The contribution of family medicine to the health system in Somaliland.

Somaliland's first specialty training programme for physicians was a master's degree in Family Medicine that began at Amoud University in 2012. A survey of the 24 Family Medicine graduates working in Somaliland demonstrates their clinical and leadership impact on the health system and their contribution to higher education. The specialists directly contribute to the health and education priorities of the government of Somaliland.

Optimal method for metabolic tumour volume assessment of cervical cancers with inter-observer agreement on [18F]-fluoro-deoxy-glucose positron emission tomography with computed tomography.

PURPOSE: Cervical cancer metabolic tumour volume (MTV) derived from [18F]-FDG PET/CT has a role in prognostication and therapy planning. There is no standard method of outlining MTV on [18F]-FDG PET/CT. The aim of this study was to assess the optimal method to outline primary cervical tumours on [18F]-FDG PET/CT using MRI-derived tumour volumes as the reference standard. METHODS: 81 consecutive cervical cancer patients with pre-treatment staging MRI and [18F]-FDG PET/CT imaging were included. MRI volumes were compared with different PET segmentation methods. Method 1 measured MTVs at different SUVmax thresholds ranging from 20 to 60% (MTV20-MTV60) with bladder masking and manual adjustment when required. Method 2 created an isocontour around the tumour prior to different SUVmax thresholds being applied. Method 3 used an automated gradient method. Inter-observer agreement of MTV, following manual adjustment when required, was recorded. RESULTS: For method 1, the MTV25 and MTV30 were closest to the MRI volumes for both readers (mean percentage change from MRI volume of 2.9% and 13.4% for MTV25 and - 13.1% and - 2.0% for MTV30 for readers 1 and 2). 70% of lesions required manual adjustment at MTV25 compared with 45% at MTV30. There was excellent inter-observer agreement between MTV30 to MTV60 (ICC ranged from 0.898-0.976 with narrow 95% confidence intervals (CIs)) and moderate agreement at lower thresholds (ICC estimates of 0.534 and 0.617, respectively for the MTV20 and MTV25 with wide 95% CIs). Bladder masking was performed in 86% of cases overall. For method 2, excellent correlation was demonstrated at MTV25 and MTV30 (mean % change from MRI volume of -3.9% and - 8.6% for MTV25 and - 16.9% and 19% for MTV30 for readers 1 and 2, respectively). This method also demonstrated excellent ICC across all thresholds with no manual adjustment. Method 3 demonstrated excellent ICC of 0.96 (95% CI 0.94-0.97) but had a mean percentage difference from the MRI volume of - 19.1 and - 18.2% for readers 1 and 2, respectively. 21% required manual adjustment for both readers. CONCLUSION: MTV30 provides the optimal correlation with MRI volume taking into consideration the excellent inter-reader agreement and less requirement for manual adjustment.

Immunotherapy-related adverse effects on 18F-FDG PET/CT imaging.

18F-Fluorodeoxyglucose positron emission tomography/CT imaging plays a key role in oncological imaging including in staging, radiotherapy planning, treatment response and recurrence assessment. Immunotherapies represent a major advance in cancer therapy for a number of tumours with resulting survival benefit. However, a wide range of immune related adverse events (irAEs), some of which can be apparent on imaging, have been reported. These involve many organ systems but particularly endocrine, cutaneous and gastrointestinal systems. Early detection of irAEs is essential to aid diagnosis and management of patients and to reduce associated morbidity. In addition, it is important to not mistake treatment related effects for disease.This pictorial review aims to identify common irAEs and changes seen on 18F-fluorodeoxyglucose positron emission tomography/CT.

Interobserver agreement of the visual Herder scale for the assessment of solitary pulmonary nodules on 18F Fluorodeoxyglucose PET/computed tomography.

BACKGROUND: British Thoracic Society guidelines recommend 18F Fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) for solitary pulmonary nodule (SPN) follow-up in high-risk individuals or if the CT Brock score is >10%. Nodule tracer uptake is assessed visually in comparison to the surrounding lung tissue and mediastinal blood pool (Herder score). This score is used to calculate the risk of malignancy and guide patient management. Despite its widespread use, there have been no studies to date looking at interobserver agreement using the Herder scale. PATIENTS AND METHODS: F-FDG PET/CT studies of 100 consecutive patients imaged for the evaluation of SPN were retrospectively analysed. Anonymized images were reviewed independently by three Consultant Nuclear Medicine Radiologists and the Herder score was documented, along with a confidence score graded 1-3, where 1 indicated 'not at all confident' and 3 indicated 'very confident'. Interobserver agreement was assessed using interclass correlation coefficient modelling. RESULTS: There was complete reviewer agreement in 81% cases, and interclass correlation with Cronbach's alpha was excellent at 0.973 (95% confidence interval, 0.962-0.981). The agreement between pairs of reviewers was good and confidence scores using the Herder scale were high, with reviewers giving a confidence score of 3 in an average of 78% of cases. CONCLUSION: Our study suggests excellent interobserver agreement for use of the Herder scale in evaluating SPNs. Reviewer confidence scores were high reflecting high confidence in the use of the Herder scale for evaluating SPN.

FDG-PET Imaging in Cervical Cancer.

FDG-PET/CT has an established role in the initial staging of locally advanced cervical cancers, particularly in evaluation of nodal disease and distant metastases. It is common practice to perform FDG-PET/CT 3 months postcompletion of chemoradiotherapy as it can predict outcome and be used to tailor management, including adjuvant therapy and follow-up. It is also routinely used prior to pelvic exenterative surgery to ensure there is no disease outside the pelvis. There is growing evidence that FDG-PET-derived parameters are prognostic and could potentially be used to tailor therapy. This review outlines the use of FDG-PET/CT imaging in cervical cancer.

Discovery of pre-therapy 2-deoxy-2-18F-fluoro-D-glucose positron emission tomography-based radiomics classifiers of survival outcome in non-small-cell lung cancer patients.

PURPOSE: The aim of this multi-center study was to discover and validate radiomics classifiers as image-derived biomarkers for risk stratification of non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Pre-therapy PET scans from a total of 358 Stage I-III NSCLC patients scheduled for radiotherapy/chemo-radiotherapy acquired between October 2008 and December 2013 were included in this seven-institution study. A semi-automatic threshold method was used to segment the primary tumors. Radiomics predictive classifiers were derived from a training set of 133 scans using TexLAB v2. Least absolute shrinkage and selection operator (LASSO) regression analysis was used for data dimension reduction and radiomics feature vector (FV) discovery. Multivariable analysis was performed to establish the relationship between FV, stage and overall survival (OS). Performance of the optimal FV was tested in an independent validation set of 204 patients, and a further independent set of 21 (TESTI) patients. RESULTS: Of 358 patients, 249 died within the follow-up period [median 22 (range 0-85) months]. From each primary tumor, 665 three-dimensional radiomics features from each of seven gray levels were extracted. The most predictive feature vector discovered (FVX) was independent of known prognostic factors, such as stage and tumor volume, and of interest to multi-center studies, invariant to the type of PET/CT manufacturer. Using the median cut-off, FVX predicted a 14-month survival difference in the validation cohort (N = 204, p = 0.00465; HR = 1.61, 95% CI 1.16-2.24). In the TESTI cohort, a smaller cohort that presented with unusually poor survival of stage I cancers, FVX correctly indicated a lack of survival difference (N = 21, p = 0.501). In contrast to the radiomics classifier, clinically routine PET variables including SUVmax, SUVmean and SUVpeak lacked any prognostic information. CONCLUSION: PET-based radiomics classifiers derived from routine pre-treatment imaging possess intrinsic prognostic information for risk stratification of NSCLC patients to radiotherapy/chemo-radiotherapy.

Radiopharmaceuticals as probes to characterize tumour tissue.

Tumour cells exhibit several properties that allow them to grow and divide. A number of these properties are detectable by nuclear imaging methods. We discuss crucial tumour properties that can be described by current radioprobe technologies, further discuss areas of emerging radioprobe development, and finally articulate need areas that our field should aspire to develop. The review focuses largely on positron emission tomography and draws upon the seminal 'Hallmarks of Cancer' review article by Hanahan and Weinberg in 2011 placing into context the present and future roles of radiotracer imaging in characterizing tumours.

Is there a correlation between degree of viremia and liver histology in chronic hepatitis C?

OBJECTIVE: To determine the correlation between degree of histological liver damage and serum HCV RNA level in patients of chronic hepatitis C, in order to evaluate the usefulness of HCV RNA estimation as an alternate to liver biopsy. METHODS: This non-interventional descriptive study, was carried out at the department of Pathology, Army Medical College, Rawalpindi, Pakistan between April and September 2002. Core needle liver biopsies of fifty five patients of chronic hepatitis C were evaluated according to Knodell's histological activity index system. The patients were categorized into four subgroups depending upon the grade and stage of disease according to Desmet's classification, and into three groups according to degree of viremia. RESULTS: Five patients had mild viremia, 43 moderate and 7 had severe viremia. Seven patients had minimal disease, 9 mild, 22 moderate and 17 had severe chronic hepatitis. Eight patients had no fibrosis, 20 had fibrous portal expansion, 19 bridging fibrosis, and 8 patients had cirrhosis. No significant correlation was found between serum HCV RNA levels and grade or stage of the disease, with correlation coefficients of rs = -.054 and rs = .034 respectively. Moreover, no individual component of the HAI correlated with serum HCV RNA levels. CONCLUSION: Serum HCV RNA level does not determine the degree of hepatic injury precisely and liver biopsy is necessary to accurately evaluate the extent of liver damage.

Morphological study of liver biopsy in Thalassaemia major.

OBJECTIVE: To see the morphological changes in liver in transfusion dependent Thalassaemia major children undergoing bone marrow transplantation. METHODS: This retrospective cross-sectional survey was conducted at Pathology department of Army Medical College and Paediatric department of Military Hospital, Rawalpindi from Jul 2000 to Aug 2003. Liver biopsies were done in 40 thalassaemic major children and histological changes including Knodell Histological activity index (HAI); grade, stage and score along with degree of haemosiderosis were noted. Serum ALT levels, ferritin assays and screening for HBsAg and Anti- HCV antibody were also carried out in these cases. RESULTS: Forty children 1.5-10.5 years of age (mean 6.1 years) with a male to female ratio of 1.2:1 were included in the study. According to Knodell HAI scoring, 24 (60%) cases had Knodell HAI score between 13/22 to 18/22 and 18 patients (45%) in grade 9-12/18. Six children had fully developed cirrhotic changes whereas 22 and 12 patients showed stage 3 and 1 respectively. Twenty eight (70%) patients had grade 3-4 haemosiderosis. HBsAg was positive in 6 and anti- HCV antibody in 14 patients. Serum ferritin and ALT levels were markedly raised in most of the patients. CONCLUSION: Seventy percent patients had moderate to severe haemosiderosis and high Knodell HAI score was found in children with severe haemosiderosis, raised ALT and Ferritin levels and with positive serology for HBsAg and anti- HCV antibody. Liver biopsy is useful in thalassaemic children to assess the stage of liver disease and selection of suitable cases for bone marrow transplantation (BMT).

Efficacy of bronchial wash cytology and its correlation with biopsy in lung tumours.

OBJECTIVE: To evaluate bronchial wash cytology with histology in our set up. METHODS: Seventy three specimens were obtained by flexible fiberoptic bronchoscope at pulmonology department of Military Hospital Rawalpindi. All the preserved samples were processed under standard conditions. The slides were stained with Papanicolaou and Haematoxylin and Eosin stains. RESULTS: A total of 73 patients were studied. The age range was 21 to 80 years. Male to female ratio was 8:1. Complete cytological and biopsy consensus was found in 55 (77.4%) cases. Cytology revealed 24 cases as malignant and nine as atypical/suspicious. Benign and inadequate were 29 and 2 respectively. Histopathology of these cases confirmed 24 (32.9%) as malignant and 29 (39.8%) as benign. True positive alongwith suspicious/atypical were 33 and true negative cases were 29. False positive was one case only whereas false negative cases were eight. The bronchial wash cytology showed sensitivity (80.5%), specificity (96.6%) and accuracy (87.3%). Positive predictive value and negative predictive value were 97% and 78.4% respectively. The commonest types of tumours were squamous cell carcinoma and small cell carcinoma. CONCLUSION: It is concluded that bronchial wash cytology is a valuable tool and yields almost same information as biopsy. It is useful in patients with evidence of obstruction or risk of haemorrhage.

An autopsy study of hypertrophic cardiomyopathy.

OBJECTIVE: To see the pathological features of this disease in our set up and to emphasise the importance of morphological examination in making the diagnosis of hypertrophic cardiomyopathy (HCM) especially in cases of sudden cardiac death. METHODS: A retrospective, descriptive study of 15 autopsies of this particular disease was carried out at the Armed Forces Institute of Pathology (AFI) Rawalpindi during the period from 1990 to 1995. The hearts along with blood vessels were fixed in 10% formalin and were dissected according to the modified Virchow's method for eliciting the gross appearance of cardiac chambers and valves. Representative sections were taken for histological examination. RESULTS: All the cases were young adult males. The age range was from 17-34 years (mean, 26-6 years). Ten cases died suddenly and five cases had an evidence of moderate to severe exertion preceding their death. Symmetrical as well as asymmetrical hypertrophy was noted in this study. The thickness of inter ventricular septum (mean 20 mm) and left ventricular wall (mean 22.5 mm) was increased. All the specimens revealed disarray of hypertrophic myocardial fibres and patchy interstitial fibroses. CONCLUSION: Sudden death is usually the first manifestation of disease. The hearts showed asymmetric as well as concentric hypertrophy. Myofibre hypertrophy and disarray was an important pathological findings in our cases. While carrying out post-mortem examination of a case of sudden cardiac death one should also keep in mind the possibility of this disease.

A comparative investigation of dental and medical student's motivation towards career choice.

OBJECTIVE: A number of recent studies have investigated the motivations underlying the career choice of dental and medical students, suggesting that they may be very different. However, as yet, no studies have been conducted which provide a direct comparison of dental and medical students studying in the same place. Accordingly, the aim of this investigation was to conduct a survey which directly compared the motivation of a selection of dental and medical students at Manchester University. STUDY DESIGN: A questionnaire was developed for this study on the basis of previous surveys investigating the motivations of dental and medical students towards career choice. Six dimensions were covered in the questionnaire including: status and security; the nature of the occupation; career opportunities; patient care and working with people; use of personal skills; and interest in science. In addition, students were asked about the role of work experience in either dentistry or medicine. The questionnaire was distributed to 80 medical students and 80 dental students chosen from a random selection of lecture slots. RESULTS: The results were analysed using the Mann-Whitney U test. Statistically significant differences were revealed in all six areas of career choice motivation. For instance, dental students were significantly more likely to be motivated by factors relating to status and security and the nature of their occupation (eg regular working hours, self employment and independence). By contrast, medical students were significantly more likely to be motivated by factors relating to career opportunities, patient care and working with people, use of personal skills, and interest in science. Work experience was a strong motivating factor in the case of both dental and medical students (though especially for dental students). CONCLUSIONS: In comparison with dental students, medical students manifested a more professional attitude in which altruism and intellectual challenge constituted central motivating factors. By contrast, dental students demonstrated more of a commitment to personal and financial gain. The paper queries how useful such attitudes are to a re-oriented dental profession whose aspiration is to provide more accountable and community oriented services.

Clonal hematopoiesis as defined by polymorphic X-linked loci occurs infrequently in aplastic anemia.

We evaluated the methylation status of the X-linked gene phosphoglycerate kinase (PGK1) and the DXS 255 locus detected by probe M27 beta to study clonality in acquired aplastic anemia (AA). A total of 30 females were suitable for clonal analysis of peripheral blood polymorphonuclear cells (PMN) and mononuclear cells using a polymerase chain reaction-based procedure in 24 patients and Southern blotting in 9. Overall, 10 of 30 patients exhibited an imbalanced X-inactivation pattern. However, in 4 patients, analysis of constitutional DNA suggested a skewed methylation pattern and 2 further cases had to be excluded because of the lack of an appropriate control. A truly clonal pattern was thus established in 4 of 30 (13%) patients. In 7 patients who later developed clonal disorders of hematopoiesis, X-inactivation analysis did not predict this event in any case. In patients with a paroxysmal nocturnal hemoglobinuria phenotype, there was no correlation between the proportion of phosphatidylinositol glycan anchored protein (PIG-AP)-deficient blood cells and the corresponding X-inactivation pattern. X-inactivation analysis detected clonal hematopoiesis in only 3 of 10 patients with a deficiency in PIG-AP in the cell population under study, but sorting of nucleated cells on the basis of PIG-AP expression showed the clonal nature of PIG-AP-deficient cells. We conclude that the majority of patients with AA show polyclonal hematopoiesis using X-linked clonal analysis, but that minor clonal populations, such as PIG-AP-deficient cells, may not be detected unless sorted cell populations are separately analyzed.

Hepatitis C as a cause of chronic liver disease in northern Pakistan.

The antibodies to hepatitis C virus (HCV) were tested in 45 histologically confirmed cases of chronic liver disease. Twelve cases had chronic hepatitis, 24 cirrhosis and 9 hepatocellular carcinoma. Anti-HCV was detected in 6 patients. Two (16.67%) were suffering from chronic hepatitis, 3 (12.5%) had cirrhosis and one (11.11%) hepatocellular carcinoma. None of the anti-HCV positive cases had past history of blood transfusion. The patients of chronic liver disease in this study had a much higher prevalence of HBV infection which indicates that in northern Pakistan hepatitis C virus infection is not a common cause of chronic liver disease whereas HBV infection plays an aetiological role in a much larger number of these cases.

Fatal amoebic liver abscess: an autopsy study.

An autopsy study of 20 cases is presented. The mean age was 32 years (range: 14-45). Four cases (20%) presented with jaundice. Another four (20%) had continuous fever with abdominal pain. Six had loose motions with blood and mucus in the stools. The mean duration of illness was 7.2 days. All cases were thin and emaciated. Liver was grossly enlarged (mean weight: 2680 g). The abscess was single in all cases except one. The right lobe was involved in 15 cases, the left in four and both in one. The average size of abscess was 13 cm. The abscess had ruptured in the abdomen in 3 patients, for which laparotomy was performed. Pulmonary involvement was seen in 3 cases. Colon showed ulceration in half the patients. In 2 cases perforation was also present. No cerebral involvement was present. A number of interesting features emerged from this study. Although amoebic liver abscess is a common disease, its diagnosis can be missed due to unusual presentation. In the present study, diagnosis of viral hepatitis, carcinoma lung, bacillary dysentery and enteric fever with perforation were made, which probably contributed materially to fatal outcome.