Heterogeneity of capillary flow in the retrograde microcirculation induced in rat limb by arteriovenous shunting

Arteriovenous (AV) fistulas have been used clinically for improving adjunctive bypass patency. Such AV shunting induces retrograde flow in the microvascular network, which may induce microvascular remodeling and angiogenesis at the chronic phase. This paper was aimed to examine heterogeneity of blood flow among capillaries in the retrograde microcirculation induced by AV shunting. An AV anastomosis was created in rat hind limb. Using a dual window method or frame-by-frame technique on the fluorescence microscopic video images, we measured velocities of red blood cells (RBCs) flowing in the capillary network in three flow conditions: control (normal flow), arterial occlusion, and AV shunting (retrograde flow). For each flow condition, RBC velocities were obtained in 155 capillaries of 6 rats. By classifying all the capillaries into four groups based on the levels of RBC velocity in the occlusion state, we evaluated the mean velocities, coefficient of variation (CV), and histograms for each group of capillaries. The mean velocity and CV in each group changed significantly from the control to AV shunting states. Especially, most significant changes appeared in capillary groups where the superficial femoral artery or its collateral arteries might have a direct influence. Though the AV shunting improved capillary perfusion in the mean level, major parts of capillaries still remained at low perfusion.     

Percutaneous transhepatic gallbladder stenting for recurrent acute acalculous cholecystitis after failed endoscopic attempt

Endoscopic gallbladder stenting is useful palliative therapy for acute cholecystitis in high‐risk patients. Although the success rate of endoscopic gallbladder stenting is 79%–100%, an alternative method has not been reported. We succeeded in employing a method for percutaneous gallbladder stenting (PTGS) and herein describe this new method. A patient with acute acalculous cholecystitis related to ischemic atherosclerotic vascular disease, cholangitis due to Lemmel syndrome, and severe congestive heart failure underwent PTGS through the cystic duct from the gallbladder to the duodenal papilla, because an endoscopic method failed in the treatment of Lemmel syndrome. Because we were unable to place endoscopic transpapillary gallbladder drainage, percutaneous transhepatic gallbladder drainage (PTGBD) was performed and both the cholecystitis and cholangitis ceased. PTGS was performed as an alternative to endoscopic gallbladder stenting. Access to the cystic duct and gallbladder was obtained by the PTGBD route, using a guidewire (0.035‐inch diameter) and seeking catheter (6.5 Fr) under fluoroscopic control. A 7‐Fr 12‐cm double‐pigtail biliary polyethylene stent was placed. The patient remained asymptomatic for 3 months after the PTGS until he died, of an acute recurrent myocardial infarction. This new PTGS placement is an alternative treatment for symptomatic gallbladder disease in patients with increased operative risk when the endoscopic method is unsuccessful.     

Genetic analysis of radiation-associated rectal cancer

Genetic aberrations in radiation-associated colorectal cancer have not been studied in detail. We analyzed genetic aberrations in five rectal cancers that developed long after radiotherapy had been performed for cervical cancer. Microsatellite instability (MSI) in tumors was examined at five loci: D2S123, D3S966, TP53, DCC, and BAT26. Mutation of simple repeat sequences within the hMSH3, BAX, and transforming growth factor type II receptor (TGFRII) genes was examined by polymerase chain reaction and single-strand conformation polymorphism (PCR-SSCP). Mutation of p53 exons 5–8 was examined by PCR-SSP and direct sequencing. Mutations of the K-ras gene were analyzed by two-step PCR. No MSI was found in tumor specimens at any of the loci examined, and no mutations in the target genes were observed. K-ras mutation was detected in two carcinomas, but not in their irradiated normal mucosa, while p53 mutation was observed in another two carcinomas, but not in their irradiated normal mucosa. Our results suggest that the radiation-associated rectal carcinomas examined in this study did not develop through the mutator phenotype pathway; rather, tumorigenesis was probably mediated through the multistep carcinogenesis pathway.     

The relationship between circulating sialyl Tn antigen and polypoid or nonpolypoid growth characteristics in colorectal cancer

Recent studies delineated two different patterns of tumor growth in colorectal carcinoma characterized as polypoid and nonpolypoid (PG-type and NPG-type, respectively). We quantified serum sialyl Lewis (Le)^a (CA19–9), sialyl Le^x (SLX), sialyl Tn (STN), and carcinoembryonic antigen (CEA) in 269 colorectal cancer patients to establish whether their levels correlated with any biological or clinical differences between PG-type and NPG-type cancer. Patients were divided into high and low antigen groups (higher or lower than a selected diagnostic-based cut-off value) and compared. Statistical testing was by univariate and multivariate (logistic regression) analyses. Forty-seven (17.5%) patients with PG-type and 222 (82.5%) with NPG-type cancer were studied. In contrast to NPG-type, the characteristics of the PG-type cancers included a low rate of lymph node metastasis and a high serum STN level. In contrast to a low STN level, a high STN level was independently related to the presence of distant metastasis in patients with PG-type cancer, and also to the presence of distant metastasis and large-sized tumor in patients with NPG-type cancer. These data suggest that differences in STN levels in the serum of patients with PG-type or NPG-type colorectal carcinomas may be at least partly responsible for different tumor progression behavior. Received: 17 December 1999 / Accepted: 6 March 2000     

Expression of blood group antigens A, B and H in carcinoma tissue correlates with a poor prognosis for colorectal cancer patients

The deletion of blood group ABH isoantigens on tumor tissues has been reported to be an adverse prognostic marker for patients with various solid tumors. In the present study, we evaluated the prognostic value of altered expression of ABH isoantigens in colorectal carcinomas. Using monoclonal antibodies, the expression of A, B, and H antigens was assessed by immunohistochemistry on paraffin-embedded carcinoma samples from 82 patients who had undergone surgery for colorectal cancer. ABH isoantigens were found to be deleted in 36 carcinomas (43.9%) and expressed in 46 (56.1%). Univariate and multivariate analysis using a logistic regression model revealed that N factor (lymph node metastasis) and blood group type were independently related to the expression of ABH isoantigens. In contrast to previous reports on other cancers, patients whose colorectal carcinomas express ABH isoantigens had a poorer prognosis than those whose carcinomas showed deletion of ABH isoantigens (P = 0.0008). The expression of ABH isoantigens was an independent prognostic variable, in addition to T (depth of tumor invasion), N, and M (distant metastasis) factors, as shown by means of Cox regression analysis. In conclusion, the expression of ABH isoantigens in carcinoma tissue is an important poor prognostic factor in patients with colorectal cancer. This variable needs to be considered in the design of future trials of therapy. Received: 20 August 1999 / Accepted: 16 December 1999     

Postoperative changes in protein-induced vitamin K absence or antagonist II levels after hepatectomy in patients with hepatocellular carcinoma: relationship to prognosis

Background. α-Fetoprotein (AFP) has been used as a marker for hepatocellular carcinoma (HCC). However, AFP levels are often high in patients with chronic hepatitis or cirrhosis. Protein-induced vitamin K absence or antagonist II (PIVKA-II) is more sensitive for the diagnosis of HCC and prediction of patient survival. Changes in these markers after treatment may reflect treatment curability and patient outcome. Methods. We conducted a retrospective analysis of prognosis of 63 HCC patients with high preoperative levels of AFP and PIVKA-II who underwent hepatectomy and examined the relationship between postoperative changes in both markers at 1 month and patient survival. Subjects were divided into three groups according to changes in these tumour markers after hepatectomy: normalization (N) group, decreased but still above the normal level (D) group and unchanged (U) group. Results. There were no significant differences in the numbers of patients who developed tumour recurrence between changes in AFP and PIVKA-II. Survival analysis showed no significant differences in tumour-free and overall survivals between groups with respect to AFP level. The PIVKA-II-N group showed significantly better tumour-free and overall survival compared with the D and U groups (p<0.01). Multivariate analysis that included other prognostic factors identified changes in PIVKA-II level as a significant and independent prognostic factor associated with overall survival. Discussion. Although changes in AFP did not correlate with patient prognosis, normalization of PIVKA-II was significantly associated with good patient survival after hepatectomy. Normalization of PIVKA-II after hepatectomy reflected the efficacy of treatment and is a suitable predictor of prognosis in HCC patients.     

Modified Japan Integrated Staging is currently the best available staging system for hepatocellular carcinoma patients who have undergone hepatectomy

Background We previously reported the effectiveness of the modified Cancer of the Liver Italian Program (CLIP) score in hepatocellular carcinoma (HCC) staging. To determine the best predictive staging system for HCC patients, we conducted a comparative analysis of prognosis using multivariate analysis in 230 Japanese HCC patients following hepatic resection. Methods We compared overall survival as predicted by different staging systems: the tumor node metastasis (TNM) system by the Liver Cancer Study Group of Japan, the Japan Integrated Staging (JIS) score (Japanese TNM and Child-Pugh classification), the modified JIS score using liver damage grade, the CLIP score, and our modified CLIP score using protein induced by vitamin K absence or the antagonist II (PIVKA-II). Results By a univariate analysis the PIVKA-II level (cut-off level, 400 mAU/ml) was significantly associated with patient survival (P = 0.031); however, alpha-fetoprotein level was not related to survival. Liver damage grade was significantly associated with patient survival (P = 0.039), although Child-Pugh classification was not related to survival. Univariate analysis showed that prediction of survival, according to disease stage, was better with the modified JIS score than with the TNM system, CLIP, modified CLIP, or JIS score. Multivariate analysis showed the modified JIS score showed the best ability to predict overall survival according to disease stage (Hazard ratio, 1.77; P = 0.002), and its Akaike information criteria statistic was the lowest (634.3). Conclusions The modified JIS score, a staging system that combines tumor factors and hepatic function, is a better predictor of prognosis than other systems in HCC patients who have undergone hepatic resection.     

Anatomic resection of segments 5, 6 and 7 of liver for hepatocellular carcinoma: prior control of right paramedian Glisson

Anatomic resection is theoretically effective in eradicating intrahepatic metastasis of hepatocellular carcinoma (HCC). In patients who undergo a larger volume of hepatectomy or who have hepatic dysfunction, the extent of hepatectomy is limited to avoid postoperative hepatic failure. In the present case, a limited anatomic resection according to Couinaud's segment was performed because of the large volume of the right hemi-liver. A 62-year-old male was found to have a 12-cm HCC in segments 5, 6 and 7, with alcoholic liver disease. The total liver function was Child-Pugh grade A, as indocyanine green retention rate at 15 minutes (ICGR15) was 12%. The resected liver volume of right hemihepatectomy estimated by CT volumetry was 72% and the permitted resected volume based on Takasaki's formula applying ICGR15 was 65%. As the portal branches of segment 8 was free from HCC involvement and the estimated volume of segments 5, 6 and 7 was 51%, we scheduled anatomic resection of these segments to secure remnant liver function. Under Pringle's maneuver, hepatic transection on the border between right and left liver was performed and the right paramedian Glisson's pedicle was exposed in the first step. Branches of segment 5 were divided and the border between segments 5 and 8 was confirmed. Then, the right lateral sector was resected and the right hepatic vein draining segment 8 was secured. Postoperative course was satisfactory and the patient was free from tumor relapse for 16 months after hepatectomy. Under a balance between tumor location and hepatic functional reserve, anatomic resection would be necessary for the treatment of HCC patients.     

Clinicopathological features of "intraductal papillary neoplasm of the bile duct" and patient outcome after surgical resection

BACKGROUND/AIMS: Intraductal papillary neoplasm of the bile duct (IPNB) represents a biliary papillary tumor mainly growing in the bile duct lumen resembling intraductal papillary mucin-producing neoplasm of the pancreas. However, its clinical spectrum and characteristics have not been fully evaluated. METHODOLOGY: To define the clinicopathologic characteristics and prognosis of IPNB patients, 6 cases of IPNB who underwent surgical resection are presented. RESULTS: Patients were 3 males and 3 females, aged between 47 and 79 years. Five patients had histories of hepatobiliary disease. Imagery showed cystic or diffuse dilatation of the bile ducts. Tumor markers were not valuable for diagnosis. All patients underwent hemihepatectomy with or without resection of the caudate lobe or extrahepatic bile duct. Examination showed polypoid tumors in 5 cases though 1 case had no evident tumor. Mucin was observed in 3 cases. Five cases were well-differentiated adenocarcinoma and 1 had poorly differentiated adenocarcinoma. Vascular invasion was rare and lymph node metastasis was not observed. In-situ spread of carcinoma was seen along biliary mucosa in 3 cases. Five cases survived without tumor relapse for long periods but 1 died of tumor recurrence at 31 months. CONCLUSIONS: Complete resection of IPNB based on accurate preoperative assessment of tumor extension provides a good prognosis.     

Cell morphological changes in venous remodeling induced by arteriovenous grafting in rat limb

Vascular remodeling induced in rat limb by arteriovenous (AV) shunting was investigated by evaluating changes in vascular diameter and cell morphology. In Wistar rats, a vein graft was implanted in situ in the hind limb. Flow-rate in the grafted vein was assessed by measuring flow in the common femoral artery using an ultrasonic flowmeter. Nuclei and actin filaments of the venous wall were stained with propidium iodine and phalloidine-FITC, and the samples were observed using confocal laser microscopy. The grafted veins became circular in cross-section with increase in diameter during two weeks after AV shunting. Owing to the increase in diameter, the estimated wall shear stress was not increased so much as the flow-rate. The confocal laser microscopic observation showed that endothelial cells (ECs) and smooth muscle cells (SMCs) in the grafted veins were either aligned well (2 out of 8 samples), or ECs were denudated and SMCs were disrupted (in 6 out of 8 samples). The cell density of ECs was unchanged from the control level. In conclusion, the grafted vein was remodeled with morphological changes in ECs and SMCs during 2 weeks after AV shunting.