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The bleeding from the upper gastrointestinal tract represent a significant medical but also socio-economic problem.A special group of patients et increased risk consists of critically ill patients in intensive care units. Particularly significant cause of bleeding in intensive care unit patients is bleeding resulting from the stress ulcers caused by damage of themucosa of the stomach and duodenum. The purpose of this review is to present current experience in prevention of upper gastrointestinal tract bleeding using proton pump inhibitors in intensive care units. Combination of endoscopic hemostatic methods and proton pump inhibitors represents golden standard in most cases. Despite some adverse effects treatment with proton pump blockers is essential when upper gastrointestinal tract bleeding appears in critically ill patients in intensive care units. Proton pump inhibitors are more effective in acid suppression, as well as in the prevention of recurrent bleeding after endoscopic hemostasis than histamine 2 receptor blockers. The efficacy of proton pump blockers is higher in the case of a continuous intravenous infusion than in the intermittent mode of administration of the drug. The need for highly elaborate strategy for the prophylaxis of bleeding from the upper parts of gastrointestinal tract in intensive care units is essential, because when it occurs in intensive care units, mortality is high, and therapeutic options become narrow.

Mucocele of the apendix is a rare clinical and pathological entity with a higher incidence in the female population, and non-specific symptomatology that includes more diagnoses including neoplastic and non-neoplastic causes of the apendix dilation and mucin proliferation. With obtained numerous variations in symptomatology, clinical picture, intraoperative presentation, surgical treatment and histopathological findings, the aim of this paper is an inspection into current knowledge of this disease, its histopathological characteristics, differential diagnosis and current treatment modalities. We present a patient with a clinical picture of the acute abdomen and numerous comorbidities. Ultrasound diagnostics indicated the presence of thin-walled dilatation of the small intestine, especially in the lower right quadrant, as well as the presence of free fluid in the peritoneal cavity. Apendectomy and removal of the mucocele and resection of the gangrenous sigmoid colon according to Hartmann were done. A definitive histopathological finding suggests ischemic colitis and retention mucocele of the apendix with normal mucosa. Histopathologically, four types of mucocele apendixes are distinguished, namely the retention mucinous cyst, mucosal hyperplasia, mucinous cystadenoma and mucinous cystadenocarcinoma. Surgical treatment is the method of choice in treating these tumors, either open or laparoscopic. Imperative is the preservation of the integrity of the entire mucocele, due to the possible dissemination of contents of the cyst and the subsequent development of pseudomyxoma peritonei.

Introduction: Hemangiopericytoma is a rare tumor arised from the pericytes, contractile spindle cells that surround the capillaries and post-capillary venules. The tumor was found equally among males and females. Case report: We report a case of a 63-year-old female who presented a giant painful mass on her right shoulder that occurred one year before admission. Limited range of motion and a sense of tingling along the affected arm was present also. An irregular, oval-shaped mass, colored dark-red, with signs of necrosis was the maximal diameter of 14cm. Routine laboratory analyzes showed results within the range of referenced values. Lung X-ray and ultrasonographic examination of the abdomen showed no signs of secondary tumor deposits, and no osteo-muscular lesions in the affected region. Ultrasonographic examination of the neck and right axillary region showed no signs of regional metastases. The surgical excision of the entire tumor was performed, with the associated subcutaneous tissue and a part of fascia underneath. Results of the histopathological analysis confirmed the diagnosis of hemangiopericytoma. The specimen showed no signs or elements of the neoplastic tissue on the edges of the resection lines. 3 years after the operation, there was found no signs of tumor relapses, regional or systemic metastases. Conclusion: Considering that there are no official clinical guides and protocols for hemangiopericytoma management, as well as the occurrence of cutaneous and subcutaneous hemangiopericytomas is exceptionally rare, more extensive research in this field and more described cases are need to gain a better understanding of that issue.

Phyllodes tumors of the breast can be benign, malignant, or borderline. Benign and borderline tumors are rare tumor types that have a positive outlook and high survival rate, while the risk of recurrence is typical for malignant breast tumors. Giant phyllodes tumors are larger than 10 cm in diameter and demand a serious diagnostic and treatment approach. In this study we present a case of a female patient treated for an exulcerated breast carcinoma- a giant borderline phyllodes tumor of the breast. The patient presented to the department for the right breast lump with ulcerated skin and nipple abnormalities. The core biopsy was performed and the patient was diagnosed with a benign tumor. Simple mastectomy was performed and final histopathological report revealed a borderline phyllodes tumor. Diagnosis and treatment of a giant phyllodes tumor remain a great challenge for the surgeons. Establishing the preoperative diagnosis based on histopathological findings is imperative to disease management. Surgery is the mainstay of treatment and mastectomy has been the traditional procedure; in cases where suspicious findings in the axilla are revealed, radical mastectomy is performed and the axilla is to be dissected.

The quality of life and patient survival rate in terminal chronic renal insufficiency depends on the duration of vascular approaches. Dialysis catheters are used to establish an adequate vascular approach when emergency hemodialysis is indicated and when all approaches are exhausted. Complications of CVC can be classified into three categories: mechanical (hematoma, arterial puncture, pneumothorax, hemothorax, catheter misplacement, and stenosis), infectious (insertion site infection, CVC colonization, and bloodstream infection) and thrombotic (deep vein thrombosis). Despite the increasing prevalence of haemodialysis patients with complex access issues, there remains no consensus on the definition of vascular access failure or end-stage vascular access. The dilema in these cases remains whether the generalized vascular insufficiency is the cause or a complication of exhausted vascular accesses. This case report is one of the examples of combined complications with generalized vascular access insufficiency. During the year and a half of the chronic dialysis program, the patient had several changes of vascular approaches, and each approach became dysfunctional in certain time due to various causes. After six months of successful hemodialysis, the patient was admitted with signs of infection and during hospitalization was again subjected to multiple changes of the vascular approach due to infection, thrombosis, and vascular access failure.

Introduction. Marjolin?s ulcer is a skin malignancy that occurs on a scar or chronic wound. It most commonly occurs on a burn scar. Squamous cell carcinoma is the most common type of this tumor in more than 90% of cases. The rate of this rare malignant transformation is 1?2%. Marjolin?s ulcer is more aggressive than other skin cancers. Wide excision is the treatment of choice. Recurrences are common. We present a large exophytic carcinoma of the lower leg as a rare form of this tumor ac-cording to the size and type together with reconstruction results. Case report. A 52-year-old man was presented with a large exophytic tumor on the left lower leg. The tumor was located at the site of the previous gunshot in-jury. The latent period was 22 years. Tumor size was 14 ? 12 cm. Wide excision was performed (2-cm surgical margin), including the deep fascia, and the defect was closed by a split-thickness skin graft from the opposite thigh. Histology showed well-differentiated squamous cell carcinoma. There were no regional or distant metastases. One year after surgery, there was no recurrence of the tumor. Conclusion. Early diagnosis of Marjolin?s ulcer and wide excision are mandatory. Surgical margins for excision should be 2 cm, and excision should include deep fascia. Multiple and repeated biopsies of chronic wounds are advised. There is no consensus on the staging of Marjolin?s ulcer and lymph node dissection.

One of the most intriguing problems in modern esophageal surgery is the acquired short esophagus. While some authors recognize this entity, others deny its existence. There is a consensus about types of the short esophagus, its etiology and pathophysiology. Definitive diagnosis can be established only intraoperatively. There are a few surgical procedures for this problem, and most frequently is used Collis gastroplasty with fundoplication. In this review we emphasize recent literature data and further perspectives of the Collis procedure.

Background: Appendiceal mucoceles represent neoplastic and non-neoplastic, dilatated, mucus filled appendix vermiformix. Appendectomy is obligatory due to a possible malignancy. It is crucially important to avoid rupturing of the mucocele because it can result in pseudomyxoma peritonei, with high morbidity and mortality. Case Report: We presented a 52-year-old man with pain and palpable mass in the lower right quadrant of the abdomen. The mucocele was removed without a rupture, and the patient was discharged from the surgical department one day after the surgery without a complication. Discussion: The resection must be done very carefully, because the rupture of a mucocele can cause pseudomyxoma peritonei, a very dangerous and often lethal condition. Due to the concern of rupture, we performed the classical resection through laparotomy. Conclusion: It is very important, especially for young, inexperienced surgeons to be aware of this rare diagnosis and perform a surgical intervention according to the guidelines of good clinical practice.

Short esophagus is well known complication of a long term gastroesophageal disease. There are several ways to solve this problem intraoperatively. One of the first steps is extensive esophageal mobilisation. In this review we emphasize different approaches and types of this procedure, with their advantages and disadvantages.

Introduction. Asymptomatic Bochdalek hernia in adults is a rarity. The aim of this paper is to present a rare case of Bochdalek hernia among adults and to point out to significance of clinical suspicion and important role of imaging techniques in reaching the exact diagnosis of this abnormality. Case report. A patient, aged 68 years, came to the Clinic of Pulmonology complaining of constant dyspnea, coughing and fatigue. Computed tomography (CT) findings were dominated by the large rear right diaphragmatic hernia with the hernial sac that reached the carina trachea and urged the principal bronchi. The stomach, duodenum and proximal part of jejunal winds, as well as a greater amount of omental and mesenteric adipose tissue were localized in hernial sac. Radiography of gastroduodenum showed: entry of the esophagus into the cardia was in the level of the right main bronchus. Stomach was mainly located in the chest (cardia, upper corpus half - to the level of the right main bronchus). Operation was indicated. First, we made right thoracotomy and the hernia sac was separated from the right lung and then we performed median laparotomy and the contents of the hernia sac were returned to the abdominal cavity; diaphragm defect was reconstructed with prolen mesh. Conclusion. We presented a rare case of right sided Bochdalek hernia which was discovered at late age and surgically treated with success.

Introduction. Malignant fibrous histiocytoma is a fast spreading pleomorphic sarcoma with a high malignant potential. Its spreading is characterized with local invasion and distant metastazes with early onset. Most common localisations of development are extremities, trunk and retroperitoneum. Given the line of rare case and specimen, lack of a clear etiology and mechanisms of this disease, as well as adequate histopathologic findings and intraoperative documentation, we presented current status, discuss putative etiology, histopathology with variant morphology, differential diagnosis and treatment modalities. Case report. We presented a 56-years-old female Serbian with tumor in the thigh that clinically resembles incapsulated hematoma. Computed tomography revealed intramuscular tumor with a heterodense structure and compression on surround tissue. Ex tempore biopsy specimen showed malignant potential of the tumor. Wide and radical excision of the nodule has been done, and definitive histopathological verification revealed malignant fibrous histiocytoma. Conclusion. Malignant fibrous histiocytoma is a most common type of soft tissue sarcomas in adults. Frequent localization is on lower extremities, and every rapidly enlarging nodule in this localization that on computed tomography is like incapsulated hematoma with necrotic zone should alert suspicion on presence of this type of sarcoma. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. III41007 and Grant no. III41010]

Accessory auricle is a rare anomaly with an estimated incidence rate of 0.2-0.5%. The most common form of this malformation is the accessory tragus. It may be a sign of other syndromes, such as oculo-auriculo-vertebral dysplasia (Goldenhar’s syndrome). In this paper, we describe two cases of accessory auricle with a focus on diagnosis and surgical treatment.

Introduction. Chylothorax is an accumulation of chyle in the pleural cavity due to a disruption of the thoracic duct. Traumatic chylothoraces are usually a result of a penetrating trauma and disruption of the thoracic duct, but blunt traumatic chylothorax is a rare condition. The aim of this paper is to present a rare case of traumatic chylothorax after blunt thoracic trauma. Case Outline. We present a case of traumatic chylothorax after blunt thoracic trauma in a patient injured in a motor vehicle accident. The patient had a right-sided fracture of rib XI, hydropneumothorax, lung contusion, and signs of pneumomediastinum. We performed thoracic drainage, but a few days later, according to the increase of amount of the fluid daily drained, and the confirmation of laboratory findings of the analyzed fluid, we made a diagnosis of chylothorax and the patient underwent a thoracotomy, where we sutured the thoracic duct. Conclusion. Chylothorax should be considered in patients after chest trauma if they develop a milky pleural effusion. Analysis of pleural fluid and level of triglycerides is important for the diagnosis and treatment of chylothorax. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. III41007]

Background/Aim. Acute pancreatitis is an inflammatory condition having the significant mortality rate in the case of severe forms of the disease. The aim of this study was to investigate putative factors of increased mortality in patients with acute pancreatitis with contradictory prior evidence, and to reveal factors that were insufficiently explored previously. Methods. This prospective cohort study with nested case/control design included all adult patients treated for acute pancreatitis in the Clinical Center of Kragujevac, Serbia, during the 3-year period (from October 2011 to December 2014). The cases (n = 19) were patients who died, while the controls (n = 113) were patients who survived. The associations between putative risk factors and the study outcomes were tested by univariate and multivariate logistic regressions, and expressed as crude and adjusted odds ratios (OR) with corresponding 95% confidence intervals (CI). Results. Significant association with the lethal outcome in acute pancreatitis was found for advanced age (adjusted OR 1.12, 95%CI 1.02?1.23), presence of significant comorbidities (adjusted OR 10.62, 95%CI 1.01?111.39), higher interleukin- 8 (IL-8) value on third day from onset of symptoms (adjusted OR 1.05, 95%CI 1.02?1.08), use of tramadol and/or morphine (adjusted OR 47.34, 95%CI 3.21?699.08), the Bedside index for severity in acute pancreatitis (BISAP) score ? 3 in the first 24 hours (adjusted OR 48.11, 95%CI 3.14?736.29), and prophylactic use of antibiotics (adjusted OR 0.07, 95%CI 0.01?0.85). Conclusion. Advanced age, significant comorbidities, use of tramadol and/or morphine and more severe disease as assessed by BISAP score can increase the risk of death in acute pancreatitis, while prophylactic use of antibiotics may have a protective role.

Introduction. Management of a polytraumatized patient is a problem that requires a multidisciplinary approach, in order to optimise patient’s outcome. The purpose of this study is to show the approach in the treatment of a patient with a severe life-threatening polytrauma, including a personalized healthcare approach, after the inadequate initial treatment with the positive outcome. Case report. We present a case of a young polytraumatized patient with trauma as a result of road traffic accident. The patient had chest injuries, abdominal injuries and right arm injuries. He was diagnosed of hepatic rupture with conquasation and retroperitoneal hematoma and the patient underwent liver tamponade. Chest trauma was treated by chest drainage. After the adequate multidisciplinary interventions for the patient, the patient was discharged. Conclusion. This case report is of great importance since it shows that severe polytraumatized patients with bad initial prognosis can successfully receive a life - saving treatment.

Differentiation of proinflammatory CD4(+) conventional T cells (T(conv)) are critical for productive antitumor responses yet their elicitation remains poorly understood. We exhaustively characterized myeloid cells in tumor draining lymph nodes (tdLN) of mice and identified two subsets of conventional type-2 dendritic cells (cDC2) that traffic from tumor to tdLN and present tumor-derived antigens to CD4(+) T(conv), but then fail to support antitumor CD4(+) T(conv) differentiation. Regulatory T cell (T(reg)) depletion enhanced their capacity to elicit strong CD4(+) T(conv) responses and ensuing antitumor protection. Analogous cDC2 populations were identified in patients, and as in mice their abundance relative to T(reg) predicts protective ICOS(+) PD-1(lo) CD4(+) T(conv) phenotypes and survival. Further, in melanoma patients with low T(reg) abundance, intratumoral cDC2 density alone correlates with abundant CD4(+) T(conv) and with responsiveness to anti-PD-1 therapy. Together, this highlights a pathway which restrains cDC2, and whose reversal enhances CD4(+) T(conv) abundance and controls tumor growth.

2573 Background: Immune checkpoint inhibitors (ICIs) have demonstrated durable clinical responses and improved survival in patients (pts) across numerous indications. Despite this progress, the benefit of ICIs is limited to a minority of overall metastatic cancer patients. There is a critical need for biomarkers agnostic of tumor type to inform which pts will benefit from nivo alone versus ipi/nivo combination treatment. Both pre-treatment tumoral CD8 + cells and recruitment of CD8+ T cells in response to ICIs are associated with improved clinical outcomes in patients treated with anti-PD-1 therapy. 1,2,3,4 Here we report the final results of a prospective clinical study in which pts with varying advanced solid tumors were assigned to nivo, with or without ipi, based on the percentage of tumoral CD8 cells at the time of treatment. Methods: We performed a prospective, non-randomized, open-label, multicenter study in which pts with tumoral CD8+ cells ≥ 15% (CD8+ high) received nivo 360mg IV Q3W, followed by nivo maintenance 480mg Q4W. Pts with tumoral CD8+ cells < 15% (CD8+ low) received nivo 360 mg IV Q3W, and ipi at 1 mg/kg IV Q3W for 2 doses and then Q6W for 2 doses, followed by nivo maintenance 480 mg IV Q4W until PD or intolerable toxicity. Primary endpoints were Disease Control Rate (DCR: CR, PR, or SD ≥ 6 months) and CD8 low to high conversion (< 15% to ≥ 15%). Baseline and on-treatment tumor, blood and stool samples were collected for multiomic biomarker analyses. This study was not powered for formal statistical analysis. Up to 200 pts could be enrolled to allow for adaptive exploration of response and CD8 changes. Results: N = 79 pts were enrolled:7 in CD8+ high arm (nivo) and 72 in CD8+ low arm (ipi/nivo). The study enrolled a wide variety of primary solid tumors; the most common were gynecological (n = 15), prostate (12), and head and neck (7). DCR was 14% (1/7; 95% CI 1 - 44) and 24% (17/72; 95% CI 15 - 34) in the CD8 high and CD8 low arms, respectively. Of 39 pts in CD8 low arm with an on-treatment biopsy, 14 (36%; 95% CI 22 - 51) had CD8 conversion; 7/14 pts (50%) who converted had DCR. Immune-related AEs (irAEs) were consistent with known safety profile of both drugs. Conclusions: Ipi/nivo demonstrated clinical responses and increased CD8% in a range of “cold” tumors with low tumoral CD8 cells. There may be an association between increasing CD8% and response. Baseline high CD8% alone does not appear to be sufficient as a pan-cancer predictive biomarker of response to nivo monotherapy. CD8 conversion, response, and irAEs associated with circulating and stool-based biomarkers are under evaluation as composite biomarkers may improve their predictive value. Clinical trial information: 03651271.

OBJECTIVE Superior semicircular canal dehiscence (SSCD) is a rare disorder characterized by the formation of a third opening in the inner ear between the superior semicircular canal and the middle cranial fossa. Aberrant communication through this opening causes a syndrome of hearing loss, pulsatile tinnitus, disequilibrium, and autophony. This study analyzed the clinical outcomes of a single-institution series of patients with SSCD undergoing surgical repair by the same otolaryngologist and neurosurgeon. METHODS All patients who underwent SSCD repair at the University of California, Los Angeles, between March 2011 and November 2014 were included. All patients had their SSCD repaired via middle fossa craniotomy by the same otolaryngologist and neurosurgeon. Outcomes were analyzed with Fisher's exact test. RESULTS A total of 18 patients with a mean age of 56.2 years (range 27–84 years) and an average follow-up of 5.0 months (range 0.2–21.8 months) underwent 21 cases of SSCD repair. Following treatment, all patients (100%) reported resolution in ≥ 1 symptom associated with SSCD. Autophony (p = 0.0005), tinnitus (p = 0.0059), and sound- and/or pressure-induced dizziness (p = 0.0437) showed significant symptomatic resolution. Following treatment, 29% (2/7) of patients developed imbalance, 20% (1/5) of patients developed sound- and/or pressure-induced dizziness, and 18% (2/11) of patients developed aural fullness. Among patients with improved symptoms following surgical repair, none reported recurrence of symptoms at subsequent follow-up visits. CONCLUSIONS SSCD remains an underdiagnosed and undertreated condition. Surgical repair of SSCD using a middle fossa craniotomy is associated with a high rate of symptom resolution. Continued investigation using a larger patient cohort and longer-term follow-up could further demonstrate the effectiveness of using middle fossa craniotomy for SSCD repair.

Summary The aim of the paper was to determine the factors related to the initial therapy that may contribute to death from severe necrotizing acute pancreatitis and to analyze their clinical importance as well as possible additive effects. A retrospective case-control study included all adult patients treated for severe necrotizing acute pancreatitis in the Clinical Center of Kragujevac, Serbia, during the five-year period (2006-2010.). The cases (n = 41) were patients who died, while the controls (n = 69) were participants who survived. In order to estimate the relationship between potential risk factors and observed outcome, crude and adjusted odds ratios (OR) with 95 % confidence intervals (CI) were calculated in logistic regression models. Significant association with observed outcome was shown for the use of gelatin and/or hydroxyethyl starch (adjusted OR 12.555; 95 % CI 1.150-137.005), use of albumin (adjusted OR 27.973; 95 % CI 1.741-449.373), use of octreotide (adjusted OR 16.069; 95 % CI 1.072-240.821) and avoiding of enteral feeding (adjusted OR 3.933; 95 % CI 1.118-13.829), while the use of nonsteroidal anti-inflammatory drugs had protective role (adjusted OR 0.057; 95 % CI 0.004-0.805). The risk of death in patients with predicted severe necrotizing acute pancreatitis could be reduced with avoidance of treatment with colloid solutions, albumin and octreotide, as well as with an early introduction of oral/enteral nutrition and use of nonsteroidal anti-inflammatory drugs.

The number of patient imaging studies has increased because of precautious physicians ordering scans when a vague symptom is presented; subsequently, the number of incidental meningiomas detected has increased as well. These brain tumors do not present with related symptoms and are usually small. MRI and computed tomographic scans most frequently capture incidental meningiomas. Incidental meningiomas are managed with observation, radiation, and surgical resection. Ultimately, a conservative approach is recommended, such as observing an incidental meningioma and then only radiating if the tumor displays growth, whereas a surgical approach is to be used only when proven necessary.

Hyperhomocysteinemia is one of the unconventional risk factors of cardiovascular morbidity - it is causally associated in both directions with oxidative stress, endothelial dysfunction, mechanisms of cell signaling and apoptosis. Numerous clinical and experimental studies have explained the mechanisms and clinical expression of atherosclerotic and prothrombotic effects of homocysteine. The main pathological substrate, previous therapy, and surgical procedure-intervention itself are associated with the state of oxidative stress and endothelial dysfunction, which is one of important factors for elevated plasma homocysteine levels. Recent studies point to the possibility of a successful correction of hyperhomocysteinemia, especially secondary one.

New findings on the activity of myeloperoxidase in the course of an inflammatory process associated with infections and vascular lesions indicate its role in the state of oxidative stress and endothelial dysfunction as well as its predictive value for cardiovascular insults. The products of actions by myeloperoxidase represent an integrative mechanism connecting the tissue lesions, infectious, inflammatory processes, oxidative stress, endothelial dysfunction and the development of vascular insult (the most common are the arterial and venous thrombosis and consecutive embolism). The most common complications of an operative surgical treatment are vascular. Seen from a conservative standpoint the most common are arterial and venous thrombosis, but more broadly suture dehiscence could be considered as a consequence of the impaired microcirculation. Operational procedures as well as the underlying pathology lead to the activation of inflammatory cascade with the activation of myeloid lineage cells whereby a release and activation of myeloperoxidase, which in addition to antimicrobial exerts multiple vascular operations. Increased concentrations of myeloperoxidase in the plasma up to three months before the clinical expression of vascular insult indicates its predictive value. Current research portrays the possibility of adjusting the successful result of the action of myeloperoxidase and prevention of vascular complications.

Cystic fibrosis transmembrane conductance regulator (CFTR) is important for normal pancreatic function. Its coding gene is polymorphic, and the variations have been associated with the increased risk for acute pancreatitis. However, their impact on the disease severity is still unknown. Therefore, the aim of our study was to determine the functional importance of common cystic fibrosis transmembrane conductance regulator variations IVS8-poly T, R117H, and M470V for the severity of acute pancreatitis. The study involved 98 acute pancreatitis patients. The severity of the disease was determined based on the Atlanta Classification system. IVS8-poly T, R117H, and M470V genotyping was performed using PCR-RFLP method. IVS8-5T, IVS8-7T, IVS8-9T, and M470V alleles were found at the frequencies of 5.7, 75.5, 18.9, and 55.7%, respectively, while R117H was not observed. Among women, the severe form of the disease was more frequent in carriers of at least one IVS8 9T allele (RR for 9T/9T + 9T/non-9T vs. non-9T/non-9T: 2.115; 95% CI: 1.241–3.605). This association was not detected in men and was not affected by M470V. In addition, co-morbidities increased the severity of acute pancreatitis (p = 0.022). Our study reveals that IVS8 poly-T variation affects severity of acute pancreatitis in women and that existent co-morbidities worsen the clinical course of the disease.

Acute pancreatitis represents an acute nonbacterial inflammation of the pancreas caused by a premature and ectopic activation of pancreatic digestive enzymes. Two of the most important genes in pancreatic autodigestion, PRSS1 and SPINK1, were implicated in the earliest discoveries of the genetic background of pancreatitis. However, the distribution of their variations displays interethnic variability, which could significantly affect the magnitude of their proposed effects on this disease worldwide. The aim of the present study was to investigate the distribution of the most important functional variations of PRSS1 (86A>T and 365G>A) and SPINK1 (101A>G), and their influence on the clinical course of acute pancreatitis in Serbian patients. The study enrolled 81 subjects, the severity of disease course was determined using the Atlanta Classification system, and the genotyping was conducted using a PCR-RFLP method. PRSS1 86A>T and 365G>A SNPs were not observed in the study population, while SPINK1 101A>G was present with the frequency of 0.62% (95% CI: 0.00, 3.83%). Due to extremely low frequencies or absences of examined variations, the proposed effect of these SNPs on the severity of acute pancreatitis could not be confirmed. The results do not support routine genotyping of either PRSS1 or SPINK1 in Serbs.

Acute necrotizing pancreatitis (ANP) is a severe form of acute pancreatitis that is associated with high morbidity and mortality. Thus, an adequate initial treatment of patients who present with acute pancreatitis (AP) based on correct interpretation of early detected laboratory and clinical abnormalities may have a significant positive impact on the disease course. The aim of the study was to determine patient- and initial treatment-related risk factors for the development of acute necrotizing pancreatitis. For the purpose of this study a case-control design was chosen, including adult patients treated for AP in the surgical Intensive Care Unit (sICU) of Clinical Center of Kragujevac, from January 2006 to January 2011. The cases (n=63) were patients who developed ANP, while the controls (n=63) were patients with AP without the presence of pancreatic necrosis. The controls were randomly selected from a study sample after matching with the cases by age and sex. Significant association with the development of ANP was found for the presence of comorbidity (adjusted OR 6.614 95%CI 1.185-36.963), and the use of somatostatin (adjusted OR 7.460, 95%CI 1.162-47.833) and furosemide (adjusted OR 2710.57, 95%CI 1.996-56.035) started immediately upon admission to the sICU. This study suggests that comorbidities, particularly the presence of serious cardio-vascular disease, can increase the risk for development of acute necrotizing pancreatitis. The probability for the development of ANP could be reduced by the avoidance of the initial use of loop diuretics and somatostatin.

Acute pancreatitis (AP) is a common, potentially lethal, acute inflammatory process with a highly variable clinical course. The aim of this study was to analyse early changes in the serum concentrations of pro- and anti-inflammatory cytokines in the peripheral blood of patients with the interstitial form of acute pancreatitis (IAP) and necrotic acute pancreatitis (NAP), especially in those patients who had lethal outcomes. The prospective study enrolled 52 patients who were divided into IAP (65.38% of patients) and NAP (34.62% of patients) groups. The serum levels of interleukins (IL) 6, 8 and 10, together with tumour necrosis factor (TNF)-alpha were measured on the 1st and 3rd day of hospitalisation. Significantly higher values of IL-6, IL-8 and IL-10 were found on day 1 and 3 in NAP than in IAP. IL-6 was significantly higher on both days of measurement, whereas IL-10 on the first day and IL-8 on the third day were significantly higher in the group of patients who did not survive in comparison with patients who had the interstitial form of AP. In conclusion, the data from this study showed that immune suppression and excessive immune stimulation in the first three days after admission could indicate the development of NAP and a potentially lethal outcome.

Total hip arthroplasty is a surgical procedure in which the hip joint is replaced with an artificial one. Performance of this procedure requires knowledge of the anatomical features of the joint, the characteristics of the endoprosthesis, and the needs and pathological and physiological characteristics of the patient. This retrospective analysis includes the data contained in 874 medical histories of patients of both sexes implanted with a unilateral total hip endoprosthesis who were treated at the Orthopedic Clinic of the Clinical Center, Kragujevac, from January 1st, 2009 to December 1st, 2014. Analysis of the data revealed that 69.3% of the patients were women. The most common type of implanted prosthesis was the cementless one, and the most frequent indication was degenerative joint damage. Total arthroplasty of the hip joint has become one of the most common interventions in orthopedic surgery. The increasing need for this method of treatment required the development of new biomaterials, as well as new types of prosthesis, which, in the future, will decrease the occurrence of adverse reactions and complications during and after implantation of the prosthesis, as well as extending their useful life.

Objective: To assess the frequency of physician business card utilization among neurosurgery residents and its impact on patient satisfaction, reflected in scores on the CI-CARE patient survey. The authors hypothesize that neurosurgeons hand out business cards less frequently and that this may have potential implications for patient satisfaction. Methods: A retrospective review of patient survey results was performed. Residents were divided into two groups: 1) business card use and 2) no business card use. Scores on survey questions, which pertained to overall communication, medical expertise, and quality of care delivered were compared between groups using a Mann-Whitney U test. Results: A total of 4222 surveys of 367 residents across 9 departments were collected. PGY-1 and -2 residents were most frequently evaluated (n = 1647, 39% and n = 1416, 33.5%, respectively) and handed out the most business cards (n = 398, 25.4% and n = 302, 22%, respectively). PGY-1 and -2 residents who handed out business cards were perceived by patients to be better overall communicators and have greater medical expertise (P

Background Superior semicircular canal dehiscence (SSCD) presents with varying degrees of auditory and vestibular dysfunction. The condition is confirmed on high-resolution computed tomography (CT) imaging, and symptoms are often improved by surgical repair. Although a classic middle fossa craniotomy has been used with good results, recent advances in technique have allowed for modification of the traditional approach into a smaller skin incision and a minimally invasive middle fossa keyhole craniectomy roughly 1.7 cm in diameter. Objective To delineate this novel approach and describe the technique for accurate localization of the dehiscence using preoperative measurements and intraoperative image guidance, thereby minimizing the need for a larger skin incision and craniotomy. Methods Patients were independently diagnosed with SSCD by the senior authors. Once relevant imaging was acquired, the novel keyhole technique was performed. Patients' vestibular and auditory symptoms before and after the procedure were assessed. Outcomes from a series of patients treated with this keyhole approach were tabulated and reported. Results Twelve cases from 11 patients were included in this series. Auditory symptoms had high rates of resolution with pulsatile tinnitus, internal amplification of sounds, and autophony being resolved in a majority of cases. Only 2 cases reported hearing decline. Sound/pressure induced vertigo and disequilibrium also demonstrated high rates of resolution. No complications were reported. Conclusion The minimally invasive middle fossa keyhole craniectomy is a novel approach for the repair of SSCD. This approach may contribute to resolved auditory and vestibular symptoms with low morbidity and quick recovery.

Objectives To review the characteristic symptoms of superior semicircular canal dehiscence, testing and imaging of the disease, and the current treatment and surgical options. Results and Conclusions Symptoms of superior semicircular canal dehiscence (SSCD) include autophony, inner ear conductive hearing loss, Hennebert sign, and sound-induced episodic vertigo and disequilibrium (Tullio phenomenon), among others. Potential etiologies noted for canal dehiscence include possible developmental abnormalities, congenital defects, chronic otitis media with cholesteatoma, fibrous dysplasia, and high-riding jugular bulb. Computed tomography (CT), vestibular evoked myogenic potentials, Valsalva maneuvers, and certain auditory testing may prove useful in the detection and evaluation of dehiscence syndrome. Multislice temporal bone CT examinations are normally performed with fine-cut (0.5- to 0.6-mm) collimation reformatted to the plane of the superior canal such that images are parallel and orthogonal to the plane. For the successful alleviation of auditory and vestibular symptoms, a bony dehiscence can be surgically resurfaced, plugged, or capped through a middle fossa craniotomy or the transmastoid approach. SSCD should only be surgically treated in patients who exhibit clinical manifestations.

Endogenous vaults are ribonucleoproteins expressed throughout various cell types and across numerous species. Several central nervous system (CNS) tumors have been reported to exhibit high levels of major vault protein (MVP). The vault has been hypothesized to play a role in cellular transport. Although further studies are needed to elucidate the mechanisms of endogenous vault function, these advances may enable the development of targeted therapies to prevent cancer cells from acquiring MVP-related drug resistance. In addition, they seem suited for use as nanocapsules for delivering various therapeutic agents and immunogenic proteins, representing a promising prospect for CNS tumor immunotherapy.

The objective of this study was to evaluate the characteristic symptoms of and treatments for lateral semicircular canal dehiscence (LSCD) and posterior semicircular canal dehiscence (PSCD) and its proposed mechanism. A dehiscence acquired in any of the semicircular canals may evoke various auditory symptoms (autophony and inner ear conductive hearing loss) or vestibular symptoms (vertigo, the Tullio phenomenon, and Hennebert sign) by creating a “third mobile window” in the bone that enables aberrant communication between the inner ear and nearby structures. A PubMed search was performed using the keywords lateral, posterior, and semicircular canal dehiscence to identify all relevant cases. Our data suggest that PSCD, although clinically rare, is most likely associated with a high-riding jugular bulb and fibrous dysplasia. Patients may experience auditory manifestations that range from mild conductive to extensive sensorineural hearing loss. LSCD is usually associated with chronic otitis media with cholesteatoma.

Pineal cysts (PCs) are benign and often asymptomatic lesions of the pineal region that are typically small and do not change in size over time. PCs appear as small, well circumscribed, unilocular masses that either reside within or completely replace the pineal gland. This article reviews and discusses the characteristic features of PCs-clinical, histological, and identifiable by various imaging modalities-which assist clinicians in narrowing the differential diagnosis for pineal lesions.

BACKGROUND: Radiation therapy has emerged as an effective alternative treatment modality for vestibular schwannomas (VS) to achieve tumor control and hearing preservation. The purpose of this study is to evaluate the radiation delivered to the cochlea during stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) and to determine its effect on hearing preservation. METHODS: Patients receiving SRS or SRT treatment for VS at UCLA from 2009 to 2013 were analyzed for clinical and hearing outcomes. The dosimetric data to the cochlea volume was associated with the hearing outcome of patients. Patients treated with SRS received a marginal dose of 12 Gy, and patients treated with SRT received a marginal dose of 50.4 Gy delivered through 28 fractions. Statistical analysis was completed using 2-tailed, Mann-Whitney U test with a significance level of 0.05. RESULTS 40 patients underwent either SRS or SRT for vestibular schwannoma with a mean follow-up of 23.2 months. The mean total radiation dose delivered to the cochlea volume ranged from 4.0 to 11.9 Gy (median: 8.7 Gy) for SRS treatment and 30.2 to 51.4 Gy (median: 44.8 Gy) for SRT treatment. Hearing was preserved in 60% of SRS patients and in 63% of SRT patients. The cochlea received statistically significantly more radiation in patients with decreased hearing in SRS (p = 0.031), but not in SRT (p = 0.097). CONCLUSIONS: Our data suggests that increased cochlear radiation dose is significantly associated with decreased rates of hearing preservation following SRS treatment but not with SRT treatment. Irradiation of cochlear structures may be a critically important aspect of radiosurgery treatment that warrants careful evaluation in the radiation treatment of vestibular schwannomas. Future prospective studies with randomization may further validate this data.

Therapies that target the programmed death-1 (PD-1) receptor have shown unprecedented rates of durable clinical responses in patients with various cancer types. One mechanism by which cancer tissues limit the host immune response is via upregulation of PD-1 ligand (PD-L1) and its ligation to PD-1 on antigen-specific CD8(+) T cells (termed adaptive immune resistance). Here we show that pre-existing CD8(+) T cells distinctly located at the invasive tumour margin are associated with expression of the PD-1/PD-L1 immune inhibitory axis and may predict response to therapy. We analysed samples from 46 patients with metastatic melanoma obtained before and during anti-PD-1 therapy (pembrolizumab) using quantitative immunohistochemistry, quantitative multiplex immunofluorescence, and next-generation sequencing for T-cell antigen receptors (TCRs). In serially sampled tumours, patients responding to treatment showed proliferation of intratumoral CD8(+) T cells that directly correlated with radiographic reduction in tumour size. Pre-treatment samples obtained from responding patients showed higher numbers of CD8-, PD-1- and PD-L1-expressing cells at the invasive tumour margin and inside tumours, with close proximity between PD-1 and PD-L1, and a more clonal TCR repertoire. Using multivariate analysis, we established a predictive model based on CD8 expression at the invasive margin and validated the model in an independent cohort of 15 patients. Our findings indicate that tumour regression after therapeutic PD-1 blockade requires pre-existing CD8(+) T cells that are negatively regulated by PD-1/PD-L1-mediated adaptive immune resistance.

Objective While typically benign, epidermoid tumors upon rare occasion can undergo malignant transformation, which carries a poor prognosis. Here, we reviewed treatment strategies and analyzed outcomes for every case of malignant epidermoid tumor reported since its original description in 1912. Methods A comprehensive literature review identified all reported cases of malignant transformation of intracranial epidermoid tumor. Treatments were categorized as follows: palliative management, stereotactic radiosurgery (SRS), chemotherapy, and surgery plus multiple (2+) adjuvant therapies. Survival data of these groups were compared to treatment outcomes for patients receiving only surgical resection, as reported in our previous study. Results We identified 58 cases of intracranial epidermoid tumor with malignant degeneration. Average survival regardless of therapy was 11.8 months. Mean survival outcomes for groups treated with palliative management, chemotherapy, SRS, and multiple postoperative adjuvant therapies were 5.3 months, 25.7 months, 29.2 months, and 36.3 months, respectively. Outcomes for the groups including SRS, chemotherapy, and multiple post-operative adjuvant therapies were statistically significant compared to surgical resection alone. Conclusion While there remains a lack of consensus regarding the best approach to the management of patients with malignant epidermoid tumors, our systematic analysis characterizes and confirms the added benefit of SRS, chemotherapy, and multimodal adjuvant therapies.

This article provides historical background and current research involving the use of bevacizumab for the treatment of recurrent glioblastoma. Although bevacizumab, approved by the Food and Drug Administration, prolongs glioblastoma progression free survivial, decreases tumor vascularization, and reduces permeability of vessels, it does not seem to prolong overall survival. Despite slowed primary tumor progression, bevacizumab treatment may facilitate transformation to a more invasive phenotype. Adaptive responses, which make glioblastoma particularly resistant to various treatment modalities have been described. Conferred benefits, adverse effects, mechanisms of resistance, and potential areas for future research are discussed.

The CD133 epitope has been identified as a tumor marker for the purification of a subpopulation of glioblastoma multiforme (GBM) cells demonstrating cancer stem cell phenotypes. Isolated tumorsphere-forming CD133(+) GBM cells demonstrated heightened in vitro proliferation, self-renewal, and invasive capacity. Orthotopic transplantation of CD133(+) cells led to the formation of heterogeneous tumors that were phenocopies of the original patient tumor. In this article, the authors discuss the complex regulation of CD133 expression in gliomas, its role in tumorigenesis, and its potential as a marker for targeted and personalized therapeutic intervention.

Malignant gliomas are the most common primary intracranial tumor, with a proclivity for widespread invasion and rampant destruction of healthy parenchyma. This infiltrative process affords high-grade gliomas protection from traditional therapies and subjects the adjacent normal tissue to potential damage from nonspecific treatment modalities.1,2 Immunotherapies involving antibodies or sensitized effector cells can offer selective targeting of protein-arbohydrate complexes on tumor cell surfaces that distinguish neoplastic from noncancerous cells.1,3 Consequently, the treatment of malignant gliomas may be enhanced not only by increased specificity for tumor tissue but also from decreased toxicity to the host’s healthy cells.1 This review focuses on published findings from the use of passive immunotherapy for the treatment of high-grade gliomas, particularly glioblastoma multiforme (GBM).

Introduction. Pneumothorax is a common clinical problem in thoracic surgery. Leading professional associations have adopted a number of guidelines and recommendations for the treatment of pneumothorax, but their clinical use is often insufficient. This study was aimed at analyzing the incidence of pneumothorax, profile of patients and surgical treatment of pneumothorax at the Clinical Center Kragujevac, in a five-year period. Material an methods. This retrospective, non-interventional study used data collected from the medical records and operative protocol of the Department of Thoracic Surgery, Clinical Centre Kragujevac in a fiveyear period. All data were statistically analyzed. Results. In the observed period, 492 patients with diagnosis of pneumothorax were hospitalized. The majority of patients were treated in 2009 (140), and the fewest in 2005 (68). Four-fifths of patients were male. Primary spontaneous pneumothorax was found in 25% and traumatic pneumothorax in 50%. Most patients were aged 21-30 years (83). The number of cases of secondary spontaneous and traumatic pneumothorax increased with the age of patients and the number of cases of primary and recurrent spontaneous pneumothorax decreased with their age. Drainage as a method of treatment was prevalent in all types of pneumothorax (p < 0.01). Conclusion. The results of study show similarities with other studies regarding both the incidence of certain forms of pneumothorax and the gender-age profile of patients and their treatment, taking into account the observed period and the target population.

Ependymomas are neoplasms that can occur anywhere along the craniospinal axis. They are the third most common brain tumor in children, representing 10% of pediatric intracranial tumors, 4% of adult brain tumors, and 15% of all spinal cord tumors. As the heterogeneity of ependymomas has severely limited the prognostic value of the World Health Organization grading system, numerous studies have focused on genetic alterations as a potential basis for classification and prognosis. However, this endeavor has proven difficult due to variations of findings depending on tumor location, tumor grade, and patient age. While many have evaluated chromosomal abnormalities for ependymomas as a whole group, others have concentrated their efforts on specific subsets of populations. Here, we review modern findings of chromosomal analyses, their relationships with various genes, and their prognostic implications for intracranial and spinal cord ependymomas.