Early oral hydration in patients with high enterocutaneous fistula.

INTRODUCTION: Enterocutaneous fistula is defined as an abnormal connection between the gastrointestinal tract and the skin. In addition to the early recognition and treatment of sepsis, nutritional support, wound management, the adequate replacement of lost fluids with a properly set and timely rehydration treatment, together with the control of fistula production represent the first steps in treatment management. MATERIAL AND METHODS: The authors present an overview of oral rehydration therapy, describing the properties and effects of individual solutions on fistula. The absorption of fluids and electrolytes into the gastrointestinal tract is performed by the group of sodium-dependent glucose cotransporters (sodium-glucose linked transporter, SGLT1). DISCUSSION: The water and electrolyte absorption mechanisms described in the article can be used in the treatment of a patient with a high fistula. The amount of administered hypotonic fluids (water, tea) should not exceed 500 ml/day. The remaining volume, depending on fistula loss, must be supplemented with isoosmolar fluids. With a good tolerance of oral rehydration solutions and compliance with the other steps of treatment, it is possible to remain on oral intake during the entire duration of treatment without the need to prohibit it completely, thus improving the patient's overall comfort. CONCLUSION: Reducing the intake of hypotonic fluids (tap water, tea) and administering an isotonic solution help to reduce the production of the fistula, thereby contributing to its spontaneous closure.

Genetic Heterogeneity, Tumor Microenvironment and Immunotherapy in Triple-Negative Breast Cancer.

Heterogeneity of triple-negative breast cancer is well known at clinical, histopathological, and molecular levels. Genomic instability and greater mutation rates, which may result in the creation of neoantigens and enhanced immunogenicity, are additional characteristics of this breast cancer type. Clinical outcome is poor due to early age of onset, high metastatic potential, and increased likelihood of distant recurrence. Consequently, efforts to elucidate molecular mechanisms of breast cancer development, progression, and metastatic spread have been initiated to improve treatment options and improve outcomes for these patients. The extremely complex and heterogeneous tumor immune microenvironment is made up of several cell types and commonly possesses disorganized gene expression. Altered signaling pathways are mainly associated with mutated genes including p53, PIK3CA, and MAPK, and which are positively correlated with genes regulating immune response. Of note, particular immunity-associated genes could be used in prognostic indexes to assess the most effective management. Recent findings highlight the fact that long non-coding RNAs also play an important role in shaping tumor microenvironment formation, and can mediate tumor immune evasion. Identification of molecular signatures, through the use of multi-omics approaches, and effector pathways that drive early stages of the carcinogenic process are important steps in developing new strategies for targeted cancer treatment and prevention. Advances in immunotherapy by remodeling the host immune system to eradicate tumor cells have great promise to lead to novel therapeutic strategies. Current research is focused on combining immune checkpoint inhibition with chemotherapy, PARP inhibitors, cancer vaccines, or natural killer cell therapy. Targeted therapies may improve therapeutic response, eliminate therapeutic resistance, and improve overall patient survival. In the future, these evolving advancements should be implemented for personalized medicine and state-of-art management of cancer patients.

Circulating metabolites in the early stage of breast cancer were not related to cancer stage or subtypes but associated with ki67 level. Promising statistical discrimination from controls.

It was documented that the presence of malignancy in an organism causes metabolomic alterations in blood plasma which applies also to breast cancer. Breast cancer is a heterogeneous disease and there are only limited known relations of plasma metabolomic signatures with the tumour characteristics in early BC and knowing them would be of great advantage in noninvasive diagnostics. In this study, we focused on the metabolic alterations in early BC in blood plasma with the aim to identify metabolomic characteristics of BC subtypes. We used 50 early BC patients (FIGO stage I and II), where no additional metabolomic changes from metastatically changed remote organs were to be expected. We compared plasma levels of metabolites against controls and among various molecular and histological BC subtypes. BC patients showed decreased plasma levels of branched-chain amino acids BCAAs (and related keto-acids), histidine pyruvate and alanine balanced with an increased level of 3-hydroxybutyrate. The levels of circulating metabolites were not related to BC molecular subtypes (luminal A/luminal B), histological finding or grade, eventually stage, which indicate that in early BC, the BC patients share common metabolomics fingerprint in blood plasma independent of grade, stage or molecular subtype of BC. We observed statistically significant correlations between tumour proliferation marker Ki-67 level and circulating metabolites: alanine, citrate, tyrosine, glutamine, histidine and proline. This may point out the metabolites those levels could be associated with tumour growth, and conversely, the rate of tumour proliferation could be potentially estimated from plasma metabolites. When analyzing metabolomic changes in BC, we concluded that some of them could be associated with the metabolomic features of cancer cells, but the other observed alterations in blood plasma are the results of the complex mutual biochemical pathways in the comprehensive inter-organ metabolic exchange and communication. In the end, statistical discrimination against controls performed with AUC >0.91 showed the very promising potential of plasma metabolomics in the search for biomarkers for oncologic diseases.

In vitro modeling of amyotrophic lateral sclerosis with induced pluripotent stem cell technology-derived cell line ORIONi002-A.

We present here a new iPS cell line for modeling sporadic form of ALS. Cell line was generated by reprogramming skin fibroblasts isolated with explant culture technology from skin biopsy, donated by ALS patient. For reprogramming, polycistronic self-replicating RNA vector was used and derived iPS cells were characterized by immunocytochemistry and FACS (pluripotent factors expression), karyotyping, STR fingerprinting analysis and in vitro differentiation assay. New cell line showed normal (46, XY) karyotype and differentiated in vitro into cells from three germ layers. STR analysis proved the origin and originality of the cell line.

Clostridium septicum foot gangrene associated with colorectal cancer.

INTRODUCTION: Since the second half of the 20th century, an association between the occurrence of Clostridium septicum and Streptococcus gallolyticus infections in patients with colorectal cancer has been described in specialist literature. Infections are manifested by bacteremia, septic embolism, cellulitis, myonecrosis, and gas gangrene of the limbs. MATERIAL AND METHODS: The authors present a case of a rare association between lower limb gangrene caused by the septic embolization of a Clostridium septicum infection and malignancy of colon ascendens in a polymorbid patient. Gangrene of the lower limb led to septic shock requiring acute amputation treatment. After managing the acute condition, the patient was operated on for a malignant colon tumour. DISCUSSION: The process of carcinogenesis often takes years and is almost asymptomatic. The occurrence of S. bovis/S. equinus (SBSEC) and C. septicum bacteremia, respectively, is relatively rare, but their presence is often associated with the occurrence of malignancy, most often of the lower gastrointestinal tract. This paraneoplastic symptom may be the first manifestation of a malignant disease. The effect of exotoxins can lead to sepsis or even septic shock with a mortality of 48-56%. CONCLUSION: Clostridium septicum and Streptococcus gallolyticus infections are rare in clinical practice. However, their presence can be a first paraneoplastic symptom, and therefore the doctor should look for a possible oncological disease when they are detected. The main diagnostic methods include colonoscopy and imaging, especially CT scan.

Radiation-associated angiosarcoma of the breast: An international multicenter analysis.

INTRODUCTION: Radiation-associated angiosarcoma (RAAS) is a rare and serious complication of breast irradiation. Due to the rarity of the condition, clinical experience is limited and publications on this topic include only retrospective studies or case reports. MATERIALS AND METHODS: All patients diagnosed with RAAS between January 2000 and December 2017 in twelve centers across the Czech Republic and Slovakia were evaluated. RESULTS: Data of 53 patients were analyzed. The median age at diagnosis was 72 (range 44-89) years. The median latency period between irradiation and diagnosis of RAAS was 78 (range 36-172) months. The median radiation dose was 57.6 (range 34-66) Gy. The whole breast radiation therapy with radiation boost to the tumor bed was the most common radiotherapy regimen. Total mastectomy due to RAAS was performed in 43 patients (81%), radical excision in 8 (15%); 2 patients were not surgically treated due to unresectable disease. Adjuvant chemotherapy followed surgical therapy of RAAS in 18 patients, 3 patients underwent adjuvant radiotherapy. The local recurrence rate of RAAS was 43% and the median time from surgery to the onset of recurrence was 7.5 months (range 3-66 months). The 3-year survival rate was 56%, the 5-year survival rate was only 33%. 46% of patients died during the follow-up period. CONCLUSION: The present data demonstrate that RAAS is a rare condition with high local recurrence rate (43%) and mortality (the 5-year survival rate was 33%.). Early diagnosis of RAAS based on biopsy is crucial for treatment with radical intent. Surgery with negative margins constitutes the most important part of the therapy; the role of adjuvant chemotherapy and radiotherapy is still unclear.

Circulating miRNA expression over the course of colorectal cancer treatment.

Colorectal cancer (CRC) is the third-most common cancer type in males and the second-most common cancer type in females, and has the second-highest overall mortality rate worldwide. Approximately 50% of patients in stage I-III develop metastases, mostly localized to the liver. All physiological conditions occurring in the organism are also reflected in the levels of circulating microRNAs (miRNAs/miRs) in patients. miRNAs are a class of small, non-coding, single-stranded RNAs consisting of 18-25 nucleotides, which have important roles in various cellular processes. The aim of the present study was to evaluate a panel of seven circulating miRNAs (miR-106a-5p, miR-210-5p, miR-155-5p, miR-21-5p, miR-103a-3p, miR-191-5p and miR-16-5p) as biomarkers for monitoring patients undergoing adjuvant treatment of CRC. Total RNA was extracted from the plasma of patients with CRC prior to surgery, in the early post-operative period (n=60) and 3 months after surgery (n=14). The levels of the selected circulating miRNAs were measured with the miRCURY LNA miRNA PCR system and fold changes were calculated using the standard ∆∆Cq method. DIANA-miRPath analysis was used to evaluate the role of significantly deregulated miRNAs. The results indicated significant upregulation of miR-155-5p, miR-21-5p and miR-191-5p, and downregulation of miR-16-5p directly after the surgery. In paired follow-up samples, the most significant upregulation was detected for miR-106a-5p and miR-16-5p, and the most significant downregulation was for miR-21-5p. Pathway analysis outlined the role of the differentially expressed miRNAs in cancer development, but the same pathways are also involved in wound healing and regeneration of intestinal epithelium. It may be suggested that these processes should also be considered in studies investigating sensitive and easily detectable circulating biomarkers for recurrence in patients.

Laparoscopic Right Hemicolectomy for Appendiceal Mucocele.

Appendiceal mucocele is a rare disease with an incidence of 0.07-0.63% of all appendectomies and was first described in 1842 by Carl von Rokitansky. It is defined as an abnormal intraluminal accumulation of mucin. The clinical picture of AM can vary from asymptomatic mass in the right lower quadrant to symptoms of acute appendicitis. In some cases, AM can be found accidentally on CT performed due to other reasons or during surgery. Diagnosis consists mainly of imaging methods such as ultrasound, CT, and MRI with the finding of encapsulated cystic mass with calcifications. The main goal of surgical treatment is to remove an intact mucocele and prevent spillage of mucin into the peritoneal cavity. We present a case of large mucocele treated with laparoscopic right hemicolectomy.

Jejunal diverticulosis: A rare cause of massive bleeding.

INTRODUCTION: Jejunal diverticulosis is a rare diagnosis that occurs mainly in old age, more often in men than in women. It is usually an incidental diagnosis of unclear aethtiology. In some cases, visceral myopathy can also be the cause. It is most often manifested by abdominal pain and bleeding. Bleeding from the small intestinal diverticula represents only 0.6-5% of all small intestinal bleeding. CASE REPORT: The authors describe the case of a 66-year-old man with massive gastrointestinal bleeding who did not respond to conservative hemostyptic treatment. Following negative gastrofibroscopic and colonoscopic examinations, an angioCT examination was indicated, which revealed a source of bleeding in the jejunal diverticula. The patient was indicated for surgical treatment. The extent of bleeding was determined by perioperative enteroscopy and subsequently, the affected jejunal segment was segmentally resected with a primary anastomosis. CONCLUSION: Bleeding from the jejunal diverticula is a very rare diagnosis, which poses challenges in the diagnostic process in particular. Capsule enteroscopy plays an important role in the diagnosis, as well as CT angiography and scintigraphy in the event of massive bleeding. In addition to conservative treatment, the embolization of a bleeding vessel may subsequently be used in therapy. In indicated cases, surgical resection treatment is also possible.

Induced Pluripotency: A Powerful Tool for In Vitro Modeling.

One of the greatest breakthroughs of regenerative medicine in this century was the discovery of induced pluripotent stem cell (iPSC) technology in 2006 by Shinya Yamanaka. iPSCs originate from terminally differentiated somatic cells that have newly acquired the developmental capacity of self-renewal and differentiation into any cells of three germ layers. Before iPSCs can be used routinely in clinical practice, their efficacy and safety need to be rigorously tested; however, iPSCs have already become effective and fully-fledged tools for application under in vitro conditions. They are currently routinely used for disease modeling, preparation of difficult-to-access cell lines, monitoring of cellular mechanisms in micro- or macroscopic scales, drug testing and screening, genetic engineering, and many other applications. This review is a brief summary of the reprogramming process and subsequent differentiation and culture of reprogrammed cells into neural precursor cells (NPCs) in two-dimensional (2D) and three-dimensional (3D) conditions. NPCs can be used as biomedical models for neurodegenerative diseases (NDs), which are currently considered to be one of the major health problems in the human population.

Surgical treatment of severe dumping syndrome.

Dumping syndrome is a common post-operative complication following gastric surgery. Clinically, severe dumping can be a serious medical condition with a negative impact on the patient's life. In our case report, we present a case of refractory dumping syndrome which developed after laparoscopic subtotal gastrectomy with gastrojejunoanastomosis due to massive gastroptosis with stomach evacuation problems. Conservative gastroenterology treatment was not successful. Due to the progression of weight loss and life-threatening hypoglycaemia, the decision for surgical treatment was made. After the corrective gastro-duodenal and jejuno-jejunal anastomoses, all clinical symptoms resolved completely. With regard to the presented case, we discuss the common treatment options for dumping syndrome: the standard recommendations for dietary habits, pharmacological treatment and finally the surgery and its pitfalls. Due to the absence of randomized trials and guidelines, every patient should be treated in a personalized way.

miRNA Expression Profiles in Luminal A Breast Cancer-Implications in Biology, Prognosis, and Prediction of Response to Hormonal Treatment.

Breast cancer, which is the most common malignancy in women, does not form a uniform nosological unit but represents a group of malignant diseases with specific clinical, histopathological, and molecular characteristics. The increasing knowledge of the complex pathophysiological web of processes connected with breast cancercarcinogenesis allows the development of predictive and prognostic gene expressionand molecular classification systems with improved risk assessment, which could be used for individualized treatment. In our review article, we present the up-to-date knowledge about the role of miRNAs and their prognostic and predictive value in luminal A breast cancer. Indeed, an altered expression profile of miRNAs can distinguish not only between cancer and healthy samples, but they can classify specific molecular subtypes of breast cancer including HER2, Luminal A, Luminal B, and TNBC. Early identification and classification of breast cancer subtypes using miRNA expression profilescharacterize a promising approach in the field of personalized medicine. A detection of sensitive and specific biomarkers to distinguish between healthy and early breast cancer patients can be achieved by an evaluation of the different expression of several miRNAs. Consequently, miRNAs represent a potential as good diagnostic, prognostic, predictive, and therapeutic biomarkers for patients with luminal A in the early stage of BC.

Generation of ORIONi001-A induced pluripotent stem cell line for in vitro modeling of sporadic form of amyotrophic lateral sclerosis.

We generated new in vitro model for sporadic form of amyotrophic lateral sclerosis by reprogramming isolated skin fibroblasts into iPSCs. Fibroblasts were reprogrammed with commercially available synthetic polycistronic, self-replicating RNA vector. As verified by FISH, an early passages of a new iPSC line showed mosaic karyotype (cells with normal and abnormal karyotype 46,XY,t(2;14)(q13;p12) were present), while late passages contained only cells with abnormal karyotype. New iPSCs differentiated into all three germ layers and formed a teratoma in nude mice. Our iPSC line represents a new model for therapy testing and drug development in the field of ALS research.

Totally Laparoscopic ALPPS: Bilobar Procedure with Preservation of the S3 Portobiliary Triad.

BACKGROUND: A laparoscopic approach for associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) would have the potential to decrease morbidity and mortality rates,1 as similarly observed with laparoscopic liver surgery.2 METHODS: A 54-year-old woman with stage IV rectal cancer (cT3dN1M1) was indicated for the 'liver-first' approach. The patient presented with a massive bilobar metastatic liver involvement, including S4. Five lesions were localized in a small left liver lobe (future liver remnant < 25%). During the first stage of ALPPS, the liver parenchyma was transected with preservation of the central part of the middle hepatic vein, followed by a non-anatomical resection of S3 and a metastasectomy in S2. The procedure was completed by radiofrequency ablation of S2 lesions close to the S2 portobiliary triad, to spare venous drainage for S3. The second stage of ALPPS was performed 8 days later. RESULTS: Operative time was 300 min for the first stage of ALPPS and 200 min for the second stage. Peroperative blood loss did not exceed 50 mL per operation, and no postoperative complications were observed. The patient was discharged 7 days after the second surgery. One month later, a laparoscopic uncomplicated low anterior resection with tumor-free resection margins was performed. Five months after surgery, no disease progression was detected. CONCLUSION: A laparoscopic ALPPS procedure with preservation of one portobiliary triad in the left lobe would be feasible in selected patients. The laparoscopic approach would be very important for patients waiting for a final primary tumor surgery.

Importance of Markers of Sepsis in Surgical Patients.

Sepsis, severe sepsis, and septic shock represent a serious medicinal and general social problem and still maintain an important position among the present issues in the basic and clinical research. In the prospective analysis of patients satisfying the criteria of septic condition, we determined serum levels of bioparameters in three consecutive days from the first signs of sepsis depending on the stage or advancement of the septic condition. We determined the most significant parameter/parameters which are able to determine the stage of sepsis or to predict patient's death. In the group of 68 patients, all monitored biomarkers showed significant difference in serum concentrations versus the control group (P = 0.001). The strongest positive connection between the seriousness of sepsis and serum level is in case of procalcitonin. Predictor of mortality (r = -0.468; P = 0.001), transferrin (r = -0.506; P = 0.003), and tumor necrosis factor-α (r = 0.939; P = 0.001). Our results show that the monitored parameters (procalcitonin, C-reactive protein, tumor necrosis factor-α, and interleukin 6) have strong correlations between the serum levels and the stage of disease. Examination of at least one cytokine in normal clinical practice might lead to better interpretation of the patient's condition, determining the risk of death.

Iatrogenic perforation of hypopharynx as a cause of severe descending necrotizing mediastinitis: A case report.

The authors present a case report of severe descending necrotizing mediastinitis (DNM) etiologically of unrecognized traumatic endotracheal intubation with hypopharynx-esophageal junction perforation. Patient was treated inadequately for seven days in local hospital what was the cause of sepsis progression into the septic shock with multiorgan dysfunction syndrome. Patient was transferred to specialized hospital and was immediately operated in general anaesthesia - combined transcervical approach and lateral thoracotomy was used for mediastinal drainage and debridement. Combination of appropriate conventional and surgical therapy led to reversing of the unfavorable situation.

Posterior mediastinotomy as an unordinary method of mediastinal drainage in patient with descending necrotizing mediastinitis: a case report.

The authors present a case report of severe descending necrotizing mediastinitis (DNM) of posterior mediastinum, etiologically of vertebral osteomyelitis treated by the drainage through the posterior mediastinotomy. Mediastinitis caused by vertebral osteomyelitis is very rare. The most important diagnostic and surveillance tool for descending mediastinitis is a CT scan of chest and neck. Every surgical approach to the mediastinum has its advantages and disadvantages, so each patient has to be treated individually and the most suitable type of drainage must be chosen. The posterior mediastinotomy is an unusual alternative of drainage of pre- and paravertebrally localized DNM in posterior mediastinum but it is not recommended as a routine strategy.