Ablation of hepatocellular carcinoma.
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Biomedical subjects
Publications and source records attributed to M Makuuchi.
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UNLABELLED: The role of lactate in liver ischemia-reperfusion injury in cirrhosis has not been clarified. Fifty patients with hepatocellular carcinoma who underwent partial liver resection under Pringle's maneuver were included in this study. We performed the indocyanine green clearance test before the operation and three times during the surgery to calculate its elimination rate. Blood lactate and base excess were measured at the corresponding times. Systolic and diastolic systemic arterial pressure, heart rate, cardiac index, and esophageal temperature were monitored. Aminotransferase levels were recorded the day before the operation, 1 h after the operation, and on the first and third postoperative days. We calculated the increase or decrease in lactate levels during the preischemic, ischemic, and postischemic phases, and examined the correlation between these results and the changes in indocyanine green elimination rate and some clinical factors. The lactate levels increased before reperfusion and began to decrease after reperfusion. The lactate increase and decrease during the ischemic and postischemic phases correlated with the change in indocyanine green elimination rate (P < 0.0001 and P = 0.02 for the respective phases). The lactate increase during the preischemic phase correlated with the duration of the preischemic phase (P < 0.0001). In cirrhotic patients who undergo liver resection with Pringle's maneuver and who do not show postoperative liver failure, the blood lactate profile might be a reliable indicator of liver metabolic capacity during surgery. IMPLICATIONS: In cirrhotic patients who underwent liver resection with Pringle's maneuver, the lactate increase and decrease during the ischemic and postischemic phases correlated with the change in the indocyanine green elimination rate. The blood lactate profile might be a reliable indicator of liver metabolic capacity during surgery.
OBJECTIVE: To evaluate retrospectively the safety and radicality of liver resection performed without total vascular exclusion (TVE). SUMMARY BACKGROUND DATA: TVE is recommended for safe liver surgery, at least in the case of resection of the paracaval portion of the liver. However, it has some drawbacks because of its invasiveness. METHODS: The authors retrospectively evaluated 329 of 471 consecutive patients who underwent liver resection from October 1994 to October 1999. All of these patients had tumors involving segments 1, 7, or 8 or the cranial portion of segment 4, or underwent major hepatectomies that required exposure of the inferior vena cava (IVC), the main trunks of the hepatic veins, or both. Sixty-four patients underwent resection that included segment 1, with or without the reconstruction of the IVC, the hepatic vein, or both. RESULTS: Three hundred twenty-four of 329 procedures were done under intermittent warm ischemia; no clamping methods were used in 6. TVE was never needed. There were no postoperative 30-day deaths. The complication rate was 25.5%, and only 2.1% had major complications. Only 13 (3.9%) patients required whole blood transfusion. Part of the wall of the IVC was resected in six patients, and the hepatic veins were reconstructed in four. Surgical clearance was achieved in all patients undergoing surgery for a tumor. CONCLUSIONS: These results show that liver surgery performed without TVE is safe and effective even in aggressive procedures for liver tumors involving the cavohepatic junction. Therefore, TVE should be further restricted to exceptional patients.
OBJECTIVE: To examine the usefulness of the authors' method involving preoperative transcatheter arterial chemoembolization followed by hepatectomy. SUMMARY BACKGROUND DATA: The presence of portal vein tumor thrombus in a patient with hepatocellular carcinoma is one of the most significant factors for a poor prognosis. No standard therapy has been established. METHODS: Forty-five of 455 patients with hepatocellular carcinoma (10%) from 1989 to 1998 were included in this study. These patients had gross portal vein tumor thrombus but no distant metastases. The 23 patients (50%) who had indications for surgery received preoperative transcatheter arterial chemoembolization: 18 underwent hepatic resection and 5 underwent ligation of the hepatic artery or portal vein on laparotomy. Among the remaining 22 patients who did not have indications for hepatectomy, 10 received regional chemotherapy and 12 underwent transcatheter arterial chemoembolization. RESULTS: The mean duration of survival was 3.4 +/- 2.7 years in the 18 patients who received transcatheter arterial chemoembolization and hepatectomy and 0.36 +/- 0.26 years in the 27 patients who did not receive hepatectomy. The survival rate of the 18 patients who received hepatic resection with preoperative transcatheter arterial chemoembolization was 82% at 1 year, 42% at 3 years, and 42% at 5 years. Portal trunk occlusion by tumor thrombus, three or more primary nodules, an indocyanine green retention rate at 15 minutes of 20% or worse, and therapeutic choice other than hepatectomy were significant predictors of a poor prognosis on univariate analysis. Hepatectomy was the only factor that was significant on multivariate analysis. CONCLUSIONS: Patients may enjoy long-term survival if they receive hepatectomy with preoperative transcatheter arterial chemoembolization, when the number of primary nodules is no more than two, the portal trunk is not occluded by tumor thrombus, and the indocyanine green retention rate at 15 minutes is better than 20%.
Pancreatic cancer shows an aggressive growth behavior which results in an extremely poor prognosis. It is presently the 4th to 5th leading cause of cancer-related deaths in Western countries with an incidence of 8-10 new cases per 100,000 inhabitants. Since current conservative oncological therapies fail to influence the long-term outcome, curative resection remains the only possibility with a potential for cure. During the past decades, a considerable decrease in postoperative mortality after pancreatic resection and a significant increase in the resection rate have been achieved. Although several types of pancreatic resection have evolved, standard procedures are the classical Whipple resection for cancers of the pancreatic head and left resection for cancers of pancreatic body and tail. Since the pylorus-preserving Whipple resection and extended Whipple resection are still debated as better alternatives to the classical Whipple procedure, large, controlled clinical trials in patients need to be conducted to reach reliable conclusions. However, there is mounting evidence that the pylorus-preserving Whipple procedure offers a better postoperative outcome than the classical Whipple operation without compromising radicality and thereby the long-term prognosis. Despite the progress in surgical treatment of pancreatic cancer, the overall prognosis following resection remains unsatisfactory to date. It is hoped that progress in multimodality treatment and modern therapies, resulting from both clinical and advanced basic research, can improve the prognosis of this malignancy in the near future.
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During the past 10 years, we have performed extended right hemihepatectomy combined with pancreatoduodenectomy (rtHPD) in eight patients with bile duct carcinoma. We compared the results in these patients with those in 43 bile duct carcinoma patients who underwent extrahepatic bile duct resection with more extensive hepatectomy than hemihepatectomy. Our indication for rtHPD is bile duct carcinoma of the diffuse type involving the intrapancreatic bile duct. For patients with obstructive jaundice, biliary drainage was performed preferentially in the part of the liver to be preserved. Portal vein embolization was performed before extended right hemihepatectomy or left trisectorectomy. Complete external drainage of pancreatic juice followed by second-stage pancreatojejunostomy was performed in five rtHPD patients. There were no hospital deaths or hepatic failures. There were four 5-year survivors after rtHPD. There was no significant difference between the cumulative 5-year survival rates after rtHPD (71%) and non-HPD (42%). Patients with bile duct carcinoma whose prognosis can be improved only by rtHPD exist and should be treated by rtHPD. However, considering the reported high mortality rate after this procedure, rtHPD should not be performed in an institution where its safety cannot be guaranteed.
We have developed a new bioartificial liver bioreactor filled with porcine hepatocytes immobilized on polyester nonwoven fabric (NWF). In this study, we investigated the efficacy of our hybrid bioartificial liver system incorporating the NWF bioreactors and an immunoglobulin adsorbent column for perfusion treatment in a canine liver failure model. Xenogeneic perfusion treatment for operative canine liver failure models were performed for 3 h, and survival time, intracranial pressure, and blood and cerebrospinal fluid data were documented. Treatment was carried out without obstruction by immunological rejection when immunoglobulin adsorbent columns were used with the NWF bioreactors in combination. Dogs treated with this system exhibited a restricted increase of intracranial pressure and significant compensatory effects on blood and cerebrospinal amino acid imbalances as shown by a significant improvement of Fischer's ratio. On the other hand, relatively low capacity for ammonia elimination was shown as compared with homologous direct hemoperfusion.
UNLABELLED: Kinetic modeling of 99mTc-diethylenetriaminepentaacetic acid galactosyl human serum albumin (Tc-GSA) measures the total amount of asialoglycoprotein receptor within a subject's liver. This study tested the hypothesis that the amount of asialoglycoprotein receptor measured by Tc-GSA modeling provides a valid index of functional liver mass. METHODS: Twenty-two patients with cirrhosis, 18 patients with chronic hepatitis, and 9 patients with normal liver parenchyma were studied with Tc-GSA using a 30-min dynamic imaging protocol. The total amount of hepatic receptor was measured by kinetic modeling of the Tc-GSA time-activity data. The total number of viable hepatocytes was calculated using standard morphometric measurements of liver biopsy samples and liver volume measurements through CT. RESULTS: The total receptor amount strongly correlated with the total hepatocyte number (r = 0.803; P < 0.0001). CONCLUSION: Tc-GSA measurement of the total receptor amount is proportional to the number of viable hepatocytes and therefore provides a valid assessment of functional liver mass.
A 63-year-old male with advanced esophageal cancer was admitted to our hospital. He received neoadjuvant chemotherapy with intravenous cisplatin and fluorouracil (5-FU), and underwent resection of the esophagus and placement of a gastric tube. Two months later, multiple metastases appeared in the right lobe of the liver. Intermittent arterial infusion chemotherapy with cisplatin and 5-FU were performed. To selectively infuse the drugs into the right hepatic artery, the left hepatic artery was embolized. Treatment had a marked effect in the right lobe, but new lesions were subsequently discovered in the left lobe. The patient died of pleuritis 27 days after the end of cisplatin infusion and 12 months after surgery. In total, 465 mg of cisplatin and 20 mg of nedaplatin were administered. At autopsy, tissue samples were collected to measure the platinum concentration. The result showed the highest value to be in the right lobe, 4.8 times as high as that in the left lobe. It is suggested that the concentration of platinum in tissue is correlated with the anticancer effect of cisplatin to the tissue, despite of the traditional view that the tissue concentration and the effect are not related.
In living-donor liver transplantation, one of the tactics of hepatic vein reconstruction is to obtain a long and wide venous orifice. The short hepatic vein should be reconstructed in the left liver graft with a caudate lobe. In the modified right liver graft, the tributaries of the middle hepatic veins should be reconstructed if there are no communicating veins between the middle and right hepatic veins.
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Transcription of hypoxia-inducible genes is regulated by hypoxia response elements (HREs) located in either the promoter or enhancer regions. Analysis of these elements reveals the presence of one or more binding sites for hypoxia-inducible factor 1 (HIF-1). Hypoxia-inducible genes include vascular endothelial growth factor (VEGF), erythropoietin, and glycolytic enzyme genes. Site-directed mutational analysis of the VEGF gene promoter revealed that an HIF-1 binding site (HBS) and its downstream HIF-1 ancillary sequence (HAS) within the HRE are required as cis-elements for the transcriptional activation of VEGF by either hypoxia or nitric oxide (NO). The core sequences of the HBS and the HAS were determined as TACGTG and CAGGT, respectively. These elements form an imperfect inverted repeat, and the spacing between these motifs is crucial for activity of the promoter. Gel shift assays demonstrate that as yet unknown protein complexes constitutively bind to the HAS regardless of the presence of these stimuli in several cell lines, in contrast with hypoxia- or NO-induced activation of HIF-1 binding to the HBS. A common structure of the HRE, which consists of the HBS and the HAS, is seen among several hypoxia-inducible genes, suggesting the presence of a novel mechanism mediated by the HAS for the regulation of these genes.
BACKGROUND: Postsurgical recurrence of hepatocellular carcinoma (HCC) is frequent and fatal. Adoptive immunotherapy is active against HCC. We assessed whether postoperative immunotherapy could lower the frequency of recurrence. METHODS: Between 1992 and 1995, we did a randomised trial in which 150 patients who had undergone curative resection for HCC were assigned adoptive immunotherapy (n=76) or no adjuvant treatment (n=74). Autologous lymphocytes activated vitro with recombinant interleukin-2 and antibody to CD3 were infused five times during the first 6 months. Primary endpoints were time to first recurrence and recurrence-free survival and analyses were by intention to treat. FINDINGS: 76 patients received 370 (97%) of 380 scheduled lymphocyte infusions (mean cell number per patient 7.1x10(10) [SD 2.1]; CD3 and HLA-DR cells 78% [16]), and none had grade 3 or 4 adverse events. After a median follow-up of 4.4 years (range 0.2-6.7), adoptive immunotherapy decreased the frequency of recurrence by 18% compared with controls (45 [59%] vs 57 [77%]) [corrected] patients. Time to first recurrence in the immunotherapy group was significantly longer than that in the control group (48% [37-59] vs 33% [22-43] at 3 years, 38% [22-54] vs 22% [11-34] at 5 years; p=0.008). The immunotherapy group had significantly longer recurrence-free survival (p=0.01) and disease-specific survival (p=0.04) than the control group. Overall survival did not differ significantly between groups (p=0.09). INTERPRETATION: Adoptive immunotherapy is a safe, feasible treatment that can lower recurrence and improve recurrence-free outcomes after surgery for HCC.
BACKGROUND: To the authors' knowledge, multiple carcinoid tumors of the duodenum have not been reported previously. However, multiple carcinoids in the stomach, ileum, and rectum, which were accompanied by the proliferation of endocrine cells, have been reported in the published literature. METHODS: A patient with multiple carcinoids including argyrophilic cell hyperplasia of the duodenum and hypergastrinemia underwent surgery. The resected stomach and duodenum were analyzed histopathologically. RESULTS: There were 11 carcinoid lesions, each of which was accompanied by peripheral endocrine cell micronests (ECMs). Increasing gastrin positive cells in the antral region and chronic duodenitis in the duodenal bulb also were observed. The peripheral ECMs usually were adjacent to proliferating argyrophilic cells in the Brunner gland ducts or the crypts of Lieberkühn, which showed focal pyloric gland metaplasia. CONCLUSIONS: In the case presented in the current study, the development of the multiple carcinoid lesions may be strongly related to the presence of multifocal pyloric gland metaplasia, as well as to the trophic action of gastrin, which is present at high levels in the setting of chronic duodenitis.
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