A new perspective on the proper timing of radiotherapy during CDK4/6 inhibitor therapy in patients with "bone-only" metastatic breast cancer.

The vast majority of hormone positive and HER2 negative advanced breast cancers can be controlled well by endocrine therapy combined with the groundbreaking use of CDK4/6 inhibitors in the metastatic first-line setting. Approximately 50%-60% of these patients have "bone-only" metastatic disease. In oligometastatic cases or if a certain number of uncontrolled lesions develop during the aforementioned therapy, ablative radiotherapy can be delivered or, in symptomatic cases, urgent irradiation is needed with palliative intent. To achieve the most effective results, parallel with good quality of life, the timing of radiotherapy must be determined precisely, taking into account that different cell cycles are involved during different treatment modalities; therefore, optimization of treatment schedules ensures longer and safer post-progression overall survival. The key question is whether the two treatment modalities are safe concurrently or whether they should be administered separately, and if so, what is the optimal sequence and why? This manuscript aims to answer this important question, with a focus on quality of life. Existing publications focus on safety and toxicity profiles, and efficacy is detailed only tangentially and minimally.

Efficacy of immune checkpoint inhibitor therapy for advanced urothelial carcinoma in real-life clinical practice: results of a multicentric, retrospective study.

Clinical trials revealed significant antitumor activity for immune checkpoint inhibitors (ICI) in metastatic urothelial carcinoma (mUC). Due to their strict eligibility criteria, clinical trials include selected patient cohorts, and thus do not necessarily represent real-world population outcomes. In this multicentric, retrospective study, we investigated real-world data to assess the effectiveness of pembrolizumab and atezolizumab and to evaluate the prognostic value of routinely available clinicopathological and laboratory parameters. Clinical and follow-up data from mUC patients who received ICIs (01/2017-12/2021) were evaluated. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and duration of response (DOR) were used as endpoints. Patients' (n = 210, n = 76 atezolizumab and 134 pembrolizumab) median OS and PFS were 13.6 and 5.9 months, respectively. Impaired ECOG-PS, the presence of visceral, liver or bone metastases, and hemoglobin levels were independently associated with poor OS and DCR. Furthermore, Bellmunt risk factors and the enhanced Bellmunt-CRP score were shown to be prognostic for OS, PFS and DCR. In conclusion, ICIs are effective treatments for a broad range of mUC patients. Our results confirmed the prognostic value of numerous risk factors and showed that Bellmunt risk scores can further be improved when adding CRP to the model.

[Oncological prehabilitation]. / Onkológiai prehabilitáció.

Cancer is currently the second leading cause of death in developed countries. Precision oncology treatments have significantly improved morbidity and mortality rates, 60% of patients can be cured or the disease can be managed as a chronic condition, so preserving and optimizing quality of life is just as important as successful treatment. The integration of rehabilitation has become generally accepted, however, preparatory treatments prior to oncological interventions should also receive more and more emphasis. In our center, we introduced the so-called oncological prehabilitation program that is a preparation treatment before oncological interventions. The program is popular among patients, and the positive feedback affects team members as well. Our goal is to present the structure and expected benefits of oncology prehabilitation as well as the possibilities of integrating it into the continuum of care, thereby introducing a change of perspective and paradigm shift. With oncological prehabilitation, we can witness a change of attitude and paradigm shift. Additional services supporting successful oncology treatments improve the quality of life, which - if there is an intention and need - could be implemented in oncology centers even with the current human resources. Orv Hetil. 2022; 163(50): 1975-1981.

Full Body Surface Coverage with Water-Equivalent Bolus as Novel Technique for Total Body Irradiation before Hematopoietic Stem Cell Transplantation in Pediatric Acute Lymphoid Leukemia.

BACKGROUND: Total body irradiation (TBI) 2 × 2 Gy for 3 consecutive days followed by chemotherapy for conditioning pediatric patients with acute lymphoid leukemia (ALL) before bone marrow transplantation is superior to chemo-conditioning alone. The globally used anterior-posterior/posterior-anterior (AP/PA) technique is the most referable method, but volumetric modulated arc therapy (VMAT) with modern linear accelerators is more precise in terms of ensuring better dose distribution, especially for skin, and higher protection of organs at risk, resulting in less side effects. METHOD: For TBI, a modern VMAT technique was used. Whole-body immobilization in the supine position was performed using a vacuum mattress with a full body coverage, with a water-equivalent bolus of 1 cm thickness. The design goal was to achieve dose inhomogeneity of less than ±10%. RESULTS: From 2020 to 2022, we performed TBI for five pediatric patients with ALL, with full body bolus and VMAT, who later received hematopoietic stem cell transplantation. No acute complications related to TBI were observed during the treatment period with a median follow-up of 1.27 (0.43-2.11) years. CONCLUSION: Using full body water-equivalent bolus with VMAT for TBI provides a safe method for children with a better organ sparing in the short term follow-up.

Treatment Algorithm for Cancerous Wounds: A Systematic Review.

BACKGROUND: In advanced cancer stage the incidence of cancerous wounds is about 5%, and the estimated life expectancy is not more than 6 to 12 months. Without interdisciplinary and individualized treatment strategy, symptoms progress, and adversely influence quality of life. METHODS: Authors collected different treatment algorithms for cancerous wound published by wide scale of medical expertise, and summarized surgical, oncological, radiation oncological, nursing and palliative care aspects based on radiological information. RESULTS: Interdisciplinary approach with continuous consultation between various specialists can solve or ease the hopeless cases. CONCLUSIONS: This distressing condition needs a comprehensive treatment solution to alleviate severe symptoms. Non-healing fungating wounds without effective therapy are severe socio-economic burden for all participants, including patients, caregivers, and health services. In this paper authors collected recommendations for further guideline that is essential in the near future.

[Successful treatment of an inoperable periauricular planocellular carcinoma]. / Inoperábilis periauricularis daganat sikeres sugárkezelése.

Surgery has been considered the first choice of treatment in planocellular skin cancers. However, adjuvant radiotherapy is often required in R1 resection or in lymph node positivity. Inoperable cases are also treated with ionizing radiation with palliative purpose. The authors present a case report of a successful treatment of an 87-year-old diabetic patient with a T4N1M0 stage periauricular destructive tumour treated with 3D conformal adaptive radiotherapy. Complete remission occurred although the initial treatment aim was only palliation.

[Data on liver enzyme and histological changes caused by intermittent clampings of the hepatoduodenal ligament in an experimental model]. / Adatok a ligamentum hepatoduodenale idoleges leszorítása által kiváltott májenzim- és szövettani változások vizsgálatához kísérletes modellen.

Intermittent compression of the structures of the hepatoduodenal ligament, is often performed during liver surgery. As a result, changes in hepatic blood supply and consequent reperfusion induced tissue damages will develop. Ischemia-reperfusion injury, which occur in local and distant regions, influence outcome of hepatic surgery, and it is in close correlation with the duration of hypoxia during the intervention. In animal model the effect of Baron/Pringle manoeuvre was investigated in terms of changes in liver function tests and histology. The study was carried out on 12 Beagle dogs, clamping of the hepatoduodenal ligament for 3×15 minutes then half an hour reperfusion was performed followed by blood and tissue sampling. Significant histological changes were observed both in the liver as well as the small intestine. In terms of liver function changes, GPT elevation occurred the earliest, GOT and LDH were also increased at the end of the 30 minutes reperfusion. In this animal model, the third 15 minutes compression turned out to be too long. Elevation in GPT levels was the most sensitive marker.

Concerning the importance of changes in hemorheological parameters caused by acid-base and blood gas alterations in experimental surgical models.

Acid-base equilibrium and pH of blood have important clinical consequences in numerous diseases and pathophysiological conditions. The micro-rheological parameters of blood, such as red blood cell deformability and red blood cell aggregation are influenced by several metabolic factors, and provide information regarding inflammatory, septic and tissue or organ ischemia-reperfusion processes. Despite the anticipated logical relation of the blood acid-base condition, blood gas parameters and pH to red blood cell deformability and aggregation, controversial data can be found in the literature. Furthermore, related to ischemia-reperfusion hemorheological studies little is known about this issue. In this paper we aimed to thought-provokingly overview some aspect of acid-base changes, blood pH and hemorheological parameters, discussing certain results from ischemia-reperfusion experimental surgical models (local versus systemic changes), laboratory technical and experimental design protocols related to in vitro and in vivo studies.

Spleen autotransplantation. Morphological and functional follow-up after spleen autotransplantation in mice: a research summary.

In 1986, we started the research on spleen surgery aimed at saving the splenic mass after its traumatic injury, with elaboration of special resection and autotransplantation techniques. The researches started on mongrel dogs and were continued on inbred mice and beagle dogs with complex histological, imaging, and laboratory investigations, following-up the function and the regeneration of autotransplanted spleen chips. Performing research on mice provided more immunological methods, such as lymphocyte subsets, immunoglobulin levels, and monitoring the phagocytic functions. Researches showed evidence also on the presence of apoptosis, furthermore, stem cell studies on regeneration and functional restoration of the spleen chips are in progress. Our results contributed to two multidisciplinary guidelines in Hungary: (1) One of them is under preparation and underlines the importance of spleen saving methods after traumatic splenic injury; (2) The second guideline shows that hemorheological changes can be early indicators of the increased sensitivity to postsplenectomy infections.

[The role of VATS in the treatment of blunt thoracic injuries]. / A VATS szerepe a tompa mellkasi serülések kezelésében.

AIMS: Video assisted thoracoscopy (VATS) is a more and more frequently used method in the diagnosis and treatment of blunt thoracic trauma. In some cases it has diagnostic and in others therapeutic effect. The authors analyze the role of VATS in the diagnosis and the treatment of 83 patients treated with haemothorax. PATIENTS AND METHODS: There were 83 patients treated (60 male, 23 female, mean age of 54.4 years) with haemothorax caused by blunt thoracic trauma. Chest tube drainage was used in 31 (37.3%) cases. Urgent thoracotomy was performed in only two (2.4%) cases. Elective, planned VATS was used in 11 (13.3) cases. All of these 3 were diagnostic and 8 were therapeutic procedures. In three cases rupture of the diaphragm was diagnosed with the use of VATS which were treated through thoracotomy. In the remaining 8 cases haematoma evacuation and in 3 cases intercostal artery bleeding were treated with VATS. RESULTS: No complications related to the procedure were observed. The thoracotomy in all 3 cases verified the diaphragmatic injuries. The 8 patients undergone therapeutic VATS recovered. The mean hospital stay after VATS was 7.8 days and 11.3 days after thoracotomy in the patients with diaphragmatic injury. CONCLUSIONS: The VATS has a significant role in the diagnosis of blunt thoracic, especially of diaphragmatic, injuries. In other cases the VATS has good therapeutic effect.

[Anterior approach for liver resection in the cases of the treatment of large liver tumors]. / Anterior májreszekció, mint a nagyméretu májtumorok ellátácsára alkalmas mutéti módszer.

The authors compare the results of the patients who underwent right hemihepatectomy through anterior approach with those by conventional hemihepatectomy. In 119 patients hemihepatectomy was done, 52 of them were anterior approaches. We used this technique when the tumor was large, or it seemed to be fragile and its mobilisation could be dangerous or infiltrated the diaphragm or the the hepatic vein's preparation was difficult or impossible. We started the operation with dissecting parenchyma from the anterior surface toward hilus without preparation and ligation of the affected vessels and bile duct. No patient died following anterior technique. Death and reoperation occurred in two cases following conventional hemihepatectomy. The operation time and the average nursing days was not significantly different. The blood transfusion was significantly less during anterior approach. However, between the two groups, in those cases when the operations were performed because of liver malignancies, there were no differences regarding to survival rate after 62 months follow up in contrast with the literature. The anterior technique used and modified by authors can be performed safely. The blood consumption is significantly less in the cases of anterior technique. There was no significant difference between the groups regarding to the operation-time and the average nursing days. The median survival rate was similar in both groups. Our team suggest this method of the anterior approach for liver resection in the above mentioned cases.

[Endoscopic stapled esophago-diverticulostomy as a new alternative to open surgery in the treatment of Zenker's diverticulum: which operation?]. / Endoszkópos oesophago-diverticulosto- mia, mint újabb lehetoség a Zenker diverticulum nyitott mutéti kezelése mellett: melyik mutétet válasszuk?

AIMS: The authors analyse the indications, contraindications, early and late results of two types of operations (resection of the diverticulum with crycopharyngeal myotomy and endoscopic stapled esophago-diverticulostomy) for the treatment of Zenker's diverticulum. PATIENTS AND METHODS: In a five year period 10 patients (5 male, 5 female, mean age 56.9 years) were operated for Zenker's diverticulum. Six open and 4 endoscopic operations were planned, although in one case the placement of the endoscope was unsuccessful. Open surgery was planned if the diverticulum was in lateral position, if it was too small or large and if endoscopic surgery was technically impossible. RESULTS: The operative time was shorter in the endoscopic group (32.3 vs. 80.7 minutes). In the open surgery group (7 patients) one saliva fistula developed caused by suture leak. The length of hospital stay was 8.1 days in the resection group and 4.7 in the endoscopic group. No recurrence developed. CONCLUSIONS: The advantages of the endoscopic oesophago-diverticulostomy are: shorter operating time and hospital stay, less complication rate and it is minimally invasive. The authors suggest endoscopic oesophago-diverticulostomy as the choice of operation in case of Zenker's diverticulum. Open surgery is indicated only if the diverticulum is in lateral position or if it is bigger than 8 cms. The technical contraindications for endoscopic surgery are: short, rigid neck and limited mouth opening.

[In vitro examination of the influence of lipase and amylase on dog's pancreas tissue incubated with endotoxins, phospholipase A2 or cytokines]. / A tripszin és lipáz hatásának in vitro vizsgálata foszfolipáz A2 enzimekkel, endotoxinokkal és cytokinekkel elokezelt kutya pancreas metszeteken.

Proinflammatory cytokines are elevated during acute pancreatitis. The endotoxins and Phospholipase A2 (PLA2) also have important role in acute pancreatitis. The aim of this study was to determine, what factors are responsible for the tissue damage in acute pancreatitis. The examinations were performed on fixed and frozen sections of healthy dog's pancreas tissue. Direct effects of endotoxins, PLA2, and proinflammatory cytokines together with pancreas enzymes were examined on pancreatic tissue. Pancreas enzymes themselves did not cause any change in the structure of pancreas. The common influence of endotoxins, PLA2 and pancreas enzymes was examined, and finally the effect of proinflammatory cytokines and enzymes was examined on pancreas tissue. Our results show, that besides enzymes many other factors are necessary to inflict tissue damage in acute pancreatitis, but for necrosis the presence of TNF alfa is a must.

[Video-assisted thoracoscopy (VATS) during the last ten years (1992-2001)]. / Video-asszisztált torakoszkópia (VATS) klinikánk 10 éves anyagában (1992-2001).

We summarize and analyse the video-assisted thoracoscopies (VATS) performed in our department during the last ten years. In this period 296 patients underwent VATS for diagnosis or therapy. We describe indications, advantages and disadvantages, we also analyse the complications. Video-assisted thoracoscopy is less demanding to the patients than thoracotomy, it reduces the length and cost of inpatient treatment. We recommend extensive use of VATS in suitable patients.

[Surgical treatment of pleural metastases in breast cancer]. / Az emlórák pleurametasztázisainak sebészi kezelése.

Pleural metastases of breast cancer is a severe progression of the disease and the treatment is difficult. Distant metastases are mainly treated by chemo-, radio- or hormone therapy, but in recent years surgical intervention is increasingly important. Between the 1st of January 1992 and 31st of December 2001 in the 2nd Department of Surgery University of Debrecen Medical and Health Science Center Medical School of Medicine 43 patients with breast cancer were operated on because of pleural metastases. In these patients biopsy and pleurodesis with talcum insufflation were performed. The surgical treatment was followed by chemotherapy. Pleurodesis was successful at 76.7 percent. The 6, 12 and 24 months survival was 58.1, 39.5 and 16.3 percent. Based on literature data and own experience we conclude that surgical intervention with adjuvant therapy extends life expectancy for patients with pleural metastases. Pleurodesis can prevent or delay hydrothorax, it improves vital functions and the quality of life for patients with pleural metastases.