ZEB1 expression is associated with prognosis of intrahepatic cholangiocarcinoma.

BACKGROUND/AIM: Intrahepatic cholangiocarcinoma (ICC) is one of the most aggressive malignant tumours, so the identification of molecular targets for ICC is an important issue. Zinc finger E-box binding homeobox 1 (ZEB1) is a key inducer of epithelial-mesenchymal transition (EMT). The aim of the present study was to clarify the clinical significance of ZEB1 in ICC and the associations between ZEB1 expression and EMT-related proteins. METHODS: We immunohistochemically examined the expression of EMT-related proteins, namely ZEB1, vimentin and E-cadherin, in ICC specimens from 102 patients. The clinicopathological and prognostic values of these markers were evaluated. RESULTS: ZEB1 and vimentin were expressed in 46.1% and 43.1% of tumours, respectively, and E-cadherin expression was lost in 44.1% of tumours. ZEB1 expression showed a significant inverse correlation with E-cadherin expression (p=0.004) and a positive correlation with vimentin expression (p=0.022). Altered expression of ZEB1 was associated with aggressive tumour characteristics, including advanced tumour stage (p=0.037), undifferentiated-type histology (p=0.017), lymph node metastasis (p=0.024) and portal vein invasion (p=0.037). Moreover, overall survival rates were significantly lower for patients with high ZEB1 expression than for patients with low ZEB1 expression (p=0.027). Kaplan-Meier analysis also identified E-cadherin expression (p=0.041) and vimentin expression (p=0.049) as prognostic indicators for overall survival. CONCLUSIONS: ZEB1 expression is associated with tumour progression and poor prognosis in patients with ICC through positive correlations with vimentin and negative correlations with E-cadherin. ZEB1 expression is associated with a poor prognosis and might be an attractive target for the treatment of ICC.

Laparoscopic liver biopsy using cup-shaped punch biopsy forceps and argon beam coagulator in children.

Needle liver biopsy is insufficient for measuring enzyme activity in liver tissue in child cases of intrahepatic cholestasis because the biopsy specimen obtained is too small. This study was undertaken to validate the feasibility of a new, relatively non-invasive laparoscopic liver biopsy technique combining the use of laparoscopic cup-shaped punch biopsy forceps (CPBF) and an argon beam coagulator (ABC) handpiece for the diagnosis and examination of liver enzyme activity in cases of intrahepatic cholestasis in children. The authors performed laparoscopic liver biopsy with the combined use of laparoscopic CPBF and an ABC handpiece in 10 children aged 4 months to 9 years old. Two 5-mm trocars were inserted in each patient after their abdomens had been filled with carbon dioxide gas at a pressure of 8 mmHg. Four to five specimens (each: 0.5 cm(3) in size) were taken at the anterior edge of the left lobe of the liver using laparoscopic CPBF. ABC was sprayed on to the cut liver surface to achieve hemostasis. The duration of the laparoscopic procedure ranged from 25 to 64 (44 +/- 12.8) min. The maximum intraoperative hemorrhage from the biopsied liver bed was 30 ml. The bleeding was easily controlled using ABC for about 1 min. There were no cases of postoperative bleeding, bile leakage from the cut surface, nor intraabdominal infection. There were also no death cases, and only one complication (hydrocele testis) was recorded. Examination by microscopy and assays of enzyme activities were performed using these biopsy specimens, which were sufficient for diagnosis in all patients. Laparoscopic liver biopsy combining the use of laparoscopic CPBF and an ABC handpiece can be performed safely, is less invasive, and provides sufficient samples for examination both by microscopy and enzyme activity assays.

[Case of solitary necrotic nodule of the liver difficult to distinguish from malignant hepatoma].

In a 72 years old woman, abdominal computed tomography (CT) disclosed multicentric hypervascular tumor in S4 of the liver, and it was T1.T2 by the MRI, and a high signal was presented together. Stenosis was shown by ERCP at the same site. Cholangiocellular carcinoma was suspected before operation, but malignant change was not recognized by frozen section, so the operation was finished. Later, a diagnosis of solitary necrotic nodule of the liver was established by pathological diagnosis. Solitary necrotic nodule of the liver is a benign tumor.

Number of lymph node metastases is a significant prognostic factor in intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (IHCC) is a rare primary hepatic tumor. Outcomes after resection and the use of lymph node dissection have not been well described. From a prospective database, we identified 53 patients with IHCC who underwent exploration between April 1983 and March 2004. Hepatic resection was performed in 44 patients, 30 of whom underwent lymph node dissection. Clinicopathological features and outcomes were analyzed. The actuarial 1-year survival was 66.2% in resected patients, compared to 0% in unresectable patients (p < 0.0001), with a 50% overall survival of 21.5 months and 3.1 months, respectively. The actuarial 3-year and 5-year overall survival rates in resected patients were 38.3% and 26.3%, respectively. Univariate analysis revealed that factors associated with poor overall survival included multiple tumors, extrahepatic bile duct involvement, noncurative resection, and involvement of lymph nodes. Multivariate analysis in resected patients revealed that multiple tumors (p < 0.0074) and non-curative resection (p = 0.0068) were significant risk factors for poor overall survival. The survival rate in patients with three or more positive nodes was significantly lower than in those with fewer than three (p < 0.0001). Three patients with solitary tumors and one or two involved lymph nodes have survived beyond 4 years after extended lobectomy with systemic lymphadenectomy. Curative resection, single tumor, and fewer than two lymph node metastases were prognostic factors for good outcome. Curative resection with lymph node dissection improved survival in patients with no more than two positive lymph nodes.

Real-time monitoring of a digestive tract marker to reduce adverse effects of moving organs at risk (OAR) in radiotherapy for thoracic and abdominal tumors.

PURPOSE: To evaluate the feasibility of real-time monitoring of a fiducial marker in/near the digestive tract and to analyze the motion of organs at risk to determine a reasonable internal margin. METHODS AND MATERIALS: We developed two methods to insert a fiducial marker into/near the digestive tract adjacent to the target volume. One method involves an intraoperative insertion technique, and the other involves endoscopic insertion into the submucosal layer of the normal digestive tract. A fluoroscopic real-time tumor-tracking radiotherapy system was used to monitor the marker. RESULTS: Fourteen markers (2 in the mediastinum and 12 in the abdomen) were implanted intraoperatively in 14 patients with no apparent migration. Seventeen of 20 markers (13/14 in the esophagus, 1/2 in the stomach, and 3/4 in the duodenum) in 18 patients were implanted using endoscopy without dropping. No symptomatic adverse effects related to insertion were observed. The mean/standard deviation of the range of motion of the esophagus was 3.5/1.8, 8.3/3.8, and 4.0/2.6 mm for lateral, craniocaudal and anteroposterior directions, respectively, in patients with intrafractional tumor motion less than 1.0 cm. CONCLUSION: Both intraoperative and endoscopic insertions of a fiducial marker into/near the digestive tract for monitoring of organs at risk were feasible. The margin for internal motion can be individualized using this system.

Laparoscopic hepatectomy with the hook blade of ultrasonic coagulating shears and bipolar cautery with a saline irrigation system.

BACKGROUND: The number of patients who have undergone laparoscopic hepatectomy is small, and the operative procedure is not yet well established. METHODS: We performed laparoscopic hepatectomy in eight patients, using the hook blade of ultrasonic coagulating shears, and bipolar cautery with a saline irrigation system, with minilaparotomy. The operative time, blood loss, and postoperative hospital stay of patients with laparoscopic left lateral segmentectomy were compared with these parameters in ten patients who had had a left lateral segmentectomy with laparotomy. RESULTS: The laparoscopic hepatectomies included seven left lateral segmentectomies and one nonanatomical partial resection of the lateral segment. The mean duration of the operation in these eight patients was 181.1 +/- 44.6 min. The mean amount of blood loss was 177.6 +/- 129.1 ml. Postoperative complications consisted of two cases of bleeding. The mean postoperative hospital stay in all eight patients was 9.88 +/- 4.36 days. The mean duration of operation (185.9 +/- 46.0 min) and mean postoperative hospital stay (9.47 +/- 4.61 days) in the seven patients with laparoscopic left lateral segmentectomies were significantly shorter than these parameters (255.7 +/- 59.4 min and 24.6 +/- 8.82 days) in the ten patients who had had left lateral segmentectomies with laparotomy. The mean amount of blood loss (160.0 +/- 128.9 ml) in the laparoscopic series was less than that (318.5 +/- 192.2 days) in the patients who had had laparotomy. CONCLUSIONS: Laparoscopic hepatectomy with the ultrasonic coagulating shears and bipolar cautery with minilaparotomy was safe, and less invasive than the open procedure, for minor hepatectomy procedures such as left lateral segmentectomy.

[In vitro chemosensitivity test for hepatocellular carcinoma using collagen-gel droplet embedded cultures].

This study evaluated an in vitro assay for chemosensitivity test using a collagen-gel droplet-embedded culture drug sensitivity test (CD-DST) for hepatocellular carcinoma (HCC). In 25 patients with HCC, in vitro chemosensitivity to 5-fluorouracil (5-FU), epirubicin (EPI), and cisplatin (CDDP) was examined by CD-DST, and 5-FU, EPI, and paclitaxel (PTX) were examined in 38 patients with breast cancer. Successful rates of chemosensitive evaluation by CD-DST were 64% for HCC and 79% for breast cancers. Although chemosensitivities of breast cancer were 5-FU 23.1%, EPI 83.3%, and PTX 67.7%, only one HCC sample was sensitive to EPI. Growth rates of HCC for 7 days of culture were significantly lower than those of breast cancers (1.04 vs 3.61). The culture methods for HCC in CD-DST should be improved to estimate accurate results.

[Postoperative adjuvant intraarterial chemotherapy of combined cisplatin and 5-FU for advanced hepatocellular carcinoma].

Postoperative adjuvant intraarterial infusion chemotherapy was performed for 22 hepatectomized patients with Stage III and Stage IV-A hepatocellular carcinoma from July, 1997, to December, 1999. One course of this chemotherapy consisted of cisplatin (10 mg/body/day on days 1-5) followed by 5-FU (250 mg/body/day on days 1-5). One hundred forty-eight patients of Stage III and Stage IV-A underwent hepatectomy from 1992 to 2001 and were enrolled as historical control. There were 9 Stage III cases treated with this adjuvant chemotherapy, and there were 7 or 6 Stage IV-A cases with and without main portal thrombosis, respectively. Survival and disease-free survival curves were not improved compared to historical control by this adjuvant chemotherapy. The number of recurrences in the remnant liver of 2 Stage IV-A cases with main portal thrombosis was limited to 3. Those cases treated with rehepatectomy and transarterial chemoembolization survived about 1,200 days without tumor recurrence.

Feasibility of insertion/implantation of 2.0-mm-diameter gold internal fiducial markers for precise setup and real-time tumor tracking in radiotherapy.

PURPOSE: To examine the feasibility and reliability of insertion of internal fiducial markers into various organs for precise setup and real-time tumor tracking in radiotherapy (RT). MATERIALS AND METHODS: Equipment and techniques for the insertion of 2.0-mm-diameter gold markers into or near the tumor were developed for spinal/paraspinal lesions, prostate tumors, and liver and lung tumors. Three markers were used to adjust the center of the mass of the target volume to the planned position in spinal/paraspinal lesions and prostate tumors (the three-marker method). The feasibility of the marker insertion and the stability of the position of markers were tested using stopping rules in the clinical protocol (i.e., the procedure was abandoned if 2 of 3 or 3 of 6 patients experienced marker dropping or migration). After the evaluation of the feasibility, the stability of the marker positions was monitored in those patients who entered the dose-escalation study. RESULTS: Each of the following was shown to be feasible: bronchoscopic insertion for the peripheral lung; image-guided transcutaneous insertion for the liver; cystoscopic and image-guided percutaneous insertion for the prostate; and surgical implantation for spinal/paraspinal lesions. Transcutaneous insertion of markers for spinal/paraspinal lesions and bronchoscopic insertion for central lung lesions were abandoned. Overall, marker implantation was successful and was used for real-time tumor tracking in RT in 90 (90%) of 100 lesions. No serious complications related to the marker insertion were noted for any of the 100 lesions. Using three markers surgically implanted into the vertebral bone, the mean +/- standard deviation in distance among the three markers was within 0.2 +/- 0.6 mm (range -1.4 to 0.8) through the treatment period of 30 days. The distance between the three markers gradually decreased during RT in five of six prostate cancers, consistent with a mean rate of volume regression of 9.3% (range 0.015-13%) in 10 days. CONCLUSIONS: Internal 2.0-mm-diameter gold markers can be safely inserted into various organs for real-time tumor tracking in RT using the prescribed equipment and techniques. The three-marker method has been shown to be a useful technique for precise setup for spinal/paraspinal lesions and prostate tumors.

[Modified pharmacokinetic modulation chemotherapy (PMC) with medication of UFT and intraarterial infusion of 5-FU for advanced unresectable HCC].

UNLABELLED: Advanced unresectable hepatocellular carcinoma (HCC) was treated with modified pharmacokinetic modulation chemotherapy (PMC). METHOD: Modified PMC consists of medication with UFT and intraarterial infusion of 5-FU. The dose of UFT is 300 or 400 mg/day. The infusion to hepatic artery of 5-FU is performed with 500 mg/body in an outpatient clinic once a week from reservoir port for 5 hours. RESULTS: The number of recurrent cases after hepatectomy was 5, and that of initial cases with unresectable HCC was 3. Three cases had tumor thrombus in the main portal branch. One patient had tumor thrombus in the inferior vena cava, which reached to the right atrium. The mean number of infusions in all cases was 21. One case showed PR, and 3 cases NC. Three of 6 mortality cases died from liver failure without tumor progression. One year survival rates of the patients with tumor thrombus in the portal trunk or IVC were 75.0%. The mean survival period of these cases was 12.5 +/- 4.2 months. CONCLUSION: Modified PMC had no severe side effect and was effective for advanced unresectable HCC.