Effect of Photobiomodulation on Salivary Cytokines in Head and Neck Cancer Patients with Oral Mucositis: A Systematic Review.

Background: Oral mucositis is a common and distressing side effect of head and neck oncology treatment. Photobiomodulation therapy can be utilized to prevent and treat oral mucositis. Its impact on salivary cytokines has yet to be thoroughly investigated. This is the first systematic review aiming to evaluate the effect of photobiomodulation on salivary cytokines in patients undergoing anticancer treatment. Methods: Numerous data resources, from the Web of Science, Embase, ScienceDirect, PubMed, Cochrane Library, and Scopus were sought. Articles published up until February 2024 were included if they met the following inclusion criteria: clinical trials reporting the effect on salivary cytokines in patients undergoing anticancer therapy. The methodological quality was assessed using several appraisal tools. Results: Four studies were deemed eligible for inclusion. All the studies were conducted in Brazil and used an InGaAlP diode laser with a wavelength of 660 nm. The included studies had a relatively low risk of bias. The head and neck cancer patients' salivary cytokines that were assessed by the studies, along with photobiomodulation therapy, included IL-12p70, TNF-α, IL-6, IL-8, IL-10, CXCL8, and IL-1ß. The results varied among the studies. Conclusions: Our results show that photobiomodulation demonstrated positive results for reducing the severity of OM in all the included studies. Among the examined salivary cytokines, IL-6 is the most relevant cytokine for oral mucositis development and severity. A variation in the cytokine levels between the studies was noted due to differences in the type of anticancer treatment and saliva sampling.

The frequency of NUDT15 rs116855232 and its impact on mercaptopurine-induced toxicity in Syrian children with acute lymphoblastic leukemia.

Introduction: Polymorphisms in NUDT15 may result in differences in mercaptopurine-induced toxicity. This study aimed to identify the frequency of the NUDT15 (c.415C>T; rs116855232) polymorphism and investigate the effect of this polymorphism on mercaptopurine-induced toxicity in a population of Syrian patients with childhood acute lymphoblastic leukemia (ALL). Methods: This is a retrospective study that included children with ALL reaching at least 6 months of maintenance therapy. The NUDT15 genotyping was determined using standard targeted sequencing of polymerase chain reaction products. The odds ratio (OR) for the association between toxicity and genotype was evaluated. Results: A total of 92 patients were enrolled. The majority of the patients in the study population were low-risk (63.04%), followed by intermediate-risk (25%), and high-risk (11.96%). There were 5 patients (5.4%) with NUDT15 (c.415C>T; rs116855232) CT genotype, and 1 patient (1.08%) with NUDT15 TT genotype, with allele frequencies of C=0.962 and T=0.038. The mercaptopurine median dose intensity was 100%, 54.69%, and 5% for the genotypes CC, CT, and TT, respectively (P=0.009). Early onset leukopenia was significantly associated with the NUDT15 polymorphism (OR: 6.16, 95% CI: 1.11-34.18, P=0.037). There was no association between the NUDT15 genotype and hepatotoxicity. Conclusion: Approximately 6.5% of the study population exhibited reduced NUDT15 activity. The mercaptopurine dose intensity was considerably low in NUDT15 rs116855232 TT genotype compared with CT and CC. The dosage of mercaptopurine should be adjusted according to the NUDT15 genotype in pediatric patients with ALL.

Knowledge and practice of breast self-examination among breast cancer patients in Damascus, Syria.

BACKGROUND: Breast cancer (BC) represents an important cause of cancer death, its incidence rate has been rising gradually in the Arab world, and in Syria, BC is the most common cancer and the leading cause of cancer death; its prognosis gets better as we detect it early in its first stages. So, it is very important to implement one or more early detection methods such as Breast Self-Examination (BSE), Clinical Breast Examination (CBE), and mammography. BSE represents an effective method to find out changes in breast structure when they happen. This study investigates the knowledge of BSE and its practice in BC patients. METHODS: A quantitative cross-sectional study in Al-Bairouni hospital in Damascus-Syria was carried out using face-to-face interviews based on a structured questionnaire, which consisted of 4 sections. The data were subjected to statistical analysis using various analytical tests, including the independent t-test, one-way analysis of variance (ANOVA), and Chi-square test. RESULTS: Five hundred patients were interviewed. Only 27.4% of patients had a good knowledge of BSE, 17.4% had average knowledge, and 55.2% had low knowledge of BSE. The factors that have an impact on the knowledge of BSE were: family breast cancer history (first and second-degree relatives), education, and the region of living (between governorates). The effect of knowledge of BSE on its practice was positive. However, only 24.8% of patients have been practicing BSE; the reasons for not practicing BSE were: no one has told the patient about it (64.8% of cases), and the patient does not have any symptoms relating to the breast (21.4%).Breast cancer was identified through breast self-examination (BSE) in 15.6% of cases. CONCLUSION: There is a low degree of knowledge and little practice of BSE among Syrian breast cancer patients. Family breast cancer history, governate, occupation, and level of education had a statistically significant effect on knowledge scores of BSE, unlike age and social status. So, some steps should be taken to increase awareness about BSE among Syrian females.

Breast cancer quality of care in Syria: screening, diagnosis, and staging.

BACKGROUND: The Syrian decade-long war has severely affected the healthcare system, including almost vanishing cancer screening practices, war-destroyed medical facilities, and lack of continuous medical education. This study aims to present data on the affected breast cancer screening practices, methods of diagnosis, and stages distribution in Syria. METHODS: Medical charts of breast cancer patients treated at Albairouni University Hospital between January 2019 and May 2022 were retrospectively reviewed. Eligible patients were women diagnosed with primary breast cancer. Exclusion criteria included females receiving neoadjuvant chemotherapy and incomplete charts. Data regarding the patient's age, city of residence, marital status, number of children, smoking habits, method of diagnosis, tumor size (T), lymph nodes (N), and distal metastasis (M) were collected. We used Microsoft Excel and Statistical Package for the Social Sciences (SPSS) to analyze data. Descriptive methodology (frequency [n], percentage) was used. RESULTS: The number of charts reviewed was 4,500. The number of remaining charts after applying the exclusion criteria was 2,367. The mean age was 51.8 (SD = 11.3). More than half of the patients (58.3%) came from outside Damascus -where the hospital is located- and its suburbs. Less than 5% of the population detected cancer by screening mammography. Only 32.4% of patients were diagnosed by a biopsy, while surgical procedures (lumpectomy and mastectomy) were used to diagnose 64.8% of the population. At the time of diagnosis, only 8% of patients presented with local-stage disease (stages 0 & I), 73% had a regional disease (stages II & III), and 19% had metastatic breast cancer (stage IV). CONCLUSION: Our retrospective chart review analysis is the first comprehensive review in Syria for female breast cancer patients. We found a significant low percentage of patients diagnosed based on a screening mammogram, much higher surgical biopsies rather than a simple imaging-guided biopsy, and much lower than the national average of early-stage disease. Our alarming findings can serve as the base for future strategies to raise the population's health awareness, create more serious national screening campaigns, and adopt a multidisciplinary approach to the disease in Syria.

The use of advanced-platelet rich fibrin (A-PRF) in the management of medication-related osteonecrosis of the jaw (MRONJ): A case report.

Medication-related osteonecrosis of the jaws (MRONJ) is a serious debilitating disease resulting from long-term treatment with Antiresorptive drugs such as Bisphosphonates or Denosumab, which significantly affects patients' quality of life. A 43-year-old female patient with stage 4 breast cancer and treated with Zoledronic Acid for bone metastases was referred to the Department of Oral Medicine at the Faculty of Dentistry, Damascus University. The main complaint was pain in the right maxilla. Intraoral examination showed an exposure of necrotic bone in the right maxillary region with presence of purulent exudate. The treatment plan was discussed with the patient. Treatment included resection of all necrotic bone and application of Advanced platelet-rich fibrin (A-PRF) clots and membranes. Follow-up and outcome were conducted by clinical measures to assess healing and recurrence (6-month follow-up). Topical treatment with A-PRF demonstrated a reduction in pain and resulted in complete wound healing within 30 days. A-PRF stimulates the release of growth factors and chemotaxis involved in tissue repair mechanisms. This method seemed to be effective in the treatment of MRONJ.

Preconditioning with Photobiomodulation as an Effective Method in Preventing Chemotherapy-Induced Oral Mucositis: A Systematic Review.

Background: Given the suffering experienced by cancer patients, effective solutions must be found to prevent the most painful and debilitating side effects of anticancer treatment. The use of photobiomodulation (PBM) with specific parameters has been proposed to prevent oral mucositis in adults undergoing hematopoietic stem cell transplantation as well as in head and neck cancer patients receiving radiotherapy alone without chemotherapy. No recommendations were possible for patients undergoing chemotherapy alone. This systematic review aims to analyze the effectiveness of preconditioning by PBM in preventing chemotherapy-induced oral mucositis. Methods: This study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, PRISMA, Checklist and registered at the International Prospective Register of Systematic Reviews (PROSPERO). We searched and identified articles of the subsequent bibliographic databases: PubMed and Cochrane. Revised Cochrane risk-of-bias tool for randomized trials (RoB 2.0) was used to assess the risk of bias of studies included in this review. Results: There were only six clinical trials examining the efficacy of PBM therapy in the primary prevention of chemotherapy-induced oral mucositis. All of the studies used lasers, except for one study that compared lasers with light-emitting diodes. The wavelength ranges from 630 to 830 nm. Irradiation parameters varied among the included studies. All studies showed good results for the use of PBM in the prevention of oral mucositis except for one study that found no benefit for the laser application. Conclusions: PBM has been shown to be effective in preventing oral mucositis when applied to healthy tissues. Finding the optimal protocol has been difficult due to the variability between studies, and therefore, further well-designed, controlled, blinded studies are recommended to precisely determine irradiation parameters and the number of sessions. This review has been registered at the International Prospective Register of Systematic Reviews (PROSPERO) under number CRD42023397771.

Optimizing the Treatment for Advanced Non-Small-Cell Lung Cancer with Mutated Epidermal Growth Factor Receptor in Low-Income Countries: A Review.

Introduction: Osimertinib is the treatment of choice for epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC). Because of its high price, many low-income countries, such as Syria, cannot provide osimertinib, which makes it difficult to choose the appropriate treatment for these patients. This study aimed to review articles that assessed tyrosine kinase inhibitors (TKIs) for advanced NSCLC and developed an appropriate treatment plan for Syrian patients. Methods: An electronic literature search was conducted of published phase II and III studies that assessed the efficacy of EGFR-TKIs for advanced NSCLC between January 2003 and May 2022. Results: Seventeen articles were reviewed. The results were similar when erlotinib or icotinib was compared with gefitinib. Progression-free survival and overall survival for afatinib and dacomitinib were longer than for gefitinib, with small significant differences. Osimertinib was the only TKI that showed efficacy against the T790M mutation, which showed an improvement over the first- and second-generation TKIs. Osimertinib as a first-line therapy is not cost-effective compared with first- and second-generation TKIs. Conclusion: Osimertinib is the preferred first-line treatment in patients with advanced EGFR-mutated NSCLC. First- and second-generation TKIs are still considered good options, especially in low-income countries that cannot cover the costs of osimertinib.

Depression, anxiety and related factors among Syrian breast cancer patients: a cross-sectional study.

INTRODUCTION: Breast cancer represents a traumatic experience with a psychological burden. The prevalence of psychological distress (which include depression and anxiety) among breast cancer patients is estimated to be 15 to 54%, but studies have shown that applying some psychological treatments has contributed to decreasing depression and anxiety. So, it is crucial to diagnose and treat patients with the appropriate means. After reviewing the literature, no studies discussed depression and anxiety among Syrian breast cancer patients. METHODS: A cross-sectional study in Al-Bairouni hospital in Damascus, Syria carried out using face-to-face interviews based on a structured questionnaire. All breast cancer patients were included, except who refused to participate, and responses with missing data were excluded. The questionnaire consisted of 2 sections: the first included Socio-demographic characteristics, and the other evaluated patients' depression using PHQ-2 and GAD-2 scales. Data were gathered using the Kobo toolbox app and then entered into an Excel sheet. RESULTS: Five hundred patients were interviewed. 35.6% of the patients had a GAD-2 score greater than or equal to 3.00, while 35% had a PHQ-2 score greater than or equal to 3.00. There is a significant negative relationship between the age of the patient and the GAD-2 score and PHQ-2 score, which means the older the patient is, the lower the GAD-2 and PHQ-2 scores are. A multivariable regression model showed that younger (age ≤ 45 years) and being widowed were associated with being positive for further evaluation for generalized anxiety disorder. Similarly, patients younger than 45 are significantly associated with the need for further evaluation for major depressive disorder (MDD). Social status had a stronger association with the need for further assessment for MDD, with divorced women showing the strongest association, followed by widowed and married women compared to single women. CONCLUSION: This study showed high anxiety and depression among breast cancer patients. The patient's age and social status were significant factors in determining the need for further psychological assessment. In General, Younger patients showed higher levels of depression and anxiety, the size of the tumor did not show significant association with psychological distress.

A Complete Response of Orbital Metastases in Breast Cancer Patient Treated with Oral Chemotherapy: Case Report and Literature Review.

Discrete extraocular muscles (EOMs) metastases are extremely rare events. Here is a case of isolated orbital metastases involving EOMs in a female patient who was previously diagnosed with triple-negative breast cancer. She received chemotherapy followed by radiotherapy. Years later, the patient complained of gradually progressive ptosis of the right eye that was associated with mild restriction of ocular movements. Magnetic resonance imaging showed a suspected metastatic lesion. An open biopsy was performed for pathological evaluation. Metastases from breast cancer were confirmed. Immunohistochemistry showed discordance of the estrogen and progesterone receptors. She received oral capecitabine (Xeloda®) and vinorelbine (NVB) followed by hormone therapy. At the time of reporting, our patient remained in remission for 28 months as from her initial diagnosis of orbital metastases.

Frequencies of CYP2D6 genetic polymorphisms in Arab populations.

CYP2D6 is a key drug-metabolizing enzyme implicated in the biotransformation of approximately 25% of currently prescribed drugs. Interindividual and interethnic differences in CYP2D6 enzymatic activity, and hence variability in substrate drug efficacy and safety, are attributed to a highly polymorphic corresponding gene. This study aims at reviewing the frequencies of the most clinically relevant CYP2D6 alleles in the Arabs countries. Articles published before May 2021 that reported CYP2D6 genotype and allelic frequencies in the Arab populations of the Middle East and North Africa (MENA) region were retrieved from PubMed and Google Scholar databases. This review included 15 original articles encompassing 2737 individuals from 11 countries of the 22 members of the League of Arab States. Active CYP2D6 gene duplications reached the highest frequencies of 28.3% and 10.4% in Algeria and Saudi Arabia, respectively, and lowest in Egypt (2.41%) and Palestine (4.9%). Frequencies of the loss-of-function allele CYP2D6*4 ranged from 3.5% in Saudi Arabia to 18.8% in Egypt. The disparity in frequencies of the reduced-function CYP2D6*10 allele was perceptible, with the highest frequency reported in Jordan (14.8%) and the lowest in neighboring Palestine (2%), and in Algeria (0%). The reduced-function allele CYP2D6*41 was more prevalent in the Arabian Peninsula countries; Saudi Arabia (18.4%) and the United Arab Emirates (15.2%), in comparison with the Northern Arab-Levantine Syria (9.7%) and Algeria (8.3%). Our study demonstrates heterogeneity of CYP2D6 alleles among Arab populations. The incongruities of the frequencies of alleles in neighboring countries with similar demographic composition emphasize the necessity for harmonizing criteria of genotype assignment and conducting comprehensive studies on larger MENA Arab populations to determine their CYP2D6 allelic makeup and improve therapeutic outcomes of CYP2D6- metabolized drugs.

Metachronous breast cancer in a male with previous history of liposarcoma: A case report from Syria.

INTRODUCTION: Multiple primary cancers (MPC) are defined as the occurrence of two or more non-related cancers. The acquiring of male breast cancer (MBC) as secondary cancer in a sequence of MPC is extremely rare. Only one case of breast cancer following liposarcoma (LP) was previously reported in a female patient. We report the first case of MBC following LP. CASE PRESENTATION: A non-smoker male patient with a history of a well-differentiated liposarcoma was treated surgically and with radiotherapy 14 years ago with no signs of recurrence. The patient presented with a left breast mass; The excisional biopsy showed poorly differentiated grade III invasive ductal carcinoma. The patient underwent a mastectomy with axillary node resection and the final diagnosis was invasive ductal carcinoma stage IIA [T:2, N:0, M:0]. The tumor markers reported; Positive Estrogen Receptor (ER+), negative Progesterone Receptor (PR-), and negative Human Epidermal Receptor (HER-). He received eight sessions of chemotherapy with Docetaxel and 16 fractions of radiotherapy. The follow-up showed no signs of recurrence. DISCUSSION: Despite the rarity of diagnosis MBC as a second primary. Studies have found a relation between different types of breast cancer in male patients, and further, a relation was also found between MBC and lymphoma. While no studies that link MBC and LP were previously reported. CONCLUSION: We found that acquiring a treated LP would not affect the MBC prognosis or its response to treatment, yet further studies are needed to confirm this outcome.

Gestational breast cancer in a patient with Crohn's disease: two case reports.

BACKGROUND: Diagnosis of breast cancer during gestation is a rare occurrence. In addition, the diagnosis of breast cancer in a patient with Crohn's disease is not common. We present a rare case of gestational breast cancer in a patient with Crohn's disease, with a concurrent breast cancer diagnosis in her sister. CASE PRESENTATION: A 31-year-old Syrian woman with Crohn's disease was diagnosed with breast cancer at 30 weeks gestation; she received neoadjuvant chemotherapy during gestation. Incidentally, her 37-year-old sister was also diagnosed concomitantly with breast cancer. Both sisters underwent and successfully completed surgery and adjuvant therapy. At a 5-year review, both patients showed no signs of recurrence. The Crohn's disease symptoms have also improved after chemotherapy, and the baby born after gestational chemotherapy is currently 5 years old with normal psychomotor development and without any congenital malformations. CONCLUSIONS: This case report highlights the impact of gestation on breast cancer outcomes, the possibility of giving chemotherapy during gestation, and the effect of chemotherapy on the symptoms of Crohn's disease.

Antibody-Drug Conjugates Used in Breast Cancers.

The prognosis of breast cancer has radically changed in recent years and continues to improve due to the broad application of effective therapies. New targeting strategies including targeted delivery of cytotoxic drugs via receptor-targeting agents have been developed. We summarize recent publications and developments of novel antibody-drug conjugates (ADCs) used to control breast cancer.

Primary Stromal Breast Sarcoma with Concomitant Contralateral Carcinoma: A Rare Case from Syria.

Bilateral breast cancers are rare cases encountered and are usually the same type in both sides. Only very few cases were reported to have different histological types of neoplasia involving sarcoma. Moreover, sarcomas rarely originate from the breast as a primary lesion whereas the common presentation is having angiosarcoma following radiotherapy. In this report, we present a rare case of a Syrian 43-year-old woman having two distinct primary lesions in the breasts: invasive ductal carcinoma and contralateral stromal sarcoma.

Targeting the oncogenic protein beta-catenin to enhance chemotherapy outcome against solid human cancers.

BACKGROUND: Beta-catenin is a multifunctional oncogenic protein that contributes fundamentally to cell development and biology. Elevation in expression and activity of ß-catenin has been implicated in many cancers and associated with poor prognosis. Beta-catenin is degraded in the cytoplasm by glycogen synthase kinase 3 beta (GSK-3ß) through phosphorylation. Cell growth and proliferation is associated with ß-catenin translocation from the cytoplasm into the nucleus. This laboratory was the first to demonstrate that selenium-containing compounds can enhance the efficacy and cytotoxicity of anticancer drugs in several preclinical xenograft models. These data provided the basis to identify mechanism of selenium action focusing on ß-catenin as a target. This study was designed to: (1) determine whether pharmacological doses of methylseleninic acid (MSeA) have inhibitory effects on the level and the oncogenic activity of ß-catenin, (2) investigate the kinetics and the mechanism of ß-catenin inhibition, and (3) confirm that inhibition of ß-catenin would lead to enhanced cytotoxicity of standard chemotherapeutic drugs. RESULTS: In six human cancer cell lines, the inhibition of total and nuclear expression of ß-catenin by MSeA was dose and time dependent. The involvement of GSK-3ß in the degradation of ß-catenin was cell type dependent (GSK-3ß-dependent in HT-29, whereas GSK-3ß-independent in HCT-8). However, the pronounced inhibition of ß-catenin by MSeA was independent of various drug treatments and was not reversed after combination therapy.Knockout of ß-catenin by ShRNA and its inhibition by MSeA yielded similar enhancement of cytotoxicity of anticancer drugs.Collectively, the generated data demonstrate that ß-catenin is a target of MSeA and its inhibition resulted in enhanced cytotoxicity of chemotherapeutic drugs. CONCLUSIONS: This study demonstrates that ß-catenin, a molecule associated with drug resistance, is a target of selenium and its inhibition is associated with increased multiple drugs cytotoxicity in various human cancers. Further, degradation of ß-catenin by GSK-3ß is not a general mechanism but is cell type dependent.

KRAS status and clinical outcome in metastatic colorectal cancer patients treated with first-line FOLFOX chemotherapy.

BACKGROUND: Two previous first-line studies showed an improved trend in response rate (RR) and progression free survival (PFS) in metastatic colorectal cancer (CRC) patients with KRAS mutation. Others have reported a worsened outlook for metastatic CRC patients with KRAS mutation and a higher likelihood of metastatic disease to the lungs. In this study, we aimed to address the impact of KRAS on the pattern of metastatic disease at presentation and on RR and PFS with first-line 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy. METHODS: Patients with CRC who underwent KRAS testing using DxS assay at Roswell Park Cancer Institute (RPCI) were identified. Patients with metastatic CRC treated with first-line FOLFOX +/- bevacizumab were assessed for response and survival using RECIST 1.1 guidelines. A two-sided Fisher's exact test was used to determine the statistical significance. RESULTS: 181 patients with metastatic CRC and KRAS testing were identified. 83/181 patients were treated with FOLFOX (+/- bevacizumab) in the first-line setting at RPCI and were evaluable as per study guidelines. KRAS mutation (MT) occurred in 40.31% cases. There was no difference in organ-metastases distribution, RR (56.60% in KRAS wild-type (WT) and 50% in KRAS mutant) or PFS (9.3 months KRAS WT and 8.7 months in KRAS MT) based on KRAS status. CONCLUSION: In this single institute study, our findings do not support any predictive role for KRAS-MT in terms of response to FOLFOX first-line chemotherapy, or in terms of sites of metastatic disease at mCRC presentation.