High-risk human papillomavirus DNA testing: a marker for atypical glandular cells

Cervical/endocervical cytology screening has decreased morbidity and mortality, and implementing adjunctive human papilloma virus (HPV) DNA testing for atypical squamous cells of undetermined significance has improved the specificity for detecting premalignant squamous lesions. Currently, there are no guidelines to perform HPV DNA testing on cervical/endocervical ThinPreps with atypical glandular cells (AGC). To assess the potential role of HPV DNA testing on AGC cases, Hybrid Capture 2 (Digene Corp.) testing was performed on 144 cervical/endocervical AGC specimens. One hundred three of 144 cases had follow-up; 60/103 (58.3%) were high-risk HPV negative and 43/103 (42.3%) were high-risk HPV positive. Of 43 HPV-positive patients, 37 had adenocarcinoma in situ (AIS), atypical squamous cells of undetermined significance (ASCUS), or cervical squamous intraepithelial neoplasia, while only one patient without high-risk HPV had a squamous intraepithelial neoplasia. Furthermore, most high-risk HPV positive AGC cases harbored high-grade squamous intraepithelial lesion (HSIL) rather than AIS. Our data support HPV DNA testing of all AGC specimens to detect cervical, especially squamous, neoplasia.     

Uterine rupture in pregnancy: a five-year study

Background  

Uterine rupture during pregnancy is a rare occurrence that frequently results in high incidence of maternal and fetal morbidity and mortality.     

High jugular bulb: different osseous landmarks and their clinical implications

Purpose

The purpose of this investigation was to compare the rate of high jugular bulb (HJB) in relation to internal acoustic meatus (IAM), round window (RW) and endolymphatic sac and to study their clinical implications.

Methods

Eighty-seven cadaveric non-pathologic human temporal bones were micro-dissected to expose the jugular fossa (JF) and RW. The minimum distance of JF from RW was measured. On the inner surface of petrous part of temporal bone, minimum vertical distance of JF from IAM and saccus endolymphaticus (E sac) was also measured. If the distance of summit of JF from RW or IAM was ≤2 mm or if there was no distance between JF and slit on which E sac opens, they were classified as HJB cases.

Results

The mean minimum distance of JF from the RW, IAM and E sac was found to be 2.85 ± 1.58, 3.83 ± 2.38 and 2.06 ± 2.38 mm and the rate of HJB was 32.2, 24.1 and 41.4 % respectively.

Conclusions

The rate of HJB varies even in a particular specimen using different landmarks i.e. the RW, IAM and E sac. The preoperative awareness in relation to these landmarks will be useful in cochlear implantation, surgical removal of vestibular schwanommas and clinical findings of Meniere’s disease.

     

LEAP: Using machine learning to support variant classification in a clinical setting

Advances in genome sequencing have led to a tremendous increase in the discovery of novel missense variants, but evidence for determining clinical significance can be limited or conflicting. Here, we present Learning from Evidence to Assess Pathogenicity (LEAP), a machine learning model that utilizes a variety of feature categories to classify variants, and achieves high performance in multiple genes and different health conditions. Feature categories include functional predictions, splice predictions, population frequencies, conservation scores, protein domain data, and clinical observation data such as personal and family history and covariant information. L2‐regularized logistic regression and random forest classification models were trained on missense variants detected and classified during the course of routine clinical testing at Color Genomics (14,226 variants from 24 cancer‐related genes and 5,398 variants from 30 cardiovascular‐related genes). Using 10‐fold cross‐validated predictions, the logistic regression model achieved an area under the receiver operating characteristic curve (AUROC) of 97.8% (cancer) and 98.8% (cardiovascular), while the random forest model achieved 98.3% (cancer) and 98.6% (cardiovascular). We demonstrate generalizability to different genes by validating predictions on genes withheld from training (96.8% AUROC). High accuracy and broad applicability make LEAP effective in the clinical setting as a high‐throughput quality control layer.     

Fine needle aspiration cytology of breast cancer in women aged 70 years and older

Aims: Elderly breast cancers are associated with a more favourable biological marker profile and higher proportion of specific subtypes, some of which are of low histological grade. We reviewed the fine needle aspiration cytology (FNAC) to assess the cytological characteristics and any clues to assist in the diagnosis. Methods: The aspirates of 140 cancers of various histological types and grades and 39 benign lesions were evaluated for 13 cytological parameters including cellularity of the direct and cytospin smears, epithelial cell clusters, cellular atypism, cytoplasmic features, vacuoles, mitotic figures, presence of myoepithelial cells, single background epithelial cells, the presence of naked nuclei, stromal fragments and necrosis. Results: We found that the presence of background single epithelial cells, atypism of such cells, absence of benign appearing epithelial fragments, nuclear atypism of the epithelial cells within the fragments, presence of moderate amount of cytoplasm of these cells, absence of myoepithelial cells within the cluster, and absence of bipolar nuclei in the background have a strong association with malignancy. Scoring only the presence of single cells in the background, single cell atypism and the absence of bipolar nuclei in a scoring system can differentiate between benign and malignant aspirates with high (>90%) sensitivity and specificity. Conclusions: Assessing the presence of single cells in the background, single cell atypism and the absence of bipolar nuclei facilitates identification of malignancy in the aspiration of breast lesions from elderly patients.     

Adenoid cystic carcinoma of the breast diagnosed by fine-needle aspiration

Fine-needle aspiration cytology remains a useful tool for preoperative diagnosis of breast lesions. We describe a case of adenoid cystic carcinoma (ACC) of the breast detected by ultrasound-guided fine-needle aspiration (FNA). Subsequent histopathology corroborated the diagnosis. ACC is a rare but distinctive neoplasm of the breast that can be accurately diagnosed by FNA. Its infrequent presentation, favorable prognosis, and relatively conservative management in the breast prompt us to reinforce its features.     

Theoretical and in vitro studies of a C-terminal peptide from PGKC of Leishmania mexicana mexicana

Trypanosomatids cause deadly diseases in humans. Of the various biochemical pathways in trypanosomatids, glycolysis, has received special attention because of being sequestered in peroxisome like organelles critical for the survival of the parasites. This study focuses on phosphoglycerate kinase (PGK) from Leishmania spp. which, exists in two isoforms, the cytoplasmic PGKB and glycosomal PGKC differing in their biochemical properties. Computational analysis predicted the likelihood of a transmembrane helix only in the glycosomal isoform PGKC, of approximate length 20 residues in the 62-residue extension, ending at, arginine residues R471 and R472. From experimental studies using circular dichroism and NMR with deuterated sodium dodecyl sulfate, we find that the transmembrane helix spans residues 448±2 to 476 in Leishmania mexicana PGKC. The significance of this observation is discussed in the context of glycosomal transport and substrate tunneling.     

Single Fraction versus Multiple Fraction Radiotherapy for Palliation of Painful Vertebral Bone Metastases: A Prospective Study

Context:

Metastatic bone disease is a commonly encountered problem in oncology practice. The most useful and cost effective treatment is radiotherapy (RT). Different fractionation schedule of RT can be used to treat such condition.

Aims:

Assessment of pain response in patients with vertebral bone metastasis after treating them with various radiation fractionations and to compare the toxicity profile in the treatment arms.

Settings and Design:

A prospective randomized study was designed to include total 64 patients from July 2010 to May 2011. Patients with histopathologically proven primary malignancy having symptomatic secondary deposits to vertebra were selected for the study. Patients were randomized to two arms receiving multiple fraction of RT with 30 Gy in 10 fractions and 8 Gy in single fraction RT, respectively.

Materials and Methods:

Patients with age >75 years, Karnofsky Performance Status (KPS) <40, features of cord compression were excluded from study. Initial pain response was assessed using Visual Analogue Scale (VAS) and compared using the same scale at weekly interval up to 1 month after treatment completion.

Results:

Arm A comprised of 33 patients while 31 patients were enrolled in Arm B. Baseline patient characteristics were comparable. Eleven patients were lost to follow-up. Initial pain scores were 7.23 ± 0.765 and 7.51 ± 0.55 in arm A and arm B, respectively. Pain scores reduced significantly in both the arms after 1 month (4.39 ± 1.82 in arm A; 5.25 ± 2.39 in arm B). Time of initiation of pain response was earlier in arm A (P = 0.0281), statistically significant. Mild G-I toxicity was noted in both the arms but differences in two arms were not statistically significant (P = 0.49), no interruption of treatment was required because of side effects.

Conclusions:

Different fractionation of radiation has same response and toxicity in treatment of vertebral bone metastasis. Single fraction RT may be safely used to treat these cases as this is more cost effective and less time consuming. Studies may be conducted to find out particular subgroup of patients to be benefitted more by either fractionation schedule; however, our study cannot comment on that issue.     

Attitudes Toward Euthanasia Among Doctors in a Tertiary Care Hospital in South India: A Cross Sectional study

Context:

Advances in expertise and equipment have enabled the medical profession to exercise more control over the processes of life and death, creating a number of moral and ethical dilemmas. People may live for extended periods with chronic painful or debilitating conditions that may be incurable.

Aim:

This study attempts to study the attitudes of doctors toward euthanasia and the possible factors responsible for these attitudes.

Settings and Design:

A cross-sectional survey of 213 doctors working at a tertiary care hospital was conducted to determine their attitudes toward euthanasia.

Materials and Methods:

A self-administered questionnaire was used to assess attitudes and personal perceptions about euthanasia.

Statistical Analysis Used:

The Chi square test was used to assess factors influencing attitudes toward euthanasia.

Results:

A majority of the respondents (69.3%) supported the concept of euthanasia. Relief from unbearable pain and suffering was the most commonly (80.3%) cited reason for being willing to consider the option of euthanasia. Majority of those who were against euthanasia (66.2%) felt that the freedom to perform euthanasia could easily be misused. Disapproval of euthanasia was associated with religious affiliation (P<0.001) and speciality (P<0.001).

Conclusions:

A majority of the doctors in this study supported euthanasia for the relief of unbearable pain and suffering. Religion and speciality appear to be significant in determining attitudes toward euthanasia.