Search results for: gastric cancer surgery

Authors: Sahar Nasr, Lin Li, Edwin Wang

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Bladder cancer (BLCA) is known as the 13th cause of death among cancer patients worldwide, and ~575,000 new BLCA cases are diagnosed each year. Urothelial carcinoma (UC) is the most prevalent subtype among BLCA patients, which can be categorized into muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). Currently, various therapeutic options are available for UC patients, including (1) transurethral resection followed by intravesical instillation of chemotherapeutics or Bacillus Calmette-Guérin for NMIBC patients, (2) neoadjuvant platinum-based chemotherapy (NAC) plus radical cystectomy is the standard of care for localized MIBC patients, and (3) systematic chemotherapy for metastatic UC. However, conventional treatments may lead to several challenges for treating patients. As an illustration, some patients may suffer from recurrence of the disease after the first line of treatment. Recently, immune checkpoint therapy (ICT) has been introduced as an alternative treatment strategy for the first or second line of treatment in advanced or metastatic BLCA patients. Although ICT showed lucrative results for a fraction of BLCA patients, ~80% of patients were not responsive to it. Therefore, novel treatment methods are required to augment the ICI response rate within BLCA patients. It has been shown that the infiltration of T-cells into the tumor microenvironment (TME) is positively correlated with the response to ICT within cancerous patients. Therefore, the goal of this study is to enhance the infiltration of cytotoxic T-cells into TME through the identification of target genes within the tumor that are responsible for the non-T-cell inflamed TME and their inhibition. BLCA bulk RNA-sequencing data from The Cancer Genome Atlas (TCGA) and immune score for TCGA samples were used to determine the Pearson correlation score between the expression of different genes and immune score for each sample. The genes with strong negative correlations were selected (r < -0.2). Thereafter, the correlation between the expression of each gene and survival in BLCA patients was calculated using the TCGA data and Cox regression method. The genes that are common in both selected gene lists were chosen for further analysis. Afterward, BLCA bulk and single-cell RNA-sequencing data were ranked based on the expression of each selected gene and the top and bottom 25% samples were used for pathway enrichment analysis. If the pathways related to the T-cell infiltration (e.g., antigen presentation, interferon, or chemokine pathways) were enriched within the low-expression group, the gene was included for downstream analysis. Finally, the selected genes will be used to calculate the correlation between their expression and the infiltration rate of the activated CD+8 T-cells, natural killer cells and the activated dendric cells. A list of potential target genes has been identified and ranked based on the above-mentioned analysis and criteria. SUN-1 got the highest score within the gene list and other identified genes in the literature as benchmarks. In conclusion, inhibition of SUN1 may increase the tumor-infiltrating lymphocytes and the efficacy of ICI in BLCA patients. BLCA tumor cells with and without SUN-1 CRISPR/Cas9 knockout will be injected into the syngeneic mouse model to validate the predicted SUN-1 effect on increasing tumor-infiltrating lymphocytes.

Keywords: data analysis, gene expression analysis, gene identification, immunoinformatic, functional genomics, transcriptomics

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Authors: Mohamed Moussaoui

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A series of thirty-one potential inhibitors targeting the epidermal growth factor receptor kinase (EGFR), derived from quinazoline, underwent 3D-QSAR analysis using CoMFA and CoMSIA methodologies. The training and test sets of quinazoline derivatives were utilized to construct and validate the QSAR models, respectively, with dataset alignment performed using the lowest energy conformer of the most active compound. The best-performing CoMFA and CoMSIA models demonstrated impressive determination coefficients, with R² values of 0.981 and 0.978, respectively, and Leave One Out cross-validation determination coefficients, Q², of 0.645 and 0.729, respectively. Furthermore, external validation using a test set of five compounds yielded predicted determination coefficients, R² test, of 0.929 and 0.909 for CoMFA and CoMSIA, respectively. Building upon these promising results, eighteen new compounds were designed and assessed for drug likeness and ADMET properties through in silico methods. Additionally, molecular docking studies were conducted to elucidate the binding interactions between the selected compounds and the enzyme. Detailed molecular dynamics simulations were performed to analyze the stability, conformational changes, and binding interactions of the quinazoline derivatives with the EGFR kinase. These simulations provided deeper insights into the dynamic behavior of the compounds within the active site. This comprehensive analysis enhances the understanding of quinazoline derivatives as potential anti-cancer agents and provides valuable insights for lead optimization in the early stages of drug discovery, particularly for developing highly potent anticancer therapeutics

Keywords: 3D-QSAR, CoMFA, CoMSIA, ADMET, molecular docking, quinazoline, molecular dynamic, egfr inhibitors, lung cancer, anticancer

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Authors: Aishik Deb, Rituparna Sinha

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We have developed an algorithm to detect the abnormal segment/"structural variation in the genome across a number of samples. We have worked on simulated as well as real data from the BAM Files and have designed a segmentation algorithm where abnormal segments are detected. This algorithm aims to improve the accuracy and performance of the existing CNV-CH algorithm. The next-generation sequencing (NGS) approach is very fast and can generate large sequences in a reasonable time. So the huge volume of sequence information gives rise to the need for Big Data and parallel approaches of segmentation. Therefore, we have designed a map-reduce approach for the existing CNV-CH algorithm where a large amount of sequence data can be segmented and structural variations in the human genome can be detected. We have compared the efficiency of the traditional and map-reduce algorithms with respect to precision, sensitivity, and F-Score. The advantages of using our algorithm are that it is fast and has better accuracy. This algorithm can be applied to detect structural variations within a genome, which in turn can be used to detect various genetic disorders such as cancer, etc. The defects may be caused by new mutations or changes to the DNA and generally result in abnormally high or low base coverage and quantification values.

Keywords: cancer detection, convex hull segmentation, map reduce, next generation sequencing

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Authors: Donghee Kang

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Background: Cancer pain is very difficult to control as the mechanism of pain is varied, and the patient has several co-morbidities. The use of Intravenous Patient-Controlled Analgesia (IV-PCA) can effectively control underlying pain and breakthrough pain. Ketamine is used in many pain patients due to its unique analgesic effect. In this study, it was checked whether there was a difference in the amount of analgesic usage, pain control degree, and side effects between patients who controlled pain with fentanyl-based IV-PCA and those who added Ketamine for pain control. Methods: Among the patients referred to this department for cancer pain, IV-PCA was applied to patients who were taking sufficient oral analgesics but could not control them or had blood clotting disorders that made the procedure difficult, and this patient group was targeted. In IV-PCA, 3000 mcg of Fentanyl, 160 mg of Nefopam, and 0.3 mg of Ramosetrone were mixed with normal saline to make a total volume of 100 ml. Group F used this IV-PCA as it is, and group K mixed 250 mg of Ketamine with normal saline to make a total volume of 100 ml. For IV-PCA, the basal rate was 0.5ml/h, the bolus was set to 1ml when pressed once, and the lockout time was set to 15 minutes. If pain was not controlled after IV-PCA application, 500 mcg of Fentanyl was added, and if excessive sedation or breathing difficulties occurred, the use was stopped for one hour. After that, the degree of daily pain control, analgesic usage, and side effects were investigated for seven days using this IV-PCA. Results: There was no difference between the two groups in the demographic data. Both groups had adequate pain control. Initial morphine milligram equivalents did not differ between the two groups, but the total amount of Fentanyl used for seven days was significantly different between the two groups [p=0.014], and group F used more Fentanyl through IV-PCA. In addition, the amount of sleeping pills used during the seven days was higher in Group F [p<0.01]. Overall, there was no difference in the frequency of side effects between the two groups, but the nausea was more frequent in Group F [p=0.031]. Discussion: When the two groups were compared, pain control was good in both groups. This seems to be because Fentanyl-based IV-PCA showed an adequate pain control effect. However, there was a significant difference in the total amount of opioid (Fentanyl) used, which is thought to be the opioid-sparing effect of Ketamine. Also, among the side effects, nausea was significantly less, which is thought to be possible because the amount of opioids used in the Ketamine group was small. The frequency of requesting sleeping pills was significantly less in the group using Ketamine, and it seems that Ketamine also helped improve sleep quality. In conclusion, using Ketamine with an opioid to control pain seems to have advantages. IV-PCA, which can be used effectively when other procedures are difficult, is more effective and safer when used together with Ketamine than opioids alone.

Keywords: cancer pain, intravenous patient-controlled analgesia, Ketamine, opioid

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Authors: Rekaya A. Shabbir, Marco Mingarelli, Glenn Flux, Ananya Choudhury, Tim A. D. Smith

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Introduction: Heterogeneity of dose distributions across a tumour is problematic for targeted radiotherapy. Gold nanoparticles (AuNPs) enhance dose-distributions of targeted radionuclides. The aim of this study is to demonstrate if tumour dose-distribution of targeted AuNPs radiolabelled with either of two radioisotopes (¹⁷⁷Lu and ⁹⁰Y) in breast cancer cells produced homogeneous dose distributions. Moreover, in vitro and in vivo studies were conducted to study the importance of receptor level on cytotoxicity of EGFR-targeted AuNPs in breast and colorectal cancer cells. Methods: AuNPs were functionalised with DOTA and OPPS-PEG-SVA to optimise labelling with radionuclide tracers and targeting with Erbitux. Radionuclides were chelated with DOTA, and the uptake of the radiolabelled AuNPs and targeted activity in vitro in both cell lines measured using liquid scintillation counting. Cells with medium (HCT8) and high (MDA-MB-468) EGFR expression were incubated with targeted ¹⁷⁷Lu-AuNPs for 4h, then washed and allowed to form colonies. Nude mice bearing tumours were used to study the biodistribution by injecting ¹⁷⁷Lu-AuNPs or ⁹⁰Y-AuNPs via the tail vein. Heterogeneity of dose-distribution in tumours was determined using autoradiography. Results: Colony formation (% control) was 81 ± 4.7% (HCT8) and 32 ± 9% (MDA-MB-468). High uptake was observed in the liver and spleen, indicating hepatobiliary excretion. Imaging showed heterogeneity in dose-distributions for both radionuclides across the tumours. Conclusion: The cytotoxic effect of EGFR-targeted AuNPs is greater in cells with higher EGFR expression. Dose-distributions for individual radiolabelled nanoparticles were heterogeneous across tumours. Further strategies are required to improve the uniformity of dose distribution prior to clinical trials.

Keywords: cancer cells, dose distributions, radionuclide therapy, targeted gold nanoparticles

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Authors: Eun Ho Kim

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Innovations have conjured up a mode of treating GBM cancer cells in the newly diagnosed patients in a period of 4.9 months at an improved median OS, which brings along only a few minor side effects in the phase III of the clinical trial. This mode has been termed the Alternating Electric Fields (AEF). The study at hand is aimed at determining whether the AEF treatment is beneficial in sensitizing the GBM cancer cells through the process of increasing the AEF –induced senescence. The methodology to obtain the findings for this research ranged across various components, such as obtaining and testing SA-β-gal staining, flow cytometry, Western blotting, morphology, and Positron Emission Tomography (PET) / Computed Tomography (CT), immunohistochemical staining and microarray. The number of cells that displayed a senescence-specific morphology and positive SA-ß-Gal activity gradually increased up to 5 days. These results suggest that p16, p21 and p27 are essential regulators of AEF -induced senescence via NF-κB activation. The results showed that the AEF treatment is functional in enhancing the AEF –induced senescence in the GBM cells via an apoptosis- independent mechanism. This research concludes that this mode of treatment is a trustworthy protocol that can be effectively employed to overcome the limitations of the conventional mode of treatment on GBM.

Keywords: alternating electric fields, senescence, glioblastoma, cell death

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Authors: Jia Yin Tan, Daniel Rambei, Kate Mann, Samuel price, Ahmed Aboelela

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Introduction: Breastfeeding is a complex process, influenced by various factors. Tongue-tie may lead to breastfeeding difficulties due to an inability to suck effectively, causing sore nipples and poor infant weight gain. In the UK, most frenotomies on infants are performed by doctors, nurses, health visitors or midwives. Objectives: Evaluation of safety and efficacy of a multispecialty nurse-led rapid access tongue-tie service at Sheffield Children’s Hospital, run jointly by the ENT and paediatric surgery departments. Methodology: A retrospective observational study, including all patients attending the ENT and paediatric surgery nurse-led tongue tie clinics between 1/10/2021 and 30/09/2022. Results: During the study period there were 1135 referrals for frenotomy, with a mean of 15 days between referral to clinic episode. 86.8% of referred patients underwent frenotomy, with a complication rate of 0.1% and revision rate of 5.4%. Conclusions: Our findings suggest that our rapid access nurse-led outpatient tongue tie service is safe and efficacious, with low complication and revision rates. This suggests a potential for developing a community-based service, allowing safe and effective care closer to home.

Keywords: tongue tie, frenotomy, cost, nurse-led

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Authors: Özgür Bahadir, Meltem Kurtuncu

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The study was designed as quasi-experimental and conducted to determine the effect of music therapy on anxiety, fear and pain management in 6-12-year-old children undergoing surgery. The present study was carried out between 01.01.2016 and 19.08.2016 in BEU. Application and Research Center. The children aged 6 -12 who applied for surgery between the mentioned dates constituted the universe of the study. In the quasi-experimental study that was conducted in the clinics where children received operational treatment, two groups were formed: experimental group (the children who received musical therapy before the surgery) and control group (the children who were administered surveys and the surgery service routines only). Each group consisted of 30 children, and the participants of the study were 60 children in total. Necessary permissions were obtained from the parents of the children hospitalized before the beginning of the implementation. The data was collected through Child Anxiety Sensitivity Index (CASI), “Fear In Medical Treatment Scale”, Face, Legs, Activity, Cry, Consolability Scale (FLACC), Visual Analog Scale (VAS) and Participant Information Form. In the analysis of the data, Kolmogorov-Smirnov distribution scale was used to examine the normality of the distribution along with descriptive statistics methods (Frequency, Percentage, Mean, Standard Deviation). Data was presented in the tables in numbers and percentages. Means were demonstrated along with the standard deviations. The research compared children received; case and control groups include socio-demographic perspective, non-significant difference statistically among similar groups are intertwined. The general level of fear regarding the medical processes before returning to service after the operation and 30 minutes before getting discharged was found to be significantly low in the experimental group compared to control group (p<0.05). No statistically significant difference was found between experimental and control groups in terms of general level of fear regarding the medical processes before the operation, during the operation day and in the recovery room after the operation (p>0.05). Total CASI AD (anxiety sensitivity) levels before the operation, day of the operation and 30 minutes before the discharge for patients in experimental group was found to be significantly higher than the control group (p>0.05). There was no statistically significant difference between the experimental and control groups in the total CASI AD levels for the post-operative recovery room and for returning to the service room after the operation (p>0.05). VAS levels for patients in the experimental group in the post-operative recovery room was significantly higher than the control group (p>0.05). There was no statistically significant difference between the groups in terms of VAS findings in returning to service room after the operation and in 30 minutes before the discharge (p>0.05). As a result of the research; applied children music therapy in the experimental group anxiety, fear, and pain of the scales, their scores average, is lower than the control group children in this situation an increase in the satisfaction of children and parents was observed. In line with this, music therapy preoperative anxiety, fear, and can be used as an effective method of decreasing postoperative pain clinics is suggested.

Keywords: anxiety, children, fear, music therapy, pain

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Authors: Nicholas Fletcher, Zachary Houston, Yongmei Zhao, Christopher Howard, Kristofer Thurecht

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One promising approach to enhance nanomedicine therapeutic efficacy is to include a targeting agent, such as an antibody, to increase accumulation at the tumor site. However, the application of such targeted nanomedicines remains limited, in part due to difficulties involved with biomolecule conjugation to synthetic nanomaterials. One approach recently developed to overcome this has been to engineer bispecific antibodies (BsAbs) with dual specificity, whereby one portion binds to methoxy polyethyleneglycol (mPEG) epitopes present on synthetic nanomedicines, while the other binds to molecular disease markers of interest. In this way, noncovalent complexes of nanomedicine core, comprising a hyperbranched polymer (HBP) of primarily mPEG, decorated with targeting ligands are able to be produced by simple mixing. Further work in this area has now demonstrated such complexes targeting the breast cancer marker epidermal growth factor receptor (EGFR) to show enhanced binding to tumor cells both in vitro and in vivo. Indeed the enhanced accumulation at the tumor site resulted in improved therapeutic outcomes compared to untargeted nanomedicines and free chemotherapeutics. The current work on these BsAb-HBP conjugates focuses on further probing antibody-nanomaterial interactions and demonstrating broad applicability to a range of cancer types. Herein are reported BsAb-HBP materials targeted towards prostate-specific membrane antigen (PSMA) and study of their behavior in vivo using ⁸⁹Zr positron emission tomography (PET) in a dual-tumor prostate cancer xenograft model. In this model mice bearing both PSMA+ and PSMA- tumors allow for PET imaging to discriminate between nonspecific and targeted uptake in tumors, and better quantify the increased accumulation following BsAb conjugation. Also examined is the potential for formation of these targeted complexes in situ following injection of individual components? The aim of this approach being to avoid undesirable clearance of proteinaceous complexes upon injection limiting available therapeutic. Ultimately these results demonstrate BsAb functionalized nanomaterials as a powerful and versatile approach for producing targeted nanomedicines for a variety of cancers.

Keywords: bioengineering, cancer, nanomedicine, polymer chemistry

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Authors: Ilirian Laçi, Alketa Spahiu

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Ageing causes an increase in the number of patients with spinal canal stenosis. Most of the patients have back pain, leg pain, numbness of the legs, as well as urinary incontinence as a very common symptoms. Urinary incontinence impairs the quality of life. Correction of the symptom of urinary incontinence is possible in the early and adequate treatment of spinal stenosis. Methods: This study observed patients with urinary incontinence and spinal canal stenosis. These patients underwent mechanical decompression of the spinal stenosis through surgery. At the same time, these patients were observed clinically with clinical consultations. Cystoscopy and urodynamic tests were conducted at intervals of 2 and 6 months. As a result of treatment, 60% of patients did recover. The patients in this group who benefit from treatment were the patients who were early diagnosed and treated. Conclusions: An important factor in the prognosis of this pathology is the early diagnosis and treatment. The proper treatment of this pathology makes it curable in most cases. An important role in this pathology is played by the neurosurgeon. Surgery accompanied by laminotomy and mechanical decompression is the best way of treatment. Other factors that played a role in this pathology are also a large number of childbirths for women, obesity, etc.

Keywords: urinary incontinence, quality of life, spinal canal stenosis, early diagnosis, treatment

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Authors: Chaoran Liu

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Bioactive polysaccharides and polysaccharide-protein complex derived from mushrooms and fungi have a wide range of immunomodulatory activity with low side-effects and have therefore the potential to be developed as an adjuvant in cancer therapies. Mushrooms sclerotium is rich in polysaccharides and the polysaccharides isolated from the sclerotium of Polyporus rhinocerus have shown potent in vivo and in vitro immunomodulatory effects. Macrophages are considered to be an important component of the innate immune response against bacterial infection and cancer. To better understanding the immunomodulatory effects and its underlying mechanisms of sclerotial water-soluble polysaccharides extracted from P. rhinocerus on macrophages, the objectives of this study are to purify the water-soluble novel sclerotial polysaccharides and to characterize the structure and properties as well as to study the detailed molecular mechanisms of the in vitro immunomodulating effects in murine macrophages. The hot water-soluble fraction PRW from the sclerotium of P. rhinocerus was obtained using solvent extraction. PRW was further fractionated by membrane ultrafiltration to a give a fraction (PRW1) with molecular mass less than 50 kDa. PRW1 was characterized to be a polysaccharide-protein complex composed of 45.7% polysaccharide and 44.2% protein. The chemical structure of the carbohydrate moiety of PRW1 was elucidated by GC and FTIR to be mainly beta-D-glucan with trace amount of galactose and mannose. The immunomodulatory effects of PRW1 on murine RAW 264.7 macrophages were demonstrated in terms of the increase in nitric oxide production and cytokine production. Mechanistically, PRW1 initiates ERK phosphorylation to activate macrophages within 15 min and significantly improves the expression level of inducible NOS (iNOS) from 6 h after treatment. In summary, this study indicates that PRW1 is a potent immunomodulatory agent for macrophages and suggests that mushroom sclerotia from Polyporus rhinocerus requires for further investigation in cancer research.

Keywords: Polyporus rhinocerus, mushroom sclerotia, Polysaccharide-Protein Complex, macrophage activation

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Authors: Daniel Hyun

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Dental implants are one of the top 3 reasons to sue a dentist for malpractice. It involves dental implant complications, usually because of the angle of the implant from the surgery. At present, surgeons usually use a 3D-printed navigator that is customized for the patient’s teeth. However, those can’t be reused for other patients as they require time. Therefore, I made a guiding device to assist the surgeon in implant operations. The surgeon can input the objective of the operation, and the device constantly checks if the surgery is heading towards the objective within the set range, telling the surgeon by manipulating the LED. We tested the prototypes’ consistency and accuracy by checking the graph, average standard deviation, and the average change of the calculated angles. The accuracy of performance was also acquired by running the device and checking the outputs. My first prototype used accelerometer and gyroscope sensors from the Arduino MPU6050 sensor, getting a changeable graph, achieving 0.0295 of standard deviations, 0.25 of average change, and 66.6% accuracy of performance. The second prototype used only the gyroscope, and it got a constant graph, achieved 0.0062 of standard deviation, 0.075 of average change, and 100% accuracy of performance, indicating that the accelerometer sensor aggravated the functionality of the device. Using the gyroscope sensor allowed it to measure the orientations of separate axes without affecting each other and also increased the stability and accuracy of the measurements.

Keywords: implant, guide, accelerometer, gyroscope, handpiece

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Authors: Rui Chen, Jinfeng Zhang, Chun-Sing Lee

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In the past couple of decades, nanoscale metal-organic frameworks (NMOFs) have been highlighted as promising delivery platforms for biomedical applications, which combine many potent features such as high loading capacity, progressive biodegradability and low cytotoxicity. While NMOF has been extensively used as carriers for drugs of different modalities, so far there is no report on exploiting the advantages of NMOF for combination therapy. Herein, we prepared core-shell nanoparticles, where each nanoparticle contains a single graphitic-phase carbon nitride (g-C3N4) nanosheet encapsulated by a zeolitic-imidazolate frameworks-8 (ZIF-8) shell. The g-C3N4 nanosheets are effective visible-light photosensitizer for photodynamic therapy (PDT). When hosting DOX (doxorubicin), the as-synthesized core-shell nanoparticles could realize combinational photo-chemo therapy and provide dual-color fluorescence imaging. Therefore, we expect NMOFs-based core-shell nanoparticles could provide a new way to achieve much-enhanced cancer therapy.

Keywords: carbon nitride, combination therapy, drug delivery, nanoscale metal-organic frameworks

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Authors: Ravshan A. Ibadov, Sardor Kh. Ibragimov

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Objective. The aim of the study was to optimize the protocol of cardiopulmonary resuscitation (CPR) after cardiovascular surgical interventions. Methods. The experience of CPR conducted on patients after cardiovascular surgical interventions in the Department of Intensive Care and Resuscitation (DIR) of the Republican Specialized Scientific-Practical Medical Center of Surgery named after Academician V. Vakhidov is presented. The key to the new approach is the rapid elimination of reversible causes of cardiac arrest, followed by either defibrillation or electrical cardioversion (depending on the situation) before external heart compression, which may damage sternotomy. Careful use of adrenaline is emphasized due to the potential recurrence of hypertension, and timely resternotomy (within 5 minutes) is performed to ensure optimal cerebral perfusion through direct massage. Out of 32 patients, cardiac arrest in the form of asystole was observed in 16 (50%), with hypoxemia as the cause, while the remaining 16 (50%) experienced ventricular fibrillation caused by arrhythmogenic reactions. The age of the patients ranged from 6 to 60 years. All patients were evaluated before the operation using the ASA and EuroSCORE scales, falling into the moderate-risk group (3-5 points). CPR was conducted for cardiac activity restoration according to the American Heart Association and European Resuscitation Council guidelines (Ley SJ. Standards for Resuscitation After Cardiac Surgery. Critical Care Nurse. 2015;35(2):30-38). The duration of CPR ranged from 8 to 50 minutes. The ARASNE II scale was used to assess the severity of patients' conditions after CPR, and the Glasgow Coma Scale was employed to evaluate patients' consciousness after the restoration of cardiac activity and sedation withdrawal. Results. In all patients, immediate chest compressions of the necessary depth (4-5 cm) at a frequency of 100-120 compressions per minute were initiated upon detection of cardiac arrest. Regardless of the type of cardiac arrest, defibrillation with a manual defibrillator was performed 3-5 minutes later, and adrenaline was administered in doses ranging from 100 to 300 mcg. Persistent ventricular fibrillation was also treated with antiarrhythmic therapy (amiodarone, lidocaine). If necessary, infusion of inotropes and vasopressors was used, and for the prevention of brain edema and the restoration of adequate neurostatus within 1-3 days, sedation, a magnesium-lidocaine mixture, mechanical intranasal cooling of the brain stem, and neuroprotective drugs were employed. A coordinated effort by the resuscitation team and proper role allocation within the team were essential for effective cardiopulmonary resuscitation (CPR). All these measures contributed to the improvement of CPR outcomes. Conclusion. Successful CPR following cardiac surgical interventions involves interdisciplinary collaboration. The application of an optimized CPR standard leads to a reduction in mortality rates and favorable neurological outcomes.

Keywords: cardiac surgery, cardiac arrest, resuscitation, critically ill patients

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Authors: Oliveira M., Gonçalves L., Francisco I., Caramelo F., Vale F., Sanz D., Domingues M., Lopes M., Moreia D., Lopes T., Santos T., Cardoso H.

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The ARTHUR project consists of a platform that allows the virtual performance of maxillofacial surgeries, offering, in a photorealistic concept, the possibility for the patient to have an idea of the surgical changes before they are performed on their face. For this, the system brings together several image formats, dicoms and objs that, after loading, will generate the bone volume, soft tissues and hard tissues. The system also incorporates the patient's stereophotogrammetry, in addition to their data and clinical history. After loading and inserting data, the clinician can virtually perform the surgical operation and present the final result to the patient, generating a new facial surface that contemplates the changes made in the bone and tissues of the maxillary area. This tool acts in different situations that require facial reconstruction, however this project focuses specifically on two types of use cases: bone congenital disfigurement and acquired disfiguration such as oral cancer with bone attainment. Being developed a cloud based solution, with mobile support, the tool aims to reduce the decision time window of patient. Because the current simulations are not realistic or, if realistic, need time due to the need of building plaster models, patient rates on decision, rely on a long time window (1,2 months), because they don’t identify themselves with the presented surgical outcome. On the other hand, this planning was performed time based on average estimated values of the position of the maxilla and mandible. The team was based on averages of the facial measurements of the population, without specifying racial variability, so the proposed solution was not adjusted to the real individual physiognomic needs.

Keywords: 3D computing, image processing, image registry, image reconstruction

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Authors: Saule Balmagambetova, Zhenisgul Tlegenova, Saule Madinova

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Cardiotoxicity associated with anticancer treatment, now defined as cancer therapy-related cardiac dysfunction (CTRCD), accompanies cancer patients and negatively impacts their survivorship. Currently, a cardio-oncological service is being created in Kazakhstan based on the provisions of the European Society of Cardio-oncology (ESC) Guidelines. In the frames of a pilot project, a cohort study on CTRCD conditions was initiated at the Aktobe Cancer center. One hundred twenty-eight newly diagnosed breast cancer patients started on doxorubicin and/or trastuzumab were recruited. Echocardiography with global longitudinal strain (GLS) assessment, biomarkers panel (cardiac troponin (cTnI), brain natriuretic peptide (BNP), myeloperoxidase (MPO), galectin-3 (Gal-3), D-dimers, C-reactive protein (CRP)), and other tests were performed at baseline and every three months. Patients were stratified by the cardiovascular risks according to the ESC recommendations and allocated into the risk groups during the pre-treatment visit. Of them, 10 (7.8%) patients were assigned to the high-risk group, 48 (37.5%) to the medium-risk group, and 70 (54.7%) to the low-risk group, respectively. High-risk patients have been receiving their cardioprotective treatment from the outset. Patients were also divided by treatment - in the anthracycline-based 83 (64.8%), in trastuzumab- only 13 (10.2%), and in the mixed anthracycline/trastuzumab group 32 individuals (25%), respectively. Mild symptomatic CTRCD was revealed and treated in 2 (1.6%) participants, and a mild asymptomatic variant in 26 (20.5%). Mild asymptomatic conditions are defined as left ventricular ejection fraction (LVEF) ≥50% and further relative reduction in GLS by >15% from baseline and/or a further rise in cardiac biomarkers. The listed biomarkers were assessed longitudinally in repeated-measures linear regression models during 12 months of observation. The associations between changes in biomarkers and CTRCD and between changes in biomarkers and LVEF were evaluated. Analysis by risk groups revealed statistically significant differences in baseline LVEF scores (p 0.001), BNP (p 0.0075), and Gal-3 (p 0.0073). Treatment groups found no statistically significant differences at baseline. After 12 months of follow-up, only LVEF values showed a statistically significant difference by risk groups (p 0.0011). When assessing the temporal changes in the studied parameters for all treatment groups, there were statistically significant changes from visit to visit for LVEF (p 0.003); GLS (p 0.0001); BNP (p<0.00001); MPO (p<0.0001); and Gal-3 (p<0.0001). No moderate or strong correlations were found between the biomarkers values and LVEF, between biomarkers and GLS. Between the biomarkers themselves, a moderate, close to strong correlation was established between cTnI and D-dimer (r 0.65, p<0.05). The dose-dependent effect of anthracyclines has been confirmed: the summary dose has a moderate negative impact on GLS values: -r 0.31 for all treatment groups (p<0.05). The present study found myeloperoxidase as a promising biomarker of cardiac dysfunction in the mixed anthracycline/trastuzumab treatment group. The hazard of CTRCD increased by 24% (HR 1.21; 95% CI 1.01;1.73) per doubling in baseline MPO value (p 0.041). Increases in BNP were also associated with CTRCD (HR per doubling, 1.22; 95% CI 1.12;1.69). No cases of chemotherapy discontinuation due to cardiotoxic complications have been recorded. Further observations are needed to gain insight into the ability of biomarkers to predict CTRCD onset.

Keywords: breast cancer, chemotherapy, cardiotoxicity, Kazakhstan

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Authors: Chutamas Thepmalee, Aussara Panya, Mutita Junking, Jatuporn Sujjitjoon, Nunghathai Sawasdee, Pa-Thai Yenchitsomanus

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Cholangiocarcinoma (CCA) is an aggressive malignancy of bile duct epithelial cells in which the standard treatments, including surgery, radiotherapy, chemotherapy, and targeted therapy are partially effective. Many solid tumors including CCA escape host immune responses by creating tumor microenvironment and generating immunosuppressive cytokines such as interleukin-10 (IL-10) and transforming growth factor-β (TGF-β). These cytokines can inhibit dendritic cell (DC) differentiation and function, leading to decreased activation and response of effector CD4+ and CD8+ T cells for cancer cell elimination. To overcome the effects of these immunosuppressive cytokines and to increase ability of DC to activate effector CD4+ and CD8+ T cells, we generated self-differentiated DCs (SD-DCs) with down-regulation of IL-10 and TGF-β receptors for activation of effector CD4+ and CD8+ T cells. Human peripheral blood monocytes were initially transduced with lentiviral particles containing the genes encoding GM-CSF and IL-4 and then secondly transduced with lentiviral particles containing short-hairpin RNAs (shRNAs) to knock-down mRNAs of IL-10 and TGF-β receptors. The generated SD-DCs showed up-regulation of MHC class II (HLA-DR) and co-stimulatory molecules (CD40 and CD86), comparable to those of DCs generated by convention method. Suppression of IL-10 and TGF-β receptors on SD-DCs by specific shRNAs significantly increased levels of IFN-γ and also increased cytolytic activity of DC-activated effector T cells against CCA cell lines (KKU-213 and KKU-100), but it had little effect to immortalized cholangiocytes (MMNK-1). Thus, SD-DCs with down-regulation of IL-10 and TGF-β receptors increased activation of effector T cells, which is a recommended method to improve DC function for the preparation of DC-activated effector T cells for adoptive T-cell therapy.

Keywords: cholangiocarcinoma, IL-10 receptor, self-differentiated dendritic cells, TGF-β receptor

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Authors: Pranporn Kuropakornpong, Srisopa Ruangnoo, Arunporn Itharat

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Liver cancer has the highest prevalence rate in the North and Northeast of Thailand. Four Thai medicinal plants such as resin of Ferula asafoetida Regel, latex of Aloe barbadensis Miller leaves, roots of Baliospermum manotanum, and latex of Garcinia hanburyi Hook are used in Thai traditional medicine as cathartic drug and detoxification in liver cancer patients. Thus, this research aimed to evaluate the cytotoxic activity of these plants against hepatocarcinoma (HepG2) and cholangiocarcinoma (KKU-M156) cells by SRB assay. These plants were macerated in 95% ethanol. The results showed that roots of Baliospermum manotanum and latex of Garcinia hanburyi Hook showed the strongest cytotoxicity against HepG2 (IC50 = 3.03+0.91 and 0.62+0.01µg/ml, respectively) and KKU-M156 (IC50 = 0.978+0.663 and 0.006+0.005 µg/ml, respectively). Latex of Garcinia hanburyi Hook also showed high cytotoxicity against normal cell line (IC50=8.86+0.31 µg/ml), and even though its selective values are high, dose of this herb should be limited.

Keywords: cholangiocarcinoma, cytotoxic activity, Garcinia hanburyi Hook, hepatocarcinoma

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Authors: T. N. Goh, M. Hashmi, O. Hussain

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Temporomandibular joint (TMJ) dysfunction (TMD) is a condition that may affect patients via restricted mouth opening, significant pain during normal functioning, and/or reproducible joint noise. TMD includes myofascial pain, TMJ functional derangements (internal derangement, dislocation), and TMJ degenerative/inflammatory joint disease. Internal derangement (ID) is the most common cause of TMD-related clicking and locking. These patients are managed in a stepwise approach, from patient education (homecare advice and analgesia), splint therapy, physiotherapy, botulinum toxin treatment, to arthrocentesis. Arthrotomy is offered when the aforementioned treatment options fail to alleviate symptoms and improve quality of life. The aim of this prospective study was to review the outcomes of jaw joint open surgery in TMD patients. Patients who presented from 2015-2022 at the Oral and Maxillofacial Surgery Department in the Doncaster NHS Foundation Trust, UK, with a Wilkes classification of III -V were included. These patients underwent either i) discopexy with bone-anchoring suture (9); ii) intrapositional temporalis flap (ITF) with bone-anchoring suture (3); iii) eminoplasty and discopexy with suturing to the capsule (3); iii) discectomy + ITF with bone-anchoring suture (1); iv) discoplasty + bone-anchoring suture (1); v) ITF (1). Maximum incisal opening (MIO) was assessed pre-operatively and at each follow-up. Pain score, determined via the visual analogue scale (VAS, with 0 being no pain and 10 being the worst pain), was also recorded. A total of 18 eligible patients were identified with a mean age of 45 (range 22 - 79), of which 16 were female. The patients were scored by Wilkes Classification as III (14), IV (1), or V (4). Twelve patients had anterior disc displacement without reduction (66%) and six had degenerative/arthritic changes (33%) to the TMJ. The open joint procedure resulted in an increase in MIO and reduction in pain VAS and for the majority of patients, across all Wilkes Classifications. Pre-procedural MIO was 22.9 ± 7.4 mm and VAS was 7.8 ± 1.5. At three months post-procedure there was an increase in MIO to 34.4 ± 10.4 mm (p < 0.01) and a decrease in the VAS to 1.5 ± 2.9 (p < 0.01). Three patients were lost to follow-up prior to six months. Six were discharged at six month review and five patients were discharged at 12 months review as they were asymptomatic with good mouth opening. Four patients are still attending for annual botulinum toxin treatment. Two patients (Wilkes III and V) subsequently underwent TMJ replacement (11%). One of these patients (Wilkes III) had improvement initially to MIO of 40 mm, but subsequently relapsed to less than 20 mm due to lack of compliance with jaw rehabilitation device post-operatively. Clinical improvements in 89% of patients within the study group were found, with a return to near normal MIO range and reduced pain score. Intraoperatively, the operator found bone-anchoring suture used for discopexy/discoplasty more secure than the soft tissue anchoring suturing technique.

Keywords: bone anchoring suture, open temporomandibular joint surgery, temporomandibular joint, temporomandibular joint dysfunction

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Authors: Warda Jabeen, Romaisa Shamim Khan, Osama Shakeel, Ahmed Faraz Bhatti, Raza Hussain

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Background: The worldwide incidence of cutaneous melanoma (CM) has been on the rise over the past few decades. Primary prevention and early treatment remain the focus of management to reduce the burden of disease. This entails identification of risk factors to prompt early diagnosis. In Pakistan, there is a scarcity of clinico-pathological data relating to cutaneous malignant melanoma. Objective: The purpose of this study was to analyze the epidemiological and clinical characteristics of patients presenting with cutaneous malignant melanoma in Pakistan, and to compare the results with other studies. Method: Shaukat Khanum Memorial Cancer Hospital and Research Centre is currently the only dedicated cancer hospital in the country, accepting patients from all over Pakistan. Majority of the patients, however, belong to the northern half of the country. From the recorded data of the hospital, all cutaneous melanoma cases were identified and evaluated. Results: Between 1997 and 2017, a total of 169 cutaneous melanoma patients were registered at Shaukat Khanum. Mean age was 47.5 years. The highest incidence of melanoma was seen in the age group 40-59 years (n=69, 40.8%). Most commonly reported clinical subtype was unspecified melanoma (n=154, 91%). Amongst those in which T stage was reported, the most frequently observed T-stage at presentation was T4 (n=23, 13.6%). With regards to body distribution, in our study CM was seen most commonly in the lower limb including the hip. The yearly incidence of melanoma has increased/remained stable from 2007 to 2017. Conclusion: cutaneous malignant melanoma is a fairly common disease in Pakistan. Patients tend to present at a more advanced stage as compared to patients in developed countries. Identification of risk factors and tumor characteristics is therefore of paramount importance to deal with these patients.

Keywords: epidemiology of cutaneous malignant melanoma, cutaneous malignant melanoma, Pakistan, skin cancer

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Authors: Shiva Naidoo, Kristena Yossef, Grimm Jimm, Mirza Wasique, Eric Kemmerer, Joshua Obuch, Anand Mahadevan

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Background: Fiducial markers effectively enhance tumor target visibility prior to Stereotactic Body Radiation Therapy or Proton therapy. To streamline clinical practice, fiducial placement guidelines from a robotic radiosurgery vendor were examined with the goals of optimizing and standardizing feasible geometries for each treatment indication. Clinical examples of prostate, renal, and pancreatic cases are presented. Methods: Vendor guidelines (Accuray, Sunnyvale, Ca) suggest implantation of 4–6 fiducials at least 20 mm apart, with at least a 15-degree angular difference between fiducials, within 50 mm or less from the target centroid, to ensure that any potential fiducial motion (e.g., from respiration or abdominal/pelvic pressures) will mimic target motion. Also recommended is that all fiducials can be seen in 45-degree oblique views with no overlap to coincide with the robotic radiosurgery imaging planes. For the prostate, a standardized geometry that meets all these objectives is a 2 cm-by-2 cm square in the coronal plane. The transperineal implant of two pairs of preloaded tandem fiducials makes the 2 cm-by-2 cm square geometry clinically feasible. This technique may be applied for renal cancer, except repositioned in a sagittal plane, with the retroperitoneal placement of the fiducials into the tumor. Pancreatic fiducial placement via endoscopic ultrasound (EUS) is technically more challenging, as fiducial placement is operator-dependent, and lesion access may be limited by adjacent vasculature, tumor location, or restricted mobility of the EUS probe in the duodenum. Fluoroscopically assisted fiducial placement during EUS can help ensure fiducial markers are deployed with optimal geometry and visualization. Results: Among the first 22 fiducial cases on a newly installed robotic radiosurgery system, live x-ray images for all nine prostatic cases had excellent fiducial visualization at the treatment console. Renal and pancreatic fiducials were not as clearly visible due to difficult target access and smaller caliber insertion needle/fiducial usage. The geometry of the first prostate case was used to ensure accurate geometric marker placement for the remaining 8 cases. Initially, some of the renal and pancreatic fiducials were closer than the 20 mm recommendation, and interactive feedback with the proceduralists led to subsequent fiducials being too far to the edge of the tumor. Further feedback and discussion of all cases are being used to help guide standardized geometries and achieve ideal fiducial placement. Conclusion: The ideal tradeoffs of fiducial visibility versus the thinnest possible gauge needle to avoid complications needs to be systematically optimized among all patients, particularly in regards to body habitus. Multidisciplinary collaboration among proceduralists and radiation oncologists can lead to improved outcomes.

Keywords: fiducial, prostate cancer, renal cancer, pancreatic cancer, radiotherapy

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Authors: Salehah Tahkin, Norlaila Mustafa, Dayang Anita Abdul Aziz

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Knowledge of medical ethics is important to all practitioners so the best care can be delivered to all patients through safe practice. Surgeons are not exceptions to this. Knowledge, attitude, and practice (KAP) of medical ethics among paediatric surgeons and trainees in Malaysia has not been evaluated before. This study aims to determine the level of KAP regarding medical ethics among these groups. This was a cross-sectional study involving three groups of samples, i.e., paediatric surgeons (PS), paediatric surgical trainees (PST), and medical officers with a special interest in paediatric surgery (MO). A validated KAP questionnaire was used. Standard formulas were used to calculate objective indexes for measuring KAP, which were then compared for statistical significance across different sample groups; p less than 0.05 is taken as significant. The index is rated into 5 classes using a score of 0 to 10, i.e., poor (1-2.99), fair (3-4.99), good (5-6.99), very good (7-8.99), and excellent (9-10). There were 117 samples, i.e., PS n=45 (38.5%), PST n=25 (21.3%), and MO n=47 (40.2%). For knowledge, all three groups display a good index score (mean score of 5.44). For attitude, PS and MO also display an index score of good (mean score of 5.81), while the PST index score was fair (4.82). For practice, our study shows a highest score of 7.14 (very good) among PST. However, these differences were not statistically significant (p> 0.05). Conclusion: Training in paediatric surgery must continue to emphasize professionalism and medical ethics education to deliver the best health care services.

Keywords: KAP, medical ethics, paediatric, surgeons, trainees

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Authors: Caren Hilger, Silke Burkert, Friederike Kendel

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Men with localized prostate cancer (PCa) have to choose among different treatment options, such as active surveillance (AS) and radical prostatectomy (RP). All available treatment options may be accompanied by specific psychological or physiological side effects. Depending on the nature and extent of these side effects, patients are more or less likely to be satisfied or to struggle with their treatment decision in the long term. Therefore, the aim of this study was to assess and explain decisional regret in men with localized PCa. The role of erectile functioning as one of the main physiological side effects of invasive PCa treatment, depressive symptoms as a common psychological side effect, and the association of erectile functioning and depressive symptoms with decisional regret were investigated. Men with localized PCa initially managed with AS or RP (N=292) were matched according to length of therapy (mean 47.9±15.4 months). Subjects completed mailed questionnaires assessing decisional regret, changes in erectile functioning, depressive symptoms, and sociodemographic variables. Clinical data were obtained from case report forms. Differences among the two treatment groups (AS and RP) were calculated using t-tests and χ²-tests, relationships of decisional regret with erectile functioning and depressive symptoms were computed using multiple regression. Men were on average 70±7.2 years old. The two treatment groups differed markedly regarding decisional regret (p<.001, d=.50), changes in erectile functioning (p<.001, d=1.2), and depressive symptoms (p=.01, d=.30), with men after RP reporting higher values, respectively. Regression analyses showed that after adjustment for age, tumor risk category, and changes in erectile functioning, depressive symptoms were still significantly associated with decisional regret (B=0.52, p<.001). Additionally, when predicting decisional regret, the interaction of changes in erectile functioning and depressive symptoms reached significance for men after RP (B=0.52, p<.001), but not for men under AS (B=-0.16, p=.14). With increased changes in erectile functioning, the association of depressive symptoms with decisional regret became stronger in men after RP. Decisional regret is a phenomenon more prominent in men after RP than in men under AS. Erectile functioning and depressive symptoms interact in their prediction of decisional regret. Screening and treating depressive symptoms might constitute a starting point for interventions aiming to reduce decisional regret in this target group.

Keywords: active surveillance, decisional regret, depressive symptoms, erectile functioning, prostate cancer, radical prostatectomy

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Authors: Mehrnaz Mostafavi

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The assessment and categorization of incidental lung nodules present a considerable challenge in healthcare, often necessitating resource-intensive multiple computed tomography (CT) scans for growth confirmation. This research addresses this issue by introducing a distinct computational approach leveraging radiomics and deep-learning methods. However, understanding local services is essential before implementing these advancements. With diverse tracking methods in place, there is a need for efficient and accurate identification approaches, especially in the context of managing lung nodules alongside pre-existing cancer scenarios. This study explores the integration of text-based algorithms in medical data curation, indicating their efficacy in conjunction with machine learning and deep-learning models for identifying lung nodules. Combining medical images with text data has demonstrated superior data retrieval compared to using each modality independently. While deep learning and text analysis show potential in detecting previously missed nodules, challenges persist, such as increased false positives. The presented research introduces a Structured-Query-Language (SQL) algorithm designed for identifying pulmonary nodules in a tertiary cancer center, externally validated at another hospital. Leveraging natural language processing (NLP) and machine learning, the algorithm categorizes lung nodule reports based on sentence features, aiming to facilitate research and assess clinical pathways. The hypothesis posits that the algorithm can accurately identify lung nodule CT scans and predict concerning nodule features using machine-learning classifiers. Through a retrospective observational study spanning a decade, CT scan reports were collected, and an algorithm was developed to extract and classify data. Results underscore the complexity of lung nodule cohorts in cancer centers, emphasizing the importance of careful evaluation before assuming a metastatic origin. The SQL and NLP algorithms demonstrated high accuracy in identifying lung nodule sentences, indicating potential for local service evaluation and research dataset creation. Machine-learning models exhibited strong accuracy in predicting concerning changes in lung nodule scan reports. While limitations include variability in disease group attribution, the potential for correlation rather than causality in clinical findings, and the need for further external validation, the algorithm's accuracy and potential to support clinical decision-making and healthcare automation represent a significant stride in lung nodule management and research.

Keywords: lung cancer diagnosis, structured-query-language (SQL), natural language processing (NLP), machine learning, CT scans

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Authors: Bassam Band, Simon Freeman, Rohan Munir, Hisham Band

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Objective: To determine efficacy of facial physiotherapy provided for patients with facial nerve palsy. Design: Retrospective study Subjects: 54 patients diagnosed with Facial nerve palsy were included in the study after they met the selection criteria including unilateral facial paralysis and start of therapy twelve months after the onset of facial nerve palsy. Interventions: Patients received the treatment offered at a facial physiotherapy clinic consisting of: Trophic electrical stimulation, surface electromyography with biofeedback, neuromuscular re-education and myofascial release. Main measures: The Sunnybrook facial grading scale was used to evaluate the severity of facial paralysis. Results: This study demonstrated the positive impact of physiotherapy for patient with facial nerve palsy with improvement of 24.2% on the Sunnybrook facial grading score from a mean baseline of 34.2% to 58.2%. The greatest improvement looking at different causes was seen in patient who had reconstructive surgery post Acoustic Neuroma at 31.3%. Conclusion: The therapy shows significant improvement for patients with facial nerve palsy even when started 12 months post onset of paralysis across different causes. This highlights the benefit of this non-invasive technique in managing facial nerve paralysis and possibly preventing the need for surgery.

Keywords: facial nerve palsy, treatment, physiotherapy, bells palsy, acoustic neuroma, ramsey-hunt syndrome

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Authors: Reta

Abstract:

Coffee is widely consumed not only because of its typical taste, but coffee has antioxidant properties because of its polyphenols, and it stimulates brain's performance. The main problem with the consumption of coffee is its content of caffeine. Caffeine, when consumed in excess, can increase muscle tension, stimulate the heart, and increase the secretion of gastric acid. In this research, we applied ohmic-based fermentation technology, which is specially designed to mimic the stomach. We used Arabica coffee, which although cheaper than Luwak coffee, has high acidity, which needs to be reduced. Hence, we applied the ohmic technology, varied the time and temperature of the process and measured the total acidity of the coffee to determine optimum fermentation conditions. Results revealed total acidity of the coffee varied with fermentation conditions; 0.32% at 400C and 12 hr, and 0.52% at 400C and 6 hr. The longer the fermentation, the lower was the acidity. The acidity of the mongoose-fermented (natural fermentation) beans was 2.34%, which is substantially higher than the acidity of the ohmic samples. Ohmic-based fermentation technology, therefore, offers improvements in coffee quality, and this is discussed to highlight the potential of ohmic technology in coffee processing.

Keywords: ohmic technology, fermentation, coffee quality, Arabica coffee

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Authors: Akshay Patil

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Objective: Mediation analysis identifies causal pathways by testing the relationships between the NCR, the OS, and an intermediate variable that mediates the relationship between the Nimotuzumab-cisplatin-radiation (NCR) and OS. Introduction: In randomized controlled trials, the primary interest is in the mechanisms by which an intervention exerts its effects on the outcomes. Clinicians are often interested in how the intervention works (or why it does not work) through hypothesized causal mechanisms. In this work, we highlight the value of understanding causal mechanisms in randomized trial by applying causal mediation analysis in a randomized trial in oncology. Methods: Data was obtained from a phase III randomized trial (Subgroup of HPVNOCP). NCR is reported to significantly improve the OS of patients locally advanced head and neck cancer patients undergoing definitive chemoradiation. Here, based on trial data, the mediating effect of NCR on patient overall survival was systematically quantified through progression-free survival(PFS), disease free survival (DFS), Loco-regional failure (LRF), and the disease control rate (DCR), Overall response rate (ORR). Effects of potential mediators on the HR for OS with NCR versus cisplatin-radiation (CR) were analyzed by Cox regression models. Statistical analyses were performed using R software Version 3.6.3 (The R Foundation for Statistical Computing) Results: Effects of potential mediator PFS was an association between NCR treatment and OS, with an indirect-effect (IE) 0.76(0.62 – 0.95), which mediated 60.69% of the treatment effect. Taking into account baseline confounders, the overall adjusted hazard ratio of death was 0.64 (95% CI: 0.43 – 0.96; P=0.03). The DFS was also a significant mediator and had an IE 0.77 (95% CI; 0.62-0.93), 58% mediated). Smaller mediation effects (maximum 27%) were observed for LRF with IE 0.88(0.74 – 1.06). Both DCR and ORR mediated 10% and 15%, respectively, of the effect of NCR vs. CR on the OS with IE 0.65 (95% CI; 0.81 – 1.08) and 0.94(95% CI; 0.79 – 1.04). Conclusion: Our findings suggest that PFS and DFS were the most important mediators of the OS with nimotuzumab to weekly cisplatin-radiation in HPVNOCP.

Keywords: mediation analysis, cancer data, survival, NCR, HPV negative oropharyngeal

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Authors: Laila Salah Seada, Ashraf Ibrahim, Fawaz Al Rashid, Ihab Abdo, Hassan Kasim, Waleed Al Mansi, Saud Al Shabli

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Background and Objectives: Colorectal carcinoma is increasing among both men and women worldwide. It has a multifactorial etiology including genetic factors, environmental factors and inflammatory conditions of the digestive tract. A clinicopathologic assessment of colorectal carcinoma in Hail region is done, considering any changing patterns in two 5-year periods from 2005-2009 (A) and from 2012 to 2017 (B). All data had been retrieved from histopathology files of King Khalid Hospital, Hail. Results: During period (A), 75 cases were diagnosed as colorectal carcinoma. Male patients comprised 56/75 (74.7%) of the study, with a mean age of 58.4 (36-97), while females were 19/75 (25.3%) with a mean age of 50.3(30-85) and the difference was significant (p = 0.05). M:F ratio was 2.9:1. Most common histological type was adenocarcioma in 68/75 (90.7%) patients mostly well differentiated in 44/68 (64.7%). Mucinous neoplasms comprised only 7/75 (9.3%) of cases and tended to have a higher stage (p = 0.04). During period (B), 115 cases were diagnosed with an increase of 53.3% in number of cases than period (A). Male to female ratio also decreased to 1.35:1, females being 44.83% more affected. Adenocarcinoma remained the prevalent type (93.9%), while mucinous type was still rare (5.2%). No distal metastases found at time of presentation. Localization of tumors was rectosigmoid in group (A) in 41.4%, which increased to 56.6% in group (B), with an increase of 15.2%. Iliocecal location also decreased from 8% to 3.5%, being 56.25% less. Other proximal areas of the colon were decreased by 25.75%, from 53.9% in group (A) to 40% in group (B). Conclusion: Colorectal carcinoma in Hail region has increased by 53.3% in the past 5 years, with more females being diagnosed. Localization has also shifted distally by 15.2%. These findings are different from Western world patterns which experienced a decrease in incidence and proximal shift of the colon cancer localization. This might be due to better diagnostic tools, population awareness of the disease, as well as changing of life style and/or food habits in the region.

Keywords: colorectal cancer, Hail Region, changing pattern, distal shift

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Authors: Saidasanov Saidazal Shokhmurodovich, Topolnickiy Orest Zinovyevich, Afaunova Olga Arturovna

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Relevance: Bilateral congenital cleft is one of the most complex forms of all clefts, which makes it difficult to choose a surgical method of treatment. During primary operations to close the hard and soft palate, there is a shortage of soft tissues and their lack during standard uranoplasty, and these factors aggravate the period of rehabilitation of patients. Materials and methods: The results of surgical treatment of children with bilateral cleft, who underwent uranoplasty using a flap from the tongue, were analyzed. The study used methods: clinical and statistical, which allowed us to solve the tasks, based on the principles of evidence-based medicine. Results and discussion: in our study, 15 patients were studied, who underwent surgical treatment in the following volume: uranoplasty using a flap from the tongue in two stages. Of these, 9 boys and 6 girls aged 2.5 to 6 years. The first stage was surgical treatment in the volume: veloplasty. The second stage was a surgical intervention in volume: uranoplasty using a flap from the tongue. In all patients, the width of the cleft ranged from 1.6-2.8 cm. All patients in this group were orthodontically prepared. Using this method, the surgeon can achieve the following results: maximum narrowing of the palatopharyngeal ring, long soft palate, complete closure of the hard palate, alveolar process, and the mucous membrane of the nasal cavity is also sutured, which creates good conditions for the next stage of osteoplastic surgery. Based on the result obtained, patients have positive results of working with a speech therapist. In all patients, the dynamics were positive without complications. Conclusions: Based on our observation, tongue flap uranoplasty is one of the effective techniques for patients with wide clefts of the hard and soft palate. The use of a flap from the tongue makes it possible to reduce the number of repeated reoperations and improve the quality of social adaptation of this group of patients, which is one of the important stages of rehabilitation. Upon completion of the stages of rehabilitation, all patients had the maximum improvement in functional, anatomical and social indicators.

Keywords: congenital cleft lips and palate, bilateral cleft, child surgery, maxillofacial surgery

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Authors: Nuhi Arslani, Aleks Brumec

Abstract:

Adhesive small bowel obstruction (ASBO) accounts for 20% of emergency surgical procedures and intraabdominal adhesions account for 65% of such cases. In a 10-year post-operative period of abdominal surgery patients, around 35% of them will be readmitted because of ASBO. The first step in approaching ASBOs is using the Bologna guidelines, which include a thorough initial evaluation to diagnose or rule out an ASBO and then proceed with either further imaging studies or emergency surgery, which can be either open or laparoscopic. The contraindications for a laparoscopic approach include hemodynamic instability of the patient and infections in the peritoneum or port sites. Studies have shown that a laparoscopic approach to adhesiolysis is linked with a significantly smaller risk of readmissions and reoperations as well as with faster recovery time and fewer postoperative infections, but has a higher risk of bowel injuries, so a careful selection of patients is required. Although studies favor a laparoscopic approach, many countries still prefer a laparotomy, often because a laparoscopic approach requires surgeons to be highly skilled in the procedure. In the US and UK, between 50 and 60% of surgeons would approach an ASBO with laparoscopy, while in Italy, this number is around 15% and it is most likely similar in Slovenia. We believe that in the right cases and in the right patients, a laparoscopic approach can be equally feasible for treating ASBOs and is associated with fewer intraoperative and postoperative complications.

Keywords: adhesive small bowel obstruction, laparoscopy, adhesions, adhesiolysis

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