In Vivo Detection of Multidrug-Resistance Related Proteins in Locally Advanced Breast Cancer Using 99mTc-MIBI SPECT/CT Imaging: Correlation with Clinical Outcomes.

OBJECTIVE: Neoadjuvant chemotherapy (NACT) is widely used for treating locally advanced Breast cancer (LABC). However, development of multidrug resistance (MDR) is the main underlying factor for chemoresistance. Technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) is a substrate for MDR. This study aimed to analyze the relationship between expression of MDR-related proteins (P-gp and Bcl-2) and 99mTc-MIBI uptake and retention in BC tumor cells, pathologic response to NACT, disease free survival (DFS) and overall survival (OS). METHODS: prospective analysis recruited 31 patients with LABC who received NACT between January 2019 and March 2020. 99mTc-MIBI planar and SPECT/CT imaging was conducted before and after NACT. Qualitative and quantitative analyses were performed, pre and post-NACT early and delayed lesion to non-lesion (LNL) ratios, and retention index (RI) of 99mTc-MIBI were calculated. Expression of P-gp and Bcl-2 in tumor cells was determined by immunohistochemistry. RESULTS: Quantitively, inter-reader ICC for SPECT/CT based quantification was consistently higher than that of planar images. Post-NACT LNL ratios were significantly higher in patients with pathologic persistent disease (PPD). A change in RI between pre- and post-NACT scans demonstrated a significant association with DFS with a hazard ratio of 0.7 (95%CI: 06-1.0). Qualitatively, SPECT/CT was significantly more accurate compared to planar imaging in identifying residual viable tumor (81% compared to 57%).  Her2neu positivity and high post-operative Bcl-2 and P-gp were associated with worse DFS. A significant association was found between increased expression of post-NACT Bcl-2 and PPD, advanced tumor stage and poor OS. CONCLUSION: 99mTc-MIBI SPECT/CT based qualitative evaluation of BC response to NACT is more accurate than planar imaging. Post-NACT MIBI retention is positively correlated with P-gp and Bcl-2 expression. 99mTc-MIBI SPECT/CT may predict MDR development. High post-NACT Bcl-2 expression is significantly associated with advanced tumor stage and OS. High post-NACT P-gp expression has a worse impact on pathologic response and DFS.

Suprasternal dermoid sinus: A case report.

INTRODUCTION: Congenital anomalies in the neck region, such as dermoid sinuses, pose diagnostic challenges in pediatrics. Surgical excisions are vital to prevent complications. PRESENTATION OF CASE: A 7-month-old male infant had presented with a congenital suprasternal dermoid sinus, which had been evident since birth. Imaging confirmed the diagnosis, prompting surgical intervention under general anesthesia. A delicate excision was performed, guided by a methylene blue dye injection, followed by histopathological confirmation. DISCUSSION: Dermoid sinuses typically manifest as cutaneous pits or sinus tracts, with a left-sided predominance and a female predilection. An accurate diagnosis relies on clinical examination and imaging studies to delineate the anomaly. Surgical excision remains crucial to prevent recurrence and complications. CONCLUSION: This case reaffirms the necessity of prompt and accurate diagnosis followed by surgical intervention for managing congenital dermoid sinuses. Ongoing research and collaborative studies are needed to further refine management strategies and improve outcomes for patients with these anomalies, particularly when presenting in atypical locations.

Painful knee.

INTRODUCTION: A bipartite patella is a rare anatomical variant of the patella. A patella bipartite is often asymptomatic and is often an incidental finding on radiological imaging. The patella remains bipartite when secondary ossification centers fail to fuse. Herein, a case of bipartite patella improved after knee arthroscopy and surgical removal. PRESENTATION OF THE CASE: A 57-year-old male with a history of polytrauma. He complained of progressive pain in the right knee area. A radiological investigation reported a right bipartite patella. The condition improved after the open removal of the accessory patella. DISCUSSION: This case is considered type III according to Saupe's classification. Due to its location and radiological appearance, it is a painful synchondrosis of a bipartite patella. CONCLUSION: After the failure of conservative management, the removal of the bipartite patella was necessary and unavoidable to restore everyday activities.

Prognostic Outcome of Mesenchymal Transition Biomarkers in Correlation with EGFR Expression in Epithelial Ovarian Carcinoma Patients.

BACKGROUND: CD44 is an epithelial-mesenchymal transition (EMT) surface receptor that regulates the interactivity between the cells and the extracellular matrix, thereby promoting cell migration. The epidermal growth factor receptor (EGFR) family is a trans-membrane kinase-related protein. It regulates cell adhesion proteins, which may promote cell proliferation and invasiveness. Mesenchymal epithelial transition (MET) is another EMT receptor that stimulates cell proliferation, invasion, survival, and angiogenesis. This study aimed to evaluate the prognostic impact of CD44, EGFR expressions, and MET gene amplification in epithelial ovarian cancer (EOC). METHODS: This is a retrospective cohort study, including 85 cases of EOC. CD44 and EGFR expressions were evaluated in both epithelial and stromal cells by immunohistochemistry. Tumor cells also underwent a cytogenetic analysis using fluorescent in situ hybridization (FISH) to detect MET gene amplification. RESULTS: High CD44 expression in tumors was significantly associated with serous subtypes (P=0.001), peritoneal deposits (P=0.002), and advanced stage (P=0.002). EGFR high tumor expression demonstrated a significant association with lymph node metastasis (P=0.038) and the advanced stage of EOC (P=0.016). Increased copy number of the MET gene was significantly associated with partial therapy response (P=0.030).  CD44 and EGFR tumor high expression was associated with poor overall survival (OS). In addition, MET gene gain in tumors was associated with a shorter OS (P=0.000). CONCLUSION: EMT biomarkers (CD44 and MET) and EGFR expression in EOC are independent prognostic factors for OS. MET gene increase copy number was detected in cases of serous neoplasm and associated with poor survival and minimal therapy response.

CD133 is an independent predictive and prognostic marker in metastatic breast cancer.

BACKGROUND: CD133 is a transmembrane glycoprotein and is considered the most common cell surface marker to identify cancer stem cells in hematological and solid tumors, including breast cancer. OBJECTIVES: To evaluate the impact of immunohistochemical expression of CD133 on response rate and survival in metastatic breast cancer, as well as to correlate it with various demographics and clinicopathological characteristics. METHODS: One-hundred metastatic breast cancer patients were prospectively recruited at the Medical Oncology Department at South Egypt Cancer Institute during the period from January 2018 to January 2020. RESULTS: There was a statistically significant correlation between CD133 positive patients with various adverse clinicopathological parameters such as high grade (p= 0.013), higher tumor (p= 0.001), and nodal staging (p= 0.024) during a median follow-up time of 17 months. In addition, cases with CD133 positive expression had a significantly lower survival time than those with negative expression (3-years OS 37.4% versus 85.5%, p= 0.024). Regarding the response rate, CD133 positive patients had a lower response rate than negative patients (50% versus 54%, p= 0.012). CONCLUSIONS: Positive CD133 is correlated with poor prognosis in metastatic breast cancer patients.

Could Argyrophilic Nucleolar Organizer Regions count mirror DNA Ploidy in Malignant Salivary Gland Tumors?

OBJECTIVE: Nucleolar organizer regions (NORs) are DNA coils that transcribe to ribosomal RNA. The NOR-associated protein, termed argyrophilic NOR (AgNOR), was visible within the nucleus by staining with silver nitrate examination via the light microscope. AgNOR counting is a proliferation marker and may help in the diagnosis and prognosis of various neoplastic lesions. Aneuploidy (abnormal DNA content) can predict the progression, survival and prognosis of the tumors. The aim of this study was to evaluate the role of AgNORs, DNA ploidy status, and total S-phase fraction (TSPF) as prognostic parameters in malignant salivary gland tumors (MSGTs). METHODS: The current study is a retrospective study on a cohort of MSGTs (N=47), to assess AgNORs using Silver Nitrate stain, DNA index (DI), and TSPF using flow cytometry (FCM). Data including tumor size and site, lymphovascular invasion (LVI), lymph node metastasis (LNM) were collected. RESULTS: The AgNORs count was statistically significant with MSGT type. DI was found to have a significant association with tumor site, tumor size and MSGT type. In addition, TSPF was found to be significantly associated with LVI. A moderate positive correlation was noted between AgNORs count and TSPF. LNM, tumor site, high AgNORs and low DI were all associated with short disease-free survival (DFS) and poor overall survival (OS). CONCLUSION: The present study revealed that high AgNORs count, DNA aneuploidy and TSPF had a poor influence on MSGTs prognosis.

Prognostic role of ALK-1 and h-TERT expression in glioblastoma multiforme: correlation with ALK gene alterations.

BACKGROUND: Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that is expressed in the developing central and peripheral nervous systems during embryogenesis. Human telomerase reverse transcriptase (h-TERT) protein resumption is the main process of preservation of telomeres that maintains DNA integrity. The present study aims to evaluate the prognostic role of ALK-1 and h-TERT protein expression and their correlation with ALK gene alterations in glioblastoma multiforme (GBM). METHODS: The current study is a retrospective study on a cohort of patients with GBM (n = 53) that attempted to detect ALK gene alterations using fluorescence in situ hybridization. ALK-1 and h-TERT proteins were evaluated using immunohistochemistry. RESULTS: Score 3 ALK-1 expression was significantly associated with male sex, tumor multiplicity, Ki labeling index (Ki LI), and type of therapeutic modality. Score 3 h-TERT expression exhibited a significant association with Ki LI. ALK gene amplifications (ALK-A) were significantly associated with increased Ki LI and therapeutic modalities. Score 3 ALK-1 protein expression, score 3 h-TERT protein expression, and ALK-A were associated with poor overall survival (OS) and progression-free survival (PFS). Multivariate analysis for OS revealed that ALK gene alterations were an independent prognostic factor for OS and PFS. CONCLUSIONS: High protein expression of both ALK-1 and h-TERT, as well as ALK-A had a poor impact on the prognosis of GBM. Further studies are needed to establish the underlying mechanisms.

Laparoscopic versus Open Complete Mesocolic Excision for Right Colon Cancer.

RESULTS: The mean operative time was significantly longer in the LCME group than that in the OCME group with less mean intraoperative blood loss. Conversion was required in 4 patients (8.3%) in the LCME group. The use of laparoscopy increased the number of harvested lymph nodes compared to the open approach (39.81 ± 16.74 vs. 32.65 ± 12.28, respectively, P=0.010). The laparoscopic approach was associated with a shorter time interval to first flatus as well as shorter time interval to liquid and normal diet after surgery. The postoperative hospital stay was significantly shorter in the LCME group. The complication rate was slightly lower in the LCME (14.7%) than in the OCME group (27.2%) (P=0.252). The 3-year OS in the LCME group was similar to that in OCME (78.2% vs. 63.2%, respectively, P value = 0.423). The three-year DFS in the laparoscopic group was higher (74.5%) than the open group (60.0%), but did not reach statistical significance (P value = 0.266). CONCLUSIONS: In conclusion, laparoscopic CME right hemicolectomy is a technically feasible and safe procedure if surgeon expertise is present. LCME has long-term oncologic outcomes (recurrence and survival) comparable to open surgery for management of patients with stage II or III colon cancer.

Utility of Single-Photon Emission Computed Tomography/Computed Tomography in Suspected Unilateral Condylar Hyperplasia: A Histopathologic Validation Study.

PURPOSE: The purpose of this study is to evaluate the utility of hybrid single-photon emission computed tomography (SPECT) and computed tomography (CT) with technetium-99m methylene diphosphonate in patients with suspected active unilateral condylar hyperplasia (UCH) using histopathology as the reference standard. METHODS: Twenty-four patients with suspected active UCH prospectively underwent technetium-99m methylene diphosphonate planar bone scintigraphy with SPECT/CT of the mandible. Qualitative and quantitative readings for growth activity were performed by 3 nuclear medicine physicians and the final diagnosis was derived from postoperative histopathological examination. Readings were reported as positive, equivocal, or negative. Total, maximum, and mean counts were recorded for each condyle on SPECT/CT images. The uptake of the index (suspected) condyle was expressed as a count ratio (Rtotal, Rmean, Rmax), a percentage uptake (Ptotal, Pmean, Pmax), background-corrected counts (Btotal, Bmean, Bmax), as well as CT-based condylar diameters (RCT,PCT) relative to the contralateral condyle. RESULTS: Interobserver agreement was 0.79 and 0.83 for planar bone scintigraphy and SPECT/CT, respectively, with a total of 5 and 1 equivocal readings from the respective modalities. Surgery was performed in 22 patients; all of them had pathologically proven UCH. SPECT/CT was slightly more sensitive than planar bone scintigraphy (91 vs 78%) with identical specificity (96%). Rtotal, Rmean, Ptotal, and Pmean demonstrated area under the curve between 84% and 86%. Metrics based on CT diameters and background-corrected counts were not associated with UCH diagnosis. CONCLUSIONS: Quantitative approaches based on total or mean count ratio or relative count percentage were equally predictive for UCH diagnosis; however, they were slightly less sensitive compared with qualitative technetium-99m methylene diphosphonate SPECT/CT evaluation. SPECT/CT evaluation has the potential to decrease the equivocal readings.

Impact of DAXX and ATRX expression on telomere length and prognosis of breast cancer patients.

BACKGROUND: Telomere stability is one of the hallmarks of cancer that promotes cellular longevity, the accumulation of genetic alterations, and tumorigenesis. The loss of death domain-associated protein (DAXX) and α-thalassemia/mental retardation X-linked protein (ATRX) plays a role in telomere lengthening and stability. This study aims to evaluate the prognostic significance of telomere length (TL) and its association with DAXX and ATRX proteins in breast cancer (BC). Our study used the FISH technique to detect peptide nucleic acid (PNA) in the peripheral blood cells of a cohort of BC patients (n = 220) and a control group of apparently healthy individuals (n = 100). Expression of DAXX and ATRX proteins was evaluated using immunohistochemistry (IHC) in all BC tissues. RESULTS: Patients with a shorter TL had worse disease-free survival (DFS) and overall survival (OS). There were significant associations between shorter TL and advanced disease stages, lymph node metastasis, and positive HER2/neu expression. DAXX protein expression was significantly correlated with TL. Lower DAXX expression was significantly with shorter DFS. CONCLUSION: Assessing TL can be used as a worthy prognostic indicator in BC patients. Specifically, short TL had a poor impact on the prognosis of BC patients. Low DAXX expression is associated with poor outcomes in BC. Further mechanistic studies are warranted to reveal the underlying mechanisms of these associations.

Assessing CD 10 Expression Level and Its Prognostic Impact in Egyptian Patients with Urothelial Carcinoma.

BACKGROUND AND AIM: CD10 is expressed in urothelial carcinoma cells and cancer associated fibroblasts (CAF). In the current study, CD10 immunohistochemical staining (IHC) and CD10 mRNA expression in urothelial carcinoma of bladder (UCB) were assessed, and its  relationship with tumor progression and prognosis was investigated. PATIENTS AND METHODS: In this study, 106 formalin fixed paraffin-embedded (FFPE) tissue of UCB, obtained through radical cystectomy specimen, and 10 matched normal tissue samples were included.CD10 expression was evaluated by immunohistochemistry and real time PCR techniques. RESULTS: CD10 expression in tumor cells and associated stromal fibroblasts was significantly associated with high tumor grade and advanced stage. Significant correlation was found between CD10 tumor expression and lymphovascular invasion (LVI) (P<0.001) as well as perineural invasion (PNI). CD10 expression in stromal fibroblasts was significantly associated with squamous differentiation of tumor cells, lymph node metastasis (LNM), and tumor necrosis. Positive CD10 expression in both tumor cells and associated stromal fibroblasts was associated with shorter OS . CD10 mRNA was overexpressed in tumors in comparison with the matched normal tissues. CD10 mRNA was significantly higher in invasive tumor, advanced stage tumor, and high grade tumor. There was significant correlation between CD10 mRNA tumor expression and LVI, PNI, and tumor recurrence. CONCLUSION: Increased expression of CD10 in the tumor and CAF was strongly correlated with tumor progression, invasion, metastasis, shorter OS, and RFS in urothelial carcinoma patients. CD10 mRNA showed significantly higher expression in tumor tissue than in matched normal tissue. CD10 mRNA was associated with depth of invasion, TNM stage, tumor grade, vascular tumor invasion, and tumor recurrence.

An ileo-ileal intussusception secondary to polypoid lipoma in a child, a case report and review of the literature.

BACKGROUND: Intramuscular intestinal lipoma is one of the rare benign tumours of the small intestine in children and acts as a lead point of intussusception. PRESENTATION OF CASE: We describe a case in which a 4-year-old boy presented with recurrent attacks of colicky abdominal pain and non-bilious vomiting. Abdominal examination was irrelevant. Per rectum (PR) examination indicated an empty rectum without red currant jelly stool and non-palpable mass. Abdominal ultrasonography revealed a target sign of intussusception. After a period of conservative treatment, the child passed normal coloured and well-formed stool. Exploratory laparotomy referred to a long segment ileo-ileal intussusception with a polypoid lipoma as a lead point. Microscopic examination showed a benign non-capsulated intramuscular ileal lipoma. DISCUSSION: Small bowel lipoma produces symptoms of intermittent bowel obstruction. Herein, the child presented with non- bilious vomiting, we attribute this to reflex sympathetic stimulation of the pylorus leading to pylorospasm. CONCLUSION: Small intestinal lipoma is a rare finding in children that may cause intussusception which does not resolve spontaneously.