SOCS-1 1478 CA/del gene polymorphism affects survival in colorectal carcinoma.

Aims and Background: Suppressor of cytokine signaling 1 (SOCS1) is a prototype molecule of the SOCS family. Alterations in the SOCS1 expression have been reported in human cancers and some studies suggest that SOCS1 might act as a tumor suppressor in carcinogenesis. In the present study, we aimed to evaluate the association of SOCS1 promoter -1478CA/del gene polymorphism detected in DNA isolated from the tissues of patients with colorectal cancer (CRC) for histopathological characteristics and survival. Patients and Methods: For the study, we retrospectively enrolled 53 patients with resected colon due to CRC and 23 control subjects with no systemic illness. SOCS1- 1478CA/del gene polymorphism was determined using the polymerase chain reaction-restriction fragment length polymorphism methodology. These results were evaluated in relation to histopathological features and survival results and analyzed statistically. A P value equal to or less than 0.05 was considered significant. Results: Neither control subjects nor the CRC group showed a significant association with SOCS1 -1478CA/del gene polymorphism (p = 0.248). SOCS1 -1478CA/del gene polymorphism was not significantly associated with histopathological features either. However, in the overall survival (OS) analysis, those patients with the del/del allele were found to have a 3.9-fold greater risk of mortality compared to those with CA/CA allele (p = 0.05). Progression-free survival (PFS) was also significantly different in such patients (p = 0.05). Conclusion: The present study examining the association of SOCS1 -1478CA/del gene polymorphism with CRC showed that CRC patients with del/del allele had both significantly shorter PFS and OS versus those with CA/CA or CA/del allele.

TWO OPPOSITE PHENOTYPES OF GLUCOSE DISORDERS IN A FAMILY WITH HETEROZYGOUS P.SER453LEU (C.1358C> T) MUTATION IN THE GLUCOKINASE (GCK) GENE: MATURITY ONSET DIABETES IN YOUNG AND INSULINOMA.

Background: Heterozygous gain-of-function mutations in the glucokinase (GCK) gene cause hyperinsulinaemic hypoglycaemia (GCK-HI), while loss-of-function mutations lead to a monogenic type of diabetes (GCK-MODY). We, herein, report a heterozygous GCK gene mutation in a large family with GCK-MODY and insulinoma in one individual from the same family. Patients and methods: The proband, an 11-year-old male, was referred for asymptomatic mild hyperglycemia (fasting glucose:121 mg/dL) and HbA1c of 6.1%. Segregation analysis of the family revealed multiplex members with asymptomatic fasting hyperglycaemia or non-insulin-dependent diabetes and 33-year-old maternal uncle of the proband case had a history of distal pancreatectomy due to the diagnosis of insulinoma. His preoperative investigations were revealed fasting glucose of 31 mg/dL, insulin: 7µU/mL, C-peptide: 2.6 mg/dL, and a low HbA1c(4.0%) which was suggestive for recurring hypoglycaemia episodes. Post-pancreatectomy he developed mild fasting hyperglycemia (115-136 mg/dL). Results: Genetic analysis revealed heterozygous p.Ser453Leu(c.1358C> T) mutation in the GCK gene in the proband. In segregation analysis, the identical heterozygous p.Ser453Leu(c.1358C> T) GCK gene mutation was detected in all of the other affected family members for whom a DNA analysis was applicable. The maternal uncle was first diagnosed with insulinoma and underwent a pancreatectomy. He also had an identical mutation in a heterozygous state. Conclusion: We, to the best of our knowledge, firstly identified these two entirely distinct phenotypes of glucose metabolism, GCK-MODY and GCK-HI, due to an identical heterozygous p.Ser453Leu (c.1358C> T) mutation in the GCK. Further studies required to elucidate this new phenomenon and understanding the genotype-phenotype relationship of GCK gene mutations.

The expression and relationship of AdipoR1/R2 in gastric intestinal metaplasia.

BACKGROUND: Adiponectin (ApN) is a 244-amino acid protein mainly secreted from the adipose tissue and involved in various physiological functions. ApN exerts its metabolic effects by binding to two major receptors: adiponectin receptor-1 (Adipo-R1) and adiponectin receptor-2 (Adipo-R2). Recent studies have reported ApN's involvement in the progression of cancer. However, there are no studies evaluating the relationship between Adipo-R1/R2 expression and gastric intestinal metaplasia (IM), which is a predisposing factor in gastric cancer (GC) development, and Helicobacter pylori H. pylori infection. AIMS: In this study we aimed to investigate the relationship between the Adipo-R1/-R2 expression and H. pylori infection in patients with GC and gastric IM. MATERIALS AND METHODS: Forty patients that underwent gastric resection and 56 patients that developed gastric IM were included in the study. The Adipo-R1/-R2 expression and the presence of H. pylori were examined immunohistochemically. The univariate analyses showed that the expression of Adipo-R1/-R2 in GC patients was significantly lower compared to both complete metaplasia (CM) and incomplete metaplasia (ICM) patients (p <0.0001 for both). RESULTS: According to multiple multinomial logistic regression analysis, Adipo-R1/-R2 expression in the CM group was significantly higher than in the GC group (p = 0.05, p = 0.014, respectively). Moreover, Adipo-R1/-R2 expression was significantly higher in ICM group compared to the GC group (p=0.012, p=0.045, respectively). However, in both analyses no significant difference was determined in terms of H. pylori positivity between the groups. CONCLUSION: The resulting data suggests that ApN plays a role in GC processes via Adipo-R1/-R2 receptors.

Overexpression of miR-21 Is Associated With Recurrence in Patients With Hepatitis B Virus-Mediated Hepatocellular Carcinoma Undergoing Liver Transplantation.

Liver transplantation (LT) is the best treatment option for hepatitis B virus (HBV)-mediated hepatocellular carcinoma (HCC). Nevertheless, recurrence is the most important issue after LT. The aims of the present study were to evaluate the relation of dysregulated expression of microRNAs (miRNAs) in recurrence formation in HBV-mediated HCC cases. A total of 42 HBV-mediated HCC patients were evaluated in this study. Among 21 miRNAs, the expression level of miR-106a and miR-21 were higher and miR-143 and miR145 were lower in patients with HCC compared with noncancerous liver tissues (P = .0388, P = .0214, P = .0321, and P = .002, respectively). Compared with nonrecurrent patients, the expression level of miR-21 was 3.54-fold higher and miR-145 was 2.42-fold lower in patients with recurrence during the 5-year follow-up (P = .004 and P = .032; respectively). In addition, according to multivariate Cox regression analysis, the overexpression of miR-21 was found to be a prognostic indicator in HBV-mediated HCC patients (P = .002). In conclusion, we show a significant association between high expression of miR-21 and recurrence in HBV-mediated HCC. Therefore, up-regulation of miR-21 could serve as a promising prognostic marker for HCC.

Simultaneous occurrence of synchronous and metachronous tumors with gastrointestinal stromal tumors.

OBJECTIVE: To examine the frequency and clinicopathological features of synchronous and metachronous tumors which occur simultaneously with gastrointestinal stromal tumors (GIST). METHODS: Clinical and pathologic records of 78 patients diagnosed with primary GIST and treated at our institution between 1997 and 2009 were reviewed. RESULTS: GIST occurred simultaneously with other primary GI malignancies in 16.1 % (n = 13) of all patients with GIST. Of the simultaneous secondary tumors, 69.2 % (n = 9) were gastrointestinal tumors, and the remaining were biliary system and breast tumors. GIST most frequently had gastric localization (n = 6, 46.1%). CONCLUSION: Although GIST are uncommon neoplasms, their synchronous and metachronous coexistence with other tumors is rather frequent, mostly as incidental tumors accompanying a gastrointestinal neoplasm. Therefore, during surgery on cases with gastrointestinal neoplasms, the surgeon needs to be careful about a synchronous GIST. At the same time, more detailed studies are needed about the carcinogenesis of dual tumors coexisting with GIST (Tab. 1, Ref. 14).

A comparison of three fibrinolytic agents in prevention of intra-abdominal adhesions.

PURPOSE: Three different drugs affecting the coagulation process at various stages were studied for their effectiveness in preventing intra-peritoneal adhesion formation in rats. MATERIAL AND METHODS: Forty female Wistar-Albino rats divided into four groups based on the drugs administered during the experimental laparotomy and caecal abrasion: the control group--no drug administered, the intra-peritoneal tissue plasminogen activator (TPA) group, the subcutaneous fondaparinux sodium (FS) group and the intra-peritoneal activated drotrecogin alfa (ADA) group. After two weeks, intra-peritoneal adhesions were macroscopically and microscopically scored. RESULTS: The macroscopic scores of the three groups were similar but all lower than the control group (p = 0.002). Inflammation (p = 0.023) and fibrosis (p = 0.019) scores were lower in just the ADA group when compared to the control group. CONCLUSIONS: All three agents were effective in preventing adhesions when compared to the control group. Nevertheless, ADA seemed the most effective except when considering clinical applicability, in which case FS seemed to offer the greatest advantage.

Vena cava resection with venous-venous shunt for hemangioma.

Mediastinal hemangiomas are rare neoplasms among mediastinal tumors. We report a rare case of hemangioma of the vena cava that was detected incidentally in a 30-year-old female patient.

Assessment of the efficacy of bio-absorbable oxidized regenerated cellulose for prevention of post-operative pericardial adhesion in the rabbit model.

Pericardial adhesions complicate re-operative cardiac surgery and several attempts have been made to reduce adhesion formation. The efficacy of bio-absorbable oxidized regenerated cellulose in preventing post-operative pericardial adhesions was evaluated in the present study. Forty New Zealand white rabbits were divided into four groups of 10. In all rabbits an area of pericardium (2 x 2 cm) was excised. The wound was left open in groups 1 and 2 but replaced with bio-absorbable oxidized regenerated cellulose in groups 3 and 4. Rabbits in groups 1 and 3 were killed 3 weeks after surgery and those in groups 2 and 4 were killed at 6 weeks. Groups 1 and 2 showed more severe pericardial adhesions, more fibrous reaction and increased visibility of coronary vessels than groups 3 and 4, although there was no difference in inflammation. Light microscopy showed a mesothelium-like cell layer in groups 3 and 4. It is concluded that bio-absorbable oxidized regenerated cellulose may be suitable in patients receiving staged cardiac surgery and in those with a high probability of re-operation.

The expression frequency of common fragile sites and genetic predisposition to colon cancer.

The expression frequency of common fragile sites induced by aphidicolin (Apc), bromodeoxyuridine (BrdU), and caffeine was evaluated on prometaphase chromosomes obtained from the peripheral blood lymphocytes of 32 patients with colon cancer, 30 of their clinically healthy family members and 30 age-matched normal controls. The proportion of damaged cells (P < 0.001), the mean number of chromosomal aberrations and the expression frequencies of fragile sites were significantly higher in the patient and relative groups compared to the control group. Our findings show an increased genetic instability in patients with colon cancer and their first-degree relatives. In addition, common fragile sites can be used as a suitable marker for determining genetic predisposition to cancer.

The expression of fragile sites in lymphocytes of patients with rectum cancer and their first-degree relatives.

Fragile sites are non-staining gaps and breaks in specific points of chromosomes. These sites also include acentric fragments, triradial figures and several rearrangements. Although this issue has been controversial recently, they may be related to structural chromosomal rearrangement in some neoplasms. In this study, the expression of fragile sites induced by aphidicolin (Apc), 5-bromodeoxyuridine (BrdU) and caffeine was investigated on prometaphase chromosomes obtained from the peripheral blood lymphocytes of 36 patients with rectum cancer, 30 first-degree relatives and 30 normal healthy controls. The results of the structural chromosome aberrations determined in patients and their first-degree relatives were significantly higher than those in control subjects (P<0.001). We determined aphidicolin type common fragile sites (1p36, 1p31, 1p21, 1q21, 1q25, 1q44, 2p24, 2q21, 2q33, 2q37, 3p14, 5q21, 5q33, 13q13, 14q24, 16q23 and 18q21). When the rates of sites such as 1p21, 1q25, 2q33, 3p14, 5q21 and 14q24 in patients and in their first-degree relatives were compared with the control group, the difference was statistically significant. Our results indicated an increased genetic instability in patients with rectum cancer and their first-degree relatives. Therefore, the increase of fragile site expression may be an important marker showing genetic predisposition to rectum cancer.

The relationship between c-erbB-2 oncogene expression and clinicopathological factors in gastric cancer.

Gastric carcinoma is one of the most common carcinomas and a leading cause of death from cancer in Turkey. The relationship between clinicopathological features of the disease and oncogenes is under investigation. In this retrospective study we investigated the relationships between expression of c-erbB-2 oncoprotein and grade, stage and pathological characteristics of the tumour, and prognosis. Formalin-fixed, paraffin-embedded tissue sections were prepared from gastrectomy specimens from 55 patients with gastric carcinoma. The tissue sections were stained immunohistochemically to reveal c-erbB-2 protein. Six (10%) of the tumours stained positively for c-erbB-2 protein. There was no statistically significant association (P > 0.5) between c-erbB-2 staining and tumour grade, stage or pathological characteristics (necrosis, lymph-node infiltration), or between staining and prognosis. The results suggest that overexpression of c-erb-B-2 protein is not related to the pathological characteristics of the tumour in gastric carcinoma and is not an important prognostic indicator.

Expression of p53 protein and prognosis in gastric carcinoma.

A study was carried out to assess whether p53 expression is related to tumour type, grade or pathological characteristics, or to prognosis, in gastric cancer. Immunohistochemical studies were performed to detect p53 protein in sections from 55 consecutive gastrectomy or partial gastrectomy specimens. Tumours were classified for T-stage, histopathological grade and pathological characteristics. Immunohistochemical staining detected p53 protein in 11 (19%) of the 55 specimens. There was no statistically significant difference between patients with p53 positively staining tumours and patients with p53 negatively staining tumours with regard to tumour grade, stage or pathological characteristics (lymph-node infiltration, depth of invasion, necrosis, or necrosis of vessels). Survival time was statistically significantly lower in patients with positively staining tumours (mean survival times 12.0 and 23.4 months, respectively). These results suggest that expression of p53 protein is related to poor prognosis in gastric carcinoma.

High expression of multidrug resistance-1 (MDR-1) and its relationship with multiple prognostic factors in gastric carcinomas in patients in Turkey.

Drug resistance remains a major problem in the treatment of gastric cancer. In Turkey, gastric carcinoma is the second most common cancer and, because the rate of early diagnosis is low, chemotherapy plays an important role in the treatment of the disease. We aimed to investigate expression of the multidrug resistance-1 gene (MDR-1) and its relationship with multiple prognostic factors in gastric cancers. Between 1996 and 1998, a total of 55 patients (37 men and 19 women; median age 55 years) were studied. Sections from specimens of gastric carcinomas were immunohistochemically stained to detect P-glycoprotein (which is associated with MDR-1 expression). We found MDR-1 expression in 48 (87%) of the patients. None of the multiple prognostic factors, including histological type of tumour, correlated with expression of MDR-1. Patients who had low MDR-1 expression had better survival. We conclude that the expression of MDR-1 in gastric cancer is high in Turkey, and this may be related to poor prognosis.

Successful treatment of cranial metastases of extrapulmonary small cell carcinoma with chemotherapy alone.

Extrapulmonary small cell carcinoma (EPSCC) is a distinct clinical and pathological entity other than small cell carcinoma of the lung. We present a case with EPSCC, with neurologic impairment due to brain metastases at initial diagnosis, which showed a complete response to combination chemotherapy. A 55-year-old male patient was first admitted with a mass of 6 x 6 cm in diameter in the right cervical region. The diagnosis of small cell carcinoma was entertained with immunohistopathologic and light microscopic findings. During the period of investigation the tumor showed rapid progression and the patient had neurologic dysfunction with right hemiparesia, and papilla oedema in fundoscopy. Cranial CT showed supratentorial multiple cranial metastases and peritumoral oedema. Since the patient refused radiotherapy, combination chemotherapy was started (Etoposide 100 mg/sq m i.v., days 1,3,5 and cisplatin 80 mg/sq m i.v., day 1). A fast response to the chemotherapy was observed with rapid disappearance of the cervical mass. Following six cycles of the chemotherapy the patient recovered fully and all the lesions disappeared with CT.

Total thyroidectomy or lobectomy in benign nodular disease of the thyroid: changing trends in surgery.

METHODS: Over a 23-month period (January 1994-December 1995) in the era of fine needle aspiration (FNA), 344 thyroid surgery operations were performed for benign diseases of the thyroid. Of these 55 total thyroidectomies or lobectomies were evaluated. Mean age was 43.6 + 9.7 and the female/male ratio was 47/8 (5.8). All cases were operated on with the consensus of the surgery + endocrinology + pathology council according to a protocol based on FNA, thyroid function tests, scintigraphy and ultrasound. Suspected FNA or suspected nodules during the surgery were verified by frozen section also. Of these 55 benign nodules, 7 (12.7%) had total bilateral, 48 (87.3%) unilateral lobectomies. RESULTS: Postoperatively 3 cases (5.8%) of seroma, one transient hypoparathyroidism (1.8%) and one unilateral vocal cord paralysis (1.8%) were seen as complications. CONCLUSIONS: In our center, FNA cytology has been a routine procedure since 1992. Surgery for benign thyroid disease has been reduced 50% since than. This study was started after two years of the FNA procedure. Resident nodules are the most common cause of recurrence in nodular thyroid disease, so some cases need radical surgery when it is decided to operate. Morbidity of surgery for recurrent disease is unacceptably high and is comparable to lifelong supplement therapy.

Helicobacter pylori and intestinal metaplasia.

Gastric carcinoma of the intestinal type is assumed to develop from precancerous gastric lesions. It is now widely accepted that Helicobacter pylori (HP) infection causes chronic gastritis and, after a period of time, intestinal metaplasia (IM). It was suggested that these gastric lesions may evolve into gastric carcinoma after a lengthy latency period. HP seropositivity is high in Turkey at early ages. This may explain the high incidence of gastric carcinoma in this geographic region. In this study, we examine the relationship between HP and IM in endoscopic gastric biopsy specimens. We examined 840 biopsies taken from 210 patients. HP positivity and the presence of IM were examined in these specimens by histopathologic methods. HP positivity was also determined by CLO testing. HP was positive in 156 of the 210 patients examined (74.3%). The distribution of HP seropositivity did not differ between age groups (p > 0.05). IM was present in 101 patients in the entire study group (48%). Among the 156 HP-positive patients, the rate of IM was 44.8% (n = 70). The rate of IM among the 54 HP-negative patients was 57.4% (n = 31), which was not statistically significant (p > 0.05). IM positivity has been shown to increase in older age, which was statistically significant (p < 0.001). We were not able to show a relationship between HP seropositivity and IM. Increased HP seropositivity at an early age is a common risk factor in our population. We must consider other factors that may contribute to the increased rate of IM in older age groups.

Subtypes of intestinal metaplasia and their relationship to Helicobacter pylori.

The presence of incomplete colonic type of intestinal metaplasia (IM) is regarded as a risk factor for gastric carcinoma. In this study, we attempted to classify the subtypes of IM in our patients and examine their relationship to Helicobacter pylori (HP). Gastric biopsies were obtained from 210 patients. The HP positivity and the presence and type of IM were determined by histopathologic methods. HP positivity was also tested by the CLO test. The subtypes of IM were classified according to Ming's classification. IM was present in 101 of 210 patients (48%). Complete type intestinal metaplasia was present in 72 of 101 patients (71.3%), incomplete type IM was seen in 29 of 101 patients (28.7%), and incomplete colonic type (Type IIc) was found in 7 of 101 patients (6.9%). No significant relationship was found between subtypes of IM and HP positivity (p > 0.05). Although our patient group is small, our findings suggest that the carcinogenity of HP is mostly related to its own mutagenic activity as well as the mutagenic activity of the inflammatory cells present in response to HP rather than to its supposed effect on precancerous gastric lesions.

A retrospective analysis of thyroid cancer.

We reviewed the results of 2071 thyroidectomies performed during the past 11 years at Uludag University School of Medicine Hospital. Of all the patients 1602 (77.4%) were women and 469 (22.6%) were men (F:M = 3.4:1). Seventy-eight of the thyroid surgery patients (3.77%) had thyroid carcinoma, with a female to male ratio of 2.0:1. The relative risk of thyroid cancer in male versus female patients with thyroid nodules was determined to be 1.75:1. Patient distribution by thyroid carcinoma type was: papillary carcinoma 49%, follicular carcinoma 24%, undifferentiated carcinoma 10%, metastatic carcinoma 10%, and medullary carcinoma 6%. Fine needle aspiration biopsy (FNAB) has been used routinely in our hospital for the last 4 years. During this period, the average number of operations decreased from 201 to 130 per year and the surgical diagnosis of thyroid carcinoma increased from 2.85 to 7.65%. We conclude that papillary carcinoma is relatively less prevalent in our population and that fine needle aspiration biopsy is the preferred method of diagnosing nodular thyroid disease.