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The application of radiofrequency ablation (RFA) for liver metastasis of colorectal cancer has not yet acquired an established status in clinical cancer therapy research. Removing as much tumor tissue as possible is desirable, but some cases do not allow optimal surgical ablation due to general condition of the patient and tumor status. We introduced endoscopic RFA for liver cancer in 2003, and have applied the procedure to 6 cases with H1 or H2 liver metastases of colorectal cancer to which surgical ablation could not be applied due to the poor general health of patients. Mean tumor diameter was 22.9 mm, and mean number of tumors per patient was 1.2. Tumor location was: S4, n = 2; S5, n = 1; S4, n = 1; S7, n = 2; and S8, n = 1. Mean frequency of session was 3.0. No complications occurred in any cases, and no reoperations were required. Although no recurrence of tumors in the vicinity of ablation was observed, 2 cases of each lung metastasis and intrahepatic recurrence were identified. Intrahepatic recurrence underwent hepatic arterial infusion (HAI) chemotherapy for simultaneous metastatic hepatic tumors (H2) prior to RFA, and relapses occurred in the metastatic focus where the efficacy of HAI was observed. At this point, 2 deaths were reported, 1 each from cancer and other diseases, and mean duration of survival after the procedure was 451.2 days. These results indicate that endoscopic RFA with good local control should be an available treatment for cases involving colorectal cancer with metastasis to the liver in which surgical ablation is difficult to apply.

The authors have been devising novel dosage forms with a sustained release of aqueous cis-platinum (CDDP), following the concept of a drug delivery system. First, we prepared biodegradable vehicles with clinically available fibrin and gelatin materials that were used with the ultraviolet (UV)-cross linking technique. Then, each carrier was loaded with CDDP to form new drugs. We basically studied degradability of the carrier, a release profile of the CDDP, and antineoplastic activities with the system. The new drugs gradually disintegrated to dissolve completely within 10-15 days, and 80-90% of the loaded CDDP was delivered in the same period. The released CDDP showed antineoplastic activities, both in vitro and in vivo, while the CDDP directly reacted with human plasma revealed little evidence of anticancer function. The scanning electron microscopic studies suggested that the release profile of the CDDP was closely related with the degradability of the carrier. We presume that UV-modification techniques play important roles in preparation of the new drug carriers. Our newly devised CDDP releasing system is promising as novel cancer chemotherapy.

The authors devised injectable drug carriers with sustained release of cis-platinum (CDDP). We formed the carriers using biodegradable medical materials applied clinically: namely, fibrin hydrogel clot (FC) made from tissue adhesive, and gelatin powder (Gp) for hemostasis. Two different types of carriers were prepared: plain fibrin hydrogel clots (FCs) and Gp-containing FCs. Each carrier was dehydrated and crushed into granules, then irradiated with ultraviolet (UV) rays. These modified materials were saturated with a CDDP solution to prepare CDDP-loaded injectable sol, which were incubated at 37 degrees C in our experimental fibrinolytic systems. We examined the in vitro release profile of the CDDP and antineoplastic activities with the drug delivered from the sol. The UV-treated materials gradually released the CDDP over more than 20-30 days. Non-UV-treated carriers released the drug within 3-5 days. More than 90% of the released CDDP was revealed to be a protein-binding type, which favorably inhibited the growth of cultured cancer cells. Conversely, the CDDP incubated with human plasma showed no inhibiting functions against the growth of cancer cells. Our newly devised material appears to have great potential for loco-regional cancer chemotherapy based on the principle of local drug delivery.

The authors devised a novel sustained release system for aqueous cis-platinum (CDDP) to study in vitro the degradability of the carrier materials and the release profile of the CDDP. We first prepared fibrin hydrogels with clinically used biomedical materials, and irradiated the gels with ultraviolet (UV)-rays to form gradually degradable drug carriers. We then loaded aqueous CDDP into the carriers under negative pressure. These prepared materials were incubated in fibrinolytic test medium at 37 degrees C for the in vitro studies. The UV-irradiated materials slowly degraded and dissolved within 10-15 days, while non-UV-treated carriers disintegrated in 4-5 days. Each carrier showed a sustained release of CDDP. Most of the CDDP delivered was revealed to be the protein-binding (larger than 10 kDa) form. Free-CDDP was almost nil. The antineoplastic efficacies of this new drug delivery system developed using an original technique are now being investigated.

The authors provide three new and different types of fibrin gels (FCs) and a chitosan sheet (BC) using an ultraviolet (UV)-crosslinking method. They are 1) FC-UV, 2) gelatin entrapped FC; FC (Gp)-UV, 3) chitosan entrapped FC; FC (Cs)-UV and 4) BC-UV. Each material was loaded with aqueous cis-platinum (CDDP), and both the degradation of the drug carriers and the release profile of the CDDP were examined in vitro. The FCs, 1)-3), gradually degraded and dissolved within 10-12 days. The BC, 4), maintained its original weight for more than 30 days. Each FC showed a sustained release of CDDP for 10 days, while BC provided an initial bursting of the loaded drug. New materials 2) and 3) show great potential as drug carriers for DDS and further in vivo studies are now proceeding.

We report a case of extramedullary plasmacytoma involving the right adrenal gland. A 52-year-old male was introduced under diagnosis of right adrenal tumor which was found incidentally by computerized tomography in a health check up. Laboratory data showed the presence of M protein and elevation of monoclonal lambda type IgG. It was a hormonally non-active tumor involving the adrenal area. Extramedullary plasmacytoma was confirmed by histological analysis of the resected specimen after laparoscopic right adrenalectomy. Extramedullary plasmacytoma is an uncommon neoplasm and occurs most frequently in the upper respiratory tract and is fairly rare in the adrenal area.

The authors devised a novel fibrin clot (FC) using an ultra-violet (UV)-crosslinking method. CDDP was impregnated into FCs, and the release profiles of the CDDP were examined in vitro. The microstructures of the FCs were studied with scanning electron microscopy (SEM). The release of CDDP from the FC-UV-CDDP was maintained for 10 days, while that from the FC-CDDP showed initial bursting with a following plateau of CDDP concentrations. SEM of UV-crosslinked FCs revealed highly organized, close and homogeneous micropore structures. Native FCs and non-crosslinked FCs showed rough fibrin networks with entangling fibrin fibers. These microstructural differences may play important roles in the release profiles of CDDP. Our newly devised UV-crosslinked material is promising as a drug carrier for sustained release.

We report a case of chromophobe cell renal carcinoma. A 27-year-old male suffered from right flank pain and gross hematuria. Drip infusion pyelography and ultrasonographic examination revealed a right renal mass and it was diagnosed as renal oncocytoma by needle biopsy of the right kidney. He was referred to our hospital for the operation and right radical nephrectomy was performed. The cut surface of the tumor was beige in color. The cytoplasm of the tumor cells stained positively for colloidal iron and showed a negative reaction for Vimentin. From these results, this tumor was given a diagnosis of chromophobe cell renal carcinoma.

Dysphagia suddenly progressed in a 69-year-old woman who had a 50-year history of intermittent difficulty in swallowing solid food. A thick circumferential who in the upper esophagus was extensive enough to be the cause of dysphagia. There was another thin semicircular web in the pharynx. Bouginage resulted in only 6-months relief of symptoms, and the same esophageal who was reformed with the same severe symptoms 3 years later. Surgical resection of the esophageal web was performed. Extensive pharyngeal carcinoma was found 4 years after surgery. She died of heart failure during combination therapy of irradiation and chemotherapy.

In order to evaluate the biological response after intraperitoneal administration of OK-432 and CDDP, we studied the changes of cytokine levels in ascitic fluid. A total of 53 gastric cancer patients were included in this study. OK-432 20KE was administered in 7 patients and CDDP was administered in 4 patients intraperitoneally during operation. The IL-6, IL-8, TNF-alpha and sTNF RI levels in ascitic fluid were measured from 0 to 5 postoperative day. These results were compared with those obtained from the control groups (42 patients). The ascitic level of IL-6 increased immediately after operation, then gradually decreased. The elevations of IL-6 from 0 to 5 postoperative day were remarkably higher in the OK-432 treated group, and those on 0 and 1 postoperative days were remarkably lower in CDDP treated group than in the control group. Similarly, the ascitic level of IL-8 elevated soon after operation and then decreased gradually. In the OK-432 treated group, the ascitic level of IL-8 was significantly higher than in the control group from 0 to 2 postoperative day. Ascitic TNF-alpha was detectable only in the ascites soon after operation in the OK-432 treated group. The ascitic level of sTNF RI peaked on 2 postoperative day in the control and the OK-432 treated group and 1 postoperative day in the CDDP treated group. There were no significant differences between these groups.

In order to evaluate the biological response after intraperitoneal administration of OK-432, we studied the changes of cytokine levels in ascitic fluid. In 6 advanced gastric cancer patients with peritoneal dissemination or extensive lymph node metastases, OK-432 20 KE was administered intraperitoneally during operation and the IL-6, IL-8 and IFN-gamma levels in ascitic fluid were measured from 0 to 5 postoperative days. These results were compared with those obtained from non-OK-432 administered control groups (17 cases). The ascitic level of IL-8 increased immediately after operation and gradually decreased. In the OK-432 treated group, the elevation of IL-8 on 0 and 1 postoperative days was remarkable, and there were statistically significant differences with the control group. Similarly, the ascitic level of IL-6 elevated soon after operation and then decreased gradually. In the OK-432 treated group, the ascitic level of IL-6 was significantly higher than in the control group after 3 postoperative days. There were no differences in changes of ascitic IFN-gamma levels between the groups. From these results, IL-6 and IL-8 appeared to be induced in ascitic fluid by intraperitoneal administration of OK-432.

In this study we examined the role of oxygen-derived free radicals in the pathogenesis of acute gastric mucosal lesion induced by obstructive jaundice in rats. Rats were divided into 4 groups as follows: control (sham operation), jaundiced (ligation and dissection of bile duct), vagotomized (truncal vagotomy), and vagotomized with jaundice group. The water immersion restraint procedure was performed. The water immersion restraint procedure was performed. The results obtained are as follows: jaundiced group showed significant increase of ulcer index (UI) and significant decrease of gastric mucosal blood flow (GMBF) and gastric mucosal potential difference (PD). However, intragastric pH (pH) was unchanged compared to the control group. Oxygen radical generating system (gastric mucosal XOD activity and thiobarbiturate acid) and oxygen radical scavenging system (gastric mucosal SOD activity and GSH-px activity) were higher than those of control group. Vagotomized group showed significant increase of pH compared to the control group. Oxygen generating system and scavenging system were unchanged compared to the control group. Vagotomized with jaundice group showed depression of UI and improvement of oxygen radical generating system and scavenging system. However GMBF, PD nad pH were unchanged compared to the jaundiced group. These results suggest that oxygen radical play some role in the development of acute gastric mucosal lesion induced by obstructive jaundice.

Two cases of double primary malignant neoplasm of renal cell carcinoma and gastric cancer are presented. Case 1 was a 59-year-old woman with right renal cell carcinoma (granular cell subtype) and gastric cancer (poorly differentiated adenocarcinoma). Case 2 was a 72-year-old man with left renal cell carcinoma (clear cell carcinoma) and gastric cancer (tubular adenocarcinoma). In both cases, the occult blood reactions of stool was strong and clear gastrointestinal symptoms developed. In these 2 cases of synchronous double cancer, gastrectomy following nephrectomy was performed in the same operation.

Clinically, most gastric ulcers are located in the region of the incisura angularis, but they are least found along the greater curvature. To elucidate this difference, following experiments were carried out. A total of 22 mongrel dogs were used. A set of bipolar electrodes and/or a water-proof strain gage were chronically implanted at both the incisura and the corresponding site of the greater curvature. Electrical and contractile activities of these two sites were compared at the fasted state and under the stimulations by food, neostigmine and tetragastrin. Results are summarized as follows. 1. Electromyographically, the propagation velocity was always greater along the greater curvature than the lesser curvature. The discharge interval of BER and incidence of antiperistalsis were identical for both the lesser and greater curvature. 2. Through the course before and after the stimulation, there was no difference in the frequency of contraction waves, while the amplitude and motility index of the contraction were definitely greater at the incisura than the corresponding greater curvature. In conclusion, the present study revealed that the contractile force of the incisura was always greater than that of the corresponding greater curvature. It is possible that the peristaltic contraction could cause stronger repetitive ischemic condition of the incisura than the corresponding greater curvature. It is estimated that the gastric motility is one of the important factors for the predilection or delayed healing of gastric ulcers seen in the region of the incisura angularis.