Soichiro Inoue

Indications and Techniques of Extended Resection for Pancreatic Cancer

IntroductionThe resectability rate and postoperative survival rate for pancreatic carcinoma are poor. Aggressive resection including vascular resection and extended lymphadenectomy represent one strategy for improving survival. This study was carried out to clarify the indications for extended resection, especially vascular resection, for pancreatic carcinoma.MethodsFrom July 1981 to March 2005, we performed curative resection in 289 of 443 patients with pancreatic carcinoma in our department (65.2%). Vascular resection was performed in 201 (69.5%) patients and portal vein resection without arterial resection in 186 patients. Combined portal and arterial resection was performed in 14 patients and arterial resection without portal vein resection in 1. Extended lymphadenectomy including paraaortic lymph nodes was done. The postoperative survival rate was stratified according to operative and pathology findings.ResultsOperative mortality (any death within 30 days after surgery) occurred in 11 of the 289 curative resection patients (3.8%), including 1 of 88 patients without vascular resection (1.1%), 5 of 186 portal vein resection patients without arterial resection (2.7%), and 5 of 14 (35.7%) arterial resection patients undergoing portal vein arterial resection as well. Most patients who survived for 2 to 3 years had carcinoma-free surgical margins.ConclusionsThe most important indication for vascular resection in patients with pancreatic cancer is the ability to obtain cancer-free surgical margins. Otherwise, vascular resection is contraindicated. Extended lymphadenectomy may be not of benefit.

Clinical significance of portal invasion by pancreatic head carcinoma

BACKGROUND The purpose of the present study was to clarify the indication of aggressive surgery for pancreatic head carcinoma. METHODS Laparatomy was performed in 153 patients with carcinoma, 101 of whom underwent resection of the carcinoma. With histologic examination the degree of carcinoma invasion into the portal vein was classified into grades 0, I, or II according to the depth of invasion by the carcinoma. Macroscopic carcinoma invasion into portal vein was classified into types A, B, C, or D according to preoperative findings on the portal phase of superior mesenteric angiography or intraoperative portography. RESULTS Macroscopic findings correlated with the histologic invasion grades. The 1-year survival rate was 39.6% in grade 0, 11.3% in grade I, and 5.5% in grade II cases. The survival rates of patients with type A (p < 0.01), B (p < 0.05), and C invasion (p < 0.01) were higher than those of patients who did not undergo resection; however, no significant difference in the survival rates between patients who did not undergo resection and patients with type D invasion was observed. CONCLUSIONS For locally advanced carcinoma of the pancreatic head or entire pancreas, patients with type D invasion have no indication of aggressive surgery.

Intrahepatic Anastomosis Formation Between The Hepatic Veins In The Graft Liver Of The Living Related Liver Transplantation: Observation By Doppler Ultrasonography

In living related liver transplantation, the right lobe has come to be used as a graft to meet the metabolic demands of adult or adolescent recipients. In harvesting the right lobe as a graft, however, there is controversy as to whether or not the middle hepatic vein (MHV) should be included and reconstructed. Anatomical intrahepatic anastomosis between the right hepatic vein (RHV) and MHV is considered to exist, but the formation process of this functional anastomosis has not been demonstrated by Doppler ultrasonography (US). In our case, a right lobe including a right branch of the MHV was used as a graft. In implanting, the RHV was anastomosed to the inferior vena cava and the right branch of the MHV was ligated. Using Doppler US, we checked the blood flow in the hepatic vein after transplantation. Within 3 days of surgery, no flow was detected in the right branch of the MHV. A flow around the right branch of the MHV was observed at postoperative day 6. At postoperative day 9, a reverse flow was detected in which the right branch of the MHV drained into the RHV via the anastomosis between them. Based on our results, it appears that a functional intrahepatic anastomosis between hepatic veins formed gradually within 10 days of ligation of an afferent branch, during which time the graft function did not deteriorate.

Extended radical resection versus standard resection for pancreatic cancer: the rationale for extended radical resection.

Objectives: This clinical study was carried out to clarify the indications for extended radical resection for pancreatic carcinoma. Methods: From July 1981 to September 2003, 250 of 391 (63.9%) patients with pancreatic carcinoma underwent tumor resection in our department. Portal vein resection was performed in 171 of these 250 (68.4%) resected cases. The postoperative survival rate was studied using the operative and histologic findings. Results: Most of the patients who survived for 2 or 3 years were in the carcinoma-free surgical margins group. Conclusion: The most important indication for an extended radical resection combined with portal vein resection for pancreatic cancer is the ability to obtain surgical cancer-free margins. There is no indication for an extended resection in patients in whom the surgical margins will become cancer positive if such an operation is employed.

Decreased expression and frequent allelic inactivation of the RUNX3 gene at 1p36 in human hepatocellular carcinoma.

Background/aims: Alteration in transforming growth factor‐β signaling pathway is one of the main causes of hepatocellular carcinoma (HCC). The human runt‐related transcription factor 3 gene (RUNX3) is an important component of this pathway. RUNX3 locus 1p36 is commonly deleted in a variety of human cancers, including HCC. Therefore, we examined genetic and epigenetic alterations of RUNX3 in human HCC.

Detection of hepatic micrometastasis in pancreatic adenocarcinoma patients by two-stage polymerase chain reaction/restriction fragment length polymorphism analysis.

Hepatic metastasis and retroperitoneal recurrence generally are considered to be the two primary modes of recurrence in pancreatic cancer. The goal of this study was to determine if patients with pancreatic adenocarcinoma have hepatic and peritoneal micrometastasis at operation. Pancreatic adenocarcinomas are known to have a high incidence of K‐ras gene mutations. Liver tissue specimens were obtained from 30 patients (17 with pancreatic adenocarcinoma and 13 with other diseases) with a hiopsy needle at operation. Peritoneal washings were obtained during operation from 20 patients with pancreatic adenocarcinoma. Two‐stage polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis were used to detect K‐ras oncogene mutation at codon 12. Thirteen of 17 pancreatic adenocarcinoma patients had K‐ras gene mutations in the liver, whereas all 13 patients with other diseases did not. However, only two of 20 pancreatic adenocarcinoma patients revealed K‐ras gene mutation in peritoneal lavage fluids. These results indicate the feasibility of detecting hepatic micrometastasis in patients with pancreatic adenocarcinoma, and imply that PCR/ RFLP analysis may be of value in the diagnosis, treatment and follow‐up of hepatic metastasis of pancreatic adenocarcinoma.

Frequent promoter methylation and gene silencing of CDH13 in pancreatic cancer

It has recently been reported that CDH13 expression is silenced by aberrant methylation of the promoter region in several cancers. We examined the methylation status of the CDH13 gene in pancreatic cancer using methylation‐specific PCR (MSP), and detected aberrant methylation of CDH13 in all 6 pancreatic cancer cell lines examined. To confirm the status of the CDH13 gene in relation to the methylation pattern, we next examined CDH13 expression in these cell lines using reverse transcription (RT)‐PCR. As expected, no CDH13 expression was detected in any of the 6 pancreatic cancer cell lines. Moreover, 5‐aza‐2′‐deoxycytidine (5‐aza‐dC) treatment of CDH13‐methylated cell lines led to restoration of CDH13 expression. Among primary pancreatic cancers, 19 of 33 (58%) cases exhibited CDH13 methylation, while no cases exhibited it in corresponding normal pancreatic tissues. CDH13 methylation was detected even in relatively early pancreatic cancers, such as stage II cancers and cancers less than 2 cm in diameter. Our results suggest that the aberrant methylation of CDH13 occurs frequently in pancreatic cancer, even at a relatively early stage.

Overexpression of pituitary tumor transforming gene 1 in HCC is associated with angiogenesis and poor prognosis

The pituitary tumor transforming gene 1 (PTTG1) protein is cell‐cycle regulated and is identified as a human securin that inhibits sister chromatid separation and is involved in transformation and tumorigenesis. PTTG1 has very low or undetectable expression in most normal human tissues, but it is abundantly expressed in malignant cell lines and pituitary tumors. In this study, we investigated human PTTG1 expression in 62 hepatocellular carcinoma (HCC) specimens using quantitative real‐time reverse transcription polymerase chain reaction analysis. We found that, compared with corresponding noncancerous liver tissues, PTTG1 was remarkably overexpressed in HCCs (PTTG1/β‐actin; 0.443 ± 0.073 vs. 0.068 ± 0.007; P < .0001). Furthermore, we found a significant correlation between PTTG1 expression and serum alpha‐fetoprotein level (P < .001). Univariate and multivariate analyses revealed that the PTTG1 messenger RNA (mRNA) expression was an independent prognostic factor for disease‐free (odds ratio 2.70; P = .037) and overall (odds ratio 5.35; P = .007) survival. Moreover, we discovered a significant relationship between PTTG1 expression and intratumoral microvessel density. Our data supported an important role for PTTG1‐mediated upregulation of fibroblast growth factor (FGF)–2, one of angiogenesis and modulation of tumor progression, in hepatocarcinogenesis. In conclusion, PTTG1 might be critically involved in the development of HCCs through the promotion of angiogenesis. PTTG1 is overexpressed in HCC and our results suggest that PTTG1 mRNA expression has prognostic significance for the survival of postoperative patients with HCC. (HEPATOLOGY 2006.)

Detection of K-ras mutations in the plasma DNA of pancreatic cancer patients.

BackgroundIn pancreatic cancers, K-ras mutations have been found frequently (80%–100%), and they could be a good marker to detect tumor DNA in the plasma. Several studies have indicated that polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) analysis of K-ras mutation was a useful method for the detection of hepatic and lymph node metastasis of pancreatic cancer. However, this method sometimes exhibited false-positive results, and the rate of K-ras mutation might thus be overestimated in these tissues. To diagnose pancreatic cancer correctly at an early stage, we attempted to detect tumor DNA in the plasma of pancreatic cancer patients using a more sensitive and specific method.MethodsWe examined 28 pancreatic cancer patients using a sensitive mutation-specific mismatch ligation assay for K-ras gene mutations in primary tumors and paired plasma samples.ResultsK-ras gene mutations were detected in 26 of the 28 (93%) pancreatic cancers. We also found the same mutations in 9 of these 26 (35%) patients in their plasma DNA. This mutation was found even in the plasma of patients with TNM stage II cancer.ConclusionsGenetic alterations present in the tumors of pancreatic cancer patients can be detected in their plasma, and this approach is potentially applicable for cancer screening and the monitoring of this deadly disease.

Delayed rupture of a pseudoaneurysm following pancreatoduodenectomy: report of a case.

Abstract We report herein the case of a 63-year-old man in whom delayed rupture of a pseudoaneurysm occurred 120 days following pancreatoduodenectomy. Color Doppler examination indicated a pseudoaneurysm originating from the ligated gastroduodenal artery. Transcatheter arterial embolization was done at the common hepatic artery, proximal and distal to the pseudoaneurysm, with microcoils. The patient had a minor elevation of liver enzymes, which subsequently returned to normal. Due to the absence of any postoperative complications such as pancreatic anastomotic leakage, we assumed that the pseudoaneurysm formation had been caused by a weakness in the arterial wall according to skeletonization resulting from lymphadenectomy and intraoperative radiation therapy. To our knowledge, this case represents the longest interval between pancreatoduodenectomy and rupture of a pseudoaneurysm ever to be reported in the literature.