Evaluation of tumor budding and its correlation with histomorphological prognostic markers in oral squamous cell carcinoma and its association with the epithelial-mesenchymal transition process

Objective: To evaluate the association of tumor budding (TB) with prognostic histomorphological parameters in oral squamous cell carcinoma (OSCC) and to investigate the correlation of TB intensity with epithelial to mesenchymal transition (EMT). Material and Method: A total of 200 cases diagnosed as OSCC were selected and their TB status was reviewed using Hematoxylin and eosin (H and E) and Immunohistochemistry (IHC). Correlation with histomorphological prognostic parameters was done. Also, IHC for Vimentin and E-cadherin was performed to look for EMT. Results: On H and E examination, TB was observed in 154/200 (77%). About 88/154 (57.14%) cases showed a high TB (>5 TB/10 hpf) which increased to 100/154 (64.9%) cases on IHC staining. The intensity of TB was significantly associated with tumor grade and depth of invasion. It was also significantly associated with reduced expression for E-Cadherin and upregulation of Vimentin establishing a pathogenetic correlation between the TB and EMT. Conclusion: Therefore, our results suggest that TB is associated with poor prognosis and histologically represents EMT in OSCC which further adds to the aggressiveness of the tumor.

Spectrum of histopathological changes and its quantification using a scoring system in patients with gastroesophageal reflux disease

Aim: The aim of this study was to evaluate the role of histopathological and histomorphometric features in oesophageal biopsy of patients presenting with symptoms of Gastroesophageal Reflux Disease (GERD). Material and Methods: Present study included 42 patients and 12 controls. Complete clinical evaluation followed by endoscopic examination of the patients was done and multipleoesophageal biopsies were taken. Biopsies were processed routinely and stained with Hematoxylin and Eosin and examined for any changes related to GERD. Morphometric assessment was done by using Leitz optical micrometer. The histological scoring was done based on the parameters: basal cell hyperplasia, stromal papillae elongation, cells with irregular nuclear contour (CINC), eosinophilic infiltrate, gastric and intestinal metaplasia. A numerical score was assigned to each parameter and sum of these scores represented the total score. Statistics: The statistical analysis was done using graph pad prism, Medcalc software and Windows MS office. P value and mean standard deviation (SD) was calculated. Results: The endoscopic findings of all the controls and 83.33% of patients were normal. Only 16.67% of patients had reflux associated changes of varying grades on endoscopy. Oesophageal biopsy of all patients had changes related to GERD on histology. Immunohistochemistry confirmed that cells with irregular nuclear contour were T- lymphocytes. The mean (SD) histological scoring of control and patients were 1.75 (0.62) and 5.66 (1.31) respectively. The difference was considered to be statistically significant (P < 0.001). Thus, it was suggested that a cut-off of histological score > 3 can be used to indicate GERD. Conclusion: Patients with gastroesophageal reflux symptoms can have normal endoscopic findings but can be diagnosed on the basis of histological changes in the squamous epithelium. Scoring of the histopathological parameters along with the cut-off value can give a definitive diagnosis of GERD.

Immunohistochemical evaluation of E-cadherin in oral epithelial dysplasia and squamous cell carcinoma

Aim: To evaluate the expression of E-cadherin (E-cad) in oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC). Material and Method: Immunohistochemistry was used to detect E-cad expression in 20 cases each of normal oral mucosa, oral epithelial dysplasia and squamous cell carcinoma. Statistical Analysis Used: Inferential statistical methods for statistical analysis used were Chi-square test for comparison of the frequency between different severity of dysplasia and OSCC. Results: Upon assessing the expression of E-cad in OED and OSCC, increase in E-cad immunoreactivity was seen in early lesions. However, the expression of E-cad decreased significantly as the grade of dysplasia increased. Conclusion: We observed a significant decrease in E-cad expression from dysplasia to poorly differentiated squamous cell carcinoma suggesting that loss of expression of E-cad is closely related to carcinoma.

Association of different patterns of expression of beta-catenin and cyclin D1 with pathogenesis of breast carcinoma

Background: Beta-catenin and cyclin D1 have attracted considerable attention in recent studies as potential proto-oncogenes in many human cancers especially colonic cancer. Beta-catenin plays multiple roles within the cell such as canonical Wnt signaling where cyclin D1 has been identified as one of its target genes. The role of beta-catenin and cyclin D1 in breast cancer has been evaluated in many studies but not established yet. Materials and Methods: The expression of beta-catenin and cyclin D1 was evaluated in 82 cases of breast carcinoma (BCa) and 32 cases of ductal carcinoma in situ(DCIS) by immunohistochemistry (IHC). Their relationship with clinicopathological features was also investigated. Statistical analysis was done to establish an association. Results: Abnormal expression of beta-catenin (ABE) was seen in 80.2% cases of invasive ductal carcinoma (IDC) and 47% cases of DCIS, while the cyclin D1 positive expression rate was 60.9% and 50%, respectively. In the cases showing ABE, cyclin D1 positivity was 88.1%. ABE showed significant association with high-grade BCa. The most common pattern of ABE was loss of membrane with nuclear positivity which is associated with worst prognosis. In addition, ABE in cases of BCa and DCIS showed concordant patterns. Conclusion: Therefore, an association exists between ABE and cyclin D1 in BCa and its precursor lesions implying that Wnt/beta-catenin oncogenic pathway may have a definite role in breast carcinogenesis and can be used for targeted therapy. Also, different patterns of beta-catenin expression may have prognostic and predictive value.

Guided Tissue Regeneration with β-Tricalcium Phosphate and Platelet-rich Plasma for Fracture Repair in Dogs using Internal Fixation

The study was conducted on 19 adult dogs referred for treatment of fracture in diaphyseal region of three long bones, viz, radius-ulna, femur and tibia-fibula. These dogs were divided randomly into three groups viz T1, T2 and T3. In group T1, the diaphyseal fractures of the long bones were immobilized by an internal fixation technique using reconstruction plate or locking compression plate. In group T2, β- tri calcium phosphate granules were incorporated at fracture site after fixation. In group T3, one milliliter of PRP was administered locally at fracture site just before the closing the first suture line. Clinical and radiographic examination were also conducted during the study. There was a significant reduction in mean inflammation score at 7th day in groups T2 and T3 and at 30th day than 0 day in all the groups. At 90th day, the mean radiographic score was highest for group T3 and it was followed by the score in group T2. At day 90th, a radiograph in both the views was not able to delineate the granules from osseous tissue. The mean weight bearing score was also higher in group T3 than in group T2 at 30th, 60th and 90th post operative day showing that restoration of the function was better and earlier in groups T2 and T3 than in group T1

Water, sanitation and hygiene survey – Use of hydrogen sulfide strip at field level as a point-of-care test: A pilot study

Safe drinking water is a basic element of primary health care. The government of India in its Indian Public Health Standards recommends the hydrogen sulfide (H2S) strip test as a desirable component at primary health centers for screening water for fecal coliforms. The objective of the present study was to conduct a water, sanitation and hygiene (WASH) survey followed by a H2S strip test of drinking water in a village with ninety households. The test was positive in 88% at the source and the point of consumption, with 100% concordance between both the points of test. A subsample of water samples was subjected to testing in microbiology laboratory, and fecal contamination was confirmed in all of them. To conclude, H2S strip test can be conveniently used at field level, and its ease of use and visual nature of results make it a useful point-of-care test of environmental and public health.

Rupture of Term Noncommunicating Rudimentary Horn of Uterus.

Pregnancy in noncommunicating rudimentary horn is rare. It occurs following transperitoneal migration of sperms or zygote. Uterine rupture usually occurs in 70-80% cases in the second trimester by 20 weeks. Neonatal survival in rudimentary horn pregnancy is poor occurring in only about 11% of cases.

A View on Combination Antiplatelet Agents in Ischemic Stroke.

The evaluation of antiplatelet agents for prevention of ischemic stroke is being focused as a strategy for stroke reduction. The aim of this analysis was to focus specifically on the necessity of combination antiplatelet agents for secondary prevention of ischemic strokes. Aspirin, clopidogrel, ticlopidine and the combination of aspirin plus extended-release dipyridamole are all effective in reducing the risk of recurrent ischemic strokes and transient ischemic attack. Furthermore, the combinations of all above drugs show some merits and demerits in one or more condition. National guideline endorses any of these antiplatelet agents as appropriate treatment options but more research into this strategy is needed. Choosing a single antiplatelet agent or the combination must be tailored according to patient characteristics, cost, disease condition and tolerability. Other classes of antiplatelet drugs should undergo clinical trials to optimize antiplatelet therapy.

Childhood T-lineage Acute Lymphoblastic Leukemia: Management and Outcome at a Tertiary Care Center in North India.

Objective: To assess the clinical features, prognostic factors and outcome of childhood T-ALL in comparison with B-lineage ALL, treated with a uniform treatment regimen (MCP 841). Setting: Pediatric oncology division of a tertiary care institution in Northern India. Design: Retrospective analysis of clinical data and survival outcome. Participants: 60 children with T-ALL and 139 with Blineage ALL, and less than 15 years of age treated over 15 years. Results: T-ALL was observed in 30%. High risk features at presentation (age 10 years, WBC >50,000/mm3, mediastinal mass, and CNS leukemia) were significantly more frequent in T-ALL as compared to B-lineage ALL (P=0.049, P<0.001, P<0.001 and P=0.02, respectively). Fifty five of 60 T-ALL patients (91.7%) achieved complete remission after induction therapy. There were 3 induction and 10 remission deaths while 11 (18.3%) relapsed. The overall survival and event-free survival of T-lineage ALL (61.5±7.6 and 49.9±7.4, respectively) were similar to that of B-lineage patients (68.7±4.7 and 47.1±5.1, respectively). National Cancer Institute risk groups emerged as significant prognostic factor for event free survival only in B-lineage patients. Conclusions: Even though high risk features were significantly more frequent in T-ALL, survival outcome was similar to that of B-lineage patients. None of the routinely described prognostic parameters significantly impacted survival.

Absolute lymphocyte count: A cost-effective method of monitoring HIV-infected individuals.

Aim: Depletion of CD4 cell count is a hallmark of disease progression in AIDS. CD4 cell count is essential for physicians to decide about the timing of initiation of antiretroviral therapy (ART) and for prophylaxis of opportunistic infections. WHO has recommended that, absolute lymphocyte count (ALC) of ≤1200/μL can substitute CD4 cell count of ≤200/μL in resource-constrained countries throughout the world. Materials and Methods: This study was undertaken to know whether there is a correlation between CD4 cell count and ALC in HIV-infected individuals. A single sample of blood was withdrawn for ALC and CD4 cell count. The samples received from December 1, 2004 to December 31, 2005 were analyzed. Results: A total of 196 samples were collected from 185 patients. After exclusion, a total of 182 samples were analyzed. Results revealed that male:female ratio was 126:56 and their age ranged from 13 to 67 years. The median ALC was 1747 cells/μL, whereas the CD4 cell count ranged from 5 to 2848. The correlation coefficient between ALC and CD4 cell count was significant (0.714). There were 49 patients with an ALC of ≤1200/μL of whom 77.6% patients had CD4 cell count ≤ 200/μL (true positive) and 22.4% had CD4 cell count > 200/μL (false positive). There were 133 patients with an ALC of >1200/μL of whom 84.2% had CD4 cell count > 200/μL (true negative) and 15.8% had CD4 cell count ≤ 200/μL (false negative). Taking ALC of ≤1200/μL as a predictor of CD4 cell count ≤ 200/μL ,the sensitivity of the test was 64.4% and specificity was 91.1%. The positive predictive value was 77.6%, negative predictive value was 84.2%, and accuracy was 82.4%. Conclusion: We found that an ALC of ≤ 1520/μL has higher sensitivity (78%) for a CD4 cell count of ≤ 200/μL. The ALC was found to be significantly cost-effective in our setup but chances of missing out patients requiring ART was 1 in 5 using the WHO guidelines.

Utility of family studies in diagnosing abnormal hemoglobins/thalassemic states.

Objective. To resolve all indeterminate cases on HPLC screening with the help of family studies and to further confirm the results by genetic analysis. Methods. In our 11 years experience with HPLC at Sir Ganga Ram Hospital, we solved many cases with the help of family studies on parental blood samples in which patient could have possibly been homozygous vs compound heterozygous. Genetic analysis was done on index case as well as on parental samples with ARMS-PCR technique to confirm the results. Results. In 100% of cases, we noted that the diagnosis obtained by family studies was commensurate with that obtained by DNA analysis. Conclusion. In centers, which do not have the facility for genetic analysis, family studies by HPLC can be equally useful.

A cardiac evoked response algorithm providing automatic threshold tracking for continuous capture verification: a single-center prospective study.

BACKGROUND: The AutoCapture algorithm as implemented in Regency and Microny pacemakers (Pacesetter Inc., Sylmar, CA, USA) provides beat-by-beat monitoring of capture based on proper detection of the evoked response, provides high output back-up pulse when loss of capture occurs, performs periodic threshold evaluations and acquires the capture threshold data in a time-based event counter for later retrieval. The safety and efficacy of this algorithm was prospectively evaluated at a tertiary care hospital of north India. METHODS AND RESULTS: Fifty-four patients (38 males, mean age 66+/-13 years) received a ventricular pacemaker model Regency SC+ with low polarization bipolar lead for high-grade atrioventricular block (n=42) and sick sinus syndrome (n=12). Evoked response and polarization signal were assessed initially at 24 hours postimplant, and follow-up measurements were systematically conducted at week 1 and months 1, 3 and 6. Further evaluation of eligible patients was performed at 6-monthly intervals. Lead implantation parameters were optimum in all patients. At 6 months, the algorithm was functional in 51 patients. The pacing threshold increased to 0.89+/-0.36 V (p<0.001) in the first month and stabilized thereafter. Significant saving of energy was accomplished by a constant output safety margin of 0.3 V instead of the traditional 100%. While the evoked response signal remained stable throughout the study period, the potential signal increased significantly from 0.6+/-0.7 mV to 1.0+/-0.6 mV (p<0.001) in the first month and remained steady subsequently. Back-up pacing in the event of exit block was confirmed in all 25 patients who underwent a 24-hour Holter test. Based on the suggested sense margins, ventricular undersensing was observed in 7 (28%) patients, the majority of whom had competitive cardiac rhythms. An elderly patient with pneumonic illness succumbed to pulmonary embolism at 6 months. CONCLUSIONS: This large single-center experience on AutoCapture demonstrates the success of this algorithm in low-energy ventricular pacing without compromising the patient's safety.

Single stage bilateral common carotid artery stenting in a patient of Takayasu arteritis.

Carotid angioplasty and stenting is increasingly becoming a safe and efficacious modality of treatment in the management of carotid artery stenosis. Although atherosclerosis is the predominant cause of this morbid disease, Takayasu arteritis assumes special importance in south east Asia. The diffuse nature of this disease with associated inflammation and scarring of the vessel make revascularisation difficult. We report a case of Takayasu arteritis in which a successful bilateral common carotid stenting was done in a single sitting.

Erythrocyte indices for discriminating thalassaemic and non-thalassaemic microcytosis in Indians.

BACKGROUND: Microcytosis is a common red cell change seen in anaemias of varied aetiology. These include iron deficiency, thalassaemia, chronic disease and sideroblastic anaemias. The microcytosis of heterozygous beta-thalassaemia needs to be distinguished from non-thalassaemic microcytosis for its role in thalassaemia control. Red cell indices derived from automated red cell analysers have been used to discriminate between microcytic patients with a high probability of thalassaemia minor from those with a low probability. There is a controversy on the choice of red cell indices to be used and the cut-off values for this distinction, because the prevalence of iron deficiency as a cause of non-thalassaemic microcytosis is variable. Since no Indian study using receiver operator characteristic (ROC) curves was available to determine the above, we conducted this study. METHODS: Red cell indices (mean corpuscular volume, total red blood cell count, red cell distribution width, linear discriminant function), serum iron, total iron binding capacity and haemoglobin A2 were estimated in 640 adults with microcytosis (mean corpuscular volume 80 fl). The ROC curves were plotted in all. RESULTS: Total red blood cell count was observed to be the most efficient single test followed by linear discriminant function and Bessman index. Mean corpuscular volume had the least efficacy. The cut-off values obtained for the Indian population were mean corpuscular volume < or = 76 fl, total red blood cell count > or = 4.9 x 10(12)/L and red cell distribution width > or = 18% and a positive linear discriminant function. These were different from those observed in the West, possibly because of the high prevalence of iron deficiency in India. CONCLUSION: In countries with a high prevalence of iron deficiency, cut-off values for red cell indices should be recalculated using ROC curves.