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We examined the significance of hepatic resection and hepatic infusion chemotherapy for multiple liver metastases from colon cancer. Twelve patients underwent curative hepatic resection for multiple liver metastases (more than five), and 10 of them received arterial infusion chemotherapy. The number of metastases ranged 5 to 30 (mean 9.4). Recurrence rates in the remnant liver were 50%, and five-year survival rates were 31%.

A 48-year-old man underwent left hemicolectomy and right extended hepatectomy for colon cancer and its synchronous multiple liver metastasis. Sixteen months after, multiple metastases in the remnant liver were found, so he was given bolus hepatic infusion of 5-FU 1,000 mg/week, total amount, 25 g. The response was CR, but he developed a liver abscess in segment 4.

The purpose of this study was to clarify the indication of prophylactic hepatic arterial-infusion chemotherapy (PHAIC) after hepatic resection for liver metastases from colorectal cancer. Sixty-one patients underwent curative hepatectomy, and 27 of them were treated with PHAIC using implantable port. According to clinicopathological factors of primary colorectal cancer and liver metastases, the prognoses were analyzed. In conclusion, PHAIC was not useful for patients who had distant lymph node metastases (paraaortic lymph node) from primary cancer.

We often use hepatic arterial infusion chemotherapy to control recurrence of metastatic cancer of liver. Recently, we encountered a case of common bile duct fistula caused by hepatic arterial infusion chemotherapy. A 61-year-old man had undergone right hepatic lobectomy for liver metastasis of gastric cancer, 7 months after total gastrectomy. A hepatic arterial infusion catheter was placed. Since then he has received continuous and/or bolus hepatic artery infusion of 5-FU, ADR and CDDP+5-FU. There was a recurrence of gastric cancer in segment 2 of the liver. On his second admission, when we administered contrast medium to the infusion port, a common bile duct was found.

A 60-year-old man underwent resection of a sigmoid colon adenocarcinoma, left hepatic lobe, part of segment 6 and 8, due to its metastasis. He received hepatic artery infusions of 5-FU total amount, 15.5 g. There was no recurrence in the liver, but he developed sclerosing cholangitis, and a large biliary cyst formed in segment 8. After drainage of the cyst by percutaneous-trans-hepatic approach, bile leakage persisted, and liver dysfunction was progressive. Sclerosing cholangitis-induced biliary cyst formation is rare. Occlusion, or necrosis of the peripheral bile duct may be the cause.

Case 1: A 63-year-old woman underwent transverse colectomy and hepatectomy for colonic cancer and liver metastasis. A hepatic arterial infusion port (HAIP) was implanted. Continuous infusion of 5-FU (total amount, 7,500 mg) caused a hemorrhagic duodenal ulcer 15 months after. Follow-up endoscopy revealed the catheter tip was in the duodenal bulb. Case 2: A 62-year-old man underwent abdominoperineal resection for rectal cancer. Repeated hepatectomy for liver metastases was performed at 3 and 5 years after the first operation. HAIP was implanted at the last operation, but was not available at all due to the wound infection. The port was removed, but the catheter remained. Three years after, the catheter tip was found in the duodenal bulb by endoscopy.

We examined the significance of hepatic arterial infusion chemotherapy (HAIC) for prophylaxis of liver metastases of colorectal cancer after hepatic resection using an implantable port. Fifty-five patients operated at the hospital from August 1988 to December 1994 were divided into two groups consisting of 23 patients with HAIC group: (HAIC (+)), and 32 patients without HAIC group: (HAIC (-)) retrospectively. The cumulative survival rates and recurrent rates of cancer free in remnant liver of HAIC (+) were improved, compared with HAIC (-). This suggests that HAIC was effective in improving the prognosis and preventing recurrence in remnant liver.

Despite the recent development of apparently effective asthma drugs, the number of deaths from asthma has not declined. The authors tried to establish an optimal strategy for the prevention of acute asthmatic death by analyzing the circumstances of acute fatal or near-fatal asthma. Data were collected from 51 adult patients admitted to Bokutoh Tertiary Emergency Center due to acute asthma between November 1985 and May 1990 and 38 asthmatic patients admitted to Yokohama City Hospital in 1990. Pre-admission data were obtained through interviews with the patients, their families, or doctors who had seen them. A total of 89 patients were classified into three subgroups: group 1 consisted of patients dead-on-arrival (DOA); group 2, non-DOA patients with disturbed consciousness; and group 3, patients with less severe episodes. Little background information was significantly different among groups, but symptomatic episodes in group 1 patients tended to occur more rapidly. The speed of onset of the episodes was also dependent on the asthma control status. Prehospital care of groups 1 and 2 patients was very poor despite severity of the symptoms. All patients in groups 2 and 3 were successfully treated and discharged, but five of the 26 patients in group 2 died during follow-up periods. Prognosis of patients after discharge appeared to be dependent upon asthma control status before the acute episodes. It was concluded that acute fatal or near fatal asthma could occur in apparently low-risk patients as well as high-risk ones. It was also suggested that the optimal strategy for preventing asthma deaths might be variable.

One hundred and thirty-seven cases of stomach cancer given fluoropyrimidines (UFT: 66 cases, Tegafur: 58 cases, 5-FU: 13 cases) after gastrectomy as the adjuvant chemotherapy were examined as to appearance of macrocytic anemia. The mean corpuscular volume (MCV) gradually elevated in all cases but seven after administration. Macrocytic anemia, defined by the elevation over 20% compared with both pre-operative and pre-administrative values of MCV, was developed 30.3% in UFT group, 8.6% in tegafur group and 30.8% in 5-FU group. The incidence was statistically higher in UFT group (p less than 0.01) and 5-FU group (p less than 0.05) than in tegafur group. The cause was attributed to fluoropyrimidine administration because the serum folate and vitamin B12 levels remained normal and the value of MCV normalized after cessation of administration. Each total dose to induce macrocytic anemia was potentially about 70g in UFT. 100g in tegafur and 30 g in 5-FU. In conclusion, periodical hematological examination is necessary for the patients given fluoropyrimidine preparations.

Sixty-eight cases of cancer were treated by combined use of Thermotron RF-8 hyperthermia and radiotherapy, and 16 cases by combined use of hyperthermia and anti-cancer drug. The results of analysis of treatment are summarized as follows. Thermo-radiotherapy of shallow-seated tumor: Shallow-seated tumor at a depth of 7 cm or less from the skin surface was present in 43 cases. Most of these were metastatic tumors of lymph node, chest wall and abdominal wall. Pathological findings and primary effect; The effect of treatment was evaluable in 40 cases, the breakdown being as follows: CR 21 cases 53%, PR 13 cases 40%, and NR 3 cases 7%. The effectiveness ratios (CR/PRa) were as follows: adenocarcinoma 13 cases out of 18, 72%; squamous cell carcinoma 12 cases out of 15, 80%. The effectiveness ratios were thus almost the same. Tumor size and primary effect: Out of 19 cases of tumor 5.9 cm or smaller, 17 cases obtained CR. Out of 17 cases of tumor 6 cm or larger, there were 5 cases of CR. Cases of larger-sized tumor thus showed a poorer effect of treatment. Recurrence after radiotherapy: Nine cases of recurrence after radiotherapy were treated by combined use of hyperthermia and radiotherapy. Irradiation of 20 to 40 Gy was combined with 5 to 10 rounds of hyperthermia. The effectiveness ratio was 78%, i.e., 7 cases out of 9. Cases of recurrence of radio-resistant tumor after radiotherapy responded well to low-dose irradiation. Thermo-radiotherapy of deep-seated tumor: Twenty-two cases of deep-seated tumor were treated with the combined use of radiation therapy and hyperthermia. They comprised 10 cases of rectal cancer, 3 cases each of gastric cancer and uterine cancer, 2 cases each of lung cancer and sarcoma, and 2 cases involving other regions. The treatment results were: 3 cases each of CR, 15 cases of PR, and 4 cases of NR. The effectiveness ratio (CR + PRa) was 8 cases out of 22, i.e., 36%. Thermo-chemotherapy: Systemic administration of anti-cancer drug was combined with hyperthermia, and 16 cases were treated. They comprised 11 cases of gastric cancer, 3 cases of colo-rectal cancer, and one case of bile duct cancer. The administered drug was 5-FU in 8 cases, MMC in 7 cases, and CDDP in one case. The treatment results were; one case of CR, 4 cases of PR, 6 cases of MR, 3 cases of NC, and 2 cases of PD. More cases of lymph node tumor showed excellent results.

Fifteen patients with advanced gastric carcinoma were treated by intraaortic infusion therapy with sequential MTX and 5-FU. Intraaortic bolus injection with 50-100 mg/body MTX was followed 3 hours later with 500-750 mg/body 5-FU and 24 hours later with 30 mg/body leucovorin. Treatment was repeated weekly. Of these 15 patients who were evaluated, 4 had PR and 3 had MR. Response rate was 27%. Two patients had WBC nadir of less than 3,000 cells/mm and other two had a platelet count nadir of less than 10/mm. Gastrointestinal symptoms such as nausea and vomiting were mild. Three patients had diarrhea and 3 had mucositis. No other toxicity was seen. This regimen has been well tolerated for long periods.

Since 1987, 14 patients (10 colorectal, 3 gastric and 1 lung cancer) with unresectable liver metastases received intra-arterial infusion chemo-embolization therapy using implantable infusion port. All patients had more than one lesion in bilateral lobe (H2 and H3). Infusion catheters were placed in the proper hepatic artery through the gastroduodenal artery on laparotomy. Infusion ports were implanted in the subcutaneous tissue of the abdominal wall. Various kinds of chemotherapeutic agents such as MMC, ADR, THP-ADR, CDDP and 5-FU were injected with embolization material (DSM or Lipiodol), every 1 to 4 weeks at the outpatient clinic. Among 10 cases of H2 grade metastases, 1 CR and 3 PR (40% clinical response) were obtained. However, all 4 cases of H3 grade were judged PD. All patients except one with H2 grade metastases are still alive, but 3 out of 4 with H3 grade died within 7 to 11 months. Catheter occlusion was observed in 4 cases for 3 to 7 months. Infection around the port occurred in 1 patient. A patient with metastatic liver cancer was treated by intermittent bolus injection with MMC and DSM. Partial response was confirmed by CT and tumor markers. Histological response was demonstrated in the specimen obtained at partial hepatectomy. It is concluded that this treatment is variable to prolong the survival of patients with H2 grade metastatic liver cancer, together with maintenance of the quality of life.

DSM, an agent which occludes arterial blood flow temporarily, was experimentally proved to enhance the uptake of co-administered anti-cancer drugs in the target organ and, conversely, to reduce the systemic side effects. Intra-arterial chemotherapy combined with MMC and DSM was performed on eight cases of unresectable metastatic liver carcinoma. The primary site of all these cases (7 gastric, 1 rectal) was resected. A catheter was inserted into the proper hepatic artery via the gastroduodenal artery, and the other end was connected to an implantable drug delivery system which was placed at the abdominal wall. DSM (180 to 900 mg) mixed with MMC (4 to 20 mg) was injected through the system every one, two or three weeks. The response rate in evaluable 7 cases was 57% (4 partial response, 1 minor response, 2 no change) and prognoses in the frequently treated group (7 times or more) were better than in the group with less frequent treatment (3 times or less). Pain (25.0%), nausea and vomiting (20.6%), and high fever (11.8%) were side effects, but they could be treated by medication. Our results suggest that intra-arterial chemotherapy combined with MMC and DSM is one of the effective treatments for unresectable metastatic liver carcinoma.

After curative surgery for gastric cancers judged macroscopically to be at stage 2 or 3, patients were divided into 4 groups by randomization. As the basic treatment, patients were given one-shot Mitomycin and Tegafur as maintenance therapy for 8 months (group A). PSK (group B), OK-432 (group C) or both PSK and OK-432 (group D) were added to the treatment of group A for 8 months. Sera were obtained from these groups of patients at 4 weeks and 3, 6, 9 and 12 months after surgery. In all of these groups, values of IAP increased slightly at 4 weeks but decreased at 3 months and were maintained at such a level by 12 months. On the other hand, suppressive effects of such sera on the blastogenesis of murine spleen cells in response to PHA varied among these group. In groups A and C, the suppressive effect of sera increased after surgery and was detected continuously by 12 months. In groups B and D, in contrast, the suppressive effect disappeared from 3 to 12 months. The rise and fall of such a suppressive effect of sera may reflect the mode of action of PSK.

Five hundred and four cases of early gastric cancer and their status of lymph node metastases were analyzed. The patients were classified into 4 groups by age; Group A: Younger than 50 years, Group B: 50-59, Group C: 60-69 and Group D: Over 70 years. The tumors were divided into 2 histologic groups, differentiated type and undifferentiated type. The results are as follows. 1. The incidence of lymph node metastasis was 2.4% in mucosal cancer and 17.1% in submucosal cancer. 2. The incidence of lymph node metastasis in Group D was remarkably lower compared to that in other younger groups. 3. No lymph node metastasis was found in mucosal cancer of differentiated type. 4. Positive node was usually found in the regional nodes near the tumor and in the nodes adjacent to the left gastric artery. 5. Extended lymph node dissection is not necessary for the patient over 70 years and for mucosal cancer of differentiated type.

The adequate esophago-gastric resection and lymph node dissection can be performed without the necessity of a thoracotomy, by using the laparosternophrenotomy approach. For tumors restricted to lower esophagus of 4cm in localized tumors or 3cm in invaded tumors above the EG junction, the sternotomy approach is utilized. However, if the tumor extends to more than the above criteria, the thoracoabdominal approach must be utilized. For 14 years, 85 cases with tumor of gastric cardia were performed by sternotomy approach and 76 cases were performed by thoracotomy approach. The lymph node metastatic rate in the lower thoracic cavity was 26% in total. The lymph node metastatic rate of No. 110 was 22.6%, No. 111 was 17.4% and No. 112 was 12.5%. These results show the lymph node dissection in the lower thoracic cavity is very important in tumors of gastric cardia. The five year survival rate was 41% in patients who undergone curative operation by the sternotomy approach, and 45% in patients performed by the thoracotomy approach. According to our study of the lymph fluid stream in gastric cardia tumors using carbon, the lymph node dissection around the renal vein is important. This approach has less respiratory disturbance than the thoracotomy. This procedure is one of the best approaches for carcinoma of gastric cardia according to our criteria.

This report describes the clinical use of MMC localized intra-arterial infusion therapy in combination with Angiotensin II for advanced gastric carcinoma which is not surgically treatable, along with some basic considerations. Since blood vessels regenerated within a tumor no longer have automatic adjustment of blood flow, there is no vascular contraction mechanism operation even when Angiotensin II is administered. The blood flow within the tumor shows a relative increase so the amount of the carcinostatic substance reaching the tumor is considered to increase. Using MMC intra-arterial infusion together with Angiotensin II, the authors were able to increase the antitumorigenic effect of the carcinostatic agent in patients with advanced gastric carcinoma. In an experiment using VX2 tumor transplanted into domesticated rabbits, the group treated with angiotensin II showed a marked reduction in the tumor. At the clinical level, differentiated gastric carcinoma patients with liver metastases very often evidenced favorable effects when treated with Angiotensin II in combination with the MMC intra-arterial infusion method. A randomized clinical study of 30 patients using either Angiotensin II together or without intraarterial infusion revealed that in 4 advanced gastric carcinoma patients could PR be obtained by the combination therapy, the non-combination treated group showed no favorable effects. In Borrmann type IV gastric carcinoma, the present combination therapy displayed no effect, while a switch to MTX-5FU sequential therapy yielded very often good results. Since the ability of the agent to reach the tumor is markedly enhanced in the Angiotensin II-intraarterial infusion approach to chemotherapy, progress in the latter science is anticipated.