Microwave coagulation therapy with interruption of hepatic blood in- or outflow: an experimental study.

PURPOSE: To determine how interruption of hepatic blood in- or outflow affects the coagulation diameter of microwave coagulation therapy (MCT) in the liver. MATERIALS AND METHODS: Laparotomic MCT at 60 W for 1 minute was performed in 11 Landrace pigs. MCT was performed under six different conditions: without occlusion (Group N; in seven lobes of seven pigs); with occlusion of the hepatic artery (Group A; in five lobes of five pigs); with occlusion of the portal vein (Group P; in five lobes of five pigs); with occlusion of the hepatic artery and portal vein (Group AP; in six lobes of six pigs); with occlusion of the hepatic vein (Group V; in five lobes of four pigs); and with occlusion of the hepatic artery and vein (Group AV; in seven lobes of seven pigs). The maximum diameters for each group were compared. RESULTS: The coagulation diameters (mean +/- SD) were 8.5 mm +/- 2.0, 10.0 mm +/- 1.6, 14.3 mm +/- 2.5, 14.4 mm +/- 2.4, 13.0 mm +/- 0.8, and 14.4 mm +/- 1.5 for Groups N, A, P, AP, V, and AV, respectively. The coagulation diameters for groups P, AP, V, and AV were statistically larger than those for groups N and A (P < .05). There was no significant difference between the coagulation diameters of Groups P, AP, V, and AV. CONCLUSION: The coagulation diameter depends mainly on the portal venous flow. In addition of direct interruption of the portal vein, interruption of the hepatic vein can also result in a substantial increase in the coagulation diameter.

[Assessment of colorectal cancer patients exhibiting bilobular multiple hepatic metastases].

We assessed 23 patients who underwent surgical therapy of hepatectomy or microwave coagulation therapy (MCT) for bilobular multiple hepatic metastatic foci following curative resection of the primary lesion of colorectal cancer. Hepatectomy was the first surgical therapy for 10 patients, and 6 of them received combined intra-arterial chemotherapy. All 13 patients in the MCT group received intra-arterial chemotherapy, and 8 of them underwent combined hepatectomy. The two-year survival rate of the hepatectomy group, classified according to the first surgical therapy, was 40% against 52% in the MCT group. In comparison with the H2 (2-5 foci) patients in the hepatectomy group, there were 7 H2 patients in the MCT group, and the two-year survival rate of these 7 patients was 50%. No significant difference was observed between hepatectomy and the MCT as the first surgical therapy. The survival rates of the 5 patients who received treatment for recurrence after the first surgery and of the 18 patients without any recurrence treatment were 80% and 40%, respectively. No significant difference existed between the two groups, but a p value of 0.06 was noted. MCT was considered to be useful local therapy for cancer as the first therapy and as a therapy following recurrence.

[A case report of intra-thoracic biliary fistula after percutaneous microwave coagulation therapy].

Among the locoregional therapies for hepatic malignant tumor, percutaneous microwave coagulation therapy (PMCT) has spread widely as a minimally invasive therapy. We performed PMCT on 40 patients under hepatic blood flow interruption with the aim of improving the radical treatment and expanding the coagulation area by single microwave delivery. A patient with a 2.5 cm lesion in S5 of the liver under PMCT transdiaphragmatically, but he developed a postoperative biliary fistula with consequent development of an intra-thoracic abscess through the diaphragm. Biliary fisture and liver abscess disappeared with open drainage under thoracotomy and laparotomy. Liver abscess has occasionally been reported as a PMCT complication, whereas there have been no reports, to the authors' knowledge, about intra-thoracic abscess as a PMCT complication, as in our case. It should be kept in mind that the penetration of the diaphragm as a route for PMCT may result in a biliary fistula flowing into the thorax, leading to a very serious condition.

[Transcatheter arterial chemo-embolization using degradable starch microspheres (DSM) markedly effective for post-hepatectomy intra-hepatic recurrence in a patient with cholangioma].

Transcatheter arterial chemo-embolization (TACE) using degradable starch microspheres (DSM) was performed for multiple recurrence after hepatectomy in a patient with cholangiocarcinoma. The patient was a 68-year-man. He received treatment for hepatitis type C starting in 1996 at a nearby hospital. In November 1997, an increased AFP level was noted and a CT scan of the abdomen revealed an abnormal shadow in the liver. On May 21, 1998, imaging results led to the diagnosis of cholangiocarcinoma or a mixed type of hepatocellular carcinoma with cholangioma. Hepatic S7 sub-sequential resection was performed. The lesion was found to be a tumor-forming type, measuring 2.2 x 2.0 cm in diameter, diagnosed histopathologically as cholangiocarcinoma, tw (-), but Stage III since a nodule suggesting intrahepatic metastasis was noted in the cut surface of the resected liver. CT scan after a month revealed multiple metastatic lesions in the liver. TACE was performed by administering 450 mg of DSM, 10 mg of MMC and 30 mg of FARM, given in three divided doses on October 30, 1998, and February 9, 1999, according to Seldinger's method. A CT scan on January 31, 2000 revealed nearly complete remission of the hepatic SOL. Accordingly, TACE was considered to be useful therapy in combination with DSM, MMC and FARM for intrahepatic recurrence of cholangiocarcinoma.

[Three long surviving patients with gastric cancer metastasizing to the liver under interdisciplinary therapy].

In 30 patients with gastric cancer metastasizing to the liver over the past 15 years at our hospital the primary foci in the stomach could be resected in a curative manner. The authors report herein three long surviving patients in this series. [Case 1] A 49-year-old male. Distal gastrectomy was performed in November 1984. Metastasis to the liver occurred in June 1986. The right lobe of the liver was resected in November 1987 after transcatheter arterial embolization (TAE). Although hepatic arterial infusion chemotherapy was conducted, the cancer metastasized to the whole body, and the patient died in December 1991. [Case 2] A 65-year-old female. Distal gastrectomy was performed in July 1994. The left hepatic lobe and segment 5 in the right lobe were resected in June 1995. Although TAE was performed six times starting in December 1996, the patient died of hepatic failure in July 1999. [Case 3] A 73-year-old male. This patient simultaneously received distal gastrectomy and extended resection of the posterior hepatic segments in September 1997. Cancer recurred in the remaining liver in July 1998. Although microwave coagulation therapy (MCT) and TAE were performed, the patient died of hepatic failure in January 2000. In these patients who survived for a long period, the primary focus was well-differentiated adenocarcinoma under sufficient local control with metastasis limited to the nearest regional lymph nodes (group 1 lymph nodes). The patients could undergo interdisciplinary therapy, including hepatectomy, MCT, TAE, and hepatic arterial infusion chemotherapy.

Microwave coagulation therapy for multiple hepatic metastases from colorectal carcinoma.

BACKGROUND: Compared with other treatments, microwave coagulation is a relatively less invasive treatment for various kinds of solid tumors. Although its effectiveness in primary hepatocellular carcinoma has been shown, its effectiveness in the treatment of hepatic metastases from colorectal carcinoma has been unclear. The aim of this study was to evaluate its effectiveness in the treatment of multiple hepatic metastases from colorectal carcinoma by comparing this technique with that of hepatic resection. METHODS: Thirty patients with multiple metastatic colorectal tumors in the liver who were potentially amenable to hepatic resection were randomly assigned to treatment with microwave coagulation (14 patients) or hepatectomy (16 patients). Tumors in the microwave group were coagulated after laparotomy at an output of 60-100 W for 2-20 minutes under the guide of ultrasonography, whereas tumors in the hepatectomy group were treated with lobectomy, segmentectomy, subsegmentectomy, and/or wedge resection. RESULTS: One-, 2-, and 3-year survival rates and mean survival times were 71%, 57%, 14%, and 27 months, respectively, in the microwave group, whereas they were 69%, 56%, 23%, and 25 months, respectively, in the hepatectomy group. The difference between these two groups was statistically not significant (P = 0.83). On the other hand, the amount of intraoperative blood loss in the microwave group (360 +/- 230 mL) was smaller than that in the hepatectomy group (910 +/- 490 mL, P < 0.05). Blood transfusion was necessary for 6 patients in the hepatectomy group, but it was not necessary in the microwave group. CONCLUSIONS: Microwave coagulation therapy is suggested to be equally effective as hepatic resection in the treatment of multiple (two to nine) hepatic metastases from colorectal carcinoma, whereas its surgical invasiveness is less than that of hepatic resection.

Negative feedback regulation of activated macrophages via Fas-mediated apoptosis.

Apoptosis is a critical event for eliminating activated macrophages. Here we show that Fas-mediated apoptosis may participate in the mechanism of negative feedback regulation of activated macrophages. Cytokine-activated macrophages released high levels of nitric oxide (NO) that induced apoptosis in macrophages themselves. This NO-induced macrophage apoptosis was inhibited by a Fas-Fc chimeric molecule that binds to Fas ligand (FasL) and prevents its interaction with endogenous cell surface Fas. High levels of NO stimulated the release of the soluble form of FasL that was inhibited by a matrix metalloproteinase inhibitor KB-8301. High levels of NO also upregulated the expression of Fas mRNA in macrophages. In addition, macrophages isolated from Fas-lacking mice were resistant to NO-induced apoptosis. Finally, inhibition of apoptosis by a caspase inhibitor augmented peroxide production from activated macrophages. These findings suggest that high levels of NO released from activated macrophages may promote the Fas-mediated macrophage apoptosis that may be a negative feedback mechanism for elimination and the downregulation of activated macrophages in the vessel wall.

Heterotopic gastric mucosa in the gallbladder: sonographic and CT findings.

We present computed tomographic (CT) and sonographic findings of heterotopic gastric mucosa incidentally found in a 63-year-old male. CT showed a slightly high density area in the gallbladder, which was intermediately enhanced early after bolus injection of contrast medium. Ultrasonography showed an echogenic sessile polyp. Histologically, the tumor consisted of gastric fundic glands containing parietal cells and chief cells.

Pranidipine enhances the action of nitric oxide released from endothelial cells.

Nitric oxide (NO) synthesis in vascular endothelium of patients with hypertension is altered. Calcium antagonists have been shown to improve endothelial function in hypertensive patients. Here we report that pranidipine, one of the latest long-acting calcium antagonists in the dihydropyridine group, enhances the actions of NO released from endothelial cells (ECs). Pranidipine significantly enhanced cGMP accumulation in vascular smooth muscle cells cocultured with ECs, whereas amlodipine and nifedipine had no significant effects. In addition, pranidipine also suppressed basal and thrombin-stimulated endothelin-1 production from ECs. Pranidipine also enhanced cGMP accumulation in rat aortic segments with endothelium but not in endothelium-denuded vessels. In contrast, pranidipine had no effect in the presence of N(G)-monomethyl-L-arginine, an inhibitor of NO synthesis. Pranidipine did not affect the basal expression of endothelial NO synthase in ECs. However, pranidipine upregulated the activity of superoxide dismutase in ECs. These findings suggest that pranidipine enhances NO action through inhibition of superoxide-induced NO decomposition in the vessel wall. Thus, pranidipine may be useful in the treatment of impaired endothelial function in patients with hypertension.

Comparison of the effects of in-vivo thermal ablation of pig liver by microwave and radiofrequency coagulation.

Microwave and radiofrequency coagulation is frequently used for the treatment of hepatic tumors. However, differences between these types of therapy have not been clearly demonstrated so far. We performed both types of thermal ablative treatment on pig liver, and compared the size and shape of the coagulated areas produced. The effects of combining both treatments and interrupting hepatic blood flow were also evaluated. The liver of an anesthetized pig was thermally coagulated, with or without interruption of hepatic blood flow, using a needle electrode at 40 W for 150 s with 2450-MHz microwaves and/or with a 460-kHz radiofrequency current. The diameters of the coagulated areas in the liver were 20 +/- 3 mm (mean +/- SD; n = 4) after microwave coagulation and 28 +/- 3 mm following radiofrequency coagulation when blood flow was not interrupted, whereas they were 31 +/- 2 mm and 37 +/- 3 mm, respectively, when blood flow was interrupted. When these treatments were combined sequentially, the diameters of the lesions were 43 +/- 3 mm and 29 +/- 2 mm with and without blood flow interruption, respectively. The ellipticity of the coagulated area, as measured by the largest-to-smallest ratio of its diameters, was 2.3 +/- 0.4 after microwave coagulation and 1.1 +/- 0.1 following radiofrequency coagulation. We conclude that radiofrequency coagulation produces a larger and more spherical coagulated area in the liver (P < 0.01) than does microwave coagulation. The lesion becomes larger (P < 0.05) with both treatments when hepatic blood flow is interrupted during the treatment. The sequential combination of these treatments produces a much larger lesion (P < 0.05) than that produced by either treatment alone.

[Microwave coagulation therapy under laparotomic ischemia for multiple liver metastases of colorectal cancer].

Microwave coagulation therapy (MCT) under laparotomic ischemia induced by partial obstruction of the hepatic artery and portal vein was conducted on patients with multiple liver metastases of colorectal cancer. The patients were then compared with those who underwent non-ischemic MCT. Among the patients with liver metastasis of colorectal cancer we encountered between August 1990 and October 1998, 14 patients who developed multiple cancer (five or more) in the bilateral liver lobes were enrolled in the study. No clear differences were observed in the sex, age, frequency of simultaneousness, therapy other than MCT, number of foci, and number of MCT between the ischemic MCT and non-ischemic MCT group. Postoperative CT revealed residual foci in one of the seven patients in the ischemic MCT group. A comparison of the cumulative survival rate revealed that the ischemic MCT group had a higher one-year survival rate (50%) than the non-ischemic MCT group (14%). A comparison of patients with a residual lesion and those with no residual lesion showed that all six patients with a residual lesion died less than one year after surgery. Eight patients with no residual lesion had a significantly better prognosis (p < 0.05). It is important to eliminate any residual metastatic lesion during surgery in multiple liver metastases of colorectal cancer If the residual lesion is non-resectable, its elimination by ischemic MCT would contribute to the long-term survival of the patients.

Reduction of risk of pneumonia associated with use of angiotensin I converting enzyme inhibitors in elderly inpatients.

Pneumonia is a major direct cause of death in the elderly. Although aspiration based on a reduced cough reflex is one of the causes of pneumonia in the elderly, there are few studies of angiotensin-I converting enzyme inhibitors (ACE inhibitors), which are antihypertensive drugs that induce cough, as a factor influencing the incidence of pneumonia in institutionalized elderly subjects. To assess the effect of ACE inhibitors and dihydropiridine calcium-channel blockers on the incidence of pneumonia, we conducted a hospital-based case-control study. Cases were 55 pneumonia patients aged > or = 65 years during a 1-year period. The controls were elderly subjects, frequency matched to the cases by age and gender (n = 220). Data were collected on known risk factors and on medication for hypertension, consisting of ACE inhibitors, calcium-channel blockers, and nonantihypertensive medication. The significance of differences in risk factors was analyzed using univariate and multivariate comparisons of cases and controls. After adjustment for potential confounding factors, the relative risk estimates for pneumonia were 0.38 (95% confidence interval [CI], 0.15-0.97) and 1.84 (95% CI, 0.89-3.78) for ACE inhibitors and calcium-channel blockers, respectively, relative to nonantihypertensive medication. The preventive effect of ACE inhibitors on pneumonia was apparent in long-acting ACE inhibitor users (0.24; 95% CI, 0.07-0.88). We conclude that ACE inhibitor use is an independent factor reducing risk of pneumonia among elderly inpatients.

Percutaneous microwave hepatic tumor coagulation with segmental hepatic blood flow occlusion in seven patients.

OBJECTIVE: We assess the usefulness of microwave hepatic tumor coagulation therapy with balloon occlusion of segmental hepatic blood flow for eight recurrent metastatic hepatic tumors in seven patients. CONCLUSION: Limited early experience with microwave hepatic tumor coagulation therapy and segmental hepatic blood flow occlusion has been positive, suggesting that further clinical evaluation is warranted.

[Clinical application of ischemic microwave coagulation therapy for malignant liver tumor].

By means of ischemic coagulation of the hepatic artery and portal vein in a microwave coagulation experiment of in vivo swine [correction of bovine] liver, we confirmed approximate doubling of the coagulation diameter compared to the usual coagulation. Based on this fact, for treatment of patients with metastatic liver tumor, we developed an ischemic percutaneous microwave tumor coagulation method using IVR method and applied it in one case, and performed laparotomy microwave tumor coagulation in three cases. We performed the ischemic percutaneous microwave tumor coagulation method on one of the cases. Coagulation was performed for one minute at a dose of 100 W for treatment of metastatic liver tumor of 2 cm in diameter via laparotomy. The postoperative CT showed an extensive coagulation larger than 3 cm. A 2 cm liver tumor was coagulated under balloon ischemia of the hepatic vein and hepatic artery for 13 minutes at a dose of 60 W. The maximum coagulation diameter was 5 cm. Extensive coagulation was possible with percutaneous microwave tumor coagulation through ischemia.

[Good response in case of hepatocellular carcinoma; a case report of interdisciplinary local therapy].

A 47-year-old male patient with chronic hepatitis had a high AFP level during the follow-up period. Abdominal CT revealed at S5, which led to a diagnosis of hepatocellular carcinoma. In August 1992, partial resection of S5 was performed, and ethanol was injected into the tumor at S2. In July 1993, recurrent tumors were observed at S5 and S3. PEIT was performed for each lesion. In December 1994, multiple recurrence was observed and 4 mg SMANCS was injected through the proper hepatic artery. In July 1995, another 4 mg of SMANCS was injected into the tumors. In June 1996, only a 20 mm lesion at S5 remained while the other lesions disappeared. Under general anesthesia, the patient underwent percutaneous microwave tumor coagulation. In December 1997, the AFP level was normal, and imaging revealed disappearance of the recurrent tumor. Selection of local therapy for hepatocellular carcinoma achieved long survival in our case considering the QOL and frequent therapy administration.

Decreased circulating levels of vitamin K and 25-hydroxyvitamin D in osteopenic elderly men.

Changes in the circulating factors participating in involutional osteoporosis have been intensively investigated in women, but little is known about this in men. We investigated the possible participation of circulating factors including testosterone, vitamin D metabolites, and vitamins K1 and K2 in osteopenia in elderly men. In a group of 27 ambulatory men aged 74 +/- 10 years (mean +/- SD; range, 60 to 90), the bone mineral density (BMD) of the second to fourth lumbar vertebrae was measured by dual-energy x-ray absorptiometry (DXA) and expressed as a Z score, the age-adjusted BMD value for the Japanese population (mean +/- SD, 0 +/- 1). Although the plasma level of total testosterone significantly decreased with age in the group, it did not significantly correlate with the Z score. However, the plasma levels of 25-hydroxyvitamin D (25-OHD), phylloquinone, menaquinone-7 (MK-7), and albumin were significantly positively correlated with the Z score. Moreover, plasma 25-OHD and both phylloquinone and MK-7 were significantly positively correlated in the subjects. These observations suggest that depressed circulating levels of 25-OHD and vitamin K concomitantly and cooperatively participate in osteopenia in elderly men, which may reflect the etiology of the type II moiety of involutional osteoporosis.

[Preoperative chemoradiation therapy for advanced rectal cancer].

Preoperative concurrent chemoradiation therapy with 5-fluorouracil and cisplatin was applied for advanced rectal cancer. Eligible criteria were as follows: no previous treatment, 4 more than hemicircular occupation, T3 or more invasion to adjacent organs or lymph node metastasis on CT scan, tumor fixation by digital examination. Eleven patients were enrolled with this regimen consisting of 5-FU; 500mg/day x5/w x4, CDDP; 10mg/day X 5/w x4 and radiation; 2Gy x 5/w x 4. As a toxicity, grade 2 leukopenia in 2 cases, grade 2 GI symptoms in one case and radiation dermatitis was observed in 8 cases. As a local response, there were PR in 10 cases and NC in 1 case. Surgical resection was performed on 8 patients. Histological responses in the resected specimens were grade 2, 5 cases; grade 1b, 1 case; and grade la, 2 cases. Operative radicalities were grade A, 3 cases; grade B, 3 cases; and grade C, 2 cases. Preoperative chemoradiation is one of the effective options in multimodal treatment for advanced rectal cancer.

[Local control of hepatic malignant tumors by percutaneous microwave].

We investigated the effects of percutaneous microwave coagulation under general anesthesia in the local control of hepatic malignant tumors. Coagulation at 60 W was done for normal liver of living swine using a percutaneous electrode. Wide-range coagulation at the tip of an electrode, 3 mm in diameter, was conducted. Clinically, echo-guided percutaneous microwave tumor coagulation was done for a total of 11 lesions in 5 patients with hepatocellular carcinoma and 4 with metastatic tumors in the liver under general anesthesia. Coagulation at 60 W of the liver of living swine for 1.5 and 10 min, using a percutaneous electrode, produced a maximal coagulation of 10, 20 and 30 mm, respectively. The trial electrode permitted coagulation almost at the tip of the electrode only. Percutaneous microwave coagulation of 11 lesions of the clinical cases resulted in complete coagulation in 7 lesions and incomplete coagulation in 4. The lesions showing complete coagulation were all less than 23 mm.

[Complication of reservoir hepatic artery infusion chemotherapy and additional treatments].

In 54 patients who underwent hepatic artery infusion chemotherapy for hepatic tumors at our hospital between January 1990 and December 1996, we investigated the complications of this therapy and the therapeutic techniques following its discontinuation. The arterial infusion was discontinued in 36 of the 54 patients; 13 due to death (mean survival period: 15.7 months), and 23 in whom occlusion of the reservoir, etc. made it impossible to use arterial infusion (mean period of use: 13.8 months), and the minimum duration of use was 41 days and maximum duration of use 992 days. The most common complication of the reservoir hepatic artery infusion was reservoir occlusion (14.8%). Another serious complication was reservoir deviation outside the blood vessel in two patients; deviation in to the gastric lumen in one case and intraperitoneal deviation in the other. Four hepatocellular carcinoma patients, in whom it became impossible to use the reservoir due to its occlusion, underwent re-hepatectomy. Three of them survived for more than two years following supplemental local therapy, including subarterial injection, TAE, PEIT, microwave tumor coagulation (MTC). Of four patients with colon cancer metastasizing to the liver, one could undergo re-hepatectomy, one received subarterial injection, and two have survived without relapse. Two of three patients with breast cancer underwent systemic chemotherapy and endocrine therapy successfully, while the third one underwent subarterial injection and TAE, and is still under observation. Hepatic artery infusion should sometimes be discontinued owing to complications caused by various factors. Even if it becomes impossible to use the reservoir, local therapeutic techniques, including re-hepatectomy, TAE, PEIT, MTC, etc., may be performed in some patients. These findings suggest that it is necessary to review the interdisciplinary treatment so as to be appropriate to the primary disease.

[CT guided percutaneous microwave tumor coagulation therapy for local recurrence of rectal cancer].

PURPOSE: To evaluate the usefulness of the CT guided percutaneous microwave tumor coagulation (PMTC) therapy for local recurrence of rectal cancer. MATERIALS AND METHODS: The CT guided PMTC was performed for two patients with local recurrence of rectal cancer. Maximum axial diameter of the tumor was 30 mm on CT images. With patients in the prone position on the CT table, a 14-gauge needle-electrode was used to penetrate the tumor under epidural and local anesthesia. PMTC was performed with an output of 60 watts for 60 seconds at a time. Effects of the PMTC were evaluated by CT images obtained three months after the therapy. RESULTS: In both cases, there was no evidence of tumor growth on the CT images. Clinical symptoms disappeared soon after the therapy, and no major complication was observed. CONCLUSION: The CT guided PMTC therapy was useful for local recurrence of rectal cancer.