Endoscopic findings of bleeding esophagogastric varices.

BACKGROUND/AIMS: Endoscopic findings of bleeding gastric and esophageal varices were compared. METHODOLOGY: Seventy patients with first bleeding esophagogastric varices without prior treatments were treated: 47 patients had bleeding esophageal varices (EV group), 11 patients had bleeding cardiac varices (CV group), and 12 patients had bleeding cardiofundic or fundic varices (FV group). RESULTS: The red color sign was more common in the EV group (45 patients) than in the CV group (4 patients) or FV group (no patients) (P < 0.0001); Mucosal erosion over the varices at the site of bleeding was more common in the CV group (9 patients, P < 0.0005) and FV group (12 patients, P < 0.0001) than in the EV group (12 patients). An ulcer at the bleeding point was more common in the CV group (7 patients, P < 0.01) and FV group (10 patients, P < 0.0001) than in the EV group (11 patients). Gastric ulcer was more common in the CV group (7 patients, P < 0.05) and FV group (10 patients, P < 0.001) than in the EV group (14 patients). Erosive gastritis was more frequent in the FV group (12 patients, P < 0.02) than in the EV group (30 patients). CONCLUSIONS: Violation of the mucosa barrier overlying gastric varices, especially cardiofundic or fundic varices, might be an important step leading to variceal hemorrhage.

A comparison of combination endoscopic therapy and interventional radiology with esophageal transection for the treatment of esophageal varices.

BACKGROUND/AIMS: The impact of long-term results of combination interventional radiology and endoscopic therapy were compared with esophageal transsection for the treatment of esophageal varices. METHODOLOGY: This study was a retrospective chart review. The outcome of 16 patients with esophageal varices who underwent endoscopic therapy plus all interventional radiologic procedures (transportal vein obliteration, partial splenic embolization, and left gastric arterial embolization) were compared with those of 23 who underwent esophageal transection. Primary endpoints during a 5-year follow-up included retreatment and death. RESULTS: The retreatment rates at 1 year, 3 years, and 5 years in the combined therapy group and transection group were 16.7% and 8.7%, 58.3% and 25.2% and 75.0% and 31.2%, respectively. The retreatment rates were lower in the transection group than in the combined therapy group (p = 0.015). Cumulative retreatment rates in Child's class C patients were significantly different between the two groups. The survival rates at 3 years and 5 years in the combined therapy group and transection group were similar 91.7% versus 91.7% and 82.5% versus 89.5%. The cumulative retreatment rates also were similar. CONCLUSIONS: The combination of interventional radiologic and endoscopic therapy is highly effective and provides an alternative to surgery in patients with esophageal varices who have poor liver function.

Long-term hematological and biochemical effects of partial splenic embolization in hepatic cirrhosis.

BACKGROUND/AIMS: Partial splenic embolization was developed as a non-surgical treatment for hypersplenism, but recently splenic embolization has been reported to improve the hepatic function. We undertook long-term evaluation of partial splenic embolization in patients with hepatic cirrhosis in comparison with patients not undergoing embolization. METHODOLOGY: We performed embolization in 26 patients with cirrhosis. The controls consisted of 26 with cirrhosis patients who were not undergone embolization. RESULTS: Red blood cell counts of embolized patients had increased significantly at 6 months after the procedure, remaining increased for up to 7.5 years. Platelet counts increased maximally by 2 weeks after embolization, followed by a gradual decrease. Nonetheless, platelets remained significantly more numerous than before embolization for up to 8 years. Neither aspartate aminotransferase nor alanine aminotransferase activities in serum changed significantly during follow-up. Choline esterase activity increased significantly by 6 months after embolization and remained increased for more than 7 years. Serum albumin concentration increased significantly, beginning at 6 months after embolization; this increase was maintained for 6 years. Survival did not differ between embolized and non-embolized groups. CONCLUSIONS: Partial splenic embolization is a beneficial non-surgical treatment that enhances hepatic protein synthetic capacity as well as alleviating hypersplenism in patients with cirrhosis.

Hepatic parenchymal resection using an ultrasonic surgical aspirator with electrosurgical coagulation.

BACKGROUND/AIMS: We introduced an ultrasonic surgical aspirator with electrosurgical coagulation to increase safety of the liver resections performed for hepatocellular carcinoma. METHODOLOGY: This system was evaluated by analyzing the intraoperative blood loss, the duration of hepatectomy, the ischemia time, and the postoperative clinical course and comparing these same parameters with the traditional forceps' fracture method. RESULTS: There was no significant difference in the duration of surgery and the mean liver resection time between the two methods. The mean blood loss by using this system was 2458 +/- 4742 mL and by forceps' fracture method 956 +/- 252 mL. The mean ischemia time was 44.4 +/- 35.9 min by using this system and 23.9 +/- 29.1 min in forceps' fracture method. There was a significant decrease in intraoperative blood loss and ischemia time using the new system. This may decrease postoperative complications. CONCLUSIONS: This system may enable all surgeons to perform liver resection easily and safely.

The natural history of gastric varices.

BACKGROUND/AIMS: Recent improvements in the treatment of gastric varices have resulted in better rates of hemostasis and eradication. This prospective study was conducted in order to examine the natural history of gastric varices and whether prophylactic treatment is required. METHODOLOGY: Between January 1991 and December 1996, 52 patients with cirrhosis and no history of prior variceal treatment were enrolled. RESULTS: Bleeding from gastric varices occurred in 4 patients. Hemorrhage was stopped successfully in all of these patients. The cumulative bleeding rates at 1, 3, and 5 years were 3.8%, 9.4%, and 9.4%, respectively. Erosive gastritis or gastric ulcer was not detected in 3 of these 4 patients at the time of entry into the study, although an ulcer or erosion was found at the point of gastric variceal hemorrhage in all four patients at the time of variceal rupture. There were no significant differences in patient characteristics with ruptured versus non-ruptured varices at the time of their study entry. CONCLUSIONS: Factors which could be used to predict bleeding from gastric varices were not identified. Furthermore, the overall incidence of hemorrhage from gastric varices was found to be low. Once gastric variceal hemorrhage did occur, bleeding from these varices was successfully stopped in all cases. Therefore, prophylactic treatment of gastric varices is not recommended.

Bleeding portal-hypertensive gastropathy managed successfully by partial splenic embolization.

The use of partial splenic embolization to decrease portal pressure and reduce gastric bleeding from portal-hypertensive gastropathy, a complication of liver cirrhosis, is described. A 62-year-old man with hepatic cirrhosis secondary to hepatitis C and documented portal hypertension was admitted with hypersplenism and bleeding esophageal varices. Endoscopic ligation successfully controlled acute bleeding, but blood loss continued over the next 45 days. Bleeding secondary to portal-hypertensive gastropathy was diagnosed endoscopically. The patient's poor surgical status precluded a portosystemic shunt procedure, so partial splenic embolization was performed radiologically by the injection of Gelfoam squares. Splenic volume decreased 50% following partial embolization. Over 3 weeks, the hemoglobin concentration increased from 8.5 g/dL to 9.8 g/dL, and the platelet count increased from 41,000 to 90,000/microL. Repeat endoscopy found no gastric bleeding 18 days post-procedure. Partial splenic embolization is a radiologic procedure which can be performed safely in patients too ill to undergo portosystemic shunt. This report documents its successful use to manage hypersplenism and reduce portal pressure in a cirrhotic patient with portal-hypertensive gastropathy and hypersplenism.

Infected hepatic cyst.

We describe an unusual case involving an infected hepatic cyst. An 88-year-old woman presented with acute onset of right upper quadrant abdominal pain, mild left lower abdominal pain, diarrhea, and fever. On admission, computed tomography revealed multiple hepatic cysts including an 8-cm cyst located in the left medial segment of the liver, which demonstrated a thickened wall enhanced with contrast media. Ultrasonography showed an 8-cm hypoechoic lesion which differed in appearance from the other, anechoic hepatic cysts. The serum concentration of C-reactive protein was 29.8 mg/dL; white blood cell count, 12,800/microL; CA19-9, 96 U/mL; and CEA, 2.2 ng/mL. Diagnosis of infected hepatic cyst was made by percutaneous transhepatic drainage of the cyst. Milky fluid was obtained and the patient's right upper quadrant abdominal pain resolved after drainage. The cyst fluid CA19-9 concentration was 18,000 U/mL. Cytology of the cyst fluid was negative. Serum CA19-9 (41 U/mL) and CEA (1.8 ng/mL) concentrations were improved 1 week after drainage. Escherichia coli was cultured from the drainage fluid. The patient was discharged 27 days after admission. Percutaneous transhepatic drainage is effective in the treatment of infected hepatic cysts.

Ultrasonography of non-perforated appendicitis in young children.

BACKGROUND/AIMS: The role of ultrasonography in diagnosing non-perforated appendicitis in young children is reviewed. METHODOLOGY: Between January 1997 and September 1999, three children with abdominal pain due to non-perforated appendicitis were admitted to the Nippon Medical School Hospital. Ultrasonography of the right lower quadrant was performed using a 7.5-MHz curved array transducer with the graded compression technique. RESULTS: Edema of the appendix was detected in all cases. The appendiceal diameter was 9 to 18 mm, and the thickness of the muscular wall was 3.5 to 6 mm. An echogenic submucosal layer, increased periappendiceal echogenicity, and the acoustic shadow of the proximal appendix was detected in each case. Localized fluid collection was not observed in any patient. Surgical and histopathological findings were nonperforated gangrenous appendicitis with fecal stone in all three cases. CONCLUSIONS: Ultrasonography provides valuable clinical information about the ileocecal region in children with acute abdominal pain. Even when the clinical diagnosis seems well established, performing ultrasonography routinely may help reduce the rate of perforation by decreasing the time required to establish the diagnosis.

Graft survival following three occurrences of hepatic arterial thrombosis after living-related liver transplantation. A case report.

Hepatic arterial thrombosis is a major cause of morbidity and graft loss in patients undergoing liver transplantation. We report the case of a patient who underwent living-related liver transplantation and suffered three instances of early hepatic arterial thrombosis requiring revascularization in the first 8 days after grafting. The patient was discharged with good graft function. A 21-month-old female with biliary atresia underwent living-related liver transplantation using her mother's extra-lateral segment. The donor middle hepatic artery was anastomosed end-to-end to the posterior branch of the donor's hepatic artery. The time of operation was 8 hr 36 min, and the blood loss was 193 mL. On postoperative day 5, the patient was returned to surgery to close a perforation in the transverse colon. At operation we found hepatic arterial thrombosis and performed a thrombectomy and redid the arterial anastomosis. Hepatic arterial thrombosis recurred during the operation, so we interposed the recipient's right radial artery between the graft artery and recipient posterior branch. On postoperative day 8, ultrasound showed a fluid collection in Winslow's pouch. After removing the fibrin clot, we discovered that hepatic arterial thrombosis had recurred in the interposed artery. We revascularized the graft using the right gastroepiploic artery. Arterial blood flow was restored, and graft function remained excellent.

Good embolization response for colorectal liver metastases with hypervascularity.

BACKGROUND/AIMS: We investigated whether tumor hypervascularity in diagnostic images predicts response to transcatheter arterial embolization in colorectal liver metastases. METHODOLOGY: Forty-five patients undergoing transcatheter arterial embolization for liver metastases were grouped by tumor vascularity on contrast-enhanced computed tomography and angiography. Group IA (n = 10) included patients with hypervascular tumors by both contrast-enhanced computed tomography and early-phase angiography; group IB (n = 15), hypervascularity by contrast-enhanced computed tomography and only late-phase angiography; group IIB (n = 2), hypovascularity by contrast-enhanced computed tomography and only early-phase angiography; group IIC (n = 18), hypovascularity by contrast-enhanced computed tomography and both angiography phases (unmentioned groups included no patients). Tumor response assessed by computed tomography and changes in serum carcinoembryonic antigen concentration at 1 month, as well as survival rates, were compared between groups. RESULTS: Patients with a partial response numbered only 5, all in group IA. Patients with no change included 26 (group IA, 4; group IB, 10; group IIB, 1; group IIC, 11), while patients with progressive disease numbered 14 (group IA, 1; group IB, 5; group IIB, 1; group IIC, 7). Serum carcinoembryonic antigen concentrations were 0.62, 1.03, 1.31, and 2.01% of pretreatment rates in groups IA, IB, IIB, and IIC, respectively. Carcinoembryonic antigen increases in group IA plus IB were significantly lower (P = 0.04) than in group IIB plus IIC. The decreases in group IA differed significantly from changes in group IB plus IIB (P = 0.05), or group IIC (P = 0.02). Survival rates were somewhat higher group IA than in other, but not significantly. CONCLUSIONS: Transcatheter arterial embolization is effective against colorectal liver metastases only when hypervascularity is evident.

Successful surgical treatment of peritoneal dissemination of hepatocellular carcinoma.

Hepatocellular carcinoma rarely disseminates intraperitoneally. When it does, it usually is considered a terminal event. The successful treatment of complications of peritoneal metastases by surgical resection in a patient with hepatocellular carcinoma is reported. A 63-year-old man with hepatocellular carcinoma in the anterior segment underwent transarterial and portal embolization followed by extended radical hepatectomy. Five years and 8 months later, he presented with an ileus that was secondary to multiple peritoneal metastases that were resected to the extent possible. Eight months later, the patient presented with a second episode of ileus and underwent another operation that included bowel resection. However, pelvic tumors that were unresectable also were present. The patient survived for another 9 months before dying with peritoneal carcinomatosis. Although surgical treatment of peritoneal dissemination of hepatocellular carcinoma is not curative, surgery may improve survival and provide a good quality of life in selected cases.

Intracystic hemorrhage of a simple hepatic cyst.

An unusual case involving hemorrhage of a benign intrahepatic cyst in which the correct diagnosis was made preoperatively is reported. A 60-year-old man presented with acute onset of left upper quadrant abdominal pain. On admission, computed tomography and ultrasonography revealed an 8-cm hepatic cyst in the left lateral segment of the liver. Serum concentrations of CA19-9 (170 mu/mL), DUPAN2 (1600 mu/mL), and SPAN1 (94 mu/mL) were elevated. Twenty-three days after admission, magnetic resonance imaging revealed a hyperintense 13-cm lesion that appeared heterogeneous on T1-weighted sequences and relative hypointensity of the bottom on T2-weighted sequences. Percutaneous transhepatic drainage of the cyst was performed 27 days after admission, and serosanguineous fluid was obtained; abdominal pain resolved. Tumor marker concentrations decreased by 1 week after drainage. Six days after drainage, the drainage fluid became purulent. The infection persisted and a left lateral segmentectomy and cholecystectomy were performed 24 days after the cyst was drained. Pathology confirmed that the cyst was benign. The use of magnetic resonance imaging and tumor markers may allow the differentiation of benign hepatic cyst from malignant lesions and obviate the need for surgery.

New techniques: combined endoscopic injection sclerotherapy and ligation for acute bleeding from gastric varices.

BACKGROUND/AIMS: Combined endoscopic injection sclerotherapy and endoscopic variceal ligation was used for the treatment of acute bleeding from gastric varices. METHODOLOGY: Between July 1995 and August 1998, three cirrhotic patients with acute bleeding from gastric varices were treated. Endoscopic variceal ligation of the puncture point and bleeding point was performed simultaneously. RESULTS: Acute bleeding from the gastric varices was successfully stopped in all cases. CONCLUSIONS: Combined endoscopic injection sclerotherapy and endoscopic variceal ligation can be used to stop bleeding and prevent rebleeding from gastric varices.

Control of isolated gastric varices by combination therapy using embolization and endoscopic scleroligation therapy.

Balloon-occluded retrograde venous obliteration is a powerful new technique for eliminating gastric varices. However anatomic considerations may preclude its use in some instances. Two cases are reported in which combination embolization followed by endoscopic injection scleroligation therapy eradicated isolated gastric varices where balloon-occluded retrograde venous obliteration was impossible. Two men with alcoholic cirrhosis were admitted with bleeding gastric varices. Inability to access variceal venous drainage precluded balloon-occluded retrograde venous obliteration. In Case 1, transileocolic vein obliteration left gastric embolization, and partial splenic embolization only partially eradicated gastric varices. In Case 2, percutaneous transhepatic obliteration, left gastric embolization, and partial splenic embolization were only partially successful. In both cases, endoscopic injection scleroligation therapy was performed adjunctively. Endoscopic injection scleroligation therapy completely eradicated gastric varices in both patients following partially successful embolization therapy. These cases demonstrate the importance of individualizing treatment of esophageal varices, the value of combination therapy, and the effectiveness of endoscopic injection scleroligation therapy for treating varices.

Detection of lymph node micrometastasis in esophageal carcinoma.

BACKGROUND/AIMS: The presence of lymph node metastasis is the most important prognostic factor in esophageal squamous cell carcinoma. Molecular biology techniques have improved the ability to recognize micrometastasis in lymph nodes, bone marrow, and peripheral blood. Previous studies have demonstrated that cytokeratin 19 reverse transcriptasepolymerase chain reaction can detect tumor cells even when lymph nodes appear normal histologically. However, the presence of pseudogenes for cytokeratin 19 have reduced the specificity of reverse transcriptase-polymerase chain reaction, thereby reducing its clinical worth as a sensitive diagnostic technique. METHODOLOGY: We examined the expression of mRNA for cytokeratin 19 using a newly designed set of primers, and compared the results with data from histologic examinations. Samples were obtained from tumors, intact tissues, resected lymph nodes and in 10 patients who underwent esophagectomy via right thoracotomy with lymph node dissection in the neck, mediastinum and abdomen. RESULTS: All tumors, non-cancerous tissues were positive for cytokeratin 19 by reverse transcriptasepolymerase chain reaction. However, 2 of the 6 lymph nodes that appeared normal on histologic examination were positive for cytokeratin 19; sensitivity and specificity were 100% and 67%, respectively. CONCLUSIONS: Reverse transcriptase-polymerase chain reaction using new primers for cytokeratin 19 detected micrometastasis in specimens of lymph nodes from patients with squamous cell carcinoma. This method may increase the accuracy of tumor staging and provide clinicians with valuable information that will help individualize treatment options.

Anti-tumor effect of N-[3,4-dimethoxycinnamoyl]-anthranilic acid (tranilast) on experimental pancreatic cancer.

The anti-tumor effect of N- [3,4-dimethoxycinnamoyl] -anthranilic acid (tranilast) was examined in experimental pancreatic cancer. Proliferation of PGHAM-1 cells was inhibited by tranilast in a dose-dependent manner, showing a significant difference at a concentration of 25 microgram/ml (p<0.05). In colony formation, tranilast reduced the number of colonies at a concentration of 25 microgram/ml (p<0.01). DNA synthesis for 12 hours was attenuated dose-dependently and a significant difference was observed at concentrations of greater than 50 microgram/ml (p<0.05). From cell cycle analysis, a dose-dependent increase in the distribution of G0-G1 phase was observed. In the dorsal air sac model, the mean angiogenesis indices in PGHAM-1 chambers were 4.17 +/- 0.22 (control group) and 2.33 +/- 0.84 (treatment group), and in VEGF chambers they were 3.60 +/- 0.67 (control group) and 1.92 +/- 0.42 (treatment group), In the peritoneal dissemination model, the quantity of sanguineous ascites, the number and the size of diaphragmatic nodules and the microvessel density (MVD) of the metastatic site were reduced by tranilast significantly. In conclusion, the anti-tumor effect of tranilast on proliferation and on tumor-angiogenesis was confirmed in experimental pancreatic cancer.

Immunohistochemical study of CYP2E1 in hepatocellular carcinoma carcinogenesis: examination with newly prepared anti-human CYP2E1 antibody.

Cytochrome P450 2E1 (CYP2E1) is known as a heme-containing enzyme that produces abundant free radicals, and its involvement in carcinogenesis has been suggested in several organs in vivo. In this study, to clarify the involvement of CYP2E1 in liver cancer and its carcinogenesis process, we investigated the expression of CYP2E1 in 42 surgically resected or biopsied specimens of hepatocellular carcinomas (HCC) and 26 cases with other liver lesions immunohistochemically using a newly prepared anti-human CYP2E1 antibody. When intracellular CYP2E1 expression was investigated in three different regions of HCC specimens, the expression in hepatocytes of the peri-tumor region was the highest (p<0.001) compared with those in the tumor and non-peri-tumor regions. Histologically, the expression of CYP2E1 in tumor cells tended to decrease as the cells were less differentiated (p<0.0001) and was the lowest in poorly differentiated HCC (p<0.01). CYP2E1 expression was highest in the pseudo-glandular type and low in the thick trabecular and solid types of HCC (p<0.0001). In mature regenerative nodules of liver cirrhosis, adenomatous hyperplasia (AH) and atypical adenomatous hyperplasia (AAH) to early-HCC, CYP2E1 expression was notably high as compared with other legions. CYP2E1 has a strong free radical-producing ability, and the cell injury and DNA damages by the free radicals are considered to be involved in carcinogenesis. Therefore, our results suggest that the different expression of CYP2E1 in hepatocytes may play important roles in the multistep carcinogenic process and the histogenesis of hepatocellular carcinoma.

[Endoscopic hemorrhoidal ligation from the rectum].

Endoscopic hemorrhoidal ligation with a rubber band was carried out on 40 patients with internal hemorrhoids. All the patients were treated in the outpatient ward. Seven patients complained of mild to moderate aches in the early postoperative days, which were easily controlled by medication. One week after the treatment, no patient complained of pain. None of the patients had any postoperative bleeding. The results of this treatment were classified as good (no complaint or symptoms after the treatment), fair (at least some improvement), or poor (no change or worse than before the treatment). Twenty-nine of the 40 patients were classified as good, and the remaining 11 patients were fair. No patients were classified as poor. EHL is a harmless and painless procedure and is easily performed in the outpatient ward. When internal hemorrhoids of operative indication are detected by colonoscopy, EHL can be easily and simultaneously carried out.

Genome-wide screening of laser capture microdissected gastric signet-ring cell carcinomas.

Gastric signet-ring cell carcinoma comprises a distinct category of gastric cancers and has been reported to have poor prognosis. In an attempt to define genetic changes involved in the pathogenesis of this lesion in an in vivo state, we isolated signet-ring cell carcinoma cells from freshly fixed smears of tumor tissues of 7 primary gastric signet-ring cell carcinomas by laser capture microdissection and applied comparative genomic hybridization (CGH) to screen for DNA sequence copy number changes. Frequent chromosomal gains were detected on 2q, 5p, 7q, 14q and 20q, each in 6/7 cases, on 9q, 12q, 17q, and 19q, each in 5/7 cases, and on 18p in 4/7 cases. Frequent losses were observed on 6p and 17p, each in 5/7 cases, on 6q, and 21p, each in 4/7 cases, and on 3p, 8p and 8q, each in 3/7 cases. Losses on 6p have rarely been observed in conventional types of gastric carcinomas reported in the literature. These data provide the first evidence for the occurrence of specific genomic aberrations in gastric signet-ring cell carcinomas. Our observation of frequent losses on 6p chromosomal arm may provide novel abnormalities of potential significance in gastric signet-ring cell carcinomas, suggesting the involvement of genes residing in this region in the genesis of the disease.

Endoscopic scleroligation is a superior new technique for preventing recurrence of esophageal varices.

This study compared a new method, endoscopic scleroligation, intravariceal injection sclerotherapy followed by ligation plus extravariceal injection sclerotherapy, with ligation plus extravariceal injection sclerotherapy. Fifty-nine patients with cirrhosis and esophageal varices were treated by endoscopic scleroligation (ESL group, n = 28) or ligation plus extravariceal injection sclerotherapy (EVL + extraEIS group, n = 31). The demographics and clinical characteristics of the two treatment groups were similar, as was the rate of complete eradication with initial treatment. However, the 1- and 3-year cumulative recurrence rates in the ESL group (3.8% and 22.4%) were very significantly lower than those in the EVL + extraEIS group (48.3% and 81.0%) (p < 0.0001). The overall survival rates in the two groups were similar. In conclusion, endoscopic scleroligation is superior to ligation plus extravariceal injection sclerotherapy in preventing variceal recurrence. The efficacy of intravariceal injection sclerotherapy before ligation is believed to arise from the eradication of feeder vessels.