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.

Hitherto undescribed venous vacuolar myopathy without mucoid degeneration in the varicose saphenous vein of a child.

Varicose vein abnormalities involving the lesser saphenous vein of a 7-year-old boy are presented. The histopathology of the vein wall revealed a vacuolar degeneration without mucoid deposits of the muscle cells, which has not been described previously in the literature in congenital varices.

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.

No evidence for overexpression of the p53 protein and mutations in exons 4-9 of the p53 gene in a large family with adenomatous polyposis.

OBJECTIVE: Familial adenomatous polyposis coli (FAP) is an autosomal dominant disease characterized by an early onset of numerous adenomatous polyps of the colon and a high risk of colon carcinoma. The role of the p53 gene in the multistage process of FAP is as yet poorly defined. In the present study, a large family with evidence of polyposis and colon cancer was screened for the mutations of the p53 gene and protein overexpression. METHODS: We examined p53 protein expression from individuals with immunohistochemical techniques using monoclonal antibody PAb1801. Polymerase chain reaction products of exons 4-9 of the p53 were examined from individuals by single strand, conformational polymorphism analysis. RESULTS: We could find no evidence of overexpression and mutations of the p53 in any lesion including adenomas and carcinomas. CONCLUSION: We found that p53 gene alterations do not contribute to the genesis of adenoma or carcinoma of FAP patients for this large family examined.

What is the association of primary sclerosing cholangitis with sex and inflammatory bowel disease in Turkish patients?

BACKGROUND/AIMS: In the Western world, primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease that is associated with inflammatory bowel disease (IBD), particularly chronic ulcerative colitis and, to a lesser degree, Crohn's disease. The goal of this study was to determine the prevalence of PSC in Turkish patients with IBD and chronic amebic colitis, a disease that is endemic in Turkey. METHODOLOGY: During a 10-year period, between 1986 and 1996, a total of 81 IBD (64 ulcerative colitis and 17 Crohn's disease) patients and 127 patients with chronic amebic colitis were seen and evaluated with radiologic, serologic, immunologic and pathologic tests. Whenever a clinical or biochemical finding suggested the presence of co-existent hepatic and/or biliary disease, the patient was further evaluated by liver biopsy, auto-antibodies and endoscopic retrograde cholangiopancreatography (ERCP) to determine whether they also had PSC or some other form of liver disease. As a disease control group, a total of 752 patients with clinical and/or laboratory evidence of pancreaticobiliary disease were also studied. In 86 of these 752 patients (10%), a primary disorder of the biliary tree was diagnosed by ultrasonography, computed tomography, peritoneoscopy, liver biopsy, ERCP and abdominal laparotomy. In addition, all 86 patients of the control group were evaluated endoscopically in order to determine whether they had any associated gastrointestinal condition of the upper or lower gastrointestinal tracts. After establishing final diagnoses of IBD, amebic colitis and PSC, these patients were evaluated with respect to their socio-economic status. A high protein diet (1.8 gram/kg/day) was administered to those patients with chronic amebic colitis and IBD during the active period of the disease. RESULTS: Of the 208 patients (81 with IBD and 127 with chronic amebic colitis), no cases of PSC were identified. Of the 86 patients in the control group with primary biliary tract disease, 45 had a biliary system malignancy, 14 had primary biliary cirrhosis (PBC), 16 had PSC, 3 had Caroli's disease, 6 had a common bile duct cyst, and 2 had gallbladder adenomatosis. All but 1 of the 16 patients with PSC were female. CONCLUSIONS: These data suggest that, in contrast to findings in Western Europe and the USA, in Turkey: 1) PSC is not regularly associated with idiopathic IBD; 2) most patients with PSC are female; 3) PSC accounts for only 18% of patients with a primary disorder of the biliary tree; 4) the incidence of small-duct primary sclerosing cholangitis is greater than that reported in the literature; and, 5) the incidence of IBD and PSC in Turkey is relatively lower than in other countries.

The usefulness of intra-operative endoscopy in Peutz-Jeghers syndrome: a case report.

The Peutz-Jeghers syndrome is an autosomal dominant inherited disease manifested by a combination of mucocutaneous pigmentation and gastrointestinal hamartomatous polyps that usually cause intussusception and intestinal hemorrhage. We report a case in which the patient has been followed-up on for 14 years and who underwent surgical and endoscopic polyp removal several times as well as one intestinal resection. This time, with the use of combined surgery and perioperative endoscopy, 27 polyps were removed, performing only 3 enterotomies. This is the highest number in one session to be reported in the literature. The usefulness of this technique is providing a "clean small intestine" that allows the patient a longer time interval between laparotomies and reduces the complications associated with multiple laparotomies and resections.

Pregnancy complicated by congenital hepatic fibrosis with cavernous transformation of the portal vein: a case report.

A 24-year-old primigravid woman with cogenital hepatic fibrosis associated with cavernous transformation of the portal vein is described. Although the neonate could not survive because of the ileal atresia, the pregnancy and delivery did not pose a significant threat to the mother.

Multiple lymphomatous polyposis.

Multiple lymphomatous polyposis (MLP) is a distinctive and particularly rare clinical type of malignant gastrointestinal lymphoma, which is classified as B-cell centrocytic non-Hodgkin's lymphoma. this rare entity has been recently reclassified as mantle cell lymphoma. We herein report three additional cases of MLP involving various segments of the gastrointestinal tract. MLP has an aggressive biologic behavior and a relatively poor prognosis and must be treated accordingly as a high-grade lymphoma with systemic chemotherapy.

Benign mesenchymoma of the esophagus.

Benign mesenchymoma is an extremely rare neoplasm mostly located in or about the kidney and is composed of a haphazard mixture of adult fat, fibrous tissue and tangled blood vessels, scattered nests or masses of smooth muscle cells, occasionally islands of cartilage, bone, and lymphoid tissue as well as other mesenchymal elements. Only two cases of benign mediastinal mesenchymomas were reported in the literature. In this report we describe a benign mesenchymoma of the mediastinum which presented itself with symptoms and signs of the traction diverticula of the esophagus.

Congenital hepatic fibrosis associated with cavernous transformation of the portal vein.

BACKGROUND/AIMS: Congenital hepatic fibrosis (CHF), which is one of the fibropolycystic diseases, occurs in various forms. Portal hypertension, a very common clinical feature of this condition, has been attributed to the compression of portal vein radicles in the fibrous bands. We investigated whether there are any other contributing factors in the development of portal hypertension in patients with CHF. METHODOLOGY: A total of 1285 patients with portal hypertension of different etiologies were studied using ultrasonography as the screening test. Forty-seven (including portal vein involvement and/or CHF) of these 1285 patients were prospectively studied to evaluate the etiology of the portal hypertension by portography, abdominal computed tomography, exploratory laparotomy, peritonoscopy, liver biopsy and laboratory tests. The patients with CHF were divided into two groups, according to whether or not they had portal vein involvement. RESULTS: Eleven (0.8%) of the 1285 patients with portal hypertension had CHF, and 41 (3.2%) had cavernous transformation of the portal vein (CTPV), resulting from different or unknown etiologies. Five patients had both pathologies (CTPV and CHF). In the 11 patients with CHF, there was CTPV in 5 patients, Caroli's disease in 2 patients, cholangiocarcinoma in 1 patient, inferior vena caval obstruction in 1 patient, and CHF in only 2 patients. There were statistically significant differences in the age of the CHF patients at clinical onset, the incidence of bleeding from esophageal varices, and laboratory findings between the 2 groups with and without CTPV. Despite a thorough investigation, we could not distinguish any predisposing factor in 25 of the 41 patients with CTPV. The incidence of CTPV was 48% in patients with CHF and 3.2% in patients with portal hypertension. CONCLUSIONS: These results suggest that the association of CTPV with CHF is not coincidental, but that CTPV may be associated with CHF and a new possible factor in portal hypertension, and that it can be a major factor in the manifestation of esophageal bleeding from varices.

Periampullary carcinoma detected after sphincterotomy.

BACKGROUND/AIMS: Although periampullary carcinoma can often be diagnosed at an early stage because of its strategic location, in a substantial number of cases (23% to 25% of periampullary carcinoma cases), the papilla can be prominent, but without an identifiable mass or ulceration. As a result, duodenoscopy alone can miss the tumor. In this series, the usefulness of sphincterotomy in establishing a diagnosis of periampullary carcinoma is documented. MATERIALS AND METHODS: A total of 664 patients, who had clinical, biochemical and/or sonographic evidence of pancreaticobiliary disorders underwent endoscopic retrograde cholangiopancreaticography (ERCP) at Hacettepe University Hospital between March 1985 and September 1994. All identified lesions were biopsied. RESULTS: In sixty-six of the 664 patients, a specific periampullary or pancreatic diagnosis could be made. These included 30 cases of pancreatic carcinoma (14 in the head, 15 in the corpus, and 1 in the tail), 10 cases of chronic pancreatitis, 15 cases of periampullary carcinoma and 11 miscellaneous. None of the 15 periampullary carcinomas was demonstrable by abdominal computed tomography, sonography or pancreatic angiography. In 12, the diagnosis was established immediately by endoscopic visualization of the tumor and biopsy. In the remaining 3, the tumor was visualized as a protruding mass only after a papillatomy was performed. All cases were treated surgically with a pylorus preserving pancreaticoduodenectomy. No symptoms of dumping were experienced postoperatively. The survival of these 15 patients was good with a mean survival of 24.2 months. CONCLUSIONS: Careful endoscopic examination of the periampullary mucosa before and after sphincterotomy is required to identify periampullary carcinoma. A pylorus preserving pancreaticoduodenectomy revealed excellent post-surgical outcome with no post operative symptoms of the dumping syndrome.

Helicobacter pylori infection in symptomatic and asymptomatic children: a prospective clinical study.

It is well known that Helicobacter pylori infection is extremely common throughout the world, but most infected persons do not develop ulceration and remain asymptomatic. This study was undertaken in order to determine the prevalence of H. pylori infection, the age distribution, and the factors that may affect the frequency of H. pylori infection. We evaluated the presence of antibody against H. pylori in children and adolescents, we also assessed the efficacy of non-invasive and invasive methods for detection of H. pylori infection in children who had undergone upper gastrointestinal endoscopy. We evaluated 43 males and 18 females whose ages ranged from 1 to 17 years (mean age: 9.4 +/- 4.2). 29 of all cases were symptomatic and 32 were asymptomatic. H. pylori infection was present in 49% of the studied cases. The data were analysed by Fisher's exact chi-square and Mantel-Haenszel tests. It was found that H. pylori infection graphically increased with age in both groups from 25% at ages 3-5 to 80% at ages 16-20. But no association was determined statistically between age and H. pylori positivity (p < 0.05). H. pylori infection was determined in 14 (48%) and 16 (50%) cases in symptomatic and asymptomatic groups respectively. There was no significant difference between H. pylori and either group (p > 0.05). According to the endoscopy findings, the symptomatic group was divided into two subgroups: children with peptic ulcer and children with non-ulcer dyspepsia (NUD). An attempt was made to compare ulcer, non ulcer dyspepsia and asymptomatic cases with H. pylori positivity, but no significant relation could be established between the groups (p > 0.05). 14 (23%) of the cases had previous gastric and/or intestinal complaints in their parents (positive family history). There was a significant, statistically positive relation between family history and symptoms (p < 0.01). Nevertheless, no association was found between H. pylori infection and family history (p > 0.05). There were no significant differences in H. pylori infection related to sex, type of housing, location of housing, socio-economic status (SES) or source of water supply. It is concluded that H. pylori infection has a high prevalence in our country. Although endoscopic evaluation is an invasive method, under our conditions, histopathological examination with 97% is shown to be much more sensitive in determination of H. pylori infection. Since no community difference was determined in the prevalence of H. pylori infection, all children should be considered to be under the threat of the same risk.

Cavernous transformation of the portal vein is associated with pancreatic duct atrophy.

BACKGROUND/AIMS: To determine whether or not portal venous obstruction affects pancreatic duct size. MATERIAL AND METHODS: The ERCP findings of 43 of 51 subjects with cavernous transformation of the portal vein (CTPV) were studied prospectively. In three, the ERCP failed to demonstrate the pancreatic duct (PD) for technical reasons and in 8 of the original 51 subjects, the ERCP was not attempted because of a lack of indications and unwillingness of the subject to undergo the procedure. The ERCP findings of the remaining 40 subjects were compared with those of 23 normal concurrent controls and those of reference controls. RESULTS: In 21 of the 51 patients, an underlying disorder responsible for portal vein thrombosis and cavernous transformation was identified. Despite a full clinical, radiologic, hematologic and biochemical evaluation, no etiology for CTPV was found in the remaining 30 patients. The pancreatic duct diameter was measured at the widest portion of the duct where it traverses the head of the pancreas. In 34 of the 40 patients with CTPV and a successful ERCP, the pancreatic duct was smaller (less than 2.28 mm in diameter) than that of concurrent control subjects and a reference control group (p < 0.05). In only 6 subjects with CTPV was the pancreatic duct size within normal limits. In 3 of these 6, a confounding common bile duct stone was shown to be present and may have accounted for the pancreatic duct enlargement as compared to the other 34 subjects with CTPV. CONCLUSIONS: These results indicate that a smoothly narrowing pancreatic duct hypoplasia or atrophy can be demonstrated in 85% of cases with CTPV. It is speculated that this finding is a consequence of the obstructed pancreatic venous drainage that occurs with CTPV.

A comparison of chemoembolization with conventional chemotherapy and symptomatic treatment in cirrhotic patients with hepatocellular carcinoma.

BACKGROUND/AIMS: The results of transcatheter arterial chemoembolization (TACE) in 28 cirrhotic patients with advanced hepatocellular carcinoma (HCC) were compared to those obtained in 15 cirrhotic patients with HCC treated with systemic chemotherapy, and 14 patients with HCC receiving no specific anti-cancer treatment. MATERIALS AND METHODS: From November, 1986 through May 1994, 235 patients with HCC were seen by the investigators. Twenty eight of these patients actually received TACE. The chemotherapeutic agent used was mitomycin C mixed with Lipiodol and arterial embolization was achieved using Gelfoam. In 19 of 28 cases treated with TACE, the embolization was limited to an artery feeding the tumor, thereby avoiding liver cell injury in non-tumor tissue. In 9 others, the main left or right hepatic artery was embolized. The results obtained in these 28 cases were compared to those obtained in 15 patients with HCC larger than 5 cm. who received systemic mitomycin C and doxorubicin chemotherapy and with those obtained in 14 patients who received no specific anti-tumor therapy. RESULTS: One patient died of liver failure related to the TACE and three patients died of bleeding from esophageal varices within weeks of the TACE procedure. Two of the remaining 24 patients are alive with a follow-up of 6 and 22 months. Twenty-six of the 28 patients treated with TACE died within 1 and 28 months of the initiation of the TACE therapy. The mean survival of those receiving TACE was 13.0 months. Chemotherapy without embolization yielded a mean survival of 7.2 months. The mean survival of the patients receiving no specific anti-cancer treatment was only 6.9 months. There was no statistical differences between the survival of those receiving systemic chemotherapy and those receiving no specific treatment. In contrast, the mean survival of the group receiving TACE was significantly greater than that of either of the other two groups (p < 0.005). CONCLUSIONS: These data suggest that TACE provides the best survival for individuals with larger hepatocellular carcinomas (> 5 cm) not eligible for surgery or percutaneous ethanol injection (PEI).

The use of deferoxamine infusions to enhance the response rate to interferon-alpha treatment of chronic viral hepatitis B.

An individual's iron status may affect the response rate achieved with the use of interferon (IFN) as therapy for chronic viral hepatitis. A total of 27 patients with chronic hepatitis B viral infection, who had elevated serum ferritin levels, were randomized to receive either IFN 5 MU, three times weekly by subcutaneous injection alone (n = 14) or in combination with cycles of deferoxamine at a dose od 80 mg kg-1 per cycle (n = 13) administered over 3 consecutive days, to reduce their iron and maintain a serum ferritin level less than 250 ng ml-1. All deferoxamine-treated patients were on a low iron-containing diet. An IFN response was defined as a normalization of the serum alanine aminotransferase (ALT) level and seroconversion from hepatitis B e antigen (HBeAg) positivity to hepatitis B e antibody (HBeAb) positivity. The deferoxamine-treated group experienced a reduction in their serum ferritin level to 226 +/- 73 ng ml-1 as a result of the deferoxamine treatment. Six of the 13 (46%) deferoxamine-treated patients and two of the 14 (14%) control patients normalized their ALT levels. Seven of the 13 (54%) deferoxamine but only 14% of the IFN-treated group seroconverted to HBeAb positivity. A greater rate of histological improvement and loss of hepatitis B virus (HBV) DNA was seen in the deferoxamine-treated group. Two of the deferoxamine-treated patients were treated only once, two were treated twice, seven were treated three times and two were treated four times to achieve a ferritin level below 250 ng ml-1. Based on these data, we conclude that deferoxamine infusion enhances the rate of response to IFN in subjects with chronic hepatitis B. The precise mechanism of this phenomenon is not clear.

Relationship between the serum alanine aminotransferase level at the end of interferon treatment and histologic changes in wild-type and precore mutant hepatitis B virus infections.

Unravelling the role of interferon (IFN) in the treatment of chronic hepatitis B compliance by many factors. Several mutant forms of hepatitis B virus (HBV) have recently been discovered; the most common of these is the precore mutant, characterized by hepatitis B e antigen (HBeAg) negativity and hepatitis B e antibody (HBeAb) positivity in an individual with an active HBV infection. The aim of this study was to compare the response rate to IFN therapy in patients with wild-type HBV infection and in individuals infected with the precore mutant. A second aim was to evaluate the role of an increased serum ferritin in terms of the IFN response rate in these two different types of HBV infection. IFN therapy was administered at a dose of 5 MU subcutaneously three times weekly for 6 months to 41 individuals with a chronic wild-type hepatitis B infection and 16 individuals with a precore mutant chronic HBV infection. An IFN response was defined as normalization of the serum alanine aminotransferase (ALT) level and an HBeAb to HBeAb seroconversion (in wild-type hepatitis infection), and a normalization of the serum ALT in individuals infected with a precore mutant infection. At entry, the two groups were matched for age, gender, serum ALT, serum iron, total iron binding capacity (TIBC), serum ferritin and liver histology. Forty-six per cent of the subjects with wild-type disease responded to IFN therapy. By contrast, only four of the 16 cases (25%) of the precore mutant cases responded (p < 0.05). Ferritin levels correlated well with the type of IFN response; as the serum ferritin level increased, the response rate to IFN declined. Hapatic infection caused by a precore HBV mutant is more resistant to IFN therapy than wild-type infection. The serum ferritin level appears to influence the type of IFN response achieved. Individuals with a serum ferritin level greater than 300 ng ml-1 failed to respond to IFN in 93% of the cases studied.

Is portal hypertension due to liver cirrhosis a major factor in the development of portal hypertensive gastropathy?

OBJECTIVES: The gastric mucosa of patients with portal hypertension frequently manifests changes in its appearance that are readily identifiable by endoscopy. Many of these can be sources of bleeding, and some imply the presence of systemic disease. Although portal hypertension is critical in development of portal hypertensive gastropathy (PHG), the role that other factors might play in its pathogenesis is uncertain. METHODS: Four groups of subjects were studied prospectively: 37 with portal hypertension due to cirrhosis, 26 noncirrhotic subjects with portal hypertension due to extrahepatic portal vein obstruction (PVO), nine cirrhotic patients with extrahepatic PVO, and 57 control subjects. The diagnosis in each case was based on a combination of clinical data, needle liver biopsy, ultrasonography, splenoportography, and upper GI endoscopy. RESULTS: Snake skin, scarlatina rash, diffuse hyperemia, and diffuse bleeding were frequent endoscopic gastric findings in cirrhotic patients. These findings were seen less frequently in noncirrhotic patients with portal hypertension due to PVO than in cirrhotic patients (p< 0.0001). The highest incidence was seen in cirrhotic patients with PVO (P< 0.001). Positive correlations existed among the endoscopic findings, the clinical estimate of the cirrhosis severity (Child-Pugh grade), and the size and appearance of esophageal varices (Beppu score). No endoscopic findings of the gastric mucosa enabled one to distinguish between groups. Hypergastrinemia was present in cirrhotics with and without PVO but not in noncirrhotic patients with portal hypertension resulting from isolated PVO. CONCLUSION: These findings suggest that the endoscopic findings of PHG are affected by the severity of the underlying liver disease and the presence or absence of coexisting PVO. There is no association between PHG and the presence of gastric varices. Thus, the development of the gastric lesions characteristic of PHG requires not only portal hypertension but also some other consequence of parenchymal liver disease.