Gülaydan Filiz

Analysis of prognostic and immunohistochemical factors in gastrointestinal stromal tumors with malignant potential

The aim of this study was to analyze 37 patients with malignant primary gastrointestinal stromal tumors and to compare the findings and their therapeutic implications with those previously reported. The medical records of 37 patients who were diagnosed and operated on between January 1996 and December 2002 were retrospectively reviewed. The patients’ age, tumor size, type of surgery, histologic type, mitotic counts, presence of necrosis, Ki-67 proliferative index, National Institutes of Health 2001 consensus classification, immunohistochemical staining, and recurrence were examined to analyze factors affecting survival. Overall actuarial survival for all patients was 46%. When analyzed by type of resection, the complete resection group (R0 resection) had a mean overall survival of 48.2 +- 6.18 months compared with the patients with incomplete resection (R1-R2) who survived a mean of 10.8 +- 3.2 months (P = 0.00). Univariate analysis showed development of recurrence (P = 0.00), tumor size of 8 cm or greater (P = 0.05), Ki-67 proliferative index greater than 0.82 (P = 0.0448), desmin staining (P = 0.0076), age younger than 49 years (P = 0.0009), and incomplete resection (P = 0.00) to be significantly correlated with a poor survival. In multivariate analysis, desmin staining (P = 0.031), tumor size (P = 0.033), age (P = 0.01), recurrence (P = 0.038), and R0 resection (P = 0.02) were significant independent prognostic factors. We recommend that more careful preoperative and more frequent postoperative follow-up examinations be performed for patients with large tumors, age of younger than 49 years, and Ki-67 proliferative index greater than 0.82.

Citicoline improves functional recovery, promotes nerve regeneration, and reduces postoperative scarring after peripheral nerve surgery in rats

BACKGROUND Citicoline has been shown to have beneficial effects in a variety of CNS injury models. The aim of this study was to test the effects of citicoline on nerve regeneration and scarring in a rat model of peripheral nerve surgery. METHODS Seventy adult Sprague-Dawley rats underwent a surgical procedure involving right sciatic nerve section and epineural suturing. Rats were assigned to the control or experiment groups to receive a topical application of 0.4 mL of saline or 0.4 mL (100 micromol/L) of citicoline, respectively. Macroscopic, histological, functional, and electromyographic assessments of nerves were performed 4 to 12 weeks after surgery. RESULTS In the control versus citicoline-treated rats, SFI was -90 +/- 1 versus -84 +/- 1 (P < .001), -76 +/- 4 versus -61 +/- 3 (P < .001), and -66 +/- 2 versus -46 +/- 3 (P < .001) at 4, 8, and 12 weeks after surgery, respectively. At 12 weeks after surgery, axon count and diameter were 16400 +/- 600 number/mm(2) and 5.47 +/- 0.25 microm versus 22250 +/- 660 number/mm(2) (P < .001) and 6.65 +/- 0.28 microm (P < .01) in the control and citicoline-treated groups, respectively. In citicoline-treated rats, histomorphological axonal organization score at the repair site was (3.4 +/- 0.1) significantly better than that in controls (2.6 +/- 0.3) (P < .001). Peripheral nerve regeneration evaluated by EMG at 12 weeks after surgery showed significantly better results in the citicoline group (P < .05). Nerves treated with citicoline demonstrated reduced scarring at the repair site (P < .001). CONCLUSION Our results demonstrate that citicoline promotes regeneration of peripheral nerves subjected to immediate section suturing type surgery and reduces postoperative scarring.

Expression of cyclin D1 in normal, hyperplastic and neoplastic endometrium and its correlation with Ki-67 and clinicopathological variables

MethodsWe investigated cyclin D1 expression in proliferative endometrium, endometrial hyperplasia and endometrioid adenocarcinoma, and examined the correlation of cyclin D1 expression with Ki67 as a cell proliferation associated marker. Immunohistochemical expression of cyclin D1 and Ki67 were studied in 30 cases with endometrial carcinoma, 14 cases with atypical hyperplasia, 15 cases with simple hyperplasia and 30 cases with proliferative endometrium.ResultsOne out of 30 patients (3.3%) with proliferative endometrium, 1 out of 14 patients (7.1%) with atypical hyperplasia, and 8 out of 30 patients (26.6%) with endometrial carcinoma were found to have immunoreactivity to cyclin D1. All cases of simple hyperplasia had negative staining for cyclin D1. A positive immunoreaction for Ki67 was obtained in all cases. Statistically significant difference was found in cyclin D1 immunoreactivity between both proliferative endometrium and adenocarcinoma, and simple hyperplasia and adenocarcinoma (p<0.05). In patients with adenocarcinoma, cyclin D1 immunoreactive cases had higher mean Ki67 values compared with the non-immunoreactive ones (p<0.05). Ki67 and cyclin D1 immunoreactivity had no impact on overall survival. Univariate analysis revealed a significant relationship between survival and grade and stage (p<0.01). Cyclin D1 expression was not correlated with age, depth of myometrial invasion, lymphovascular space involvement, grade, lymph node metastasis and stage.ConclusionCyclin D1 expression in endometrial carcinoma is higher than proliferative endometrium and simple hyperplasia. These findings support that cyclin D1 may play a role in endometrial carcinogenesis.

Aldosterone Blockage in Proliferative Glomerulonephritis Prevents Not Only Fibrosis, but Proliferation as Well

Studies performed recently have determined that aldosterone has not only a major role in electrolyte and water balance and K excretion, but it also modulates myofibroblast growth in the heart and blood vessels and causes fibrosis. This study investigated the effects of aldosterone blockers in rats with anti-thy 1.1 nephritis, both on proliferation and fibrosis, by comparing it to an angiotensin receptor inhibitor valsartan. Rats with anti-thy 1.1 nephritis were randomly allocated to one of the three following groups of treatment: the control group (group 1); those treated with the aldosterone receptor blocker spironolactone (group 2); and those treated with the ATRB valsartan (group 3). On day 7, the parameters of glomerular fibrosis [transforming growth factor beta, TGF staining areas %], proliferation (Ki-67), and renal damage scores were determined. The TGF-β and Ki-67 levels of control group were significantly more than the other two groups (p<0.01). The TGF staining areas percentages were significantly decreased compared to control group. The artery, glomerular, and renal injury scores evaluated between the groups were found to be significantly decreased compared to control group. In line with previous studies, this study found that in anti–thy 1.1 mesangioproliferative glomerulonephritis, aldosterone blockage affected proliferation and fibrosis.

Metacarpal brown tumor in secondary hyperparathyroidism due to vitamin-D deficiency. A case report.

B rown tumors are locally destructive bone lesions caused by rapid osteoclastic bone resorption due to severe hyperparathyroidism1. For years, brown tumors have been considered to be characteristic of primary hyperparathyroidism. However, brown tumors also have been reported to occur in patients with severe hyperparathyroidism secondary to chronic renal failure2-4, especially those on long-term hemo-dialysis. Hypocalcemia, hyperphosphatemia, and vitamin-D deficiency are the basic characteristics of chronic renal failure associated with secondary hyperparathyroidism. Fig. 1 Photograph of the lesion at presentation. The appearance of brown tumor lesions in a patient with secondary hyperparathyroidism due to malabsorption has been reported5; but, to our knowledge, there are no reported cases of a patient in whom brown tumor developed secondary to osteomalacia due to inadequate sunlight exposure and dietary vitamin-D deficiency. Our patient was informed that data concerning the case would be submitted for publication. A twenty-eight-year-old woman who had been in purdah (no skin exposed in public except the hands and face) since she was thirteen years old presented with a 4 × 3-cm painful mass in the region of the fourth metacarpal of the right hand without redness or warmth (Fig. 1). Her hand movement was extremely restricted. Radiographs revealed an expansile lytic lesion …

Rhabdomyosarcoma of the perianal region presenting as acute leukemia

Rhabdomyosarcoma (RMS) is the most common malignant soft tissue tumor in adolescence and childhood, which becomes manifest by the locally destructive growth of the primary tumor or its metastases. Sometimes no discernible primary lesion can be detected despite widespread dissemination or in some rare cases the disease may be confined to the marrow. Although approximately 60% of soft tissue sarcomas of children are RMS, it constitutes only 2–5% of all soft tissue sarcomas in adults [1–3]. A 25-year-old female presented with pain and mass of the perianal region, fatigue, fever, and weight loss. Her history revealed that she had developed a papular lesion in her perianal region 4 months before her admittance, which enlarged and acquired a large mass with time. Concomitantly she had symptoms of anemia and weight loss. One month before her admittance, she underwent drainage of the mass as an abscess and had five erythrocyte transfusions at that time. Two weeks before admission, she developed dizziness, epistaxis, and 38°C fever and was referred to our unit with a diagnosis of acute leukemia. Physical examination revealed severe pallor, petechiae on the lower extremities, lymph node with dimension 2×2 cm in the right inguinal region, and a hyperemic, ulcerated, and infected mass with dimensions of 15×10 cm in the lower right gluteus. Her hematologic findings were: hemoglobin 5.3 g/dl, hematocrit 15.3%, mean corpuscular volume (MCV) 80 fl, mean corpuscular hemoglobin (MCHb) 28 pg, WBC 7.69×10/l with 53% polymorphonuclear cells, 16% bands, 18% lymphocytes, 9% monocytes, and 4% blasts, and platelets 107×10/l. Bone marrow smear showed that 90% of marrow cells were tumor cells. They were characterized by vacuolated cytoplasm and the propensity to form pairs, clusters, and multinucleated forms (Fig. 1a–c). Flow cytometric studies of the bone marrow cells revealed no lineage markers for B cells, T cells, or myeloid cells. Trephine biopsy showed complete replacement of marrow (Fig. 1d) and infiltration of the mass by small round cells (Fig. 1e), which stained positively for actin, desmin, and vimentin, but negatively for leukocyte common antigen (LCA) and cytokeratin. The diagnosis of alveolar rhabdomyosarcoma (ARMS) was established. Abdominopelvic computed tomography showed a mass with dimensions of 14×12×10 cm in the medial region of right gluteus and the other masses with 4×3 cm near the inferior ramus pubis and in the anterior part of the right piriform muscle (Fig. 1f). The patient underwent a combined regimen of chemotherapy. Initially the neoplasm responded to chemotherapy, but disease progressed after 4 months. The histological diagnosis of tumor often remains difficult in a variety of solid tumors characterized by round cell morphology including RMS, neuroblastoma, Ewing’s sarcoma, and some cases of non-Hodgkin’s lymphoma [3]. Relatively few conditions spuriously may mimic a hematological disease such as acute leukemia; one of these is ARMS. ARMS in cases of bone marrow involvement is easily confused with acute leukemia and also the clinical picture may mimic the similar systemic symptoms of acute leukemia. The cells of ARMS resemble hematologic blasts (particularly lymphoblasts) and are difficult to differentiate from leukemic cells [2, 4]. R. Ali (*) . F. Özkalemkaş . Ü. Ozan . T. Özçelik . V. Özkocaman . A. Tunalı Department of Internal Medicine, Division of Hematology, Uludağ University School of Medicine, Bursa, Turkey e-mail: ridvanali@uludag.edu.tr Tel.: +90-224-4428400 Fax: +90-224-4428060

End-to-side nerve coaptation: is an additional proximal coaptation useful when available?

The aim of this experimental study was to evaluate the effects of end-to-side coaptation of the proximal end of a severed nerve to the same intact nerve, in addition to traditional end-to-side coaptation of the distal end, with an aim to use the intact nerve as a nerve conduit in a rat model and to compare the functional and histologic results of this modality to those obtained after nerve grafting and traditional end-to-side nerve coaptation. In group A, a peroneal nerve defect measuring 1 cm was created in the left hind limb, and a nerve graft 1 cm long was used to bridge the defect. In group B, only the distal stump of the peroneal nerve was coapted to the intact tibial nerve. In group C, both ends of the peroneal nerve defect were coapted to the intact tibial nerve in an end-to-side fashion 1.5 cm apart from each other, and in group D, the peroneal nerve defect was left unrepaired. Group E was consisted of nonoperated peroneal nerves that were used to obtain normative data. Although significantly higher myelinated axon densities were observed in groups B and C compared with group A and group E, total number of the myelinated axons was significantly higher only in group C. Peroneal functional index assessments demonstrated that nerve recovery in the peroneal nerve was similar in groups A and C, and both were better than those observed in groups B and D. Collectively, these results suggest that end-to-side coaptation of both ends of a severed nerve to an intact nerve, in case of a nerve defect in this length, may serve as an alternative for nerve grafting.

Touch imprint cytology of prostate core needle biopsy specimens: A useful method for immediate reporting of prostate cancer

Background: Cytology plays an important role in the preoperative assessment of many cancers. It is used as a first-line pathological investigation in both screening and diagnostic purposes. Aims: To determine the diagnostic value and accuracy of touch imprint cytology (TIC) smear of prostate core needle biopsy (CNB) specimens in the diagnosis of prostate carcinoma. Materials and Methods: One hundred and twenty-one patients had ultrasound-guided transrectal prostate CNB. A total of 1210 TIC smears were prepared from all CNB specimens. Results: Diagnoses of 1210 TIC smears were compared with the histopathological findings of the CNB specimens. One hundred and seventy (14%) TIC smears were found positive for malignancy, 35 (2.9%) were diagnosed as suspicious for malignancy and 1005 (83.1%) were found negative for malignancy. Twenty-five of 35 suspicious imprints and 150 of 170 malignant smears were confirmed to be malignant on histopathological evaluation. Although 20 malignant TIC smears were defined as benign in standard histological preparations, 10 of them had definitive diagnosis of malignancy following extensive serial sectioning. Last of all, there were 10 false-positive cytology results. Moreover, 10 of the 35 suspected TIC smears were false negative when compared with the histopathological diagnosis. The sensitivity, specificity, positive predictive value and negative predictive value of touch imprint smear results were 100%, 98%, 90.2% and 100%, respectively. Conclusions: TIC smears can provide an immediate and reliable cytological diagnosis of prostate carcinoma. It may clearly help the rapid detection of carcinoma, particularly in highly suspected cases that had negative routine biopsy results for malignancy with abnormal serum prostate specific antigen (PSA) levels and atypical digital rectal examination.

Effect of lyophilized heterologous collagen on new cartilage formation from perichondrial flaps in rabbits: an experimental study.

New cartilage formation originated from perichondrium has previously been researched in many clinical and experimental studies. 1–6 After these studies, the use of perichondrium for the repair of cartilage defects has been used clinically when enhancing neochondrogenesis has been found to be of great value in decreasing the recovery period. Collagen is the major protein of whole connective tissue, and in vitro positive effects of collagen matrices on neochondrogenesis have also been studied before. 7–9 In this experimental study, in vivo effects of heterologous collagen sponge in perichondrial neochondrogenesis were examined in an animal model, and acceleration and enhancement effects were observed.

Cardiac metastasis in a laryngeal carcinoma and associated electrocardiographic changes.

In patients with cancer, metastases to the heart are rare and usually difficult to diagnose unless they cause symptoms. Cardiac metastasis of laryngeal carcinoma is also rarely reported in the literature. This report deals with a 63-year-old male patient with carcinoma of the larynx that involved the heart. The patient presented with chest pain, and the electrocardiogram revealed new ST segment elevation in the precordial leads. The cardiac markers were negative, and the electrocardiogram showed no changes during the course in the cardiology clinic. Although the patient was stable, he had massive hemorrhage at his tracheotomy site and died on the sixth day of hospitalization. A necropsy of the myocardium showed metastasis of squamous cell carcinoma to the heart. We conclude that the electrocardiographic changes in cancer patients during the course of the disease may provide a clue for detection of cardiac involvement. Heart metastasis in cancer patients is rare. When this rare events occurs, diagnoses are usually based on postmortem examinations. However, electrocardiographic changes may serve as a clue for detection of involvement of the myocardium. Here we present a male patient, aged 63 years, with laryngeal carcinoma with heart metastasis, a rare condition reported 3 decades ago by Harrer et al. A male patient aged 63 years was admitted to the emergency clinic because of dull sternal pain, nausea, and diaphoresis that had been present for the preceding 5 hours. His general condition was poor. His blood pressure and pulse rate were 130/80 mm Hg and 90/min, respectively. The presence of tracheotomy and coarse crackles in the lower right lung were remarkable in his lung exam. The patient had completed chemotherapy for squamous cell carcinoma