Sonographic Features of Atypical and Initially Missed Parathyroid Adenomas: Lessons Learned From a Single-Center Cohort.

CONTEXT: Awareness of typical and atypical ultrasonographic (US) features of parathyroid adenomas (PAs) is crucial since US is the most widely used first-line imaging modality. OBJECTIVE: The purpose of this study was to describe the atypical features of PAs on US and other possible factors leading to a false negative examination in a large single-center cohort. MATERIALS AND METHODS: The US records of 457 PAs in 445 patients with biochemically proven primary hyperparathyroidism (PHPT) were evaluated in a prospectively maintained database. Atypical size, composition, shape, echogenicity, location, and vascular pattern on US were noted. For patients who previously had at least one negative US examination in referring centers, the main possible reason was defined accordingly. RESULTS: The study group included 359 female and 86 male patients with PHPT. Typical sonographic features were observed in 231 PAs (51%), whereas 226 (49%) had at least one atypical US feature. The most common atypical features were atypical size (29%), followed by atypical echogenicity (19%), shape (8%), location (7%), and composition (7%), respectively. There were 122 initially missed PAs in all groups. The most frequent main atypical US features leading to false negative examinations were atypical size (22.1%) and atypical location (18.8%). Inexperience was third most common reason (16.3%) for false negative US examinations. CONCLUSIONS: Almost half of PAs have at least one atypical feature on US. Awareness of the high prevalence of atypical US features could increase the accuracy of US examination and potentially decrease demand for more expensive second-line imaging modalities.

The sonographer's and pathologist's perspective of echogenic microfoci in papillary thyroid carcinoma.

Objective: Punctate echogenic foci (PEF)/microcalcifications are thought to represent psammoma bodies (PB) in histopathology. However, there are few and contradictory data on this. Different types of sonographic echogenic microfoci (EMF) are seen in papillary thyroid carcinoma (PTC), and their histopathological equivalents are not clearly known. There is also conflicting data on the interobserver agreement between the sonographers on EMF. Methods: We prospectively collected US video records of PTC nodules with and without EMF in two large thyroid centers. All video recordings were independently interpreted by three blinded, experienced sonographers. EMF were classified as true microcalcifications (punctate echogenic foci (PEF) ≤1 mm long), linear microechogenities (>1 mm long, posterior acoustic enhancement of the back wall of a microcystic area), comet-tail artifacts/reverberations or linear microechogenities with comet-tail artifacts/reverberations, non-shadowing coarse echogenic foci (>1 mm nonlinear areas) and unclassifiable. Histopathological evaluation was performed by two blinded, qualified pathologists. Results: A total of 114 malignant nodules were included. The average Cohen's kappa (κ) of three sonographers for the EMF presence was 0.775, indicating substantial agreement. A substantial agreement for PEF with 0.658 κ, only fair agreement for other types of EMF with 0.052 to 0.296 κ were detected. EMF were significantly associated with PB and papillae. PEF had an evident relationship with PB in multivariate analysis. There was a strong positive correlation between the amount of PEF and PB (r = 0.634, P < 0.001). Conclusions: PEF in PTC mainly correspond to PB on histopathology. Although observation of EMF varies among sonographers, this inconsistency can be reduced by classifying EMF into subgroups and keeping the term 'PEF' only for true microcalcifications.

Effects of Intracameral Drugs and Dyes on Corneal Endothelial Cell Apoptosis in a Rat Model: An In Vivo and In Vitro Analysis.

Objectives: To evaluate the effects of intracameral drugs and dyes on rat corneal endothelial apoptosis and cell morphology. Materials and Methods: The right eyes of 72 rats were injected intracamerally with 1% lidocaine, 0.01% adrenaline, triamcinolone acetonide (TA) 4 mg/mL, 1% trypan blue (TB), 0.5% indocyanine green (ICG), and fortified balanced salt solution as control. Corneal samples were taken 1 day and 1 week post-injection. Corneal endothelial apoptosis was assessed by the TUNEL technique, and the ratio of apoptotic cells in each group was compared with the control. Corneal endothelial cell morphology was evaluated in each specimen by transmission electron microscopy. Results: The mean apoptotic endothelial cell ratio was significantly higher at 1 day and 1 week after intracameral adrenaline injection when compared to controls (p=0.03 and 0.021, respectively). TB caused a significantly higher apoptotic cell ratio when compared to controls at 1 week after injection (p=0.043). Lidocaine caused a higher apoptotic cell ratio compared to TA and ICG at 1 week, although not statistically significant (p=0.058, 0.09, 0.69, respectively). In all experimental specimens, transmission electron microscopy showed morphological changes associated with apoptosis. Conclusion: This study showed that intracameral adrenaline, TB, and lidocaine injections may have toxic effects on corneal tissue, as indicated by ultrastructural and histopathological alterations. Therefore, these agents should be used with caution in intraocular surgery.

Radioguided occult lesion localization for minimally-invasive parathyroidectomy without quick PTH monitoring and frozen section: impact of the learning curve.

OBJECTIVES: Minimally-invasive parathyroidectomy (MIP) is a surgical procedure that reduces the duration of operation, hospital costs, and hypocalcemia, and shortens the length of hospital stay. This study addressed the important procedural details of the radioguided occult lesion localization (ROLL)-MIP technique and evaluated the consequences of the learning curve from a series of patients. PATIENTS AND METHODS: A total of 80 patients who underwent ROLL-MIP for a single parathyroid adenoma were included into this retrospective study. In order to analyze the effect of the learning curve, these subjects were then divided into 2 groups per time period and the operative times were compared. Group A consisted of 22 previously reported patients who served as the control group. Group B consisted of 58 consecutive patients. RESULTS: Serum calcium and parathyroid hormone (PTH) levels were normalized in all of the patients within 2 days and remained normal during the follow-up period (31 ± 18.5 months). None of the patients who underwent ROLL-guided parathyroidectomy suffered temporary or permanent recurrent laryngeal nerve injuries. Mean operation time (time from incision to excision of the adenoma) was 23 ± 6 min in Group A and 18 ± 7 min in Group B. Mean operative times were significantly shorter in group B. CONCLUSION: The success of MIP administered with the ROLL technique in a single adenomatous patient was quite high. This method seems especially valuable in patients with atypically located or small adenomas.

Ginger (zingiber officinale) might improve female fertility: A rat model.

BACKGROUND: Ginger (Zingiber officinale) is a well known and extensively used antioxidant in traditional remedies. In this study, we aimed to investigate the effects of ginger powder on ovarian folliculogenesis and implantation in rats. METHODS: There were two study groups. In the 5-day treatment group (one estrous cycle), 100 mg ginger powder, 200 mg ginger powder or distilled water was given for 5 days to the three subgroups each containing seven rats. In the 10-day treatment group, same doses were given for 10 days (two estrous cycle) to the three subgroups each containing seven rats. At the end of the 5th and 10th days, ovarian volumes, ovarian weights, primordial follicles, antral follicles, atretic follicles, and corpus luteum counts were assessed. To evaluate the angiogenic effects of ginger, vascular endothelial growth factor (VEGF) and for the antioxidant effects of ginger endothelial nitric oxide synthase (eNOS) were examined in the ovaries and in the endometrium immunohistochemically. RESULTS: In the 5-day treatment group, antral follicle count and ovarian stromal VEGF were significantly high in the 100 mg ginger subgroup in comparison to the control group (p < 0.05). In the 10-day treatment group, endometrial VEGF and ovarian stromal eNOS were significantly high in the 100 mg ginger subgroup in comparison to the control group (p < 0.05). There was no statistically significant difference at 200 mg ginger dose both in 5-day and 10-day treatment groups. CONCLUSION: The increases in the antral follicle count and ovarian stromal VEGF in the 100 mg/5-day treatment subgroup indicate that ginger have positive effects on folliculogenesis in short term with low dose. Additionally, ginger may enhance implantation in rats in long term with low dose.

Slowly Growing Nodule on the Trunk: Cutaneous Granular Cell Tumor.

Granular cell tumor (GCT) is a rare benign neoplasm of the skin that accounts for 0.5% of all soft-tissue tumors. The tumor mostly presents with a symptomatic slowly growing solitary nodule and overlying normal skin; therefore, it is not always considered in the differential diagnosis. Here, we report a 58-year-old female patient who presented with a 4-year history of a slowly growing mass, with a dimension of 5 × 4 cm on her left waist, diagnosed as a GCT at the histopathological examination. The neoplastic cells had centrally located nuclei and granular eosinophilic cytoplasm and stained positively for S100, neuron-specific enolase, and CD68 antibodies. Fifteen months after surgery, the patient still showed no signs of local recurrence or metastases. Although a large diameter is a feature of malignant GCT, our case with cutaneous GCT was localized on the trunk and did not present malignant features clinically and histopathologically.

Primary intrarenal neuroblastoma in a 13-month-old girl presenting as a Wilms' tumor with pulmonary metastasis.

We report a 13-month-old girl with primary intrarenal neuroblastoma initially diagnosed as Wilms' tumor. Intrarenal neuroblastoma is exceedingly rare in pediatric age that may masquerade as Wilms' tumor clinically and radiographically and it is important to differentiate for management.

Cavernous Hemangioma in the Breast.

Although the observation of breast vascular tumors is rare, the most common tumor is hemangioma in the benign group, and these tumors are observed incidentally in lumpectomy or mastectomy specimens during histological examinations. They are classified into capillary, cavernous, and venous hemangiomas. Cavernous hemangioma is the most common subtype. Cavernous hemangiomas are benign vascular tumors, which malformation from mature blood vessels. Hemangiomas in the benign group may show a suspicion of ductal carcinoma in situ (DCIS) in mammographic analysis. Ultrasonography (US) and magnetic resonance imaging (MRI) are the most useful imaging methods for analyzing the structure of breast vessels. In this case, a 54-year-old female who have any complaint. Scanning mammography (MG) detected the tumor, but physical examination and US could not identify the mass. According to the MG analysis, the lesion was evaluated as BIRADS 4b, and the patient underwent excisional biopsy after wire localization. Pathological analysis revealed cavernous hemangioma.

Invasive Ductal Carcinoma Developing From Fibroadenoma.

Fibroadenomas are the most common benign breast lesions in adolescent and young women. It is most frequently observed in the 3rd decade. Although it is considered benign, evidence of malignant transformation is available. Cancer development may be from ground of fibroadenoma or near breast tissue. A case of a fibroadenoma coexisting with an invasive ductal carcinoma of the breast in a 31-year-old female is presented. The patient presented with the chief complaint of having a palpable mass in her right breast for the last 10 years. Mammography revealed a mass with microcalcifications. Core biopsy was performed, and the results indicated an invasive carcinoma. Breast-conserving surgery with sentinel lymph node biopsy was performed. The pathological features revealed a fibroadenoma coexisting with an invasive ductal carcinoma. This case suggests that clinicians and radiologists should always pay attention to the associated malignant imaging characteristics whenever a mass was followed up as fibroadenoma.

Radioguided occult lesion localization for minimally invasive parathyroidectomy: technical consideration and feasibility.

PURPOSE OF THE REPORT: Minimally invasive parathyroidectomy (MIP) constitutes one of the main surgical approaches for the patient with primary hyperparathyroidism (PHPT) caused by a single parathyroid adenoma. The purpose of the study was to investigate the feasibility of radioguided occult lesion localization (ROLL) for MIP and the potential effects of the method in histopathologic evaluation. MATERIALS AND METHODS: Twenty-two patients, diagnosed with PHPT biochemically and candidates for surgery, underwent ROLL-guided MIP (ROLL-MIP). Parathyroid adenomas were searched for and identified with the guidance of an intraoperative gamma probe. The final diagnosis was confirmed by histopathologic analysis. All specimens were analyzed for the presence of parenchymal hemorrhage, congestion, neutrophil leukocyte infiltration, necrosis, cystic degeneration, subcapsular hematoma, subcapsular fibrin/neutrophil leukocyte infiltration, and disarray of the fibrous capsule of adenoma. RESULTS: All injected lesions were effectively located over the skin with very high count rates depending on the injected activity and location of the lesion. Serum calcium and parathyroid hormone (PTH) levels normalized in all patients and stayed within the normal range during the follow-up period. None of the patients who underwent ROLL-MIP suffered temporary or permanent recurrent laryngeal nerve injuries. The mean operative time was 23 ± 7 min. Parenchymal hemorrhage, congestion, subcapsular hematoma, and fibrin/neutrophil leukocyte infiltration were common histopathologic features. CONCLUSION: The use of ROLL-MIP in patients with PHPT due to a single parathyroid adenoma in the neck is technically safe and effective. It is more valuable in scintigraphy-negative patients when parathyroid adenoma is either demonstrated on ultrasonography by typical findings or confirmed by PTH washout. The ROLL-MIP technique does not impair the postoperative histopathologic examination of the parathyroid glands.

Methylation profile analysis of DNA repair genes in hepatocellular carcinoma with MS-MLPA.

Hepatocellular carcinoma (HCC) is one of the rare tumors with well-defined risk factors. The multifactorial etiology of HCC can be explained by its complex molecular pathogenesis. In the current study, the methylation status of 7 genes involved in DNA repair mechanisms, namely MLH1, PMS2, MSH6, MSH2, MGMT, MSH3, and MLH3, was investigated in tumor samples from HCC patients, using the methylation-specific-multiplex ligated probe amplification method and the results were correlated with available clinical findings. The most common etiological factor in these cases was the presence of hepatitis B alone (47.2%). Among the 56 cases that were studied, promoter methylation was detected in at least one of the genes in 27 (48.2%) cases, only in 1 gene in 13 (23.2%) cases, and in >1 gene in 14 (25%) cases. Of the 7 genes investigated, methylation was most frequently observed in MSH3, in 14 (25%) cases. Methylation of at least 1 gene was significantly more frequent in patients with single tumors than multifocal tumors. There were significant differences regarding hepatitis B status, Child Class, tumor number, grade, and TNM stage in cases where PMS2 methylation was detected. Our results suggest that methylation of genes involved in mismatch repair may be responsible in the pathogenesis of HCC, and evaluating changes in multiple genes in these pathways simultaneously would be more informative. Despite being a robust and relatively inexpensive method, the methylation-specific-multiplex ligated probe amplification assay could be more extensively applied with improvements in the currently intricate data analysis component.

Injectable tissue-engineered cartilage using commercially available fibrin glue.

OBJECTIVES/HYPOTHESIS: To achieve injectable tissue-engineered cartilage using a commercially available fibrin sealant, and to determine the most suitable fibrin glue concentration, cartilage source, and cultured chondrocyte concentration. STUDY DESIGN: Animal research. METHODS: A total of 28 immunocompetent New Zealand white rabbits were divided into four groups. The cultured chondrocytes from different anatomical sources carried in fibrin glue with and without aprotinin in different concentrations of fibrinogen and thrombin (Tisseell), were injected into forehead and interocular regions of the rabbits. The new tissue formation was harvested at 8 weeks and analyzed through gross and histological analysis. RESULTS: The new tissue formations were found in round, elliptical, and flat forms. The mean value of Tisseell and cell suspension was 0.8 cc in all of the rabbits' injection regions, but the mean volume of the samples in which immature cartilage matrix and mature cartilage was 0.1 cc. In the 20 of the 55 injection regions of rabbits (36, 36%), mature and/or immature cartilage formation were observed. We observed inflammatory reactions, abscess formation, and foreign body reactions around the new cartilage tissue of tissue-engineered cartilage. The comparison of results using different cartilage sources, chondrocyte concentrations, or different fibrin glue concentrations did not show any significant difference. CONCLUSIONS: We observed that changing the concentrations of ingredients of commercially available fibrin glue, the source of the cartilage, or the cultured chondrocyte concentration did not have significant effect on neocartilage formation.

Peritoneal washing cytology in an adult granulosa cell tumor: A case report and review of literature.

Adult-type granulosa cell tumors (AGCT) account for 1-2% of all ovarian tumors and 95% of granulosa cell tumors. In AGCT, at the time of peritoneal washing, tumor cells are rarely seen to exfoliate and FIGO stage is raised from IA/IB or IIA/IIB to stage IC or IIC despite the absence of a gross intraepithelial tumor. Patients with positive peritoneal washing cytology must be followed up for pelvic recurrence and metastasis. A more sensitive cytologic evaluation, histopathologic correlation and immunohistochemical staining can advance our practice. Here, we describe a case of AGCT with the emphasis on cytologic features observed in specimens obtained from peritoneal washing fluid.

Serrated polyps of the colon: how reproducible is their classification?

For several years, the lack of consensus on definition, nomenclature, natural history, and biology of serrated polyps (SPs) of the colon has created considerable confusion among pathologists. According to the latest WHO classification, the family of SPs comprises hyperplastic polyps (HPs), sessile serrated adenomas/polyps (SSA/Ps), and traditional serrated adenomas (TSAs). The term SSA/P with dysplasia has replaced the category of mixed hyperplastic/adenomatous polyps (MPs). The present study aimed to evaluate the reproducibility of the diagnosis of SPs based on currently available diagnostic criteria and interactive consensus development. In an initial round, H&E slides of 70 cases of SPs were circulated among participating pathologists across Europe. This round was followed by a consensus discussion on diagnostic criteria. A second round was performed on the same 70 cases using the revised criteria and definitions according to the recent WHO classification. Data were evaluated for inter-observer agreement using Kappa statistics. In the initial round, for the total of 70 cases, a fair overall kappa value of 0.318 was reached, while in the second round overall kappa value improved to moderate (kappa = 0.557; p < 0.001). Overall kappa values for each diagnostic category also significantly improved in the final round, reaching 0.977 for HP, 0.912 for SSA/P, and 0.845 for TSA (p < 0.001). The diagnostic reproducibility of SPs improves when strictly defined, standardized diagnostic criteria adopted by consensus are applied.

Long-term results of incidental hepatocellular carcinoma after liver transplant.

OBJECTIVES: The incidence of detecting hepatocellular carcinoma in a removed recipient liver after a liver transplant is not rare. Here, we sought to evaluate incidental hepatocellular carcinoma at our center. MATERIALS AND METHODS: Among 296 patients who had undergone a liver transplant between September 2001 and November 2010, we retrospectively analyzed the outcomes of 6 patients with incidental hepatocellular carcinoma. The proportion of incidental hepatocellular carcinoma was 2%. The rate of incidental hepatocellular carcinoma among all hepatocellular carcinoma patients is 11.5%. There were 3 children and 3 adults (mean age, 28.3 ± 26 years; age range, 1-57 years). Two of the 6 patients were 1 year old. Alpha-fetoprotein levels were mildly elevated in 3 patients. RESULTS: The results of preoperative imaging studies in all patients were normal, except for those that demonstrated regenerative or dysplastic nodules. One of the grafts was from a deceased donor, the remaining 5 were from living-related donors. We encountered no complications after the transplants. Pathology findings showed a mean tumor size of 0.8 ± 0.3 cm (range, 0.5-1.2 cm) and multiplicity in 1 patient. One patient with multiple tumors had microvascular invasion. According to the Tumor Node Metastasis staging system, 5 patients had Stage I, and the remaining patient had Stage II carcinoma. There were no recurrences of hepatocellular carcinoma, and no deaths occurred during a mean follow-up of 63 ± 16.5 months (range, 33-79 months). CONCLUSIONS: The incidence of hepatocellular carcinoma in patients with cirrhosis who have undergone a liver transplant at our hospital is similar to those reported in other studies. Incidentally found hepatocellular carcinomas showed less-invasive pathologic features and better prognoses than did preoperatively found hepatocellular carcinomas.

Acute appendicitis after diaphragmatic hernia after pediatric liver transplant.

Multiple complications in liver transplant have been described in the literature. However, appendicitis and diaphragmatic hernia have rarely been reported after solid-organ transplant. The clinical presentation of appendicitis is similar to that of nontransplant patients, but complications are more frequent, because the majority of the patients do not have leukocytosis. Diaphragmatic hernia can present with a variety of atypical clinical symptoms. In this report, 1 patient who developed a diaphragmatic hernia and appendicitis after liver transplant is presented. A 2-year-old boy with end-stage liver cirrhosis owing to progressive familial intrahepatic cholestasis type-2 received a living-donor liver transplant. The posttransplant course was complicated. The diagnosis of diaphragmatic hernia was confirmed by thoracoabdominal computed tomography, and we decided to proceed with surgical repair. The patient had evidence of perforation, and the appendix was removed. After repositioning the intestine in the abdomen, a chest tube was placed, and the defect repaired with interrupted polypropylene sutures. The patient recovered after surgery without untoward sequelae.

Value of the Likert dyspepsia scale in differentiation of functional and organic dyspepsia in children.

AIM: Dyspeptic symptoms may not allow clinicians to differentiate organic and functional gastrointestinal disorders. According to our dyspeptic patients' answers to dyspepsia questionnaire, we aimed to define the symptom scores directing organic dyspepsia (OD) before upper gastrointestinal endoscopy. PATIENTS AND METHODS: One hundred sixty-one patients (ages 10-17 years, mean 13.5 ± 2.3 years, male/female: 2/3) with chronic upper gastrointestinal system symptoms lasting for at least 3 months were enrolled. Patients with predominated reflux symptoms were excluded by 24-hour pH monitoring. Before upper gastrointestinal endoscopy, severity and incidence of 8 gastrointestinal symptoms (epigastric pain, upper abdominal discomfort, retrosternal pyrosis, bitter or sour taste in mouth, halitosis, belching, nausea, and early satiety) were measured by 5-point Likert scale. Total score indicated severity score multiplied by incidence score. Antral biopsy samples were obtained. OD is defined as peptic ulcer, erosive esophagitis, erosive or nodular gastritis, and erosive duodenitis in endoscopy and/or moderate to severe antral gastritis in histology. Functional dyspepsia (FD) is defined as normal findings/mucosal hyperemia in endoscopy and/or mild antral gastritis in antral histology. We evaluated the relation among severity and incidence scores of each dyspeptic symptom in patients with OD or FD. Age, sex, body mass index, drug history, nutritional habits, the quality of life related to dyspepsia were also investigated in patients with OD and FD. RESULTS: According to patients' histological and endoscopic findings, 100 (62%) patients were in the OD group and 61 (38%) patients were in the FD group. Of the dyspeptic complaints, the severity, incidence, and total scores of epigastric pain were significantly correlated with dyspepsia type (respectively, P = 0.042, P = 0.028, and P = 0.005). Of 93 patients who had an epigastric pain severity of 4 and 5 (namely, moderate to severe pain), 65 (70%) patients were in the OD group and 28 (30%) patients were in the FD group. Of 68 patients who had an epigastric pain severity of 0 to 3 (no epigastric pain or mild pain), 33 (48.5%) were in the OD group and 35 (51.5%) were in the FD group, and the difference was statistically significant (P = 0.042). After analyzing the total scores of 8 dyspeptic symptoms, one by one or in different combinations, we could not find a threshold (cutoff) score value that was able to indicate OD definitely. Age, sex, body mass index, and nutritional habits were not significantly different between patients with OD or FD. Nocturnal abdominal pain, pain before meals, and resolution of symptoms after meals or ingestion of antacid drugs were not significantly related to OD. Nocturnal abdominal pain was observed to be higher in the group with moderate to severe gastric inflammation. CONCLUSIONS: In the present study, the severity, incidence, and total scores of epigastric pain were significantly related to OD; however, a cutoff value of dyspepsia symptom score for differentiation of OD and FD could not determined. In our study, Likert dyspepsia scale was not beneficial in differentiation of the OD/FD groups. We suggest that the Likert dyspepsia scale should be redesigned for children or the same scale should be applied in a larger cohort of dyspeptic children.