Yasuro Niwa

Percutaneous ethanol injection therapy for hepatocellular carcinoma. A histopathologic study

Histopathologic examination was done on 18 cases after percutaneous ethanol injection therapy (PEIT) for hepatocellular carcinoma. In eight cases, the lesion was treated by PEIT alone; in the other ten cases, PEIT was combined with transcatheter arterial embolization. The lesion was completely necrotic in 13 cases, 90% necrotic in four cases, and 70% necrotic in the rest. In addition, PEIT seemed to be effective against intercapsular, extracapsular, and vascular invasions. In the four cases of incomplete necrosis, the viable cancer tissue remained in small tumor nodules around the main tumor, in portions isolated by septa, or along the edge of the lesion. Therefore, ethanol should be injected not only into the center of the lesion, but also into sites close to its edge. Ethanol did not damage noncancerous liver parenchyma distant from injected sites. Local dissemination of the cancer cells was not found in any case. Therefore, PEIT seems to be a valuable therapy and may be an alternative to surgery in some cases.

Quantitation of α‐fetoprotein and albumin messenger RNA in human hepatocellular carcinoma

To analyze gene expression of α‐fetoprotein (AFP) and albumin in hepatocellular carcinoma (HCC), messenger RNAs (mRNAs) of these proteins in six human hepatoma cell lines and in 30 cases of HCC were quantitatively analyzed by competitive reverse transcription (RT) followed by polymerase chain reaction (PCR). The transcriptional levels of both AFP and albumin genes in HepG2 and Huh 7 cell lines were 1010 copies/μg RNA, in contrast to approximately 105 copies/μg RNA in HLE and HLF cell lines. AFP and albumin mRNA levels in three normal livers were 105 and 1010 transcripts/μg RNA, respectively. In 30 cases with HCC AFP mRNA level in neoplasm was 10 to 105‐fold enhanced as compared with that of nonneoplastic portion, and correlated with serum AFP level and tumor size (P < .01). In contrast, albumin mRNA level was not reduced in the neoplasms presenting enhanced AFP mRNA levels, indicating that AFP and albumin gene expression in situ is not necessarily mutually exclusive. Prospective analysis revealed that an increased serum AFP was shown at the time of recurrence among patients with enhanced AFP mRNA levels in neoplasm only, indicating that AFP mRNA levels in neoplasm could be a clinically predictable tool.

Presence of α-fetoprotein mRNA in blood correlates with outcome in patients with hepatocellular carcinoma

Abstract Background/Aims: Since hematogenous spread of tumor cells may adversely affect the prognosis of patients with hepatocellular carcinoma, we prospectively analyzed whether the presence of alpha-fetoprotein (AFP) messenger RNA (mRNA) in blood, used as a marker of circulating hepatocellular carcinoma cells, correlates with outcome. Methods: Eighty-eight patients were enrolled between December 1993 and August 1995, and 81 were followed until the end of 1997. All patients were treated with percutaneous ethanol injection therapy and/or transarterial embolization during follow-up. The status of AFP mRNA in blood was serially determined. Cumulative metastasis-free survival and overall survival were analyzed in relation to AFP mRNA and other clinical and laboratory variables. Results: Among 81 patients followed, 54 were positive for AFP mRNA at entry and 27 were negative. Extrahepatic metastasis developed more frequently among the AFP mRNA-positive patients (13 of 54) than among the AFP mRNA-negative patients (2 of 27) ( p =0.0296). After treatment, AFP mRNA became negative in 24 of 54 patients (44%). Cumulative metastasis-free survival and overall survival were significantly better in the 24 patients whose AFP mRNA became negative after treatment than in the 30 patients with persistently positive AFP mRNA ( p =0.0001 and p Conclusions: The presence or absence of AFP mRNA in blood is a predictor of outcome in patients with hepatocellular carcinoma.

Churg-Strauss syndrome (allergic granulomatous antiitis) with multiple perforating ulcers of the small intestine, multiple ulcers of the colon, and mononeuritis multiplex

A case of Churg-Strauss syndrome with multiple perforations of the small intestine is described. A 31-year-old woman was admitted with a complaint of epigastric pain. She had a history of bronchial asthma. One week before admission, white blood cell count was 20 800/mm3 with 59% eosinophils. Neurological examination on admission disclosed mononeuritis multiplex with paresthesia in both the lower and upper extremities. At colonoscopy, there were scattered aphthous ulcers in the colon. Ophthalmological examination revealed allergic conjunctivitis. After admission, hypereosinophilia increased to as high as 36 000/mm3. Oral administration of prednisolone (60 mg/day) was begun. On the 3rd day of the treatment, the eosinophil count decreased dramatically, to 400/mm3, while severe abdominal pain developed. Since abdominal X-ray film revealed free air in the abdominal cavity, emergency laparotomy was performed and multiple intestinal ulcers with perforations were found. Partial ileectomy was performed. Pathological findings of the resected specimen were interpreted as a necrotizing angiitis with extravascular granuloma. Since the operation, the patient has been asymptomatic, except for neurological symptoms. Hypereosinophilia has decreased without treatment to counts averaging 270/mm3, within 3 months. On the basis of the clinical features and histopathological findings, a diagnosis of Churg-Strauss syndrome was established.

Multiple-needle insertion method in percutaneous ethanol injection therapy for liver neoplasms

SummaryOne of the shortcomings of percutaneous ethanol injection therapy (PEIT) is that many sessions are necessary to accomplish the treatment. In order to reduce the number of treatment sessions, we inserted two or three needles before injection of ethanol was begun. Using the multiple-needle insertion method, we markedly reduced the number of treatment sessions. Histopathologic examination, imaging techniques, and serum alpha-fetoprotein levels showed efficacy of PEIT using the multiple-needle insertion method. No serious complication occurred. Levels of transient pain, fever, and the feeling of intoxication did not seem to be different from those occurring with the conventional method. Multiple-needle insertion method may be valuable as a method for reducing the number of treatment sessions necessary and thus shortening the treatment period.

Effect of anti-allergic agents on chemotaxis of neutrophils by stimulation of chemotactic factor released from hepatocytes exposed to ethanol

In an attempt to clarify a mechanism of neutrophil infiltration in the liver of alcoholics and possible therapeutic effect of antiallergic agents on accumulation of these cells in the liver, we investigated chemotaxis of neutrophils by stimulation of a chemotactic factor released from rat hepatocytes exposed to ethanol. When hepatocytes were incubated with more than 30 mM ethanol for 24 hr, chemotactic activity for both rat and human neutrophils was demonstrated in the conditioned medium. An enhanced chemotactic activity of the conditioned medium was reduced in the presence of antibody against KC/gro protein, one of the interleukin-8-related cytokines in rodents. Antiallergic agents such as azelastine or ketotifen at a concentration of >0.01 µM markedly reduced chemotaxis of neutrophils. Prednisolone at a concentration of >10 µM also reduced chemotaxis of neutrophils. These results suggest that neutrophil accumulation in the liver of human alcoholics could be induced by a chemotactic factor produced by the ethanol-treated hepatocytes and that antiallergic agents could be effective against the extent of alcoholic hepatitis by reducing chemotaxis of neutrophils.

Effect of splenectomy on hepatic metastasis of colon carcinoma and natural killer activity in the liver

We have previously demonstrated that administration of killed streptococcal preparation (OK432), a biological response modifier, increased the number of asialo GM1-positive cells in the liver, enhanced NK activity of hepatic mononuclear cells, and reduced the number of hepatic metastases of colon 38 adenocarcinoma that were inoculated into the superior mesenteric vein of C57BL/6 strain mice. In the present study, to clarify the role of the spleen in immune surveillance of the liver, the effect of splenectomy on hepatic metastasis of colon carcinoma and on hepatic NK activity has been examined. The number of hepatic metastasis increased in the splenectomized mice, compared with that in sham-operated mice. Administration of OK432 increased the number of asialo GM1-positive cells in the liver and enhanced NK activity of hepatic mononuclear cells in both groups, but NK activity of hepatic mononuclear cells in the splenectomized mice was less than that of the sham-operated mice. An enhanced NK activity of these cells was abolished by treatment with anti-asialo-GM1 antibody plus complementin vitro. Interleukin-2 mRNA expression was increased in the spleen 2 hr after OK432 administration and persisted until 8 hr, but was scarcely noted in the liver. On the other hand, NK activity of hepatic mononuclear cells in the asialo GM1-positive cell-depleted (previous administration of antiserum against asialo GM1) mice was enhanced after OK432 administration in the sham operated and splenectomized mice, but an enhanced NK activity in these mice was only partially or not at all abolished by treatment with anti-asialo GM1 antibody plus complementin vitro, respectively. These results suggest that the spleen could play an important role in an immune surveillance of the liver. In addition, OK432 first enhanced NK activity of hepatic mononuclear cells, which are sensitive to the antibody against asialo GM1. However, when asialo GM1-positive cells were depleted, OK432 enhanced NK activity of hepatic mononuclear cells, which are resistant to anti-asialo GM1 serum.

Cholestatic hepatocellular carcinoma diagnosed by deposits of Lipiodol and treated by combination of endoscopic retrograde biliary drainage and transcatheter arterial embolization

Cholestatic hepatocellular carcinoma, which grows into the bile duct and causes obstructive jaundice, is rare and difficult to diagnose. A case is presented in which cholestatic hepatocellular carcinoma was detected by deposit of Lipiodol. This is also the first case that was successfully treated by endoscopic retrograde biliary drainage and transcatheter arterial embolization.

A case of malignant lymphoma in the liver treated by percutaneous ethanol injection therapy under peritoneoscopic observation

SummaryA 41-year-old woman with non-Hodgkin’s lymphoma in the liver was treated with percutaneous ethanol injection therapy. Ethanol injection was performed twice under ultrasonographic guidance for a lesion inside the liver and once under peritoneoscopic observation for lesions on the surface of the liver. CT performed after treatment showed that sizes of the lesions decreased and that the lesions were not enhanced by contrast medium, indicating Iack of blood supply and necrosis of the lesion. Ultrasonography performed after treatment did not show any lesions in the liver. There was no sign of recurrence or metastasis.