Search results for: metastatic lesion

Authors: Aliakbar Hafezi, Jalal Taherian, Jamshid Abedi, Mahsa Elahi

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Background: Bones are commonly affected by renal cell carcinoma (RCC) (primarily or secondary), and this condition causes bone fragility. The aim of this study was to evaluate the diagnostic value of noninvasive methods for the diagnosis of ROD in RCC patients on hemodialysis (HD) in northern Iran. Methods: In this cross-sectional study, 50 RCC patients with ESRD referred to dialysis units in northern Iran during 2021-2024 were randomly selected and investigated. The biochemical and radiographic evaluation of ROD and its subtypes was performed, and then all patients underwent bone biopsy and histopathological study, and finally, the diagnostic value of the noninvasive methods was assessed. Results: The mean age of patients was 58.9 ± 11.7 years, and 27 cases (54.0%) were female. 38 (76.0%) of RCC patients with ESRD had ROD, and 12 patients (24.0%) had no evidence of bone disorders. The sensitivity, specificity, positive and predictive values and accuracy of the noninvasive methods for the diagnosis of ROD were 92%, 82%, 95%, 75% and 90%, respectively. Conclusion: This study showed that the frequency of ROD in RCC patients with ESRD in northern Iran was high and the biochemical and radiographic markers have a high diagnostic value for ROD as well as histopathological assessment.

Keywords: renal cell carcinoma, renal osteodystrophy, hemodialysis, non-metastatic

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Authors: Sanjaya Humagain, Rajendra Koju

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Background: Rheumatic heart disease (RHD) is the most common cardiovascular disease in children and young adults. Though declined and almost non-existent in developed nations, RHD is still one of the leading cause for premature death and disability in developing countries. Prevalence of RHD is high in both rural as well as urban area of Nepal. Present study is designed to look at the pattern of valvular involvement and demographic features in RHD. Methods: 326 patients indicated for inj. Benzathine penicillin were selected and echocardiograph performed to see the pattern of vavular involvement. Data analysis was done using SPSS 17. Result: The most common type of lesion was mixed type with mitral valve involvement. MR was the most common isolated lesion. MS was more commonly seen in females whereas AS was more common in males. Secondary prophylaxis was more common than primary prophylaxis. Conclusion: RHD still being a major problem and a preventable disease so extensive screening program is required to identify them early and prevent the complication.

Keywords: acute rheumatic fever, RHD, MS, MR, AS, AR, Inj benzathine penicillin

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Authors: Mohamed Shafi Bin Mahboob Ali

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Introduction: Synchronous tumor is defined as the presence of more than one primary malignant lesion in the same patient at the indexed diagnosis. It is a rare occurrence, especially in the spectrum of colorectal cancer, which accounts for less than 4%. The underlying pathology of a synchronous tumor is thought to be due to a genomic factor, which is microsatellite instability (MIS) with the involvement of BRAF, KRAS, and the GSRM1 gene. There are no specific sites of occurrence for the synchronous colorectal tumor, but many studies have shown that a synchronous tumor has about 43% predominance in the ascending colon with rarity in the sigmoid colon. Case Report: We reported a case of a young lady in the middle of her 30's with no family history of colorectal cancer that was diagnosed with a synchronous adenocarcinoma at the descending colon and rectosigmoid region. The lady's presentation was quite perplexing as she presented to the district hospital initially with simple, uncomplicated hemorrhoids and constipation. She was then referred to our center for further management as she developed a 'football' sized right gluteal swelling with a complete intestinal obstruction and bilateral lower-limb paralysis. We performed a CT scan and biopsy of the lesion, which found that the tumor engulfed the sacrococcygeal region with more than one primary lesion in the colon as well as secondaries in the liver. The patient was operated on after a multidisciplinary meeting was held. Pelvic exenteration with tumor debulking and anterior resection were performed. Postoperatively, she was referred to the oncology team for chemotherapy. She had a tremendous recovery in eight months' time with a partial regain of her lower limb power. The patient is still under our follow-up with an improved quality of life post-intervention. Discussion: Synchronous colon cancer is rare, with an incidence of 2.4% to 12.4%. It has male predominance and is pathologically more advanced compared to a single colon lesion. Down staging the disease by means of chemoradiotherapy has shown to be effective in managing this tumor. It is seen commonly on the right colon, but in our case, we found it on the left colon and the rectosigmoid. Conclusion: Managing a synchronous colon tumor could be challenging to surgeons, especially in deciding the extent of resection and postoperative functional outcomes of the bowel; thus, individual treatment strategies are needed to tackle this pathology.

Keywords: synchronous, colon, tumor, adenocarcinoma

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Authors: Andrea L. Arnett, Ann T. Packard, Yolanda I. Garces, Kenneth W. Merrell

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Objective: Pathologic response following neoadjuvant chemoradiation (CRT) has been associated with improved overall survival (OS). Conflicting results have been reported regarding the pathologic predictive value of positron emission tomography (PET) response in patients with stage III lung cancer. The aim of this study was to evaluate the correlation between post-treatment PET response and pathologic response utilizing novel FDG-PET parameters. Methods: This retrospective study included patients with non-metastatic, stage IIIA (N2) NSCLC cancer treated with CRT followed by resection. All patients underwent PET prior to and after neoadjuvant CRT. Univariate analysis was utilized to assess correlations between PET response, nodal clearance, pCR, and near-complete pathologic response (defined as the microscopic residual disease or less). Maximal standard uptake value (SUV), standard uptake ratio (SUR) [normalized independently to the liver (SUR-L) and blood pool (SUR-BP)], metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured pre- and post-chemoradiation. Results: A total of 44 patients were included for review. Median age was 61.9 years, and median follow-up was 2.6 years. Histologic subtypes included adenocarcinoma (72.2%) and squamous cell carcinoma (22.7%), and the majority of patients had the T2 disease (59.1%). The rate of pCR and near-complete pathologic response within the primary lesion was 28.9% and 44.4%, respectively. The average reduction in SUVmₐₓ was 9.2 units (range -1.9-32.8), and the majority of patients demonstrated some degree of favorable treatment response. SUR-BP and SUR-L showed a mean reduction of 4.7 units (range -0.1-17.3) and 3.5 units (range –1.7-12.6), respectively. Variation in PET response was not significantly associated with histologic subtype, concurrent chemotherapy type, stage, or radiation dose. No significant correlation was found between pathologic response and absolute change in MTV or TLG. Reduction in SUVmₐₓ and SUR were associated with increased rate of pathologic response (p ≤ 0.02). This correlation was not impacted by normalization of SUR to liver versus mediastinal blood pool. A threshold of > 75% decrease in SUR-L correlated with near-complete response, with a sensitivity of 57.9% and specificity of 85.7%, as well as positive and negative predictive values of 78.6% and 69.2%, respectively (diagnostic odds ratio [DOR]: 5.6, p=0.02). A threshold of >50% decrease in SUR was also significantly associated pathologic response (DOR 12.9, p=0.2), but specificity was substantially lower when utilizing this threshold value. No significant association was found between nodal PET parameters and pathologic nodal clearance. Conclusions: Our results suggest that treatment response to neoadjuvant therapy as assessed on PET imaging can be a predictor of pathologic response when evaluated via SUV and SUR. SUR parameters were associated with higher diagnostic odds ratios, suggesting improved predictive utility compared to SUVmₐₓ. MTV and TLG did not prove to be significant predictors of pathologic response but may warrant further investigation in a larger cohort of patients.

Keywords: lung cancer, positron emission tomography (PET), standard uptake ratio (SUR), standard uptake value (SUV)

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Authors: K. Hinde, R. Bookun, P. Tran

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Percutaneous CT guided biopsies provide a fast, minimally invasive, cost effective and safe method for obtaining tissue for histopathology and culture. Standards for diagnostic yield vary depending on whether the tissue is being obtained for histopathology or culture. We present a retrospective audit from Western Health in Melbourne Australia over a 12-month period which aimed to determine the diagnostic yield, technical success and complication rate for CT guided bone biopsies and identify factors affecting these results. The digital imaging storage program (Synapse Picture Archiving and Communication System – Fujifilm Australia) was analysed with key word searches from October 2015 to October 2016. Nineteen CT guided bone biopsies were performed during this time. The most common referring unit was oncology, work up imaging included CT, MRI, bone scan and PET scan. The complication rate was 0%, overall diagnostic yield was 74% with a technical success of 95%. When performing biopsies for histologic analysis diagnostic yield was 85% and when performing biopsies for bacterial culture diagnostic yield was 60%. There was no significant relationship identified between size of lesion, distance of lesion to skin, lesion appearance on CT, the number of samples taken or gauge of needle to diagnostic yield or technical success. CT guided bone biopsy at Western Health meets the standard reported at other major clinical centres for technical success and safety. It is a useful investigation in identification of primary malignancy in distal bone metastases.

Keywords: bone biopsy, computed tomography, core biopsy, histopathology

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Authors: Aferdita Stroka Koka, Laver Stroka, Juna Musa, Samanda Celaj

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Non-melanoma skin cancers (NMSCs) are the most common human malignancies. About 5.4 million basal and squamous cell skin cancers are diagnosed each year in the US and new cases continue to grow. About eight out of ten of these are basal cell cancers. Squamous cell cancers occur less often. NMSC usually are treatable, but treatment is expensive and can leave scars. In 2019, 167 patients of both sexes suffering from NMSC were treated by traditional medicine. Patients who have been diagnosed with Basal Cell Carcinoma were 122 cases, Squamous Cell Carcinoma 32 cases and both of them 13 cases. Of these,122 cases were ulcerated lesions and 45 unulcerated lesions. All patients were treated with the herbal solution called NILS, which contains extracts of some Albanian plants such as Allium sativum, Jugulans regia and Laurus nobilis. The treatment is done locally, on the surface of the tumor, applying the solution until the tumor mass is destroyed and, after that, giving the necessary time to the wound to make the regeneration that coincides with the complete healing of the wound. We have prepared a collection of photos for each case. Since the first sessions, a shrinkage and reduction of the tumor mass were evident, up to the total disappearance of the lesion at the end of treatment. The normal period of treatment lasted 1 to 2 weeks, depending on the size of the tumor, then take care of it until the closure of the wound, taking the whole process from 1 to 3 months. In 7 patients, the lesion failed to be dominated by treatment and they underwent standard treatment with radiotherapy or surgery, while in 10 patients, the lesion recurred and was treated again. The aim of this survey was to put in evidence the good results obtained by treatment of NMSC with Albanian traditional medicine methods.

Keywords: local treatment, nils, NMSC, traditional medicine

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Authors: Nadeen Eltoukhy, Sahar S. Sheta, Walaa Elnaggar, Karim Bakr

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Purpose: The aim of this study is to compare the clinical efficacy and side effects of oral versus intralesional propranolol treatment of infantile capillary hemangiomas in infants. Methods: The study enrolled 40 infants diagnosed with infantile capillary hemangiomas. Patients were divided into 2 groups: Group A (Non-invasive group) included 20 infants who received oral propranolol hydrochloride starting at a dose of 1 mg/kg/day BID, then increased to a max of 2 mg/kg/day BID gradually over 2 weeks for 3 months. Group B (Invasive group) included 20 infants who received intralesional propranolol injection at a dose of 1 mg/mL; the volume of the injected drug depended on the size of the lesion (0.2 mL injected per cm of lesion diameter), with a maximum volume of 1 mL for a lesion of 5 cm diameter under complete aseptic conditions in the operating theater. Results: At three months after initiating treatment, the circumferential size of the hemangioma showed a statistically significant decrease in both groups; in Group A from 3.66±2.89 cm to 1.56±1.26 cm with p-value <0.05 and in Group B from 2.99±2.73 cm to 1.32±1.18 cm with p-value <0.05. There is no statistically significant comparative difference between the two groups (p-value = 0.538 = insignificant). Regarding the complications of oral propranolol, one patient (5%) had bradycardia, and one patient (5%) had diarrhea. In the injection group, 20 patients (100%) had local edema, and one patient (5%) had a local infection. Conclusions: Both oral non-invasive and intralesional invasive propranolol are safely used to successfully treat and decrease the size of infantile hemangioma while showing no statistically comparative difference between both treatment techniques.

Keywords: hemangioma, oral beta blocker, intralesional beta blocker, infants

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Authors: Kim Kennedy, Daren Gibson, Stephanie Flukes, Chandra Diwakarla, Lisa Spalding, Leanne Pilkington, Andrew Redfern

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Introduction: The mortality gap in Aboriginal Head and Neck Cancer is well known, but the reasons for poorer survival are not well established. Aim: We aimed to evaluate the locoregional and metastatic involvement, and stage at diagnosis, in Aboriginal compared with non-Aboriginal patients. Methods: We performed a retrospective cohort analysis of 320 HNC patients from a single centre in Western Australia, identifying 80 Aboriginal patients and 240 non-Aboriginal patients matched on a 1:3 ratio by sites, histology, rurality, and age. We collected data on the patient characteristics, tumour features, regions involved, stage at diagnosis, treatment history, and survival and relapse patterns, including sites of metastatic and locoregional involvement. Results: Aboriginal patients had a significantly higher incidence of lung metastases (26.3% versus 13.7%, p=0.009). Aboriginal patients also had a numerically but non-statistically significant higher incidence of thoracic nodal involvement (10% vs 5.8%) and malignant pleural effusions (3.8% vs 2.5%). Aboriginal patients also had a numerically but not statistically significantly higher incidence of adrenal and bony involvement. Interestingly, non-Aboriginal patients had an increased rate of cutaneous (2.1% vs 0%) and liver metastases (4.6% vs 2.5%) compared with Aboriginal patients. In terms of locoregional involvement, Aboriginal patients were more than twice as likely to have contralateral neck involvement (58.8% vs 24.2%, p<0.00001), and 30% more likely to have ipsilateral neck lymph node involvement (78.8% vs 60%, p=0.002) than non-Aboriginal patients. Aboriginal patients had significantly more advanced disease at diagnosis (p=0.008). Aboriginal compared with non-Aboriginal patients were less likely to present with stage I (7.5% vs 22.5%), stage II (11.3% vs 13.8%), or stage III disease (13.8% vs 17.1%), and more likely to present with more advanced stage IVA (42.5% vs 34.6%), stage IVB (15% vs 7.1%), or stage IVC (10% vs 5%) disease (p=0.008). Number of regions of disease involvement was higher in Aboriginal patients (median 3, mean 3.64, range 1-10) compared with non-Aboriginal patients (median 2, mean 2.80, range 1-12). Conclusion: Aboriginal patients had a significantly higher incidence of lung metastases, and significantly more frequent involvement of ipsilateral and contralateral neck lymph nodes. Aboriginal patients also had significantly more advanced disease at presentation with a higher stage at diagnosis. We are performing further analyses to investigate explanations for these findings.

Keywords: head and neck cancer, Aboriginal, metastases, locoregional, pattern of relapse, sites of disease

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Authors: Roland Benedict Reyes, Marc Edsel Ayes, Regina Berba, Cybele Lara Abad

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Background: Three AIDS-defining malignancies have been associated with the human immunodeficiency virus (HIV): Kaposi’s sarcoma, non-Hodgkin’s lymphoma, and cervical carcinoma. However, new cases of non-AIDS defining malignancies also have been increasingly associated with HIV. One of these is a rare intracranial malignancy, meningeal hemangiopericyotma. Case Description: A 32-year old HIV-positive male, not on highly active antiretroviral therapy, was admitted to our hospital due to generalized weakness and sudden onset hearing loss. Cranial MRI was done, which revealed a temporal nodule with the following considerations: granuloma, meningioma or metastases. A craniotomy was performed and the mass excised. Results from the biopsy showed meningeal hemangiopericytoma. The patient was then started on antiretroviral therapy (Lamivudine, Tenofovir, and Efavirenz) and was discharged for radiation therapy and metastatic work-up as an outpatient. On follow-up seven months later, metastatic work up revealed multiple hepatic foci not previously documented suggestive of metastasis short of biopsy sampling. Conclusions: This case of an intracranial hemangiopericytoma in an HIV-positive patient is the second case thus far presented, based on our systematic and extensive search of the literature.

Keywords: Hemangiopericytoma, Human Immunodeficiency Virus, Meningeal hemangiopericytoma, Neoplasm

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Authors: K. Santacruz-Gomez, E. Silva-Campa, S. Álvarez-García, V. Mata-Haro, D. Soto-Puebla, M. Pedroza-Montero

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Blood gamma irradiation is the only available method to prevent transfusion-associated graft versus host disease (TA-GVHD). However, when blood is irradiated, determine blood shelf time is crucial. Non-irradiated blood has a self-time from 21 to 35 days when is preserved with an anticoagulated solution and stored at 4°C. During their storage, red blood cells (RBC) undergo a series of biochemical, biomechanical and molecular changes involving what is known as storage lesion (SL). SL include loss of structural integrity of RBC, a decrease of 2,3-diphosphatidylglyceric acid levels, and an increase of both ion potassium concentration and hemoglobin (Hb). On the other hand, Atomic force Microscopy (AFM) represents a versatile tool for a nano-scale high-resolution topographic analysis in biological systems. In order to evaluate SL in irradiated and non-irradiated blood, RBC topography and morphometric parameters were obtained from an AFM XE-BIO system. Cell viability was followed using flow cytometry. Our results showed that early markers as nanoscale roughness, allow us to evaluate blood quality since another perspective.

Keywords: AFM, blood γ-irradiation, roughness, storage lesion

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Authors: Renjith George Pallivathukal, Preethy Mary Donald

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Asymptomatic oral lesions are often ignored by the patients and usually will be identified only in advanced stages. Early detection of precancerous lesions is important for better prognosis. It is also important for the oral health care person to be aware of the regional prevalence of oral lesions in order to provide early care for the same. We conducted a retrospective study to assess the prevalence of oral lesions based on the information available from patient records in a teaching dental school. Dental records of patients who attended the department of Oral medicine and diagnosis between September 2014 and September 2016 were retrieved and verified for oral lesions. Results: The ages of the patients ranged from 13 to 38 years with a mean age of 21.8 years. The lesions were classified as white (40.5%), red (23%), ulcerated (10.5%), pigmented (15.2%) and soft tissue enlargements (10.8%). 52% of the patients were unaware of the oral lesions before the dental visit. Overall, the prevalence of lesions in dental patients lower to national estimates, but the prevalence of some lesions showed variations.

Keywords: oral mucosal lesion, pre-cancer, prevalence, soft tissue lesion

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Authors: Alyaa Abdlwahab

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Cutaneous leishmaniasis represents a serious health problem in Syria; this problem has become noticeably aggravated after the civil war in the country. Leishmania tropica parasite is the main cause of cutaneous leishmaniasis in Syria. In order to control the disease, we need an effective vaccine against leishmania parasite. DNA vaccination remains one of the favorable approaches that have been used to face cutaneous leishmaniasis. Ribosomal protein S4 is responsible for important roles in Leishmania parasite life. DNA vaccine based on S4 gene has been used against infections by many species of Leishmania parasite but leishmania tropica parasite, so this gene represents a good candidate for DNA vaccine construction. After proving the existence of ribosomal protein S4 gene in a Syrian strain of Leishmania tropica (LCED Syrian 01), sequencing it and cloning it into pCI plasmid, BALB/C mice were inoculated with pCI-S4 DNA vaccine. The immune response was determined by monitoring the lesion progression in inoculated BALB/C mice for six weeks after challenging mice with Leishmania tropica (LCED Syrian 01) parasites. IL-12, IFN-γ, and IL-4 were quantified in draining lymph nodes (DLNa) of the immunized BALB/C mice by using the RT-qPCR technique. The parasite burden was calculated in the final week for the footpad lesion and the DLNs of the mice. This study proved the existence and the expression of the ribosomal protein S4 gene in Leishmania tropica (LCED Syrian 01) promastigotes. The sequence of ribosomal protein cDNA S4 gene was determined and published in Genbank; the gene size was 822 bp. Expression was also demonstrated at the level of cDNA. Also, this study revealed that pCI-S4 DNA vaccine induces TH1\TH2 response in immunized mice; this response prevents partially developing a dermal lesion of Leishmania.

Keywords: ribosomal protein S4, DNA vaccine, Leishmania tropica, BALB\c

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Authors: H. Hadjeris, R. B. Ghoul, Lekhlaf, M. Nebbal

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Introduction: Adenoid cystic carcinomas of the lacrimal gland or orbital cylindroma constitute the second cause of epithelial tumors of this gland. It is a malignant tumor usually developed at the expense of the salivary glands; its orbital location is exceptional. It is a rare clinical entity, formidable by its malignancy and local aggressiveness; the recurrence rate is high. Materials and methods: Clinical case: 63 years old woman who presents with irreducible no pulsatile painful left exophthalmos with inflammatory chemosis and a decrease in visual acuity with a moderate intracranial hypertension syndrome that has been evolving for 03 months. Antecedent; a biopsy of the tumor was made; the histological examination was in favor of an adenoid cystic carcinoma of the lacrimal gland. Lesion assessment: computed tomography and brain MRI: show an intra and extra-conical mass; with sinus (ethmoido-frontal) and cerebral (left frontal) extension strongly enhanced after injection of contrast product surrounded by edema around the lesion, associated with left frontal bone lysis extension assessment: unremarkable treatment: Patient operated by left frontotemporal approach, a total exenteration was performed with macroscopically complete excision of the frontal lesion and wide frontal craniectomy with craniofacial reconstruction, followed by complementary radiotherapy. Results: The patient was seen again after 3 months in consultation; she does not present any signs in favor of a recurrence. Conclusion: Adenoid cystic carcinomas of the lacrimal gland are rare malignant tumors; they are very infiltrating and invasive. The prognosis is strongly linked to the treatment time.

Keywords: adenoid cystic, lacrimal gland, orbital location, fronto-temporal approac

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Authors: Suhaida Salleh, Tee Yei Kheng

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Black pod is the most commonly destructive disease of cacao (Theobroma cacao) which cause major losses to global production of cocoa beans. The genus of Phytophthora is the important pathogen of this disease worldwide. The species of P. megakarya causes black pod disease in West Africa, whereas P. capsici and P. citrophthora cause the incident in Central and South America. In Malaysia, this disease is caused by P. palmivora which infect all stages of pod development including flower cushion, cherelle, immature and mature pods. This pathogen destroys up to 10% of trees yearly through stem cankers and causes 20 to 30% pod damages through black pod rot. Since P. palmivora has a high impact on cocoa yield, it is crucial to identify some of the abiotic factors that can constrain their growth. In an effort to evaluate the effect of different substrates and temperatures to the growth of P. palmivora, a laboratory study was done under a different range of temperatures. Different substrate for the growth of P. palmivora were used which are corn meal agar (CMA) media and detached pod of cocoa. An agar plug of seven days old of P. palmivora growth was transferred on both substrates and incubated at 24, 27, 30, 33 and 36ᵒC, respectively. The diameter of lesion on pod and the cultural growth of pathogen was recorded for 7 consecutive days. The optimum incubation temperature of P. palmivora on both substrates is at 27ᵒC. However, the growth tends to be inhibited as the temperature increases. No lesion developed on pod surface incubated at 36ᵒC and only a small lesion observed at 33ᵒC. The sporulation with the formation of white mycelial growth on pod surface was only visible at optimum temperature, 27ᵒC. On CMA, the pathogen grew over the entire range of temperatures tested. The study is, therefore, concluded that P. palmivora grow the best at temperature of 27ᵒC on both substrates and their growth begin to inhibit when the temperature rises to more than 27ᵒC. The growth pattern of this pathogen is similar on both pod surface and cultural media.

Keywords: cocoa, Phytophthora palmivora, substrate, temperature

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Authors: Delphine Morales, Florian Lombart, Agathe Truchot, Pauline Maire, Pascale Vigneron, Antoine Galmiche, Catherine Lok, Muriel Vayssade

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Targeted therapy molecules are used as a first-line treatment for metastatic melanoma with B-Raf mutation. Nevertheless, these molecules can cause side effects to patients and are efficient on 50 to 60 % of them. Indeed, melanoma cell sensitivity to targeted therapy molecules is dependent on tumor microenvironment (cell-cell and cell-extracellular matrix interactions). To better unravel factors modulating cell sensitivity to B-Raf inhibitor, we have developed and compared several melanoma models: from metastatic melanoma cells cultured as monolayer (2D) to a co-culture in a 3D dermal equivalent. Cell response was studied in different melanoma cell lines such as SK-MEL-28 (mutant B-Raf (V600E), sensitive to Vemurafenib), SK-MEL-3 (mutant B-Raf (V600E), resistant to Vemurafenib) and a primary culture of dermal human fibroblasts (HDFn). Assays have initially been performed in a monolayer cell culture (2D), then a second time on a 3D dermal equivalent (dermal human fibroblasts embedded in a collagen gel). All cell lines were treated with Vemurafenib (a B-Raf inhibitor) for 48 hours at various concentrations. Cell sensitivity to treatment was assessed under various aspects: Cell proliferation (cell counting, EdU incorporation, MTS assay), MAPK signaling pathway analysis (Western-Blotting), Apoptosis (TUNEL), Cytokine release (IL-6, IL-1α, HGF, TGF-β, TNF-α) upon Vemurafenib treatment (ELISA) and histology for 3D models. In 2D configuration, the inhibitory effect of Vemurafenib on cell proliferation was confirmed on SK-MEL-28 cells (IC50=0.5 µM), and not on the SK-MEL-3 cell line. No apoptotic signal was detected in SK-MEL-28-treated cells, suggesting a cytostatic effect of the Vemurafenib rather than a cytotoxic one. The inhibition of SK-MEL-28 cell proliferation upon treatment was correlated with a strong expression decrease of phosphorylated proteins involved in the MAPK pathway (ERK, MEK, and AKT/PKB). Vemurafenib (from 5 µM to 10 µM) also slowed down HDFn proliferation, whatever cell culture configuration (monolayer or 3D dermal equivalent). SK-MEL-28 cells cultured in the dermal equivalent were still sensitive to high Vemurafenib concentrations. To better characterize all cell population impacts (melanoma cells, dermal fibroblasts) on Vemurafenib efficacy, cytokine release is being studied in 2D and 3D models. We have successfully developed and validated a relevant 3D model, mimicking cutaneous metastatic melanoma and tumor microenvironment. This 3D melanoma model will become more complex by adding a third cell population, keratinocytes, allowing us to characterize the epidermis influence on the melanoma cell sensitivity to Vemurafenib. In the long run, the establishment of more relevant 3D melanoma models with patients’ cells might be useful for personalized therapy development. The authors would like to thank the Picardie region and the European Regional Development Fund (ERDF) 2014/2020 for the funding of this work and Oise committee of "La ligue contre le cancer".

Keywords: 3D human skin model, melanoma, tissue engineering, vemurafenib efficiency

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Authors: Chung-Ming Lo, Chung-Chien Lee

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In many countries, the lifetime prevalence of shoulder pain is up to 70%. In America, the health care system spends 7 billion per year about the healthy issues of shoulder pain. With respect to the origin, up to 70% of shoulder pain is attributed to rotator cuff lesions This study proposed a computer-aided diagnosis (CAD) system to assist radiologists classifying rotator cuff lesions with less operator dependence. Quantitative features were extracted from the shoulder ultrasound images acquired using an ALOKA alpha-6 US scanner (Hitachi-Aloka Medical, Tokyo, Japan) with linear array probe (scan width: 36mm) ranging from 5 to 13 MHz. During examination, the postures of the examined patients are standard sitting position and are followed by the regular routine. After acquisition, the shoulder US images were drawn out from the scanner and stored as 8-bit images with pixel value ranging from 0 to 255. Upon the sonographic appearance, the boundary of each lesion was delineated by a physician to indicate the specific pattern for analysis. The three lesion categories for classification were composed of 20 cases of tendon inflammation, 18 cases of calcific tendonitis, and 18 cases of supraspinatus tear. For each lesion, second-order statistics were quantified in the feature extraction. The second-order statistics were the texture features describing the correlations between adjacent pixels in a lesion. Because echogenicity patterns were expressed via grey-scale. The grey-scale co-occurrence matrixes with four angles of adjacent pixels were used. The texture metrics included the mean and standard deviation of energy, entropy, correlation, inverse different moment, inertia, cluster shade, cluster prominence, and Haralick correlation. Then, the quantitative features were combined in a multinomial logistic regression classifier to generate a prediction model of rotator cuff lesions. Multinomial logistic regression classifier is widely used in the classification of more than two categories such as the three lesion types used in this study. In the classifier, backward elimination was used to select a feature subset which is the most relevant. They were selected from the trained classifier with the lowest error rate. Leave-one-out cross-validation was used to evaluate the performance of the classifier. Each case was left out of the total cases and used to test the trained result by the remaining cases. According to the physician’s assessment, the performance of the proposed CAD system was shown by the accuracy. As a result, the proposed system achieved an accuracy of 86%. A CAD system based on the statistical texture features to interpret echogenicity values in shoulder musculoskeletal ultrasound was established to generate a prediction model for rotator cuff lesions. Clinically, it is difficult to distinguish some kinds of rotator cuff lesions, especially partial-thickness tear of rotator cuff. The shoulder orthopaedic surgeon and musculoskeletal radiologist reported greater diagnostic test accuracy than general radiologist or ultrasonographers based on the available literature. Consequently, the proposed CAD system which was developed according to the experiment of the shoulder orthopaedic surgeon can provide reliable suggestions to general radiologists or ultrasonographers. More quantitative features related to the specific patterns of different lesion types would be investigated in the further study to improve the prediction.

Keywords: shoulder ultrasound, rotator cuff lesions, texture, computer-aided diagnosis

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Authors: Nan Deng, Zhenqiu Liu

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Thousands of patients with metastatic tumors were diagnosed with cancers of unknown primary sites each year. The inability to identify the primary cancer site may lead to inappropriate treatment and unexpected prognosis. Nowadays, a large amount of genomics and transcriptomics cancer data has been generated by next-generation sequencing (NGS) technologies, and The Cancer Genome Atlas (TCGA) database has accrued thousands of human cancer tumors and healthy controls, which provides an abundance of resource to differentiate cancer types. Meanwhile, deep convolutional neural networks (CNNs) have shown high accuracy on classification among a large number of image object categories. Here, we utilize 25 cancer primary tumors and 3 normal tissues from TCGA and convert their RNA-Seq gene expression profiling to color images; train, validate and test a CNN classifier directly from these images. The performance result shows that our CNN classifier can archive >80% test accuracy on most of the tumors and normal tissues. Since the gene expression pattern of distant metastases is similar to their primary tumors, the CNN classifier may provide a potential computational strategy on identifying the unknown primary origin of metastatic cancer in order to plan appropriate treatment for patients.

Keywords: bioinformatics, cancer, convolutional neural network, deep leaning, gene expression pattern

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Authors: Oleg Sapelnikov, Ruslan Latypov, Darina Ardus, Samvel Aivazian, Andrey Shiryaev, Renat Akchurin

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OBJECTIVE: MAZE procedure is one of the most effective surgical methods in atrial fibrillation (AF) treatment. Nowadays we are all aware of its modifications. In our study we conducted clinical analysis of “Box lesion+” approach during MAZE procedure in two-year follow-up. METHODS: We studied the results of the open-heart on-pump procedures performed in our hospital from 2017 to 2018 years. Thirty-two (32) patients with atrial fibrillation (AF) were included in this study. Fifteen (15) patients had concomitant coronary bypass grafting and seventeen (17) patients had mitral valve repair. Mean age was 62.3±8.7 years; prevalence of men was admitted (56.1%). Mean duration of AF was 4.75±5.44 and 7.07±8.14 years. In all cases, we performed endocardial Cryo-MAZE procedure with one-time myocardium revascularization or mitral-valve surgery. All patients of this study underwent pulmonary vein (PV) isolation and ablation of mitral isthmus with additional isolation of LA posterior wall (Box-lesion+ procedure). Mean follow-up was 2 years. RESULTS: All cases were performed without any complications. Additional isolation of posterior wall did not prolong the operative time and artificial circulation significantly. Cryo-MAZE procedure directly lasted 20±2.1 min, the whole operation time was 192±24 min and artificial circulation time was 103±12 min. According to design of the study, we performed clinical investigation of the patients in 12 months and in 2 years from the initial procedure. In 12 months, the number of AF free patients 81.8% and 75.8% in two years of follow-up. CONCLUSIONS: Isolation of the left atrial posterior wall and perimitral area may considerably improve the efficacy of surgical treatment, which was demonstrated in significant decrease of AF recurrences during the whole period of follow-up.

Keywords: atrial fibrillation, cryoablation, left atrium isolation, open heart procedure

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Authors: Bharti Arora, Michael Chen, Steven Lun

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Plasmacytoid urothelial carcinoma (PUC) of the bladder is a rare and aggressive subtype of urothelial carcinoma that usually presents at an advanced clinical stage, has a predilection for early metastatic potential and is associated with poor prognosis. The first reported case of PUC was in 1991 and approximately 100 cases were reported in the literature worldwide. We present a case of a 43 year old female presenting with a 3-month history of urgency and frequency. Failing medical management of her urinary symptoms with anticholinergic medication, she underwent a diagnostic cystoscopy which revealed an erythematous and indurated bladder. Bladder biopsies of these regions revealed plasmacytoid urothelial carcinoma. Pre-operative staging scans were clear of any metastatic disease and the patient subsequently underwent a radical cystectomy and pelvic clearance with the formation of ileal conduit for urinary diversion. Histology confirmed plasmacytoid urothelial carcinoma with involvement of right upper vagina and focally positive margins in soft tissue at right and left sides of bladder. She received adjuvant chemotherapy but passed away within a year from disease progression. PUC can present atypically and our case highlights the role of cystoscopy in patients with persistent urinary symptoms. By reviewing the literature on PUC, we aim to raise awareness and improve understanding of this rare bladder cancer subtype amongst urologists.

Keywords: urology, bladder cancer, plasmacytoid urothelial cancer, literature review

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Authors: Philip Friedlander, John Rutledge, Jason Suh

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Inhibition of programmed death-1 (PD-1) or its ligand PD-L1 confers therapeutic efficacy in a wide range of solid tumor malignancies. Primary or acquired resistance can develop through activation of immunosuppressive immune cells such as tumor-associated macrophages. The renin angiotensin system (RAS) systemically regulates fluid and sodium hemodynamics, but components are expressed on and regulate the activity of immune cells, particularly of myeloid lineage. We hypothesized that inhibition of RAS would improve the efficacy of PD-1/PD-L-1 treatment. A retrospective analysis was performed through a chart review of patients with solid metastatic malignancies treated with a PD-1/PD-L1 inhibitor between 1/2013 and 6/2019 at Valley Hospital, a community hospital in New Jersey, USA. Efficacy was determined by medical oncologist documentation of clinical benefit in visit notes and by the duration of time on immunotherapy treatment. The primary endpoint was the determination of efficacy differences in patients treated with an inhibitor of RAS ( ace inhibitor, ACEi, or angiotensin blocker, ARB) compared to patients not treated with these inhibitors. To control for broader antihypertensive effects, efficacy as a function of treatment with beta blockers was assessed. 173 patients treated with PD-1/PD-L-1 inhibitors were identified of whom 52 were also treated with an ACEi or ARB. Chi-square testing revealed a statistically significant relationship between being on an ACEi or ARB and efficacy to PD-1/PD-L-1 therapy (p=0.001). No statistically significant relationship was seen between patients taking or not taking beta blocker antihypertensives (p= 0.33). Kaplan-Meier analysis showed statistically significant improvement in the duration of therapy favoring patients concomitantly treated with ACEi or ARB compared to patients not exposed to antihypertensives and to those treated with beta blockers. Logistic regression analysis revealed that age, gender, and cancer type did not have significant effects on the odds of experiencing clinical benefit (p=0.74, p=0.75, and p=0.81, respectively). We conclude that retrospective analysis of the treatment of patients with solid metastatic tumors with anti-PD-1/PD-L1 in a community setting demonstrates greater clinical benefit in the context of concomitant ACEi or ARB inhibition, irrespective of gender or age. This data supports the development of prospective assessment through randomized clinical trials.

Keywords: angiotensin, cancer, immunotherapy, PD-1, efficacy

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Authors: Ebenezer O. Ige, Funmilayo H. Oyelami, Joshua Olutayo-Irheren, Joseph T. Okunlola

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Hyperthermia therapy is an adjuvant procedure during which perfused body tissues is subjected to elevated range of temperature in bid to achieve improved drug potency and efficacy of cancer treatment. While a selected class of hyperthermia techniques is shouldered on the thermal radiations derived from single-sourced electro-radiation measures, there are deliberations on conjugating dual radiation field sources in an attempt to improve the delivery of therapy procedure. This paper numerically explores the thermal effectiveness of combined infrared hyperemia having nanoparticle recirculation in the vicinity of imposed magnetic field on subcutaneous strata of a model lesion as ablation scheme. An elaborate Spectral relaxation method (SRM) was formulated to handle equation of coupled momentum and thermal equilibrium in the blood-perfused tissue domain of a spongy fibrous tissue. Thermal diffusion regimes in the presence of external magnetic field imposition were described leveraging on the renowned Roseland diffusion approximation to delineate the impact of radiative flux within the computational domain. The contribution of tissue sponginess was examined using mechanics of pore-scale porosity over a selected of clinical informed scenarios. Our observations showed for a substantial depth of spongy lesion, magnetic field architecture constitute the control regimes of hemodynamics in the blood-tissue interface while facilitating thermal transport across the depth of the model lesion. This parameter-indicator could be utilized to control the dispensing of hyperthermia treatment in intravenous perfused tissue.

Keywords: spectra relaxation scheme, thermal equilibrium, Roseland diffusion approximation, hyperthermia therapy

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Authors: Sweta Agrawal, Sachin Chaugule, Gargi Rane, Shashank More, Madhavi Indap

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Angiogenesis and metastasis are two of the most important hallmarks of cancer. Hence, most of the cancer therapies nowadays are multi-targeted so as to reduce resistance and have better efficacy. As synthetic molecules arise with a burden of their toxicities and side-effects, more and more research is being focussed on exploiting the vast natural resources of drugs, in the form of plants and animals. Although, the idea of using marine organisms as a source of pharmaceuticals is not new, the pace at which marine drugs are being discovered, has definitely up surged! In the present study, we have assessed the anti-angiogenic and in vitro anti-metastatic activity of aqueous fraction from the extract of marine gastropod Euchelus asper. The soft body of Euchelus Asper was extracted with methanol and named EAME. Partition chromatography of EAME gave three fractions EAME I, II and III. Biochemical analysis revealed the presence of proteins in EAME III. Preliminary analysis had revealed the anti-angiogenic activity was exhibited by EAME III out of the three fractions. Hereafter, EAME III (concentration 25µg/ml-400µg/ml) was tested on chick chorioallantoic membrane (CAM) model for the detailed analysis of its potential anti-angiogenic effect. In vitro testing of the fraction (concentration 0.25µg/ml - 1µg/ml), involved cytotoxicity by SRB assay, cell cycle analysis by flow cytometry and anti-proliferative effect by scratch wound healing assay on A549 lung carcinoma cells. Apart from this, a portion of treated CAM as well as conditioned medium from treated A549 were subjected to gelatin zymography for assessment of matrix metalloproteinases MMP-2 and MMP-9 levels. Our results revealed that EAME III exhibited significant anti-angiogenic activity on CAM which was also supported by histological observations. During histological studies of CAM, it was found that EAME III caused reduction in angiogenesis by altering the extracellular matrix of the CAM membrane. In vitro analysis disclosed that EAME III exhibited moderate cytotoxic effect on A549 cells and its effect was not dose-dependent. The results of flow cytometry confirmed that EAME III caused cell cycle arrest in A549 cell line as almost all of the treated cells were found in G1 phase. Further, the migration and proliferation of A549 was significantly reduced by EAME III as observed from the scratch wound assay. Moreover, Gelatin zymography analysis revealed that EAME III caused suppression of MMP-2 in CAM membrane and reduced MMP-9 and MMP-2 expression in A549 cells. This verified that the anti-angiogenic and anti-metastatic effects of EAME III were correlated with the suppression of MMP-2 and -9. To conclude, EAME III shows dual anti-tumour action by reducing angiogenesis and exerting anti-metastatic effect on lung cancer cells, thus it has the potential to be used as an anti-cancer agent against lung carcinoma.

Keywords: angiogenesis, anti-cancer, marine drugs, matrix metalloproteinases

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Authors: Yun-Tsuen Chen, Shih-Ting Huang, Pi-Fen Cheng, Yu-Ting Su, Joffrey Hsu, Hui-Zhu Chen

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Acute intestinal obstruction is one of the differentials of acute abdomen and requires timely alleviation of intestinal distention and abdominal pain to avoid perforation, intra-abdominal infection, and peritonitis. Investigation to identify the cause of obstruction will direct treatment planning and allow for more effective management. In this study, we present a 71-year-old female presenting with symptoms of acute intestinal obstruction for five days. After extensive history taking, physical exam, medical imaging, and pathology, the patient was diagnosed with colon cancer with lung metastasis and acute intestinal obstruction. The patient was placed on nil per os status with intravenous fluid support, intravenous antibiotics, and a decompression nasogastric tube was placed. The patient received decompression with colostomy creation surgery. After assessing the patient’s clinical condition and tumor staging, a multidisciplinary healthcare team created an individualized treatment plan, which included plans to prepare the patient for home self-care and maintain good mental health with regular monitoring in the clinic setting. This case demonstrates the importance of early diagnosis, effective treatment, and a multidisciplinary approach to the management of acute intestinal obstruction secondary to colon cancer.

Keywords: acute intestinal obstruction, colostomy surgery, metastatic colon cancer, multidisciplinary healthcare team

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Authors: Piotr Muzyk, Beata Morawiec, Mariusz Opara, Andrzej Tomasik, Brygida Przywara-Chowaniec, Wojciech Jachec, Ewa Nowalany-Kozielska, Damian Kawecki

Abstract:

Background: Coronary bifurcation is one of the most complex lesion in patients with coronary ar-tery disease. Provisional T-stenting is currently one of the recommended techniques. The aim was to assess optimal methods of treatment in the era of drug-eluting stents (DES). Methods: The regis-try consisted of data from 1916 patients treated with coronary percutaneous interventions (PCI) using either first- or second-generation DES. Patients with bifurcation lesion entered the analysis. Major adverse cardiac and cardiovascular events (MACCE) were assessed at one year of follow-up and comprised of death, acute myocardial infarction (AMI), repeated PCI (re-PCI) of target ves-sel and stroke. Results: Of 1916 registry patients, 204 patients (11%) were diagnosed with bifurcation lesion >50% and entered the analysis. The most commonly used technique was provi-sional T-stenting (141 patients, 69%). Optimization with kissing-balloons technique was performed in 45 patients (22%). In 59 patients (29%) second-generation DES was implanted, while in 112 pa-tients (55%), first-generation DES was used. In 33 patients (16%) both types of DES were used. The procedure success rate (TIMI 3 flow) was achieved in 98% of patients. In one-year follow-up, there were 39 MACCE (19%) (9 deaths, 17 AMI, 16 re-PCI and 5 strokes). Provisional T-stenting resulted in similar rate of MACCE to other techniques (16% vs. 5%, p=0.27) and similar occurrence of re-PCI (6% vs. 2%, p=0.78). The results of post-PCI kissing-balloon technique gave equal out-comes with 3% vs. 16% of MACCE in patients in whom no optimization technique was used (p=0.39). The type of implanted DES (second- vs. first-generation) had no influence on MACCE (4% vs 14%, respectively, p=0.12) and re-PCI (1.7% vs. 51% patients, respectively, p=0.28). Con-clusions: The treatment of bifurcation lesions with PCI represent high-risk procedures with high rate of MACCE. Stenting technique, optimization of PCI and the generation of implanted stent should be personalized for each case to balance risk of the procedure. In this setting, the operator experience might be the factor of better outcome, which should be further investigated.

Keywords: coronary bifurcation, drug eluting stents, long-term follow-up, percutaneous coronary interventions

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Authors: Yousef Reda

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Pancreatic cancer has an overall dismal prognosis. CT, MRI and Endoscopic Ultrasound are most often used to establish the diagnosis. We present a case of a patient found on abdominal CT and MRI to have an 8 mm cystic lesion within the head of the pancreas which was thought to be a benign intraductal papillary mucinous neoplasm (IPMN). Further evaluation by EUS demonstrated a 1 cm predominantly solid mass that was proven to be an adenocarcinoma by EUS-guided FNA. The patient underwent a Whipple procedure. The final pathology confirmed a 1 cm pT1 N0 pancreatic ductal adenocarcinoma. Case: A 63-year-old male presented with left upper quadrant pain and an abdominal CT demonstrated an 8 mm lesion within the head of the pancreas that was thought to represent a side branch IPMN. An MRI also showed similar findings. Four months later due to ongoing symptoms an EUS was performed to re-evaluate the pancreatic lesion. EUS revealed a predominantly solid hypoechoic, homogeneous mass measuring 12 mm x 9 mm. EUS-guided FNA was performed and was positive for adenocarcinoma. The patient underwent a Whipple procedure that confirmed it to be a ductal adenocarcinoma, pT1N0. The solid mass was noted to be adjacent to a cystic dilation with no papillary architecture and scant epithelium. The differential diagnosis resided between cystic degeneration of a primary pancreatic adenocarcinoma versus malignant degeneration within a side-branch IPMN. Discussion: The reported sensitivity of CT for pancreatic cancer is approximately 90%. For pancreatic tumors, less than 3 cm the sensitivity of CT is reduced ranging from 67-77%. MRI does not significantly improve overall detection rates compared to CT. EUS, however is superior to CT in the detection of pancreatic cancer, in particular among lesions smaller than 3 cm. EUS also outperforms CT and MRI in distinguishing neoplastic from non-neoplastic cysts. In this case, both MRI and CT failed to detect a small pancreatic adenocarcinoma. The addition of EUS and FNA to abdominal imaging can increase overall accuracy for the diagnosis of neoplastic pancreatic lesions. It may be prudent that when small lesions although appearing as a benign IPMN should further be evaluated by EUS as this would lead to potentially identifying earlier stage pancreatic cancers and improve survival in a disease which has a dismal prognosis.

Keywords: IPMN, MRI, EUS, CT

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Authors: Nasrin Hosseinzad, Ramin Ghasemi Shayan

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Chemotherapy is the most common procedure in the treatment of advanced cancers but is justsoberlyoperativeand toxic. Nevertheless, the efficiency of chemotherapy is restrictedowing to multiple drug resistance(MDR). Lately, plentiful preclinical experiments have revealedthatPaclitaxel-Curcumin could be an ultimateapproach to converse MDR and synergistically increase their efficiency. The connotationsamongst B-cell-lymphoma2(BCL-2) and multi-drug-resistance-associated-P-glycoprotein(MDR1) consequence of patients forecast the efficiency of paclitaxel-built chemoradiotherapy. There are evidences of the efficacy of paclitaxel in the treatment of surface-transmission of bladder-cell-carcinoma by manipulating bio-adhesive microspheres accomplishedthroughout measured release of drug at urine epithelium. In Genetically-Modified method, muco-adhesive oily constructionoftricaprylin, Tween 80, and paclitaxel group showed slighter toxicity than control in therapeutic dose. Postoperative chemotherapy-Paclitaxel might be more advantageous for survival than adjuvant chemo-radio-therapy, and coulddiminish postoperative complications in cervical cancer patients underwent a radical hysterectomy.HA-Se-PTX(Hyaluronic acid, Selenium, Paclitaxel) nanoparticles could observablyconstrain the proliferation, transmission, and invasion of metastatic cells and apoptosis. Furthermore, they exhibitedvast in vivo anti-tumor effect. Additionally, HA-Se-PTX displayedminor toxicity on mice-chef-organs. Briefly, HA-Se-PTX mightprogress into a respectednano-scale agentinrespiratory cancers. To sum up, Paclitaxel is considered a profitable anti-cancer drug in the treatment and anti-progress symptoms in malignant cancers.

Keywords: cancer, paclitaxel, chemotherapy, tumor

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Authors: Phill-Seung Jung, Dae-Yeon Kim

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Objectives: In young, especially nulliparous women, it is not easy to decide on excisional therapy for cervical intraepithelial neoplasia (CIN). We aimed to evaluate how effective topical imiquimod is in the treatment of high-grade CIN so that excisional therapy can be avoided in young women. Methods: Patients with CIN were allocated to this pilot study. They did not want excisional therapy and agreed with topical imiquimod therapy, which required once-a-week hospital visit for 8 weeks for the application of imiquimod to the cervix by a gynecologic oncologist. If the lesion got worse during treatment, it was decided to convert imiquimod therapy to excisional therapy. Results: A total of 36 patients with a median age of 29 years (range, 22–41 years) agreed to receive topical imiquimod therapy. Of these, 32 patients (88.9%) were positive for high-risk human papillomavirus (HR HPV). Twenty-five patients (69.4%) had low-grade squamous intraepithelial lesion (LSIL), and 11 (30.6%) had high-grade squamous intraepithelial lesion (HSIL) on their initial LBC. Twenty-eight patients underwent punch biopsy, which showed CIN 1 in 7 (19.4%), CIN 2 in 11 (30.6%), and CIN 3 in 10 (27.8%) patients. Twenty patients finished the 8-week imiquimod therapy. Among them, 14 patients had CIN 2 or 3, and 6 patients had CIN 1. HR HPV was positive in 12 patients. On the last examination, 14 patients (70.0%) had negative intraepithelial lesions, 3 (15.0%) had atypical squamous cells of undetermined significance, and 1 (5.0%) had LSIL. Two patients had persistent HSIL: 1 patient underwent loop electrosurgical excision procedure, resulting in CIN 3 with positive resection margin, and the other patient underwent punch biopsy, resulting in intermediate cells and restarted imiquimod therapy. Only 7 patients were negative for HR HPV. Conclusions: This study showed that topical imiquimod therapy was effective for the treatment of high-grade CIN, with a histologic regression rate of 85.7% (14/20) and HPV eradication rate of 25.0% (8/32). Based on our findings, topical imiquimod therapy might have a successful therapeutic effect in young women with CIN 2-3 so that they can avoid excisional therapy. In addition, it could be a more reassuring treatment option for CIN 1 than just follow-up after few months. To confirm its efficacy, a phase II study with larger cohort would be needed.

Keywords: Imiquimod, Cervical Intraepthelial Neoplasia, Cervical Dysplasia, Human Papillomavirus

Procedia PDF Downloads 251

Authors: Michio Kurosu

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Alterations in glycosylation not only directly impact cell growth and survival but also facilitate tumor-induced immunomodulation and eventual metastasis. Identification of cell type-specific glycoconjugates (tumor markers) has led to the discovery of new assay systems for certain cancers via immunodetection reagents. N- and O-linked glycans are the most abundant forms of glycoproteins. Recent studies of cancer immunotherapy are based on the immunogenicity of truncated O-glycan chains (e.g., Tn, sTn, T, and sLea/x). The prevalence of N-linked glycan changes in the development of tumor cells is known; however, therapeutic antibodies against N-glycans have not yet been developed. This is due to the lack of specificity of N-linked glycans between normal/healthy and cancer cells. Abnormal branching of N-linked glycans has been observed, particularly in solid cancer cells. While the discovery of drug-like glycosyltransferase inhibitors that block the biosynthesis of specific branching has a very low likelihood of success, altered glycosylation levels can be exploited by suppressing N-glycan biosynthesis through the inhibition of dolichyl-phosphate N-acetylglucosaminephosphotransferase1 (DPAGT1) activity. Inhibition of DPAGT1 function leads to changes of O-glycosylation on proteins associated with mitochondria and zinc finger binding proteins (indirect effects). On the basis of dynamic crosstalk between DPAGT1 and Snail/Slung/ZEB1 (a family of transcription factors that promote the repression of the adhesion molecules), we have developed pharmacologically acceptable selective DPAGT1 inhibitors. Tunicamycin kills a wide range of cancer and healthy cells in a non-selective manner. In sharp contrast, our DPAGT1 inhibitors display strong cytostatic effects against 16 solid cancers, which require the overexpression of DPAGT1 in their progression but do not affect the cell viability of healthy cells. The identified DPAGT1 inhibitors possess impressive anti-metastatic ability in various solid cancer cell lines and induce their mitochondrial structural changes, resulting in apoptosis. A prototype DPAGT1 inhibitor, APPB has already been proven to shrink solid tumors (e.g., pancreatic cancers, triple-negative breast cancers) in vivo while suppressing metastases and has strong synergistic effects when combined with current cytotoxic drugs (e.g., paclitaxel). At this conference, our discovery of selective DPAGT1 inhibitors with drug-like properties and proof-of-pharmaceutical concept studies of a novel DPAGT1 inhibitor are presented.

Keywords: DPAGT1 inhibitors, anti-metastatic drugs, natural product based drug designs, cytostatic effects

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Authors: Habib Alah Dadgar, Nasim Norouzbeigi

Abstract:

The precise definition margin of high and low-grade gliomas is crucial for treatment. We aimed to assess the feasibility of assessment of the resection legions with post-operative positron emission tomography (PET) using [18F]O-(2-[18F]-fluoroethyl)-L-tyrosine ([18F]FET). Four patients with the suspicion of high and low-grade were enrolled. Patients underwent post-operative [18F]FET-PET, pre-operative magnetic resonance imaging (MRI) and CT for clinical evaluations. In our study, three patients had negative response to recurrence and progression and one patient indicated positive response after surgery. [18F]FET-PET revealed a legion of increased radiotracer uptake in the dura in the craniotomy site for patient 1. Corresponding to the patient history, the study was negative for recurrence of brain tumor. For patient 2, there was a lesion in the right parieto-temporal with slightly increased uptake in its posterior part with SUVmax = 3.79, so the study was negative for recurrence evaluation. In patient 3 there was no abnormal uptake with negative result for recurrence of brain tumor. Intense radiotracer uptake in the left parietal lobe where in the MRI there was a lesion with no change in enhancement in the post-contrast image is indicated in patient 4. Assessment of the resection legions in high and low-grade gliomas with [18F]FET-PET seems to be useful.

Keywords: FET-PET, CT, glioma, MRI

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Authors: Javad Vaezi, Ashraf Mohammadzadeh, Behjatalomoluk Ajami, Azin Vaezi, Aradokht Vaezi

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Introduction: Neonatal period is the first developing phase after birth, followed by different developmental processes up to the age of puberty. A neonate may be born with different oral lesions. The aim of this study was to evaluate oral lesions in newborns at Mashhad Imam Reza Hospital, which belongs to Mashhad University of Medical Sciences. Materials and Methods: In this cross–sectional descriptive study, 600 newborns were observed during 2.5 months in 2001. The total oral cavity, including the soft palate, hard palate, tongue, alveolar ridge, and oral cavity floor, was examined with a tongue blade and light. Results: Results showed that 52.6% of newborns (316 cases) had oral lesions. 0.66% cases had natal and neonatal teeth, 0.5% cases had congenital epulis, 1.8% cases were with ankyloglossia, 41.5% cases with Epstein’s pearls, 22.3% cases with Bohn nodules and 0.16% case with exostosis. There were no cases of cleft lip or cleft palate. The most frequent oral lesion observed was Epstein’s pearls. Conclusion: Our study showed that the prevalence of natal teeth in the city of Mashhad was more than in other countries except for Bohn nodule and Epstein’s pearls, which occurred less frequently than in other countries.

Keywords: newborn, oral lesion, epidemiology, frequency

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