Hepatocellular adenomas in the Turkish population: reclassification according to updated World Health Organization criteria.

AIMS: Hepatocellular adenoma (HCA) is an uncommon liver neoplasm, and studies of HCA subtypes have been primarily limited to France, the USA, and Japan. The aim of this study was to describe the clinicopathological features of HCA subtypes in Turkey. METHODS AND RESULTS: The resection specimens of 59 cases diagnosed as 'hepatocellular adenoma' collected from 15 institutions were reviewed to confirm the diagnosis and to classify them according to the current World Health Organization 2019 classification. Immunostaining for glutamine synthetase, liver fatty acid-binding protein, C-reactive protein, ß-catenin and reticulin was performed. Of the 59 cases, 48 (81%) were diagnosed as HCA. We identified 24 (50%) hepatocyte nuclear factor 1α (HNF1α)-inactivated HCAs, five (10%) inflammatory HCAs, 15 (32%) ß-catenin-activated HCAs, three (6%) ß-catenin-activated inflammatory HCAs, and one (2%) unclassified HCA. HCA patients were predominantly female (female/male ratio of 5:1); they had a median age of 34 years and a median tumour diameter of 60 mm. In the ß-catenin-activated HCA group, nine cases (19%) showed cytoarchitectural atypia, and were also referred to as atypical hepatocellular neoplasms. In the ß-catenin-activated HCA group, three cases (6%) showed focal areas supportive of transition to HCA. The original diagnosis of HCA was changed to well-differentiated hepatocellular carcinoma in nine cases and to focal nodular hyperplasia in two cases. CONCLUSION: In our series, the major HCA subtype was HNF1α-inactivated HCA. We found a low incidence of inflammatory-type HCA. Our data also showed that ß-catenin-activated hepatocellular neoplasms, including cases with atypical histology, constituted a relatively high proportion of the cases. These findings are in contrast to those of most other studies of HCA subtypes.

The Role of 18F-FDG PET/MRI in the Assessment of Primary Intrahepatic Neoplasms.

RATIONALE AND OBJECTIVES: To evaluate the results of 18F-FDG PET/MRI in relation to the histopathologic subtypes and histologic grades of mass-forming primary intrahepatic neoplasms. MATERIALS AND METHODS: We retrospectively evaluated 18F-FDG positron emission tomography/magnetic resonance imaging (PET/MRI) results for 39 patients with histopathologically confirmed primary hepatic neoplasms, 15 with mass-forming intrahepatic cholangiocarcinoma (ICC) and 24 with hepatocellular carcinoma (HCC). The apparent diffusion coefficient (ADC) and standardized uptake value (SUV) were analyzed in relation to the histopathologic diagnosis and histologic grade, including calculating the sensitivity and specificity of the imaging findings. RESULTS: The median SUV of ICC (6.0 [interquartile range, 5-10]) was significantly higher than that of HCC (4.0 [2.62-6.50]) (p = 0.002). An area under the curve (AUC) of 0.79 (95% confidence interval 0.649-0.932) had a sensitivity of 86.7% and a specificity of 67% at the best cut-off SUV of 4.41 to differentiate between ICC and HCC. ADC values did not differ significantly between HCCs and ICCs (p = 0.283). Both SUV and ADC values differed significantly between low-grade (well- and moderately differentiated) and high-grade (poorly differentiated) HCCs. Combining ADC and SUV further improved differentiation of low- from high-grade HCCs to a significant level (0.929). The SUV did not differ significantly between ICC histologic grades (p = 0.280), while the ADC differed significantly only between well and poorly differentiated ICCs (p = 0.004). CONCLUSION: Assessing primary hepatic neoplasms with 18F-Fluorodeoxyglucose PET/MRI may help to predict tumor grade and differentiate between types of intrahepatic neoplasms.

The prognostic relationship between histopathological and immunohistochemical features of hepatocellular carcinoma, intrahepatic cholangiocarcinoma and mixed type.

Hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and combined hepatocellular and cholangiocarcinoma are the most common cancers of the liver. In this study, our first aim is to evaluate the relationship between prognosis and clinicopathological parameters. The second aim involves investigating the need for immunohistochemical staining and patterns of tumours to differentiate between them. Sixty-one cases were included in this study. For IHC, we used Hep par-1, CK7, CK19, CD56 and p53 staining, and the patterns of tumours were evaluated in haematoyxylin-eosin sections. No significant differences were found in Kaplan-Meier life analysis between the tumour types and OS and DFS values, but these values were greater in HCC than in ICC. There were no relationships between clinicopathologic parameters and OS and DFS. Although the multifocality, stage and grade of tumour were higher in HCC than in ICC, the perineural invasion and lymph node metastasis were more common in ICC than in HCC. The diagnosis was changed in 4 cases, from HCC to ICC in one case and to combined type in 3 cases after IHC. Pathologist should be alert to mixed patterns in terms of diagnosis and IHC, because it helps differential diagnosis in these cases.

Value of Intravoxel Incoherent Motion for Hepatocellular Carcinoma Grading.

BACKGROUND: To evaluate the diagnostic accuracy of intravoxel incoherent motion (IVIM) parameters in estimation of hepatocellular carcinoma (HCC) grading. MATERIALS AND METHODS: Twenty-nine patients with histopathologically diagnosed as 42 HCC at explant were included in this retrospective study. All patients were examined by 1.5T magnetic resonance imaging with the use of 4-channel phased array body coil. In addition to routine pre- and postcontrast sequences, IVIM (16 different b factors varying from 0 to 1300 s/mm2) and conventional diffusion-weighted imaging (3 different b factors of 50, 400, 800 s/mm2) were obtained with single-shot echo planar spin echo sequence. Apparent diffusion coefficient (ADC) and IVIM parameters including mean D (true diffusion coefficient), D* (pseudo-diffusion coefficient associated with blood flow), and f (perfusion fraction) values were calculated. Histopathologically, HCC was classified as low (grade 1, 2) and high (grade 3, 4) grade in accordance with the Edmondson-Steiner score. Quantitatively, ADC, D, D*, and f values were compared between the low- and high-grade groups by Student t test. The relationship between the parameters and histologic grade was analyzed using the Spearman's correlation test. To evaluate the diagnostic performance of the parameters, receiver operating characteristic analysis was performed. RESULTS: High-grade HCCs had significantly lower ADC and D values than low grade groups (P = .005 and P = .026, retrospectively); ADC and D values were inversely correlated with tumor grade (r = -0.519, P = .011, r = -0.510, P = .026, respectively). High-grade HCCs had significantly higher f values when compared with the low-grade group (P = .005). The f values were positively correlated with tumor grade (r = 0.548, P = .007). The best discriminative parameter was f value. Cut-off value of 32% of f values showed sensitivity of 75.6% and a specificity of 73.5%. CONCLUSION: ADC values and IVIM parameters such as f values appear to reflect the grade of HCCs.

Body Mass Index and Unenhanced CT as a Predictor of Hepatic Steatosis in Potential Liver Donors.

BACKGROUND: In living-donor liver transplantation, donor hepatic steatosis is crucial for both the donor and the recipient. Body mass index (BMI) and the unenhanced computed tomography liver attenuation index (CT LAI) are noninvasive methods to predict hepatic steatosis in living-donor liver candidates. AIM: To analyze the diagnostic accuracy of CT LAI in conjunction with different BMI values for macrovesicular steatosis in living-donor liver candidates. METHODS: A total of 264 potential liver donors were included. The diagnostic accuracy of 2 CT LAI cut-offs and 3 BMI cut-off values for the assessment of hepatic steatosis ≥15% and ≤5% was determined. RESULTS: Using CT LAI, the area under the receiver operating characteristic curve was 0.97 (95% CI = 0.89-0.99) for hepatic steatosis ≥15% in donors with BMI <25 kg/m2. For detecting hepatic steatosis ≥15%, a CT LAI ≤0 had specificities of 100%, 76.2%, and 55.6% and positive predictive values of 100%, 95.5%, and 93.5% for patients with BMI values <25 kg/m2, 25 to 29.9 kg/m2, and ≥30 kg/m2, respectively. According to logistic regression analyses, only CT LAI ≤0 was found to be independently associated with hepatic steatosis ≥15%. CONCLUSIONS: In donors with BMI <30 kg/m2 and a CT LAI value >6, liver biopsy might be avoided. Biopsy may be reserved solely for donors with CT LAI value >0 and BMI ≥30 kg/m2 as the diagnostic accuracy of computed tomography for predicting hepatic steatosis decreases with increasing BMI.

Congenital midline cervical cleft: a case report.

BACKGROUND: Midline cervical cleft is a very rare congenital anomaly. According to a literature search, until 2014 only 205 cases were reported. CASE PRESENTATION: We present a classic case of congenital midline cervical cleft. This was a case of a 3-year-old Middle Eastern boy. The lesion was excised and the defect was closed via multiple Z-plasties. CONCLUSIONS: Midline cervical cleft, although a rarity, when presented needs surgical treatment, which comprises surgical excision and closure that lessens the possibility of scar visibility and contracture.

The effects of hyperthermic intraperitoneal chemoperfusion on colonic anastomosis: an experimental study in a rat model.

INTRODUCTION: Cytoreductive surgery (CRS) with subsequent hyperthermic intraperitoneal chemotherapy (HIPEC) is a promising modality to treat and prevent peritoneal metastases. However, this treatment is associated with signficant morbidity and mortality. Whether or not CRS with HIPEC interferes with anastomotic healing has also been debated. This study was designed to investigate the effects of mitomycin C, cisplatin, oxaliplatin, and doxorubicin used in HIPEC treatment on colonic anastomosis healing in a rat model. METHODS: Sixty Wistar albino rats were employed in the study. Sigmoid resection and end-to-end colorectal anastomosis was performed in all rats. Group 1 rats underwent the surgical procedure alone, while group 2 rats were given hyperthermic intraperitoneal lavage with heated saline following surgery. Groups 3, 4, 5, and 6 had surgery with concomitant HIPEC treatment with mitomycin C, cisplatin, oxaliplatin, and doxorubicin, respectively. Anastomotic bursting pressures and hydroxyproline levels were evaluated. RESULTS: Regarding the hydroxyproline levels, groups 1 and 2 showed significantly higher values than other groups (p<0.001). However, there was no significant difference between the HIPEC treatment groups (groups 3, 4, 5, and 6) (p>0.05). When groups were compared regarding bursting pressure values, no significant differences were observed (p = 0.81). CONCLUSIONS: This study demonstrated that the HIPEC procedure with mitomycin C, cisplatin, oxaliplatin and doxorubicin had negative effects on hydroxyproline levels, but had no detrimental effect on anastomotic bursting pressure in a rat model.

Long-Term Palliative Effect of Stenting in Gastric Outlet Obstruction Due to Transarterial Chemoembolization with Yttrium-90 in a Patient with Metastatic Neuroendocrine Tumor.

Internal radioembolization with yttrium-90 is a promising treatment method, predominantly for liver tumors. However, the shifting of yttrium-90-loaded spherules into the arteries and veins that supply the duodenum and stomach, leading to ulceration, hemorrhage, perforation, and outlet obstruction of these organs, is one of the major undesirable consequences of this technique. We report a case of gastric outlet obstruction (GOO) due to antropyloric stenosis with ulceration, edema, and inflammation following transarterial yttrium-90 treatment for a metastatic neuroendocrine tumor in a 58-year-old man. Stenting was used for palliation in this case. GOO improved after stenting and recovery of oral intake was permanent after stent removal.

Clinical and pathological characteristics and their effect on survival in elderly patients with gastrointestinal stromal tumors.

PURPOSE: Gastrointestinal stromal tumors (GISTs) are common tumors of the gastrointestinal tract. Their most frequent location is the stomach. Although the clinical and pathological characteristics of the disease are well-known, the clinical and pathological characteristics and the response to treatment are not clear in elderly patients. The purpose of this study was to evaluate the characteristics of GISTs in elderly patients with an aim at improving the therapeutic methodology and survival. METHODS: In this study, clinicopathological characteristics, evaluation of treatments administered and survival analyses were performed in patients aged 65 years or above, whose data were registered via a web-based patient records system following admission to three centers. RESULTS: A total of 85 patients aged 65 years or above were included in the study. According to the risk classification, 24 (28.2%) were in the low risk group, 20 (23.5%) in the moderate risk group, and 41 (48.3%) in high risk group, while no patient was in the very low risk group. At baseline, 70% of the patients had localized disease and 30% metastatic disease. The tumor was located in the stomach in the majority of the patients (45.6%). The tumor size most commonly seen was 5-10 cm (N=31; 36.4%). Of the 85 patients 23 (27%) were treated with imatinib 400 mg/d. Eight patients (9.4%) with metastatic disease switched from imatinib to sunitinib. At a median follow-up of 76 months (range 1-323), median overall survival (OS) was 72 months, without significant difference between elderly and younger patients. CONCLUSION: Clinicopathological characteristics and their prognostic impact on the disease course of elderly GIST patients should be elucidated in depth. Since age didn't show prognostic importance, other parameters should be used as prognostic/predictive factors in the tyrosine kinase inhibitors era in order to obtain improved therapeutic results.

Evaluation of the likelihood of reflux developing in patients with recurrent upper respiratory infections, recurrent sinusitis or recurrent otitis seen in ear-nose-throat outpatient clinics.

Gastroesophageal reflux is considered a risk factor for recurrent or persistent upper and lower respiratory tract conditions including asthma, chronic cough, sinusitis, laryngitis, serous otitis and paroxysmal laryngospasm. Fifty-one subjects with recurrent (more than three) episodes of upper respiratory tract infection (URTI), serous otitis or sinusitis who had been admitted to an earnose- throat (ENT) outpatient clinic during the previous year were enrolled in the present study to evaluate the presence of laryngeal and/or esophageal reflux. The participants, who were randomly selected, were questioned about symptoms of reflux, including vomiting, abdominal pain, failure to thrive, halitosis, bitter taste in the mouth, chronic cough, heartburn, constipation and hoarseness. All subjects had an endoscopic examination, an otoscopic examination, a tympanogram and upper GI system endoscopy. Esophagitis was diagnosed endoscopically and histologically. The likelihood of occurrence of esophagitis was found to be higher only among subjects with postglottic edema/erythema as determined by pathological laryngeal examination. The reflux complaints reported did not predict the development of esophagitis, but the odds of esophagitis occurring were ninefold greater among subjects with recurrent otitis. Of the subjects, 45.1% were Helicobacter pylori-positive. However, no association was found between esophagitis and Helicobacter pylori positivity. The likelihood of the occurrence of esophagitis was found to be increased in the presence of recurrent otitis media and/or postglottic edema, irrespective of the presence of reflux symptoms. We concluded that, in contrast to the situation where adults are concerned, the boundaries for discriminating laryngopharyngeal reflux from gastroesophageal reflux are somewhat blurred in pediatric patients.

Living donor right lobe liver transplantation as a treatment for hepatic alveolar echinococcosis: report of three cases.

Echinococcus alveolaris is a parasite from tenia family which causes tumor-like lesions in the livers of infected people. If it is not diagnosed in the early stage of the disease, it frequently causes multiple cysts in the liver. The clinical importance of the disease is rapid progression, infiltration into different tissues like a malignant tumor and capacity of creating metastatic masses. The disease could be treated either by surgical resection or liver transplantation. The resection of the cystic disease is the preferred treatment method. In cases where resection is not possible, liver transplantation is the choice of treatment. Here we present three cases which were admitted to the hospital with unresectable hepatic alveolar echinococcosis and treated by liver transplantation successfully. Patients for whom surgical resection is not possible, we recommend liver transplantation as the treatment method.

Predictive and prognostic significance of p27, Akt, PTEN and PI3K expression in HER2-positive metastatic breast cancer.

BACKGROUND: The phosphatidylinositol 3'-kinase/Akt (PI3K/Akt) pathway is a key regulator for HER2- overexpressing breast cancer, but data about whether activation of PI3K/Akt is associated with poor prognosis and resistance to trastuzumab therapy is controversial. In this study we investigated predictive and prognostic significance of expression of p27, Akt, PTEN and PI3K, which are components of the PI3K/Akt signaling pathway, in HER2-positive metastatic breast cancer (MBC), retrospectively. MATERIALS AND METHODS: Fifty-four HER2- positive MBC patients who had received first-line trastuzumab-based therapy were recruited for the study group. All of the patient's breast tissue samples were examined for p27 and Akt expression. In addition, twenty-five patients with sufficient amount of tumor tissue were also examined for PTEN and PI3K expression. p27, Akt, PTEN and PI3K were evaluated by immunohistochemistry and their relationship with patient demographic features, tumor characteristics, response to trastuzumab-based treatment and survival outcomes were analyzed. RESULTS: p27, Akt, PTEN and PI3K were positive in 25.9%, 70.4%, 24% and 96% of the cases, respectively. Nomne were significantly associated with response to trastuzumab and time to progression (TTP). A trend toward statistical significance for longer overall survival (OS) was found for PTEN-positive patients (p=0.058); there was no significant relationship between the other immunohistochemical variables and OS. When we analyzed groups regarding co-expression, the PTEN-negative/Akt-negative group had a significantly lower objective response rate (ORR) (20% vs 80%, p=0.023) and the PTEN-negative/p27-negative and PTEN-negative/Akt-negative groups had significantly lower median OS compared to other patients (26.4 months vs 76.1 months, p=0.005 and 25.6 months vs 52.0 months, p=0.007, respectively). CONCLUSIONS: p27, Akt, PTEN and PI3K expression is not statistically significantly associated with ORR, TTP and OS, individually. However, the combined evaluation of p27, Akt and PTEN could be helpful to predict the response to trastuzumab-based therapy and prognosis in HER2-positive MBC.

Prevalence of K-Ras mutations in hepatocellular carcinoma: A Turkish Oncology Group pilot study.

Hepatocellular carcinoma (HCC) is the fifth most common male-predominant type of cancer worldwide. There is no effective treatment regimen available for advanced-stage disease and chemotherapy is generally ineffective in these patients. The number of studies on the prevalence of K-Ras mutations in HCC patients is currently limited. A total of 58 patients from 6 comprehensive cancer centers in 4 metropolitan cities of Turkey were enrolled in this study. Each center committed to enroll approximately 10 random patients whose formalin-fixed paraffin-embedded tumor tissues were available for K-Ras, exon 2 genotyping. Two methods were applied based on the availability of adequate amounts of tumor DNA. In the first method, the samples were processed using TheraScreen. The genomic DNA was further used to detect the 7 most frequent somatic mutations (35G>A; 35G>C; 35G>T; 34G>A; 34G>C; 34G>T and 38G>A) in codons 12 and 13 in exon 2 of the K-Ras oncogene by quantitative polymerase chain reaction (PCR). In the second method, the genomic DNA was amplified by PCR using primers specific for K-Ras exon 2 with the GML SeqFinder Sequencing System's KRAS kit. The identified DNA sequence alterations were confirmed by sequencing both DNA strands in two independent experiments with forward and reverse primers. A total of 40 samples had adequate tumor tissue for the mutation analysis. A total of 33 (82.5%) of the investigated samples harbored no mutations in exon 2. All the mutations were identified via a direct sequencing technique, whereas none were identified by TheraScreen. In conclusion, in our patients, HCC exhibited a remarkably low (<20%) K-Ras mutation rate. Patients harboring K-Ras wild-type tumors may be good candidates for treatment with epidermal growth factor inhibitors, such as cetuximab.

Emerin expression in well differentiated epithelial lesions of thyroid: implications in papillary thyroid carcinoma diagnosis and predicting malignant behavior.

Recently, it has been reported that identifying nuclear membrane irregularities with anti-emerin antibody is useful for papillary thyroid carcinoma diagnosis. However, literature regarding the significance of emerin immunohistochemistry in thyroid is limited. We evaluated the diagnostic accuracy of the well-established nuclear alterations, nuclear protrusions and recently described nuclear shapes (garlands and star-like shapes) with emerin immunohistochemistry and hematoxylin- eosin stain in thyroid lesions. We further evaluated the diagnostic accuracy measures of tissue microarrays evaluated with both stains, to detect whether emerin immunohistochemistry improves the diagnostic accuracy for papillary thyroid carcinoma. For papillary thyroid carcinoma, pseudo- inclusions were best performers with emerin (diagnostic accuracy: 0.91), whereas with hematoxylin- eosin diagnostic accuracy of grooves was the highest (0.92). For follicular variant of papillary thyroid carcinoma, with both stains, predominately oval nuclear shape had the best diagnostic performance (diagnostic accuracy: 0.95). Nuclear protrusions were poor identifiers for papillary thyroid carcinoma. However, with emerin immunohistochemistry, they could successfully identify malignancy in 83% of the cases. Using emerin immunohistochemistry, in addition to hematoxylin- eosin improved the diagnostic accuracy for papillary thyroid carcinoma when compared to hematoxylin- eosin evaluation only (sensitivity: 0.70 vs 0.86, negative predictive value: 0.81 vs. 0.94, diagnostic accuracy: 0.87 vs. 0.94). Consistent with the previous literature, our findings indicate that emerin immunohistochemistry may be used as an adjunct diagnostic method to identify papillary thyroid carcinoma. Additionally, we suggest that nuclear protrusions detected with emerin imunohistochemistry may be used as indicators of malignant behavior in small tissue samples of thyroid.

Patients with epithelial cell abnormality in PAP smears: correlation of results with follow-up smears and cervical biopsies.

OBJECTIVE: Cervical carcinoma has been included in the preventable diseases category ever since the use of cervical cytology in routine practice. The Pap test is an efficient screening test. We aimed to compare the cervical cytology diagnosis with biopsy and smear follow up results in our institution. MATERIAL AND METHOD: We aimed to compare the diagnosis of cytology material examined in our institution during the 2009-2012 period with their biopsy and smear follow ups. The diagnoses were compared with the follow up smears and/or cervical biopsies. RESULTS: 13610 Pap tests were examined during September 2009-July 2012. Among these cases, there were 370 atypical squamous cells of undetermined significance (ASCUS), 29 atypical squamous cells-high grade intraepithelial lesions cannot be excluded (ASC-H), 155 low grade squamous intraepithelial lesion (LSIL), 33 high grade squamous intraepithelial lesion (HSIL), and 5 atypical glandular cell (AGC) diagnoses. The ratio of atypical squamous cell (ASCUS and ASC-H) to squamous intraepithelial lesions was 2.12. Squamous intraepithelial lesion was verified in 47 of 91 ASCUS cases. Among patients who had a cervical biopsy, 52 of 64 LSIL cases and all of the 21 HSIL cases had biopsy-proven SIL. CONCLUSION: Atypical squamous cell (ASC) is the most common diagnosis in abnormal cervical cytology. As it is indefinite, ASC is used as a quality assurance parameter and the aim is to decrease its use. As the ratio of epithelial cell abnormality is variable in different populations, the ASC/SIL is a more definite variable to be used for quality assurance. The efficiency in clinical use of the cervical cytology screening test is determined by biopsy verification. Our epithelial cell abnormality, ASC/SIL ratio and cytology-histology correlation values were parallel to the literature, proving that the methods are used reliably at our institution.

Gastrointestinal stromal tumors in Turkey: experiences from 3 centers.

BACKGROUND: Gastrointestinal stromal tumors (GIST) are rare tumors of the gastrointestinal system. The most common primary site of GIST is the stomach. The treatment is primarily surgery, and the standard medical therapy is imatinib. Long-term survival can be obtained with good follow-up and treatment. MATERIALS AND METHODS: In this study, data entry was performed using a web-based patient registry system for patients who were referred to 3 centers and retrospectively were diagnosed with GIST. RESULTS: The study cohort consisted of 249 patients, including 160 men (64.3%) and 89 women (35.7%). The mean age was 59 years (range 21-90 years). Initially, 69.9% of the patients had local disease, while 30.1% had metastatic disease. The tumor was located in the stomach in 45.6% of patients. According to the Fletcher risk classification, the very low risk group included 8 subjects (3.2%), the low risk group included 40 subjects (16.1%), the moderate risk group included 56 subjects (22.5%), and the high risk group included 117 subjects (47%); the unspecified group included 28 subjects (11.5%). CONCLUSION: These data are important for revealing the clinicopathologic characteristics and survival data of patients with GIST, who are treated and followed up in Turkey.

Xanthomatous hyperplastic polyps of the stomach: clinicopathologic study of 5 patients with polypoid gastric lesions showing combined features of gastric xanthelasma and hyperplastic polyp.

Gastric xanthelasmas are uncommon benign lesions that are macroscopically well-demarcated yellow or yellow-white plaques and are microscopically formed by collections of foamy macrophages. Because gastric hyperplastic polyps may rarely be associated with xanthelasma, we aimed to report 5 cases of combined lesions showing features of gastric xanthelasma and hyperplastic polyps observed over the past 3 years at our institution among 4497 patients who underwent gastric endoscopy. The patients were 3 men and 2 women aged 45 to 78 years. The lesions were located in oxyntic mucosa, except one in the antrum, and measured 2 to 6 mm. Three patients showed associated chronic gastritis; none showed evidence of Helicobacter pylori infection. Combined lesions of hyperplastic polyp with xanthelasma appear to have an association with chronic gastritis, and the lipid accumulation may be the cause of hyperplasia in the overlying mucosa.

The Predictive and Prognostic Significance of c-erb-B2, EGFR, PTEN, mTOR, PI3K, p27, and ERCC1 Expression in Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common fatal cancer and an important healthcare problem worldwide. There are many studies describing the prognostic and predictive effects of epidermal growth factor receptor 2 (c-erb-B2) and epidermal growth factor receptor 1 (EGFR), transmembrane tyrosine kinases that influence cell growth and proliferation in many tumors. OBJECTIVES: The current study aimed to investigate the expression levels of c-erb-B2, EGFR, PTEN, mTOR, PI3K, p27, and ERCC1 in hepatocellular carcinoma (HCC) and their correlation with other clinicopathologic features. PATIENTS AND METHODS: Fifty HCC cases were stained immunohistochemically with these markers. Correlations between the markers and clinicopathologic characteristics and survival rates were analyzed. RESULTS: No membranous c-erb-B2 staining was seen, whereas cytoplasmic positivity was present in 92% of HCC samples, membranous EGFR was observed in 40%, PI3K was found in all samples, and mTOR was seen in 30%, whereas reduced or absent PTEN expression was observed in 56% of samples and loss of p27 was seen in 92% of the cases. c-erb-B2 and mTOR overexpression, as well as reduced expression of p27, all correlated with multiple tumors (P = 0.041, P < 0.001, and P < 0.001, respectively). P27 loss, and mTOR and EGFR positivity were significantly correlated with AFP (P = 0.047, P = 0.004, and P = 0.008, respectively). Angiolymphatic invasion was more commonly seen in EGFR- and ERCC1-positive cases (P = 0.003 and P = 0.005). EGFR was also correlated with histological grade (P = 0.039). No significant correlations were found among PTEN , PI3K, and the clinicopathological parameters. Disease-free or overall survival rates showed significant differences among therapy modalities, AFP levels, angiolymphatic or lymph node invasions, and ERCC1 and p27 expression levels (P < 0.05). CONCLUSIONS: c-erb-B2, EGFR, mTOR, ERCC1 overexpression levels, and loss of p27 may play roles in hepatocarcinogenesis and may be significant predictors of aggressive tumor behavior. These markers were found to be correlated with certain clinicopathologic features, therapy modalities, and survival rates in the current study. These findings may help in planning new, targeted treatment strategies .

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.

CDX2, COX2 and MUC2 expressions in Barrett's esophagus: can they be useful in determination of the dysplasia?

OBJECTIVE: The description of Barrett's esophagus which is a risk factor for esophageal adenocarcinoma has differences, and the need of goblet cells for diagnosis is controversial. However, the pathophysiology in the metaplasia seen in Barrett's esophagus is not totally understood and new methods are searched for the assessment of progression to dysplasia. We aimed to search the immunohistochemical expression of CDX2, COX2 and MUC2 in Barrett's esophagus to detect any early evidence of intestinal metaplasia or dysplasia. MATERIAL AND METHOD: The staining properties were examined in the intestinal metaplastic (goblet cell-containing columnar epithelium), columnar (non-goblet columnar epithelium), distant columnar (non-goblet columnar epithelium distant from intestinal metaplastic epithelium) and squamous epithelium in 59 pathologically diagnosed Barrett's esophagus, 22 of which having dysplasia. The results were compared statistically with Pearson and Fisher exact tests. RESULTS: The distribution of the staining of intestinal metaplastic, non-goblet columnar distant columnar, and squamous epithelium, respectively were as follows: for CDX2 76.3%, 23.7%, 1.7%, 0%; for COX-2 93.2%, 47.5%, 8%, 62.9%; for MUC2 93.2%, 11.9%, 4% and 0%. The expression of CDX2, COX2 and MUC2 in the intestinal metaplastic epithelium was higher than the expression in distant and non-goblet columnar epithelium. The expression of CDX2, COX2 and MUC2 in the foci of dysplasia decreased significantly (18.2%, 27.3%, 31.9%, and p=0.039, 0.0001, 0.0001, respectively). COX2 expression in squamous epithelium was also lower when the adjacent mucosa has dysplasia (p=0.014). CONCLUSION: The CDX2, COX2 and MUC2 expressions were seen in the intestinal epithelium having goblet cells. The use of the markers in the diagnosis is controversial but the difference in the Barrett esophagus-dysplasia sequence seems to be meaningful.