Twelve ESMO Congress 2022 breakthroughs: practicing oncologists' perceptions and potential application on presented data.

BACKGROUND: During the European Society for Medical Oncology (ESMO) Congress 2022, outcome data of a great number of clinical trials were presented. For the attending medical oncologist, it is important to structure these data in a way that facilitates a trade-off between treatment burden and benefit. MATERIALS AND METHODS: To illustrate this, we carried out a narrative non-systematic review of 12 selected oral presentations with potential impact on future daily practice, focusing on trial methodology, possible study flaws, reported clinical benefit and implementability. RESULTS: The selected presentations encompassed 10 phase III trials, 1 randomized phase II trial and 1 phase II trial. In 7 out of 12 trials, quality of life and/or patient-reported outcomes had been evaluated. None of the trials, which reported progression-free survival (PFS) data, provided information, which could exclude informative censoring bias. In none of the trials reporting overall survival (OS) data, potential flaws due to undesirable crossover and imbalance between study groups regarding post-progression treatments were addressed. For the 11 reviewed randomized trials, the ESMO-Magnitude of Clinical Benefit Scale (MCBS) grade achieved with the new intervention was calculated based on the presented data. The MCBS grade varied from 1 to 5. CONCLUSIONS: Our review confirms the high-quality standard of current cancer research and the clinical relevance of the research questions answered. However, during presentation of PFS and/or OS data, factors known to affect PFS and OS analysis should be structurally addressed. In order to keep cancer care affordable and sustainable, it could be considered to include an ESMO-MCBS threshold in the drug appraisal process of regulatory authorities.

Protective effects of whey on rat liver damage induced by chronic alcohol intake.

In 2012, alcohol liver disease resulted in 3.3 million-5.9% of global deaths. This study introduced whey protection capacity against chronic alcohol-induced liver injury. Rats were orally administered to 12% ethanol solution in water (ad libitum, average 8.14 g of ethanol/kg body weight (b.w.)/day) alone or combined with whey ( per os, 2 g/kg b.w./day). After 6-week treatment, chronic ethanol consumption induced significant histopathological liver changes: congestion, central vein dilation, hepatic portal vein branch dilation, Kupffer cells hyperplasia, fatty liver changes, and hepatocytes focal necrosis. Ethanol significantly increased liver catalase activity and glutathione reductase protein expression without significant effects on antioxidative enzymes: glutathione peroxidase (GPx), copper-zinc-containing superoxide dismutase (CuZnSOD) and manganese-containing superoxide dismutase (MnSOD). Co-treatment with whey significantly attenuated pathohistological changes induced by ethanol ingestion and increased GSH-Px and nuclear factor kappa B (NF-κB) protein expression. Our results showed positive effects of whey on liver chronically exposed to ethanol, which seem to be associated with NF-κB-GPx signaling.

Metabolic syndrome in patients with chronic obstructive pulmonary disease: frequency and relationship with systemic inflammation.

BACKGROUND: Metabolic syndrome (MetS) is frequent in patients with chronic obstructive pulmonary disease (COPD). Systemic inflammation plays an important role in both COPD and MetS. The aim of this study was to assess the frequency of MetS in COPD patients and to evaluate the status of systemic inflammation in COPD patients with MetS and those without MetS. METHODS: This cross-sectional study included 98 consecutive stable COPD patients. The MetS was defined using the criteria of the International Diabetes Federation. Components of MetS and markers of systemic inflammation: C-reactive protein (CRP), fibrinogen, and leukocyte count were measured. All patients underwent spirometry. The staging of COPD was made according to the Global initiative for chronic obstructive lung disease (GOLD) criteria. RESULTS: MetS was present in 37.8 % COPD patients. The frequencies of MetS in patients with GOLD stages I, II, III, and IV were 33.3 %, 48.8 %, 31.6 %, and 23.1 %, respectively. MetS frequencies were not significantly different between GOLD stages. The multivariate logistic regression analysis revealed leukocyte count and CRP level as significant independent predictors of the presence of Mets in COPD patients (OR =1.321, 95%CI: 1.007-1.628, p =0.009 and OR =1.184, 95%CI: 1.020-1.376, p =0.027 respectively). CONCLUSIONS: This study shows that MetS is frequent in patients with COPD. Systemic inflammatory markers are higher in COPD patients with MetS than in patients without MetS. These findings suggest that physicians should screen COPD patients for associated MetS and elevated circulatory inflammatory markers. Management of these disorders should reduce the risk of cardiovascular morbidity and mortality in these patients. Hippokratia 2016, 20(2):110-114.

Expression analysis of genes involved in epigenetic regulation and apoptosis in human malignant haematopoietic cell lines treated with 5-azacytidine.

PURPOSE: The aim of this study was to investigate the modulation of the expression status of 10 different genes involved in epigenetic regulation and apoptosis by the DNA methyltransferase (DNMT) inhibitor 5-azacytidine (5-Aza), as markers of response to treatment, in two different human malignant haematopoietic cell lines. METHODS: In our analysis we used the SybrGreen technology and gene-specific primers for the qRT-PCR analysis of 10 genes, in cDNA of PC-MDS and K562 cell lines, treated by 1 micromole of 5-Aza for 24h. RESULTS: DNMT1 and DNMT3A showed statistically significant decrease of expression in 5-Aza-treated PC-MDS cells, whereas DNMT3B showed significantly decreased expression in 5-Aza-treated K562 cells. The members of the Bcl- 2 family of apoptosis-regulating genes Bcl-2 and Bax showed statistically significant differences in expression, in comparison with non-treated PC-MDS cells. Our most interesting result was the significant upregulation (re-expression) of p15, in 5-Aza-treated PC-MDS cells. CONCLUSION: The re-expression of p15 in PC-MDS cell line evaluated by qRT-PCR makes this novel cell line a suitable model for the studies of pharmacologic demethylation as a plausible mechanism resulting in hematologic response in myelodysplastic syndrome (MDS).

Multimodal BCI-mediated FES suppression of pathological tremor.

Tremor constitutes the most common movement disorder; in fact 14.5% of population between 50 to 89 years old suffers from it. Moreover, 65% of patients with upper limb tremor report disability when performing their activities of daily living (ADL). Unfortunately, 25% of patients do not respond to drugs or neurosurgery. In this regard, TREMOR project proposes functional compensation of upper limb tremors with a soft wearable robot that applies biomechanical loads through functional electrical stimulation (FES) of muscles. This wearable robot is driven by a Brain Neural Computer Interface (BNCI). This paper presents a multimodal BCI to assess generation, transmission and execution of both volitional and tremorous movements based on electroencephalography (EEG), electromyography (EMG) and inertial sensors (IMUs). These signals are combined to obtain: 1) the intention to perform a voluntary movement from cortical activity (EEG), 2) tremor onset, and an estimation of tremor frequency from muscle activation (EMG), and 3) instantaneous tremor amplitude and frequency from kinematic measurements (IMUs). Integration of this information will provide control signals to drive the FES-based wearable robot.

Calyceal plication with pyeloplasty in the treatment of giant hydronephrosis in children.

The relief of obstruction alone is frequently not sufficient to ensure renal salvage in giant hydronephrosis. We report on our experience with plication of the renal calyces used as an adjunct to dismembered pyeloplasty in patients with giant hydronephrosis. We describe the operative technique and outcomes in ten children after a follow-up period of six months. Ten patients (six girls and four boys) with a mean age of 8.1 years (range 2-14 years) with giant hydronephrosis caused by primary ureteropelvic junction obstruction underwent a dismembered pyeloplasty followed by plication of the dilated renal calyces. The preoperative evaluation included an excretory urography, ultrasonography, 99mTc-DMSA and 99mTc-DTPA scans. The same tests were repeated six months after the operation to evaluate the outcomes. There were no intraoperative or postoperative complications. Excretory urography and ultrasonography performed six months after the operation demonstrated a significant improvement of the morphology of the operated kidneys. The kidneys shrunk in diameter from a mean of 149.5 mm (range 89-224 mm) to 93.6 mm (range 68-121 mm) and the mean diameter of the calyces was reduced from 26.9 mm (range 15-42 mm) to 14.7 mm (range 10-24 mm). Renal 99mTc-DTPA scans showed improved perfusion and renal function after surgery, with the mean elimination rate decreasing from 22.41 min (range 17.84 - 28.22 min) to 11.7 min (range 8.16-13.76 mm). 99mTc-DMSA scans demonstrated no new scars and no deterioration of renal parenchyma after surgery. We believe that plication of the renal calyces is the method of choice to be used as an adjunct to the Anderson-Hynes pyeloplasty in the treatment of paediatric patients with giant hydronephrosis.

Primary vesicoureteric reflux--our 20 years' experience.

AIM: The aim of this study is to compare the Lich-Gregoir procedure and antireflux ureterocystoneostomy at the vertex of the bladder (AUVB) based on 20 years' clinical experience. METHODS: Over a period of 20 years (1978 - 1998) 1280 children were operated on, 368 bilaterally, which resulted in 1648 antireflux ureterocystoneostomies being performed. Of the total of 1648 antireflux ureterocystoneostomies, AUVB was performed in 1032 ureteric units and the Lich-Gregoir procedure in 616 ureteric units. Between 1978 and 1992 we performed only AUVB, and from 1992, both AUVB and the Lich-Gregoir procedure. RESULTS: The final result was evaluated 2 years after the operation. Satisfactory results were achieved in 93.5 % with AUVB and in 96 % with the Lich-Gregoir procedure. The postoperative failure rate was 6.5 % for the AUVB and 4 % for the Lich-Gregoir operations. The recurrence rate was higher with AUVB (5 %) than with the Lich-Gregoir procedure (1.5 %), but postoperative stenosis was more frequent with the Lich-Gregoir procedure (2.5 %). CONCLUSIVE: Today, as the first operative method we prefer to employ the Lich-Gregoir procedure. If the result of the Lich-Gregoir procedure is unsatisfactory, we recommend the AUVB for the first and second recurrence operation. Finally, in cases of repeated VUR recurrence of postoperative stenosis, as the last operation we perform antireflux ureteroileocystoplasty with an intussuscepted segment of the ileum.

[Analysis of results of surgical treatment of malleolar fractures]. / Analiza kasnih rezultata kirurskog lijecenja maleolarnih prijeloma.

Late results of operatively treated malleolar fractures were analyzed. 101 patients were operated on, 58 (57.4%) were available for follow-up. There were 5 patients with A-type fractures according to Weber's classification, 28 with type-B and 25 with type-C fractures. One year or more after the treatment the patients were evaluated on follow-up checks where ranges of ankle dorsiflexion, plantar extension, pronation and supination were recorded, circumference of the injured ankle was measured and the patients were interviewed about subjective complaints. Normal range of motion of the injured ankle (normal range of motion represented by the healthy ankle) was found only in patients with type-A fractures while in other two groups the patients had significantly decreased motility of the injured ankle (P < 0.05). The circumference of the injured ankle was increased in most patients with 25.9% patients ankles being 20 mm or more thicker than the uninjured side. Only seven patients (12.1%) were without subjective complaints while other patients experienced pain with load, pain with weather changes, swelling of the ankle etc. Malleolar fractures still represent a significant surgical problem and only an early operation, anatomic reduction and fixation as well as proper rehabilitation guarantee good results.

[Hepatic portoenterostomy and primary liver transplantation in the treatment of biliary atresia]. / Hepatoportoenterostomija ili primarna transplantacija jetre u lijecenju bilijarne atrezije.

Results show that the use of sequential surgical treatment, employing Kasai portoenterostomy in infancy, followed by selective liver transplantation for children with progressive hepatic deterioration yields improved overall survival. All children with successful Kasai portoenterostomy procedures who do not require orthotopic liver transplantation are survivors. Using newer transplant techniques, the 5-year survival rate for children who receive transplants with a primary diagnosis of biliary atresia was 82%. This yields an overall survival rate of 86% in this entire study population. Limited donor availability and increased complications after liver transplantation in infants less than 1 year of age mitigate against the use of primary liver transplantation without prior portoenterostomy for infants with biliary atresia. At present, these two operative procedures should be used as sequential and complementary modes of treatment rather than as competitive procedures. When biliary atresia is not recognized in infancy and established cirrhosis has resulted, primary transplantation should be offered as the initial surgical treatment.

[Treatment of pseudarthroses of the olecranon with the anatomical hook plate]. / Lijecenje pseudartroze olekranona anatomskom kukastom plocicom.

We report the results in seven patients treated surgically for nonunion of the olecranon. Four nonunions occurred after primary treatment with tension band wiring and three nonunions occurred after open reduction internal fixation with plates and screws or lag screws only. All patients were treated with cancellous bone grafting and open reduction internal fixation using anatomical hook plates. All nonunions united within 6 months after the treatment. In all patients the range of motion of the elbow improved significantly.

[Effect of improved surgical anesthesiologic factors on the results of treatment of aneurysms of the abdominal aorta]. / Vrednovanje utjecaja poboljsanja operacijskih anestezioloskih cimbenika na rezultate lijecenja aneurizmi abdominalne aorte.

The purpose of this study was to compare the recent results of the abdominal aortic aneurysm (AAA) surgery, with the results for the patients operated ten years ago, and to identify the factors influencing the operative results. Two groups of patients were selected using a retrospective case series study. First group of patients (A) consisted of 32 cases operated in the period between 1984 and 1986, and the second group (B) consisted of those operated ten years later (from 1994 to 1996). Mortality rate, presence of risk factors, demographic data, and operative factors were analyzed and compared between the groups. The mortality rate decreased from 10.7% in period A, to 5.3% in period B for elective operations, and from 75% to 44.4% for emergency operations. The prevalence of straight graft technique in period B showed statistically significant difference compared to period A (p < 0.005). Besides, the operating time and the amount of the transfused blood between the groups differed significantly (p < 0.05). On the basis of this data, we concluded that the modifications in the operative technique, as well as the increased number of operations within the second period led to the decreased mortality rate in patients operated for AAA.

Proliferation of spleen cells in culture stimulated by 7-thia-8-oxoguanosine: evidence that both B- and T-cells are the targets of its action.

7-thia-8-oxoguanosine (immunosine) is a nucleoside analog showing efficient antiviral activity in rodent models as a consequence of enhancement of the immune response. However, little is known about the mechanisms of its action. In this work the effect of immunosine on proliferation of mouse and rat splenocytes in culture was studied. It was found that the compound stimulated proliferation of lymphocytes in a dose-dependent manner without any additional stimuli. The effect is predominantly mediated by interleukin-2 (IL-2) as judged by increased IL-2 production, upregulation of IL-2 receptor alpha (IL-2R alpha) expression and by significant inhibition (60-75%) of cell proliferation by anti-IL-2R alpha monoclonal antibodies (mAbs). Immunosine also stimulated proliferation both of T- and B-cells purified by immunomagnetic sorting. The response of B-cells was much higher than that of T-cells. The stimulatory effect of immunosine on both lymphocyte subpopulations was further increased by the addition of enriched splenic antigen-presenting cells or purified dendritic cells. Proliferation of purified T-cells to immunosine was also significantly potentiated by an anti-alpha beta T-cell receptor mAb (R 73). All these data suggest that T-, B- and accessory cells in splenic cultures are the targets of immunosine action.

[Posterior sagittal anorectoplasty (PSARP) in children with high anal atresia]. / Posteriorna sagitalna anorektoplastika (PSARP) u djece s visokom atrezijom rektuma.

Anorectal anomalies are highly significant (the incidence of 1:3000 infants). The knowledge of the factors related to fecal continence encouraged the introduction of new surgical approaches in the second half of this century. With high supralevator anorectal anomalies the percentage of incontinence in children was earlier 50-80% although in all surgical procedures efforts were made to reconstruct the normal anatomy of the small pelvis. It was only in 1982 that by the PSARP method the anatomic reconstruction was achieved. In this operation an electric stimulator is used to identify the entire muscle-sphincter complex (external sphincter, the cross-striated muscle complex and the levator musculature) and then by stimulation of muscles a mobilized and modeled rectum is inserted into the muscle-sphincter complex. During the ten-year application of the PSARP method 15 children underwent the operation, of which 14 boys and 1 girl. The girl had rectovaginal fistula and 11 boys had rectourethral fistula. More than 70% of our children showed accompanying anomalies. Control examinations of children older than 3 years show the 67% continence in our children operated by the Pena-de Vries method.

[Brain concussion--a minor craniocerebral injury]. / Potres mozga--laka kraniocerebralna povreda.

INTRODUCTION: Brain concussion is a brain dysfunction without any macroscopic structural damage, caused by mechanical force. This research paper presents the occurrence and basic characteristics of patients with brain concussion without skull fracture. The second aim of this paper is to answer questions, related to this problem, neurosurgeons are most often asked by doctors of other specialties. MATERIAL AND METHODS: Posttraumatic amnesia (patient unable to remember events before and/or after injury) was a condition to diagnose the brain concussion. In 1995 there were 240 patients with brain concussions without skull fracture at the Department of Urgent Surgery of our Institute. Eighty of them (33%) have been admitted to the Neurosurgical Clinic for observation and/or treatment. In all patients with brain concussion the following diagnostic procedure was applied: personal history, physical and neurological examination, basic blood tests and skull x-rays. CT imaging of the brain is not a routine because of our economic and technical circumstances. RESULTS: 240 patients were examined; 67% were males. Glasgow coma score (GSC) was 13-15 in all patients, while in nonhospitalized patients it was 15 (GSC = 15). 54% of patients were 15-40 years old; 35% were 41-60 years old and 11% were older than 60 years of age. Average hospitalization lasted for 3.48 days. According to the Glasgow outcome scale all patients had a good recovery. DISCUSSION: Patients with brain concussion have always amnesia with normal neurologic status. Legal and clinical definition of the minor head injury are not completely equal. Brain concussion is legally always a minor head injury. Patients with organic damage of brain (legally severe injury) can clinically look like having minor injury initially or till the end of the illness. Risk for brain damage in patients with amnesia is about 3%. Posttraumatic amnesia is always established by asking patients to remember events and not asking them if they were unconscious. Brain concussion is often associated with headache, vegetative or/and psychotic difficulties. Diagnostic protocol should comprise at least personal history, physical and neurological examination and skull x-ray. Consultation of a neurosurgeon and hospitalization are not indicated in all cases. In our series it was done in 33% according to indications which are established. In these cases patients should be transported with documents describing the type of injury, diagnostic results and treatment performed. The therapy is symptomatic. After brain concussion gradual return to everyday activities is indicated. Sick leave of 7-10 days is usually sufficient. Postconcussion syndrome (headache, vegetative or psychotic disturbances) occurs often and may last for a long period of time. CONCLUSION: We tried to describe a doctrine for diagnostic and treatment of patients suffering from brain concussion most appropriate according to our technical and economical circumstances.

The relation between plasma lipid levels and pseudocholinesterase activity in hypothyroidism.

The relation of plasma lipids and pseudocholinesterase (PChE) activity was studied in rats made hypothyroid by treatment with propylthiouracil (0.05% in drinking water for 28 days) and in hypothyroid patients prior and after L-thyroxine-therapy (1. week 25-50 microg, 2.-4. week 100 microg daily). In rats, thyroid hormone deficiency caused a significant increase in plasma and adipose tissue PChE activity as well as total plasma cholesterol (TC) concentration, and a decrease in plasma triglyceride (TG) concentration. In contrast to rats, thyroid-deficient humans demonstrated a decrease in plasma PChE activity and an increase in both TC and TG, in comparison with euthyroid controls. After one month's therapy with L-thyroxine, reversion of PChE activity and lipid concentrations occurred. The opposite changes of PChE elicited by thyroid hormone deficiency in men and rats are similar to the respective changes in lipoprotein lipase (LPL) activity, observed by other authors. The inverse correlation between both PChE and LPL activity and TG concentration suggests that PChE, similarly to LPL, may be involved in TG hydrolysis.

[Laparoscopic cholecystectomy in a child with sickle cell disease]. / Laparoskopska kolecistektomija u djecaka s drepanocitozom.

Laparoscopic cholecystectomy has become the procedure of choice for the removal of the diseased gallbladder in children. Its use in small children and infants is rare. At the Department of Pediatric Surgery of the Medical faculty in Zagreb five children underwent laparoscopic cholecystectomy. One of them was a five year old boy with sickle cell disease and cholelithiasis. Before the advent of laparoscopy, few children with sickle cell disease and cholelithiasis underwent cholecystectomy, because of the high morbidity associated with open cholecystectomy. The authors use the case to present details of the operative procedure of laparoscopic cholecystectomy in small children and infants. Laparoscopic cholecystectomy is the procedure of choice in the management of cholelithiasis in small children and infants, especially those with sickle cell disease.

[The Institute of Surgery in Novi Sad as a trauma center--10 years' experience]. / Institut za hirurgiju u Novom Sadu kao trauma centar--desetogodisnje iskustvo.

UNLABELLED: Trauma is a surgical disease and a leading cause of death in the population in the age of forties. The Institute for Surgery in Novi Sad (trauma center of the first rank) takes care of all injured people brought to the Institute either directly from the place of accident or from other centers. AIM OF THE STUDY: Retrospective analysis of the injured people treated at the Institute for Surgery in the period 1987-1996. MATERIAL AND METHODS: Multivariate analysis of the traumas from the register of the Institute for Surgery according to the trauma system elements: number of injured individuals, sex and age structure, categorization of injuries, etiology of injuries, distribution of serious injuries by regions, results obtained from the treatment of serious injuries. RESULTS: They show a global representation of all elements involved with injured people: due to moderately serious, serious and critically serious injuries 21.6% of patients were hospitalized; in the age of 29-30 years men with traumas caused on work or in traffic were predominant, while women with injuries caused by falling were predominant in the age of 60-69 years; drastically increased injuries caused by fire-arms in the period 1991-1993 were directly caused by the state of war and these injuries are still numerous; in case of hospitalized patients isolated trauma (80%) was predominant, multiple trauma was under 20% and polytrauma was registered in 5% of patients; after surgical treatment of injuries approximately 17% of patients were indicated for postoperative prolonged treatment and in intensive care unit at the Institute for Surgery; the average mortality of hospitalized patients was 5-7% but with extremely high mortality rate (< 70%) in the group of patients with polytraumas.

[The psychological profile using the Minnesota Multiphasic Personality Inventory and the value of this test in the evaluation of post-traumatic stress disorder in combat participants]. / Psiholoski profil na Minesota multifaznom personalnom inventaru i vrednost ovog testa za procenu posttraumatskog stresnog poremecaja kod ucesnika rata.

Different stress disorders, including the posttraumatic stress disorder (PTSD), developed as the consequence of traumatic stress experience, represent the most frequent patterns of reactive mental disorders of the soldiers in war. Clinical picture of those events has mostly been described in details in the literature, but the search for simple and reliable methods of detection still lasts. The aim of this study was to determine psychological profile and value of Minnesota Multiphasic Personality Inventory (MMPI) for the detection and description of PTSD in psychotraumatized examinees. It was investigated totally 119 soldiers--the participants of combat actions in the area of former Yugoslavia, among whom 71 examines formed part of clinical group that manifested symptoms of posttraumatic stress disorder, and control group consisted of 48 war participants, but without psychopatologic consequences. The investigation was performed by application of MMPI-personality test (form MMPI-201). Significant differences between clinical and control groups of examinees were determined, which confirmed the value of that inventory in the detection of PTSD symptoms. The most discriminative value was noticed in the next test scales: atypical behavior (F), depression (D), and paranola (Pa), that was also observed in relevant foreign studies carried in war veterans.