Abdullah Zorluoglu

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.

Is it necessary to retrieve dropped gallstones during laparoscopic cholecystectomy

Abstract.Background: An experimental study was planned to evaluate the effect of bile alone and bile in combination with gallstones on intraperitoneal adhesion and abscess formation in the peritoneal cavity of the rat. Methods: One hundred Sprague-Dawley rats were assigned to ten groups (n: 10). Groups 1–3 received a 1-ml intraperitoneal injection of saline, sterile bile, and infected bile. Groups 4–10 underwent a lower 5-mm midline abdominal incision. In groups 5, 7, and 9, a single gallstone (3-mm diameter) was placed in the right upper quadrant and injected with sterile saline, sterile bile, and infected bile, respectively. In groups 6, 8, and 10, four gallstones (3-mm diameter) were placed in the right upper quadrant together with sterile saline, sterile bile, and infected bile, respectively. Group 4 only underwent a 5-mm midline incision. All animals were sacrificed at the end of 4 weeks and the peritoneal cavity was carefully examined to investigate adhesions and abscess formation. The adhesions were graded according to Nairs gross pathologic grading of adhesions. The Kruskal-Wallis nonparametric test (KW) was used for statistical analysis. Results: No intraabdominal lesions were noted in groups 1–3. The adhesion score was increased by number of stone and infected bile (G4: 3, G5: 3, G6: 11, G7: 7, G8: 10, G9: 15, G10: 18). But there was only a significant difference between the groups that received sterile saline + single stone (G5) and that receiving infected bile + four stones (G10) (KW: 24.3 P < 0.05). There was abscess formation in three rats in group 9 and two in group 10. Conclusions: In conclusion, infected bile in combination with multiple stones increases the gross grading of adhesion and intraabdominal abscess formation. Thus, in cases with multiple stones and infected bile, the dropped stones should be retrieved and the peritoneal cavity should be copiously irrigated during laparoscopic cholecystectomy.

Colorectal cancer in young adults.

The study was carried out to promote a greater awareness of the potential for colorectal cancer in young adults under 40 years of age. During the 8 years between 1986 and 1993, 237 patients with adenocarcinoma of the colon and rectum were operated at the Uludağ University Hospital. Of these 237 cases, 46 patients under 40 years old were reviewed retrospectively. They accounted for 19.4% of the total number of patients with carcinoma of the colon and rectum operated during the same period. Rectal bleeding was the most common presenting symptom. The mean duration of time from the onset of symptoms to diagnosis was 5.8 months. The rectosigmoid area was the most frequently involved site (80%). Seventy-six percent of the patients had Dukes’ stage C or D tumors. Forty-eight percent of the tumors were either poorly differentiated or mucinous. The cumulative survival rate at 5 years was 43.4%. Patients under 40 years old with carcinoma of the colon and rectum are usually symptomatic and have advanced disease at the time of presentation. Although colorectal cancer is usually a disease of older patients it is becoming more common in younger populations.

Colonic Actinomycosis: Report of a Case and Review of the Literature

Abdominal actinomycosis is a rare entity which presents some difficulty in establishing a correct preoperative diagnosis. We report herein the case of a 41-year-old woman who developed abdominal actinomycosis involving the left colon and the surrounding retroperitoneum. The patient, who had an intrauterine contraceptive device (IUCD) in situ, presented with left flank pain and the signs and symptoms of an intraabdominal mass, which was initially diagnosed as a neoplasm originating from the left colon or the retroperitoneal space. Thus, a left colectomy was performed, but the histopathological diagnosis revealed abdominal actinomycosis. We evaluated the diagnosis and treatment of this disease in light of the knowledge acquired from the available literature on this rare entity.

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.

Ideal combination of MRI sequences for perianal fistula classification and the evaluation of additional findings for readers with varying levels of experience.

PURPOSE The aim of our study was to assess the contribution of various magnetic resonance imaging (MRI) sequences in determining the type of perianal fistula and in obtaining critical information for surgical decisions, as well as to define the optimal combination of sequences for readers with varying levels of experience. MATERIALS AND METHODS The study included 33 MRI examinations in 26 patients with suspected perianal fistula. The following sequences were obtained in both the coronal and axial planes: thin slice, high resolution T1-weighted (W) spin echo; T2-weighted turbo spin echo; short tau inversion recovery (STIR); and native and contrast enhanced T1-weighted gradient echo fast low-angle shot (FLASH) images with fat suppression (FS-CE-T1W-GRE). The examinations were interpreted by three radiologists with varying degrees of experience in two different sessions, and the inter-reader agreement was assessed. Seventeen of the patients underwent surgery. The agreement between the surgical findings and the MRI results were evaluated. RESULTS A statistically significant concordance between the fistula classification and surgery was achieved with the FS-CE-T1W-GRE sequence for Reader 1 (Cramers V=0.701, P = 0,022) and Reader 3 (Cramers V=0.716, P = 0,043). For Reader 2, statistically significant concordance between fistula classification and surgery was achieved with the FS-CE-T1W-GRE (Cramers V=0.703, P = 0,011) and the T2W images (Cramers V=0.648, P = 0,027). For all sequences, there was statistically significant agreement between readers for fistula classification, internal opening location, and the presence of sinus tracts, abscess, a horseshoe component, and inflammation. CONCLUSION For experienced readers, combining FS-CE-T1W-GRE images with either T2W or STIR images collected in both the coronal and axial planes was sufficient to make an assessment before deciding the surgical extent of the procedure.

Analysis of mismatch repair gene mutations in Turkish HNPCC patients

Hereditary non-polyposis colorectal cancer (HNPCC or Lynch syndrome) is caused by the inheritance of a mutant allele of a DNA mismatch repair gene. We aimed to investigate types and frequencies of mismatch repair (MMR) gene mutations in Turkish patients with HNPCC and to identify specific biomarkers for early diagnosis of their non-symptomatic kindred’s. The molecular characteristics of 28 Turkish colorectal cancer patients at high-risk for HNPCC were investigated by analysis of microsatellite instability (MSI), immunohistochemistry and methylation-specific PCR in order to select tumors for mutation analysis. Ten cases (35.7%) were classified as MSI (+). Lack of expression of the main MMR proteins was observed in MSI (+) tumors. Hypermethylation of the MLH1 promoter region was observed in one tumor. Nine Lynch syndrome cases showed novel germ-line alterations of the MMR gene: two frame-shifts (MLH1 c.1843dupC and MLH1 c.1743delG) and three missense mutations (MLH1 c.293G>C, MLH1 c.954_955delinsTA and MSH2 c.2210G>A). Unclassified variants were evaluated as likely to be pathogenic by using the in-silico analyses. In addition, the MSH2 c.2210G>A alteration could be considered as a founder mutation for the Turkish population due to its identification in five different Lynch syndrome families and absence in control group. The present study adds new information about MMR gene mutation types and their role in Lynch syndrome. This is the first detailed research on Turkish Lynch syndrome families.

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.

Microsatellite instability status affects gene expression profiles in early onset colorectal cancer patients.

BACKGROUND The association between microsatellite instability (MSI) status and gene expression profiles in the early onset sporadic colorectal cancer (CRC) has not been clearly established. The aim of this study was to identify the altered gene expression patterns depending on the MSI status of early onset CRC and determine specific biomarkers that could provide novel therapeutic molecular targets in the Turkish population. MATERIALS AND METHODS MSI markers (BAT25, BAT26, D2S123, D5S346, and D17S250) were investigated in tumors from 36 early onset sporadic CRC patients in whom gene expression profiles were analyzed previously. The relationship between the gene expression profiles depending on MSI status was evaluated. RESULTS A total of 15 tumors (16.66%) were identified as having MSI and 21 tumors (58.33%) were identified as having microsatellite stability (MSS). CK20 and MAP3K8 upregulation, observed in MSS tumors, was significantly associated with lymph node metastasis, recurrence, and/or distant metastasis and a short median survival (P < 0.05). REG1A upregulation is also correlated with recurrence and/or distant metastasis and a short median survival in patients with MSI tumors (P < 0.05). CONCLUSIONS High expression levels of CK20 and MAP3K8 in MSS tumors and REG1A in MSI tumors correlated with a poor prognosis in CRC patients. Further studies and validations are required; these genes may provide novel therapeutic molecular targets for the development of anticancer drugs related to MSI status for early onset CRC treatment.

Investigation of APC mutations in a Turkish familial adenomatous polyposis family by heterodublex analysis.

PURPOSEFamilial adenomatous polyposis is an autosomal dominant disease characterized by the presence of 100 or more colorectal adenomatous polyps. Mutations in the adenomatous polyposis coli gene are primarily responsible for the development of this disease. This study was designed to investigation of adenomatous polyposis coli (APC) gene mutations in members of familial adenomatous polyposis family to identify individuals at risk of the disease.METHODSWe examined one patient with familial adenomatous polyposis and 21 family members including one affected person from familial adenomatous polyposis and 20 nonsymptomatic persons. We studied E, D, F, and G segments of exon 15 of the adenomatous polyposis coli gene by heteroduplex analysis.RESULTSWe used silver staining method for staining. We found a mutation for five persons at segment F of exon 15 of the adenomatous polyposis coli gene. Two of them were affected by colorectal cancer, one of whom was the proband, and the other three were nonsymptomatic family members. The pathogenetic mutation was a T deletion at codon 1172, causing a frameshift in the adenomatous polyposis coli gene, as a result of the sequencing analysis of these cases.CONCLUSIONSInvestigation of adenomatous polyposis coli gene mutations is very important for the identification of genetic susceptibility to colorectal cancer and for the definition of tumor developing at an early stage. Furthermore, the identification of this mutation for the first time in a Turkish family will be useful to foster further studies on familial adenomatous polyposis in Turkey.