Articles

The Significance of CD3 Marker in the Diagnosis of Celiac Disease
Saja Hammo, Professor Wahda Mohammad Taib Al-Nuaimy, Mohammed Hayawi (Author)
January 2021 ,Pages 99.0-108.0

Abstract: ABSTRACT Background: Celiac disease is a common, permanent and reversible health problem of small intestine occurring all over the world in genetically predisposed individuals and in combination with other environmental factors. It causes chronic inflammation of small intestine which is of autoimmune origin. The histopathological features of Celiac disease in duodenal biopsy was stated according to the modified Marsh classification. The immunohistochemical application of CD3 marker in duodenal biopsy could facilitate the count and the distribution of intraepithelial lymphocytes along the villi, which is regarded as a key for the correct diagnosis in early stages ( Marsh 1). Objectives: This study was conveyed to correlate the significance of CD3 immunohistochemical expression of intraepithelial lymphocytic population to histopathological changes in Celiac disease, to identify the distribution of CD3 marker along the villi (crescendo or decrescendo) and (diffuse or patchy ) and to delineate the age and sex of Celiac disease in our locality. Materials and methods: The research was both prospective and retrospective case series study, carried out on 100 cases of endoscopically obtained duodenal biopsies. Data obtained from archives of the pathology department, at AL-Jamhory, AL-Khansaa and AL-Salam Teaching Hospitals/ Mosul city, and collected in a period spanning from January 2019 to May 2020. The information included age, sex and duodenal biopsy location. then assessed histologically and immunohistochemically. Results: In a total of 100 duodenal samples, patients age was ranged 1 to 69 years ( mean age of 20.74 years), with a female to male ratio ( 2.2:1). By applying modified Marsh classification: Marsh 0 was detected in 8 % of the cases, Marsh 1 in 30 % , Marsh 2 in 10% , Marsh 3 a in 20%, Marsh 3 b in 17%, Marsh 3 c in 15% and Marsh 4 in 0%. Immunohistochemical expression of CD3 in the sampled cases i.e. CD3 + ≥30 /100 epithelial cells was detected in 79 %. There was a statistically significant difference between CD3+ and modified Marsh classification by Hematoxylin & Eosin (P Value<0.001) for detection of intraepithelial lymphocytosis. Conclusion: There is a significant relationship between the count of CD3+ T-lymphocytes per 100 epithelial cells and the histopathological changes in the duodenal biopsy according to modified Marsh classification. the immunohistochemical expression of CD3 in intraepithelial T-lymphocyte could lead to a definite assessment in 13 % of the sampled cases with Marsh type 1. All the positive cases are of crescendo pattern of distribution of CD3+ T-lymphocytes as the distribution is more important than the actual count and they distributed diffusely except that associated with Helicobacter pylori infection observed with patchy distribution. The IHC expression of CD3+ marker provides a hint about the distribution of CD3+ marker within the lymphocyte whether global surface or clonal surface and intracytoplasmic to diagnose Refractory Celiac disease. Females were more affected than males and there is a significant relationship between the gender and the histopathological changes. It can be diagnosed at any age and there is no significant relationship between the age distribution and the histopathological changes.

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Diagnostic Yield of PAX5 in Lymphoma
Hiba Rafea, Abdul Kareem Al-Tae, Nazar Jawhar (Author)
January 2021 ,Pages 109.0-118.0

Abstract: Background: Lymphoma is a heterogeneous group of neoplasm affecting any stage of lymphocyte development. Nowadays, WHO (2017) adapted their classification depending on their morphological, immunohistochemical appearance, and their clinical and molecular characteristics. Objective: To determine the expression of PAX5 in Hodgkin and Non Hodgkin lymphoma and their association with clinical parameters (age &site). Patients & Methods: During a period of 1 year starting from June 2019 to June 2020, 60 lymphoma patients" were included in this"prospective-retrospective"case series study from"medical records and histopathological results in governmental and private labs. Immunohistochemistry examination using PAX5 was performed, and data of the positive PAX5 expression were analyzed. Results: A total of 60 patients were recruited in this study with the majority (58%) were Non Hodgkin lymphoma, dominated by diffuse large B- cell lymphoma subtype (42.8%) and (42%) were Hodgkin lymphoma where nodular sclerosis subtype formed (52%) and mainly of the nodal site in both of them. The age range of Non Hodgkin lymphoma 7-76 years (median 50 years) and 5-67 years (median 21 years) for Hodgkin lymphoma and male predominance in both of them and there is no significant association between the site and lymphoma (p value=0.0647) while a significant association with age (p value =0.037). Moreover, the immunohistochemical examination demonstrates that positive PAX5 was expressed in 77% of Non Hodgkin lymphoma and 100% of Hodgkin lymphoma. The P-value between them was 0.016, which was statistically significant ,no matter of using PAX5 or CD30 in"the diagnosis of Hodgkin lymphoma,in other hand"there is a significant difference between PAX5 and CD3 expression (P value=0.004), while it is not statistically significant when comparing PAX5 and CD20 (P-value =0.317) in the diagnosis of Non Hodgkin lymphoma . Conclusion: This study demonstrates that PAX5 is one of the most sensitive and reliable immunohistochemical marker in diagnosing Hodgkin lymphoma and B-cell Non Hodgkin lymphoma.

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Evaluation of the Patients with spinal metastasis of unknown primary tumor origin.
Alya A.Zobair (Author)
January 2021 ,Pages 119.0-125.0

Abstract: Abstract Background: The spine is not only the most frequent site of skeletal metastasis of a known carcinoma but it is also the most frequent site of bone metastasis of unknown primary tumor origin, however, most of the existing reports that analyzed the clinical features of patients who presented with skeletal metastasis of unknown origin have included cases of bone metastasis at any location. Objective: This study was conducted to analyze the clinical features, survival, and specific diagnostic implications in patients presented with spinal metastasis of unknown primary malignant tumor. Method: In this prospective study, 40 patients presented with spinal metastasis of unknown primary tumor origin to Mosul Oncology Hospital were followed up. Result: The primary malignant tumor was identified in (97.5%) of cases, lung cancer was the most frequently identified primary tumor (35%) followed by carcinoma of the breast (30%) and prostatic cancer (12.5%). We found that Computed tomography scan of the chest, abdomen, and pelvis were the most useful diagnostic modality to identify the primary malignant tumor and there was a significant difference in the overall survival of patients with different primary tumor sites, shorter survival time was observed for aggressive tumor like lung cancer compared to patients having less aggressive primary tumor like breast and prostatic cancer. Conclusion: Spinal metastasis of unknown primary carries a diagnostic challenge to the clinician, it is possible to detect the primary site in the majority of patients if we follow optimal diagnostic strategies. Detection of primary tumor site could help the clinician to provide the best therapeutic strategies.

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Prevalence of Caesarean Sections in Mosul City Hospitals :A Cross – Sectional Study
Noor Al-Sanjary, Omaima Abdulrazzaq Zubair, Raida Al-Wazzan (Author)
January 2021 ,Pages 126.0-132.0

Abstract: Background: Caesarean section rates had been increasing markedly in the world and the procedure as it become more safe than before (although it still a major surgical operation) and the objective of this study is to estimate the prevalence of caesarean section in Mosul city hospitals. Methods: A cross-sectional study was conducted at eight hospitals in Mosul city from both river sides including five governmental hospitals and three private hospitals, (671) women who delivered by caesarean section in Mosul city hospitals during a period of data collection were included from beginning 15th of November 2019 and ending at 15th of April 2020. Results: Women delivered by caesarean section aged between 20-35 years in (70.6%), (74.8%) of low educational level and (91.8%) were unemployed. The rate of caesarean section during the period of data collection in Mosul city hospitals was (28.8%) while the rate of caesarean section during the period of data collection showed that the highest rate of caesarean section were in private hospital and especially at Al-Zahrawi and Al-Rabee Private Hospitals (100%) while Al-Batool Hospital include (37.6%) from governmental hospitals in spite that the highest numbers of deliveries and caesarean section was in Al-Khansa Teaching Hospital. Conclusions: Caesarean section rate was higher than WHO recommendation among Mosul hospitals. Further improvement and attention to primary health care should be applied.

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Application of FISH Technique in Evaluation of Equivocal Cases of HER2/neu in Breast Carcinoma
Saja Faisal Jaafar, Ekhlas Ali, Nazar jawher (Author)
January 2021 ,Pages 133.0-140.0

Abstract: Background: Breast cancer in Iraqi females is one of the extreme popular malignant tumors. It represents the third of registered female cancers. Management and outcome of breast cancer are affected by variables such as tumor size and grade, as well as histologic type, HER2/neu status of the tumor and hormone receptor status. HER2/neu (or erbB-2) is a proto-oncogene found on chromosome 17, that is overexpressed and/or amplified in 15% to 25% of invasive breast carcinomas and is connected to worse clinical outcome. Patients with HER2/neu positive breast carcinoma have showed a good response to targeted therapy (Herceptin) that improving the prognosis. Objectives: To assess the immunohistochemical overexpression of HER2/neu in breast carcinoma, to detect the frequency of amplified HER2/neu by FISH on immunohistochemically equivocal cases, and to correlate HER2 overexpression & or amplification with various clinicopathological parameters. Patients and Method: A total of hundred breast carcinoma patients at different ages were included in this retrospective and prospective case series study design. Formalin fixed paraffin embedded blocks were collected from different private labs in Mosul, between 1st November 2019 to 1st April 2020. FISH technique was performed on 25 equivocal cases of HER2/neu tested by immunohistochemistry technique using Leica KreatechTM FISH Dual Probe (Red/Green). Results: Among a total of 100 patients with mean age was (52) years old diagnosed as breast carcinoma via histopathological findings, 58% were tested negative for HER2/neu,17% positives for HER2/neu, and 25% were equivocal by Immunohistochemistry. However, FISH method is conducted for those patients indicated as equivocal at immunohistochemistry and has identified 7(28%) positive cases and 18(72%) negative cases. The association between HER2/neu and the grade of the tumor was statistically considerable (P value=0.03). Furthermore, the analysis indicated that the HER2/neu was not statistically related with histological type of the tumor and age of the patients (P value=0.35, P value= 0.75, respectively). In this study, HER2/neu was statistically inversely associated with both ER and PR receptors (P value=0.03, P value=0.05, respectively). Conclusion: HER2/neu is overexpressed by immunohistochemistry in 17%. HER2/neu is amplified by FISH (in equivocal cases) in 28%. HER2/neu is statistically significant correlation with tumor grade, and is in inverse statistically significant correlation with estrogen and progesterone receptors while not statistically significant with age and histological types of tumors.

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The Frequency of Blood Donors and Polycythemia among General Population in Nineveh Governorate, Iraq.
Rana Al-Nuri (Author)
January 2021 ,Pages 141.0-147.0

Abstract: abstract: Objectives: the aim of the study is to determine the percentages of blood donors among general population in Mosul, Nineveh, Iraq, in an attempt to increase their proportion through encouraging healthy voluntary donation. Then to report the issue of polycythemia and discouraging the contributing unhealthy habits like smoking, especially among young people. Methods: subjects enrolled in this study were the blood donors at Mosul Central Blood Bank in Nineveh, Iraq. Data were reviewed retrospectively, from March, 2019 to March 2020. For whole blood donors in general and for polycythemic ones, who donate blood as a therapeutic measure. Results: the total number of donors were 36940. Percentage of blood donors among general population was 2.27 %, while 99.43 % were male donors. Prevalence of polycythemic subjects among general population of Mosul city was 0.04 %, among blood donors was 1.65 %. while 88.87 % of polycythemic donors were male, and the distribution of polycythemia was higher in those aged 35 years and less (38.46 %). Conclusions: the percentages of blood donors in general population was low, which need to increase through encouragement and improve commitment. The prevalence of polycythemic subjects in those aged ≤ 35 years was high which necessity intensification of the awareness among those productive age groups.

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The Effect of Maternal Obesity on The Placental Histology
Harith Al-Ali, luma Al-Allaf (Author)
January 2021 ,Pages 148.0-156.0

Abstract: Background: Obesity become one of the most universal medical problem that affect women at reproductive periods. . It has complicated drawbacks in mother and child appeared immediately or after long time. Aims: so the aim of this study to evaluate the placental histological changes of obese mothers in comparison to women with normal body mass index. Methods: This work is prospective case- control study which were examined placentas that were obtained from 40 singleton pregnant women who delivered at Al-Khanssa Maternity Teaching Hospital, Mosul, Northern of Iraq starting from December 2019 to February 2020. The women were classified into two groups: Group 1 which includes 20 women with BMI ranged between 18-24.9 kg/m2, and Group 2 which includes 20 women with BMI ≥ 30. Two placental biopsies were obtained from maternal side and fetal side of each case and submitted for histological examination via light examination. Results: The histopathological examination of placental sections obtained from obese mothers showed several placental changes compared to those of control group. The most frequent feature among these sections is the presence of syncytial knotting in 13(65%) out of 20 placentas.In addition, features of hypovascular villi, villous fibrinoid necrosis are noticed in 10 (50%) of these sections, while thickening of trophoblastic basement membrane was occur in 9 (45%) of these sections. On the other hand, the histopathological examination of placental sections obtained from obese mothers revealed presence of perivillous fibrin deposition which was appeared in 10 (50%) of these sections .Features of stromal fibrosis were noticed in (40%) of sections. Other placental changes are seen in placental sections obtained from obese mothers including presence of nucleated red blood cells (NRBC) in fetal capillaries, chorangiosis, villous edema, paucity of vasculosyncytial membrane VSM, inflammation, apoptosis and decidual fibrinoid necrosis. Conclusion: this work revealed a marked increase in the frequencies of different placental changes in obese mothers in comparison with controls. Further studies are recommended to clarify the exact mechanisms that stand behind these histological changes.

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Hematological parameters of β-thalassemia Trait in Premarital Screening in Nineveh Province
bassma adnan, Professor Muna Abdulbasit Kashmoola (Author)
January 2021 ,Pages 157.0-161.0

Abstract: ABSTRACT Background: β-Thalassaemia syndromes are inherited group of abnormalities of hemoglobin synthesis. These abnormalities characterized by a defect in β-globin genes which may result either in the reduction or absence of one or more of the β-globin chains of hemoglobin. This genetic defect can be homozygous or heterozygous. Aim of this study was to detect the hematological parameters of β-thalassaemia trait in premarital screening individuals in Nineveh province. Subjects and Methods: This is a cross sectional study that was performed in Nineveh province in three main centers for premarital screening program. In the period between the 15 November 2019 and the 15 May 2020 a total of 1127 subjects who attend to these centers were screened for carrier conditions of β-thalassemia. Blood samples of the couples were obtained during attendance to the marriage office. Complete blood counts and hemoglobin variant analysis were performed with automated counter and high performance liquid chromatography technique. Results : Out of 1127, β-thalassaemia trait was diagnosed in 47 subjects, 31 were male (66 %) and 16 were female (34 %). The mean of their hemoglobins was 14.4 g/dl in males, and 12.5 g/dl in females. The mean of mean cell volume and mean cell hemoglobin were 68.3fl and 22.4pg respectively. The mean for HbA2 concentration was 4.9 % and for HbF was 1.2%. Conclusion: β-thalassaemia trait is usually presented with low MCV and/or low MCH but the accurate and dependable technique in detecting carriers is the use of High Performance Liquid Chromatography (HPLC).

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Evaluation of Interleukin- 6 in Lymphoma
Anfal Saleh Mohammed AL-jubory, Sanaa mohammed taib Al- Hayali (Author)
January 2021 ,Pages 162.0-168.0

Abstract: ABSTRACT Background: Cytokines play a pivotal role in lymphoma ,cytokines either can be produced or exert effects on neoplastic or reactive cells. The elevated level of cytokines can contribute to the clinical and histopathologic alterations associated with malignant lymphoma. Objectives: to assess the level of IL-6 in newly diagnosed lymphoma patients in relation to their level in normal control subjects and to evaluate the correlation between IL-6 and hemoglobin (Hb), stage of disease and B-symptoms ,age and sex. Methods: This is a case control study, a total of 40 patients with lymphoma (HL & NHL) who attended private Clincs and hospitals in Mosul city and 40 age and sex matched control were included. A venous blood sample were taken for Complete blood count, Retic and IL-6 level. Enzyme-linked immunosorbent assay(ELISA)was used to determined IL-6 level. Results: There were a significant difference between the mean level of IL-6 of lymphoma cases and control (p-value=0.00). In the subset of patients with anemia, IL-6 levels inversely correlated with hemoglobin levels (p-value=0.00). There was significant correlation between IL-6 and patients with more advanced stage Ⅲ- IV disease(p-value=0.04). there was positive correlation between IL-6 levels and B-symptoms)p=0.05( Conclusion: IL-6 level was elevated in lymphoma and it was significantly higher in lymphoma patients .IL-6 plays important role in the development of anemia in lymphoma.The adverse impact of elevated IL-6 is consistent with demonstration of higher level of IL-6 in patients with advanced stage of disease.

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Comparative study between sharp dissection and electro cautery dissection in incisional hernia surgery.
Omar Mahmood, khalaf jadoa (Author)
January 2021 ,Pages 169.0-176.0

Abstract: Background: Incisional hernia is a common problem in our surgical practice and it poses a challenge due to its high incidence of complications like seroma and surgical site infection (SSI). The objective of this study is to assess the contribution of diathermy to postoperative seroma formation and wound complications in incisional hernia surgery and also to assess other predictors for wound complications including comorbidities, personal and hernia characteristics. Patients and Methods: This is a prospective case series study comparing two types of flap dissection in cases of open incisional hernia mesh repair. Sixty patients randomized in to two groups of abdominal flap dissection, one group with electro cautery dissection and other group with sharp dissection by scissors and knife. Surgical procedure was the same between the two groups. Primary outcome measures were postoperative seroma, SSI and wound dehiscence. Results: There was no significant difference in seroma formation (p=0.738), SSI rate (p=0.641) and wound dehiscence rate (p=0.150) between the electro cautery group and the sharp dissection group. The use of cautery leads to reduction in the intraoperative blood loss (p<0.0001) and operative time (p<0.0001). The relation between body mass index (BMI), diabetes mellitus (DM), hernia length, width and postoperative seroma was highly significant (p=0.002, 0.034, 0.002, Conclusions: The use of cautery instead of scissors during flap dissection does not result in increased postoperative wound complications in incisional hernia patients. The use of cautery lead to reduction in the operative time and intraoperative blood loss. The relation between DM, BMI, hernia defect size and increased rate of wound complications was significant.

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Obesity, adipose tissue types and adipocytokines
Nuha Shareef, Maryam Abduljalal (Author)
January 2021 ,Pages 177.0-183.0

Abstract: The prevalence of obesity has increased worldwide in the last 50 years, reaching pandemic levels. The etiology of obesity is multifactorial, involving a complex of interaction among genetics, hormones and the environment. The adipose tissue plays a central role in regulating whole body energy. In one hand, the adipose tissue stores energy in the form of lipid and controls the lipid mobilization and distribution in the body, and on the other hand, adipose tissue acts as an endocrine organ and produces numerous bioactive factors such as adipocytokines. Moreover, brown and beige adipose tissue burn lipid by dissipating energy in the form of heat to maintain euthermia and have been considered as a new way to counteract obesity. In this review, we will summarize the recent findings of the types of adipose tissue and their role in controlling metabolism, focusing on its endocrine function. This review describes the molecular actions and clinical significance of the some important adipocytokines.

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complications related to posterior hypospadias repair
Professor Abdulrahman sulaiman, Thayer Aboush, ahmad hamodat (Author)
January 2021 ,Pages 184.0-189.0

Abstract: Background: Proximal hypospadias repair carries high complications rates. single stage is the standard practice for management but sometimes it is not easy to perform single stage for posterior hypospadias and here appears the need for staged surgery in this study we assess the out coms and complications of the most commonly used techniques in Mosul pediatric surgery center at alkhansaa teaching hospital Objective: To assess the results of management of posterior hypospadias by Tubularized incised plate as single stage and staged repair and to knew the most important complications associated with these two procedures. Methods: this is prospective study for forty patients who were admitted to Mosul pediatric surgery center at alkhansaa teaching hospital from October 2011 till October 2013, their age ranged from 9 month to 15 years, five of them were operated before with complete failure, 31 patient operated by single stage Tubularized Incised Plate technique and the other 9 by two stage technique and they were followed for 6-18 months. Results: The total complications rate was (52%) as follow: (7) cases (17.5%) develop meatal stenosis, (4) patients (10%) develop retrusive meatus, No one develops stricture, (10) cases (25%) develop fistula and none of them develop diverticulum, the total complication rate for Single stage TIP technique was (48.3%) the total complication rate of complications for staged surgery was (66.6%). Conclusion: proximal hypospadias repair is very challenging with high complication rate which need a good experience to deal with it. Single stage or multistage procedure can be utilized to repair this type of hypospadias. Most of the published papers has low number of cases in comparison to the anterior type which represent 70_80% of all cases and for that reason may be the great difference in between different centers in the incidence of complications rate.

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Incidentally diagnosed papillary carcinoma in a thyroglossal duct cyst. What is the next step? A case report and review of the literature
Professor Nashwan mahgoob (Author)
January 2021 ,Pages 184.0-189.0

Abstract: Thyroglossal duct cyst is the commonest congenital disorders of the thyroid gland. Rarely, it can be a malignant tumor which is picked up incidentally in postoperative histopathology. Although management is still a controversy, a careful treatment and follow up planning is necessary for the management of such condition. We present a case of a 16-year-old female patient with thyroglossal duct cyst carcinoma.

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The white banner test. A simple intra-operative leak test during laparoscopic sleeve gastrectomy.
Professor Nashwan mahgoob (Author)
January 2021 ,Pages 190.0-194.0

Abstract: ABSTRACT: Objective: To evaluate the efficacy of a simple intra-operative test (white banner test) for the detection of a leak during laparoscopic sleeve gastrectomy. Design: A prospective case series study. Setting: Obesity center at Soran private hospital, Erbil, Iraq, during the period from January 2017 to June 2019. Participants: eighty patients underwent the white banner test during laparoscopic sleeve gastrectomy. The records of intraoperative findings and post-operative follow up were analyzed. Patients and methods: After completing the sleeve process and hemostasis, a gauze of 4*12 cm was introduced through the 12mm trocar and displayed along the course of remaining sleeved stomach, nasogastric tube inserted to the upper portion of the stomach, compression of the pylorus by grasper against the vertebrae, 100 milliliters of saline stained by methylene blue dye were injected slowly by the anesthetist through the nasogastric tube, waiting for 30 seconds, any discoloration of the gauze was recorded and the site of leak (if any) was identified and managed. If the gauze appeared white, gauze withdrawn and the procedure finished. Results: In 80 patients, only two patients showed a blue spot at the gauze, which were fixed by suture. In all other patients, the gauzes were completely clean and (white). Postoperatively no early leak was detected. Conclusion: This is a simple and not time-consuming intraoperative procedure that can be used to detect intra-operative leaks during laparoscopic sleeve gastrectomy. Keywords: obesity. Sleeve gastrectomy. Leak. Intraoperative test. Acknowledgment: The author thanks all the staff who works at the obesity center at Soran Private Hospital for their unlimited support for this study. The study received no outside funding and no relevant financial disclosures. The researcher declares that there is no conflict of interest regarding the publication of this research

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RARE AND DEMANDING: PARATHYROID ADENOMA LOCALIZATION, SURGERY AND OUTCOME.
Saad Attash, Nazar Mohammed Jawhar, Mohammed yahya, Professor Muzahm K. Al-Khyatt (Author)
January 2021 ,Pages 199.0-206.0

Abstract: ABSTRACT Objectives: To assess the methods of preoperative parathyroid adenoma localization and to compare it with operative findings. Patients and methods: Between June 2017 and June 2019, we had operated 8 cases of parathyroid adenomas. Three patients were males and 5 patients were females. Age ranged from 26 year old to 72 year old with average of 42 year old. Seven cases were sporadic while one case was part of MEN2a. All patients had ultrasonography for preoperative localization, all had CT scan and 4 patients had Sestamibi scan. In all patients, intraoperative measurements of parathyroid hormone was done before and 10 minutes after surgical excision. Results: Ultrasonography was successful in localizing only one case with certainty. CT scan located the adenoma in another 2 patients. In 4 patients who performed Sestamibi scan, the adenomas were located precisely in all of them including one case of ectopic parathyroid adenoma behind the sternum. In one patient, all the modalities failed in localization which was achieved easily intraoperatively. Single adenoma was found in 6 patients and two adenomas in two patients. The adenomas were located in the neck in 7 patients and in the anterior mediastinum in one patient .Surgical removal was done through neck incision in 7 cases while midline sternotomy in one case. All the patients had resolution of symptoms within the follow up period. Conclusion: Sestamibi scan is the best investigation in preoperative localization of parathyroid adenoma. Ultrasonography and CT scan can aid in the diagnosis with less sensitivity. Intraoperative localization is possible even in cases of negative investigations.

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