Repeat Smear Research Articles

"Modernizing Cervical Cytology Screening with Liquid-Based Methods at Community-Level Hospitals: A Much-Needed Breakthrough for India".

Cervical cancer still ranks highest causing cancer-related morbidity and mortality in women in India. It is prudent to emphasise and implement cervical cancer screening strategies in the population efficiently and with regular intervals. Conventionally, PAP smear cytology is obtained by wooden spatula-Ayre's spatula. To improve sensitivity and specificity of the procedure and detection rate, better techniques of cells retrieval are available mainly liquid-based cytology (LBC), with help of cyto-brush. Literature has consistently proven efficiency of the technique and also reduced the proportion of inadequate sampling. We conduct this study to compare both the techniques and efficiency in a community hospital from data over 6years,to asses its role and benefits among Indian women. To compare conventional PAP smear and liquid-based cytology techniques analysing detection rates of positive lesions (CIN and also includes ASCUS and malignant), incidence of inadequate sampling, efficiency and cost-effectiveness. This is retrospective study at tertiary care obstetric hospital affiliated to government-run medical college in a metropolitan city of Mumbai. Data are retrieved from the Pathology Department, Medical Records Department, laboratory books and OPD registers. Pap's smear sampling was done mainly from OPD with all indications including routine tests as a part of gynaecological evaluation and screening, as well as for suspicious lesions on inspection. Group A consists women who had conventional PAP smear test for 3years (Dec 2015-Nov 2018) and Group B had women who benefited by LBC method for 3years (Dec 2018-Nov 2021). COVID-19 pandemic majorly affected the routine gynaecological OPD practice during 2021 as hospital was COVID facility hospital. Demographic parameters and presentations were comparable and similar. LBC methods have higher detection rate for positive reports, including ASCUS. But results were comparable in both groups and not statistically different. Importantly, incidences of inadequate sampling are reduced significantly with the LBC method. Unsatisfactory smears war high in Group A (7.752%) compared to Group B (3.712%) p-value 0.005, stating the increased rate of requirement of sending repeat smears, which involves higher engagement of time, resources and active participation from healthcare personnel. Good detection rates and significantly low rates of unsatisfactory smears make LBC rational and cost-effective. These are the times to switch to liquid-based cytology techniques, especially at the community level hospitals; in order to detect more women with cervical premalignant as well as malignant neoplastic lesions and to save lives. This can be made possible by emphasising the policy makers to incorporate these services through quality resources.

The gray zone squamous lesions: ASC-US / ASC-H.

The unequivocal and easily recognizable entities of LSIL and HSIL pose no diagnostic problems for a trained eye. However, when the defining morphologic features are either qualitatively or quantitatively insufficient, it is then that the borderline category of “Atypical Squamous cells” (ASC) may have to be used. Scant and suboptimal preparations (mainly in conventional smears) are the common causes that hinder confident decision-making. The binary classification of the ASC category has been retained in The Bethesda System 2014. It includes ASC of undetermined significance (ASC-US) when the atypia is seen in mature cells and ASC-cannot rule out high-grade lesion (ASC-H) when borderline changes are seen in less mature, smaller metaplastic cells or smaller basaloid cells. There are many criticisms of the ASC category. The major one is its subjective and inconsistent applications and the low interobserver and intraobserver reproducibility. However, studies have shown that if we eliminate ASC-US, the LSIL rate will increase. If ASC-H is eliminated, the chances of detecting true lesions are reduced. Hence, there are strong reasons to retain the ASC category. The usual problems leading to the categorization of such cells as atypical are hyperchromasia beyond that acceptable as reactive change; abnormal chromatin pattern that is not overt dyskaryosis; minor variations in nuclear shape; and membrane outlines. Qualifying the atypical cells precisely in one of the categories has bearing on the clinical management and follow-up of the patient. Surveillance of women under the ASC-US category is either by repeat smear at 6 months and 1 year or by reflex human papillomaviruses DNA testing. Women with a Pap smear interpretation of ASC-H are directed to undergo immediate colposcopy. This article describes in detail the morphologic features of the ASC category, doubts about the correct interpretation of the chromatin pattern of the cells in question, and the differential diagnosis between normal, reactive, or inflammatory conditions, and LSIL/HSIL.

A comparative study of Pap smear cytology and histopathology of cervix biopsy

Background: Carcinoma cervix is one of the leading causes of death of the female population in developing countries. By virtue of its accessibility, cancer of the cervix can be readily diagnosed even in its preinvasive stage. If treated in the earlier stages the patient can often be cured of the disease. Carcinoma of the cervix is the fourth most frequent cancer in women worldwide and the leading cause of death from cancer in several developing countries including India. The use of cervical smear (Papanicolaou/Pap) as a screening tool has significantly reduced the incidence of cervical cancer. The present study has been carried out to evaluate the pattern of cervical cytology and its correlation with histopathological findings. Materials and Methods: The present study was carried out in the department of pathology in a tertiary care hospital over a period of two years. In the two year study period, 2568 pap smears were received. Among these, 194 abnormal smears were identified and they were categorized under The Bethesda System 2014. The histopathological examination of biopsy cervix results of the smears was compared and analyzed. Results: Out of 194 smears studied, reactive changes was 69 (35.57%). Atypical squamous cells of undetermined significance were 47 (24.23%). Low grade squamous intraepithelial lesions were 3 (1.55%) and high grade squamous intraepithelial lesions were 29 (14.95%). Atypical endocervical cells were 2 (1.03%). Atypical endocervical cells favor neoplastic was 4 (2.06%) and endocervical adenocarcinoma in situ was 1 (0.5%). Squamous cell carcinoma was 39 (20.10%). The histopathological examination of biopsy cervix results of the above smears was compared and analyzed. In the histopathological examination results, non-neoplastic lesions were 90 (46.4%), premalignant lesions were 31(16%) and malignant lesions were 73 (37.6%). Conclusion: This correlative study of Pap smear and histopathological examination of the cervix revealed the overall sensitivity of 97%, the specificity of 74% and an accuracy of 87%. The false-negative and false-positive cases in this study can be minimized by proper sampling, screening, interpretation and further follow up study of repeat smears.

Complete Cessation of Recurrent Cervical Intraepithelial Neoplasia (CIN) by the Paleolithic Ketogenic Diet: A Case Report

Background: Ketogenic diets have repeatedly been suggested for the treatment of cancer. To date, only a few case studies reporting long term benefits associated with such diets have been published. Case report: Here we present a case where recurrent cervical intraepithelial neoplasia (CIN), a premalignant condition of cervical cancer, was successfully treated with the paleolithic ketogenic diet. The patient had a history of high grade CIN in 2011, which was successfully treated with cervical conization and fractional curettage. In October 2015 she was found to have a recurrence of high grade CIN (HSIL: High Grade Squamous Intraepithelial Lesion). The patient was then commenced on the paleolithic ketogenic diet and her repeat Pap (Papanicolaou) smear three months later was found to have reverted to normal. The patient has remained on the paleolithic ketogenic diet for 26 months, her repeat smears have stayed normal, and she is free of symptoms and side effects. Conclusion: We conclude that the diet was effective and safe in this patient. As a major benefit the patient was able to avoid a hysterectomy, which is the standard treatment for recurrent high-grade CIN. We believe that the paleolithic ketogenic diet combines benefits of both paleolithic and classical ketogenic diets, while excluding their disadvantages.

Cervical Pap Smear Cytology at Kamuzu Central Hospital in Malawi: A Quality Assurance Study

Abstract 53 Background: Cervical cancer remains the most common cancer in women of the developing world, largely as a result of a lack of screening. The gold standard screening test for cervical cancer, the Pap smear, has been effective in reducing cervical cancer incidence and mortality by identifying precancerous and cancerous lesions; however, little is known about quality assurance practices for gynecologic cytopathology in resource-limited settings. The goal of this study was to document baseline clinical and laboratory characteristics in the hope of improving the efficacy of cervical cancer screening and informing future quality improvement initiatives. Methods: A retrospective study of cervical cytology at Kamuzu Central Hospital, Malawi, from January 1, 2013, to April 30, 2016, was conducted. Results: Of 2,809 Pap smears processed, 2,396 (85.3%) samples were diagnostic, with 92.3% of nondiagnostic smears (381 of 413) deemed unsatisfactory because of improper collection techniques. The 18-month patient follow-up rate for unsatisfactory Pap smear was found to be 23.0% (n = 95), with repeat smears reflecting a similar satisfactory rate (n = 82; 86%). Of diagnostic Pap smears, 6.1% (n = 147) were premalignant, whereas 2.0% (n = 48) were malignant. Cytology-histology correlation was also investigated one the basis of the corresponding samples collected concurrently. Of 70 pairs, 55 pairs (78.6%) were concordant, whereas six (8.6%) and nine (12.9%) were majorly and minorly discordant, respectively. The sensitivity and specificity of the Pap smear as a screening test were 83.8% and 81.8%, respectively. Conclusion: The Pap smear is a sensitive and specific screening method for cervical cancer in our setting. We hope that documentation of baseline quality and services of cervical cytology will inform future quality assurance programs and assist other laboratories in the development of similar programs in resource-limited settings. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST Daniel Liauw No relationship to disclose Bal Mukunda Dhungel No relationship to disclose Tamiwe Tomoka No relationship to disclose Robert Krysiak No relationship to disclose Coxcilly Kampani No relationship to disclose Fred Chimzimu No relationship to disclose Yuri Fedoriw Honoraria: Alexion Pharmaceuticals Consulting or Advisory Role: Alexion Pharmaceuticals

The prevalence and course of preinvasive cervical lesions during pregnancy in a Northern Nigerian Teaching Hospital.

Background:In spite of knowledge of the causes and prevention of cervical cancer, screening programs for cervical cancer have not yet been fully implemented in most developing countries including Nigeria. Documented data on the prevalence of preinvasive cervical lesion in pregnancy are scarce in our environment.Objectives:To determine the prevalence, risk factors, and course of preinvasive cervical lesion in pregnant women attending an antenatal clinic in Ahmadu Bello University Teaching Hospital (ABUTH) Zaria, Northern NigeriaStudy Design:This was a cross-sectional longitudinal study.Setting:The study was conducted in an antenatal clinic of ABUTH Zaria.Materials and Methods:A prospective cross-sectional longitudinal analysis was carried out at an Antenatal Clinic of ABUTH Zaria, Nigeria. A total of 250 consecutive pregnant women who fulfilled the inclusion criteria and have given their consent were recruited into the study at the time of their first prenatal (booking clinic) visit for antenatal care. Data from the pregnant women were obtained using a pro forma to evaluate sociodemographic characteristics and risk factors for preinvasive disease. Conventional Papanicolaou smear was taken using the standard procedure. The cytopathologic findings of initial and postpartum Pap smear were documented in the pro forma. Prevalence, persistence, progression, and regression rates of preinvasive diseases were determined.Results:Out of the 250 pregnant women who had cervical cytology by Pap smear during the study, 15 had preinvasive cervical lesion, giving a prevalence rate of 6%; 13 (87%) were low-grade squamous intraepithelial lesion (LGSIL) while 2 (13%) were high-grade squamous intraepithelial lesion (HGSIL). Negative smears were seen in 158 women (63.2%). Inflammatory and other conditions of the cervix which are technically negative smears made up the remaining 30.8%. At postpartum follow-up of the 13 women with LGSIL, 2 (15.4%) became negative while persistence of the disease was observed in 9 (69.2%) of the cases. Two women with LGSIL were lost to follow-up. Of the two women with HGSIL, persistence of the disease was seen in one woman (50%) and regression of the disease was seen in the other woman. Risk factors that were found to be associated with preinvasive cervical lesion were age at coitarche <16 years, number of sexual partners since coitarche, and previous history of sexually transmitted infection and human immunodeficiency virus. Parity, smoking, and use of contraception were found not to be significant risk factors.Conclusion:Preinvasive lesion of the cervix is relatively common among antenatal clients in our center. Antenatal clients with HGSIL should have a repeat smear at the end of the puerperium before treatment. Routine Pap smear should be offered to all antenatal clients in our setting.

Cost analysis of different diagnostic algorithms for pulmonary tuberculosis varying in placement of Xpert MTB/RIF

BackgroundWe undertook cost analysis for diagnosis of pulmonary tuberculosis (PTB) using present algorithm under Revised National Tuberculosis Control programme and using Xpert MTB/RIF (Xpert) as frontline test or in conjunction with smear microscopy and/or chest radiography. MethodsCosts were estimated for different strategies: (A) present algorithm involving sputum smear examination followed by antibiotic trial in smear negative patients, repeat smear examination (RE) if symptoms continue and chest radiography if RE negative; (B) direct Xpert; (C) smear microscopy followed by Xpert in smear negative patients; (D) radiography followed by Xpert in those having abnormal pulmonary shadows; and (E) smear examination followed by radiography among smear negative patients and Xpert in presence of abnormal pulmonary shadow. ResultsCost to program was estimated lowest with Strategy A and highest with Strategy B. Compared to the latter, program cost reduces by 7%, 4.5%, and 17.4% by strategies C, D, and E, respectively.Cost to the group of individuals with presumptive PTB and their attendants is significantly higher for Strategy A compared to other four strategies. Among the latter, the patients’ cost was minimum with Strategy B and maximum with Strategy C.Program cost per case diagnosed was lowest by Strategy A and highest by Strategy B. Patient cost per case diagnosed was highest by Strategy A and lowest by Strategy B. Using Xpert, Strategy E had the lowest program as well as overall cost per case diagnosed. ConclusionStrategy E may be chosen for diagnosis of PTB. When resources would no longer be a constraint, direct Xpert would reduce costs incurred by the patients.

Colposcopic Evaluation of Cervix with Persistent Inflammatory Pap Smear

Background and Objectives: The cervical screening algorithm for benign cellular changes on the Pap smear recommends treatment of infection if indicated and a repeat Pap smear should be done in 4-6 months time. If repeat smear suggests continuation of inflammatory changes, the patient is subjected to colposcopic evaluation. During this lag time, a good number of patients in their premalignant stage may be missed or undergo malignant transformation. Recent studies advocate a repeat Pap smear if treatment of infection for 2-4 weeks does not respond and if repeat Pap smear suggests persistence of inflammatory changes, the patient should be evaluated colposcopically to determine the rate of undetected cervical intraepithelial neoplasia/dysplasia in patients with persistent inflammatory Pap smear. The present study was undertaken to that end.&#x0D; Patients &amp; Methods: This cross-sectional study was carried out in the Department of Obstetrics and Gynaecology, Institute of Child &amp; Mother Health (ICMH), Dhaka, over a period of 12 months from July 2013 to June 2014. Patients with two consecutive reports of inflammatory cellular changes without atypia on Pap smears despite anti-inflammatory therapy were the study population. A total of 1456 women underwent Paps test at the above mentioned place during the study period for gynaecological problems. Of them 312(21.4%) were reported as ‘inflammatory cellular changes'. After giving anti-inflammatory treatment most of them were cured leaving 128(8.8%) cases with repeat report of inflammatory cellular changes on Pap smear and hence were included in the study.&#x0D; Results: The mean age of the enrolled women was 32.6 ± 7.2 years. Mean age of the patients at marriage and mean age at first child birth were 14.9 years (range: 12-23 years) and 16.5 years (range: 13-26 years) respectively. Majority (94.5%) of the patients were multipara. Of the 128 women, 66(51.6%) were colposcopically positive for CIN. Of them over two-thirds (68.2%) were graded as CIN-1, 25.8% as CIN-2, and 6% as CIN-3. Histological evaluation of biopsy material taken from these 66 cases revealed 25(37.9%) with abnormal cytology (3-CIN-1, 18-CIN-2 and 4 with invasive carcinoma) which accounts for 19.5% of the persistent Paps smear cases. Comparing age at marriage, age at first childbirth and parity between patients with CIN (including invasive disease) and without CIN revealed that the former group married and experienced child birth relatively earlier than the latter group (p = 0.001 and p &lt; 0.001 respectively). The average parity was also significantly higher in the CIN group.&#x0D; Conclusions: A high proportion of patients with persistent inflammatory Pap smear can harbour CIN and sometimes even early stage of invasive carcinoma. So patients with persistent inflammatory cellular changes on Pap smear if does not respond to treatment, they should be subjected to a repeat smear within 2-4 weeks and if inflammatory changes continue, they should be immediately evaluated by colposcopy.&#x0D; Ibrahim Cardiac Med J 2014; 4(1): 9-15

Extensive size variability of the GGGGCC expansion in C9orf72 in both neuronal and non-neuronal tissues in 18 patients with ALS or FTD.

A GGGGCC-repeat expansion in C9orf72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) among Caucasians. However, little is known about the variability of the GGGGCC expansion in different tissues and whether this correlates with the observed phenotype. Here, we used Southern blotting to estimate the size of hexanucleotide expansions in C9orf72 in neural and non-neural tissues from 18 autopsied ALS and FTD patients with repeat expansion in blood. Digitalization of the Southern blot images allowed comparison of repeat number, smear distribution and expansion band intensity between tissues and between patients. We found marked intra-individual variation of repeat number between tissues, whereas there was less variation within each tissue group. In two patients, the size variation between tissues was extreme, with repeat numbers below 100 in all studied non-neural tissues, whereas expansions in neural tissues were 20-40 times greater and in the same size range observed in neural tissues of the other 16 patients. The expansion pattern in different tissues could not distinguish between diagnostic groups and no correlation was found between expansion size in frontal lobe and occurrence of cognitive impairment. In ALS patients, a less number of repeats in the cerebellum and parietal lobe correlated with earlier age of onset and a larger number of repeats in the parietal lobe correlated with a more rapid progression. In 43 other individuals without repeat expansion in blood, we find that repeat sizes up to 15 are stable, as no size variation between blood, brain and spinal cord was found.

Severe Mycobacterium tuberculosis-related immune reconstitution syndrome in an immunocompetent patient

We present a young immunocompetent male with diagnosed sputum culture-positive tuberculosis on intensive phase with observed daily four-drug antituberculosis therapy. He presented at 1-month of treatment with sequential bilateral pneumothoraces, increase in cavitation and consolidation and respiratory failure. Repeat smears for acid-fast bacilli had downgraded, and cultures were negative. Quantiferon-GOLD (initially negative) was now strongly positive. A diagnosis of possible immune reconstitution syndrome was considered and 0.25 mg/kg/day oral steroids administered. We also discuss an approach to differential diagnosis of a patient worsening on treatment for microbiologically confirmed tuberculosis in this manuscript.

Cost effective analysis of recall methods for cervical cancer screening in Selangor--results from a prospective randomized controlled trial.

Cervical cancer screening in Malaysia is by opportunistic Pap smear which contributes to the low uptake rate. To overcome this, a pilot project called the SIPPS program (translated as information system of Pap smear program) had been introduced whereby women aged 20-65 years old are invited for Pap smear and receive recall to repeat the test. This study aimed at determining which recall method is most cost-effective in getting women to repeat Pap smear. A randomised control trial was conducted where one thousand women were recalled for repeat smear either by registered letter, phone messages, phone call or the usual postal letter. The total cost applied for cost-effectiveness analysis includes the cost of sending letter for first invitation, cost of the recall method and cost of two Pap smears. Cost-effective analysis (CEA) of Pap smear uptake by each recall method was then performed. The uptake of Pap smear by postal letter, registered letters, SMS and phone calls were 18.8%, 20.0%, 21.6% and 34.4%, respectively (p<0.05). The CER for the recall method was lowest by phone call compared to other interventions; RM 69.18 (SD RM 0.14) compared to RM 106.53 (SD RM 0.13), RM 134.02 (SD RM 0.15) and RM 136.38 (SD RM 0.11) for SMS, registered letter and letter, respectively. ICER showed that it is most cost saving if the usual method of recall by postal letter be changed to recall by phone call. The possibility of letter as a recall for repeat Pap smear to reach the women is higher compared to sending SMS or making phone call. However, getting women to do repeat Pap smear is better with phone call which allows direct communication. Despite the high cost of the phone call as a recall method for repeat Pap smear, it is the most cost-effective method compared to others.

Yield and complications of frame-based and frameless stereotactic brain biopsy – The value of intra-operative histological analysis

Objectives. Image-guided brain biopsy is an established method to obtain histopathological diagnosis and guide management for cerebral lesions. The study aimed to establish negative biopsy and symptomatic haemorrhage rates at a single centre, and to assess the influence of factors such as lesion location, final pathology and the use of intra-operative smears. Methods. A retrospective analysis of all frame-based and frameless stereotactic biopsies carried out over 57 months from July 2006 to March 2011. Results. A total of 351 biopsies were undertaken, 256 frame-based (73%) and 95 frameless (27%). Mean age was 57 years (range 18–87). Negative biopsy rate was 5.1%. There was a significantly greater negative biopsy rate in deep brain biopsies (p = 0.011) and in the cerebellum (p < 0.001). Intra-operative smear significantly reduced negative biopsy rates from 11.1% to 3.7% (p = 0.011). If repeat smear was requested, yet not provided, then the negative biopsy rate was 57.1% (p = 0.0085). The overall symptomatic haemorrhage rate was 3.7%. There was a significant increase in haemorrhage rate in deep versus superficial biopsies (p = 0.023) and a significantly greater haemorrhage rate in lymphoma biopsies (p = 0.015). There was no significant increase in haemorrhage rate in high-grade- compared with low-grade tumour biopsies. Mortality rates at 7 and 30 days post-operatively were 0.6% and 1.7%, respectively, with mortality after 7 days unrelated to biopsy. Conclusion. We advocate intra-operative histopathological analysis to decrease negative biopsy rates and advise increased caution when undertaking biopsies of deep lesions or suspected lymphoma cases due to the potentially increased risk of haemorrhage.

English

The following is a case report of a woman who presented to the hospital with severe anemia with features of HELLP syndrome and initial slide for P.vivax negative but on constant observation and monitoring turned out to be a case of severe malaria caused by vivax species of malaria. Primigravida with 35week5day pregnancy was admitted with complaints of severe anemia and history of fever 14 days back. Initially 3 pint blood was transfused i/v/o severe anemia. Investigations revealed Hb-3gm% and platelet count 30, 000, LFT deranged, Hemolysis in peripheral smear, smear negative for malarial parasite. HELLP syndrome was in mind and this required termination but on repeat investigations and smear vivax was positive. Her platelet count kept deteriorating despite transfusions till antimalarial regimen was not started. Once smear positive the fastest antimalarial artesunate regimen with clindamycin was started and after 48 hrs. her counts improved. Overall 14 pints of platelets were transfused and patient delivered uneventfully with mild PPH at platelet count of 30, 000. Severe malaria is usually caused by p falciparum but recently reports of severe malaria caused by vivax is increasing and HELLP syndrome is an important differential diagnosis which needs to be excluded as management is entirely different.

Is the Phone Call the Most Effective Method for Recall in Cervical Cancer Screening? - Results from a Randomised Control Trial

To compare the effectiveness of different methods of recall for repeat Pap smear among women who had normal smears in the previous screening. Prospective randomized controlled study. All community clinics in Klang under the Ministry of Health Malaysia. Women of Klang who attended cervical screening and had a normal Pap smear in the previous year, and were due for a repeat smear were recruited and randomly assigned to four different methods of recall for repeat smear. The recall methods given to the women to remind them for a repeat smear were either by postal letter, registered letter, short message by phone (SMS) or phone call. Number and percentage of women who responded to the recall within 8 weeks after they had received the recall, irrespective whether they had Pap test conducted. Also the numbers of women in each recall method that came for repeat Pap smear. The rates of recall messages reaching the women when using letter, registered letter, SMS and phone calls were 79%, 87%, 66% and 68%, respectively. However, the positive responses to recall by letter, registered letter, phone messages and telephone call were 23.9%, 23.0%, 32.9% and 50.9%, respectively (p<0.05). Furthermore, more women who received recall by phone call had been screened (p<0.05) compared to those who received recall by postal letter (OR=2.38, CI=1.56-3.62). Both the usual way of sending letters and registered letters had higher chances of reaching patients compared to using phone either for sending messages or calling. The response to the recall method and uptake of repeat smear, however, were highest via phone call, indicating the importance of direct communication.

Study Protocol for the Most Effective Recall Method in a Cervical Cancer Screening Program in Klang, Malaysia

Cervical cancer is the second most common cancer among Malaysian women with an ASR of 17.9 and a mortality rate of 5.6 per 100,000 population in 2008 (GLOBOCAN, 2008). The 5 year prevalence was estimated to be 14.5 per 100,000 population. As the second most common cancer affecting productive females, cervical cancer imposes an impact to the socioeconomic aspect of the country. However, the poor uptake of cervical cancer screening is a major problem in detecting early pre-cancerous lesions and thus, delay in initiating treatment for cervical cancer. Realizing the urgency to increase the uptake of PAP smear, besides enhancing the promotion of PAP smear screening for women above 35 years old, the call-recall system for pap smear screening had been piloted in one of the suburban districts which aimed to improve regular participation of women for cervical and breast cancer screening. This is of public health importance as identifying the best feasible option to increase patient's respond to participate in the screening program effectively in our setting will be helpful in implementing an organized regular population based screening program tailored to our setting. The pilot program of cervical cancer screening in Klang was an opportunity to assess different options in recalling patients for a repeat pap smear to increase their participation and adherence to the program. This was a population based randomized control trial. Women aged 20-65 years in the population that matched the inclusion and exclusion criteria were re-called for a repeat smear. There are four different intervention groups; letter, registered letters, short messages services (SMS) and phone calls where 250 subjects were recruited into each group. Samples were generated randomly from the same population in Klang into four different groups. The first group received a recall letter for a repeat smear similar to the one that has been given during the first invitation. The intervention groups were either be given a registered letter, an SMS or a phone call to re-call them. The socio-demographic data of the patients who came for uptake were collected for further analysis. All the groups were followed up after 8 weeks to assess their compliance to the recall. The study will provide recommendations about the most effective methods for recall in a population based pap smear screening program on two outcomes: i) patients response; ii) uptake for repeat pap smear.

Modelling borderline and mild dysplasia associated with HPV 6 and 11 infection

Introduction Low risk HPV types 6/11 are responsible for some low-grade cytological abnormalities. Most economic analyses of HPV vaccination have estimated the additional benefit of HPV 6/11 protection by the quadrivalent vaccine, over the bivalent, based on reduction of genital warts but have not included reduction in repeat smears and colposcopies due to low-grade abnormalities. We investigate the contribution of HPV types 6/11 to abnormal smears and associated costs in England. Methods The risk of borderline or mild dysplasia due to HPV 6/11 infection was estimated from a study of type-specific HPV DNA in cervical screening specimens collected throughout England. A Markov model representing 10 million women with HPV 6/11 or with no HPV infection from 24 to 64 years was developed to estimate the number of abnormal smears, subsequent repeat smears and colposcopies due to HPV 6/11 associated with borderline or mild dysplasia. Fitting was achieved by varying the force of infection, probability of borderline or mild dysplasia if HPV-uninfected or infected with HPV 6/11 and the duration of infection. Results The relative risks of borderline or mild dysplasia when infected with HPV 6/11 compared to not being HPV infected were 6.32 (95% credible interval 1.56–25.6) and 17.5 (1.02–300) respectively. Using best fitting parameters we find the costs incurred are between £170 and £195 per abnormal smear due to infection with HPV 6/11. Conclusions In England, the impact of cytological abnormalities due to HPV 6/11 is relatively small, but not negligible. A vaccine that protects against HPV 6/11 infections could reduce costs associated with borderline and mild dysplasia, and associated colposcopies. These benefits should be considered when formulating immunisation policy, if possible. Smears and colposcopies in those uninfected with HPV far outnumber those in women infected with HPV 6/11.

Microfilariae coexisting with a follicular lesion in thyroid aspirate smears in an uncommon case of a retrosternal thyroid mass, clinically presenting as malignancy

To the Editor, Filarial infection is a public health problem in the tropical regions of South-east Asia, including the Indian subcontinent that includes certain areas of heavy infestation, like Madhya Pradesh, Bihar, Jharkhand, along with others. It is caused by the nematodes Wuchereria bancrofti, Brugia malayi, Brugia tumori and others, transmitted through a mosquito Culex fastigens. Its disease manifestations include lymphoedema and superficial swellings.[1–3] Varied sites of involvement documented on aspirate smears include breast, epididymis, spermatic cord, lungs, etc.[4–6] Over the years, it has been uncommonly identified in the thyroid.[7–13] Herein, we present an uncommon case of a retrosternal thyroid mass that clinically presented as malignancy and on aspiration cytology disclosed a follicular lesion with coexisting microfilariae. A 55-year-old gentleman from Ranchi (Jharkhand, India) was referred to our hospital with complaints of anterior neck swelling since 2 months, associated with dysphagia to solids and alteration of voice for a month. He had been a tobacco chewer for 30 years. He also disclosed history of aspiration a month ago, along with breathlessness. On clinical examination, his general condition was good. On local examination, a soft swelling was noted over his right thyroid and isthmus and a 10×7 cm hard swelling was noted over his left thyroid, extending into the retro sternum that did not move with deglutition. Left vocal cord palsy was noted. There was no stridor. Clinically, he was presumed with a diagnosis of stage IV carcinoma thyroid. He underwent laboratory and radiological investigations, including an outside computed tomography (CT) scan, followed by fine-needle aspiration cytology (FNAC) on three occasions, including twice at our hospital. His hemoglobin was normal i.e. 12 gm/dl (Normal: 13-17 gm/dl). Total leukocyte count was high i.e., 13.7×10e9/L (Normal: 4-10×10e9/L), including absolute neutrophilia. Percentage and absolute eosinophil counts were normal 4.73% and 0.65×10e9/L (Normal: 1-6% and 0.2-1×10e9/L). Basophil percentage was marginally high i.e., 0.33% (Normal: 0-0.2%). His thyroid function tests were within normal limits. There was no access for thyroid scan results. Limited accessible imaging findings included a CT scan report that disclosed a left thyroid lobe lesion, eroding the thyroid cartilage, trachea and thoracic inlet. His chest X-ray was normal. FNAC was performed by multiple passes in the thyroid using a 23-gauge needle. Smears were fixed in alcohol stained with Papanicolaou (Pap), while air-dried smears were stained with Giemsa stain. The initial smears were reported as papillary carcinoma thyroid. Repeat smears were hypercellular, comprising benign appearing follicular cells in focal acinar formations, flat monolayered sheets and focal papillaroid arrangements, lacking anatomical edge. Cells exhibited focal nuclear overlapping, focal grooves and fine chromatin clearing in rare cells. No nuclear elongation, uniform nucleomegaly or intranuclear inclusions were noted within the hypercellular smears. Besides, there were sheets of cystic macrophages and Hurthle cells in a background of thick and thin colloid. Diagnosis of an atypical follicular lesion of undetermined significance was considered. On critical examination, microfilariae of W. bancrofti were identified that displayed presence of sheath and were deficient in somatic nuclei at the posterior end of the body that was curved. A few rhomboid-shaped Charcot Leyden (CL) crystals were noted. There were no inflammatory cells. The previous smears were reviewed and a final diagnosis of microfilarial infestation, along with follicular lesion (of undetermined significance) was offered. [Figure ​[Figure1a1a–e] Figure 1 a) Hypercellular smear showing clusters of follicular cells. Pap stain ×100; b) Follicular cells with surrounding macrophages. Pap stain ×400; c) Cells showing focal nuclear overlapping. Pap stain ×1000; d) Flat monolayered sheet ... Following, the patient succumbed to death within a week. However, post-mortem examination could not be performed.

The value of colposcopy, high risk HPV-DNA and histopathologic examination in the management of abnormal Pap smear results

SUMMARY Objective: Pap smear test is a major screening test for early diagnosis and treatment of cervix cancer. The aim of our study was to assess the value of HPV-DNA, colposcopy and histopathologic examination in the management of patients with abnormal cervical cytology. Materials and methods: This prospective cohort study was conducted in Ankara University Cebeci Hospital gynecology outpatient clinic. The study compromised 86 patients with smear results of ASCUS, AGC, L-SIL and H-SIL. Age, gravity, parity, age at first coitus, smoking status, number of partners, high risk HPV-DNA status and pathologic colposcopy findings were investigated. Results: Mean age of the patients was 35 years and the most common abnormal smear result was ASCUS, with 55 patients (63%). There was no significant difference between the groups regarding demographic characteristics except age at first coitus and pathologic colposcopy findings. Among patients diagnosed as ASCUS 34.5% had been upgraded with histopathologic examination. Among patients diagnosed as L-SIL 73.6% had been down-graded with histopathologic examination. However, after the histopathologic exam of 9 H-SIL patients two (22.2%) were diagnosed as CIN II, two (22.2%) were diagnosed as CIN III and one (11.1%) was diagnosed as cervical cancer. In the groups of ASCUS, L-SIL and H-SIL the presence of high risk HPV-DNA were 11%, 5% and 33%, respectively. Conclusion: If we are sure that the patient will attend the follow-up visits, then for the ones with ASCUS and L-SIL a repeat smear test would be the appropriate. However, in the management of patients with H-SIL colposcopic biopsy would be the best approach.

Effects of Streamlining Cervical Cancer Screening the Dutch Way

To analyze the impact of the 1995 revision of the Dutch cervical screening program guidelines (e.g., the introduction of more stringent criteria for cytologic diagnosis of atypical squamous cells of undetermined significance [ASCUS]) on the negative side effects of screening in Region West.The data for this study were retrieved as two complementary datasets, both of which contained data on the invited screenees, including their cytology and histology follow-up. One dataset additionally included data on other smears. For invited screenees, we analyzed changes in cytoscores and histoscores between 1994, the last year before new screening guidelines were implemented, and 2003, the latest year for which follow-up to screening abnormalities was available in the retrieved data. Additionally, we analyzed changes in the total number of primary and repeat smears made.Between 1994 and 2003, the cytoscore for ASCUS decreased from 19.4% to 1.3% of screenee smears. The total number of smears taken decreased by 30%. The cervical intraepithelial neoplasia 3+ histoscore remained the same (OR = 0.97, p = 0.91).The reduction of equivocal ASCUS diagnoses resulted in a decrease of costly repeat smears, without measurably decreasing the effectiveness of the screening program.

Human infection associated with methicillin-resistant Staphylococcus pseudintermedius ST71

Sir, Staphylococcus pseudintermedius is one of the most common pathogens isolated from skin and post-operative infections in dogs and cats and can also occasionally cause infections in humans. People working or living with animals are more likely to be colonized with S. pseudintermedius in their nasal cavities and human infection acquired from dogs has been recently reported. In recent years, there have been increasing numbers of infections in dogs and cats caused by methicillin-resistant S. pseudintermedius (MRSP) and a predominant MRSP clone is disseminating in dogs and cats throughout Europe. This MRSP clone belongs to the multilocus sequence type (MLST) ST71, spa type t02 and SmaI PFGE group J (ST71-t02-J) and contains the staphylococcal cassette chromosome element SCCmec II–III. It displays resistance to many classes of antibiotics and represents a challenge for therapy. Here, we report, to our knowledge, the first case of a human infection caused by MRSP ST71 emphasizing its zoonotic potential and therapeutic challenge. An adult patient presented to the doctor in 2009 with headache, watery eyes and a small oedema over the right eye. The patient had a history of recurrent rhinosinusitis and three surgical interventions had been performed over the previous 6 years, the last one in 2005. CT illustrated an obliteration of the right sinus frontalis with an expansive mucocele. Yet another surgical intervention was absolutely essential and post-operative treatment for 3 weeks with 500 mg of ciprofloxacin twice per day and 300 mg of clindamycin three times per day was given. Five weeks post-operatively, a purulent infection appeared. After 10 days of treatment with 875 mg of amoxicillin/125 mg of clavulanic acid twice daily and 300 mg of clindamycin three times daily and no improvement, a sample was sent for bacteriological analysis. The laboratory identified a multidrug-resistant Staphylococcus belonging to the Staphylococcus intermedius group (SIG) using the ID 32 STAPH system (bioMerieux, Marcy l’Etoile, France) and disc diffusion susceptibility testing (Oxoid Ltd, Basingstoke, UK). Based on these results, a local treatment with fusidic acid gauze and application of 2% mupirocin ointment four times a day for 8 days followed by a topical glucocorticoid/antibiotic combination therapy (0.5 mg/g fluocinonide, 2.5 mg/g neomycin, 0.25 mg/g gramicidin and 100000 IU/g nystatin) packing for 4 days improved the local condition. Six weeks after the purulent infection, the wound had healed with scarring and no bacterium was detectable in a repeat smear. Local follow-up treatment with steroids and routine check-ups confirmed the absence of residual infection. The multidrug-resistant Staphylococcus isolate was further identified as MRSP ST71-t02-J containing SCCmec II–III using MLST typing, spa typing, PFGE and SCCmec typing methods described previously. MICs of antibiotics were determined in Mueller–Hinton broth using custom Sensititre susceptibility NLV73 plates (Trek Diagnostics System, East Grinstead, UK) except for rifampicin, trimethoprim, kanamycin and fusidic acid, which were tested using home-made microbroth dilution plates. Antibiotic resistance genes were detected using a microarray. Mutations in topoisomerase genes gyrA and grlA were identified by sequencing of PCR products (Table 1). The isolate was susceptible to the antibiotics amikacin, chloramphenicol, fusidic acid, linezolid, nitrofurantoin, the combination quinupristin/dalfopristin, rifampicin and vancomycin (Table 1). The patient owned a male dog that needed home care because of various clinical problems such as diabetes, recurrent warts and abdominal tumour. The dog had consultations in various clinics and underwent several antibiotic treatments (details of substances could not be ascertained). The dog was euthanized before samples could be taken to determine whether it was a carrier of the strain. The patient also owned horses and cats; all of them were in good health without clinical signs. Even if the ultimate source of the MRSP infection could not be identified, the patient was infected with the same MRSP clone (ST71-t02-J with SCCmec II–III) that has been disseminating in dogs over Europe in recent years. A case similar to the one reported here has been described in the USA, where a woman developed sinusitis caused by a methicillinresistant SIG whose origin could be attributed to her pet dog. In that case, vancomycin and linezolid were used for treatment. The increasing number of dogs carrying MRSP constitutes a risk for pet owners to become colonized with MRSP, and MRSP infections in humans may also increase in the near future. It is therefore important to recognize MRSP as a zoonotic pathogen and have antibiotics available for the treatment of MRSP infections in humans. Therefore, antibiotics such as mupirocin, linezolid, quinupristin/dalfopristin, rifampicin and vancomycin that are used for decolonization or as ‘last resort antibiotics’ against methicillin-resistant staphylococci in humans should not be used for treatment in animals.