Radioguided occult lesion localisation (ROLL) and sentinel node biopsy for impalpable invasive breast cancer.

AIM: The aim of this study was to simplify the technique of ROLL and sentinel node biopsy without compromising tumour excision and sentinel node biopsy. METHODS: Twenty patients with impalpable primary invasive breast carcinoma underwent an injection of 99mTc-nanocolloid mixed with radiographic contrast medium Iohexol into the centre of the lesion under ultrasound or stereotactic guidance pre-operatively. No guidewire localisation was performed. Under general anaesthesia, a periareolar intradermal/subcutaneous injection of patent blue-V dye was performed. The sentinel node was identified by blue-stained lymphatics and node and a hot spot on the gamma probe. Surgical excision of the primary tumour was then carried out using the gamma probe. RESULTS: In eight of 20 cases an immediate re-excision was carried out and on histological assessment, all 20 patients were clear of invasive disease at the margins. In two patients, in situ disease was present at the margins and a further re-excision was therefore performed. The sentinel node was identified in all cases. In all, five of 20 patients were node positive on routine HE staining. In a further two patients, tumour cells were identified by immunohistochemistry with CAM5.2 antibody. Completion axillary clearance in six patients confirmed that the sentinel node was the only positive node. CONCLUSIONS: This modification of the previously described ROLL technique is feasible and safe and does not compromise tumour excision or sentinel node detection.     

Chemotherapy induces the expression of cyclooxygenase-2 in non-small cell lung cancer.

PURPOSE: To determine the effect of taxane-based chemotherapy on intratumoral levels of cyclooxygenase-2 (COX-2) and prostaglandin E(2) (PGE(2)) in patients with non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Lung specimens obtained at the time of surgery were used to measure levels of COX-2 and PGE(2) in tumors and adjacent nontumorous tissues in three subsets of NSCLC patients who underwent: (A) surgical resection only (n = 16); (B) surgical resection after preoperative taxane-based chemotherapy (n = 13); or (C) surgical resection after preoperative chemotherapy coadministered with the selective COX-2 inhibitor, celecoxib 400 mg bid (n = 17). RESULTS: Levels of intratumoral PGE(2) were nearly 3-fold higher among patients who received preoperative chemotherapy compared with those treated by surgery alone (P < 0.001). This difference was abrogated by the addition of celecoxib to preoperative chemotherapy (P < 0.001). Amounts of intratumoral COX-2 were approximately 3-fold higher in groups of patients who received preoperative chemotherapy with celecoxib (P < 0.0001) or without celecoxib (P < 0.001), compared with the group who underwent surgical resection only. Importantly, statistically significant positive correlations between COX-2 and PGE(2) were observed in the surgery only (r = 0.502, P = 0.047) and preoperative chemotherapy groups (r = 0.740, P = 0.004); this correlation was abrogated when celecoxib was given with chemotherapy (r = 0.005, P = 0.98). CONCLUSIONS: Treatment with chemotherapy led to increased amounts of COX-2 and PGE(2) in NSCLC. Cotreatment with celecoxib abrogated the increase in levels of PGE(2) but not COX-2 induced by chemotherapy. Importantly, these results clearly show that levels of a pharmacologic target (i.e., COX-2) can be affected by both the intrinsic molecular properties of a tumor and therapy.     

Challenges in the management of pleomorphic lobular carcinoma in situ of the breast

BackgroundPleomorphic Lobular Carcinoma in Situ (PLCIS) is a pathological variant of Lobular Carcinoma in Situ (LCIS) with distinct features. Since first described over a decade ago there are only few papers published about this condition.MethodsMedline and Pubmed based literature overview was done with the aim of describing the different histopathological, radiological and clinical features of this pathological entity to highlight the different clinicopathological presentations and modalities of treatment described.ResultsPLCIS has different biological features when compared to LCIS. It is more likely to be associated with invasive disease and the immuno-histochemical profile shows it is less likely to be ER and PR positive with higher positivity of HER2, Ki-67and p53. It has been suggested that PLCIS should be treated more aggressively than LCIS and surgically excised in similar fashion to DCIS.ConclusionPLCIS is a more aggressive variant of LCIS that needs to be managed differently. Surgical excision with clear margins is advised. Further adjuvant treatments have been described in the literature with little evidence to support their use.     

Serum biomarkers for diagnosis and monitoring viral hepatitis and hepatocellular carcinoma

Introduction: Chronic liver disease due to viral hepatitis continues to be a major global health concern. Timely diagnosis and treatment will prevent cirrhosis, risk of hepatocellular carcinoma (HCC), and requirement for liver transplantation. Numerous serum biomarkers are available for viral hepatitis that are helpful in diagnosis, measuring severity, progression of disease, evaluating the best therapeutic options, and monitoring antiviral treatment response. Determining the clinical use of available diagnostic tests can be challenging for the health care provider.

Areas covered: This review article attempts to summarize the established and emerging serological markers for diagnosis and managing viral hepatitis. The literature search was performed in February 2018 and included MEDLINE and Embase databases for recent relevant literature on biomarkers for viral hepatitis.

Expert Commentary: Despite the discovery of several candidate biomarkers, translating these to clinical practice in viral hepatitis and HCC remains challenging. While limited availability of the new biomarkers in prevalent geographic areas and significant cost remain major obstacles, there have been exciting developments in this field. Understanding the detection limits and sensitivity of these markers and translating them into clinical use is important in management of viral hepatitis and complications of liver disease such as cirrhosis and hepatocellular cancer.     

Subungual glomus tumors of the hand: Treated by transungual excision

Background:Glomus tumors are benign hamartomas arising from the glomus body, mostly occurring in the subungual region of the digits. A triad of excruciating pain, localized tenderness and cold sensitivity is the key to diagnosing these tumors. Two surgical approaches are described in the literature for excision of subungual glomus tumors-transungual and periungual. We reviewed retrospectively the results of subungual glomus tumors of the hand treated by transungual excision.Results:All patients had complete pain relief. There was no new nail deformity and no recurrence till last followup. One patient had deformity of the nail preoperatively due to previous surgery, which persisted after excision of the tumor. All of them returned to their preoperative occupation and regained full function of the hand.Conclusions:The transungual approach provides good access to the entire lesion and facilitates complete excision. Contrary to reported literature, we did not find the development of any new nail deformity with this approach.     

Synthesis,biological evaluation,and molecular modeling of (<Emphasis Type="Italic">E</Emphasis>)-2-aryl-5-styryl-1,3,4-oxadiazole derivatives as acetylcholine esterase inhibitors

A library of 2,5-disubstituted 1,3,4-oxadiazole derivatives of (E)-2-aryl-5-(3,4,5-trimethoxystyryl)-1,3,4-oxadiazoles 4(a–o) and (E)-2-aryl-5-(2-benzo[d][1,3]dioxol-5-yl)vinyl)-1,3,4-oxadiazoles 5(a–q) were synthesized and evaluated for their in vitro acetylcholinesterase (AChE) inhibitory activity. All the synthesized compounds exhibited moderate to good inhibitory activity toward the AChE enzyme. Among the oxadiazole derivatives examined, compounds 4a, 4g, 5c, and 5m (IC₅₀ values of 24.89, 13.72, 37.65, and 19.63 μM, respectively) were found to be promising inhibitors of AChE. Molecular protein–ligand docking studies were examined for these compounds using GOLD docking software and their binding conformations were determined and the simultaneous interactions mode was also established for the potent derivatives.     

Designing,docking and molecular dynamics simulation studies of novel cloperastine analogues as anti-allergic agents: homology modeling and active site prediction for the human histamine H1 receptor

The present study predicts a three-dimensional model for the histamine H1 receptor and the design of antihistamine inhibitors using cloperastine as the core molecule by docking studies. In this work, we predicted a three-dimensional structure of the histamine H1 receptor using the MODELLER9V7 software. The protein structure was developed based on the crystal structure of the histamine H1 receptor, the lysozyme chimera of Escherichia virus T4 (PDB ID: 3RZE_A) target collected from the PDB data bank. Using molecular dynamics simulation methods, the final predicted structure is obtained and further analyzed by VERIFY3D and PROCHECK programs, confirming that the final model is reliable. The drug derivatives of cloperastine were designed and docking was performed with the designed ligands along with the drug. The predicted model of the histamine H1 receptor structure is stable and confirms that it is a reliable structure for docking studies. The results indicate that MET 183, THR 184 and ILE 187 in the histamine H1 receptor are important determinant residues for binding as they have strong hydrogen bonding with cloperastine derivatives. The drug derivatives were docked to the histamine H1 receptor protein by hydrogen bonding interactions and these interactions played an important role in the binding studies. The molecule 1-{2-[(4-chlorophenyl) (phenyl) methoxy] ethyl}-4-methylenepiperidine showed the best docking results with the histamine H1 receptor. The docking results predicted the best compounds, which may act as better drugs than cloperastine and in the future, these may be developed for anti-allergy therapy.

The present study predicts a three-dimensional model for the histamine H1 receptor and the design of antihistamine inhibitors using cloperastine as the core molecule by docking studies.