Early gastric carcinomas in the cardiac region: diagnosis with double-contrast x-ray studies.

BACKGROUND: The ratio of early to advanced gastric carcinomas in the cardiac region is significantly low. It is necessary to establish methods of early diagnosis of gastric carcinomas in the cardiac region. METHODS: Twenty cases (21 lesions) of early gastric carcinomas in the cardiac region were resected between 1997 and 2001. We studied the macroscopic characteristics of the specimens, films of double-contrast upper gastrointestinal studies before operations, and the detectabilities of findings in each projection. RESULTS: Four of 21 early gastric carcinomas in the cardiac region were on the anterior wall, 10 were on the lesser curvature, and seven were on the posterior wall. In seven of 21 lesions the carcinomas were not detected in the resected specimens macroscopically; in five, the area of carcinoma was not clearly traced in the resected specimens; and in nine, the area of carcinomas was clearly traced. In the morphologic study, 16 (76.2%), two (9.5%), two (9.5%), and one (4.8%) of the 21 lesions showed the superficial depressed type (IIc), superficial elevated type (IIa), superficial elevated and superficial depressed type (IIa + IIc), flat and superficial depressed type (IIb + IIc), respectively. Mucosal reddening was seen in 11, and mucosal discoloration was seen in one; change of color was not seen in the remaining nine lesions. Twenty lesions were diagnosed as differentiated adenocarcinomas, and one lesion was diagnosed as undifferentiated adenocarcinoma. Radiologically, early gastric carcinomas in the cardiac region had the following features: localized shallow barium deposits, localized abnormal barium coating, and niche and radiolucent lesions. Four (100%) of four lesions on the anterior wall, 10 (100%) of 10 lesions on the lesser curvature, and seven (100%) of seven lesions on the posterior wall were detected in the half-standing, prone, right anterior, oblique projection. Seven (100%) of seven lesions on the posterior wall and 10 (100%) of 10 lesions on the lesser curvature were detected in the half-standing, supine, left anterior, oblique projection. CONCLUSION: Even though most early gastric carcinomas in the cardiac region demonstrate few macroscopic findings, the half-standing, prone, right anterior, oblique projection and the half-standing, supine, left anterior, oblique projection are useful in the double-contrast studies.

High trough levels of oral FK506 induced by loss of small intestine.

To establish a safe and effective usage of oral tacrolimus (FK506) in small bowel transplantation (SBTx) recipients, trough levels and area under the curve (AUC) values of FK506 were assessed using swine models of SBTx and short bowel. Thirty-eight Landrace male piglets were divided into four groups as follows: Group 1, controls (n=13); Group 2, a one-third small bowel model (n=5); Group 3, a short bowel model (n=10); and Group 4, a one-third small bowel allograft model (n=10; five donors and five recipients). Piglets of Groups 1 and 3 were further divided into two sub-groups, according to the route of drug administration: Groups 1a (n=10) and 3a (n=7) received FK506 orally, and Groups 1b (n=3) and 3b (n=3) received FK506 intravenously. Oral or intravenous FK506 was started on post-operative day 3 and continued until day 7 in each group. On day 7, trough levels and AUC values were measured. In Groups 1a, 2, 3a and 4, trough levels of FK506 were 2.1+/-1.2 (p<0.01 vs. Group 2, 3a or 4), 11.2+/-2.1, 23.3+/-4.8 (p<0.05 vs. Group 2 or 4) and 14.6+/-3.0 ng/mL, and AUC values were 101+/-90 (p<0.01 vs. Group 3a or 4), 319&+/-155, 808+/-200, and 531+/-113 ng.h/mL, respectively. Both trough levels and AUC values were lowest in Group 1a and highest in Group 3a. Between Groups 1b and 3b, there was no significant difference in the blood levels of intravenous FK506. The shorter the functioning residual small intestine was, the higher the trough level of oral FK506 was, while the presence or absence of small intestine did not affect blood levels of intravenous FK506. These results suggest that oral FK506 is metabolized in the functioning small intestine during its absorption. Therefore, events which cause intestinal malfunction, such as graft rejection in SBTx, inflammation and loss of small intestine, may adversely raise the trough level of oral FK506.

CD8+ T cells infiltrating into bile ducts in biliary atresia do not appear to function as cytotoxic T cells: a clinicopathological analysis.

It is speculated that immune mechanisms are involved in bile duct damage in biliary atresia (BA), as in primary biliary cirrhosis (PBC). In BA, however, no reports have described the in situ distribution of cytotoxic T lymphocytes (CTLs) using specific markers, nor has the clinical association been clarified. The present study describes the immunohistochemical distribution of CD8+ T cells and the relevant markers [perforin, granzyme B, FasL (CD95L)] in 47 cases of BA operated upon at days 12-79. The results were compared with those of PBC. In BA, CD8+ T cells infiltrated bile ducts in a way similar to that observed in PBC. However, in sharp contrast to PBC, none of the inflammatory cells infiltrating into the bile ducts in BA expressed cytotoxic markers such as perforin, granzyme B, or Fas ligand (FasL). Clinical follow-up of patients with BA revealed that a greater degree of infiltration of bile ducts by CD8+ T cells is associated with better liver function. Taken together, these data suggest the absence of direct CTL activity against bile ducts in BA in the postnatal period.

Problems during and after pregnancy of former biliary atresia patients treated successfully by the Kasai procedure.

BACKGROUND/PURPOSE: The aim of this study was to investigate the problems and the quality of life during and after pregnancy of the patients who had undergone Kasai operation and to find out a strategy for follow-up during the period of their pregnancy. METHODS: A questionnaire was sent to 134 institutions of the Japanese Biliary Atresia Society with the following questions: (1) Do you have any pregnancy cases in patients who had undergone Kasai operation? (2) Did she have any menstrual problem? (3) Did she have any problem during pregnancy and delivery? (4) Did she have any change in liver function tests after delivery? (5) Did she have any early and long-term problem after delivery? (6) Did the baby have any problem? (7) Was there any special care or comment about the pregnancy of the biliary atresia patients? The responses were analyzed. RESULTS: Fourteen institutions reported 16 cases of pregnancy, 23 cases of delivery, and 2 cases of abortion. The causes of abortion in the 2 cases were attributed to hemorrhagic shock after massive bleeding from esophageal varices and serious atopic dermatitis, respectively. Other problems during pregnancy were abruption of placenta, fetal distress leading to caesarian section, and development of liver dysfunction leading liver transplantation. Problems after delivery included deterioration of liver function in 6 patients (37.5%), attacks of ascending cholangitis in 4 patients (25.0%), and severe fatigue with liver dysfunction from nursing the baby leading to liver transplantation. Only 3 of 16 (18.8%) patients were free of any problems. No abnormality was seen in the babies. CONCLUSIONS: Even if the patients with biliary atresia lead a good postoperative course, unexpected complications can occur when they become pregnant. Close long-term follow-up is required for proper management of pregnancy in biliary atresia patients.

The role of thymidine phosphorylase expression in the invasiveness of gastric carcinoma.

BACKGROUND: Thymidine phosphorylase (TP) has angiogenic activity in various cancer tissues. Gastric carcinomas are classified into two histologic groups: differentiated and undifferentiated adenocarcinomas. There are differences in the modes of development and the extent of infiltration between the two groups. The purpose of the current study was to determine whether TP is involved in the invasiveness and progression of these two types of gastric carcinoma. METHODS: To investigate the expression and localization of TP and the microvessel counts, the authors examined specimens from 149 gastric carcinoma patients. The specimens were stained using monoclonal antibody against TP and polyclonal antibody against factor VIII. To determine the cell type expressing TP, immunohistochemical staining using a monoclonal antibody against CD68 that is specific for macrophages and double staining using antibodies to both TP and CD68 were performed. RESULTS: The proportion of TP positive tumors in differentiated adenocarcinomas was higher than that in undifferentiated adenocarcinomas. The TP positive differentiated adenocarcinomas invaded more deeply than the TP negative ones, but this was not the case with undifferentiated adenocarcinomas. TP was expressed mainly in the invasive edges of tumors and was expressed more frequently in macrophages than in tumor cells. TP expression was correlated with microvessel count and CD68 expression. Patients with TP positive carcinomas had a poorer prognosis than those with TP negative differentiated adenocarcinomas. CONCLUSIONS: TP expressed in macrophages may be correlated with microvessel count and play an important role in tumor invasiveness and progression in differentiated gastric adenocarcinoma.

The action of a novel vitamin D3 analogue, OCT, on immunomodulatory function of keratinocytes and lymphocytes.

Topical vitamin D3 has relatively recently been introduced for the treatment of psoriasis. Synthetic vitamin D3 analogues with a high potential for inducing differentiation of cells, but with a low hypercalcemic effect have recently been developed. One such synthetic analogue of 1,25-dihydroxyvitamin D3 (calcitriol), 22-oxacalcitriol (OCT), is a novel agent for the topical treatment of psoriasis. The activity of OCT in vitro was investigated and compared with that of a series of vitamin D3 analogues as to their ability to inhibit murine T lymphocyte proliferation stimulated by con-A, to suppress IL-6 and IL-8 production by keratinocytes stimulated with IL-1alpha and TNFalpha, and to inhibit AP-1- and NFkappaB-dependent reporter gene expression. OCT inhibited the proliferation of lymphocytes and suppressed IL-8 and IL-6 production by keratinocytes to the same extent as the other vitamin D3 analogues. It also inhibited AP-1- and NFkappaB-controlled luciferase activity to the same extent as the other vitamin D3 analogues, which demonstrates its mechanism of action in the suppression of inflammatory processes.

Abnormal distribution of nerve fibers in the liver of biliary atresia.

We investigated changes in the pattern of hepatic innervation in liver specimens from 15 infants with biliary atresia and 4 age-matched controls by immunohistochemical methods. In the control, nerve fibers identified by immunoreactivity for neural cell adhesion molecule (NCAM) and S100 protein were present around the branches of hepatic arteries, portal veins and bile ducts in the portal areas and the hepatic lobules. In biliary atresia, NCAM and S100 positive nerve fibers were increased in the vicinity of the hepatic arteries and the portal veins in the enlarged portal areas, while no nerve fibers were observed around bile ducts and periportal ductules which became NCAM positive. No innervation in the lobules was seen in any cases regardless of the histological alteration. These findings may suggest that the abnormal innervation in the liver with biliary atresia does not occur as a result of structural changes in liver architecture caused by portal fibrosis and inflammation, but is associated with immaturity or malformation of hepatic innervation in the patients.

Living related partial liver transplantation in biliary atresia: 11 cases of experience.

Eleven children, 4 males and 7 females, with biliary atresia receiving living related liver graft were studied. The mean age was 1.8 years and the mean body weight was 10.3 kg. The donors were 4 fathers and 7 mothers. The graft was the lateral segment or left lobe. ABO blood group matching was compatible in 9 and incompatible in 2. All patients except one were crossmatch negative. Immunosuppression at induction was triple therapy (cyclosporine, azathioprine and steroid) or FK506 plus steroid. Acute rejection episodes were treated with pulse steroids. When the signs of rejection persisted despite steroid pulse therapy, 15-deoxyspergualin (DSG) was added. The survival rate of the patients was 73%. Three patients died of portal vein thrombosis, hepatic artery thrombosis and sepsis respectively. Other major complications included hyperbilirubinemia, bile duct stenosis, bile leakage and portal vein anastomosis narrowing. Complications of the donor were sepsis in one, and liver dysfunction in two. Although there are some complications related to graft size mismatch and operative procedure, living related partial liver transplantation is an effective therapy in countries where donor source is restricted.

Clinical significance of 99mTc-DTPA galactosyl human serum albumin scintigram in follow-up after Kasai operation.

The scintigram using 99mTechnetium-DTPA galactosyl human serum albumin (99mTc-GSA) which binds to asialoglycoprotein receptors on hepatocytes is a good index of hepatocyte function in various liver diseases in adult patients. In 43 patients (4 months to 30 years old) who had undergone Kasai procedure, we performed 53 series of 99mTc-GSA scintigrams and checked the laboratory data of blood draw and the clinical status. The indices for blood clearance and liver accumulation were evaluated on the basis of the dynamic data after 99mTc-GSA injection. HH15 as an index of the blood clearance, and LHL15 as an index of the accumulation of the hepatocytes were calculated and the HH15/LHL15 ratio (H/L15) was examined. 99mTc-GSA scintigram correlated with liver function and clinical status. Our results revealed that 1) The deterioration of the liver functions and clinical status correlates proportionally with H/L15, 2) The results of 99m Technetium-GSA scintigram correlate with several liver function tests, especially direct bilirubin, albumin and choline esterase, 3) This scintigram is an useful index of clinical status and hepatic function as well as the change of the hepatic parenchymal reserve in BA patients, especially for the evaluation of liver transplantation.

The outcome of surgery for biliary atresia and the current status of long-term survivors.

Between 1953 and 1995, 300 patients with biliary atresia underwent surgery at Tohoku University Hospital. The 10-year survival of patients who were operated on in or before 1965 was 9%. But the survival rate went up to 61% in patients operated on between 1976 and 1985. Eighty-five patients including 2 who developed liver failure after Kasai operation and underwent liver transplantation have survived more than 10 years. Eleven of them (13%) have recurrent or persistent jaundice. Of the 30 patients who have survived more than 20 years (10 males and 20 females, age range; 20 to 41 years), 20 underwent hepatic portoenterostomy, 8 underwent hepaticoenterostomy and the remaining 2 underwent hepatic portocholecystostomy. None of these patients has undergone liver transplantation. Twenty-two patients have led near-normal lives. The remaining 8 patients have experienced some troubles due to cholangitis, portal hypertension, intrahepatic gallstones and so on. Two of them are considered as candidates for liver transplantation. While the majority of long-term survivors of biliary atresia have good quality of life, close long-term follow-up is essential even in patients with biliary atresia aged 20 years or more.

[Long-term outcome of surgery for biliary atresia].

Between 1953 and 1995, 300 patients with biliary atresia underwent surgery at Tohoku University Hospital. Among them, 31 patients survived more than 20 years, while one of these patients died of hepatic failure at the age of 28 years. Of the 30 surviving patients (10 males and 20 females, age range; 20 to 41 years), 20 underwent hepatic portoenterostomy, 8 underwent hepaticoenterostomy and the remaining 2 underwent hepatic portocholecystostomy. None of these patients has undergone liver transplantation. Twenty-two patients have led near normal lives. This includes three married women, one of whom gave birth to 2 healthy babies. The remaining 8 patients have had experienced some troubles due to cholangitis, portal hypertension and intrahepatic gallstones. Two of them who have progressive liver dysfunction are being considered as candidates for liver transplantation. The quality of life of one patient has been severely affected by an unrelated (Turner's syndrome). While the majority of long-term survivors of biliary atresia have good quality of life, close long-term postoperative follow-up is required.

Hepatocyte growth factor/scatter factor expressed in follicular papilla cells stimulates human hair growth in vitro.

Hepatocyte growth factor/scatter factor (HGF/SF) is a multifunctional polypeptide which acts as mitogen, motogen, or morphogen. In this study, we examined the effect of HGF/SF on human hair growth using organ and cell culture systems. HGF/SF was found to stimulate hair length and DNA synthesis in hair follicles at increasing concentrations up to 10 ng/ml (P < 0.05 and P < 0.01, respectively). HGF/SF stimulated [3H]thymidine incorporation by hair bulb-derived keratinocytes with the strongest response at 30 ng/ml of HGF/SF (P < 0.05). Cultured follicular papilla cells secreted HGF/SF, measured by an enzyme-linked immunoassay, in response to interleukin 1-alpha (IL1-alpha, 10 ng/ml), tumor necrosis factor-alpha (TNF-alpha, 10 ng/ml), or tetradecanoylphorbolacetate (100 nM) at levels ranging from 0.2 to 0.3 ng/mg protein/48 h. HGF/SF mRNA expressions, measured by the reverse transcription-polymerase chain reaction, were detected in follicular papilla cells, and were also stimulated by the three reagents. Transforming growth factor-beta (10 ng/ml) suppressed both protein and mRNA levels. These results suggest that hair follicle elongation induced by HGF/SF in organ culture occurs partly due to the mitogenic activity of HGF/SF expressed in follicular papilla cells on hair bulb-derived keratinocytes.

Dermal papilla cells express hepatocyte growth factor.

In the induction, development and maintenance of hair follicles, it is thought that an epithelial-mesenchymal interaction is important and that the dermal papilla plays some important roles. Hepatocyte growth factor is a multifunctional polypeptide which acts as mitogen, motogen or morphogen depending on the biological context. Recently, we found that HGF stimulates hair follicle growth in a mouse organ culture system, and therefore proceeded to investigate the expression of HGF on cultured human dermal papilla cells (DPC) and the effect of HGF on cultured human keratinocytes derived from hair bulb. Using an enzyme immuno assay, HGF immunoreactivities were not detected in conditioned media of DPC that were either non-treated or treated with TGF-beta, but were detected in conditioned media of DPC treated with IL1-alpha, TNF-alpha and TPA. Using the reverse transcription-polymerase chain reaction (RT-PCR) method, HGF mRNA was also detected in DPC. This expression was enhanced by IL1-alpha, TNF-alpha and TPA, but suppressed by TGF-beta. Furthermore, HGF stimulated the DNA synthesis in keratinocytes derived from human hair bulb in a dose-dependent manner. These results indicate that DPC express HGF in vitro and that HGF stimulates the growth of human keratinocytes derived from hair bulb in vitro.

Use of distal splenorenal shunt in children referred for liver transplant evaluation.

Variceal bleeding remains a common cause of morbidity for children with both intrahepatic and extrahepatic portal hypertension. Occasionally, patients referred for liver transplant evaluation have significant variceal bleeding, despite adequate synthetic liver function. During a 7-year period, 322 children were referred for liver transplant evaluation. Six underwent distal splenorenal shunt surgery after evaluation. There were four boys and two girls. The average age was 11 +/- 4 years, and the average weight was 39 +/- 15 kg. The etiology of variceal bleeding was intrahepatic portal hypertension in five (1 biliary atresia, 2 chronic hepatitis, 2 congenital hepatic fibrosis) and extrahepatic portal vein thrombosis in one. Two patients had no previous attempts at sclerotherapy (one because of an abnormality in platelet function, the other because of extensive gastric varices), and four had multiple previous sclerotherapy treatments. No patient had preoperative encephalopathy. Three cases were Child's class A, and three were Child's class B. Preoperative evaluation of the portasystemic system was performed with magnetic resonance (MR) imaging or splenoportography. All patients underwent a distal splenorenal shunt procedure, four of whom also had splenopancreatic disconnection. One patient required 100 mL of blood replacement, and five required no blood. The average length of hospital stay was 9.8 +/- 2.2 days. Postoperative complications were minimal. All patients are alive, without recurrent gastrointestinal bleeding or encephalopathy, and they have patent shunts, which was confirmed by MR or Doppler ultrasound at a mean of 25 +/- 20 months after shunt surgery.(ABSTRACT TRUNCATED AT 250 WORDS)