Excellent antibacterial activity of Slovak honeys on bacteria mostly infecting chronic wounds.

INTRODUCTION AND AIM OF STUDY: Chronic wounds are commonly colonized by various bacterial species and colonization frequently turns into wound infection, severely impairing healing process. With increasing antimicrobial resistance, the antimicrobial treatment of chronic wounds may be extremely challenging. Rediscovery of old and forgotten antimicrobial therapeutic options, such as apitherapy, may contribute to solving the problem of incurable chronic wound infections. Aim of this study was to evaluate the antimicrobial properties of four kinds of Slovak honey from ecological beekeeping against the most common bacterial species contaminating and infecting chronic wounds, and to compare these antimicrobial activities with those of the approved medical-grade Manuka honey. The impact of honey sterilisation methods and long-lasting storage on the bactericidal activity was also examined. MATERIAL AND METHODS: Antimicrobial activity of honey was detected against 7 bacterial collection strains by broth microdilution antimicrobial susceptibility test according to EUCAST. The results were statistically analysed by Fisherꞌs exact test. RESULTS AND CONCLUSIONS: Slovak ecologically produced honey samples demonstrated an excellent in vitro antibacterial activity, superior to the monofloral medical-grade Manuka honey activity. Neither the gamma-irradiation, nor the three-year-long storage had impact on the bactericidal activity of the tested honey (Tab. 4, Fig. 2, Ref. 53).

DRY EYE DISEASE. A REVIEW.

This article provides a comprehensive view of the issue of dry eye. It emphasizes provisions of the Tear Film and Ocular Surface Society, discusses the new classification and definition of dry eye based on its pathophysiology, and emphasizes the correct diagnostic and therapeutic approaches, which appears in the form of algorithms. Dry eye is a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles. Dry eye disease is a dynamic and complex disease of the ocular surface and ocular adnexa with known risk factors. It is a disease with a cyclical character, in which the most important step is to find the etiological trigger, to restore homeostasis and break the vicious circle. The key elements in the diagnosis are increased osmolarity of the tear film and inflammation of the ocular surface, which are accompanied by ocular symptoms (discomfort, visual disturbance). Inflammation is not always associated with hyperemia and can be confirmed by several techniques and methods. However, in current clinical practice, there is still no "gold standard" and sufficient tests to diagnose inflammation of the ocular surface. The treatment of dry eye disease must be individualized, dynamic and optimized for each stage of the disease.

AMNIOTIC MEMBRANE TRANSPLANTATION AT THE DEPARTMENT OF OPHTHALMOLOGY OF THE UNIVERSITY HOSPITAL BRNO.

BACKGROUND: The aim of the work is a discussion of amniotic membrane transplantation at the Eye Clinic of the University Hospital Brno and a retrospective evaluation of a group of patients for the period 2014-2019 who were treated for various indications. METHODS: Retrospective evaluation of the number and effectiveness of individual types of amniotic membrane in a group of patients after amniotic membrane transplantation (AMT) for various indications. A total of 134 patients were included in the study group, of which 68 were men and 66 were women. The median age was 70 years. The total number of amniotic membrane transplants performed during the selected six years was 139, with half the distribution using frozen (69 eyes) and lyophilized amniotic membrane (70 eyes). The AMT technique was chosen based on the initial finding and diagnosis. The type of amniotic membrane used (lyophilized vs. frozen) depended on the urgency of the procedure. RESULTS: The number of amniotic membrane transplantations was evaluated in a group of 134 patients (139 eyes) and their effectiveness in individual diagnoses was demonstrated. During the follow-up period, more transplantations of amniotic membranes were performed during hospitalization than in the outpatient department, both types of membranes (frozen and lyophilized). Amniotic membrane transplantation during hospitalization was performed in 89 eyes, in the outpatient mode in 50 eyes. Indications for amniotic membrane transplantation included microperforation and corneal perforation (30 eyes), non-healing corneal defects (21 eyes), descemetocele (19 eyes), neurotrophic defects (16 eyes), ablation of pterygium (12 eyes) and corneal lysis (11 eyes). eyes). Other conditions (conjunctival lesions, fornix reconstruction, burns, peripheral ulcerative keratitis, ocular cicatricial pemphigoid and keratectomy) were represented in smaller numbers. Despite the very diverse group of indications and the advanced age of the patients, a very good efficacy of the performed amniotic membrane transplantations was found. Some patients died during the follow-up period, so the limitation of work is short and unequal follow-up period. CONCLUSION: The success of the procedure depends not only on the correct timing, indication and technique of transplantation, but also on patient compliance and well-functioning cooperation of regional ophthalmologists.

The value of 18F-FDG-PET testing in the management of esophageal and gastroesophageal junction adenocarcinoma - review.

BACKGROUND: Preoperative chemoradiotherapy (CRT) and perioperative chemotherapy (CHMT) are a standard of care for distal esophageal and gastroesophageal junction adenocarcinomas. PET/CT using 18F-fluorodeoxyglucose (18F-FDG-PET/CT) is one of the basic staging examinations with a certain prognostic significance and has recently been studied for the possibility of showing prognostic or predictive results suitable for the individualization of treatment strategy. PURPOSE: The aim of this review is to map the role of 18-FDG-PET/CT in predicting the response to CHMT and CRT, which could be a starting point for personalized treatment. CONTENT: The change in metabolic activity in the maximum standardized uptake value is most often used to quantify the treatment response; total lesion glycolysis is a volumetric parameter. A method for standardizing measurements was offered in the PERCIST system. Several studies have been published showing that the decrease in metabolic activity after chemotherapy correlates with a surrogate measure of the treatment outcome, which is the degree of tumor regression in the resected tissue, but also with survival or time to progression. The cut-off value separating sensitive and resistant tumors varied from 33 to 78%, the measurement took place either at the end of neoadjuvant treatment or „early“, about 2 weeks after the first cycle of CHMT. However, this value has not yet been validated and the parameters of sensitivity, specificity and negative and positive predictive values for the prediction of treatment outcome fluctuated significantly. In the case of preoperative CRT, PET/CT could not predict the complete response to the treatment with satisfactory accuracy. Studies using early metabolic response to change the treatment strategies in non-responders have not yet shown whether changing the treatment in patients without an early metabolic response to CHMT will improve survival. In the case of randomization, a standard arm with a continuation of the original CHMT was never used. CONCLUSION: Evaluation of an early PET-based response has the potential to modify the treatment in patients who have not demonstrated an early response to CHMT. However, this is not an approach suitable for routine practice outside of clinical trials. So far, it seems possible to use an early metabolic response for small, exploratory studies evaluating new agents and their combinations in the preoperative treatment of localized esophageal cancer or gastroesophageal junction cancer.

Design of abdominal retractor.

INTRODUCTION: The purpose of this paper is to present the development and design of an abdominal retractor which allows a single person to perform operations and the fixation of the operation instruments can be done with one hand. The additional devices make the operation more comfortable for surgeons. METHODS: Conventional measuring devices have been designed and applied for determining axial forces in a surgeon's forearm during operations. The same forces must be transmitted by the frame of the retractor. Thus a simple truss structure of a retractor was done. Several types of fixations have been proposed and tested using the rapid prototyping. Finally, the abdominal retractor was manufactured from stainless steel. RESULTS: The simple-to-use abdominal retractor was built. The standard surgery instruments were modified due to the fixation system of the frame. A wide variety of additional useful devices, such as a lamp, video camera etc., were also proposed. CONCLUSION: The present abdominal retractor is user-friendly and all components are easily sterilized by conventional methods (Fig. 7, Ref. 6) Keywords: abdominal retractor, stainless steel retractor, standard surger, fixation system of the frame, lamp, video camera, conventional methods.

Usage of shear wave elastography for diagnosis of changes of oculomotor muscles in endocrine orbitopathy.

BACKGROUND: Shear wave elastography (SWE) is an imaging modality using advantage of ultrasound to detect differences of elastic properties (mechanical rigidity) of tissues. SWE increasingly develops across medical specialities and is already used in hematology, urology and oncology. In the field of ophthalmology using SWE to evaluate corneal mechanical properties, peripapillary biomechanical qualities in glaucoma patients several papers were published Also SWE ultrasound mechanical specificity safety studies were published. Aim of this work is to review SWE technique and its potentional using during examination in patients with endocrine orbitopathy (EO). In practical part of this work is evaluated the elasticity of oculomotor rectus muscles in healthy population, in patients with EO in early stage of disease (oculomotor muscles oedema) and in patients with EO in terminal stage of this disease (oculomotor muscles fibrosis) is determinate. Also possibility of using SWE (in comparison with standard ultrasound examination) for measuring thickness of oculomotor muscles is evaluated. METHODS: There were 60 eyes in 30 patients with EO examined and the elasticity of oculomotor muscles was determined. Results were compared with values of elasticity in 40 eyes in healthy population of 20 people. All measurements were performed with ultrasonic system Aixplorer of SuperSonic manufacturer in standardized terms and been undertaken by the same performer. Each value was measured several times to reduce measurement errors. RESULTS: Oculomotor rectus muscle elasticity values in healthy population measured by using SWE were as follows: musculus rectus superior (MRS) 19.7 ± 3.2 kPa, musculus rectus medialis (MRM) 20.5 ± 3.6 kPa, musculus rectus inferior (MRI) 20.4 ± 3.1 kPa and musculus rectus temporalis (MRT) 20.2 ± 1.7 kPa. As statistical analysis shows, there is no significant difference between muscles (ANOVA test p > 0.05); overall elasticity of oculomotor muscles in healthy population is 20.3 ± 3.0 kPa. Elasticity of muscles in group of EO patients in oedema stage and EO patients in fibrosis stage is 18.4 ± 3.2 kPa and 34.6 ± 7.5 kPa respectively. Both values show statistical significance in the comparison with healthy population (p.

Shear wave elastography in ophthalmic diagnosis.

Shear wave elastography (SWE) is a non-invasive diagnostic imaging technique that maps the elastic properties of tissues. This modality is being increasingly developed in other areas of medicine, offering a new type of high-quality ultrasound examination, since it increases specificity and thus improves diagnostic accuracy. This method is similar to manual palpation, showing the elastic properties of biological tissues and providing a kind of reconstruction of the internal structure of soft tissues based on measurement of the response to tissue compression. In ophthalmology, it already appears promising for diagnosis and in evaluating changes in extraocular muscles and orbital tissues in patients with endocrine orbitopathy. Shear wave elastography offers three main innovations: the quantitative aspect, dimensional resolution, and real-time imaging ability. Determination of the utilization rate of this method and its inclusion in the diagnosis of endocrine orbitopathy is still a question and the object of clinical studies currently under way.

[18 F]Fluorodeoxyglucose PET/CT and prediction of histopathological response to neoadjuvant chemotherapy for adenocarcinoma of the oesophagus and oesophagogastric junction.

BACKGROUND: The aim of this prospective study was to assess whether [18 F]fluorodeoxyglucose PET can be used to predict histopathological response early in the course of neoadjuvant chemotherapy in patients with adenocarcinoma of the oesophagus and oesophagogastric junction. METHODS: Following the PET response criteria in solid tumours (PERCIST 1.0) as a standardized method for semiquantitative assessment of metabolic response, FDG-PET/CT was performed before (PET1) and after (PET2) initiation of the first cycle of chemotherapy. The relative changes in the peak standardized uptake value (ΔSUL) and total lesion glycolysis (ΔTLG) between PET1 and PET2 were correlated with histopathological response, defined as less than 50 per cent viable tumour cells in the resection specimen. A receiver operating characteristic (ROC) curve analysis was used to identify the optimal cut-off value with the highest accuracy of histopathological response prediction. RESULTS: PET2 was performed a median of 16 (range 12-22) days after the start of chemotherapy. Some 27 of 90 patients who underwent surgery had a histopathological response. There was no association between the median ΔSUL or median ΔTLG and the histopathological response. A post hoc analysis in 47 patients with PET2 performed 16 days or less after the start of chemotherapy showed that ΔTLG, but not ΔSUL, was associated with the histopathological response (P = 0·009). The optimal cut-off value of ΔTLG was 66 per cent or more. CONCLUSION: FDG-PET/CT after the first cycle of chemotherapy does not predict histopathological response in patients with adenocarcinoma of the oesophagus and oesophagogastric junction.

Effect and Toxicity of Radiation Therapy in Selected Palliative Indications.

BACKGROUND: Radiotherapy (RT) is a mainstay of oncology treatment in both curative and palliative situations. With respect to palliative and supportive care, RT improves local control of disease and relieves symptoms, particularly pain, compression of surrounding structures, and/or bleeding. The aim here was to evaluate the effects and toxicity of palliative RT in our department from April 2015 to April 2018. PATIENTS AND METHODS: During this period, 338 cases received palliative RT, representing approximately one third of indications for this treatment method. We evaluated selected subgroups of patients: those with advanced lung cancer, bone metastases, or soft tissue metastases. Patients were irradiated by the IMRT (intensity modulated radiation therapy) technique using the TomoTherapy HD (Accuray, USA) platform. RESULTS: Palliative RT for primary lung cancer was performed for 29 patients. Of these, symptoms were relieved in 22 patients (76%) and local control (confirmed by imaging) was achieved in 19 patients (66%). Treatment-related toxicity was acceptable. Overall, 104 patients received irradiation for bone metastases; pain relief was achieved in more than 75% of cases. Another 71 patients were irradiated to treat soft tissue metastases; symptoms were relieved in 60% of cases. Treatment-related toxicity in our patients was lower than reported previously, suggesting improved quality of life for patients irradiated using modern RT technologies. CONCLUSION: Palliative RT provided excellent symptom control in our patients, with minimal toxicity. Thus, RT is an effective and easy-to-use method for many palliative indications. Key words: palliative care - radiotherapy - lung neoplasms - neoplasm metastasis - bone metastases - pain management The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 28. 8. 2018 Accepted: 29. 10. 2018.

[Benefits and Negatives of Corticosteroid Therapy in Corneal Pathologies]. / Prínos a kontraproduktivita terapie kortikosteroidy u afekcí rohovky.

INTRODUCTION: Corticosteroid therapy is very beneficial in many types of eye diseases. Corticosteroids are used in the treatment of inflammatory and immunological diseases of the eye. PURPOSE: The aim is to present basic informations about effects of steroids in tissues, their side effects and treatment strategy. METHODS AND RESULTS: Authors process overview of local and systemic steroids and their dosage forms. They refer to the most common problems associated with corticosteroid therapy. CONCLUSION: Although corticosteroids include medicine across to one of the most frequently prescribed drugs at all, it is always necessary to treat very carefully indicate any corticosteroid preparation and prior to its administration to eliminate all infectious diseases, take a thorough anamnesis and complete examine the patient.Key words: cornea, corneal healing, inflammatory cascade, corticosteroids.

[New Diagnostic Imaging Technique - Shear Wave Elastography]. / Nová diagnostická zobrazovací metoda - shear waves elastografie.

Shear wave elastography (SWE) is a new non-invasive diagnostic imaging technique, that maps the elastic properties of tissues. Nowadays this modality develops increasingly in medicine across its disciplines and opens a new era of high-quality ultrasound examination because it increases the specificity and thus improves diagnostic assurance. This method is similar to manual palpation, shows elastic properties of biological tissues and provides a kind of reconstruction of the internal structure of soft tissues based on measurement of the response of tissue compression. Various biological tissues have different elasticity and changes of these elastic properties often reflect pathological processes in the tissue and its abnormalities. This method is already used routinely on some foreign institutions in the detection and diagnosis of breast cancer and thyroid cancer, prostate cancer, in hepatology, cardiology, view the carotid arteries and lymphatic nodules. Finally examines its unquestioned benefit in ophthalmology. The output of elastography is an ultrasound image B-mode superimposed color-coded map. Shear waves elastography provides three major innovations: the quantitative aspect, the spatial resolution and the ability to run in real time.Key words: ultrasound, elastography, Youngs modulus, shear-wave, SonicTouchTM, UltrafastTM display.

Monitoring of hands movement trajectories in the field of laparoscopic and endoscopic surgeries and options in the clinical practice.

Within the project "Applied research trajectory hands in laparoscopic and endoscopic operations", ITMS Project code 26240220056, funded by the European Regional Development Fund and the state budget of the Slovak Republic, we created a technical background and algorithms for monitoring and evaluating the hand movements of the surgeon during laparoscopic and endoscopic operations. This is a unique idea and unique project transformed into clinical practice, which is promising to assist in laparoscopic training and inclusion of surgeon / endoscopist to "skilfulness" group on the evaluation of the effectiveness of movements of his hands (Tab. 2, Ref. 11).

Sorafenib treatment of advanced renal cell carcinoma patients in daily practice: the large international PREDICT study.

BACKGROUND: Patients with advanced renal cell carcinoma in routine clinical practice can differ considerably from those in phase III studies. PATIENTS AND METHODS: PREDICT (Patient characteristics in REnal cell carcinoma and Daily practICe Treatment with sorafenib) was a prospective, noninterventional study of open-label sorafenib for the treatment of advanced RCC conducted in 18 countries. Patient characteristics, therapy duration, tumor status, and tolerability were assessed at baseline and during routine follow-up. RESULTS: Overall, 2599 patients were evaluable for safety and 2311 for efficacy. The diverse population included patients with brain metastases (5%), non-clear-cell histologies (17%), high Memorial Sloan-Kettering Cancer Center risk score (11%), poor Eastern Cooperative Oncology Group performance status (PS ≥ 2, 29%), and patients with no previous nephrectomy (16%) or no previous systemic therapy (37%). The median duration of sorafenib therapy was 7.3 months and was similar in clinically relevant subgroups (eg, patients with PS 2, brain metastases, or concomitant hypertension or diabetes [range, 6.7-7.0 months]). The median duration of therapy was shorter for patients with PS 3 or non-clear-cell histologies (4.6 and 4.8 months, respectively). The most common drug-related adverse events were hand-foot skin reaction (20%), diarrhea (17%), and rash (8%). CONCLUSION: Sorafenib was generally well tolerated and provided clinical benefit in a large, diverse population of patients with advanced RCC treated in routine clinical practice.

Analysis of radiation-induced angiosarcoma of the breast.

Breast angiosarcoma may occur de novo, or as a complication of radiation therapy, or chronic lymphedema secondary to axillary lymph node dissection for mammary carcinoma. Both primary and secondary angiosarcomas may present with bruise like skin discoloration, which may delay the diagnosis. Imaging findings are nonspecific. In case of high-grade tumours, MRI may be used effectively to determine lesion extent by showing rapid enhancement, nevertheless earliest possible diagnostics is crucial therefore any symptoms of angiosarcoma have to be carefully analysed. The case analysed here reports on results of 44-year old premenopausal woman who was treated for a T1N1M0 invasive ductal carcinoma. After a biopsy diagnosis of carcinoma, the patient underwent quadrantectomy with axillary lymph node dissection. She received partial 4 cycles of chemotherapy with adriamycin and cyclophosphamide, followed by radiation treatment. Thereafter, a standard postoperative radiotherapy was applied at our institution four months after chemotherapy (TD 46 Gy in 23 fractions followed by a 10 Gy electron boost to the tumour bed). Adjuvant chemotherapy was finished six months after operation, followed by tamoxifen. Follow up: no further complications were detected during regular check-ups. However, 12-years later, patient reported significant changes at breast region which was exposed to radiation during treatment of original tumour. In this article, we describe the clinical presentation, imaging and pathological findings of secondary angiosarcoma of the breast after radiotherapy (Fig. 2, Ref. 26).

Peri-operative chemotherapy in patients with oesophageal and gastro-oesophageal junction cancer - three years of experience.

Peri-operative chemotherapy has been found to benefit patients with oesophageal and gastro-oesophageal junction adenocarcinoma. This study's aim was to evaluate the efficacy and tolerance of this treatment. The study included patients with carcinoma of the lower oesophagus and gastro-oesophageal junction in whom the disease was evaluated as potentially operable. Chemotherapy (CHT) consisted of three preoperative and three postoperative cycles of intravenous epirubicin and cisplatin on day 1 plus a continuous infusion of fluorouracil for 21 days (ECF) or oral capecitabine for 14 days (ECCap). Postoperative radio-chemotherapy (CRT) with fluorouracil or capecitabine after CHT was indicated in patients with two and more positive lymph nodes. Sixty-three patients started the treatment. Median follow-up was 32 months. Preoperative CHT was completed by 62 patients, 52 had surgery, 46 had radical resection, 25 patients had pN0 and 21 patient pN plus findings. Postoperative CHT was started in 39 (62%) patients and completed in 32 (51%). Ten (16%) patients had postoperative CRT. Adverse events of grade 3 and 4 were: neutropenia 17%, vomiting 8%, fatigue 5%, diarrhoea 3%. Reasons for omitting surgery in 11 (17%) patients were: progression in 7 patients, medically unfit in 3 patients, other in 1 patient. In the reporting period there were recurrences in 39 of all patients, in 7 locoregional only, in 10 distant plus locoregional, and in 19 distant metastases. Median survival was 24.1 months and 3-year survival rate was 42%. Peri-operative chemotherapy ECF/ECCap was feasible and well tolerated. Radical resection was performed in most patients.

Preoperative radiotherapy of locally advanced rectal cancer: clinical outcome of short-course and long-course treatment with or without concomitant chemotherapy.

BACKGROUND: Preoperative radiotherapy is considered to be standard treatment for locally advanced rectal cancer. The timing and dosage of radiotherapy with or without preoperative chemotherapy remain controversial issues. The objective of this study was to evaluate relevant clinical outcomes of two preoperative radiotherapy regimens - the short-course and -long-course radiotherapy with or without chemotherapy for patients with locally advanced rectal cancer. PATIENTS AND METHODS: 151 patients with stage II-III rectal cancer (103 males and 48 females) treated with preoperative radiotherapy between 01/1999 and 01/2008 were involved in this study. Analysed patterns included sphincter preservation, tumor down-staging, pathological complete remission, frequency of local recurrence, acute and late toxicity, peri-operative complications, overall survival and disease-free survival. RESULTS: Tumor downstaging has been achieved by long-course radiotherapy alone (46%) or in combination with chemotherapy (5-FU or capecitabine, 61%). Pathological complete remission has also been achieved only in the group with long-course radiotherapy (13%). Long-course radiotherapy combined with chemotherapy significantly decreased post treatment local recurrence rates (5% versus 15% in the group after long-course radiotherapy alone, p = 0.0132). Statistically significant difference was confirmed in overall survival of patients treated with long-course radiotherapy combined with chemotherapy vs long-course radiotherapy alone (p = 0.015). Significant difference between the rate of perioperative complications, of acute and late toxicity, 3 and 5 years disease-free survival of treated patients after short-course radiotherapy and long-course radiotherapy was not confirmed. CONCLUSION: Our findings provide convincing evidence that in comparison to preoperative short-course radiotherapy, the preoperative long-course radiotherapy in combination with chemotherapy is the most effective treatment modality for patients with operable locally advanced rectal cancer in terms downstaging and pathologic complete response. Increase in overall survival time as well as lower local recurrence rate makes this modality superior to other preoperative radiotherapy alternatives.

Outcomes of patients with oesophageal cancer treated with preoperative chemoradiotherapy, followed by tumor resection: influence of nutritional factors.

PURPOSE: To assess the impact of clinical and nutritional factors on overall survival (OS) and time to disease progression of oesophageal cancer patients treated with neoadjuvant chemoradiotherapy (CRT) and surgery. METHODS: We retrospectively studied and analysed several clinical and nutritional factors, such as performance status, weight changes before and during CRT, dysphagia, nutritional support, and serum albumin to see whether they exerted any impact on OS and time to disease progression. RESULTS: In 107 patients the average weight loss was 9.7% from the onset of signs of disease to the beginning of therapy and 3% during CRT. In univariate analysis, significant unfavorable impact on survival was proved for low performance status, severe dysphagia, need for nasogastric tube insertion, above-average weight loss before treatment, weight loss >5% during CRT, and serum albumin ≤ 35 g/l before or after CRT. Patients supported by oral nutritional supplements (ONS) had higher probability to attain full dosage of CRT and radical resection than did those obtaining dietary advice alone. In multivariate analysis, serum albumin level, nasogastric (NG) tube insertion and pretreatment body weight loss were independent prognostic factors for OS, while serum albumin level after CRT and NG tube insertion were prognosticators for time to progression. CONCLUSION: Serum albumin level can serve as a useful prognostic factor for the outcome of patients with oesophageal cancer treated with neoadjuvant CRT and surgery. Appropriate nutritional support of these patients increased the probability of attaining full dosage of CRT and radical disease resection.