Diagnostic Accuracy of Ultrasonography in Axillary Staging in Breast Cancer Patients.

Background: Breast cancer is the most common malignancy affecting women all over the world and represents 7% of all cancer-related deaths in the UK. One of the most crucial elements in assessing a patient's prognosis and chance of survival with breast cancer is the condition of their axillary lymph nodes. Ultrasonography (US) is now used as a routine preoperative diagnostic tool for pretherapeutic axillary evaluation. The aim of the current study is to investigate the diagnostic accuracy of US in axillary staging in breast cancer patients. Methods: We carried out this retrospective study for all invasive breast cancer patients who had surgery in addition to preoperative axillary staging using US during the period from January 2020 to February 2021. The final histology results were compared with the preoperative US findings to ascertain the sensitivity, specificity, positive predictive value, and negative predictive value of AUS in axillary staging. Results: One hundred and twenty-eight patients were included in our study. The average age of diagnosis was 63.9 ± 12.3 years of age. We calculated sensitivity rate of 59.6%, specificity rate of 95.1%, positive predictive value of 87.5%, and negative predictive value of 80.2% with overall diagnostic accuracy of 82.2%. Conclusion: Despite the important role of preoperative US in axillary staging in breast cancer patients; it failed to detect metastatic diseases in 14.8% of our patients. These findings necessitate the routine histological evaluation of the axilla for more accurate staging of the disease.

Haploinsufficiency of a Circadian Clock Gene Bmal1 (Arntl or Mop3) Causes Brain-Wide mTOR Hyperactivation and Autism-like Behavioral Phenotypes in Mice.

Approximately 50-80% of children with autism spectrum disorders (ASDs) exhibit sleep problems, but the contribution of circadian clock dysfunction to the development of ASDs remains largely unknown. The essential clock gene Bmal1 (Arntl or Mop3) has been associated with human sociability, and its missense mutation is found in ASD. Our recent study found that Bmal1-null mice exhibit a variety of autism-like phenotypes. Here, we further investigated whether an incomplete loss of Bmal1 function could cause significant autism-like behavioral changes in mice. Our results demonstrated that heterozygous Bmal1 deletion (Bmal1+/-) reduced the Bmal1 protein levels by ~50-75%. Reduced Bmal1 expression led to decreased levels of clock proteins, including Per1, Per2, Cry 1, and Clock but increased mTOR activities in the brain. Accordingly, Bmal1+/- mice exhibited aberrant ultrasonic vocalizations during maternal separation, deficits in sociability and social novelty, excessive repetitive behaviors, impairments in motor coordination, as well as increased anxiety-like behavior. The novel object recognition memory remained intact. Together, these results demonstrate that haploinsufficiency of Bmal1 can cause autism-like behavioral changes in mice, akin to those identified in Bmal1-null mice. This study provides further experimental evidence supporting a potential role for disrupted clock gene expression in the development of ASD.

A Double-Blind, Randomized Controlled Trial of Pre-incision Wound Infiltration Using Diclofenac Versus Bupivacaine for Post-operative Pain Relief in Open Thyroid and Parathyroid Surgery.

BACKGROUND: Pre-incision wound infiltration using NSAID is an alternative method to manage post-operative pain in surgery. It is postulated that NSAID delivered peripherally exerts efficient analgesic and anti-inflammatory effect with minimal systemic complication. This study explored the efficacy of using diclofenac for wound infiltration in open thyroidectomy and parathyroidectomy as compared to conventional agent, bupivacaine. METHODOLOGY: The study was designed as a double-blind, randomized controlled trial involving 94 patients who underwent open thyroidectomy or parathyroidectomy in Hospital Pulau Pinang, Malaysia, from November 2015 to November 2016. The study compared the efficacy of pre-incision wound infiltration of diclofenac (n = 47) versus bupivacaine (n = 47) in post-operative pain relief. Wound infiltration is given prior to skin incision. Mean pain score at designated time interval within the 24-h post-operative period, time to first analgesia, total analgesic usage and total analgesic cost were assessed. RESULTS: Ninety-four patients were recruited with no dropouts. Mean age was 49.3 (SD = 14.2) with majority being female (74.5%). Ethnic distribution recorded 42.6% Chinese, 38.3% Malay, followed by 19.1% Indian. Mean duration of surgery was 123.8 min (SD = 56.5), and mean length of hospital stay was 4.7 days (SD = 1.8). The characteristics of patient in both groups were generally comparable except that there were more cases of total thyroidectomy in the diclofenac group (n = 31) as compared to the bupivacaine group (n = 16). Mean pain score peaked at immediate post-operative period (post-operative 0.5 h) with a score of 3.5 out of 10 and the level decreased steadily over the next 20 h starting from 4 h post-operatively. Pre-incision wound infiltration using diclofenac had better pain control as compared to bupivacaine at all time interval assessed. In the resting state, the mean post-operative pain score difference was statistically significant at 2 h [2.1 (SD = 1.5) vs. 2.8 (SD = 1.8), p = 0.04]. During neck movement, the dynamic pain score difference was statistically significant at post-operative 1 h [2.7 (SD = 1.9) vs. 3.7 (SD = 2.1), p = 0.02]; 2 h [2.7 (SD = 1.6) vs. 3.7 (SD = 2.0), p = 0.01]; 4 h [2.2 (SD = 1.5) vs. 2.9 (SD = 1.7), p = 0.04], 6 h [1.9 (SD = 1.4) vs. 2.5 (SD = 1.6), p = 0.04] and 12 h [1.5 (SD = 1.5) vs. 2.2 (SD = 1.4), p = 0.03]. Mean dose of tramadol used as rescue analgesia in 24 h duration was lower in the diclofenac group as compared to bupivacaine group [13.8 mg (SD = 24.9) vs. 36.2 mg (SD = 45.1), p = 0.01]. The total cost of analgesia used was significantly cheaper in diclofenac group as compared to bupivacaine group [RM 3.47 (SD = 1.51) vs. RM 13.43 (SD = 1.68), p < 0.01] or [USD 0.83 (SD = 0.36) vs. USD 3.21 (SD = 0.40), p < 0.01]. CONCLUSION: Pre-incision wound infiltration using diclofenac provides better post-operative pain relief compared to bupivacaine for patient who had underwent open thyroidectomy or parathyroidectomy. Diclofenac is cheap and easily available in the limited resource setting. This approach offers a superior alternative for post-operative pain relief as compared to bupivacaine.

The Role of MRI in Assessing Residual Breast Cancer After Neoadjuvant Chemotherapy.

INTRODUCTION: Breast cancer is the most common malignancy among women in the world. The role of neoadjuvant chemotherapy (NAC) in the management of breast cancer is increasing. The decision about the management after NAC depends mainly on the tumor response to NAC. OBJECTIVES: The role of the current study is to evaluate the role of the MRI scan in assessing the residual disease after NAC, which would help in decision making regarding the best treatment plan for the patient. PATIENTS AND METHODS: We did this retrospective review for all patients who were diagnosed with breast cancer in our center and had NAC over four years. All patients in our study had a post-NAC magnetic resonance imaging (MRI) scan to assess the residual tumor size. A 2×2 table was used to calculate the diagnostic accuracy, and SPSS software version 25 was used to get the correlation coefficients between the post-NAC MRI measurements and pathological size. RESULTS: 28 female patients were included in our study. The average age was 45.25 ± 10 years. We utilized the tumor size on histology as the standard for comparison. We calculated MRI sensitivity, specificity, PPV, and NPV rates of 90.9%, 100%, 100%, and 94.4%, respectively. The correlation coefficient was strong (r = 0.859, P = 0.01). CONCLUSION: Magnetic resonance imaging is a good test to assess the residual tumor disease after NAC in breast cancer patients. However, cases of under- and overestimation are still seen, which require more caution when making a decision regarding the management of such cases.

Breast lymphoma: General review.

BACKGROUND: Lymphoma of the breast can be classified as either primary breast lymphoma (PBL) or secondary to systemic lymphoma (SBL). PBL is a rare disease with Diffuse Large B cell Lymphomas (DLBCL) being the most common subtype. OBJECTIVES: In the current study, we represented eleven cases diagnosed with breast lymphoma in our trust; two of them had PBL and nine had SBL. We focused mainly on the clinical presentation, diagnosis, management and outcomes. METHODS: We did this retrospective review for all breast lymphoma patients who were diagnosed in our trust during the periods from 2011-2022. Patients' data were obtained from the hospital recording system. We followed up these patients thus far to identify the outcome of treatment in each patient. RESULTS: Eleven patients were included in our review. All patients were females. Average age of diagnosis was 66.1 ± 13 years of age. Eight patients were diagnosed with DLBCL, two patients were diagnosed with follicular lymphomas, and the last one had lymphoplasmacytic lymphoma. Chemotherapy +∕- radiotherapy was the standard treatment regimen in all patients. Four patients passed away within one year of chemotherapy, five patients achieved complete remission, one patient had two relapses and is still under treatment, while the last patient was diagnosed recently and still awaiting treatment. CONCLUSION: Primary breast lymphoma is an aggressive disease. The treatment for PBL is mainly systemic with chemoradiotherapy. The role of surgery is now limited to the diagnosis of the disease. Early diagnosis and proper treatment are crucial for the management of such cases.

Health Literacy, Knowledge on Cervical Cancer and Pap Smear and Its Influence on Pre-Marital Malay Muslim Women Attitude towards Pap Smear.

BACKGROUND: Cervical cancer is preventable. In Malaysia, women are found to have good awareness of the disease and yet, the Pap smear uptake is still poor. Measuring health literacy level could explain this discrepancy. This study aims to determine the relationship between health literacy, level of knowledge of cervical cancer and Pap smear with attitude towards Pap smear among women attending pre-marital course. METHODS: A cross sectional study was performed in three randomly selected centres that organised pre-marital courses. All Malay Muslim women participants aged 18 to 40 years old were recruited while non-Malaysian, illiterate, and had hysterectomy were excluded. Validated self-administered questionnaires used were European Health Literacy Questionnaire (HLS-EU-Q16 Malay) and Knowledge and attitude towards Cervical Cancer and Pap Smear Questionnaire. The mean percentage score (mean± SD) was calculated, with higher scores showed better outcomes. Multiple linear regression was used to measure the relationship of independent variables with attitude towards Pap smear. RESULTS: A total of 417 participants were recruited with a mean age of 24.9 ± 3.56 years old. Prevalence of awareness of cervical cancer was 91.6% (n=382, 95% CI: 89.0%, 94.2%) and mean percentage score was 74.7%±7.6. Prevalence of awareness of Pap smear was 59.0% (n=246, 95% CI: 54.2%, 63.8%) and mean percentage score was 80.2% ± 6.5. The health literacy mean score was 13.3±3.6, with minimum score 0 and maximum score 16. The mean percentage score of attitudes towards Pap smear was 64.8%±9.3. Multiple linear regression analysis demonstrated significant relationship between health literacy (p=0.047) and knowledge of Pap smear (p<0.001) with attitude towards Pap smear. CONCLUSION: A higher health literacy with high knowledge of Pap smear improves the attitude towards Pap smear. Pre-marital course is an opportunistic platform to disseminate information to improve health literacy and knowledge of cervical cancer and Pap smear screening.

Comparative validity of a Food Frequency Questionnaire (MyUM Adolescent FFQ) to estimate the habitual dietary intake of adolescents in Malaysia.

BACKGROUND AND OBJECTIVES: The food frequency questionnaire (FFQ) is a dietary tool used to assess the habitual intake of the population. The goal of this study is to examine the reproducibility and validity of the FFQ that was developed for a multi-ethnic population in Malaysia. METHODS AND STUDY DESIGN: Collective food data from MyHeARTs 2012 database were used to construct the MyUM Adolescent FFQ. Seventy-eight participants between 13 and 15 years old in 2014 were selected through convenient sampling for test-retest study. They completed the MyUM Adolescent FFQ twice, with an interval period of one week. One hundred and fifty-six MyHeARTs study participants who were 15 years old in 2014 were randomly selected for this comparative valid-ity study. They completed a 7-day diet history (7DDH) and subsequently completed the self-administered MyUM Adolescent FFQ. RESULTS: Pearson's correlations between the FFQ and 7DDH for all macronutrients were statistically significant. Energy-adjusted correlations for protein, carbohydrate, and fat were 0.54, 0.63 and 0.49 respectively. Most of the micronutrients and minerals, were statistically correlated ranging from 0.31 to 0.49 after energy adjustment. Cross-classification analyses revealed that more than 70 percent of adolescents were classified into either the same or adjacent quartile of nutrient intake when comparing data of 7DDH and FFQ. No serious systematic bias was evident in the Bland-Altman plots. CONCLUSION: The 200-item FFQ developed for Malaysian adolescents has moderate to good comparative validity for assessment of macronutrient and micronutrient intake.

Cell cycle: how, when and why cells get rid of cyclin A.

Sequences outside the 'destruction box' direct the degradation of cyclin A to completion before the metaphase-anaphase transition; cyclin A that escapes timely degradation can block the metaphase-anaphase transition, impede anaphase and telophase, and impair a cell's ability to arrest in G1 of the next cell cycle.

Contribution of growth and cell cycle checkpoints to radiation survival in Drosophila.

Cell cycle checkpoints contribute to survival after exposure to ionizing radiation (IR) by arresting the cell cycle and permitting repair. As such, yeast and mammalian cells lacking checkpoints are more sensitive to killing by IR. We reported previously that Drosophila larvae mutant for grp (encoding a homolog of Chk1) survive IR as well as wild type despite being deficient in cell cycle checkpoints. This discrepancy could be due to differences either among species or between unicellular and multicellular systems. Here, we provide evidence that Grapes is needed for survival of Drosophila S2 cells after exposure to similar doses of IR, suggesting that multicellular organisms may utilize checkpoint-independent mechanisms to survive irradiation. The dispensability of checkpoints in multicellular organisms could be due to replacement of damaged cells by regeneration through increased nutritional uptake and compensatory proliferation. In support of this idea, we find that inhibition of nutritional uptake (by starvation or onset of pupariation) or inhibition of growth factor signaling and downstream targets (by mutations in cdk4, chico, or dmyc) reduced the radiation survival of larvae. Further, some of these treatments are more detrimental for grp mutants, suggesting that the need for compensatory proliferation is greater for checkpoint mutants. The difference in survival of grp and wild-type larvae allowed us to screen for small molecules that act as genotype-specific radiation sensitizers in a multicellular context. A pilot screen of a small molecule library from the National Cancer Institute yielded known and approved radio-sensitizing anticancer drugs. Since radiation is a common treatment option for human cancers, we propose that Drosophila may be used as an in vivo screening tool for genotype-specific drugs that enhance the effect of radiation therapy.

PET/CT of esophageal cancer: its role in clinical management.

Positron emission tomography (PET)/computed tomography (CT) has important utility and limitations in the initial staging of esophageal cancer, evaluation of response to neoadjuvant therapy, and detection of recurrent malignancy. Esophageal cancer is often treated by using a combined modality approach (chemotherapy, radiation therapy, and esophagectomy); correct integration of PET/CT into the conventional work-up of esophageal cancer requires a multidisciplinary approach that combines the information from PET/CT with results of clinical assessment, diagnostic CT, endoscopic gastroduodenoscopy, and endoscopic ultrasonography. PET/CT has limited utility in T staging of esophageal cancer and relatively limited utility in detection of dissemination to locoregional lymph nodes. However, PET/CT allows detection of metastatic disease that may not be identifiable with other methods. PET/CT is not sufficiently reliable in the individual patient for determination of treatment response in the primary tumor. Interpretation of PET/CT results is optimized by understanding the diagnostic limitations and pitfalls that may be encountered, together with knowledge of the natural history of esophageal cancer and the staging and treatment options available.