Search results for: thyroid tumor diagnosis

Authors: K. Mardaleishvili, G. Loladze, G. Shatirishivili, D. Chakhunashvili, A. Vishnevskaya, Z. Kakabadze

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Benign osteoblastoma is a benign tumor of the bone, usually affecting the vertebrae and long tubular bones. It is a rarely seen tumor of the facial bones. The authors present a case of a 28-year-old male patient with a tumor in mandibular body. The lesion was radically resected and histological analysis of the specimen demonstrated features typical of a benign osteoblastoma. The defect of the jaw was reconstructed with titanium implants and decellularized and lyophilized cattle bone matrix with mesenchymal bone marrow stem cells transplantation. This presentation describes the procedures for rehabilitating a patient with decellularized bone scaffold in the region of the face, recovering the facial contours and esthetics of the patient.

Keywords: facial bones, osteoblastoma, stem cells, transplantation

Procedia PDF Downloads 398

Authors: Chao Wu

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Thioredoxin reductase 2 is a mitochondrial enzyme that belongs to the cellular defense against oxidative stress. We deleted mitochondrial Txnrd2 in a KrasG12D-driven pancreatic tumor model. Despite an initial increase in precursor lesions, tumor incidence decreased significantly. We isolated cancer cell lines from these genetically engineered mice and observed an impaired proliferation and colony formation. Reactive Oxygen Species, as determined by DCF fluorescence, were increased. We detected a higher mitochondrial copy number in Txnrd2-deficient cells (KTP). However, measurement of mitochondrial bioenergetics showed no impairment of mitochondrial function and comparable O₂-consumption and extracellular acidification rates. In addition, the mitochondrial complex composition was affected in Txnrd2 deleted cell lines. To gain better insight into the role of Txnrd2, we deleted Txnrd2 in clones from parental KrasG12D cell lines using Crispr/Cas9 technology. The deletion was confirmed by western blot and activity assay. Interestingly, and in line with previous RNA expression analysis, we saw changes in EMT markers in Txnrd2 deleted cell lines and control cell lines. This might help us explain the reduced tumor incidence in KrasG12D; Txnrd2∆panc mice.

Keywords: PDAC, TXNRD2, epithelial-to-mesenchymal-transition, ROS

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Authors: Mateusz Bilski, Jakub Klas, Emilia Kowalczyk, Sylwia Koziej, Katarzyna Kulszo, Ludmiła Grzybowska- Szatkowska

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Background: Liver metastases are a common complication of primary solid tumors and sig-nificantly reduce patient survival. In the era of increasing diagnosis of oligometastatic disease and oligoprogression, methods of local treatment of metastases, i.e. MDT, are becoming more important. Implementation of such treatment can be considered for liver metastases, which are a common complication of primary solid tumors and significantly reduce patient survival. To date, the mainstay of treatment for oligometastatic disease has been surgical resection, but not all patients qualify for the procedure. As an alternative to surgical resection, radiotherapy techniques have become available, including stereotactic body radiation therapy (SBRT) or high-dose interstitial brachytherapy (iBT). iBT is an invasive method that emits very high doses of radiation from the inside of the tumor to the outside. This technique provides better tumor coverage than SBRT while having little impact on surrounding healthy tissue and elim-inates some concerns involving respiratory motion. Methods: We conducted a systematic re-view of the scientific literature on the use of brachytherapy in the treatment of liver metasta-ses from 2018 - 2023 using PubMed and ResearchGate browsers according to PRISMA rules. Results: From 111 articles, 18 publications containing information on 729 patients with liver metastases were selected. iBT has been shown to provide high rates of tumor control. Among 14 patients with 54 unresectable RCC liver metastases, after iBT LTC was 92.6% during a median follow-up of 10.2 months, PFS was 3.4 months. In analysis of 167 patients after treatment with a single fractional dose of 15-25 Gy with brachytherapy at 6- and 12-month follow-up, LRFS rates of 88,4-88.7% and 70.7 - 71,5%, PFS of 78.1 and 53.8%, and OS of 92.3 - 96.7% and 76,3% - 79.6%, respectively, were achieved. No serious complications were observed in all patients. Distant intrahepatic progression occurred later in patients with unre-sectable liver metastases after brachytherapy (PFS: 19.80 months) than in HCC patients (PFS: 13.50 months). A significant difference in LRFS between CRC patients (84.1% vs. 50.6%) and other histologies (92.4% vs. 92.4%) was noted, suggesting a higher treatment dose is necessary for CRC patients. The average target dose for metastatic colorectal cancer was 40 - 60 Gy (compared to 100 - 250 Gy for HCC). To better assess sensitivity to therapy and pre-dict side effects, it has been suggested that humoral mediators be evaluated. It was also shown that baseline levels of TNF-α, MCP-1 and VEGF, as well as NGF and CX3CL corre-lated with both tumor volume and radiation-induced liver damage, one of the most serious complications of iBT, indicating their potential role as biomarkers of therapy outcome. Con-clusions: The use of brachytherapy methods in the treatment of liver metastases of various cancers appears to be an interesting and relatively safe therapeutic method alternative to sur-gery. An important challenge remains the selection of an appropriate brachytherapy method and radiation dose for the corresponding initial tumor type from which the metastasis origi-nated.

Keywords: liver metastases, brachytherapy, CT-HDRBT, iBT

Procedia PDF Downloads 83

Authors: Amani Waheed, Mostafa Kofi, Shaymaa Attia, Soha Younis, Basma Abdel Hadi

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Background: Exposure to pesticides is one of the most important occupational risks among farmers in developing countries. Along with the wide use of pesticides in the world, the concerns over their health impacts are rapidly growing. Objective: To investigate thyroid and reproductive hormones and fasting blood glucose levels among farmers chronically exposed to pesticide from East Almnaif district, Ismailia governorate. Methods: An analytical cross-sectional study was conducted on 43 farmers with active involvement pesticides handling and 43 participants not occupationally exposed to pesticides as the control group. A structured interview questionnaire measuring the sociodemographic characteristics, pesticides exposure characteristics, and safety measures was used. General examination including measurements of height, weight, and blood pressure was done. Moreover, levels of plasma cholinesterase enzyme (PChE), glucose, as well as reproductive and thyroid hormones (TSH, T4, and testosterone) were determined. Results: There were no statistically significant differences between both groups regarding their age, educational level, smoking status, and body mass index. The mean duration of exposure was 20.60 11.06 years. Majority of farmers (76.7%) did not use any personal protective equipment (PPE) during pesticides handling. The mean systolic blood pressure among exposed farmers was greater (134.88 17.18 mm Hg) compared to control group (125 14.69 mm Hg) with statistically significant difference (p = 0.003). The mean diastolic blood pressure was higher (84.02 8.69 mm Hg) compared to control group (78.79 8.98 mm Hg) with statistically significant difference (p = 0.006). The pesticide exposed farmers had statistically significant lower level of PChE (3969.93 1841U/L) than control group (4879.29 1950.08 U/L). Additionally, TSH level was significantly higher in exposed farmers (median =1.39µIU/ml) compared to controls (median = 0.91 µIU/ml) (p=0.032). While, the exposed group had a lower T4 level (6.91 1.91 µg/dl) compared to the control group (7.79 2.10µg/dl), with the statistically significant difference between the two groups (p = 0.045). The exposed group had significantly lower level of testosterone hormone (median=3.37 ng/ml) compared to the control group (median= 6.22 ng/ml) (p=0.003). While, the exposed farmers had statistically insignificant higher level of fasting blood glucose (median =89 mg/dl) than the controls (median=88 mg/dl). Furthermore, farmers who did not use PPE had statistically significant lower level of T4 (6.57 1.81µg/dl) than farmers who used PPE during handling of pesticides (8.01 1.89 µg/dl). Conclusion: Chronic exposure to pesticides exerts disturbing action on reproductive function and thyroid function of the male farmers.

Keywords: chronic occupational pesticide exposure, Diabetes mellitus, male reproductive hormones, thyroid function

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Authors: Mohamed A. Hammad, Dzul Azri Mohamed Noor, Syed Azhar Syed Sulaiman, Majed Ahmed Al-Mansoub, Muhammad Qamar

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There is a progressive increase in the prevalence of early onset Type 2 diabetes mellitus. Early detection of Type 2 diabetes enhances the length and/or quality of life which might result from a reduction in the severity, frequency or prevent or delay of its long-term complications. The study aims to determine the onset age for the first diagnosis of Type 2 diabetes mellitus. A retrospective study conducted in the endocrine clinic at Hospital Pulau Pinang in Penang, Malaysia, January- December 2016. Records of 519 patients with Type 2 diabetes mellitus were screened to collect demographic data and determine the age of first-time diabetes mellitus diagnosis. Patients classified according to the age of diagnosis, gender, and ethnicity. The study included 519 patients with age (55.6±13.7) years, female 265 (51.1%) and male 254 (48.9%). The ethnicity distribution was Malay 191 (36.8%), Chinese 189 (36.4%) and Indian 139 (26.8%). The age of Type 2 diabetes diagnosis was (42±14.8) years. The female onset of diabetes mellitus was at age (41.5±13.7) years, while male (42.6±13.7) years. Distribution of diabetic onset by ethnicity was Malay at age (40.7±13.7) years, Chinese (43.2±13.7) years and Indian (42.3±13.7) years. Diabetic onset was classified by age as follow; ≤20 years’ cohort was 33 (6.4%) cases. Group >20- ≤40 years was 190 (36.6%) patients, and category >40- ≤60 years was 270 (52%) subjects. On the other hand, the group >60 years was 22 (4.2%) patients. The range of diagnosis was between 10 and 73 years old. Conclusion: Malay and female have an earlier onset of diabetes than Indian, Chinese and male. More than half of the patients had diabetes between 40 and 60 years old. Diabetes mellitus is becoming more common in younger age <40 years. The age at diagnosis of Type 2 diabetes mellitus has decreased with time.

Keywords: age of onset, diabetes diagnosis, diabetes mellitus, Malaysia, outpatients, type 2 diabetes, retrospective study

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Authors: B. S. Premalatha, Kausalya Sahani

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Background: Glomus jugulare tumors arise within the jugular foramen and are commonly seen in females particularly on the left side. Surgical excision of the tumor may cause lower cranial nerve deficits. Cranial nerve involvement produces hoarseness of voice, slurred speech, and dysphagia along with other physical symptoms, thereby affecting the quality of life of individuals. Though oncological clearance is mainly emphasized on while treating these individuals, little importance is given to their communication, voice and swallowing problems, which play a crucial part in daily functioning. Objective: To examine the functions of voice, speech and swallowing outcomes of the subjects, following excision of glomus jugulare tumor. Methods: Two female subjects aged 56 and 62 years had come with a complaint of change in voice, inability to swallow and reduced clarity of speech following surgery for left glomus jugulare tumor were participants of the study. Their surgical information revealed multiple cranial nerve palsies involving the left facial, left superior and recurrent branches of the vagus nerve, left pharyngeal, left soft palate, left hypoglossal and vestibular nerves. Functional outcomes of voice, speech and swallowing were evaluated by perceptual and objective assessment procedures. Assessment included the examination of oral structures and functions, dysarthria by Frenchey dysarthria assessment, cranial nerve functions and swallowing functions. MDVP and Dr. Speech software were used to evaluate acoustic parameters of voice and quality of voice respectively. Results: The study revealed that both the subjects, subsequent to excision of glomus jugulare tumor, showed a varied picture of affected oral structure and functions, articulation, voice and swallowing functions. The cranial nerve assessment showed impairment of the vagus, hypoglossal, facial and glossopharyngeal nerves. Voice examination indicated vocal cord paralysis associated with breathy quality of voice, weak voluntary cough, reduced pitch and loudness range, and poor respiratory support. Perturbation parameters as jitter, shimmer were affected along with s/z ratio indicative of voice fold pathology. Reduced MPD(Maximum Phonation Duration) of vowels indicated that disturbed coordination between respiratory and laryngeal systems. Hypernasality was found to be a prominent feature which reduced speech intelligibility. Imprecise articulation was seen in both the subjects as the hypoglossal nerve was affected following surgery. Injury to vagus, hypoglossal, gloss pharyngeal and facial nerves disturbed the function of swallowing. All the phases of swallow were affected. Aspiration was observed before and during the swallow, confirming the oropharyngeal dysphagia. All the subsystems were affected as per Frenchey Dysarthria Assessment signifying the diagnosis of flaccid dysarthria. Conclusion: There is an observable communication and swallowing difficulty seen following excision of glomus jugulare tumor. Even with complete resection, extensive rehabilitation may be necessary due to significant lower cranial nerve dysfunction. The finding of the present study stresses the need for involvement of as speech and swallowing therapist for pre-operative counseling and assessment of functional outcomes.

Keywords: functional outcome, glomus jugulare tumor excision, multiple cranial nerve impairment, speech and swallowing

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Authors: Junaid Mahmood Alam

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Revalidating and harmonizing clinical chemistry analytical principles and optimizing methods through quality control programs and assessments is the preeminent means to attain optimal outcome within the clinical laboratory services. Present study reports revalidation of our existing IFCC regularized analytical methods, particularly hepatic and thyroid function tests, by optimization of precision analyses and processing through external and internal quality assessments and regression determination. Parametric components of hepatic (Bilirubin ALT, γGT, ALP), cardiac (LDH, AST, Trop I) and thyroid/pituitary (T3, T4, TSH, FT3, FT4) function tests were used to validate analytical techniques on automated chemistry and immunological analyzers namely Hitachi 912, Cobas 6000 e601, Cobas c501, Cobas e411 with UV kinetic, colorimetric dry chemistry principles and Electro-Chemiluminescence immunoassay (ECLi) techniques. Process of validation and revalidation was completed with evaluating and assessing the precision analyzed Preci-control data of various instruments plotting against each other with regression analyses R2. Results showed that: Revalidation and optimization of respective parameters that were accredited through CAP, CLSI and NEQAPP assessments depicted 99.0% to 99.8% optimization, in addition to the methodology and instruments used for analyses. Regression R2 analysis of BilT was 0.996, whereas that of ALT, ALP, γGT, LDH, AST, Trop I, T3, T4, TSH, FT3, and FT4 exhibited R2 0.998, 0.997, 0.993, 0.967, 0.970, 0.980, 0.976, 0.996, 0.997, 0.997, and R2 0.990, respectively. This confirmed marked harmonization of analytical methods and instrumentations thus revalidating optimized precision standardization as per IFCC recommended guidelines. It is concluded that practices of revalidating and harmonizing the existing or any new services should be followed by all clinical laboratories, especially those associated with tertiary care hospital. This is will ensure deliverance of standardized, proficiency tested, optimized services for prompt and better patient care that will guarantee maximum patients’ confidence.

Keywords: revalidation, standardized, IFCC, CAP, harmonized

Procedia PDF Downloads 233

Authors: Luciano Tarantino, Emanuele Balzano, Aurelio Nasto

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S.R. 53 years. January 2009: HCV-related cirrhosis, Child-Pugh A5 class, EGDS no aesophageal Varices. No important comorbidities. Treated with PEG-IFN+Ribavirin (march-november 2009) with subsequent sustained virologic response. HCVRNA absent overtime. October 2016 :CT detected small HCC nodule in the VIII segment (diam.=12 mm). Treated with US guided RF-ablation. November 2016 CT: complete necrosis. Unfortunately, the patient dropped out US and CT follow-up controls.September 2018: asthenia and weight loss. CT showed a large tumor infiltrating V-VII-VI segments and complete PVTT of right portal vein and its branches . Surgical Consultation excluded indication to Liver resection and OLT . 23 october 2018: ECT of a large peri-hilar area of the tumor including the PVTT. 1 and 3 months post-treatment CT showed complete necrosis and retraction of the thrombus and residual viable tumor in the peripheral portion of the right lobe . Therefor, the patient was reevaluated for OLT and considered eligible in waiting list . March 2019: CT showed no perihilar or portal vein recurrence and distant progression in the right lobe . March 2019 : Trans-arterial-Radio-therapy (TARE) of the right lobe. Post-treatment CT demonstrated no perihilar or portal vein recurrence and extensive necrosis of the residual tumor . December 2019: CT demonstrated several recurrences of HCC infiltrating the VI and VII segment . Howewer no recurrence was observed at hepatic hilum and in portal vessels . Therefore, on February 2020 the patient received OLT. At 44 months follow-up, no complication or recurrence or liver disfunction have been observed.

Keywords: hepatocellular carcinoma, portal vein tumor thrombosis, interventional ultrasound, liver tumor ablation, liver transplantation

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Authors: Angelis P. Barlampas

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Introduction: The term phantom lung mass describes the ovoid collection of fluid within the interlobular fissure, which initially creates the impression of a mass. The problem of correct differential diagnosis is great, especially in plain radiography. A case is presented with three nodular pulmonary foci, the shape, location, and density of which, as well as the presence of chronic loculated pleural effusions, suggest the presence of multiple phantom tumors of the lung. Purpose: The aim of this paper is to draw the attention of non-experienced and non-specialized physicians to the existence of benign findings that mimic pathological conditions and vice versa. The careful study of a radiological examination and the comparison with previous exams or further control protect against quick wrong conclusions. Methods: A hospitalized patient underwent a non-contrast CT scan of the chest as part of the general control of her situation. Results: Computed tomography revealed pleural effusions, some of them loculated, increased cardiothoracic index, as well as the presence of three nodular foci, one in the left lung and two in the right with a maximum density of up to 18 Hounsfield units and a mean diameter of approximately five centimeters. Two of them are located in the characteristical anatomical position of the major interlobular fissure. The third one is located in the area of the right lower lobe’s posterior basal part, and it presents the same characteristics as the previous ones and is likely to be a loculated fluid collection, within an auxiliary interlobular fissure or a cyst, in the context of the patient's more general pleural entrapments and loculations. The differential diagnosis of nodular foci based on their imaging characteristics includes the following: a) rare metastatic foci with low density (liposarcoma, mucous tumors of the digestive or genital system, necrotic metastatic foci, metastatic renal cancer, etc.), b) necrotic multiple primary lung tumor locations (squamous epithelial cancer, etc. ), c) hamartomas of the lung, d) fibrotic tumors of the interlobular fissures, e) lipoid pneumonia, f) fluid concentrations within the interlobular fissures, g) lipoma of the lung, h) myelolipomas of the lung. Conclusions: The collection of fluid within the interlobular fissure of the lung can give the false impression of a lung mass, particularly on plain chest radiography. In the case of computed tomography, the ability to measure the density of a lesion, combined with the provided high anatomical details of the location and characteristics of the lesion, can lead relatively easily to the correct diagnosis. In cases of doubt or image artifacts, comparison with previous or subsequent examinations can resolve any disagreements, while in rare cases, intravenous contrast may be necessary.

Keywords: phantom mass, chest CT, pleural effusion, cancer

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Authors: Valeria Panzetta, Ida Musella, Sabato Fusco, Paolo Antonio Netti

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The study of the biophysics of living cells drew attention to the pivotal role of the cytoskeleton in many cell functions, such as mechanics, adhesion, proliferation, migration, differentiation and neoplastic transformation. In particular, during the complex process of malignant transformation and invasion cell cytoskeleton devolves from a rigid and organized structure to a more compliant state, which confers to the cancer cells a great ability to migrate and adapt to the extracellular environment. In order to better understand the malignant transformation process from a mechanical point of view, it is necessary to evaluate the direct crosstalk between the cells and their surrounding extracellular matrix (ECM) in a context which is close to in vivo conditions. In this study, human biopsy tissues of lung adenocarcinoma were analyzed in order to define their mechanical phenotype at cell and ECM level, by using particle tracking microrheology (PTM) technique. Polystyrene beads (500 nm) were introduced into the sample slice. The motion of beads was obtained by tracking their displacements across cell cytoskeleton and ECM structures and mean squared displacements (MSDs) were calculated from bead trajectories. It has been already demonstrated that the amplitude of MSD is inversely related to the mechanical properties of intracellular and extracellular microenvironment. For this reason, MSDs of particles introduced in cytoplasm and ECM of healthy and tumor tissues were compared. PTM analyses showed that cancerous transformation compromises mechanical integrity of cells and extracellular matrix. In particular, the MSD amplitudes in cells of adenocarcinoma were greater as compared to cells of normal tissues. The increased motion is probably associated to a less structured cytoskeleton and consequently to an increase of deformability of cells. Further, cancer transformation is also accompanied by extracellular matrix stiffening, as confirmed by the decrease of MSDs of matrix in tumor tissue, a process that promotes tumor proliferation and invasiveness, by activating typical oncogenic signaling pathways. In addition, a clear correlation between MSDs of cells and tumor grade was found. MSDs increase when tumor grade passes from 2 to 3, indicating that cells undergo to a trans-differentiation process during tumor progression. ECM stiffening is not dependent on tumor grade, but the tumor stage resulted to be strictly correlated with both cells and ECM mechanical properties. In fact, a greater stage is assigned to tumor spread to regional lymph nodes and characterized by an up-regulation of different ECM proteins, such as collagen I fibers. These results indicate that PTM can be used to get nanomechanical characterization at different scale levels in an interpretative and diagnostic context.

Keywords: cytoskeleton, extracellular matrix, mechanical properties, particle tracking microrheology, tumor

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Authors: Hala M. El-hanbuli, Mohammed F. Darweesh

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The incidence rates of any tumor vary hugely with geographical location. Basal Cell Carcinoma (BCC) is one of the most common skin cancer that has many histopathologic subtypes. Objective: The aim was to study the histopathological features of BCC cases that were received in the Pathology Department, Kasr El-Aini hospital, Cairo University, Egypt during the period from Jan 2004 to Dec 2013 and to evaluate the clinical characters through the patient data available in the request sheets. Methods: Slides and data of BCC cases were collected from the archives of the pathology department, Kasr El-Aini hospital. Revision of all available slides and histological classification of BCC according to WHO (2006) was done. Results: A total number of 310 cases of BCC representing about 65% from the total number of malignant skin tumors examined during the 10-years duration in the department. The age ranged from 8 to 84 years, the mean age was (55.7 ± 15.5). Most of the patients (85%) were above the age of 40 years. There was a slight male predominance (55%). Ulcerated BCC was the most common gross picture (60%), followed by nodular lesion (30%) and finally the ulcerated nodule (10%). Most of the lesions situated in the high-risk sites (77%) where the nose was the most common site (35%) followed by the periocular area (22%), then periauricular (15%) and finally perioral (5%). No lesion was reported outside the head. The tumor size was less than 2 centimeters in 65% of cases, and from 2-5 centimeters in the lesions' greatest dimension in the rest of cases. Histopathological reclassification revealed that the nodular BCC was the most common (68%) followed by the pigmented nodular (18.75%). The histologic high-risk groups represented (7.5%) about half of them (3.75%) being basosquamous carcinoma. The total incidence for multiple BCC and 2nd primary was 12%. Recurrent BCC represented 8%. All of the recurrent lesions of BCC belonged to the histologic high-risk group. Conclusion: Basal Cell Carcinoma is the most common skin cancer in the 10-year survey. Histopathological diagnosis and classification of BCC cases are essential for the determination of the tumor type and its biological behavior.

Keywords: basal cell carcinoma, high risk, histopathological features, statistical analysis

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Authors: Hannah Yael Ephraim

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During reproductive age (between 15 and 44), women are particularly susceptible to psychiatric illness. Depression and anxiety disorders are especially common for women during reproductive age. Women of reproductive age are also at greater risk for multiple physical conditions during this time. Existing literature focuses on the impact of mental health on physical health, showing that people with anxiety and depression repeatedly show greater physical health risk among those with developing chronic medical illness. However, there is limited research on the impact physical health has on mental health in women of reproductive age, a large and vulnerable population. For this reason, the current study seeks to ask the following questions: are women of reproductive age with a diagnosis of a chronic physical condition more likely to experience symptoms of mental illness than women without a diagnosis of a chronic physical condition? Does the type of physical illness relate to signs and symptoms of depression and anxiety? A quasi-experimental research design was implemented to compare the mental health outcomes of women with the diagnosis of chronic medical conditions and women without the diagnosis of a chronic medical condition. Quantitative data was collected through an anonymous ten-minute Qualtrics survey. The survey was sent out through multiple online platforms. The sample includes two groups of women: one group with the diagnosis of a chronic medical illness, and one group without a diagnosis and/or symptoms (N = 541). Participants identify as a woman and are between the ages of 15 and 44. A comparison of women with a diagnosis of a chronic physical condition and those without a diagnosis will be conducted to explore differences in depression and anxiety symptoms between women with and without a chronic medical diagnosis. The impact race, SES, and occupation will also be addressed in relation to anxiety and/or depression in women of reproductive age. This study will further the understanding of the relationship between mental illness in women of reproductive age with chronic medical conditions. The results of this study will have implications for the integration of mental health care in women’s health centers and perhaps training of clinicians and physicians providing psychological and medical care to women of reproductive age.

Keywords: mental health, physical health, reproductive age, women

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Authors: Tanushree Jaitly, Shailendra Gupta, Leila Taher, Gerold Schuler, Julio Vera

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Genomics-based personalized medicine is a promising approach to fight aggressive tumors based on patient's specific tumor mutation and expression profiles. A remarkable case is, dendritic cell-based immunotherapy, in which tumor epitopes targeting patient's specific mutations are used to design a vaccine that helps in stimulating cytotoxic T cell mediated anticancer immunity. Here we present a computational pipeline for epitope-based personalized cancer vaccines using patient-specific haplotype and cancer mutation profiles. In the workflow proposed, we analyze Whole Exome Sequencing and RNA Sequencing patient data to detect patient-specific mutations and their expression level. Epitopes including the tumor mutations are computationally predicted using patient's haplotype and filtered based on their expression level, binding affinity, and immunogenicity. We calculate binding energy for each filtered major histocompatibility complex (MHC)-peptide complex using docking studies, and use this feature to select good epitope candidates further.

Keywords: cancer immunotherapy, epitope prediction, NGS data, personalized medicine

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Authors: Mustafa M. Donma, Orkide Donma

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Cardiovascular pathology is one of the expected consequences of excessive fat gain. The role of zinc in thyroid hormone metabolism is an important matter. The concentrations of both thyroid stimulating hormone (TSH) and zinc are subject to variation in obese individuals. Zinc exhibits protective effects on cardiovascular health and is inversely correlated with cardiovascular markers in childhood obesity. The association between subclinical hypothyroidism (SCHT) and metabolic disorders is under investigation due to its clinical importance. Underactive thyroid gland causes high TSH levels. Subclinical hypothyroidism is defined as the elevated serum TSH levels in the presence of normal free thyroxin (T4) concentrations. The aim of this study was to evaluate the associations between TSH levels and zinc concentrations in morbid obese (MO) children exhibiting SCHT. The possibility of using the probable association between these parameters was also evaluated for the discrimination of metabolic syndrome positive (MetS+) and metabolic syndrome negative (MetS-) groups. Forty-two children were present in each group. Informed consent forms were obtained. Institutional Ethics Committee approved the study protocol. Tables prepared by World Health Organization were used for the definition of MO children. Children, whose age- and sex-dependent body mass index percentile values were above 99, were defined as MO. Children with at least two MetS components were included in MOMetS+ group. Elevated systolic/diastolic blood pressure values, increased fasting blood glucose, triglycerides (TRG)/decreased high density lipoprotein-cholesterol (HDL-C) concentrations in addition to central obesity were listed as MetS components. Anthropometric measures were recorded. Routine biochemical analyses were performed. Thirteen and fifteen children had SCHT in MOMetS- and MOMetS+ groups, respectively. Statistical analyses were performed. p<0.05 was accepted as statistically significant. In MOMetS- and MOMetS+ groups, TSH levels were 4.1±2.9 mU/L and 4.6±3.1 mU/L, respectively. Corresponding values for SCHT cases in these groups were 7.3±3.1 mU/L and 8.0±2.7 mU/L. Free T4 levels were within normal limits. Zinc concentrations were negatively correlated with TSH levels in both groups. The significant negative correlation calculated in MOMetS+ group (r= -0.909; p<0.001) was much stronger than that found in MOMetS- group (r= -0.706; p<0.05). This strong correlation (r= -0.909; p<0.001) calculated for cases with SCHT in MOMetS+ group was much lower (r= -0.793; p<0.001) when all MOMetS+ cases were considered. Zinc is closely related to T4 and TSH therefore, it participates in thyroid hormone metabolism. Since thyroid hormones are required for zinc absorption, hypothyroidism can lead to zinc deficiency. The presence of strong correlations between TSH and zinc in SCHT cases found in both MOMetS- and MOMetS+ groups pointed out that MO children were under the threat of cardiovascular pathologies. The detection of the much stronger correlation in MOMetS+ group in comparison with the correlation found in MOMetS- group was the indicator of greater cardiovascular risk due to the presence of MetS. In MOMetS+ group, correlation in SCHT cases found higher than correlation calculated for all cases confirmed much higher cardiovascular risk due to the contribution of SCHT.

Keywords: cardiovascular risk, children, morbid obesity, subclinical hypothyroidism, zinc

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Authors: A. D. Zikiryahodjaev, L. V. Bolotina, A. S. Sukhotko

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Purpose. To evaluate the expediency and timeliness of performance of surgical treatment as a component of multi-therapy treatment of patients with stage IV breast cancers. Materials and Methods. This investigation comparatively analyzed the results of complex treatment with or without surgery in patients with metastatic breast cancer. We analyzed retrospectively treatment experience of 196 patients with generalized breast cancer in the department of oncology and breast reconstructive surgery of P.A. Herzen Moscow Cancer Research Institute from 2000 to 2012. The average age was (58±1,1) years. Invasive ductul carcinoma was verified in128 patients (65,3%), invasive lobular carcinoma-33 (16,8%), complex form - 19 (9,7%). Complex palliative care involving drug and radiation therapies was performed in two patient groups. The first group includes 124 patients who underwent surgical intervention as complex treatment, the second group includes 72 patients with only medical therapy. Standard systemic therapy was given to all patients. Results. Overall, 3-and 5-year survival in fist group was 43,8 and 21%, in second - 15,1 and 9,3% respectively [p=0,00002 log-rank]. Median survival in patients with surgical treatment composed 32 months, in patients with only systemic therapy-21. The factors having influencing an influence on the prognosis and the quality of life outcomes for of patients with generalized breast cancer were are also studied: hormone-dependent tumor, Her2/neu hyper-expression, reproductive function status (age, menopause existence). Conclusion.Removing primary breast tumor in patients with generalized breast cancer improve long-term outcomes. Three- and five-year survival increased by 28,7 and 16,3% respectively, and median survival–for 11 months. These patients may benefit from resection of the breast tumor. One explanation for the effect of this resection is that reducing the tumor load influences metastatic growth.

Keywords: breast cancer, combination therapy, factors of prognosis, primary tumor

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Authors: Md Abdullah Al Mashud, M. Tariquzzaman, M. Jahangir Alam, Tapan Kumar Godder, M. Mahbubur Rahman

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This paper presents a Monte Carlo (MC) method-based dose distributions on lung tumor for 6 MV photon beam to improve the dosimetric accuracy for cancer treatment. The polystyrene which is tissue equivalent material to the lung tumor density is used in this research. In the empirical calculations, TRS-398 formalism of IAEA has been used, and the setup was made according to the ICRU recommendations. The research outcomes were compared with the state-of-the-art experimental results. From the experimental results, it is observed that the proposed based approach provides more accurate results and improves the accuracy than the existing approaches. The average %variation between measured and TPS simulated values was obtained 1.337±0.531, which shows a substantial improvement comparing with the state-of-the-art technology.

Keywords: lung tumour, Monte Carlo, polystyrene, Elekta synergy, Monaco planning system

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Authors: Ahmad Jawad Fardin

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Over 60% of patients with breast cancer in Afghanistan present late with advanced stage III and IV, a major cause for the poor survival rate. The objectives of this study were to identify the contributing factors for the diagnosis and treatment delay and its outcome. This cross-sectional study was conducted on 318 patients with histologically confirmed breast cancer in the oncology department of Jamhoriat hospital, which is the first and only national cancer center in Afghanistan; data were collected from medical records and interviews conducted with women diagnosed with breast cancer, linear regression and logistic regression were used for analysis. Patient delay was defined as the time from first recognition of symptoms until first medical consultation and doctor form first consultation with a health care provider until histological confirmation of breast cancer. The mean age of patients was 49.2+_ 11.5years. The average time for the final diagnosis of breast cancer was 8.5 months; most patients had ductal carcinoma 260.7 (82%). Factors associated with delay were low education level 76% poor socioeconomic and cultural conditions 81% lack of cancer center 73% lack of screening 19%. The stage distribution was as follows stage IV 4 22% stage III 44.4% stage II 29.3% stage I 4.3%. Complex associated factors were identified to delayed the diagnosis of breast cancer and increased adverse outcomes consequently. Raising awareness and education in women, the establishment of cancer centers and providing accessible diagnosis service and screening, training of general practitioners; required to promote early detection, diagnosis and treatment.

Keywords: delayed diagnosis and poor outcome, breast cancer in Afghanistan, poor outcome of delayed breast cancer treatment, breast cancer delayed diagnosis and treatment in Afghanistan

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Authors: Zoe Goldberger, Priscilla S. Briquez, Jeffrey A. Hubbell

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Tumor cells have mutations resulting from genetic instability that the immune system can actively recognize. Immune checkpoint immunotherapy (ICI) is commonly used in the clinic to re-activate immune reactions against mutated proteins, called neoantigens, resulting in tumor remission in cancer patients. However, only around 20% of patients show durable response to ICI. While tumor mutational burden (TMB) has been approved by the Food and Drug Administration (FDA) as a criterion for ICI therapy, the relevance of the subcellular localizations of the mutated proteins within the tumor cell has not been investigated. Here, we hypothesized that localization of mutations impacts the effect of immune responsiveness to ICI. We analyzed publicly available tumor mutation sequencing data of ICI treated patients from 3 independent datasets. We extracted the subcellular localization from the UniProtKB/Swiss-Prot database and quantified the proportion of membrane, cytoplasmic, nuclear, or secreted mutations per patient. We analyzed this information in relation to response to ICI treatment and overall survival of patients showing with 1722 ICI-treated patients that high mutational burden localized at the membrane (mTMB), correlate with ICI responsiveness, and improved overall survival in multiple cancer types. We anticipate that our results will ameliorate predictability of cancer patient response to ICI with potential implications in clinical guidelines to tailor ICI treatment. This would not only increase patient survival for those receiving ICI, but also patients’ quality of life by reducing the number of patients enduring non-effective ICI treatments.

Keywords: cancer, immunotherapy, membrane neoantigens, efficacy prediction, biomarkers

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Authors: Yushen Dai, Tao Deng, Miaoying Chen, Baoqin Huang, Yan Ji, Yongshen Feng, Shaofei Liu, Dongmei Zhong, Tao Zhang, Lifeng Zhang

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Background: Detection and diagnosis are prerequisites for early interventions in the care of children with Autism Spectrum Disorder (ASD). However, few studies have focused on this topic. Aim: This study aims to characterize the timing from symptom detection to intervention in children with ASD and to identify the potential predictors of early detection, diagnosis, and intervention. Methods and procedures: A cross-sectional survey was conducted with 314 parents of children with ASD in Guangzhou, China. Outcomes and Results: This study found that most children (76.24%) were diagnosed within one year after detection, and 25.8% of them did not receive the intervention after diagnosis. Predictors to ASD diagnosis included ASD-related symptoms identified at a younger age, more serious symptoms, and initial symptoms with abnormal development and sensory anomalies. ASD-related symptoms observed at an older age, initial symptoms with the social deficit, sensory anomalies, and without language impairment, parents as the primary caregivers, family with lower income and less social support utilization increased the odds of the time lag between detection and diagnosis. Children whose fathers had a lower level of education were less likely to receive the intervention. Conclusions and Implications: The study described the time for detection, diagnosis, and interventions of children with ASD. Findings suggest that the ASD-related symptoms, the timing at which symptoms first become a concern, primary caregivers’ roles, father’s educational level, and the family economic status should be considered when offering support to improve early detection, diagnosis, and intervention. Helping children and their families take full advantage of support is also important.

Keywords: autism spectrum disorder, child, detection, diagnosis, intervention, social support

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Authors: Anoosh Eghdami

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Background and aim: Conventional anticancer drugs display significant shortcomings which limit their use in cancer therapy. For this reason, important progress has been achieved in the field of nanotechnology to solve these problems and offer a promising and effective alternative for cancer treatment. Tumor markers may also be measured periodically during cancer therapy. Tumor markers may also be measured after treatment has ended to check for recurrence the return of cancer. The aim of this study was to evaluate the effect of nano drug delivery in induced breast cancer with DMBA by using CA15-3 tumor marker. Material and method: the rats were divided into five groups. The first group (control n=15) were fed only sesame oil as a gavage. In the second group n=15,10 mg DMBA was dissolved in 5ml of sesame oil and were fed as a gavage. In addition to DMBA treatment as the second group, in the 3,4and 5 groups after cancer creation, respectively affected by alpha interferon (α-IFN),alpha interferon conjugated with single walled carbon nano tube (α-IFN-SWNT) and encapsulated in poly lactic poly glycolic acid (α-IFN-PLGA). Tumor marker was measured in recent three groups. Results: The ANOVA test was used to determine the differences among the groups. Cancer inducing in rats (group 2) caused a significant increase in blood levels of CA15-3 (P<0.05). Administration of α-IFN, α-IFN –SWNT and α-IFN-PLGA in 3 groups of cancerous rats caused a significant decrease in blood levels of CA15-3 only the group that treated with α-IFN-PLGA (p<0.05). Conclusion: the results of this study indicate that nano drugs more effective than traditional drug in cancer treatment, although further work is needed to elucidate the safety and side effect of these compound in human.

Keywords: breast cancer, nano drug, tumor markers, CA15-3, α-IFN-PLGA, -IFN –SWNT

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Authors: Li Yin, Xiaoqin Wang

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Background and purpose: Cancer diagnosis is part of a complex stochastic process, in which patients' personal and social characteristics influence the choice of diagnosing methods, diagnosing methods, in turn, influence the initial assessment of cancer stage, the initial assessment, in turn, influences the choice of treating methods, and treating methods in turn influence cancer outcomes such as cancer survival. To evaluate diagnosing methods, one needs to estimate and test the causal effect of a regime of cancer diagnosis and treatments. Recently, Wang and Yin (Annals of statistics, 2020) derived a new general formula, which expresses these causal effects in terms of the point effects of treatments in single-point causal inference. As a result, it is possible to estimate and test these causal effects via point effects. The purpose of the work is to estimate and test causal effects under various regimes of cancer diagnosis and treatments via point effects. Challenges and solutions: The cancer stage has influences from earlier diagnosis as well as on subsequent treatments. As a consequence, it is highly difficult to estimate and test the causal effects via standard parameters, that is, the conditional survival given all stationary covariates, diagnosing methods, cancer stage and prognosis factors, treating methods. Instead of standard parameters, we use the point effects of cancer diagnosis and treatments to estimate and test causal effects under various regimes of cancer diagnosis and treatments. We are able to use familiar methods in the framework of single-point causal inference to accomplish the task. Achievements: we have applied this method to stomach cancer survival from a clinical study in Sweden. We have studied causal effects under various regimes, including the optimal regime of diagnosis and treatments and the effect moderation of the causal effect by age and gender.

Keywords: cancer diagnosis, causal effect, point effect, G-formula, sequential causal effect

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Authors: Noura Al-Ajmi, Mohammed A. Almulla

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With the increased utilization of technology devices around the world, healthcare and medical diagnosis are critical issues that people worry about these days. Doctors are doing their best to avoid any medical errors while diagnosing diseases and prescribing the wrong medication. Subsequently, artificial intelligence applications that can be installed on mobile devices such as rule-based expert systems facilitate the task of assisting doctors in several ways. Due to their many advantages, the usage of expert systems has increased recently in health sciences. This work presents a backward rule-based expert system that can be used for a headache diagnosis and medication recommendation system. The structure of the system consists of three main modules, namely the input unit, the processing unit, and the output unit.

Keywords: headache diagnosis system, prescription recommender system, expert system, backward rule-based system

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Authors: Sujeet Poudyal

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Introduction: Renal cell carcinoma is the most common malignancy associated with Inferior vena cava (IVC) thrombosis. Radical nephrectomy with tumor thrombectomy provides durable cancer-free survival. Other renal malignancies like Wilms’ tumors are also associated with IVC thrombus. We describe our experience with the management of renal malignancies associated with IVC thrombus. Methods: This prospective study included 28 patients undergoing surgery for renal malignancies associated with IVC thrombus from February 2017 to March 2023. Demographics of patients, types of renal malignancy, level of IVC thrombus, intraoperative details, need for venovenous bypass, cardiopulmonary bypass and postoperative outcomes were all documented. Results: Out of a total of 28 patients, 24 patients had clear cell Renal Cell Carcinoma,1 had renal osteosarcoma and 3 patients had Wilms tumor. The levels. of thrombus were II in eight, III in seven, and IV in six patients. The mean age of RCC was 62.81±10.2 years, renal osteosarcoma was 26 years and Wilms tumor was 23 years. There was a need for venovenous bypass in four patients and cardiopulmonary bypass in four patients, and the Postoperative period was uneventful in most cases except for two mortalities, one in Level III due to pneumonia and one in Level IV due to sepsis. All cases followed up till now have no local recurrence and metastasis except one case of RCC with Level IV IVC thrombus, which presented with paraaortic nodal recurrence and is currently managed with sunitinib. Conclusion: The complexity in the management of renal malignancy with IVC thrombus increases with the level of IVC thrombus. As radical nephrectomy with tumor thrombectomy provides durable cancer-free survival in most cases, the surgery should be undertaken in an expert and experienced setup with a strong cardiovascular backup to minimize morbidity and mortality associated with the procedure.

Keywords: renal malignancy, IVC thrombus, radical nephrectomy with tumor thrombectomy, renal cell carcinoma

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Authors: Elham Ahmadi, Mehrdad Ravanshad, Joyce Fingeroth, Mazyar Ziyaeyan, Rajesh Panigrahi, Jun Xie, Gao Guangping

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B-cell proliferative disorders often occur among persons that are T-cell compromised. These disorders are primarily EBV+ and can first present with a focal lesion. Direct introduction of oncolytic viruses into localized tumors provides theoretical advantages over chemotherapy and immunotherapy by reducing systemic toxicity, to which the immunocompromised host is most vulnerable. Widely studied as a vehicle for gene therapy, AAV has only rarely been applied to treat cancer. As a prelude to development of a therapeutic vehicle, we assessed the ability of 15 distinct recombinant AAV serotypes (rAAV1, rAAV2, rAAV3b, rAAV4, rAAV5, rAAV6, rAAV6.2, rAAV6TM, rAAV7, rAAV8, rAAVrh8, rAAV9, rAAVrh10, rAAV39, rAAV43) bearing eGFP to infect human B-cell tumor lines compared with primary B-cells in vitro. Enhanced infection of tumor lines by AAV 6.2 was demonstrated by flow cytometry. EBV superinfection of EBV negative B-cell tumor lines increased susceptibility to AAV6.2 infection. As proof of concept, AAV6.2 bearing HSV-1 thymidine kinase in place of eGFP eliminated tumor cells upon exposure to ganciclovir.

Keywords: AAV, gene therapy, lymphoma, malignancy, tropism

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Authors: Yogita Tulsian, R. S. Gupta, K. F. Laserson

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Background: Delays in the diagnosis and treatment of TB facilitates disease transmission in the community, so we conducted a study to evaluate the burden of and risk factors for delay in TB diagnosis and initiation of TB treatment among patients in the private and public sectors in Udaipur district, Rajasthan, India. Methods: A retrospective cohort study was conducted among 100 new sputum-positive TB. Patients were interviewed in the intensive phase of treatment September 2013-November 2013 Long total diagnosis delay (TDD) was defined as a time interval between first symptom to confirmed diagnosis > 30 days. Long health treatment delay (HTD) was defined as a time interval between confirmed diagnosis to treatment initiation > 7 days. Results: We observed a median TDD of 55 days (range: 7-136 days) in the public sector and of 92 days (11-380 days) in the private sector. Long TDD in the private sector was significantly associated with middle-higher socio-economic status (Risk Ratio (RR): 2;95% CI: 1.3-3). The reasons reported from the private sector for long TDD were suspect TB patients not advised for sputum examination (RR: 42; 95% CI:2.6-660), practise of self-medication (RR: 17.4; 95% CI: 1.1-267), or lack of awareness (RR: 9.7;95% CI: 0.6-145). The median HTD in the public sector was 3 days (range: 0-14 days), and in the private sector, 2 days (range: 0-11 days) (non-significant difference). Conclusions: Long TDD in private sector may be improved through sputum referral for all suspect TB cases and better education to all regarding TB.

Keywords: diagnosis delay, treatment delay, privatesector, public sector

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Authors: Sait Ozsoy, Asude Gokmen, Mehtap Yondem, Hanife A. Alkan, Gulnaz T. Javan

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Deep neck infection often develops due to upper respiratory tract and odontogenic infections. Gastrointestinal System perforation can occur for many reasons and is in need of the early diagnosis and prompt surgical treatment. In both cases late or incorrect diagnosis may lead to increase morbidity and high mortality. A patient with a diagnosis of deep neck abscess died while under treatment due to sepsis and multiple organ failure. Autopsy finding showed duodenal ulcer and this is reported in the literature.

Keywords: peptic ulcer perforation, peritonitis, retropharyngeal abscess, sepsis

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Authors: Dominika Pihikova, Stefan Belicky, Tomas Bertok, Roman Sokol, Petra Kubanikova, Jan Tkac

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Since aberrant glycosylation is frequently accompanied by both physiological and pathological processes in a human body (cancer, AIDS, inflammatory diseases, etc.), the analysis of tumor-associated glycan patterns have a great potential for the development of novel diagnostic approaches. Moreover, altered glycoforms may assist as a suitable tool for the specificity and sensitivity enhancement in early-stage prostate cancer diagnosis. In this paper we discuss the construction and optimization of ultrasensitive sandwich biosensor platform employing lectin as glycan-binding protein. We focus on the immunoassay development, reduction of non-specific interactions and final glycoprofiling of human serum samples including both prostate cancer (PCa) patients and healthy controls. The fabricated biosensor was measured by label-free electrochemical impedance spectroscopy (EIS) with further lectin microarray verification. Furthermore, we analyzed different biosensor interfaces with atomic force microscopy (AFM) in nanomechanical mapping mode showing a significant differences in the altitude. These preliminary results revealing an elevated content of α-2,3 linked sialic acid in PCa patients comparing with healthy controls. All these experiments are important step towards development of point-of-care devices and discovery of novel glyco-biomarkers applicable in cancer diagnosis.

Keywords: biosensor, glycan, lectin, prostate cancer

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Authors: Mohamed A. Morsy, Azza A. K. El-Sheikh, Abdulla Y. Al-Taher

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The aim of the present study is to investigate the effect of resveratrol (RES) on methotrexate (MTX)-induced testicular damage. RES (10 mg/kg/day) was given for 8 days orally and MTX (20 mg/kg i.p.) was given at day 4 of experiment, with or without RES in rats. MTX decreased serum testosterone, induced histopathological testicular damage, increased testicular tumor necrosis factor-α level and expression of nuclear factor-κB and cyclooxygenase-2. In MTX/RES group, significant reversal of these parameters was noticed, compared to MTX group. Testicular expression of multidrug resistance protein (Mrp) 3 was three- and five-folds higher in RES- and MTX/RES-treated groups, respectively. In vitro, using prostate cancer cells, each of MTX and RES alone induced cytotoxicity with IC50 0.18 ± 0.08 and 20.5 ± 3.6 µM, respectively. RES also significantly enhanced cytotoxicity of MTX. In conclusion, RES appears to have dual beneficial effect, as it promotes MTX tumor cytotoxicity, while protecting the testes, probably via up-regulation of testicular Mrp3 as a novel mechanism.

Keywords: resveratrol, methotrexate, multidrug resistance protein 3, tumor necrosis factor-α, nuclear factor-κB, cyclooxygenase-2

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Authors: Deepa Vasudevan, Thomas Northrup, Angela Stotts, Michelle Klawans

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To date, we have conducted three studies on this subject. The research done to date is through three studies. The initial study was to document that modified criteria independently identified higher numbers of overweight/obese South Asian Indians. The second study was to document physician knowledge of appropriate diagnosis of obesity among South Asian Indians. The final study was an intervention to evaluate the efficacy of a training module on improving physician diagnosis and counseling of overweight/obese Asian patients.

Keywords: South Asian Indians, obesity, physicians, BMI and waist circumference

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Authors: Mark Berry

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A number of studies have identified several factors involved in the malignant progression of cancer cells. The Primary modulator in driving inflammation to these transformed cells has been identified as the transcription factor known as nuclear factor-κB. This essential regulator of inflammation and the development of cancer, combined with a microenvironment of inflammation and signaling molecules, plays a major role in the malignant progression of cancer, and this progression is the result of the mutagenic predisposition of persistent substances that combat infection at tumor sites and other areas of chronic inflammation. Inflammation-induced tumors, and their inflammatory cells and regulators may be the primary source of metastasis of tumor cells through angiogenesis. Previous research on cytokines and chemokines, including their downstream targets, has been the focus of the cancer/inflammation connection. The identification of the biological mechanisms of other proteins vital to the inflammation cascade and their interactions are crucial to novel and effective therapeutic protocols for the treatment of inflammation-induced cancers. The Ancelim HSRP Protocol is just such a therapeutic intervention.

Keywords: ancelim, cancer, inflammation, tumor

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