Spectrum of Abnormal Cervical Cytology in Papanicolaou (PAP) Smears

Background: To determine the frequency ofabnormal cytological findings in pap smears ofwomen in a local population in Pakistan.Methods: In this observational study conventionalPAP smear was collected, from squamocolumnarjunction, using an Ayer’s spatula in clockwisedirection for 3600 after exposing the cervix by aCusco speculum. The endocervical smears weremade by rotating the endocervical brush. Thesamples collected were transferred to glass slide andthen slides were fixed in 95% ethyl alcohol. Theslides were then sent to pathology laboratory forhistopathological examination . The adequacy andreporting of pap smears was based on 2001 Bethesdasystem.Results: Majority of the patients in thereproductive age group (18- 38 years). Most of thepatients (49.6%) had no cervical complaint and theyunderwent the procedure for screening. Insymptomatic patients common presentingcomplaints were cervicitis (17.1%) and vaginaldischarge (11.3%).Out of the total 1984 pap smears,99.1% were negative for intraepithelial lesion ormalignancy. The precursor neoplastic lesions wereobserved in 0.8%, which included AtypicalSquamous Cells of Uncertain Significance (ASCUS)(0.6%), Atypical Glandular Cells of UncertainSignificance (AGUS) (0.2%) and High GradeSquamous Intraepithelial Lesion (HSIL)(0.1%).ASCUS was seen mostly in young age group that is18- 38 years while HSIL and AGC were identified inpatients more than 50 years of age. Non-specificinflammatory pattern was seen in 17.6%. Atrophicpattern was observed in 2.5% smears.Conclusion- A significant number of abnormalpap smears were negative for intraepithelial lesionor malignancy.Epithelial cell abnormalities, thoughless prevalent were also seen

Correlation of Molecular Subtypes with Clinico-pathological Parameters in Breast Carcinoma

Background: To determine the correlation between clinic-pathological parameters, like age of the patient, size of the tumour, histologic type and grade with molecular subtype. Methods : This observational study included cases of breast cancer (n=50) . Histological grade was assessed according to Nottingham modification of Bloom-Richardson system. Representative sections with tumour and the adjacent normal tissue ( internal control) were processed for ER, PR and HER-2neu immune-histochemical staining. Thescoring of ER and PR was carried out using Allred scoring system. Molecular subtypes were defined as, triple negative/basal type(HER 2 -,ER- and PR-), hormone receptor(HR) +,HER2-/luminal A(HER2-, ER+ and PR+ or -), HR+,HER2+/luminal B(HER2 +,ER+ and PR+ or-), HR-,HER2+/HER2 enriched(HER2+, ER- and PR -). Results: Majority (96%) were infiltrating ductal carcinoma, one was invasive lobular carcinoma and one was colloid carcinoma. Three cases (6%) grade 1 carcinoma were recorded of which one case (2%) each was of luminal A, luminal B and HER2 enriched type. There were 23 (46%) grade 2 cases of which 8(16%) were luminal A, 7(14%) of luminal B, 7(14%) of HER2 enriched and one (2%) was basal like. There were 24(48%) grade 3 cases of which 6(12%) were luminal A, 9(18%) of luminal B, 6(12%) were HER2 enriched and 4(8%) were basal like. Conclusion: Along with other variables, molecular subtype is important in predicating prognosis of carcinoma breast .Luminal A cancers are more common in older age, while Luminal B are common in younger age group. Key Words: Carcinoma breast,Molecular Subtypes, Estrogen receptor, progesterone receptor, Human epidermal growth factor recepto

Calcifying fibrous pseudotumour of maxilla: A rare entity mimicking malignancy: A case report

Occurrence of inflammatory pseudotumour in head and neck region or nose and paranasal sinuses is rare. However, when they do occur, they could be quite aggressive. Etiologically, they are believed to be reactive than neoplastic, and calcification may suggest end-stage. Their clinical presentation and radiologic features may resemble a malignancy. Grossly, they are not encapsulated, but multilobulated and can be circumscribed or infiltrative. Histologically, they constitute of bland spindle cells with scant cytoplasm and occasional mitotic figures. Scattered lymphocytic and plasma cell infiltrates with abundant dense hyalinized collagenous stroma and focal small calcifications are seen. Presence of atypia, DNA aneuploidy, and abnormal p53 expression may suggest malignant potential. Though not known to metastasize, they can lead to local complications, causing destruction of bone and surrounding tissues. Management is mainly by surgical excision though adjunct corticosteroids have been advocated. We report such a rare case of calcifying fibrous pseudotumour of maxilla

Pleomorphic xanthoastrocytoma: Clinicopathological spectrum of an intriguing neoplasm

Background & Objective: Pleomorphic xanthoastrocytoma (PXA) is a rare primary WHO Grade II astrocytic tumor comprising of \u3c 1% of all astrocytomas. It is generally benign and slow growing however disease progression and malignant transformation with anaplastic features have been infrequently reported. Our objective was to assess clinicopathological characteristics of this rare tumor at our center. Methods: A retrospective study was conducted at Aga Khan University Hospital from January 1992 till January 2016. Data was entered on a proforma including patient demographics, clinical features, tumor location, histological features and follow-up, where available. Results: Forty Seven cases of PXA were retrieved during the study period. The mean age was 23.8 years (SD=15.1) and median age was 19 years. The most frequent symptom was head ache (n=31). Male were more frequently affected (n=26). The commonest location was temporal lobe. On microscopic examination, tumors were pleomorphic without mitoses or necrosis, however two cases showed increased mitotic activity, and one case revealed associated gliosarcoma. Follow-up of only 29 cases was available for a period ranging between 2 and 184 months (85 months +/- 56 months). Outcome was good in 27 patients with the last follow up showing no radiographic or clinical evidence of tumor recurrence. Conclusions: PXA is an infrequent tumor in our population also, with less than 50 cases identified in two decades study period. Due to its rarity and its bizarre histomorphology, it should be diagnosed correctly, as it has got better prognosis than other astrocytic tumors

Gastroenteropancreatic neuroendocrine tumours: Clinicopathological evaluation at Shifa international hospital, Islamabad

Objective: Clinicopathological features of gastroenteropancreatic neuroendocrine tumours (GEP-NETs) have rarely been studied in Pakistani population. We investigated clinical characteristics of these tumours according to updated World Health Organization (WHO) 2010 classification.Methods: The data of Shifa International Hospital, Islamabad was retrospectively analysed for pathologically confirmed GEP-NETs from January 2013 to March 2018.Results: One hundred and eighteen patients (mean age, 52.2± 16.4 years; Of these 65(55.1%) were males. Majority, 98(83.1%) of the patients were symptomatic including 6(5.1%) with functional tumours. Pancreas was the most frequent primary site noted in 33(28%) patients. The most common histologic type was well differentiated neuroendocrine tumour (WDNET) in 96(81.4%) patients followed by neuroendocrine carcinoma (NEC) in 11(16.1%) patients. Almost half the cases or 54(45.8%) of WDNET were grade 1, 32 (27.1%) were grade 2, and 10 (8.5%) were grade 3. Distant metastasis at the time of diagnosis was found in 18(15.3%) cases with 14,(77.7%) in liver as the most common metastatic site. Synaptophysin positivity was seen in 60 (96.8%) cases of grade 1, 32(27.2%) of grade 2 WDNET, 8(100%) cases of grade 3 WDNET and 12(92.3%) of NEC and chromogranin was positive in 49(94.2%) of grade 1 and grade 2 WDNET, 5 (83.3%) cases of grade 3 WDNET and 5 (45.4%) cases of NEC.Conclusions: GEP-NETs showed a wide clinicopathological spectrum. Pancreas is the most common site of involvement by the GEP-NET, however, grade 3 WDNET had a predilection for colon. Small cell carcinoma was commonly observed in the oesophagus

Balanced Transmissions Based Trajectories of Mobile Sink in Homogeneous Wireless Sensor Networks

Mobile Sink (MS) based routing strategies have been widely investigated to prolong the lifetime of Wireless Sensor Networks (WSNs). In this paper, we propose two schemes for data gathering in WSNs: (i) MS moves on random paths in the network (RMS) and (ii) the trajectory of MS is defined (DMS). In both the schemes, the network field is logically divided into small squares. The center point of each partitioned area is the sojourn location of the MS. We present three linear programming based models: (i) to maximize network lifetime, (ii) to minimize path loss, and (iii) to minimize end to end delay. Moreover, a geometric model is proposed to avoid redundancy while collecting information from the network nodes. Simulation results show that our proposed schemes perform better than the selected existing schemes in terms of the selected performance metrics

SLC11A1 polymorphisms and host susceptibility to cutaneous leishmaniasis in Pakistan.

Background:The vector-borne cutaneous leishmaniasis (CL) is endemic in several regions of Pakistan mainly affecting poor populations. Host genetic factors, particularly SLC11A1 (solute carrier transmembrane protein) within macrophages, play a crucial role in disease pathology and susceptibility. Association of SLC11A1 with cutaneous leishmaniasis, a neglected tropical disease, is not well established. Inconsistencies have been observed within different populations worldwide with respect to genetic susceptibility. This study was designed to investigate genetic variation(s) in SLC11A1 and to assess possible association with cutaneous leishmaniasis in Pakistan. Results: Eight polymorphisms (rs2276631, rs3731864, rs2290708, rs2695342, rs201565523, rs17215556, rs17235409, rs17235416) were genotyped across SLC11A1 in 274 patients and 119 healthy controls. Six polymorphisms were studied by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing. Two single nucleotide polymorphisms were analyzed with newly designed semi-nested PCR assays. Case-control analysis showed no association between selected polymorphisms in SLC11A1 and cutaneous leishmaniasis. No significant difference was observed in the distribution of alleles between leishmaniasis patients and healthy individuals. Strong pairwise linkage disequilibrium was observed between rs2276631 and rs2290708 (r 2 = 64); and rs17235409 and rs17235416 (r 2 = 78). Conclusions: This study shows that genetic variations in the candidate gene SLC11A1 do not affect susceptibility to cutaneous leishmaniasis in the sample population from Pakistan

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial