Significance of High-Mobility Group A Protein 2 Expression in Pancreatic Ductal Adenocarcinoma and Ampullary Adenocarcinoma.

BACKGROUND/AIMS: Pancreatic and ampullary adenocarcinoma (AAC) are quite resistant to chemotherapy with high metastasis potential. Our study aimed to interpret high-mobility group A protein 2 (HMGA2) expression in benign and precursor pancreatic lesions and pancreatic and ampullary carcinoma and to evaluate its relationship with epithelial-mesenchymal transition (EMT) and clinicopathological parameters. MATERIALS AND METHODS: In this study, normal-appearing pancreas, chronic pancreatitis (CP), low- (L) and high (H)-grade pancreatic intraepithelial neoplasia (PanIN), pancreatic ductal adenocarcinoma (PDAC), and AAC were evaluated with the immunohistochemical marker of HMGA2. Vimentin and E-cadherin immunohistochemical stains were applied in PDAC and AAC. RESULTS: The HMGA2 expression was not detected in normal-appearing pancreas, CP, and L-PanIN. A statistically significant expression was observed in PDAC and H-PanIN (P < .001). A statistically significant correlation was found between loss of membranous E-cadherin expression and vimentin positivity and HMGA2 expression (P > .05). The HMGA2 expression was observed to increase the risk of diseaserelated death and decrease overall survival (OS) in AAC and the neoplasia group (P = .002 and P = .016, respectively). There was no significant difference in OS and risk of death in PDAC (P > .05) with respect to HMGA2 positivity. CONCLUSION: High-mobility group A protein 2 is a helpful immunohistochemical marker in differentiating CP from PDAC. It also plays a role in EMT and may serve as a potential new prognostic agent and therapeutic target in tumors of the periampullary region, especially AAC.

Lateral lymph node involvement presents another challenge in rectum cancer in the age of neoadjuvant chemoradiotherapy + total mesorectal excision: an evaluation of survival outcomes.

PURPOSE: In the last decades, total mesorectal excision (TME) and neoadjuvant chemoradiotherapy (nCRT) have produced an undeniable improvement in the treatment of rectal cancer. However, local recurrence is still an important problem, and the effect of lateral lymph node (LLN) involvement on local recurrence is a controversial issue. The aim of this study was to investigate the effects of LLN status on local recurrence and survival in rectal cancers treated with nCRT + TME. METHODS: Clinical features, pre- and post-nCRT lateral pelvic region imaging, long-term local recurrence, and the survival outcomes of 114 patients who underwent nCRT + TME for rectal cancer were evaluated. RESULTS: On MRI before nCRT, 20 (17.5%) patients had lateral lymph nodes (LLN+), and 94 (82.5%) patients had no lymph nodes in the lateral pelvic compartments (LLN-). Local recurrences at 1 year in LLN+ and LLN- patients were 3 (15.8%) and 2 (2.3%), respectively (p=0.039). Five-year local recurrence-free survival rates and the mean duration of recurrence-free survival in LLN+ and LLN- patients were 56.2%, 42.6 months, and 87.3% 66.9 months, respectively (p=0.001). Disease-free survival and overall survival were shorter in LLN+ patients, but the difference was not statistically significant (p=0.096 and p=0.46, respectively). In the multivariate analysis, LLN involvement was determined to be an independent risk factor for local recurrence-free survival (Hazard Ratio 4.54, p=0.003). CONCLUSION: Lateral lymph node involvement causes local recurrence to remain high after nCRT + TME. LLN status should be considered in treatment planning. Further studies are needed to define precise criteria for LLN involvement and the effect of LLND on local recurrence and survival.

Adjunctive role of immunohistochemical expression of Nucleostemin in differentiation of grade II and III diffuse astrocytomas.

AIMS: Astrocytomas are common tumors and grade is an important parameter in determining the treatment modalities. Tumor proliferation activity should be determined for the differentiation of grades II and III tumors. In difficult cases, an auxiliary parameter is required. Nucleostemin (NS) is nucleolar Guanosine triphosphate (GTP)-binding protein 3. It has important roles in cell proliferation, cell cycle regulation, self-renewal, and apoptosis. In this study, we investigated whether the level of NS expression is different in grades II and III astrocytomas. SETTINGS AND DESIGN: Adults diagnosed with grades II and III astrocytomas were included in the study. MATERIAL AND METHODS: Paraffin blocks that best reflected tumor morphology were studied via immunohistochemical staining for NS. Only nuclear staining was evaluated; cytoplasmic staining was not considered. STATISTICAL ANALYSIS USED: Fisher's exact test, continuity corrections, and Pearson's Chi-square tests were used in the crosstabs. The survival analysis was based on the Kaplan-Meier method. RESULTS: Only 20% (6/30) of grade II tumors had high intensity staining, while 54,2% (13/24) of grade III tumors had high staining intensity. NS was significantly more intense in grade III tumors than grade II tumors. In cases with high NS expression, survival was significantly shorter than the cases with low expression. CONCLUSION: NS is significantly higher expressed in grade III tumors than grade II tumors. In difficult cases, it can be used as a useful proliferation marker in the differentiation of grades II and III astrocytomas.

Effects of astaxanthin on metastasis suppressors in ductal carcinoma. A preliminary study.

BACKGROUND: Breast cancer (BC) is a major public health problem diagnosed in more than 2 million women worldwide in 2018, causing more than 600,000 deaths. 90% of deaths due to breast cancer are caused by metastasis. Metastasis is a complex process that is divided into several steps, including separation of tumor cells from the primary tumor, invasion, cell migration, intravasation, vasculature survival, extravasation, and colonization of the secondary site. Astaxanthin (AXT) is a marine-based ketocarotenoid that has many different potential functions such as anti-oxidant, anti-inflammatory and oxidative stress-reducing properties to potentially reduce the incidence of cancer or inhibit the expansion of tumor cells. This study aims to investigate the effects of astaxanthin as a new metastasis inhibitor on T47D human invasive ductal carcinoma breast cancer cell. MATERIAL AND METHODS: To investigate the effects of the astaxanthin as a new metastasis inhibitor on T47D cell, expression levels of anti-maspin, anti-Kai1, anti-BRMS1, and anti-MKK4 were examined by western blot. Also, we evaluated differences of these suppressors expression levels in tissue sections of 10 patients diagnosed with in situ and invasive ductal carcinoma by immunohistochemistry method. RESULT: 250 µM astaxanthin increased the activation of all metastasis suppressing proteins. Also, these metastasis suppressors showed higher expression in invasive ductal carcinoma tissues than in situ ductal carcinoma patients. CONCLUSION: We think that astaxanthin is a promising therapeutic agent for invasive ductal carcinoma patients. The effects of astaxanthin on metastasis in breast cancer should be investigated further based on these results. KEY WORDS: Breast, cancer, metastasis.

Role of Notch, IL-1 and leptin expression in colorectal cancer.

An increasing number of studies have shown that angiogenesis has an important role in the progression of cancer. The growth of a new network of blood vessels is crucial for tumor growth and metastasis, which is promoted by several proangiogenic factors. Leptin, an essential adipokine that is secreted from fat tissue, is one of these pro-angiogenic factors. It has been shown that the inhibition of leptin-induced angiogenesis resulted in decreased levels of vascular endothelial growth factor (VEGF)/VEGFR2, hypoxia inducible factor (HIF) 1α, NF-κB, IL-1 and Notch and reduced the tumor growth in breast cancer. Leptin induces angiogenesis in breast cancer either by upregulating VEGFR2 in endothelial cells or by increasing VEGF/VEGFR2 expression through the Notch, IL-1 and leptin crosstalk outcome (NILCO) pathway. NILCO is a novel mechanism that interacts with proinflammatory and proangiogenic signals, which are critical for cell proliferation and angiogenesis in cancer. Several studies have shown that components of NILCO may affect human cancer incidence and progression. However, to the best of our knowledge, the interactions between Notch, IL-1 and leptin in human colorectal cancer have not been yet studied at the molecular level. The aim of the present study was to investigate the expression levels of genes related to the NILCO pathway in human colorectal cancer specimens. The current results demonstrated that leptin, leptin receptor (ObR) b, Notch-1, Notch-4, IL-1α, IL-1ß, IL-1R, IL-6, JAK-2, STAT-1, STAT-3, VEGFA, VEGFR1, VEGFR2, TNF-α and NF-κB mRNA expression levels in the cancer tissue were increased compared with the normal tissue. No significant changes in the mRNA expression levels of Jagged-1, HIF-1α and TNF receptor 1 were observed. Western blotting revealed that the protein expression levels of IκB were increased in the cancer tissue compared with normal tissue, whereas HIF-1α and phosphorylated STAT-1 levels were decreased. IL-6 and VEGFA plasma concentrations were statistically raised and the leptin plasma concentration was also raised, although significantly, patients with cancer compared with control individuals. Together, the present findings indicated that Notch, IL-1 and leptin may serve a crucial role in the development of colorectal cancer.

Uncommon Childhood Unilateral Cervical Giant Thymic Cyst.

Cervical thymic cysts are rare and present in the first decade of life. They constitute 0.3% to 1% of congenital neck masses. Thymic tissue foci, which exist between the mandible and the mediastinum, can be found at the descent of the thymic primordium. Thymic cysts should be considered in pediatric patients who present with cervical neck masses. The diagnosis of thymic cysts can only be made by histopathologic examinations. In recent years, the number of reports of thymic cyst cases have increased, one possible cause being the heightened awareness of thymic cysts among pathologists.

Which of the fluorine-18 fluorodeoxyglucose positron emission tomography/computerized tomography parameters are better associated with prognostic factors in breast cancer?

The aim of the present study is to evaluate the relationship between the immunohistochemical and histopathological prognostic factors and the metabolic fluorine-18 fluorodeoxyglucose positron emission tomography/computerized tomography (PET/CT) parameters in breast cancer.A total of 94 female patients diagnosed with primary breast cancer (median age: 54.5 years, 94 lesions with size >15 mm) who underwent PET/CT imaging before any treatment were enrolled to this retrospective study. Maximum and average standardized uptake values (SUVmax and SUVavg), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and tumor/liver uptake ratio (TLR) of the primary tumors were calculated and compared between various histopathological and immunohistochemical prognostic factor groups.All metabolic parameters were associated with clinical T stage, metabolic M stage, and nuclear grade. The MTV, TLG, and TLR were significantly higher in patients with suspected lymph node metastasis. There were significant differences according to estrogen receptor and human epidermal growth factor-2 status in the metabolic values other than MTV. In case of progesterone receptor, there were significant differences in the metabolic characteristics except for the MTV and TLG values. The Ki-67 labeling index was moderately correlated with SUVmax, SUVavg, and TLR. All metabolic characteristics except MTV were significantly higher in triple negative breast cancer compared with the other molecular subtypes.The results of the present study suggest that the TLG and TLR values have stronger associations with several prognostic factors in breast cancer (BC) compared with other metabolic parameters.

Efficacy of Platelet-Rich Plasma on Fat Grafts in the Repair of Tympanic Membrane Perforations: An Experimental Study.

OBJECTIVE: We investigated the use of autologous platelet-rich plasma (PRP) to improve the success rate of fat graft myringoplasty in perforated tympanic membranes of rats. MATERIALS AND METHODS: A total of 20 healthy Wistar albino female rats were divided into two groups. In Group 1, the left tympanic membranes were perforated and grafted with a fat graft that was harvested from the inguinal region. In Group 2, the left tympanic membranes were perforated, and a fat graft was also harvested from the inguinal region. Then, the fat was soaked in 0.5 mL PRP and grafted at the perforation. After the procedure, the rats were examined, and the graft situation was assessed at 3, 5, 7, 10, and 14 days. All of the rats were sacrificed 21 days after perforation, and a histopathological examination was made. RESULTS: We compared fat graft histopathological and otomicroscopic findings between the groups. While we did not observe graft rejections in Group 2, we saw 1 case of graft rejection in Group 1. In the histopathological examination, PRP prevents fat graft resorption by the terms of the adipocyte area, granulation tissue area, and vacuolization area. CONCLUSION: This study demonstrated the efficacy of fat grafts prepared with PRP on rat tympanic membranes. The fat graft with PRP did not statistically improve the success rate compared to the graft without PRP. Histopatologic findings of the study showed that PRP prevents fat graft resorption. Further studies are needed to further examine the advantages of the graft with PRP.

Superimposed Segmental Manifestation of Juvenile Amyopathic Dermatomyositis in a 9-year-old Boy.

Dermatomyositis is a well-known autoimmune disorder. On the other hand, juvenile amyopathic dermatomyositis (JADM) occurs rather rarely. Here, we report an unusual case in a 9-year-old Turkish boy showing a unilateral linear inflammatory skin lesion that was followed, after 16 months, by the appearance of bilateral disseminated features JADM.

WITHDRAWN: Bilateral painless testicular mass, acute uveitis and annular cutaneous lesions: an unusual presentation of sarcoidosis and literature review.

Ahead of Print article withdrawn by publisher.

Nephrogenic adenoma of the urinary tract: A 6-year single center experience.

BACKGROUND: Nephrogenic adenoma is an uncommon benign lesion that occurs at several sites in urinary tract, from the renal pelvis to urethra, with the highest frequency in urinary bladder. Nephrogenic adenoma displays a broad spectrum of architectural and cytological features. Hence, recognition of its characteristic histopathological features is needed to distinguish this lesion from its mimickers. MATERIALS AND METHODS: A retrospective series of 21 cases of nephrogenic adenoma in 18 patients, which were diagnosed in our department between 2010 and 2016, were analyzed. All histological slides were reviewed by two pathologists and the diagnosis of each case was confirmed. Immunohistochemistry was performed for PAX-8 in all cases. CK7, PAX-2, PSA, p53, p63, GATA-3 and α-methylacyl-CoA racemase (AMACR) were applied in problematic cases. RESULTS: The most common location of the lesion was urinary bladder (14 patients) followed by renal pelvis (2 patients), ureter (1 patient) and urethra (1 patient). A history of urothelial carcinoma and repeated TUR procedures were observed in 12 patients. There were 2 pediatric patients aged 3 years. Both of them had undergone previous urosurgery because of megaureter in one and bladder exstrophy in the other. Other clinical antecedents included bladder diverticulum (1 patient), cystitis (1 patient) and nephrolithiasis (1 patient). Recurrence of lesion was seen in two patients (once in one case and twice in the other one). The median time to disease recurrence in these patients was 11 months (range, 2-20 months). Histologically, the lesions exhibited various morphological findings, with mixed (15 cases, 71.4%), pure tubular (3 cases, 14.3%), pure papillary (2 cases, 9.5%) and pure flat (1 case, 4.8%) growth patterns. Of the 15 cases with mixed patterns, 8 cases were tubulocystic and flat, 3 cases were tubular and flat, 2 cases were tubular, papillary and flat, 1 case was tubulocystic, papillary and flat, and 1 case was tubular and papillary. Flat pattern was observed in 15 cases (71.4%). It was seen in association with other patterns in 14 cases (mixed morphology) and purely in 1 case. Our findings suggested that the flat pattern is a frequent finding in nephrogenic adenomas. Notably one case in this series showed superficial extension into bladder muscularis propria. CONCLUSIONS: Histologically nephrogenic adenoma may simulate a variety of malignancies. Awareness of characteristic morphologic features of nephrogenic adenoma is needed to diagnose this lesion correctly.

Adrenocortical Oncocytic Carcinoma: A Case Report and Review of the Histopathologic Diagnostic Criteria.

Oncocytic tumors are rare in the adrenal gland. The histopathological diagnosis of adrenocortical carcinoma is difficult due to the lack of precise diagnostic criteria for malignancy. A 44-year-old man was admitted to our hospital with left flank pain. Radiologically an adrenal mass was detected. After the excision and histopathologic evaluation of the mass, a diagnosis of adrenocortical oncocytic carcinoma was made. At least one of the features of more than 5 mitoses in 50 high power fields, atypical mitotic figures or venous invasion is required for the diagnosis of malignancy in adrenocortical tumors. It has been suggested that tumors that have more than one of the minor criteria of large size ( > 10 cm or > 200 gr), necrosis, capsular or sinusoidal invasion, should be evaluated as having uncertain malignant potential.

Abdominal Inflammatory Myofibroblastic Tumor: A Rare Case.

An inflammatory myofibroblastic tumor, also known as inflammatory pseudotumor, is a rare neoplasm characterized by myofibroblastic spindle and inflammatory cells that cause masses in many sites of body. It is often benign, but in some cases neoplastic transformation has been reported as a result of aggressive growing. In our case, an inflammatory myofibroblastic tumor was reported by biopsy of a 25 × 15 cm abdominal mass. HOW TO CITE THIS ARTICLE: Tastekin F, Ersoy M, Temel T, Ozgenel SM, Canaz F, Özakyol A. Abdominal Inflammatory Myofibroblastic Tumor: A Rare Case. Euroasian J Hepato-Gastroenterol 2016;6(2):183-185.

A Case Report of Ulcerative Colitis Induced by Therapy of Colorectal Carcinoma.

Although patients with ulcerative colitis have an increased risk for colon cancer which is associated with disease activity, location of involvement or the accompanying primary sclerosing cholangitis, ulcerative colitis induced by resections for colorectal carcinoma or chemotherapy drugs are very rare as case presentations in the literature. Fifty-nine year-old female patient with the diagnosis of sigmoid colon carcinoma have been developed ulcerative colitis 2 months after low anterior resection and oral capecitabine treatment. Development of colitis after colon cancer may be associated with some causes as mutual genetic factors that take part at the pathophysiological mechanisms liable from occurrence of ulcerative colitis and colorectal carcinoma, chemotherapy agents, perioperative stress and underlying silent ulcerative colitis. It is unclear which role is certain. Increasing reports like this case will be useful in resolving this issue. HOW TO CITE THIS ARTICLE: Temel T, Ozgenel SM, Canaz F, Arik D, Tokmak S, Ozakyol AH. A Case Report of Ulcerative Colitis Induced by Therapy of Colorectal Carcinoma. Euroasian J Hepato-Gastroenterol 2015;5(2):115-117.

The effects of bupivacaine injection and oral nitric oxide on extraocular muscle in the rabbit.

AIM: Nitric oxide (NO) plays a key role in muscle regeneration, which is the primary response, observed during bupivacaine-induced extraocular muscle (EOM) hypertrophy. Our aims were to investigate the effects of bupivacaine injection into the rabbit EOM and the interaction with NO. MATERIALS AND METHODS: Superior rectus (SR) muscles of 24 New Zealand albino rabbits were studied. Single muscle twitch tension (SMTT) and tetanic muscle tensions at 50, 75, and 100 Hz were recorded using a 15 V stimuli. The rabbits were equally allocated into three groups. Measurements were performed without any drug treatments in group 1. In groups 2 and 3, bupivacaine, 0.5 ml of a 0.50 % solution, was injected into the EOM, and after 21 days, measurements were performed. Oral isosorbide dinitrate (NO donor) at 20 mg/day was given each day prior to measurements in group 3. RESULTS: SMTTs were 69.9 (66.7-77.6), 187.7 (114.9-252.1) and 204.2 (135.3-311.6) mg in groups 1, 2, and 3 respectively. SMTTs for both groups 2 and 3 were significantly higher than that for group 1 (p < 0.05). Compared with group 1, group 2 exhibited a 3.8-11.7 % increase in the tetanic tensions at 50, 75, and 100 Hz, but none of these differences were statistically significant. The increase was 47.5-137.5 % in group 3 relative to group 2, and the differences were statistically significant except at 100 Hz. The enlargement of the muscle fibers after bupivacaine injection was shown histopathologically. CONCLUSION: Bupivacaine injection increased the EOM tension in rabbits to some extent. NO augmented the effect of bupivacaine.

Survival of diced and block cartilage grafts in combination with injectable calcium hydroxylapatite.

OBJECTIVES/HYPOTHESIS: Dorsal nasal irregularities after trauma, and various procedures such as excessive nasal hump resection, are major problems for patients who have undergone rhinoplasty. Many grafts have been described for the correction of dorsal nasal irregularities. In this study, we used an injectable implant, in combination with diced or block cartilage grafts, to test the efficacy of injectable calcium hydroxylapatite on the survival of diced or block cartilage grafts. STUDY DESIGN: Prospective, controlled, parallel group animal study. METHODS: Fourteen New Zealand white rabbits were used. Block cartilage and diced cartilage grafts, alone and in combination with injectable calcium hydroxylapatite, were placed subcutaneously in the rabbits' dorsal thoracolumbar region. On the 90th day following surgery, the graft areas were extracted immediately after the rabbits were sacrificed. Pathological examination was conducted on all specimens. RESULTS: The pathologic and histochemical findings were compared between groups. There was chronic inflammation observed in all of the groups. However, none of the groups had metaplastic bone formation or calcification. The group that received diced cartilage in combination with the injectable implant received the highest scores for peripheral chondrocyte proliferation, matrix collagen, elastic fiber, and proteoglycan content (P < 0.05). A comparison of the block and diced cartilage grafts revealed that peripheral chondrocyte proliferation was more pronounced in the diced cartilage grafts (P < 0.05). CONCLUSION: The use of calcium hydroxylapatite in combination with diced cartilage grafts does not have any long-term negative effects on chondrocyte viability.

The type of lymphocyte infiltration near urothelial carcinoma is diagnostic for chronic lymphocytic leukemia.

T-lymphocytic infiltration near the tumor site is an expected immune response in bladder cancers. However, reports of patients with bladder cancer exhibiting small lymphocytic infiltration of the bladder tissue are very rare in the literature. Here, the patient was presented to our group with hematuria, but subsequently diagnosed as exhibiting invasive bladder cancer and chronic lymphocytic leukemia with suspicious lymphocytic infiltration in a transurethral resection specimen. This case emphasizes the importance of lymphocytic infiltration's nature near urothelial carcinoma.

Unusual renal manifestation of Caroli disease: AA amyloidosis.

Congenital hepatic fibrosis is a fairly uncommon disorder and it is usually associated with other fibropolycystic disorders, including renal involvement. Main clinical features are hepatic fibrosis, portal hypertension, and renal cystic disease. There are multifocal saccular dilatations of segmental bile ducts, usually with accompanying calculi formation and recurrent bacterial cholangitis. Renal cystic disorders are common complications of Caroli disease (CD), but renal amyloidosis is fairly uncommon. We present a patient who was diagnosed with CD at the age of 31 years and in whom renal AA amyloidosis developed at the age of 45 years due to recurrent bacterial cholangitis.

Prognostic significance of galectin-3 and cyclin D1 expression in undifferentiated nasopharyngeal carcinoma.

Galectin-3 was shown to be involved in various biological events, including cell growth, adhesion, differentiation, angiogenesis, apoptosis, tumorigenesis, and metastasis. The prognostic significance of galectin-3 expression has already been evaluated in several cancers. However, its prognostic role has not been investigated in nasopharyngeal carcinoma. The loss of cell cycle control is one of the critical steps in the development of nasopharyngeal carcinoma. Cyclin D1 is one of the key proteins involved in cell cycle control and is essential for G1/S phase transition. Overexpression of cyclin D1 has been observed in several human cancers. In the present study, the expression of galectin-3 and cyclin D1 was evaluated with immunohistochemical analysis in 45 patients diagnosed as undifferentiated nasopharyngeal carcinoma and expression of these proteins was correlated with clinicopathological parameters and prognosis. Multivariate analysis showed that older age (>50 vs. ≤50) (P = 0.028), distant metastasis at presentation (M(1) vs. M(0)) (P = 0.001), and increased galectin-3 expression (>5% vs. ≤5%) (P = 0.025) were independently correlated with poor overall survival. We found no statistically significant correlation between cyclin D1 immunoexpression and disease outcome. The Spearman's correlation coefficient revealed a significant correlation between galectin-3 and cyclin D1 expression (r = 0.425; P = 0.004). Our findings suggested that the immunohistochemical analysis of galectin-3 might be useful in predicting prognosis in nasopharyngeal carcinoma.