Most early hepatocellular carcinomas (HCCs) are well differentiated, with an ill-defined nodular appearance. When a well-differentiated HCC reaches a size of about 1.5 cm in diameter, less-differentiated cancerous tissues with greater proliferative activity evolve within it. Clonally-related HCC cell lines (HAK-1A and HAK-1B) established from a single HCC nodule with a variety in the histological grade suggest that less-differentiated cancerous tissues develop from clonal dedifferentiation of well-differentiated HCC tissues. Subsequently, moderately to poorly differentiated HCC tissues gradually replace the initial surrounding HCC.
HCC frequently occurs multicentrically whether synchronously or metachronously, defying complete cure by conventional therapies; therefore, chemoprevention of HCC is very important. Interferon (IFN)-α has been used for the treatment of chronic viral liver diseases to eradicate virus. Recently, IFN-α has been shown to possess highly suppressive effects on hepatocellular carcinogenesis. We found that type I IFN preparations inhibit the growth of 13 liver cancer cell lines at various degrees in vitro and in vivo, and the clinical dose of IFN preparations was effective in vivo. The data suggest that IFNs may inhibit the growth of clinically undetectable HCC cells and prevent or delay the development of HCC in patients with chronic viral liver diseases.

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The cases of multiple-metastasized liver cancer especially from colo-rectal cancer are increasing year by year. Many times a lot of efforts for medical or surgical treatment are in vain. However, from the view point of nutritional-metabolic therapy, it has been proved that cancerous lesions can be improved.
We experienced the case of complete remission one time after two months intra-hepatic artery 24 hours continuous infusion chemotherapy combined with macrobiotic diet guide. One year later, the patient had the recurrence of several liver nodes and we adopted microwave tissue coagulation (MTC) therapy and it worked over half a year.
We conclude the MCT is very useful in late stage metastasized liver cancer and more effective in case combined with diet therapy.

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Hepatocellular carcinoma (HCC) is an important clinical issue in Japan because of high prevalence and poor prognosis. HCC is treated by surgical operation including liver transplantation, microwave coagulo-necrotic therapy, radiofrequency ablation (RFA), percutaneous ethanol injection therapy (PEIT) and/or transcatheter arterial chemoembolization (TACE). Recent advance in these treatments can improve the prognosis of HCC. HCC is, however, multi-centrically occurred based on liver cirrhosis and chronic hepatitis. Therefore, physicians should treat not only HCC but also liver cirrhosis and hepatitis to patients with HCC.

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Today I wish to lecture you about the hepatic resection and loco-regional ablation therapy of the treatments for hepatocellular carcinoma.
Up until 1980's hepatic resection was thought a very risky attempt. But since then the technological advance for hepatic resection was remarkable and how to assess the liver function before the hepatic resection was improved.
Now hepatic resection can be done safely for the patients with well-preserved liver function.
The local ablation methods have been also developed. RFA (radio frequency ablation) is good at the treatment for HCC, especially for 3 or few HCC with 3 cm or less in diameter. And MCN (microwave coagulo-necrotic therapy) has the good ability of loco-regional control of HCC and it is especially suitable for the treatment with multiple tumors in initial or recurrent states.

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Transcervical microwave myolysis assisted by transvaginal ultrasonic guidance for myomas was developed. Using the system, a feasibility study of microwave myolysis was performed. After completion of microwave endometrial ablation for menorrhagia, a 14 gauge guiding needle was transcervically introduced to the uterine cavity and inserted into the myoma tissue under ultrasonography using a transvaginal probe with a puncture attachment. An inner needle of the guiding needle was replaced by a microwave applicator 1.6 mm in diameter. Three submucous myoma nodes 5-7 cm in size were irradiated by microwaves at 2.45 GHz. Main part of the nodes became avascular in Gd-enhanced MRI after one month. Usual myoma nodes shrank by 44-53% at three months that followed. No severe complications were encountered during and after the operation. Ultrasonically guided microwave myolysis is feasible and a promising treatment.

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Purpose: The purpose was to evaluate the effectiveness of Cool-tip^® radiofrequency ablation system for uterine endometrial ablation.
Methods: Eleven women with a complaint of hypermenorrhea underwent endometrial ablation with Cool-tip^® RFA system.
Results: The ablation was smoothly performed in all women, and they could leave our hospital the following day. Ten women could avoid the hysterectomy. However, intestine perforations caused by burn injury occurred in one woman two days after the surgery.
Conclusions: Endometrial ablation using Cool-tip^® RFA system is not safe in the present situations.

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Endoscopic microwave coagulation therapy (EMCT) was successfully applied to two male patients aged 94 and 84 with obstructive jaundice due to upper bile duct and lower bile duct carcinoma, because of their refusal of resection. A single 15-second exposure of microwave (30 W) was delivered during each treatment to the cancerous tissue using a monopolar shielded wire electrode under guidance of percutaneous cholangioendoscopy. Treatment was repeated a total of two times at interval of a week and no complication was encountered. Patients have subsequently lived for 26 and 20 months without jaundice. These results indicate that EMCT for patients with bile duct cancer without no metastasis and high operative risk might be an effective therapy for local control.

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We report a patient with bile duct carcinoma with longer than 13-year survival with no surgical treatment but cholangioscopic MTC.
A 67-year-old female who had undergone coronary arterial bypass grafting was referred to our institution because of increased obstructive jaundice with bile duct carcinoma. Because she had undergone the coronary bypass operation using pedicle right gastroepiploic artery, it was not possible to apply pancreatoduodenectomy as radical operation. Therefore, percutaneous transhepatic cholangioscopic and X-ray image-guided MTC using Microtaze^® (Heiwa Electronic Industrial Co. Ltd., Osaka, Japan) and 1.8 mm φ spherical, 5 mm φ bullet-shaped antennas was carried out under radiation of 45 watts and repetitions of 3-5 second duration. Serial cholangioscopic examination was conducted once a month for 3 years and sometimes disclosed involvements which were biopsied and shown to be recurrences histologically and followed by retreatment using MTC. The patient has been alive for more than 13 years since onset of jaundice, and is 81 years old. No adverse side effects were noted.
Our method uses not only coagulation but also a mild hyperthermic condition with a 5 mm φ antenna on the tumor margin at the depth of invasion as well as on the ductal lumen. MTC may be useful for palliation of inoperable patients with bile duct carcinoma, and sometimes for cure of the patients in the early stage of progression.

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We have performed alternative methods of ablation, which are laparoscopic radiofrequency ablation (LRFA) and percutaneous radiofrequency ablation with artificial pleural effusion (PRFA with APE), for hepatocellular carcinoma (HCC) located close to the hepatic dome. HCC located in this area is considered to be difficult to achieve complete necrosis by radiofrequency ablation. We treated total 27 cases of HCCs located in this area. Nine and 18 cases were treated by LRFA and PRFA with APE, respectively. The tumor size and number of session in LRFA group were significantly high in PRFA with APE. As a result, 2-year survival rate in LRFA group (76%) and PRFA with APE group (80%) was not significantly different from standard PRFA (93%). Thus, LRFA and PRFA with APE were efficient approaches for HCC located in hepatic dome.

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Endoscopic microwave coagulation therapy (MCT) or radio-frequency ablation (RFA) was developed in 1994. 213 endoscopic ablations (37% of 570 ablations) and 40 endoscopic hepatectomies (12% of 328 hepatectomies) were performed in our department. Appropriate selection of thoraco- and laparoscopic approach, marginal pre-ablation method, pre-coagulation method using RFA, and laparoscopic hand-assisted approach are important points. To evaluate the efficacy of endoscopic surgery, the operative outcomes were compared to 86 patients who underwent open non-systematic partial hepatectomy, smaller than 4 cm, and up to three tumors, in the same period. In endoscopic ablation, endoscopic hepatectomy, and open hepatectomy, the percent of liver damage B/C, intraoperative blood loss, operating time, percent requiring blood product, postoperative hospital stay, 5-year cumulative survival rate and complication rate was 49%, 20%, 17%, 23g, 346g, 850g, 3.2 hrs, 5.2 hrs, 6.6 hrs, 1%, 12%, 21%, 8 days, 9 days, 18 days, 54%, 68%, 63%, and 8.2%, 6.7%, 12% respectively. No implantation of malignant cells was encountered in endoscopic surgery. Endoscopic surgery can become a new therapeutic modality in treatment strategy for HCC.

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Between July 1994 and December 2006, 1,567 patients underwent hepatic surgery in our institute. Of these patients, 613 patients who received their initial therapy for HCC were analyzed this time. MCN (Microwave Coagulo-Necrotic Therapy) was performed in 456 patients, hepatic resection (Hr) was in 111, and Hr + MCN was in 42. The remaining 4 patients were treated with laparotomic ethanol injection.
The 1-, 3-, 5-, and 10-year cumulative survival rates for all patients treated with MCN (mean tumor size, 28.2 mm; mean number of lesion, 2.62) were 97.5%, 77.6%, 58.7%, and 37.3%, respectively. Five-year survival rate was 58.7% in MCN and 56.4% in Hr group (p = 0.9480).
The 1-, 3-, 5-, and 10-year cumulative survival rates for 238 patients treated with MCN who had 3 or fewer lesions and 3 cm or less in diameter were 98.1%, 85.2%, 70.3% and 43.5%. No significant differences were found in cumulative survival rates after MCN or Hr (p = 0.7358), nor were there any differences in disease free survival rates and local recurrence rates between MCN and Hr groups.
Of 613 patients, 319 patients had recurrences after on average 639.6 post operative days. Including 61 patients who had four or more recurrent lesions, 204 patients could be treated with MCN (mean tumor size, 3.7 mm; mean number of lesion, 3.08).
Based on the above, it was suggested that MCN has the good ability of loco-regional control of HCC and it is especially suitable for the treatment with multiple tumors in initial or recurrent states. Therefore, we recommend that not only Hr but also MCN should be used as a first choice for the treatment of HCC.

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The outcomes of hepatocellular carcinoma treated with percutaneous ethanol injection therapy (PEIT), percutaneous microwave coagulation therapy (PMCT) and percutaneous radiofrequency wave ablation (PRFA) were compared. The cumulative 5-year survival rate was most favorable, at 92%, with PRFA, followed by PMCT, PEIT, and concomitant percutaneous ablation therapy in this order, at 61%, 50% and 30% respectively. However, as determined by modified Japan Integrated Staging score (mJIS), the outcome following PEIT was equivalent to that following PMCT. Due to the short observation period and small number of cases, it was not possible to accurately compare these therapies based on mJIS, but, the outcome with PRFA appeared similarly favorable.

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Laparoscopic thermal ablation for hepatocellular carcinoma (HCC) is thought to be more accurate technique than percutaneous ablation, because HCC can be treated under direct vision. However, it is difficult to puncture deep-seated whepatic tumors under standard linear-type laparoscopic ultrasonography. Forward-viewing laparoscopic ultrasonography (End-Fire array), which was recently been developed, enables us to puncture deep-seated HCC exactly. We have performed laparoscopic thermal ablation for 8 HCCs out of 7 patients by using this End-Fire array. Among them, three were treated by microwave coagulation and four were by radiofrequency ablation. Six of 7 patients were completely and easily treated with this array. One patient had multiple HCCs and two relatively large HCCs were ablated for mass reduction. Thus, this new array is useful to perform laparoscopic thermal ablation against deep-seated HCC.

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Intrahepatic portal spreading and its extent of multiple hepatocellular carcinomas were assessed by multi-detector CT to confirm theoretical background of anatomical resection. 44 patients were examined and a main tumor was classified into Hilar type and Peripheral type. In Peripheral type, a number of the relevant portal branches was 1 or 2, and extent of the accessory tumors were relatively localized. In 43% of the cases, accessory tumors located within the sub-segment of 3rd relevant portal branch. And, in 79% of cases, those located within the lobe of 1st relevant portal branch. However, local ablation thought not to be coped for the possible portal spreading tumors. In Hilar type, a number of the relevant portal branches were many and accessory tumors were spread extensively. In conclusion, resection of the relevant portal segment of the main tumor as wide as a grade of hepatic extent should be curative for Peripheral type hepatocellular carcinoma.

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Eighteen patients of hepatocellular carcinoma were treated by percutaneous transthoracic radiofrequency ablation (RFA) with computed tomographic (CT) guidance. In this series, artificially induced pnemothorax was made to allow the access route to the tumor clear from the pulmonary parenchyma. The RFA needle electrode was punctured with transthoracic extrapulmonary transdiaphragmatic access. Hemothorax was found just after RFA in 1 patient, however, he had no fatal postoperative course without transfusion. No complication was observed in other patients. All patients survive with 343 days of a mean follow up duration. Intrahepatic single recurrence after RFA developed in 6 patients and multiple recurrence in 3. Among them, one patient had local recurrence at RFA site. No extrahepatic tumors or seeding tumors were developed. Artificially induced pnemothorax should be useful technique to achieve safe and effective transthoracic RFA.

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Aims: To clarify the effectiveness of microwave coagulo-necrotic therapy (MCN) as a surgical treatment for colorectal liver metastases to the caudate, which is anatomically difficult to treat.
Patients and Methods: From 1994 to 2006, a total of 185 consecutive patients underwent surgical treatment for colorectal liver metastases and 14 (7.6%) were found to have caudate metastases. Two had isolated caudate metastases. For 12 of the 14 patients, MCN was performed, while hepatectomy was for the other two.
Results: All tumors (7.1-35 mm in diameter) were completely ablated by MCN. Intraoperative bleeding of MCN was much less than that associated with hepatectomy. There was no morbidity associated with MCN. No local recurrence was noted in the caudate.
Conclusion: MCN is markedly effective treatment for caudate metastases.

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Non-surgical treatment for hepatocellular carcinoma (HCC) is increasing, thanks to the progress in ablation technology attained with the latest radiowave devices. However, hepatectomy is clearly the best treatment in terms of radicality. Recently, laparoscopic hepatectomy has increased as a treatment balancing radicality with minimal invasiveness. Laparoscopic hepatectomy is useful for tumor located in the front or the border region of the liver. Laparoscopic surgery requires a dry field, and control of bleeding is the key to its success or failure. To decrease an amount of bleeding, we perform previous coagulation by a microwave tissue coagulator along the incision line before the actual liver excision. It is very useful for laparoscopic hepatectomy.

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The case is a 72-year-old-male who was treated with percutaneous transhepatic low output microwave tissue coagulation therapy (PLMCT) using a new needle electrode 1 mm in diameter for metastatic liver tumor in touch with liver surface and the intestine. This needle electrode is more useful than an old type 16 G needle electrode in strength and the point that coagulated tissue is hard to adherent to the electrode. PLMCT was performed at the output of 40 watt for 90 seconds at a time. Tumor 1.7 cm in diameter was completely coagulated by irradiation 2 times and the intestine in touch with the liver surface was preserved judged by enhanced CT.
The results suggested that PLMCT using a new electrode 1 mm in diameter is a useful therapy even for small solitary liver tumor in touch with liver surface.

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