Defining prognostic parameters of well-differentiated gastric neuroendocrine tumors based on metastatic potential: a two-center experience.

Background: Gastric neuroendocrine tumors [gNETs] are heterogeneous tumors and we are still unable to predict the behavior of these tumors. We aim to define the prognostic parameters of well-differentiated gNETs based on metastatic potential and to evaluate the current classification systems. Patients and methods: We retrospectively retrieved 44 well differentiated gNET cases who underwent radical surgery between 2000-2015 at two tertiary-care centers. Results: Among the 44 well-differentiated gNET patients, 17 (38%) patients had metastatic disease to lymph nodes and/or distant sites, while 27 (62%) were confined to the stomach. Higher risk of metastasis was observed with increasing tumor size, grade, depth of invasion and with type-3 and solitary tumors. 30 (68%) patients had type-1 gNET and 14 (32%) had type-3 gNET. Majority of the type-1 cases (76,6%) were Grade 1 [G1] and type-3 cases (78,5%) were Grade 3 [G3]. Type-1 subgroup had no G3 tumor, and type-3 had no G1. Grade 2 [G2] tumors were more controversial, with metastatic and non-metastatic cases. G2 cases with a >10% Ki67 expression or type-3, had a worse prognosis. Although most of the type-1 gNETs had an indolent course, 6 of 30 (20%) patients had metastatic disease. Metastasizing type-1 gNETs were >10 mm in diameter or extended to/beyond the submucosa. Conclusion: Regarding our results, tumor type, grade, size, focality and depth of invasion are the prognostic parameters for gNETs, based on metastatic potential. Besides these parameters, a two-tiered grading system with a 10% Ki-67 proliferation index cut-off value could be considered for right treatment choice.

Co-existence of Echinococcus granulosus infection and cancer metastasis in the liver correlates with reduced Th1 immune responses.

A possible relationship between cancer and Echinococcus granulosus infection has been postulated. As T cells are critical players in immune responses against both infections and malignancies, in an experimental model of secondary echinococcosis and breast cancer, this study aims to observe the progression of cancer and to determine the characters of T-cell responses. 4T1 breast tumour cells were subcutaneously injected into mammary region, whereas protoscoleces were intraperitoneally inoculated into the mice. Hydatid cysts, tumours and metastases were determined with macroscopic and histopathological evaluation. T cells found in spleen, liver and tumour were characterised by flow cytometric analysis of CD3, CD4, CD8, CD25, CCR5, CCR3, IL-4 and IFN-γ. In the mice inoculated both with protoscoleces and with breast tumour cells, increased frequency of cancer metastasis was observed in the liver. The amount of CD4(+) T cells was increased in the liver and in the spleen of mice infected with E. granulosus. However, co-existence of echinococcosis and metastatic lesions in the liver was associated with significant reduction in the IFN-γ(+) and CCR5(+) Th1 cells and increase in the CD25(+) T cells. Our results may indicate an immunological link between cystic echinococcosis and cancer that allows tumour metastasis to flourish in the liver.

Hepatic microcirculation in inflow and inflow-outflow occlusion of the liver.

BACKGROUND: Total vascular exclusion (TVE) causes warm liver ischemia. The aim of this study was to investigate the patterns of injury caused by inflow-outflow obstruction in the rat liver. MATERIALS AND METHODS: Twenty-four Wistar-Albino rats were divided into three groups: liver inflow occlusion (Group A), inflow-outflow occlusion (Group B) and intermittent inflow-outflow occlusion applied for 15 minutes. Microcirculation was measured with laser Doppler flowmetry during the procedure. Samples for biochemical and histopathological analyses were collected at the end of the ischemia period. RESULTS: Significant alterations in microcirculation were determined by application of vascular control maneuvers. Microcirculation in the central and dome segments were affected adversely compared with the dome segments in all experimental groups. TVE induced severe disturbances in hepatic microcirculation with more prominent hepatocellular damage. Damage to central segments of the rat liver was more prominent with inflow occlusion; whereas inflow-outflow occlusion produced more prominent damage to dome segments. Intermittent application of TVE clamping was associated with more hepatocellular damage compared with continuous TVE. CONCLUSION: Our mapping methodology within the liver parenchyma suggested that hepatovenous back-perfusion is a principle source of continuity of microcirculation in the rat liver during inflow occlusion. Inflow-outflow occlusion caused more tissue damage compared with inflow occlusion. Ischemic preconditioning during TVE did not increase the tolerance of the liver against ischemia.

Heterogeneity of damage between segments of rat liver after inflow-outflow obstruction.

BACKGROUND: Total vascular exclusion (TVE) causes warm liver ischemia. The complete explanation of the events during inflow and outflow obstruction of the liver during selective TVE has not yet been studied. The aim of this study was to investigate the liver injury caused by inflow-outflow obstruction in the rat liver. MATERIALS AND METHODS: Forty Wistar-Albino rats were divided into four groups. Liver inflow occlusion (groups A and C) or inflow-outflow occlusion (groups B and D) was applied for 30 minutes. Samples were collected at the end of the ischemia period. We examined oxidative injury in the liver tissue and liver histopathology. RESULTS: Oxidative stress and histopathologic alterations were more prominent with TVE application. Significant alterations were shown in hepatic superoxide dismutase, glutathione, and glutathione S-transferase levels. Central segments of the rat liver were affected significantly from inflow occlusion, whereas dome segments were significantly damaged from inflow-outflow occlusion. CONCLUSIONS: Inflow-outflow occlusion of the liver caused more tissue damage compared with inflow occlusion. The pattern of distribution of the damage due to TVE seemed different from other well-known ischemia-reperfusion injuries.

Effect of ticlopidine in the prevention of radiation enteropathy.

Impairment of vascular function is considered to play an important role in chronic radiation enteropathy. In this experimental study, the role of ticlopidine, an inhibitor of ADP-induced platelet aggregation, was investigated in radiation enteropathy. 80 male Wistar albino rats, each weighing 170-200 g, were divided into four groups: (a) radiation alone (n = 20); (b) radiotherapy plus ticlopidine (n = 20); (c) ticlopidine control (n = 20) and (d) control (n = 20). Both radiation groups received 19 Gy radiation to the exteriorized intestinal segments in a single fraction. Ticlopidine or vehicle was administered 12 h after radiotherapy and continued for 1 month. Rats from every group were euthanized randomly at intervals of 6 weeks from 2 weeks to 26 weeks. Histopathological radiation injury was assessed using radiation injury scoring (RIS). Radiation with ticlopidine or radiation alone groups showed significant RIS deterioration compared with controls in all time points studied. Comparison of median RIS of radiotherapy and radiotherapy+ticlopidine groups at the 2nd, 14th and 26th weeks yielded statistically significant RIS in favour of radiotherapy+ticlopidine group (p = 0.05). However, these differences were less pronounced at the 8th and 20th week (p = 0.07). Both radiation groups had poor weight gain when compared with control and ticlopidine groups. The weight gain in radiotherapy+ticlopidine group was significantly superior to only radiation group between 10th and 20th weeks (p = 0.05). This study showed that inhibition of platelet aggregation with ticlopidine might be useful in radiation enteropathy. However, the precise role of antiaggregant therapies on radiation enteropathy should be comprehensively studied before clinical consideration.

Evaluation of liver damage after application of TVE in the rat model.

INTRODUCTION: The aim of this study was to investigate the effects of total vascular exclusion (TVE) on the liver during the early period of reperfusion. MATERIALS AND METHODS: Forty Wistar-Albino rats were divided into four groups. Portal pedicle clamping (groups 1 and 2) or TVE (groups 3 and 4) were applied for 10 minutes. Samples were collected at the time of clamp release (groups 1 and 3) and at 30 minutes of reperfusion (groups 2 and 4). We examined oxidative injury to and histopathology of the liver. RESULTS: Oxidative stress was more prominent with TVE application. Significant alterations were shown in hepatic superoxide dismutase, catalase, glutathione, and glutathione S-transferase levels. The levels of malondialdehyde and myeloperoxidase were not altered significantly. CONCLUSION: Inflow-outflow occlusion of the liver causes more oxidative stress compared with inflow occlusion.

Hyperfunctioning parathyroid cysts: a case report.

Parathyroid cysts are infrequent lesions of which most are non-functional. They are often misdiagnosed as thyroid cysts. Pre-operative diagnosis and differentiation from thyroid cysts is generally difficult. We hereby report a case that was admitted to the emergency room and was diagnosed as hypercalcemic crisis. The mass found during the neck examination was thought to be a thyroid nodule. A right total and left subtotal thyroidectomy was performed. Palpable thyroid nodule was diagnosed as cystic parathyroid adenoma postoperatively. When a cystic lesion is found in the neck of a patient, a pararthyroid cyst should be considered.

A patient presenting with spinal cord compression who had two distinct follicular cell type thyroid carcinomas.

A 61-yr-old woman presented with complaints of weakness and pain in her legs. A magnetic resonance imaging showed a 3 x 5.6 x 7.8 cm mass lesion destructing the T1 and T2 vertebral bodies and compressing the spinal cord. The mass was excised surgically. It was follicular carcinoma metastasis of the cervicodorsal region. Then, she underwent a total thyroidectomy. Pathological examination showed two different types of carcinomas in two different focuses; follicular carcinoma in the left lobe and follicular variant papillary carcinoma in the isthmic lobe. After the operation she was given 100 mCi 131I. This is the first report of a patient who had both metastatic follicular carcinoma and follicular variant papillary carcinoma together.

Importance of proliferation markers in gastrointestinal carcinoid tumors: a clinicopathologic study.

BACKGROUND/AIMS: Carcinoid tumors are common tumors in the gastrointestinal tract. Certain criteria such as the depth of invasion, the localization, the tumor size, the mitotic index and the pattern of ploidy are used to determine the potential biological behavior of these tumors some of which might be malignant. The goal of this study was to assess the prognostic significance of proliferation markers (Ki67 and PCNA) in carcinoid tumors by using immunohistochemistry. METHODOLOGY: An immunostaining in 37 carcinoid tumors arising in various locations of the gastrointestinal tract was performed. The best stained area was selected and 1000 neoplastic cells were counted in order to determine the proliferation index in each case. RESULTS: The results of proliferation index were compared with the depth of invasion, the embryologic type, the tumor size, the presence of metastases and disease-free survival by using statistical methods. The Ki67 tumor proliferation index in the tumors > 2.1 cm was significantly different from the tumors < or = 2 cm (P = 0.032). CONCLUSIONS: The presence of significant correlation between Ki67 positivity and the tumor size might suggest that Ki67 antibody can be useful for the determination of potential behavior of gastrointestinal carcinoid tumors.

Ovarian lymphomas. A clinicopathological analysis of 10 cases.

Analysis of 10 cases of Non-Hodgkin's lymphoma with initial manifestation in the ovaries is presented with the histologic and immunohistochemical findings.

An experimental study of the adhesive potential of different meshes.

OBJECTIVE: To assess the adhesive potential and incidence of incisional hernia with three meshes. DESIGN: Open experimental study. SETTING: Surgical Research Laboratory, Turkey. ANIMALS: 75 Wistar albino rats INTERVENTIONS: Abdominal walls were excised, and defects closed primarily or with polyglactin 910, polypropylene, or dura mater. Adhesions were graded and hydroxyproline concentrations measured on days 14 and 180. On day 180, the incidence of incisional hernia, and the grades of inflammation and fibrosis were also recorded. RESULTS: The polyglactin 910 group had a higher adhesion grading than the control and dura mater groups on day 14, whereas the polypropylene group had higher adhesion grading than controls. Both polypropylene and polyglactin 910 groups had significantly higher concentration of hydroxyproline than the control and dura mater groups. On day 180, the polypropylene group had a higher adhesion grading than the controls. There were no differences in hydroxyproline concentrations, incidence of hernias, or grading of fibrosis levels among the groups. CONCLUSION: Polyglactin 910 induced more fibrotic adhesions in the early postoperative period whereas polypropylene did in both the early and late postoperative periods.

Extrahepatic Hodgkin's disease with intrahepatic cholestasis: report of two cases.

Liver is involved in about 5-8% of newly diagnosed Hodgkin's disease (HD) cases. The incidence reaches up to 50-60% in postmortem studies. In the literature only a few cases of idiopathic cholestatic jaundice have been described without an apparent cause and a paraneoplastic etiology has been suggested. We report 2 cases with HD presenting with obstructive jaundice without obvious liver involvement. The first case died soon after diagnosis; the second case received chemotherapy and radiotherapy, and she is well at 26 months' follow-up. Extrahepatic HD with intrahepatic cholestasis is an extremely rare situation without an established approach. Such cases like the present ones may help to understand the pathogenesis of the liver involvement of HD and determine the best management of these cases.

The role of neutrophils in the formation of peritoneal adhesions.

The most common cause of intraperitoneal adhesions which may result in infertility and intestinal obstruction is previous abdominal surgery. Surgical trauma of the peritoneum in the absence of infection elicits a rapid and transient influx of polymorphonuclear leukocytes (PMN) into the peritoneal cavity. The role of neutrophils in intraperitoneal adhesion formation has not been studied. We aimed to study the effects of PMN counts and PMN functions on peritoneal adhesion formation. Forty peritoneal adhesion-induced rats were randomly divided into three groups; group I, receiving saline; group II, receiving cyclophosphamide; and group III, receiving granulocyte-macrophage colony-stimulating factor (GM-CSF). In all groups, peritoneal lavage was performed to determine PMN counts the day after adhesion induction. Blood neutrophil counts and neutrophil functions were also determined. Adhesions were evaluated blindly 14 days after the operation. Adhesion tissue samples were microscopically evaluated. Tissue hydroxyproline and collagen concentrations were measured. The neutrophil counts and phagocytosis significantly increased in group III and neutrophil counts decreased in group II (P < 0.05). The score of adhesion formation in group II was significantly less than that in groups I and III (P < 0.05). Hydroxyproline concentrations of adhesion tissue were significantly decreased in group II when compared with group III (P < 0.05). The present study shows that neutropenia lowers the degree of postoperative adhesion formation. It is concluded that PMN may have a role to play in modulating post-operative adhesion formation.

Neuroblastoma with spermatic cord metastasis in a child: sonographic findings.

We report a case of neuroblastoma in a patient who had no involvement of the spermatic cord at diagnosis but who developed spermatic cord metastasis 2 months later. The metastasis appeared on sonography as a hypoechoic, highly vascular, fusiform, hard, 14x10x7 mm mass located in the right inguinal canal and extending into the scrotum. The diagnosis of spermatic cord metastasis was confirmed by resection and histopathologic examination. We recommend that the scrotum and spermatic cord be evaluated by high-resolution sonography in children with neuroblastoma, both at the time of diagnosis and during follow-up.

Four cases with chronic intestinal pseudo-obstruction due to hollow visceral myopathy.

BACKGROUND/AIMS: Chronic intestinal pseudo-obstruction is a rare clinical syndrome characterized by symptoms and signs of intestinal obstruction without any organic lesion obstructing the intestine. Visceral myopathy is one of the etiological causes and full thickness intestinal biopsy is essential for reaching a diagnosis. In this article we describe 4 cases of hollow visceral myopathy; our aim is to stress the importance of full thickness biopsy. METHODOLOGY: Four cases of hollow visceral myopathy are studied herein. All the patients had recurrent abdominal pain and constipation. The onset of symptoms was early in life or in the second to third decade. A diagnosis was established in all cases by full thickness intestinal biopsy obtained during laparotomy. Associated disorders were noted in 2 cases. One patient had Axenfelt syndrome, non-descended testicles and primary hypogonadism, and another had a diagnosis of Kleinfelter syndrome. RESULTS: All of the 4 cases were diagnosed to be suffering from hollow visceral myopathy by full thickness intestinal biopsy and 2 had additional disorders as well. CONCLUSIONS: Patients with chronic intestinal pseudo-obstruction should be carefully evaluated as to whether there is an associated disorder and the diagnosis may be delayed unless full thickness intestinal biopsy is obtained.