Ayşegül Özakyol

Primary appendiceal adenocarcinoma

Adenocarcinoma of the appendix is rarely encountered and is usually discovered at the pathology examination of the surgical specimen. Adenocarcinoma of the vermiform appendix is a rare neoplasm and constitutes <0.5% of all gastrointestinal neoplasms. There is no symptom of appendiceal cancer, and it is very difficult to diagnose preoperatively. Most female patients are diagnosed as having a gynecologic disease. Second primary synchronous and metachronous neoplasms, especially in the gastrointestinal tract, are found in up to 35% of patients with appendix adenocarcinoma. We report a case of adenocarcinoma in a 56-year-old woman misdiagnosed as having right ovarian carcinoma, and we review the literature.

Breast metastasis of primary colon cancer

TO THE EDITOR: Metastatic tumors of the breast are very rare. The clinical incidence of breast metastasis is 0.5–2%, whereas the accurate incidence obtained by autopsy is 6.6% (1, 2). Our English literature review has shown ,15 cases of colon cancer metastatic to breast. This case report describes a patient with breast metastasis from colon adenocarcinoma. A 42-yr-old woman was admitted to the state hospital with a history of nausea, vomiting, abdominal pain and weight loss. She had had abdominal pain and weight loss during the past 4 months, and nausea and vomiting in last few days. Her physical examination revealed abdominal tenderness, involuntary guarding, and rebound phenomenon. She underwent emergency exploratory laparotomy for a presumed colonic obstruction. At laparotomy, a tumor obstructing the sigmoid colon was observed, and left hemicolectomy was performed. After the operation, the patient was referred to our university hospital for follow-up and therapy. Histopathological examination of tumor revealed that the tumor was a moderately well differentiated adenocarcinoma, composed of irregularly shaped and branching cords of tumor cells. The glands were lined by tall columnar to cuboidal epithelium and included goblet cells. Carcinomatous change in mucosa and tumor invasion from submucosa through subserosa was observed. No distant metastasis was detected. Chemotherapy of 5 fluorouracil, etoposide, and mytomicine was begun. Six months later, a round, well circumscribed, painless, 3-cm (in diameter) breast mass was found in the upper quadrant of the right breast. Mammography showed a well defined nodule without microcalcifications. The left breast was found to be normal by physical examination and mammography. The breast nodule was excised. Histopathological appearance of this nodule was similar to colonic tumor. It had atypical glands, some of which had mucin secretions (Fig. 1) and some of which had goblet cells. Immunohistochemical staining was performed to the colonic tumor and breast mass. Estrogen and progesterone receptors were found to be negative, and carcinoembryonic antigen (CEA) was positive in both locations. The breast lesion was considered to be metastasis of primary colon cancer. A year later from first diagnosis, recurrence in the colon, and 2 months later, metastasis in the abdominal wall and retroperitoneal site were found. The disease was considered to be disseminated. The most common radiographic findings in patients with blood-borne metastasis is well circumscribed, usually single or multiple discrete nodules without calcifications (3). Tumoral calcification is virtually conclusive in excluding metastatic disease, except for rare instances of metastases from ovarian carcinoma (4). Histological features also have characteristics of metastasis, which are tumor with multiple satellite foci, the absence of intraductal component, and the presence of many lymphatic emboli (5). In our patient, mammography revealed no calcifications. Histopathological appearance of breast nodule and immunohistochemical staining were similar to primary tumor, and goblet cell was observed in the breast mass as well. In conclusion, breast metastasis of colon cancer is very rare. Metastasis to the breast is usually indicative of disseminated disease, and the prognosis is poor.

Spontaneous Bacterial Peritonitis Due to Brucella Melitensis in a Cirrhotic Patient

TO THE EDITOR: Recently, I came across a 54-yr-old white woman with a history of abdominal pain and weight loss. Evaluation included EGD (Fig. 1), colonoscopy, and CT scan of the abdomen. She was found to have multiple benign gastric polyps. Her records revealed a past history of multiple intradermal and junctional nevus. Later, she developed obstructive jaundice, and ERCP detected pancreatic cancer. There are many well-known syndromes reported with an association between gastrointestinal polyps, ectodermal neoplasia and pancreatic cancer. Examples of such syndromes (1) are Peutz-Jegher syndrome (mucocutaneous pigmentation and intestinal polyposis) and Cronkhite-Cananda syndrome (ectodermal defects such as alopecia, excessive skin pigmentation, and generalized gastrointestinal popyposis) and Gardener’s syndrome (soft tissue tumors such as sebaceous cysts and fibromas, bony tumors such as osteoma, adenomatous polyps of the colon and rectum associated with development of periampullary tumors). The case reported here had a somewhat different configuration: pancreatic cancer, multiple benign gastric polyps, multiple intradermal and junctional nevus, and no colonic or rectal polyposis. The purpose of this letter is to find out whether any similar cases have been noticed by readers. Is this reported combination just a coincidence, or could here be any relationship that should be explored further?

A Rare Entity: Cutaneous Metastasis From Gastric Adenocarcinoma

TO THE EDITOR: We read the study by Luthra et al. (1), in which they compared histology and serology, in adult patients, in detection of Helicobacter pylori(Hp) infection. Briefly, 46.7% (112 of 240) of the patients were Hp-positive by histopathology. These patients were accepted as having current infection with Hp. Of the 240 serum samples, 152 (63.3%) had elevated levels of IgG antibody to Hp ( p , 0.001, serologyversushistopathology). They found the sensitivity of the serology for detecting current infection, when histopathology was considered as the gold standard, as 95.5% and the specificity as 64.8%, respectively. The infection rate was slightly higher in women than that in men. We conducted a similar study in 77 children (48 female, mean age (SD), 12.5 (2.9) yr, range 3–18 yr) with recurrent abdominal pain. Fifty-eight of them (75.3%) had Hp on histological examination and 60 (77.9%) had elevated levels of IgG antibody to Hp with ELISA. The difference in the prevalence of current infection and seropositivity was insignificant. Compared with histopathology, the sensitivity of the ELISA for detecting current infection was 82.7% and the specificity, 41.1%. The positive predictive value of serology in detecting current infection was 80% and the negative predictive value, 36.8%. Gastritis associated with Hp infection is the most common chronic infectious disease in the world. Both invasive and noninvasive tests have been used to diagnose Hp infection. Serological tests are easy to perform, inexpensive, and easily acceptable to patients, including children. However, it is not known whether serology represents the current infection. The study by Luthraet al. described a 15.4% difference in the prevalence of infection according to whether biopsy or serological methods were used (1), whereas we found only a 2.6% difference between the two methods. In another study (2), a 17.9% difference was reported, similar to that found by Luthraet al. Titers of antibody to Hp are known to fall with eradication of bacteria (3). The low level of difference in our study may reflect the difference between developed countries and developing countries, in which the Hp infection rate is high (4). Continuing exposure to Hp in developing countries may prevent disappearance of antibodies. Further studies should be performed in this area, particularly in developing countries. Gönül Dinler, M.D. Hasan Özen, M.D. Nurten Koçak, M.D. Aysel Yu ̈ce, M.D. Figen Gürakan, M.D. Division of Pediatric Gastroenterology Hacettepe University Faculty of Medicine Ankara, Turkey

Effect of nitric oxide inhibition on rat liver ischemia reperfusion injury

Objective: to determine the role of nitric oxide (NO) in rat liver ischemia reperfusion we examined the effects of competitive NO synthesis inhibitor L-nitro-arginine-methyl-ester (L-NAME) and NO precursor L-arginin. Methods: 46 Sprague-Dawley rats were divided into five groups. Group 1, sham operated; group 2, 30-min ischemia administered; group 3, 60-min reperfusion administered after ischemia; group 4, 50 mg/kg L-NAME was given i.v. immediately before reperfusion; group 5, 50 mg/kg L-NAME+250 mg/kg L-arginin was given i.v. immediately before reperfusion. At the end of the experiment, liver was removed and superoxide dismutase (SOD), catalase, and malondialdehyde (MDA) were measured, transaminases SGOT and SGPT were measured in sera. Liver was also evaluated histopathologically. Results: transaminase levels were the highest in ischemia reperfusion group. Transaminases in this group were high compared with sham, ischemia, L-NAME and L-arginin groups (***P<0.001, ***P<0.001, *P<0.05, *P<0.05, respectively). SOD activity was 29.8+4 U/mg protein in L-arginin group. This level was the lowest level in all groups. SOD activity in L-arginin group was lower than that of sham and ischemia reperfusion groups (**P<0.01, *P<0.05, respectively). There were no significant differences in catalase activity and MDA levels among groups. Tissue damage was significant in ischemia and ischemia reperfusion groups. Tissue damages in these groups were greater than that of sham group (***P<0.001). In L-NAME treated group, tissue damage was similar to sham group, and significantly less than ischemia reperfusion group and L-arginin group (**P<0.01). Conclusion: even though there was significant tissue damage, we have not observed oxidative stress in the length of ischemia reperfusion period that we have performed. Mechanism of this damage seems to be independent from lipid peroxidation. NO supplementation decreased SOD, but did not cause further tissue damage. NO may dispose O(2)(-) by formation of peroxynitrite. L-NAME did not change lipid peroxidation, but clearly reduced reperfusion injury.

Serum Thrombopoietin Levels and Its Relationship With Thrombocytopenia in Patients With Cirrhosis

Background: Patients with cirrhosis usually have thrombocytopenia in discrete levels. The mechanism of thrombocytopenia is thought as splenic sequestration and destruction of platelets, impaired bone marrow generation and diminished hepatic thrombopoietin synthesis. Objectives: The aim of this study was to evaluate serum thrombopoietin levels and its relationship with thrombocytopenia at patients with cirrhosis. Patients and Methods: Ninety–two cirrhotic patients and 45 healthy controls without history or findings of pathologies that can effect thrombopoietin levels were enrolled by simple random sampling to patient and control groups of this case control study performed at Eskisehir-Turkey. Thrombopoietin was measured in serum samples with a solid phase enzyme-linked immune absorbent assay. Additionally, spleen size and volume index were determined. Results: Platelet counts were lower in patients with cirrhosis (97000 ± 8000/mm3) than in healthy subjects (240000 ± 51000/mm3, P < 0.001). Significant difference was determined for platelet counts among child A, B and C stages (Child A vs. Child B P < 0.05 Child A vs. Child C P < 0.001–Child B vs. Child C P < 0.05). Serum TPO concentration was higher (69 ± 12 pg/mL) in cirrhotic group than healthy controls (49 ± 9 pg/ml) (P < 0.05). No significant difference in TPO levels were found among the Child A, B and C stages (64 ± 11 pg/mL, 75 ± 13 pg/mL and 68 ± 10 pg/mL, respectively). Spleen size and SVI was significantly higher in the cirrhotic patients than healthy controls (148 ± 14 mm vs. 98 ± 11 mm, P < 0.001-9167 ± 287 cm2 vs. 4118 ± 123 cm2). Significant difference was determined for spleen size and spleen index among child A, B and C stages (Child A vs. Child B P < 0.05 Child A vs. Child C P < 0.001–Child B vs. Child C P < 0.05). TPO levels were significantly different between cirrhotic patients with platelet levels below 50.000/mm3 (n = 16, plt-count: 41000 ± 8300/mm3, TPO levels: 73 ± 7 pg/mL) and above 50.000/mm3 (n = 76, plt-count: 105000 ± 9500/mm3, TPO levels: 65 ± 10 pg/mL) (P < 0.01). In correlation analysis, there was a strong negative correlation between platelet count-spleen size (P < 0.001, r = -0.74) and platelet count–serum TPO levels (P < 0.001, r = -0.71). Conclusions: Our results suggest that liver cirrhosis does not cause impaired thrombopoietin production even in the late stage of disease. Thrombopoietin has no contribution for the occurrence of thrombocytopenia in cirrhosis; splenic sequestration seems to be the main factor.

The long-term effects of anti-TNF-α agents on patients with chronic viral hepatitis C and B infections

To evaluate the long‐term effects of anti‐tumor necrosis factor‐alpha (TNF‐α) therapy on patients with chronic hepatitis B and C infections.

Global Epidemiology of Hepatocellular Carcinoma (HCC Epidemiology).

Hepatocellular carcinoma (HCC) is the primary liver cancer derived from hepatocytes and accounts for 85–90% of all primary liver cancers. It is the 5th common cancer in men and the 7th common cancer in women overall in the world [1]. However, it is the third leading cause of cancer-related death, exceeded only by cancers of the lung and stomach. Even HCC is not in the most frequent cancers in the majority of the world, its highmortality and short survival time causes a serious worldwide health burden. Incıdence to mortality rate is 0.95 for HCC and 5 years survival is only 6.9%. Because only a minority of the patients are diagnosed in early stages, overall median survival time is as short as 11 months [2]. Annually, the estimated number of new cases is about 782,000 and causing 600,000 deaths globally per year [1]. HCC burden is not distributed evenly throughout the world. More cases of HCC occur in Asia and Africa than in Western countries and more common in middleand low-income countries than in developed nations. HCC percentages for Asia and Africa are, respectively, 76 and 7.5% of the world [1]. High HCC incidence and dense population of Asia makes Asia the biggest HCC pool continent in the world. Several countries in East Asia have a very high incidence of HCC (over 20 cases/100,000 population). For example, the incidence is 99 per 100,000 persons in Mongolia, 49 per 100,000 in Korea, 29 per 100,000 in Japan. China by itself has half of the world’s HCC burden with annually 395,000 cases with the incidence of 35 in 100,000. A high incidence of HCC also occurs in the Sub-Saharan Africa, particularly the western region of Africa, for example, Cameroon and Mozambique, with incidence rates of over 20 per 100,000 individuals. Mediterranean countries such as Italy, Spain, and Greece have intermediate incidence rates of 10–20 per 100,000 individuals, while North and South America have a relatively low incidence <5 per 100,000 individuals. The most important risk factors for HCC are hepatitis B virus (HBV), hepatitis C virus (HCV), consumption of aflatoxin B1-contaminated food stuffs, excessive consumption of alcohol, and non-alcoholic liver disease. Risk factors for HCC vary by region. Geographical variability in the incidence of HCC has been attributed to the mainly distribution of HBV and HCV infection [3]. Eighty to ninety percent of HCCs are associated with either of two viruses. In Africa and East Asia, the largest attributable fraction is due to hepatitis B (60%), whereas in the developed western world, approximately 20% of cases can be attributed to HBV infection [4]. HBV infection is the predominant HCC risk factor worldwide. Countries with prevalences of chronic HBV infection of greater than 2% have increased incidence and mortality rates of HCC. Chronic HBV infection is the most common etiologic factor in the high-incidence HCC areas. The strong positive correlation between the incidence of HCC and the prevalence of HBV surface antigen in a population, termed Bgeographic parallelism,^ was first described in 1969 [5]. The incidence of HCC in HBV-related cirrhosis in this area of the world has been reported to be 2.7% [6, 7]. The annual risk of HCC is 0.5% for asymptomatic HBsAg carriers and 0.8% for patients with chronic hepatitis B, while patients with HBV cirrhosis have 100 times higher risk of developing HCC, compared to HBsAg-negative individuals. The probability of acquiring HCC increases with severity of underlying liver disease. The lifetime HCC risk for somebody with chronic HBV infection is 10–25%. HBV is a notorious HCC cause in the absence of cirrhosis; however, the majority (70–90%) of HBV-related * Aysegul Ozakyol ahozakyol@yahoo.com

Comparison of 64-Detector CT Colonography and Conventional Colonoscopy in the Detection of Colorectal Lesions

Background: Colon cancer is a leading cause of morbidity and mortality in developed countries. The early detection of colorectal cancer using screening programs is important for managing early-stage colorectal cancers and polyps. Modalities that allow examination of the entire colon are conventional colonoscopy, double contrast barium enema examination and multi-detector computed tomography (MDCT) colonography. Objectives: To compare CT colonography and conventional colonoscopy results and to evaluate the accuracy of CT colonography for detecting colorectal lesions. Patients and Methods: In a prospective study performed at Gastroenterology and Radiology Departments of Medical Faculty of Eskisehir Osmangazi University, CT colonography and colonoscopy results of 31 patients with family history of colorectal carcinoma, personal or family history of colorectal polyps, lower gastrointestinal tract bleeding, change in bowel habits, iron deficiency anemia and abdominal pain were compared. Regardless of the size, CT colonography and conventional colonoscopy findings for all the lesions were cross - tabulated and the sensitivity, specificity, and positive and negative predictive values were calculated. To assess the agreement between CT colonography and conventional colonoscopy examinations, the Kappa coefficient of agreementt was used. Statistical analysis was performed by SPSS ver 15.0. Results: Regardless of the size, MDCT colonography showed 83% sensitivity and 95% specificity, with a positive predictive value of 95% and a negative predictive value of 83% for the detection of colorectal polyps and masses. MDCT colonography displayed 92% sensitivity and 95% specificity, with a positive predictive value of 92% and a negative predictive value of 95% for polyps ≥ 10 mm. For polyps between 6mm and 9 mm, MDCT colonography displayed 75% sensitivity and 100% specificity, with a positive predictive value of 100% and a negative predictive value of 90%. For polyps ≤ 5 mm MDCT colonography displayed 88% sensitivity and 100% specificity with a positive predictive value of 100% and a negative predictive value of 95%. Conclusions: CT colonography is a safe and minimally invasive technique, a valuable diagnostic tool for examining the entire colon and a good alternative compared to other colorectal cancer screening tests because of its high sensitivity values in colorectal lesions over 1 cm.

C-Reactive Protein and Platelet-Lymphocyte Ratio as Potential Tumor Markers in Low-Alpha-Fetoprotein Hepatocellular Carcinoma

The hepatocellular carcinoma (HCC) tumor marker alpha-fetoprotein (AFP) is only elevated in about half of the HCC patients, limiting its usefulness in following the effects of therapy or screening. New markers are needed. It has been previously noted that the inflammation markers C-reactive protein (CRP) and platelet-lymphocyte ratio (PLR) are prognostically important and may reflect HCC aggressiveness. We therefore examined these 2 markers in a low-AFP HCC cohort and found that for HCCs > 2 cm, both markers significantly rise with an increasing maximum tumor diameter (MTD). We calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Youden index value for each marker, and their area-under-the-curve values for each MTD group. Patients were dichotomized into 2 groups based on the CRP and PLR from the receiver-operating characteristic curve analysis. In the logistic regression models of the 4 different MTD patient groups, CRP and PLR levels were statistically significant to estimate MTD in univariate logistic regression models of MTD groups > 2 cm. CRP and PLR were then combined, and the combination was statistically significant to estimate MTD groups of 3-, 4-, and 5-cm cutoffs. CRP and PLR thus have potential as tumor markers for low-AFP HCC patients, and possibly for screening.