Could Amifostine Prevent Experimental Radiotherapy-Induced Acute Pericarditis?

BACKGROUND: Amifostine is a powerful antioxidant that is one of the documented three chemo-radio prototectants recommended for clinical use. There is no data exploring amifostine in prevention of acute pericardial damage. We aimed to investigate whether amifostine has protective effect against acute pericardial injury due to radiotherapy in an experimental rat model. METHODS: Twenty-four rats were divided into four groups: control group, radiotherapy-only group, amifostine-only group, radiotherapy+amifostine group. In groups receiving radiotherapy, hearts were irradiated with a Co 60 teletherapy device at a distance of 80 cm and 20 Gy at a depth of 2 cm. Thirty minutes before interventions, 200 mg/kg amifostine or same volume 0.9% NaCl were administered intraperitoneally. Subjects were sacrificed 24 hours after the procedure. Pericardial histopathological changes were investigated by light microscopy. RESULTS: There was focal inflammation of >= 50% in all rats exposed-to-radiotherapy. All groups receiving radiotherapy revealed a significant increase in pericardial inflammation compared to the groups that did not receive irradiation (p<0.05). There was no difference between the radiotherapy-only group and amifostine+radiotherapy group for pericardial inflammatory response (p>0.05). CONCLUSION: Acute pericarditis was detected in all rats receiving radiotherapy. There was no positive effect of amifostine administration before radiotherapy on acute pericardial inflammation.

PD-L1 expression in invasive solid papillary breast carcinomas.

Background: Invasive solid papillary carcinomas (ISPC) are rare malignant neoplasms in the classification of WHO 2019 breast tumors. Aims: We aimed to investigate the correlations between programmed cell death ligand-1 (PD-L1) expression status of tumor and immune cells and clinicopathological parameters by molecular classification of this rare morphological subtype. This study will contribute to the literature about the PD-L1 expression state of ISPCs for the first time. Material and Methods: The study included 19 invasive solid papillary carcinoma cases diagnosed between 2009 and 2019 in Pathology Department. Molecular subtyping was performed in 19 cases by immunohistochemical studies (ER/PR, Her-2/neu, Ki-67), and PD-L1 expression was evaluated in neoplastic and immune cells. Results: PD-L1 expression was detected in 4 (21%) cases, 3 (75%) of them were in luminal B and 1 (25%) were in the luminal A group. The correlation between molecular subtypes and PD-L1 expression was statistically significant (P = 0.016). Patients with PD-L1 expression had a higher Ki-67 index than patients without PD-L1 expression (P = 0.037). In addition, there was a statistically significant correlation between PD-L1 expressions of intratumoral lymphocytes and PD-L1 expressions of neoplastic cells (P = 0.004). Conclusions: While predicting the group that will benefit more from immunotherapy in solid papillary carcinoma cases, not only PD-L1 expression of tumor cells but also PD-L1 expression in tumor infiltrating lymphocyte (TIL) can help. In addition, PD-L1 staining rates of tumor cells as well as clinicopathological parameters (molecular subtype, high Ki-67 index, presence of TIL) can be predictive about immunotherapy.

Is It Rational to Perform Liver Resection for Patients with Intermediate and Advanced Stages of Hepatocellular Carcinoma?

This study aimed to investigate clinical characteristics of hepatocellular carcinoma and the outcome of our aggressive treatment policy which follows the Barcelona Clinic Liver Cancer (BCLC) guidance. In this study, we retrospectively analyzed data of 102 patients who were treated for hepatocellular carcinoma between January 2007 and October 2016. Male predominance (81.4%) and a median age of 61 years were observed. Cirrhosis was evident in 88.2 per cent of patients. Viral hepatitis (77.5%) was the most common underlying etiology. The majority of our patients (71.6%) were in BCLC B and C stages. Liver resection was performed in 53.4 per cent of patients in those stages. Transarterial chemoembolization was the leading interventional treatment. Overall survival rates at three and five years were 75 per cent and 75 per cent in BCLC 0, 69 per cent and 58 per cent in BCLC A, 50 per cent and 41 per cent in BCLC B, and 11 per cent and 11 per cent in BCLC C, respectively. The BCLC treatment algorithm should consider the role of liver resection also for intermediate stages.

Electrophysiological, functional and histopathological assessments of high dose melatonin on regeneration after blunt sciatic nerve injury.

The aim of this study was to determine the curative effects of high-dose (100 mg/kg) melatonin on peripheral nerve injury. Forty male Wistar albino rats were randomized into four groups as sham, vehicle, melatonin, and ischemia and their right sciatic nerves were exposed. The process was terminated in the sham group. In the other groups, nerve injury was induced by clip compression. The vehicle group was intraperitoneally administered ethanol 0.1 cc (melatonin solvent), while the melatonin group was intraperitoneally administered a single dose of melatonin (100 mg/kg). Following the surgery, sciatic nerve functional index (SFI) was measured using walking track analysis on days 7, 14, and 21, and latency, amplitude, and muscle action potentials (MAP) field values were measured using electroneuromyography (ENMG) on day 21. Histopathologically, edema, axonal degeneration, myelin damage, and inflammatory response were evaluated in all groups. SFI values were noted to be statistically significantly different among the vehicle, melatonin, and ischemia groups, and the melatonin group showed a faster recovery. In the ENMG evaluations, higher amplitude and field values in the melatonin group indicated that melatonin accelerated peripheral nerve recovery. Histopathologically, although fibers with loss of myelin were identified in the melatonin group, the myelin sheath was preserved in general and the axonal structure was noted to be normal. A single injection of high-dose melatonin was found to preserve myelin sheath, prevent axonal loss, and accelerate functional recovery during the nerve regeneration in peripheral nerve injury.

Systemic Amyloidosis in a Patient With Familial Mediterranean Fever and Hodgkin Lymphoma: A Case Report.

Systemic amyloidosis is a clinical manifestation of the accumulation of amyloid fibrils in tissues because of persistent acute phase elevation and chronic inflammation. Its most common causes are inflammatory diseases and malignancies. Here, we present a 12-year-old girl diagnosed with systemic amyloidosis and Hodgkin lymphoma (HL) who was also previously diagnosed with familial Mediterranean fever (FMF). Despite colchicine treatment for FMF, the patient had a persistent elevation of acute phase reactants and AA-type amyloid deposits were observed in a kidney biopsy. Anakinra, an interleukin-1 antagonist, was added to the treatment. Shortly after the diagnosis of amyloidosis, mediastinal lymphadenopathy was recognized, and she was also diagnosed with HL. A chemotherapy protocol of doxorubicin, bleomycin, vinblastine, and dacarbazine was initiated. After 6 cycles of the chemotherapy and 8 months of the anakinra treatment, no recurrence or residual malignancy was observed and proteinuria was decreased. To the authors' knowledge, this is the first reported case of systemic amyloidosis in the literature associated with both FMF and HL.

Comparison of the effect of isotretionin and alitretionin on endometriotic implants and serum vascular endothelial growth factor level: an experimental study.

OBJECTIVE: To compare the effects of alitretionin and isotretionin on endometrial peritoneal implants and serum vascular endothelial growth factor (VEGF) levels. STUDY DESIGN: Forty-eight female Sprague Dawley rats were used. Initially surgical rat endometriosis model was done. The endometrial implant volume was measured and rats were randomly divided into four groups. Group 1: Control group (rats did not get any drug but having endometriotic implants), group 2: rats receiving po isotretionin 10 mg/kg per day for 10 d, group 3: rats receiving po isotretionin 20 mg/kg per day for 10 d and group 4: rats receiving po alitretionin 80 mg/kg per day for 10 d. After 1-week medication, rats were sacrificed and size, histopathology of endometriotic implant and levels of VEGF were evaluated. RESULTS: Volumes of peritoneal endometrial implants were significantly decreased in Group 2 and Group 3 compared with initial values. However, there were no significant changes in histopathological scores and serum VEGF levels in all groups. CONCLUSIONS: This study finding may suggest the possible medical treatment modality of isotretionin on endometriosis. However, alitretionin (potent retinoid) does not have potent regressive effect on endometriotic implants as in isotretionin.

Nuclear morphometric findings in undetermined cytology: A possible clue for prediction of BRAF mutation in papillary thyroid carcinomas.

PURPOSE: To investigate the possible relationship between the nuclear morphometric characteristics (nuclear perimeter, roundness, nuclear area, and nuclear shape) and BRAF mutation status in papillary thyroid carcinoma cases with a prior diagnosis of undetermined cytology. MATERIALS AND METHODS: Total thyroidectomy specimens obtained from 48 patients with papillary thyroid carcinoma with a prior diagnosis of undetermined cytology were included. Morphometric analysis under light microscopy included measurements of the perimeter, shape factor, nuclear area, and roundness of thyrocyte nuclei from the cytological smear preparations. Mutational analysis, including immunohistochemistry and polymerase chain reaction, was performed in formalin fixed paraffin embedded tissue blocks. RESULTS: BRAF V600E mutation was detected in 7 of 48 cases (14.5%). The nuclear perimeter and nuclear area in mutated cases were significantly higher than the wild type (p = 0.005). Shape factor (p = 0.681) and roundness (p = 0.752) values did not significantly differ between the wild-type and mutant groups. No significant relationship was evident between BRAF expression and BRAF point mutation. CONCLUSION: In cases with positivity for BRAF mutation, the nuclear perimeter and nuclear area were significantly increased. These findings suggest that morphometric variables are predictive markers for papillary thyroid carcinoma cases with positivity for BRAF mutation. However, further trials on larger series are warranted to understand the significance and predictive value of nuclear morphometric analysis in these circumstances.

[A rare case: Kikuchi-Fujimoto disease]. / Nadir görülen bir olgu: Kikuchi-Fujimoto hastaligi.

Kikuchi-Fujimoto's disease (CFD) is a disease that usually exhibits self-limited benign lymph node involvement. Etiology of illness is not fully understood.Differential diagnosis should be performed well because lymph node involvement can be confused with lymphoma type diseases. A 35-year-old male patient with weakness, joint aches, fever, loss of appetite, weight loss, night sweating symptoms presented with the literature.

Celiac disease in children with chronic constipation.

BACKGROUND/AIM: Chronic constipation (CC) and celiac disease (CD) are the most common conditions encountered in pediatric gastroenterology. The association of these two disorders has not been evaluated properly. We analyzed the prevalence and outcome of CD in children with CC. MATERIALS AND METHODS: The study included children with CC (n = 313) and healthy children (n = 990). Serum IgA and IgA antitissue transglutaminase antibodies (IgA-tTG) were studied in all subjects. Intestinal biopsy and HLA-DQ2/DQ8 typing was performed in subjects with elevated IgA-tTG. RESULTS: Serology was positive in 8 children (2.5%) with CC and 6 children (0.6%) from the control group (P < 0.05). Histopathological examination revealed total villous atrophy in two subjects in the control group. Other subjects had Marsh 0-1 lesions. All patients with CC and 4 children from the control group were classified as having potential CD. Two children in the control group had silent CD. Spontaneous loss of serum tTG-IgA occured in 75% of the subjects with potential CD at the end of the 1st year. CONCLUSION: Our study revealed that serological evaluation CD may be omitted in children with CC at initial examination. It may be perform in selected patients such as those associated with prolonged symptoms or malnutrition.

Investigation of the expression of irisin and some cachectic factors in mice with experimentally induced gastric cancer.

BACKGROUND: The purpose of this study was to determine whether irisin is secreted by gastric tumor cells experimentally induced in mice, and also if it has any effect on cancer cachexia. DESIGN AND METHODS: 12 out of 60 BALB/c mice were used as a control group, while N-nitroso-N-methylurea (MNU) was administered orally to the remaining 48. After 150 days, the surviving mice were sacrificed by decapitation, blood and stomach, skeletal muscle, brown and white adipose tissue specimens were collected. Following histopathological evaluation of the stomach tissues, it was decided to create four groups, one control group and three consisting of mice administered MNU, no cancer, pre-cancer and cancer. Gene expression analyses of fibronectin type III domain containing protein 5 (FNDC5) and some cachexia-related proteins were performed in tissue samples, while levels of irisin, and various inflammatory and tumor markers together with cachectic factors were determined in serum samples. RESULTS: The levels of inflammatory, tumor markers and cachectic factors in serum samples were significantly higher in the cancer group compared with the control group. No expression of FNDC5 or zinc-α-2 glycoprotein, a cachectic factor, was observed in gastric tissues from the control and MNU groups, whereas significantly increased FNDC5 expression was determined in the both white and brown adipose tissues from the cancer group. CONCLUSION: Increased FNDC5 expression in white and brown adipose tissues may have a cachectic effect in mice with induced cancer. However, it is not possible to explain the mechanism of the relationship between irisin and gastric cancer development on the basis of the results of this study.

Hepcidin levels in children with chronic liver disease.

BACKGROUND/AIM: We aimed to analyze serum hepcidin level in children with chronic liver disease (CLD) and its relationship with serum cytokines level, liver function tests, hepatic iron content, and liver fibrosis. PATIENTS AND METHODS: The study included 34 children with CLD, and 15 age- and gender-matched healthy children. Serum hepcidin, ferritin, iron level, interleukin-6 (IL-6), transforming growth factor-ß (TGF-ß ), total oxidant status (TOS), and antioxidant status (TAS) were studied in all patients and in the control group. Liver iron content (LIC) was measured from the liver biopsy specimen. RESULTS: Serum ferritin levels were higher in patients with CLD than control group (100.1 ± 98.2 ng/mL vs 50.5 ± 32.2 ng/mL, P = 0.016). No significant difference was found in hepcidin levels. Hepcidin levels in children with CLD was positively correlated with ferritin (r = 0.75, P = 0.001), pediatric end-stage liver disease (PELD) score (r = 0.56, P = 0.001), TAS (r = 0.42,P = 0.02), but negatively correlated with albumin level (r = -0.45,P = 0.008). Transferrin saturation and hepcidin:ferritin ratio were significantly low in patients with severe fibrosis compared with patients with mild/without fibrosis (15.5 ± 5.5 vs 34.3 ± 30.1, P = 0.017 and 1 ± 0.5 vs 1.9 ± 1.4,P = 0.04, respectively). CONCLUSION: Serum hepcidin levels in children with CLD reflect both liver functions and TAS, and severe fibrosis is associated with low hepcidin:ferritin ratio in children with CLD.

Preoperative arterial embolization of large liver hemangiomas.

PURPOSE: We aimed to investigate the efficacy and safety of preoperative selective intra-arterial embolization (PSIAE) in the surgical treatment of large liver hemangiomas. METHODS: Data of 22 patients who underwent resection of large liver hemangiomas were retrospectively analyzed. PSIAE was performed in cases having a high risk of severe blood loss during surgery (n=11), while it was not applied in cases with a low risk of blood loss (n=11). RESULTS: A total of 19 enucleations and six anatomic resections were performed. Operative time, intraoperative bleeding amount, Pringle period, and blood transfusion were comparable between the two groups (P > 0.05, for all). The perioperative serum aspartate transaminase level was not different between groups (P = 1.000). Perioperative total bilirubin levels were significantly increased in the PSIAE group (P = 0.041). Postoperative hospital stay was longer in the PSIAE group. Surgical complications were comparable between groups (P = 0.476). CONCLUSION: Patients who underwent PSIAE due to a high risk of severe blood loss during resection of large liver hemangiomas had comparable operative success as patients with a low risk of blood loss who were operated without PSIAE. Hence, PSIAE can be used for the control of intraoperative blood loss, especially in surgically difficult cases.

Could pyelonephritic scarring be prevented by anti-inflammatory treatment? An experimental model of acute pyelonephritis.

OBJECTIVES: This study aimed to demonstrate if the addition of anti-inflammatory treatment to antibiotic therapy shows any superiority to the treatment with antibiotic only. METHODS: Forty-nine Wistar rats were divided into 7 groups. Pyelonephritis was performed by E. coli injection to upper pole of kidneys except control group. Group 2 was not treated. Ceftriaxone, ketoprofen, "ceftriaxone + ketoprofen," methylprednisolone, and "ceftriaxone + methylprednisolone" were given in the groups. The technetium-99m-dimercaptosuccinic acid scintigraphies were performed in 3rd day to detect pyelonephritis and 10th week to detect renal scarring. All kidneys were also histopathologically evaluated. RESULTS: When 3rd day and 10th week scintigraphies were compared, initial 2.00 ± 0.30 point pyelonephritis score resulted in 0.71 ± 0.36 renal scar score in "ceftriaxone + ketoprofen" group (P = 0.039). Initial 2.00 ± 0.43 point pyelonephritis score resulted in 0.86 ± 0.26 renal scar score in "ceftriaxone + methylprednisolone" group (P = 0.041). Renal scar score was declined in "ceftriaxone + ketoprofen" group and "ceftriaxone + methylprednisolone" group compared with no-treatment group on 10th week of the study (P = 0.026, P = 0.044). On histopathological evaluation, it was seen that renal scar prevalence and expansion declined significantly in "ceftriaxone + ketoprofen and ceftriaxone + methylprednisolone" (P = 0.011, P = 0.023). CONCLUSION: It was evidenced that ceftriaxone treatment in combination with ketoprofen or methylprednisolone declined scar formation in scintigraphic and histopathologic examinations of the kidneys.

Synchronous occurrence of hepatocellular carcinoma and intrahepatic cholangiocarcinoma in both lobes of the liver.

Occurrence of synchronous double primary liver cancer is a very rare condition. A 48-year-old man underwent lateral sectorectomy and tumor resection from segment (S) 7 and S5 for 3 separate liver tumors. Pathological examination revealed intrahepatic cholangiocarcinoma (ICC) in the lateral sector and hepatocellular carcinoma (HCC) in S7 and S5. This report presents the second case in the literature describing the resection of synchronous double cancers of HCC and ICC localized in both lobes of the liver. We also reviewed the clinical and pathological aspects of this coincidental situation.

Fibrosing cholestatic hepatitis after methotrexate and prednisone therapy for rheumatoid arthritis.

OBJECTIVES: Fibrosing cholestatic hepatitis is an aggressive and usually fatal form of viral hepatitis in immunosuppressed patients. We assessed the hepatotoxicity of methotrexate and prednisolone combination therapy in the background of hepatitis B virus infection. MATERIALS AND METHODS: We report the clinical course of a 55-year-old woman who underwent a deceased-donor liver transplant for fulminant liver failure. RESULTS: The patient's medical history was significant for hepatitis B virus infection and rheumatoid arthritis. Methotrexate and prednisolone combination therapy were started 5 months earlier. The patient was hospitalized because of an elevation in her liver enzymes and total bilirubin. Deterioration of liver functions and encephalopathy were developed 5 weeks after hospital admission. A deceased-donor liver transplant was performed, and pathological examination of recipient liver revealed fibrosing cholestatic hepatitis. The patient was reoperated on for bile leak and discharged 40 days after the deceased-donor liver transplant. CONCLUSIONS: The natural course of the current case was similar to previously reported cases with fibrosing cholestatic hepatitis. Clinicians should consider the potential hepatotoxicity of methotrexate and steroid therapy in hepatitis B virus infected patients.

Hormone-secreting large adrenal ganglioneuroma in an adult patient: a case report and review of literature.

BACKGROUND. Ganglioneuromas (GNs) are neural crest cell-derived tumors and rarely occur in the adrenal gland. They are usually asymptomatic and hormonally silent. The majority of cases are detected incidentally during work-up for unrelated conditions. Hormone-secreting pure adrenal GNs in adults are extremely rare. To date, only four cases have been reported in the English literature. CASE REPORT. We describe an adult case of endocrinologically active adrenal GN incidentally diagnosed in a 64-year-old male patient with history of uncontrolled hypertension. On physical examination, he had a blood pressure (BP) of 160/100 mmHg. Abdominal computed tomography and magnetic resonance imaging showed a large solid tumor (8.5 × 7.5 × 7 cm) in the right adrenal gland. Urinary levels of norepinephrine, normetanephrine, vanillylmandelic acid and dopamin were elevated, although urinary level of epinephrine was suppressed. Right adrenalectomy was performed for treatment purposes. The histological diagnosis of the resected tumor was adrenal GN. CONCLUSIONS. Hormone-secreting pure adrenal GN occurs very rarely in adults and preoperative diagnosis is difficult. Adrenal GN may present with hormonal activity such as increased secretion of catecholamines and their metabolites. There are no specific diagnostic signs and symptoms discriminating GN and pheochromocytoma. Therefore, histopathological examination need for a definitive diagnosis of adrenal GN. The prognosis after completed surgical resection without further therapy seems to be excellent. To our knowledge, the present case is the second report that describes hormone-secreting pure adrenal GN in an adult from Turkey in the English literature. We discuss this case and review the literature on this unusual entity.

The effects of bile duct obstruction on liver volume: an experimental study.

Objectives. This study is aimed at investigating alterations in liver volume during obstructive jaundice in rat liver. Materials and Methods. Thirty-six rats were divided into four groups. Abdominal tomography was performed for baseline volumetric analyses. The main bile ducts were ligated (BDL). Volumetric analyses were repeated 3 days after BDL in group 1, 7 days after BDL in group 2, 15 days after BDL in group 3, and 25 days after BDL in group 4, and total hepatectomy was performed in all animals. Control group (n = 4) was created with the rats that died before bile duct ligation. Results. There was no difference found in liver volume in group 1 compared to control animals. The liver volume was increased 7 days after BDL (P = 0.01). It was increased up to 60% of baseline values 25 days after BDL (P = 0.002). Wet liver weights of animals were also increased compared to control group. Liver weights were increased up to 40% percent of baseline values in group 4 (P = 0.002). Conclusions. Liver volume and weight were increased after BDL. Liver surgery in patients with huge liver mass is generally associated with significant difficulty. The surgeon should be aware of the time-dependent alteration in liver volume after obstructive jaundice.