HYBRID BONE SCINTIGRAPHY IN GASTROINTESTINAL MALIGNANCIES – INSTITUTIONAL EXPERIENCE

Objective: Bone metastases in gastrointestinal (GI) malignancies are uncommon and known to be predominantly lytic thus rendering a limited role for conventional bone scintigraphy. The aim of the study is to review Tc99m MDP bone scans performed in patients with known GI malignancy and the utility of Single-photon emission computed tomography (SPECT)/CT in characterization of bone lesions.Methods: Retrospective review of bone scans was done from June 2014 to December 2016 in patients with known GI malignancy, using electronic Hospital Information System.Results: A total of 110 patients (60 males, 50 females; Age range: 22–84 years, Mean Age 51.4 years with SD of 14.8) had bone scan over a period of 30 months. The commonest indications for referral were suspected bone metastasis on other imaging modalities including [CT (n = 56), Magnetic resonance imaging (n = 10), Positron emission tomography/CT (n = 6)], musculoskeletal pain (n = 37), pathological fracture (n = 1), neurological symptoms (n = 1), hypercalcemia (n = 1) and others (n =14) including restaging workup etc. Metastatic lesions were identified in 32 (29%) patients whereas 78 (71%) patients had benign non-aggressive lesions leading to normal bone scans. Among 32 patients with osseous metastasis, 8 (25%) patients had unifocal lesion; axial skeleton (n = 2) appendicular skeleton (n = 6), 24 (75%) patients had multifocal lesions; axial skeleton (n = 6), appendicular skeleton (n = 6) and both axial + appendicular (n = 12). Four (12%) patients had concurrent visceral metastases. In our cohort, based on the location of primary tumour, the frequencies of osseous metastasis were; esophagus = 15 out of 43 (35%), gastric = 7 out of 18 (39 %), gastro-esophageal junction = 1 out of 8 (1.5%) and colorectal = 9 out of 40 (22.5). SPECT/CT was acquired in 29 out of 110 patients, which characterized metastatic lesions (n = 12) and benign looking non-aggressive entities (n =17). Overall, bone scan upstaged disease in 31% and down staged 15% patients.Conclusion: Bone metastases in GI malignancies, though uncommon, show an aggressive pattern, with axial and appendicular involvement, and can be readily identified with hybrid bone scintigraphy in symptomatic patients. Key words: Hybrid imaging, Tc99m MDP, bone metastases, gastrointestinal malignancie

Infiltrating syringomatous adenoma of nipple

Infiltrating syringomatous adenoma of the nipple is a rare, benign lesion with distinct clinical and histological features. Origin from ducts of dermal sweat glands has been postulated. Important differential diagnosis include nipple adenoma, tubular carcinoma and adenosquamous carcinoma. Appropriate local management includes accurate diagnosis and complete excision to avoid local recurrences. This report describes the condition in a 39-year-old parous lady

Expression of androgen receptor and cancer stem cell markers (CD44 +/CD24 - and ALDH1 +): Prognostic implications in invasive breast cancer

Background: Androgen receptor (AR) has emerged as a significant prognostic marker in early breast cancer (BCa). Association of AR with cancer stem cell (CSC) markers in BCa is unknown. Aim of the present study was to evaluate the immunohistochemical expression of AR, CD44, CD24 and ALDH1 in a cohort of Pakistani patients diagnosed with invasive BCa and to correlate the expression with 5- year disease free survival.Patients and methods: We evaluated immunohistochemical expression AR, CD44, CD24 and ALDH1 in formalin fixed paraffin embedded archival blocks of 166 cases of primary invasive BCa (stage I-III) and correlated the expression with clinicopathological variables and outcome using univariable and multivariable analysis. Survival data was computed by Kaplan Meier curves.Results: Expression of AR was observed in 62.7% tumors whereas CD44, CD24 and ALDH1 were expressed in 61.4%, 44% and 30.1% tumors, respectively. AR expression was significantly associated with T1-T2 tumors, lower grade, estrogen and progesterone receptor expression (P \u3c .05) and remained an independent prognostic indicator in multivariable analysis (adjusted HR 0.33, 95% CI 0.13-0.81; P = .016). Significant association was observed between concordant expression of AR and CD24 (P = .001) with a favorable impact on survival (P = .007) whereas expression of CSC phenotypes (CD44+, CD44+/CD24- and ALDH1+) did not correlate with adverse outcome (P \u3e .05). However, AR expression retained the association with better prognosis even in patients whose tumors exhibited a CSC phenotype.Conclusions: Expression of AR and CD24 in stage I-III invasive BCa correlates with favorable clinicopathological features and delineates a subgroup of patients with better disease-free survival

Proteomics-derived basal biomarker DNA-PKcs is associated with intrinsic subtype and long-term clinical outcomes in breast cancer

Precise biomarkers are needed to guide better diagnostics and therapeutics for basal-like breast cancer, for which DNA-dependent protein kinase catalytic subunit (DNA-PKcs) has been recently reported by the Clinical Proteomic Tumor Analysis Consortium as the most specific biomarker. We evaluated DNA-PKcs expression in clinically-annotated breast cancer tissue microarrays and correlated results with immune biomarkers (training set: n = 300; validation set: n = 2401). Following a pre-specified study design per REMARK criteria, we found that high expression of DNA-PKcs was significantly associated with stromal and CD8 + tumor infiltrating lymphocytes. Within the basal-like subtype, tumors with low DNA-PKcs and high tumor-infiltrating lymphocytes displayed the most favourable survival. DNA-PKcs expression by immunohistochemistry identified estrogen receptor-positive cases with a basal-like gene expression subtype. Non-silent mutations in PRKDC were significantly associated with poor outcomes. Integrating DNA-PKcs expression with validated immune biomarkers could guide patient selection for DNA-PKcs targeting strategies, DNA-damaging agents, and their combination with an immune-checkpoint blockade

The immune microenvironment and relation to outcome in patients with advanced breast cancer treated with docetaxel with or without gemcitabine

Preclinical studies suggest that some effects of conventional chemotherapy, and in particular, gemcitabine, are mediated through enhanced antitumor immune responses. The objective of this study was to use material from a randomized clinical trial to evaluate whether patients with preexisting immune infiltrates responded better to treatment with gemcitabine + docetaxel (GD) compared to docetaxel alone. Formalin fixed, paraffin-embedded breast cancer tissues from SBG0102 phase 3 trial patients randomly assigned to treatment with GD or docetaxel were used. Immunohistochemical staining for CD8, FOXP3, LAG3, PD-1, PD-L1 and CD163 was performed. Tumor infiltrating lymphocytes (TILs) and tumor associated macrophages were evaluated. Prespecified statistical analyses were performed in a formal prospective-retrospective design. Time to progression was primary endpoint and overall survival secondary endpoint. Correlations between biomarker status and endpoints were evaluated using the Kaplan-Meier method and Cox proportional hazards models. Biomarker data was obtained for 237 patients. There was no difference in treatment effect according to biomarker status for the whole cohort. In planned subgroup analysis by PAM50 subtype, in non-luminal (basal-like and HER2E) breast cancers FOXP3 was a significant predictor of treatment effect with GD compared to docetaxel, with a HR of 0.22 (0.09-0.52) for tumors with low FOXP3 compared to HR 0.92 (0.47-1.80) for high FOXP3 TILs (Pinteraction = 0.01). Immune biomarkers were not predictive of added benefit of gemcitabine in a cohort of mixed breast cancer subtypes. However, in non-luminal breast cancers, patients with low FOXP3+ TILs may have significant benefit from added gemcitabine

Feeding potential of the predatory ladybird beetle Coccinella septempunctata (Coleoptera; Coccinellidae) as affected by the hunger levels on natural host species

Ladybird beetles/Ladybugs, both adults and larvae, are well-known primarily as predators of aphids (plant lice); however, they also prey upon many other soft bodied insects and eggs of different borers.  Laboratory rearing of predatory ladybirds often need a live host particularly aphids.  Studies were conducted to check the suitability of live and frozen rose and mustard aphids to rear seven spotted ladybird beetle under two feeding conditions i.e., fed normally (unstarved beetles) or hungry (starved) for 16 hours.  Results showed that hungriness may affect the food consumption efficiency. When the beetles were not starved, they showed preference for eating live mustard aphids as compared to frozen (Mean ± SE = 6.24 ± 0.37 live aphids, 4.43 ± 0.40frozen aphids).  Similar trend was observed on rose aphids (6.51 ± 0.5 (live aphids) and 4.86 ± 0.49 (frozen aphids)). But the adults in starved condition consumed equal number of live and frozen aphids.  During the 1st hour, starved beetles consumed more aphids of both species as compared to unstarved beetles. Also, more number of mealybugs was consumed in starved condition.  This study highlights that feeding potential of predatory seven spotted ladybird is not only affected by the type of host but also the condition of host (live vs frozen).  Moreover, starvation level of the predator can also be an important factor in determining its devouring capacity.

Expression analysis and prognostic significance of androgen receptor and cancer stem cell markers in invasive breast cancer with emphasis on metaplastic carcinoma

A large body of experimental data supports hierarchical organization of breast cancer (BCa) such that tumor initiation, progression and therapeutic resistance are driven by rare population of cancer stem cells (CSCs). In breast, CSCs have been identified by expression of CD44\u27/CD24-and ALDH1+ phenotypes. It has been suggested that CSCs exhibit plasticity and transition between epithelial and mesenchymal phenotypes, favoring metastasis. While metaplastic carcinoma of breast (MCa) is a prototype enriched in CSCs and epithelial to mesenchymal transition gene signature, formation of metaplastic elements within the tumor is not well studied. There has been a renewed interest in understanding the biological role of androgens and androgen receptor (AR) in BCa however, prognostic significance of AR in relation to CSC markers across BCa subtypes is not known. To evaluate the potential prognostic value of AR and CSC markers, expression of AR, CD44, CD24 and ALDH1 was determined by immunohistochemistry (IHC) on formalin fixed paraffin embedded (FFPE) sections of 166 stage I-III invasive BCa cases. Expression of AR was observed in 62.7% tumors whereas CD44, CD24 and ALDH1 were expressed in 61.4%, 44% and 30.1% tumors, respectively. AR expression correlated with small tumors, lower grade, ER/PR expression (p \u3c 0.05) and remained an independent prognostic indicator associated with improved outcome (p = 0.016). Significant association was observed between concordant expression of AR and CD24 (p = 0.001) with favorable impact on survival (p = 0.007), whereas expression of CSC phenotypes (CD44+, CD44+/CD24-and ALDH1±) did not correlate with adverse outcome (p \u3e 0.05). However, AR retained the association with better survival even in patients whose tumors expressed CSC markers. Prognostic significance of AR and CSC markers was further evaluated in 197 stage I-III triple negative breast cancer (TNBC) cases. AR expression was found in 18.7% tumors while CD44, CD24 and ALDH1 were expressed in 29.4%, 33% and 13.2% cases, respectively. Lack of AR expression correlated with grade III tumors (p \u3c 0.001), basal markers (CK5, CK14 and nestin), Bc12 (p = 0.04), COX2 (p =0.02) and CD44+/CD24-phenotype (p \u3c 0.001). Significantly adverse overall survival (OS: p = 0.01) and breast cancer specific survival (BCSS: p = 0.04) were observed in tumors lacking AR expression. This work was extended to 29 cases of stage I-III MCa and the analysis revealed that AR was expressed in 41.6% of the evaluable cases, while expression of CD44, CD24 and ALDH1 was found in 44.3%, 51.7% and 20.7% cases, respectively. MCa cases displayed poor OS compared to TNBC cases (p = 0.054) and worst BCSS when TNBC cases were stratified by basal and non-basal subtypes (p =- 0.021). To investigate occurrence of EMT in MCa, a cell line model, AKU-BC42, was established from primary culture of a breast tumor biopsy. AKU-BC42 expressed AR, luminal and basal cytokeratins. In addition, expression of vimentin and low expression of E-cadherin was observed. Expression of mesenchymal stern cell (MSC) markers was assessed by flow cytometry and revealed that CD73, CD90 and CD105 were expressed in 49.4%, 2.9%, 4.7% of cells in AKU-BC42, respectively. AKU-BC42 demonstrated adipogenic, osteogenic and chondrogenic differentiation potential when cultured under defined conditions. Further in vitro and in vivo studies are needed to understand the biological role of AR in TNBC and modulation of EMT in MCa. These studies will provide insight into rationale for AR targeted therapies in these aggressive tumors

Acute small bowel obstruction secondary to ileal endometrioma

Pelvic endometriosis, a common disease of the female genital tract, may also affect the bowel, especially the rectosigmoid colon. Involvement of small intestine occurs very infrequently. A case of small bowel obstruction caused by ileal endometriosis is reported