Ethyl pyruvate treatment ameliorates pancreatic damage: evidence from a rat model of acute necrotizing pancreatitis.

INTRODUCTION: Ethyl pyruvate (EP), a natural flavoring and fragrance agent, has been shown to exert anti-inflammatory and antioxidant actions. We tested the potential beneficial effects of EP in a rat model of acute necrotizing pancreatitis (ANP), a serious condition with a significant inflammatory explosion and oxidative stress. MATERIAL AND METHODS: Fifty-two adult male Sprague-Dawley rats were divided into four groups: sham + saline, sham + EP, ANP + saline, and ANP + EP. The ANP was induced by glycodeoxycholic acid and cerulein. Animals were sacrificed at 48 h and biochemical, hematological, and histological markers of ANP and inflammation were assessed. The extent of mortality, systemic cardiorespiratory variables, pancreatic microcirculation, renal/hepatic functions, acinar cell injury and enzyme markers for pancreas and lung tissues were investigated. RESULTS: The EP-treated ANP group presented significantly lower mortality than the untreated ANP group (44% (7/16) vs. 19% (3/16), respectively, p < 0.05). Administration of EP resulted in significantly lower levels of IL-6 (ANP + saline: 5470 ±280 vs. ANP + EP: 2250 ±180 pg/ml, p < 0.05). Compared with the ANP group, the ANP + EP group had a lower pancreatic necrosis score (1.45 ±0.2 vs. 0.96 ±0.2, p < 0.05). Moreover, intraperitoneal EP administration had a positive effect on most indices of pancreatitis (amylase and alanine transaminase levels) and lung damage (except lung malondialdehyde levels) as they decreased towards baseline values. CONCLUSIONS: The results from this experimental study indicate that EP, a nontoxic chemical approved by the Food and Drug Administration as a food additive, provides positive effects on the course of pancreatitis, suggesting potential usefulness in management of ANP.

Characteristics of Special Type Breast Tumors in Our Center.

OBJECTIVE: Breast cancer is a heterogeneous disease with different histological types. Ductal breast cancer constitutes the vast majority of the breast cancers. However limited data are present in the rest of breast cancers called special or rare type breast cancers. Here in this study, we tried to describe the clinical features of special type breast cancers in our center. MATERIALS AND METHODS: Retrospective descriptive study was performed in Kocaeli University School of Medicine, Department of General Surgery between January 2000 and January 2016. Women diagnosed with primary breast cancer other than ductal carcinoma were included to the study. In total, 101 patients were evaluated according to histologic types, molecular types, Tumor Node Metastasis (TNM) stages, and grades. Survival of the patients was also evaluated. RESULTS: Medullary and metaplastic types showed basal type; tubular, mucinous, micropapillary carcinoma, cribriform, lobular and apocrine tumors showed luminal type molecular pattern. Neither the existence of ductal carcinoma nor any histologic types had any effects on survival. Apocrine tumors were presented in younger ages. CONCLUSION: Histologic types of breast cancer are closely related with the molecular types of the breast cancer. Tumor size, grade, stage of the disease can show differences among histological types which might be due to the genetic background, late onset or limited number of patients. In order to achieve more significant results, multicenter national studies are needed.

The anti-inflammatory effect of hydrogen sulphide on acute necrotizing pancreatitis in rats.

OBJECTIVE: The aim of this study was to investigate the dose-dependent anti-inflammatory effect of the Hydrogen sulfidedonor sodiumhydrosulphide on acute necrotizing pancreatitis in rats. MATERIAL AND METHODS: A total of 42 male Sprague-Dawley rats were divided into 4 groups: sham+saline (group 1), sham+NaHS (group 2), acute necrotizing pancreatitis+saline (group 3), and acute necrotizing pancreatitis+NaHS (group 4). Acute pancreatitis was induced in rats in groups 3 and 4 with the infusion of glycodeoxycholic acidinto the biliopancreatic canal and infusion of cerulein parenterally. In group 4, 10 mg/kg NaHS was administered intraperitoneally after cerulein infusion. Tests for liver and kidney function, interleukin-6, lactate dehydrogenase in bronchoalveolar lavage, and malonyaldehyde and myeloperoxidase activities in pancreas and lung tissue were performed, and histopathologic examination of pancreas was conducted. RESULTS: In groups 3, a significant increase in amylase, alanine aminotransferase, urea, interleukine-6, lungmalondialdehyde and myeloperoxidase activities, pancreas myeloperoxidase activity, edema, and necrosis in pancreas tissue and a significant decrease in serum calcium levels were detected (p<0.05). In group 4, addition of NaHS resulted in a significant decrease in lactate dehydrogenase level in bronchoalveolar lavage, amount of urea, lung myeloperoxidase activity, and pancreatic edema (p<0.05). CONCLUSION: Although not in pancreatic necrosis, hydrogen sulphide has an anti-inflammatory effect especially in the inflammatory process in lung and edema in pancreasin acute necrotizing pancreatitis at particular doses. With further studies evaluating the anti-inflammatory effects of hydrogen sulphide, we believe it can be used in the treatment of edematous acute pancreatitis and the related complications in lungs.

The distribution of CD44+/CD24- cancer stem cells in breast cancer and its relationship with prognostic factors.

PURPOSE: The purpose of this study was to investigate the correlation between the percentages of CD44+/CD24- cancer stem cells (CSCs) and the clinicopathological and prognostic factors in breast cancer patients. METHODS: Twenty three women who underwent surgery for breast cancer were enrolled in this study. The mean age of the patients was 46.65 years and 52% had early-stage disease. Tumor tissues obtained during surgery were digested enzymatically. CD44+/CD24- cell phenotype was identified by using surface marker antibodies and percentages were determined by surface marker expression of the cells. RESULTS: Sixty five percent of the tumors were positive for estrogen (ER)/ progesterone receptors (PR) and 38% of the tumors were positive for HER-2. All of the patients with hormone receptor positive tumors had ER positive tumors, while only 11 patients had PR positive breast cancer. CD44+/CD24- cells were present in all tumor tissues. The mean proportion of the CD44+/CD24- cells was 1.43±1.6. The mean percentages of CD18+ cells and MUC1+ were 27.9±26.5% and 6.07±11.34%, respectively. The percentage of CD18+ cells was significantly higher in PR positive tumors (p=0.042). There was no significant correlation between the percentage of CD44+/CD24- cells and clinicopathological features. CONCLUSION: This study showed that CD44+/CD24- cells were present in all tumor tissues. The percentage of CD44+/CD24- cells was higher in early-stage disease, yet without statistical significance. No correlation was found between prognostic factors and the percentage of the CD44+/CD24- cells.

An Unusual Presentation of Gout: Tophi in the Middle Ear.

Gout is a common metabolic disease and is characterized by episodic acute and chronic arthritis caused by the deposition of monosodium urate (MSU) crystals in joints and connective tissues. The most commonly involved joint is the first metatarsophalangeal joint. It may also present with nonspecific complaints caused by gouty tophi in unusual sites of the body such as the spine, bone, and middle ear. Such involvements can be disabling and impair the quality of life. In this report, we describe the case of a patient who had complaints of hearing loss and otorrhea. A 34 year-old male patient presented with complaints of recurrent otorrhea and hearing loss for several months. He had no history of joint pain or constitutional symptoms at the time of admission. An otoscopic examination of the left ear revealed subtotal tympanic membrane perforation, and white middle ear plaques were detected. The patient underwent intact canal mastoidectomy under general anesthesia, and middle ear sclerosis was determined as Wieling Kerr classification type 2. Postoperative histopathologic examination of the specimen revealed amorphous eosinophilic deposits within fibrous stroma and tophi containing negatively birefringent MSU crystals by polarized light. After the histopathologic diagnosis of gout, the patient was assessed for peripheral joint involvement. He had no radiographic abnormalities. The patient was administered a serum urate-lowering therapy, given a low purine diet, and followed with the diagnosis of tophaceous gout. Unusual localizations of gouty tophi have been reported in the literature. Gouty tophi should also be considered in the differential diagnosis of middle ear masses alongside common pathologies.

N-acetylcysteine amid reduces pancreatic damage in a rat model of acute necrotizing pancreatitis.

BACKGROUND: Inflammatory explosion and oxidative stress are important mechanisms of injury in acute necrotizing pancreatitis (ANP). This study investigated the effects of N-acetylcysteine amid (NACA), a novel cell-permeant antioxidant with anti-inflammatory activity, on experimental ANP in rats. MATERIALS AND METHODS: Fifty-two adult male Sprague-Dawley rats were used, and ANP was induced by cerulein. The animals were divided into four groups which were sham + saline, sham + NACA, ANP + saline, and ANP + NACA. NACA (2.2 mg/kg, i.p) was administered for 6 h, after the induction of ANP. The extent of acinar cell injury, mortality, systemic cardiorespiratory variables, functional capillary density, renal/hepatic functions, and changes in some enzyme markers for pancreas and lung tissues were investigated. RESULTS: Induction of ANP increased mortality from 0% in the sham group to 43.75% in the ANP + saline group (P < 0.05), and administration of NACA significantly reduced mortality to 12.5% (P < 0.05). Induction of ANP also caused increases in pancreatic necrosis, serum amylase, alanine aminotransferase (ALT), interleukin-6, LDH in bronchoalveolar lavage fluid, serum urea, tissue myeloperoxidase in pancreas and lung tissues and malondialdehyde. There was less pronounced increase in these parameters in NACA treated group. Compared with ANP group, ANP + NACA group had lower levels of pancreatic necrosis (0.5 ± 0.2 versus 1.45 ± 0.2, P < 0.05) and inflammation (0.6 ± 0.2 versus 1.29 ± 00.3, P < 0.05) scores. CONCLUSIONS: Administration of NACA significantly decreased the ANP-induced mortality and also provided significant improvements in hemodynamic changes. The obtained positive effects of NACA on the course of pancreatitis indicates its potential usefulness in the management of ANP.

Nonsyndromic Juvenile Myelomonocytic Leukemia With PTPN11 Mutation in a 9-Year-old Girl.

A 9.5-year-old girl with malaise, fever, massive hepatosplenomegaly, anemia, leukocytosis (37.9 × 10(9)/L), monocytosis (1.48 × 10(9)/L), and thrombocytopenia is presented. Hemoglobin F was increased (18%). Bone marrow erythroid/myeloid ratio was 40/1 with 7% myeloblast and 5% monocyte suggesting erythroleukemia or juvenile myelomonocytic leukemia (JMML). The patient had a fulminant course with respiratory compromise and died in 2 weeks before heterozygous somatic mutation in the PTPN11 gene was shown. JMML must be considered also in the patients older than 6 years. A cytopenic phase may precede JMML. Leucocytosis may be transient and there may be predominance of erythroid precursors in the bone marrow.

Prognostic factors and treatment results of pediatric Hodgkin's lymphoma: A single center experience.

The aim of this study was to assess the demographic, clinic data, prognostic factors and treatment/follow-up results of children who were diagnosed with Hodgkin lymphoma and followed in our center of Pediatric Oncology, Kocaeli University Medical Faculty, Kocaeli, Turkey, for 10 years. This retrospective study evaluated 41 patients with Hodgkin lymphoma who were younger than 18 years-old. All patients were treated with risked adapted ABVD (Adriamycin, Bleomycin, Vincristine, Dacarbazine) chemotherapy and also received involved field radiotherapy. Thirty-two patients (78%) were males and 9 (22%) were females, with a mean age of 10.7±4.0 years. The histopathological diagnosis was mixed cellular type in 51.2% of the patients. B symptoms (unexplained fever, unexplained weight loss, drenching night sweats) were present in 53.7% of the patients and 36.6% of the patients were at advanced stage at the time of the diagnosis. The 3-year overall and event-free survival rates were 88% and 5-year overall and event-free survival rates were 88%, 78%. Age, stage, treatment risk groups, presence of B symptoms and hematological parameters had no significant effect on overall and event-free survival in univariate analysis while bulky disease was the only significant factor on overall survival. Our treatment policy was succesful regarding the similar survival rates in the treatment risk groups, however novel treatment strategies adopting the early response with the reduction of adverse effects are planned in the near future.

Effects of glutamine alone on the acute necrotizing pancreatitis in rats.

BACKGROUND: The effects of the glutamine on the acute pancreatitis are controversial in the clinical and experimental studies. The aim of this study was to investigate the influence of glutamine alone on acute necrotizing pancreatitis (ANP) induced by glycodeoxycholic acid in rats. MATERIAL AND METHODS: Fifty-two male Sprague-Dawley rats weighing 300-350 g were used. Rats were divided into four groups as sham + saline, sham + glutamine, ANP + saline and ANP + glutamine. ANP in rats was induced by glycodeoxycholic acid. The extent of acinar cell injury, mortality, systemic cardiorespiratory variables, functional capillary density, renal/hepatic functions, and changes in some enzyme markers for pancreatic and lung tissue were investigated during ANP in rats. RESULTS: The induction of ANP resulted in a significant increase in the mortality rate, pancreatic necrosis, and serum activity of amylase, alanine aminotransferase, interleukin-6, lactate dehydrogenase in bronchoalveolar lavage fluid, serum concentration of urea, and tissue activity of myeloperoxidase and malondialdehyde in the pancreas and lung, and a significant decrease in concentrations of calcium, blood pressure, urine output, pO2, and functional capillary density. The use of glutamine alone improved these changes. CONCLUSIONS: Glutamine demonstrated beneficial effect on the course of ANP in rats. Therefore, it may be used by itself in the treatment of acute pancreatitis.

Hereditary Cystinosis Detected by CD68 Staining of the Bone Marrow Biopsies of 2 Siblings.

Cystinosis is an autosomal recessive lysosomal storage disease. We present 2 siblings in whom cystinosis was detected by CD68 immunohistochemical analysis of bone marrow biopsies. The older patient was a 6-year-old boy who had been receiving erythrocyte suspension therapy for 5.5 years because of low hemoglobin levels. The patient was admitted to our hospital because of hepatomegaly, anemia, and thrombocytopenia and underwent a trephine bone marrow biopsy based on a preliminary diagnosis of lipid storage disease. Macrophage-like cells were observed in the hematoxylin/eosin-stained sections. These cells were stained for CD68 to confirm that they were macrophages. Some crystalline structures were seen in the cytoplasm of the macrophages after CD68 staining. These structures were thought to be cystine crystals. The diagnosis of cystinosis was confirmed by a clinical assessment. The 1-year-old sibling of the patient was also examined; this sibling exhibited renal disease and had a family history of consanguineous marriage. Cystinosis was also detected in this sibling by clinical assessment and staining of the patient's trephine bone marrow biopsy for CD68. The staining of the bone marrow biopsies for CD68 enabled the patient and his sibling to be diagnosed with cystinosis; these patients were not correctly diagnosed over the previous 6-year period. No similar report was found in the literature regarding this topic.

Effects of clotrimazol on the acute necrotizing pancreatitis in rats.

This study aims to investigate the influence of clotrimazol (CLTZ) on acute necrotizing pancreatitis (ANP) induced by glycodeoxycholic acid in rats. Rats were divided into five groups as sham + saline, sham + CLTZ, sham + polyethylene glycol, ANP + saline, and ANP + CLTZ. ANP in rats was induced by glycodeoxycholic acid. The extent of acinar cell injury, mortality, systemic cardiorespiratory variables, functional capillary density (FCD), renal/hepatic functions, and changes in some enzyme markers for pancreatic and lung tissue were investigated during ANP in rats. The use of CLTZ after the induction of ANP resulted in a significant decrease in the mortality rate, pancreatic necrosis, and serum activity of amylase, alanine aminotransferase, interleukin-6, lactate dehydrogenase in bronchoalveolar lavage fluid, serum concentration of urea, and tissue activity of myeloperoxidase, and malondialdehyde in the pancreas and lung and a significant increase in concentrations of calcium, blood pressure, urine output, pO2, and FCD. This study showed that CLTZ demonstrated beneficial effect on the course of ANP in rats. Therefore, it may be used in the treatment of acute pancreatitis.

Value of autofluorescence in video-assisted thoracoscopic surgery in pleural diseases.

BACKGROUND: Autofluorescence (AF) examination in thoracoscopy has not been used frequently. Here, our aim was to determine whether AF examination contributes additional information to white-light (WL) examination when attempting to detect malignant pleural lesions. We also liked to know whether the effectiveness of WL and AF-mode combination would be different for various pathologies or lesions of the pleura. METHODS: It is a retrospective study. Thirty-three patients with unexplained exudative pleural effusions underwent AF-assisted video-assisted thoracic surgery (VATS). Patients' data from the files were evaluated. In each case, the pleural cavity was thoroughly examined under WL alone and then in AF mode. RESULTS: The sensitivity and specificity of AF-assisted VATS for detecting malignant pleural lesions were 78.7 and 85%, respectively, and there were 21.3% false negatives. In the group with metastatic pleural disease, AF VATS correctly identified all lesions as AF positive, whereas sensitivity was lower for the group with malignant mesothelioma. Seven lesions, which were not diagnosed under WL, were detected in AF mode. CONCLUSION: The overall sensitivity of AF-assisted VATS for detecting pleural malignancies was not satisfactory because of diagnostic errors in malignant mesothelioma. But it would be useful in detecting small malignant pleural lesions, which are not diagnosed under WL.

Sentinel lymph node biopsy with a gamma probe in patients with high-risk cutaneous squamous cell carcinoma: follow-up results of sentinel lymph node-negative patients.

OBJECTIVE: Lymphoscintigraphy (LS) and sentinel lymph node biopsy have become the standard of care for melanoma and breast cancer. However, the data on patients with cutaneous squamous cell carcinoma (SCC) are limited. We aimed to evaluate and identify the role of LS and sentinel lymph node biopsy in patients with high-risk cutaneous SCC. METHODS: Nineteen patients (13 men, six women; 47-87 years of age, mean age 67.5 ± 12.3) with SCC were included in the study. LS was performed on all patients after intracutaneous injection of Tc-99m nanocolloid. Primary lesions and sentinel lymph nodes (SLNs) were excised with the help of a gamma probe. RESULTS: A total of 26 SLNs and 32 secondary lymph nodes were imaged on LS and were marked. During surgery, 29 SLNs, 21 secondary lymph nodes and three nonactive lymph nodes were excised. In total, 53 lymph nodes were removed surgically. A histopathological study revealed that all lymph nodes were negative for metastasis. Patients were followed up for an average of 41.1 ± 22.2 months (7-80 months). Until the time of data collection, 14 patients were alive and had no regional lymph node or distant metastasis. Local recurrence was seen in only one patient. He was reoperated upon 38 months ago. CONCLUSION: The feasibility of determining SLNs using LS and an intraoperative gamma probe in patients with cutaneous SCC was shown. Unnecessary elective lymph node dissection and possible complications could be avoided in 19 patients.

Effect of heat shock protein-90 (HSP90) and vascular endothelial growth factor (VEGF) on survival in acute lymphoblastic leukemia: an immunohistochemical study.

BACKGROUND: The significance of vascular endothelial growth factor (VEGF) and heat shock protein-90 (HSP90) has received only limited attention especially in acute lymphoblastic leukemia (ALL). In this study, we assessed expressions of HSP90 and VEGF in bone marrow samples of patients with ALL and effect of these expression quantities on the mean overall survival. PATIENTS AND METHODS: Using immunohistochemical methods, we assessed expression of HSP90 and VEGF in 22 cases of ALL. RESULTS: Expression of HSP90 was detected in 19/22 (86.4%) and 3/22 (13.6%) of patients with ALL, for strongly positive and moderate-weakly positive, respectively. Negative HSP90 expression was not detected in patients with ALL. Expression of HSP90 in patients with ALL and in control group were statistically significant (P<0.001), however, did not reflect the mean overall survival (P=0.910). Mean OS was evaluated 992±181 and 724.8±88.2 days for moderate-weak and high HSP90 expression, respectively. VEGF expressions were not significantly different between ALL and control groups (P<0.087). We did not find any relationship between HSP90 and VEGF expressions in bone marrow specimens of patients with ALL. CONCLUSION: This study demonstrated that HSP90 expression grades in patients with ALL were significantly higher than that in controls and presence of strong HSP90 expression was associated with worse overall survival. VEGF expression in patients with ALL was not different from that in control samples. Determination HSP90 with immunohistochemical method in bone marrow can provide information about prognosis.

Effect of smoking on rat basilar artery: correlation with inducible nitric oxide synthase and endothelin converting enzyme-1.

AIM: Smoking is an extremely important risk factor for subarachnoid hemorrhage and seems to increase rupture risk of unruptured aneurysms by accelerating their growth rate. The aim of the study was to investigate the effect of smoking on the luminal diameter with wall thicknesses of rat basilar arteries and to detect alterations of inducible nitric oxide synthase and endothelin-converting enzyme -1 in the endothelial cells. MATERIAL AND METHODS: Rats were divided into two groups. The level of middle pons slices were embedded in paraffin before they were stained with hematoxylin and eosin. Rabbit anti-human inducible nitric oxide synthase and endothelin converting enzyme-1 antibodies were used. RESULTS: Significant decrease of the vessel luminal diameter and increase of the vessel wall thickness were found in chronic smokers in our study. There was a linear and significant (p= 0,023, r =0,704) correlation between thickness of the wall and endothelin converting enzyme-1 immune reaction. Correlation was not found with inducible nitric oxide synthase (p > 0.05). CONCLUSION: This study on the comparison of vessel luminal diameter and vessel wall thickness with inducible nitric oxide synthase and endothelin converting enzyme-1 immune reactions revealed that the main effect of smoking on the vessel wall is associated with endothelin converting enzyme-1.

Acute lymphoblastic leukaemia presenting with acute renal failure: report of two cases.

Acute renal failure is a well-recognized complication of acute leukaemias. Howevcr, serious renal failure caused by leukaemic infiltration as a primary manifestation is unusual. Here we report two patients with acute lymphoblastic leukaemia presenting with acute renal failure due to leukaemic infiltration. The first patient died before the administration of specific therapy for leukaemia, whereas the second case recovered after chemotherapy. She was discharged without necessitating dialysis therapy.

Laryngeal adenoid cystic carcinoma in an adolescent.

Malignant tumors of the larynx are extremely rare in children and adolescents. Adenoid cystic carcinoma accounts for less than 1% of all malignant tumors in the larynx. We presented a 16-year-old girl with subglottic adenoid cystic carcinoma, whose symptoms of prolonged and exacerbating dyspnea had been attributed to asthma at another medical center. Indirect flexible and rigid laryngoscopy revealed a smooth mass in the subglottic region occupying 80% of the airway passage. The lesion was also confirmed by both CT and MRI. There was no lymphadenopathy in the neck. The patient was successfully treated by surgery and postoperative radiotherapy. Pathological staging was T4N0M0 according to the AJCC, 2003. During six years of follow-up, there was no evidence for local recurrence or regional and distant metastasis.