Hepatic infarction following percutaneous ethanol injection therapy for hepatocellular carcinoma

We report on two patients who developed hepatic infarction after undergoing percutaneous ethanol injection therapy (PEIT) for hepatocellular carcinoma (HCC). In both cases, liver function parameters deteriorated immediately after the ethanol injection, and enhanced computed tomography images showed a wedge-shaped avascular low-density area due to hepatic infarction. In one patient, PEIT was performed for a nodule treated with transcatheter arterial infusion (TAI) using a suspension of styrene maleic acid neocarzinostatin (SMANCS) 4 weeks before. In the other patient, TAI with SMANCS had been carried out 14 months previously for a different nodule in the same segment where the nodule treated with PEIT was located. When PEIT is used for patients with HCC who have previously undergone TAI, especially with SMANCS, PEIT may induce hepatic infarction.     

Left trisegmentectomy for hepatocellular carcinoma with tumor thrombi extending to the third branches in the remnant liver

BACKGROUND/AIMS: A successful left trisegmentectomy and tumor thrombectomy for hepatocellular carcinoma (HCC) of the right third branches in the remnant liver is described. METHODOLOGY: In this case, the hepatocellular carcinoma originated in the internal segment of an HBs- and HBe-Ag positive cirrhotic liver, involved the portal vein of the umbilical portion across the portal trunk to the contralateral third branches, and had many metastatic nodules in the anterior segment of the liver. To remove tumor thrombi by directly visualizing the lumen of the third branches of the portal vein, the portal trunk to the anterior branch of the portal vein was completely isolated by transecting the hepatic parenchyma along the intersegmental plane through a hilar approach. Tumor thrombi were removed by incising the portal trunk toward the anterior branch of the portal vein. Portal flow to the remnant liver was restored preceding liver resection to preserve hepatic function. After division of the anterior Glissonean code, the left trisegment and caudate lobes of the liver were resected. RESULTS: The patient was discharged 10 weeks after surgery and remained well for the first six months thereafter. Recurrent tumors, however, appeared in the remnant liver 7 months after surgery. CONCLUSIONS: This procedure may be applicable in cases of HCC with portal tumor thrombi extending into the third branches in the remnant liver.     

A study of treatment modalities for nonresectable primary liver cancer

This paper reports the results of multimodality treatment in 200 patients with nonresectable primary liver carcinoma (PLC) from April 1964 to July 1993. PLC was verified histologically in all cases. They were divided into two groups according to the methods of treatment. In group 1, 115 cases received anticancer agents by hepatic artery infusion (HAI). The 1- and 2-year survival rate was 10.4% and 1.7%, respectively and only one patient survived 65 months. In group 2, 85 cases received multimodality treatments by various combinations of hepatic artery chemoembolization (HACE), hepatic artery ligation (HAL), microwave coagulation (MIC) of tumor and ethanol injection into tumor (EIT). The 1-, 2-, 3- and 5-year survival rate was 34.1%, 21.2%, 12.0% and 6.7%, respectively. Five patients had been alive for 41 to 63 months and second-stage hepatic resection performed in another 6 patients. The results suggest that multimodality treatment is an effective approach to improve the long-term survival of patients with nonresectable PLC.     

Transarterial immuno-embolization therapy in patients with hepatocellular carcinoma

Surgical resection, transcatheter arterial embolization (TAE) and percutaneous ethanol injection therapy (PEIT) are effective for hepatocellular carcinoma (HCC), but the recurrence rate is high. We have devised a new therapy of transarterial immuno-embolization (TIE) with OK-432, fibrinogen and thrombin, and 2 cases are reported. Case 1: A 78-year-old Japanese male with HCC (diameter, 4 cm in subsegment 5) received TIE. The tumor size was markedly decreased, and the patient survived for more than 3 years without recurrence. Case 2: A 61-year-old Japanese male with HCC (diameter, 4.5 cm in segment 5) received hepatic subsegmentectomy following TIE. Histological examination of resected specimens following TIE showed massive infiltration of mononuclear cells in the main tumor. Tumor recurrence had developed three times thereafter, but was effectively treated by TIE. TIE may be an effective therapy for HCC.     

Hepatocellular carcinoma cases with five-year survival and prognostic factors affecting the survival time

Between 1980 and 1994, 178 patients were confirmed to have hepatocellular carcinoma (HCC) in our hospital. The 5-year survival rates in patients with HCC of stage I, II and IVA were 38.1%, 31.8% and 3.9%, respectively. No patient in stage III or IVB survived for more than four years. The 5-year survival rates of the patients treated by hepatic resection, ultrasonically guided percutaneous ethanol injection and transcatheter hepatic arterial embolization were 53.7%, 38.7% and 13.5%, respectively. The logrank test showed a significant difference in cumulative survival rates obtained in patients with HCC according to the tumor stage (p < 0.001) or principal treatment procedure (p < 0.001). Twelve patients survived for more than five years. We employed a Cox's proportional hazards model to estimate the factors significantly affecting the survival time. Variables with statistical significance were the clinical stage (p < 0.001), tumor size (maximal tumor diameter) (p < 0.001) and patient's age (p < 0.05). Conclusively, patients in the early stage of HCC associated with mild liver cirrhosis have a significantly better chance for long survival.     

Stimulation of alpha1A-adrenoceptors in Rat-1 cells inhibits extracellular signal-regulated kinase by activating p38 mitogen-activated protein kinase

We report a patient with cholangiocellular carcinoma with tumor thrombi in the main portal trunk who has survived for 9.5 years after hepatic resection. A 57-year-old woman underwent an extended left lobectomy, and resection of the caudate lobe plus the main portal trunk for a liver tumor that had a portal tumor thrombus in the main portal trunk. The portal vein was reconstructed with an autologous vein graft obtained from the external iliac vein. Histological examination of the resected specimen revealed moderately differentiated tubular adenocarcinoma compatible with cholangiocellular carcinoma. Factors contributing to the patient's long-term survival are discussed. Aggressive surgical resection can be effective even for such an advanced case of cholangiocellular carcinoma.     

Resection for extrahepatic recurrence of hepatocellular carcinoma

A total of 277 patients with hepatocellular carcinoma (HCC) underwent hepatic resection over a 20-year period. Twelve of 36 patients with recurrence confined to extrahepatic organs underwent surgical resection. There were no complications but one patient died in hospital from secondary intrahepatic recurrence. The 1-, 2- and 5-year survival rates for these 12 patients after hepatic resection were 92, 52 and 26 per cent respectively and were better than those of 24 patients who did not undergo resection for recurrence. The mean survival following resection for recurrent disease was 19.7 months and the longest survival time was nearly 8 years. Secondary recurrence after resection of metastases developed more commonly in the liver than in extrahepatic organs. Among the eight patients who survived for more than 4 months after the second operation, secondary recurrence developed in the liver and extrahepatic organs in eight and four patients respectively. In selected patients with isolated extrahepatic recurrence of HCC, surgery is effective in controlling extrahepatic disease and offers the only chance of long-term survival.     

Localization of gap junctions and tracer coupling in retinal Müller cells

BACKGROUND: The objective of this study was to evaluate the indications for percutaneous ethanol injection (PEI) performed in a single session under general anesthesia for treating patients with cirrhosis and large (tumors > 5 cm) hepatocellular carcinoma (HCC), and relevant survival curves. METHODS: Between November 1991 and November 1996, 108 patients were treated (a total of 128 procedures). They fell into 3 groups: 24 patients with single, encapsulated HCC measuring from 5-8.5 cm (Group A); 63 patients with single, infiltrating HCC measuring from 5-10 cm or multiple HCC (Group B); and 21 patients with advanced disease, either hepatic (Child's Class C) or neoplastic (symptomatic HCC or with portal thrombosis) type (Group C). The mean amount of ethanol injected was 62 mL. The average hospital stay was 3.8 days. The mean follow-up time was 40 months. RESULTS: The 1-, 2-, 3-, and 4-year survival rates were: 72%, 65%, 57%, and 44%, respectively, for Group A; 73%, 60%, 42%, and 18%, respectively, for Group B; and 46%, 25%, and 0%, respectively, for Group C. Mortality was 0.7% (bleeding from esophageal varices in a Child's Class C patient). The rate of major complications was 4.6% (1 case of peritoneal hemorrhage, 1 case of severe liver failure, 1 case of transient renal insufficiency, 1 case of peritoneal seeding, and 2 cases of infarctions of a segment adjacent to the tumor). CONCLUSIONS: Single session PEI has been proven to be a valid alternative in patients otherwise treated surgically or with transcatheter arterial chemoembolization who present with adverse prognostic factors or risks for these therapies, and may be an option for selected patients with advanced disease previously excluded from any therapy. Risk conditions are marked portal or pulmonary hypertension or esophageal varices at risk of bleeding, superficial tumors with severe coagulation disorders, hyperfibrinolysis, chronic renal insufficiency, and obstructive jaundice.     

Characterization of allergenic fractions from Drechslera monoceras

The present status of hepatic resection for hepatocellular carcinoma (HCC) is reviewed with special reference to the vascular aspects. Hepatic resection combined with portal tumor thrombectomy has been attempted in Japan. This procedure may be effective in the prevention of rupture of esophageal varices and making transcatheter arterial embolization possible. According to the report of Yamaoka and his associates, the 1- and 3-year survival rates of 29 patients treated with this combined procedure were 53% and 12%, respectively. This surgical strategy may thus yield survival benefits. In patients with a tumor near the confluence of the major hepatic vein and inferior vena cava, resection of segments 4b, 7, and 8 combined with hepatic vein reconstruction has been performed, which allows functional preservation of the residual liver. The historical development of hepatic vascular exclusion (HVE) is also reviewed. HVE can be performed safely using a centrifugal active pump, even in patients with cirrhosis. Hepatic resection combined with removal of tumor thrombus in the right atrium has been carried out using extracorporeal circulation. There are reports that at least two patients undergoing this operation survived more than 2 years after surgery. The hepatic warm ischemic time should be less than 60 min. Vascular surgery techniques are being increasingly applied in Japan for the treatment of HCC. Such surgery can be performed safely even in patients with cirrhosis. Improvement of long-term survival in patients undergoing such procedures remains an unresolved problem, however.     

Surgical intervention for patients with stage IV-A hepatocellular carcinoma without lymph node metastasis: proposal as a standard therapy

OBJECTIVE: The aim of this study was to evaluate the effects of surgical treatments for patients with stage IV-A hepatocellular carcinoma (HCC) without lymph node metastasis. SUMMARY BACKGROUND DATA: Nonsurgical therapy for highly advanced HCC patients has yielded poor long-term survival. Surgical intervention has been initiated in an effort to improve survival. METHODS: The outcome of 150 patients who underwent hepatic resection was studied. Survival analysis was made by stratifying stage IV-A HCC patients into two groups-those with and those without involvement of a major branch of the portal or hepatic veins. Those with involvement were further divided into subgroups according to major vascular invasions. RESULTS: Patients who had multiple tumors in more than one lobe without vascular invasion had a significantly better 5-year survival rate (20%) than those with vascular invasion (8%) (p < 0.01). The survival rate of patients with hepatic vein tumor thrombi (10%) was better than the rate for those with tumor thrombi in the inferior vena cava (0%), in whom no patients survived more than 2 years, although the survival rate for those with portal vein tumor thrombi in the first branch (11%) was no different from the rate for that in the portal trunk (4%). The operative mortality decreased from 14.3% in the first 6 years to 1.4% in the following 5 years. CONCLUSIONS: Surgical intervention for stage IV-A HCC patients brought longer survival rates for some patients. We recommend surgical intervention as an effective therapeutic modality for patients with advanced HCC.     

Percutaneous ethanol injection therapy by ethanol mixed with CO2 microbubble for hepatocellular carcinoma

One of the shortcomings of percutaneous ethanol injection therapy (PEIT) for hepatocellular carcinoma (HCC) is that many sessions are necessary to accomplish the treatment. This may be caused by which the ultrasonography (US) image does not reflect correctly to the kinetics of injected ethanol into HCC nodule. It is considered that number of treatment sessions are able to be reduced if we just enough injected labelled ethanol under US into HCC nodule. Therefore, we tried PEIT by ethanol mixed with CO2 microbubble (CO2 ethanol). The injected CO2 ethanol was aquired as hyperechoic image without strong acoustic shadow to the end of injection. Consequently we could reduce the number of treatment sessions to almost 1 for lesions < or = 3 cm in diameter and markedly reduce total dose of injected ethanol. The detectable rate of CO2 ethanol leaked out HCC nodule was high. No serious complication occurred. There have been only 1 lesion of local recurrence and no case of intrahepatic and peritoneal dissemination for 11.5 months on average of observation after PEIT by CO2 ethanol (CO2PEIT). These findings suggest that CO2PEIT is useful method for reducing the number of treatment sessions and total dose of injected ethanol, moreover preventing complication by ethanol leakage.     

Hepatic arterial chemotherapy for liver cancer over a period of 8 years

Hepatic arterial chemotherapy was performed for 27 patients with primary (3), metastatic liver cancer (21), and 3 other cases, over a period of 8 years. Chemotherapy was performed by intermittent hepatic arterial infusion of 5-FU or FAM (in case of metastatic tumor from colorectal cancer), FAM (from gastric cancer), and CDDP or Farmorubicin (HCC). Hepatic resection was performed in 10 cases of metastatic tumor from colorectal cancer, and 8 cases of 10 were curative operation. The 5-year survival rates of curative liver resection group, and non-curative liver resection or non-resection group were 57.1% and 12.5%, respectively. As is the case with metastatic cancer from gastric cancer, pancreatic cancer, and hepatocellular carcinoma (HCC), the prognosis was poor except for one CR case of HCC. We concluded that hepatic arterial chemotherapy may be recommended for a curative resected case of liver metastasis from colorectal cancer.     

Surgical therapy for hepatocellular carcinoma with liver cirrhosis

Approximately 80% of hepatocellular carcinoma (HCC) patients in Japan have associated liver cirrhosis, which increases the difficulty of surgical treatment. Liver dysfunction associated with liver cirrhosis is one of the most important predictive prognostic factors for HCC patients. Percutaneous ethanol injection therapy (PEIT) is useful for patients with small HCC or with poor hepatic functional reserve. Transcatheter arterial chemoembolization (TACE) is also useful both for patients with unresectable HCC and patients with multiple intrahepatic recurrence. Liver resection, however, lead to better outcome than other treatments when liver function is maintained after surgery. To determine operative procedures, it is important to evaluate the exact function of remnant liver, based on the preoperative liver function test and the evaluation of tumor character. For advanced HCC patients with vascular invasion, non-surgical treatments such as PEIT or TACE are not indicated, and surgical intervention can be an effective modality to improve their survival. Improvements of surgical technique and perioperative management have decreased fatal complications at a major liver resection and allowed us to carry out liver resection on patients with advanced HCC.     

Changes in epidemic patterns of Kawasaki disease in Japan

Cholangiocarcinoma is the second most common primary tumor of the liver after hepatocellular carcinoma and accounts for 5 to 25% of primary hepatic malignancies. Patients with intrahepatic or peripheral cholangiocarcinoma (ICC) most often present at an advanced stage leading to a poor prognosis. A review of the literature has produced only 10 patients who have survived over five years. We review the case of a young woman with a large cholangiocarcinoma, who has been disease free for eight years. The patient was treated with a right hepatic lobectomy, and received 4 cycles of 5-fluorouracil and levamisole postoperatively. Known factors associated with longer survival in patients with ICC include lack of evidence of local invasion (i.e. capsular, lymphatic, or vascular), negative margins, mucoblia, and well differentiation of the tumor, as well as the absence of lymph node metastases. Our patient had negative margins and lymph nodes, and showed no local invasion. However, no mucobilia was noted, and the tumor was only moderately differentiated. Young age has never been associated with increased survival. ICC remains a relatively uncommon tumor with an insidious onset and late presentation contributing to poor survival. Surgical resection remains the only therapeutic option. Since few patients are potentially resectable at the time of presentation, efforts at early diagnosis and options for adjuvant therapy are imperative.     

Natural history and prognosis of adenomatous hyperplasia and early hepatocellular carcinoma: multi-institutional analysis of 53 nodules followed up for more than 6 months and 141 patients with single early hepatocellular carcinoma treated by surgical resection or percutaneous ethanol injection

BACKGROUND: The natural history and posttherapeutic outcome of adenomatous hyperplasia and early hepatocellular carcinoma have rarely been analyzed. METHODS: Fifty-three hepatic tumors diagnosed as adenomatous hyperplasia or early hepatocellular carcinoma and followed up for more than 6 months and 141 patients with single early hepatocellular carcinoma treated by surgical resection or ethanol injection were collected retrospectively and analyzed. RESULTS: Some of the adenomatous hyperplasias developed to early and to advanced hepatocellular carcinoma. Tumors tended to grow faster in the order adenomatous hyperplasia, early hepatocellular carcinoma and advanced hepatocellular carcinoma, with respective mean (SD) tumor volume doubling times of 21.2 (10.7), 13.9 (11.7) and 6.0 (5.2) months. Overall survival rates at 5 years in 53 patients treated by surgery and 88 patients treated by ethanol injection were 89.6 and 71.9%, respectively. CONCLUSION: Progression of adenomatous hyperplasia and early HCC was confirmed pathologically. Early HCC was shown to have a good prognosis.     

Use of 20 cm or longer interposition vein grafts in free flap reconstruction of the trunk

Between January of 1993 and September of 1995, six microsurgical free tissue transplants were performed using saphenous vein grafts ranging from 20 to 39 cm in length. All six free flaps survived. Two wounds were caused by radiation injury and two by tumor resection. The remaining two free flaps were performed for contour deformity and spinal cord coverage. All of the recipient sites were located on the trunk. In each case, an arteriovenous loop was created before the microvascular anastomosis to the free flap. There was one arterial thrombosis requiring thrombectomy and revision of the anastomosis. Three patients developed minor wound complications that responded to local wound care. Each of the flaps successfully provided wound coverage, and in two cases the flaps tolerated further radiation results. Long interposition vein grafts can be used for difficult microsurgical reconstructive procedures with reliable results when no local recipient vessels are available. Versatility is therefore afforded in placement of the flap and the choice of recipient vessels, making this option a useful one in the treatment of complex wounds of the trunk.     

America: where kids are getting killed

Two cases of liver metastasis from colon cancer were treated by percutaneous ethanol (PEI) and acetic acid (PAI) injection for the recurrent lesion after surgery. Case 1 was a 60-year-old female who received sigmoidectomy with partial hepatectomy, and intraarterial 5-FU infusion was done after surgery. One year later, recurrence of liver tumor was detected, and PEI and PAI were performed for the metastatic lesions of the liver. Tumor regression and histopathological examination revealed coagulative necrosis. The patient died of lung metastasis 2 years and 10 months after treatment. Case 2 was a 58-year-old-male with ascending colon cancer and liver metastasis, who received surgery, and chemotherapy with intraarterial 5-FU infusion was continued. Four months later, recurrence of liver metastasis with elevation of serum CEA was noted. The patient received PEI three times and CEA decreased. Re-operation of hepatectomy revealed complete necrosis at the site of PEI. The patient has been alive for 1 year and 6 months with a new recurrence in the liver and is receiving repeated PEI therapy. PEI and PAI seem to be useful for the treatment of unresectable liver metastasis.     

Laparoscopic hepatic resection: a new and safe procedure by abdominal wall lifting method

HCC is well known for its high incidence of intrahepatic tumor recurrence and many patients suffering from them, usually undergo further treatments, such as PEI, TAE, MCNT or hepatic resection. However, conventional hepatic resection by large skin incision causes severe intraabdominal adhesions, which disturb US examination and further treatments. The aim of the laparoscopic procedure is to prevent intraabdominal adhesions. This is a study of the feasibility of laparoscopic hepatic resection without CO2 pneumoperitoneum, which is not yet popular, as a safe and effective procedure. The patient in this study had a solitary HCC in the lateral segment. Mobilization of the lateral segment, dissections of the left hepatic artery and portal venous branches, i.e. P2 and P3, were performed under CO2 gas insufflation. However, to avoid CO2 gas embolism, further procedures, including parenchymal compression and hepatic venous dissection, were performed using the abdominal wall lifting method without pneumoperitoneum. The patient could eat on the second postoperative day and had an uneventful postoperative recovery and was discharged from the hospital 13 days after surgery. Hospital stay was shorter than conventional hepatic resections with large skin incisions. The importance of this procedure lies in that it is not only a minimally invasive procedure, but also provides us with the possibilities of further treatments, including PEI and re-hepatic resection.     

Development of an MRI-compatible needle insertion manipulator for stereotactic neurosurgery

At the University of California, San Francisco, 17 patients who met the following criteria-hepatic tumor unresectable because of location or inadequate liver reserve, no metastases, HBsAg negative, no tumor larger than 5 cm in diameter, and no more than three tumors--were enrolled prospectively in a protocol employing preoperative chemoembolization to assess whether orthotopic liver transplantation (OLT) could cure a majority of highly selected patients with hepatocellular carcinoma (HCC). Thirteen patients had biopsy-proven HCC, 2 had the fibrolamellar variant, and 2 had radiological findings of HCC but no biopsy confirmation. Fourteen had underlying liver disease. All arteriographically apparent lesions were chemoembolized using a mixture including Gelfoam powder, doxorubicin, mitomycin-c, and cisplatin. Eight patients with poor hepatic reserve were chemoembolized when a donor organ became available, whereas 9 patients were chemoembolized and then placed on the waiting list. The only complication of chemoembolization was a gangrenous gallbladder in 1 patient. Thirteen patients underwent liver transplantation (2 patients without prior histological confirmation of carcinoma had no identifiable tumor at OLT); 3 patients developed metastases between the time of enrollment and donor organ availability and subsequently died; and 1 patient underwent a trisegmentectomy. Ten of the 11 patients with biopsy-proven HCC who underwent transplantation remain free of recurrent cancer at a median of 40 months; 1 patient died at 6 months of lymphoproliferative disease with no cancer found at autopsy. Although the role of chemoembolization is uncertain, these data show that the majority of carefully selected patients with HCC may achieve long-term survival with OLT.     

Needle tract implantation of hepatocellular carcinoma after percutaneous ethanol injection

BACKGROUND: Percutaneous ethanol injection (PEI) therapy currently is widely used for small hepatocellular carcinoma (HCC). However, only limited information is available regarding needle tract implantation after PEI treatment. METHODS: Records of HCC patients who underwent PEI between March 1990 and April 1997 at the National Cancer Center Hospital (n = 177) were reviewed to clarify the incidence, risk factors, and outcome of needle tract implantation of HCC. RESULTS: PEI was performed for 348 HCC patients with a median tumor size of 20 mm. Needle tract implantation was found in 4 patients (10, 13, 15, and 46 months, respectively, after PEI). The size of the PEI-treated HCC tumors in these patients was 20, 27, 28, and 30 mm, respectively, in greatest dimension. All tumors were enhanced in the early phase on dynamic computed tomography (CT), and were found to have moderate tumor cell differentiation on biopsied specimens. Of the four implanted tumors, three were resected and the remaining tumor was treated with extrabeam radiotherapy. At last follow-up, 2 of the 4 patients had died (1 of variceal bleeding 60 months after PEI and the other from cancer 61 months after PEI) and 2 were still alive (14 and 20 months, respectively, after PEI) with no evidence of active tumor. CONCLUSIONS: Needle tract implantation after PEI is not unusual, especially when HCC tumors are > or =2 cm in greatest dimension, enhanced in the early phase on dynamic CT, and/or moderately differentiated on biopsied specimens.