option and the overall prognosis of patients suffering from the disease remains poor. Therefore, estimation of prognosis based on known and novel biomarkers is essential for therapy guidance of CCA in both, curative and palliative settings. Areas covered:An extensive literature search on biomarkers for CCA with special emphasis on prognosis was performed. Based on this, prognostic biomarkers from serum, tumor tissue and other compartments that are currently in use or under evaluation for CCA were summarized in this review. Furthermore, an overview of new biomarkers was provided including those determined from extracellular vesicles (EVs), metabolites and nucleic acids. Finally, prognostic markers associated with potential new therapy options for the treatment of CCA were summed up. Expert opinion:So far, an optimal prognostic biomarker for CCA has not been described. However, based on the increasing knowledge about the molecular basis of CCA but also due to novel, innovative technologies, a plethora of novel prognostic biomarkers is currently under evaluation and will be available for CCA in future.

Fluorescent Diagnostic Probes in Neurodegenerative Diseases.

Neurodegenerative diseases are debilitating disorders that feature progressive and selective loss of function or structure of anatomically or physiologically associated neuronal systems. Both chronic and acute neurodegenerative diseases are associated with high morbidity and mortality along with the death of neurons in different areas of the brain; moreover, there are few or no effective curative therapy options for treating these disorders. There is an urgent need to diagnose neurodegenerative disease as early as possible, and to distinguish between different disorders with overlapping symptoms that will help to decide the best clinical treatment. Recently, in neurodegenerative disease research, fluorescent-probe-mediated biomarker visualization techniques have been gaining increasing attention for the early diagnosis of neurodegenerative diseases. A survey of fluorescent probes for sensing and imaging biomarkers of neurodegenerative diseases is provided. These imaging probes are categorized based on the different potential biomarkers of various neurodegenerative diseases, and their advantages and disadvantages are discussed. Guides to develop new sensing strategies, recognition mechanisms, as well as the ideal features to further improve neurodegenerative disease fluorescence imaging are also explored.

Detection of Insulinomas Using Dual-Time-Point 68Ga-DOTA-Exendin 4 PET/CT.

Insulinomas are predominantly benign neuroendocrine tumors originating from beta cells within the islets of Langerhans of the endocrine pancreas. Because surgical resection represents the only curative therapy option, exact tumor localization and discrimination of insulinomas from focal or diffuse manifestations of congenital hyperinsulinism are crucial for optimal treatment strategies. We investigated the diagnostic value of glucagon-like peptide 1 receptor PET/CT using Ga-DOTA-exendin 4 for detecting insulinomas and compared the diagnostic value of PET scans performed at 2 time points. In 10 patients with clinically and biochemically suspected insulinoma, PET/CT was performed at 1 hour (PET1) and 2 hours (PET2) after injection of Ga-DOTA-exendin 4. In this retrospective analysis, tracer uptake was visually assessed in both scans by 2 independent readers. SUVmax and tumor-to-background ratio (TBR) of focal lesions were assessed. Imaging results were compared with histopathologic findings, if patients underwent resection. Increased focal Ga-DOTA-exendin 4 uptake was observed in 8 of 10 patients concordantly by both readers. Seven patients with focal uptake underwent surgery with tumor enucleation and histopathologic proof of insulinoma (7/8). Two of 10 patients without focal uptake were considered to suffer from diffuse form of congenital hyperinsulinism and consequently received medical treatment. A significant increase of tumoral SUVmax on PET2 (PET1: SUVmax 20.2 ± 8.2 g/mL; PET2: SUVmax 24.7 ± 7.9 g/mL; P = 0.0018) did not result in a significant improvement in TBR (PET1: TBR 4.9 ± 1.7; PET2: TBR 4.3 ± 1.2; P = 0.2892). Focal uptake of Ga-DOTA-exendin 4 reliably indicated insulinomas as histopathologically confirmed in all patients undergoing consecutive surgery. The diagnostic value of PET2 was not found to be superior to PET1, indicating that a single 1-hour Ga-DOTA-exendin 4 PET/CT scan is a sufficient and convenient approach for patient care.

ARC-4 study: Efficacy and safety of AB928 plus carboplatin, pemetrexed and a PD-1 antibody in participants with metastatic non-small cell lung cancer (mNSCLC).

e21659 Background: Adenosine, derived from ATP released by dying cancer cells in response to chemotherapy, binds to and activates the A2a and A2b receptors on immune cells, resulting in an ineffective anti-tumor immune response. Adenosine receptor blockade may therefore enhance the efficacy of chemotherapy when co-administered with a checkpoint inhibitor. AB928, the first clinical-stage small molecule dual A2aR/ A2bR antagonist, is highly potent and was well tolerated in dose escalation studies as a single agent or in combination with chemo/immunotherapy. Methods: ARC-4 (NCT03846310) is a Phase 1/1b, open-label study in participants (pts) with metastatic, locally advanced, or recurrent non-squamous NSCLC with no alternative or curative therapy option. Pts whose tumor has a genetic alteration for which targeted therapy exists must be chemo/immunotherapy naïve. Pts must have ECOG PS 0-1 and at least one measurable lesion. Two escalating doses of AB928 (75 or 150 mg) administered orally daily were given with standard doses of carboplatin, pemetrexed and pembrolizumab. Results: As of 27Dec19, 7 pts have received AB928 in Ph 1: 75 mg (n = 3), 150 mg (n = 4). Number of prior therapies range from 0 to 6 (median = 3). Most treatment emergent AEs (TEAEs) were Grade 1 or 2, with no Grade 5 events. The most common AEs were anemia, nausea and AST elevation. One pt experienced an SAE (Gr4 thrombocytopenia) that was at least possibly related to AB928. One pt discontinued before assessment due to adverse event (muscle weakness). Of the 6 patients with post-baseline disease assessments, all demonstrated decrease size of target lesion. Three patients (43%) achieved a confirmed partial response: one treatment naïve patient, one patient with EGFRmut disease that had previously progressed on treatment with erlotinib and osimertinib, and one patient who had progressed on therapy with ipilimumab and nivolumab. One additional pt had a &gt; 30% decrease in target lesions and findings consistent with new lesions but opted to continue study treatment. Conclusions: Addition of AB928 to carboplatin, pemetrexed and pembrolizumab did not significantly add to the established safety profile of the standard agents. Combination treatment was associated with disease control in all evaluable pts, including responses in those with PD after TKI and immunotherapy. Expansion is on-going in pts with EGFRmut NSCLC that has failed treatment with TKI. Additional updates on the safety, clinical activity, and correlative biomarker results will be presented. Clinical trial information: 03846310.

Retrospective Evaluation of Relationship Between Iron Overload and Transplantation Complications in Pediatric Patient Who Underwent Allogeneic Stem Cell Transplantation Due to Acute Leukemia and Myelodysplastic Syndrome.

Hematopoietic stem cell transplantation (HSCT) is a curative therapy option for hematologic malignancies. Iron overload is common in this patient group and can impact short-term and long-term nonrelapse mortality. Retrospective observational cohort study. To evaluate the effect of iron load on early and late HSCT outcomes in patients with acute leukemia and myelodysplasia to assess the necessity of reducing iron load. Sixty patients who underwent HSCT in pediatric stem cell transplantation unit between 2000 and 2012 were evaluated retrospectively. The patients were divided into those with pretransplantation serum ferritin levels above and below the median value of 1299 ng/mL. Forty-two (70%) of the patients were male, mean ages of the low and high ferritin groups were 85.43±9.42 and 118.56±10.04 months, respectively. Acute graft-versus-host disease (GVHD) within the first 100 days and acute liver GVHD were significantly more common in the high ferritin group (P<0.011 for both). Ferritin level was not associated with rates of engraftment syndrome, veno-occlusive disease, early/late infection, relapse, or overall and disease-free survival. In our study, significant result especially in terms of acute liver GVHD, was important to emphasize the need to be more careful in terms of acute liver GVHD risk in early liver pathologies in patients with high levels of ferritin after transplantation. In future large studies may be helpful to explain the relationship between acute liver GVHD and high ferritin levels.

Towards the Development of a Biohybrid Lung as Alternative to Lung Transplantation

Lung transplantation is the only curative therapy option for patients suffering from end stage lung diseases. However, it is associated with high risks and only available for selected patients. In order to provide an alternative treatment option, this project aims for the development of an implantable biohybrid lung (BL), based on hollow fibre membrane (HFM) technology used in extracorporeal membrane oxygenators. A crucial requirement to achieve long-lasting durability of the BL is the optimized bio- and haemocompatibility of all blood contacting surfaces, which can be achieved by endothelialisation. Albumin/Heparin (A/H) and Fibronectin (FN) coated HFM were compared for their eligibility to mediate the establishment of a viable, confluent and non-thrombogenic endothelial cell (EC) monolayer. Activation status of the seeded ECs was analyzed and verified by leukocyte- and thrombocyte adhesion assays. The behavior of HFM-seeded ECs under workload conditions, i.e. fluid flow and oxidative stress exposure, was assessed in a customized flow chamber setup. To identify a clinically relevant EC source, comparative studies including human cord blood derived endothelial cells (hCBECs) induced pluripotent stem cell derived endothelial cells and immunotolerable MHC-silenced hCBECs were conducted. A physiologic, viable and confluent EC monolayer could be sustained under both, static and flow dynamic culture conditions. All tested EC types preserved their non-thrombogenic and non-inflammatory status on both tested HMF. Exposure to relevant levels of hyperoxia or hypoxia did not affect the physiological function of the ECs. However, FN coated HFMs demonstrated an improved EC-monolayer resistance towards flow conditions. Endothelialisation of HFM improves their hemocompatibility. Moreover, the endothelial monolayer on HFM can resist clinically relevant settings, like flow exposure and hyperoxia/hypoxia. MHC-silenced ECs could be considered as suitable cell source, escaping the recipient's immune response. These results may bring BL as alternative of lung transplantation for patients with end-stage lung diseases closer to reality.

A Dual-Mode Coaxial Slot Applicator for Microwave Ablation Treatment

Recent developments of microwave ablation systems pursue a treatment monitoring technique in order to provide a curative therapy option for cancer patients. In this paper, such an approach is realized by a dual-mode microwave applicator that enables the permittivity extraction of the tissue surrounding the applicator during the intervention. The additional sensing mode facilitates the positioning of the applicator by detecting dielectric contrasts to indicate the presence of tumors as well as providing tissue state information during the thermal therapy. This feature is based on a one-port calibration scheme which is applied before each intervention. Measurements of various sodium chloride solutions reveal a measurement error below 4%. Furthermore, ex-vivo liver ablation experiments with the input powers of 10 and 20 W are performed to evaluate the treatment monitoring feature and ablation efficacy. A significant permittivity drop down to 82% of the initial permittivity value can be observed after 2 min of ablation. The achieved ablation zones show a preferably spherical shape and clinically relevant volumes with a maximum size of 7.1 cm3.

Image-guided, minimally invasive surgery and other local therapeutic procedures for primary liver tumors

The incidence of primary liver tumors is rising. Modern minimally invasive, image-guided procedures offer apotentially curative therapy option. The aim of this study was to evaluate the multitude of image-guided minimally invasive procedures concerning their evidence-based effect on local tumor control and overall survival. Asystematic search of MEDLINE focused on hepatocellular cancer, minimally invasive treatment, local ablative therapy, therapeutic stratification and comparative studies was performed. The level of evidence varied greatly depending on the procedure used. The highest quality evidence including prospective randomized studies was found for radiofrequency ablation (RFA) of hepatocellular cancer. The RFA is superior with respect to local tumor control and overall survival in comparison to other ablative procedures. Prospective randomized studies comparing surgery and RFA showed diverging and contradictory results. Microwave ablation and robotic stereotactic irradiation showed sufficient potential in retrospective studies in comparison to RFA and surgery in order to confirm the techniques in randomized studies. There is only anecdotal evidence concerning high intensity focused ultrasound (HIFU) and irreversible electroporation. Percutaneous ethanol injection(PEI), cryoablation and laser-induced thermal therapy (LITT) were inferior techniques to RFA in most studies. Minimally invasive resection and local ablative therapies based on structured imaging and image reporting can improve the prognosis of patients with hepatocellular cancer even in patients that exceed the BCLC0/A stage.

High-Intensity Focused Ultrasound for the Treatment of Prostate Cancer: A Review.

Over the past 25 years, the average life expectancy for men has increased almost 4 years, and the age of prostate cancer detection has decreased an average of 10 years with diagnosis increasingly made at early-stage disease where curative therapy is possible. These changing trends in the age and extent of malignancy at diagnosis have revealed limitations in conventional curative therapies for prostate cancer, including a significant risk of aggressive cancer recurrence, and the risk of long-term genitourinary morbidity and its detrimental impact on patient's quality of life (QOL). Greater awareness of the shortcomings in radical prostatectomy, external radiotherapy, and brachytherapy has prompted the search for alternative curative therapies that offer comparable rates of cancer control and less treatment-related morbidity to better preserve QOL. High-intensity focused ultrasound (HIFU) possesses characteristics that make it an attractive curative therapy option. HIFU is a noninvasive approach that uses precisely delivered ultrasound energy to achieve tumor cell necrosis without radiation or surgical excision. In current urologic oncology, HIFU is used clinically in the treatment of prostate cancer and is under experimental investigation for therapeutic use in multiple malignancies. Clinical research on HIFU therapy for localized prostate cancer began in the 1990s, and there have now been ∼65,000 prostate cancer patients treated with HIFU, predominantly with the Ablatherm (EDAP TMS, Lyon, France) device. Neoadjuvant transurethral resection of the prostate has been combined with HIFU since 2000 to reduce prostate size, facilitate tissue destruction, and to minimize side effects. Advances in imaging technologies are expected to further improve the already superior efficacy and morbidity outcomes, and ongoing investigation of HIFU as a focal therapy in salvage and palliative indications is serving to expand the role of HIFU as a highly versatile noninvasive therapy for prostate cancer.

Treatment allocation in hepatocellular carcinoma: Assessment of the BCLC algorithm

Background and aims. The Barcelona Clinic Liver Cancer (BCLC) staging system is the algorithm most widely used to manage patients with hepatocellular carcinoma (HCC). We aimed to investigate the extent to which the BCLC recommendations effectively guide clinical practice and assess the reasons for any deviation from the recommendations.Material and methods. The first-line treatments assigned to patients included in the prospective Bern HCC cohort were analyzed.Results. Among 223 patients included in the cohort, 116 were not treated according to the BCLC algorithm. Eighty percent of the patients in BCLC stage 0 (very early HCC) and 60% of the patients in BCLC stage A (early HCC) received recommended curative treatment. Only 29% of the BCLC stage B patients (intermediate HCC) and 33% of the BCLC stage C patients (advanced HCC) were treated according to the algorithm. Eighty-nine percent of the BCLC stage D patients (terminal HCC) were treated with best supportive care, as recommended. In 98 patients (44%) the performance status was disregarded in the stage assignment.Conclusion. The management of HCC in clinical practice frequently deviates from the BCLC recommendations. Most of the curative therapy options, which have well-defined selection criteria, were allocated according to the recommendations, while the majority of the palliative therapy options were assigned to patients with tumor stages not aligned with the recommendations. The only parameter which is subjective in the algorithm, the performance status, is also the least respected.

Surgery for lymph node metastases of medullary thyroid carcinoma: A review.

Medullary thyroid carcinoma (MTC) is a neuroendocrine malignancy of the thyroid C cells that occurs in hereditary and sporadic clinical settings. Metastatic spread commonly occurs to cervical and mediastinal lymph nodes. MTC cells do not concentrate radioactive iodine and are not sensitive to hormonal manipulation, and therefore surgery is the most effective option for curative therapy, reduction in tumor burden, or effective palliation. In patients undergoing preventative surgery for hereditary MTC, central lymph node dissection should be considered if the calcitonin level is elevated. Preservation of parathyroid function in these young patients is of paramount importance. In patients with established primary tumors, systematic surgical removal of lymph node basins (compartmental dissection) should be guided by ultrasound mapping of lymph node metastases and level of serum calcitonin. A "berry-picking" approach is discouraged. Newly approved targeted molecular therapies offer wider treatment options for patients with progressive or metastatic disease.

Surgery for Lymph Node Metastases of Medullary Thyroid Carcinoma

Medullary thyroid carcinoma (MTC) is a neuroendocrine malignancy of the thyroid C cells, and can commonly spread to cervical and mediastinal lymph nodes. MTC cells do not concentrate radioactive iodine and are not sensitive to hormonal manipulation, and therefore surgery is the only effective option for curative therapy, reduction in tumor burden or effective palliation. In patients undergoing preventative operations for hereditary MTC, central lymph node dissection should be considered if the calcitonin level is above 40 pg/ml. Systematic removal of at-risk or involved lymph node compartments should be performed in all patients with palpable primary tumors and recurrent disease, and a ‘berry-picking’ approach should be avoided.