Makoto Fujita

A new approach to chemoembolization therapy for hepatoma using ethiodized oil, cisplatin, and gelatin sponge

This article reports on a new approach to hepatic arterial chemoembolization therapy using ethiodized oil (Lipiodol, Ultra Fluide), cisplatin, and gelatin sponge (Gelfoam, Upjohn, Kalamazoo, MI) for hepatocellular carcinoma (HCC). The anticancer effects of this therapy on 20 patients who underwent subsequent hepatic resection were evaluated mainly by histologic examination. All main tumors were reduced in size following this therapy. It is notable that in 65% of the patients the tumor size was reduced to less than 50% of that before therapy. All the values of serum α‐fetoprotein (AFP) in the patients who exhibited pretreatment levels exceeding 100 ng/ml dropped by more than 50%, and in 55% of them it fell below 20 ng/ml. The concentration of platinum in the tumor tissue was significantly higher than that in the nontumorous tissue. In 15 of 20 patients (75%), the main nodules were completely necrotic. Thirteen of the patients had daughter nodules and/or small intrahepatic metastases (Group A); nine had tumor emboli in the portal (hepatic) vein (Group B); 17 had intracapsular invasions (Group C); and ten had extracapsular invasions (Group D). The ratios of patients with completely necrotic cancer cells in Group A were nine of 13 (69%); in Group B, seven of nine (78%); in Group C, 11/17 (65%); and in Group D, four of 10 (40%). In eight of the 20 patients (40%) no viable cancer cells were recognized at any foci. Lesions other than those with extracapsular invasion could be considerably eliminated with this form of therapy. It is expected that this method will become the therapy of choice not only for palliative treatment but also for preoperative treatment.

Preoperative indications for extended pancreatectomy for locally advanced pancreas cancer involving the portal vein.

This retrospective study attempted to determine the indications for extended pancreatectomy for locally advanced carcinoma of the pancreas, in terms of postoperative prognosis. An extended pancreatectomy with portal vein or superior mesenteric vein (PV/ SMV) resection and regional lymphadenectomy was performed in 35 of 50 consecutive cancers that extended into the retroperitoneal spaces and involved the PV or SMV. Among the many background factors in the 35 resected specimens, the degree of PV/SMV invasion by the cancer was most closely associated with prognosis, despite resection of all involved PV/SMV. This factor generally correlated with the preoperative findings on the portal phase of superior mesenteric arteriograph. In 17 selected patients in whom PV/SMV invasion had been angiographically both semicircular or less and 1.2 cm (1.4 cm on the film) or less in length, the 3-year survival rate was 59%. This survival rate was significantly higher than the 29% 3-year survival rate in all 35 patients (p < 0.05). Conversely, among the 18 patients in whom invasion was angiographically either beyond semicircular or more than 1.2 cm (1.4 cm on the film) in length, there were no 1.5-year survivors, and this result was even worse than that of 15 nonresectable cases. Based on postoperative survival, the degrees of PV/SMV invasion on preoperative angiography (narrowing pattern and length) are good indicators for aggressive pancreatectomy for locally advanced pancreatic cancer.

Treatment of hepatocellular carcinoma by transcatheter arterial embolization combined with intraarterial infusion of a mixture of cisplatin and ethiodized oil

The therapeutic effectiveness of transcatheter arterial embolization (TAE) with intraarterial infusion of cisplatin/ethiodized oil mixture in treatment of resectable and unresectable hepatocellular carcinoma was compared with TAE with intraarterial infusion of doxorubicin mixed with and without ethiodized oil. The series included 97 patients with unresectable hepatocellular carcinoma and 40 patients with resectable hepatocellular carcinoma. With TAE using doxorubicin infusion, a partial response of the tumor was seen in only 11%, and the 2-yr survival was calculated to be only 5%. Histologic examination of the specimens obtained by hepatectomy also showed that this treatment was relatively ineffective in daughter tumor and portal tumor thrombi. In contrast, TAE with infusion of cisplatin/ethiodized oil mixture significantly increased the rate of partial response (38%), and significantly prolonged the 2-yr survival (45%). Histologically this treatment gave severe necrosis in daughter tumors (69%) and tumor thrombi (78%) as well as main tumor (75%). This treatment was significantly better than TAE with doxorubicin and ethiodized oil infusion in terms of the tumor regression and histologic responses of main tumor and portal vein tumor thrombi, but not in terms of the 2-yr survival. However, 2 patients (8%) died within 4 wk of the latter treatment, whereas no deaths were reported after the former treatment. Therefore, TAE combined with intraarterial infusion of cisplatin/ethiodized oil mixture may be a safe and useful treatment modality for hepatocellular carcinoma.

Regional therapy in the management of intrahepatic recurrence after surgery for hepatoma.

The significance of regional therapy against the intrahepatic recurrence for hepatocellular carcinoma (HCC) was evaluated. During the past 6 years, 101 patients who had radical operations for HCC (liver cirrhosis, 75%; chronic hepatitis, 22%) were followed. Forty-seven patients (47%) had recurrences; the liver was the site of first recurrence in 43 patients and distant site recurrence in four patients. In the patients where the liver was the recurrent site, 33 patients (77%) received regional therapies for an aggregate total of 60 times. Transcatheter arterial chemoembolization was chosen as the first preferred therapy against recurrence in the liver in 30 of 33 patients (91%). Postrecurrence survival of the patients treated with regional therapy was significantly better than disease-free survival (p less than 0.001). Disease-free survival after surgery, postrecurrence survival, and postsurgery survival were compared in the patients treated with regional therapy and untreated patients. Fifty per cent survival after recurrence of the treated patients was 27 months, and that of the untreated patients was 3 months. Postrecurrence survival (p less than 0.001) and postsurgery survival (p less than 0.01) of the treated patients were significantly better than those of the untreated patients. To obtain successful long-term survival after surgery for the cirrhotic patients with HCC, it is necessary to repeat active regional therapies against the recurrent liver.

A pre-operative chemoembolization therapy using lipiodol, cisplatin and gelatin sponge for hepatocellular carcinoma

SummaryThe significance of pre-operative transcatheter arterial chemoembolization therapy using lipiodol, cisplatin and gelatin sponge (Gelfoam) for the prevention of the recurrence of hepatocellular carcinoma (HCC) was evaluated. On the 103 patients who underwent radical operations for HCC with a tumor size less than 10 cm, 52 patients received no pre-operative therapy (group C), and 51 patients received pre-operative chemoembolization using lipiodol, a chemotherapeutic agent and Gelfoam. Of these 51 patients, 37 patients received a combination of lipiodol, cisplatin and Gelfoam (group A), while the remaining 14 patients received lipiodol, adriamycin and Gelfoam (group B). The disease-free survival rates after surgery were compared between group A, group B and group C. The 2-year disease-free survival rates in group A, group B and group C were 72%, 46% and 54%, respectively. These rates therefore suggest that pre-operative chemoembolization using lipiodol, cisplatin and Gelfoam is a useful method to prevent the recurrence of HCC after surgery.

Clinical features of small hepatocellular carcinomas as assessed by histologic grades

BACKGROUND Ninety-seven patients with small hepatocellular carcinomas (HCCs) measuring 3 cm or less in size and three patients with adenomatous hyperplasia who underwent radical hepatic resection were examined in this study. METHODS The lesions were classified into four groups according to the following histologic grading criteria: group A, adenomatous hyperplasia (n = 3); group B, early HCC (n = 6); group C, well-differentiated HCC (wHCC) (n = 32); and group D, moderately or poorly differentiated HCC (n = 59). The involvement factors that seemed to be important or to characterize the progression of HCC and the survival rates were compared among the four histologic groups. RESULTS The frequency of patients with tumors larger than 2.0 cm in size and that of patients with 200 or more ng/ml serum alpha-fetoprotein increased with the progression of histologic malignancy. Tumor staining on the angiogram, capsular formation, and extranodular invasion were never seen in groups A and B, but they began to appear in group C and increased remarkably in group D. The 5-year survival rates of the patients in groups B, C, and D were 100%, 60%, and 27%, respectively, and statistically significant differences were seen among them. In comparative evaluation of the group C patients the lesions that showed no tumor staining had no capsule, and those that had no capsule had no extranodular invasion. The 5-year survival rate of patients with wHCC without extranodular invasion (81%) was significantly higher than that of patients with extranodular invasion (35%) (p < 0.05). CONCLUSIONS It may be recommended to provide the category of wHCC without extranodular invasion for pathologic classification of clinically early HCC (i.e., HCC of high curability).

Double Phase Ct Arteriography of the Whole Liver in the Evaluation of Hepatic Tumors

PURPOSE Our goal was to evaluate the contribution of double phase CT arteriography (CTA) of the whole liver to differentiate hepatic tumors from false-positive areas on CT during arterial portography (CTAP). METHODS In 38 candidates for surgical resection of hepatic tumors, both CTAP and double phase CTA were performed. A total of 68 perfusion defects were identified at CTAP. Of 68 perfusion defects, 47 were found to represent hepatic tumors [hepatocellular carcinoma (HCC), n = 31; hepatic metastasis, n = 13; cholangiocarcinoma n = 2; focal nodular hyperplasia, n = 1]. The other 21 perfusion defects were defined as perfusion abnormalities in which focal hepatic masses had not been identified at surgery or pathologic analysis. The phase one CTA scanning started 12 s after the beginning of the injection of contrast material, and the phase two CTA scanning started 20 s after the end of the phase one CTA, with 60 ml of contrast agent (150 mg I/ml) injected at a rate of 2 ml/s. RESULTS On phase one CTA, only 1 lesion in 31 HCCs showed rim enhancement and 26 HCCs (84%) had rim enhancement on phase two CTA. Twelve lesions (80%) of the hepatic metastases and cholangiocarcinomas had rim enhancement on phase one CTA and 11 lesions (73%) showed rim enhancement on phase two CTA. Twenty-one perfusion abnormalities on CTAP did not show rim enhancement on either phase one or phase two CTA. CONCLUSION Double phase CT arteriography of the whole liver was useful to differentiate hepatic tumors from perfusion abnormalities on CTAP.

Comparison between conventional and spiral CT in patients with hypervascular hepatocellular carcinoma

To determine the usefulness of spiral CT in the detection of hypervascular hepatic lesions, we compared conventional contrast enhanced CT (CECT) with whole liver dynamic scanning during the artery-dominant phase by spiral CT (SDCT), using hypervascular hepatocellular carcinoma (HCC) as a model. Twenty-nine patients with 56 hypervascular nodular type HCCs detected by hepatic digital subtraction angiography were examined by both CT techniques. These nodular type HCCs were divided into three groups according to diameter: < 10 mm (n = 7), 10-20 mm (n = 17), and over 20 mm (n = 32). None of seven lesions less than 10 mm in diameter was seen by either technique. Of 17 lesions 10-20 mm in diameter, four (24%) were detected by precontrast CT plus CECT, whereas 14 (82%) were detected by precontrast CT plus SDCT. There were no lesions detected by CECT only, whereas 10 lesions were detected by SDCT only (P < 0.01 by signed test). For 32 lesions over 20 mm in diameter, there was no significant difference in detection rates between the CT techniques. Our results indicate that spiral CT is useful for the detection of relatively small hypervascular hepatic lesions such as hypervascular HCCs.

Pancreatic invasion as the prognostic indicator of duodenal adenocarcinoma treated by pancreatoduodenectomy plus extended lymphadenectomy

UNLABELLED Pancreatoduodenectomy has become the standard procedure in resection of the duodenal adenocarcinoma, and some adjuvant therapies can be added to obtain further improvement in postoperative outcome. However, for patient selection, it is necessary to have a predictive indicator showing, if possible before laparotomy, which instances are noncurable by surgery alone or need adjuvant therapies. METHODS A retrospective analysis was made for 24 consecutive patients whose duodenal adenocarcinoma were treated by pancreatoduodenectomy plus a wide range of lymphadenectomies without any adjuvant therapies at Osaka Medical Center for Cancer and Cardiovascular Diseases. Patient survival rates were related to macroscopic and microscopic findings and to findings obtained by preoperative imaging techniques. RESULTS The overall survival rate was 69% at 3 years and 57% at 5 years; locoregional recurrence was the primary cause of death. Although the 5-year survival rate was 44% in patients with nodal involvement and 76% in those without, this difference did not reach statistical significance (P = .079). Instead, invasion into the pancreatic parenchyma at a macroscopic level was the most significant prognostic factor; the 5-year survival rate was 78% in the 16 patients without and 16% in the 8 patients with pancreatic invasion (P = .0047). Invasion into the pancreas correlated well with the angiographic findings; the 5-year survival rate was 25% in patients whose angiograms delineated the pancreatic invasion and 83% in patients whose angiograms did not (P = .0084). CONCLUSION When duodenal adenocarcinoma was treated by pancreatoduodenectomy plus a wide range of lymphadenectomy, pancreatic invasion at a macroscopic level was most associated with patient survival. Pancreatic invasion was well delineated by the preoperative angiogram, which would be helpful in patient selection.

Value of contrast-enhanced color Doppler sonography in diagnosing hepatocellular carcinoma with special attention to the "color-filled pattern".

The purpose of this study is to evaluate the effectiveness of contrast‐enhanced color Doppler sonography in the diagnosis of hepatocellular carcinoma (HCC), with special attention to the value of a “color‐filled pattern.”