Search

A 57-year-old woman was diagnosed as in the chronic myeloid leukemia-chronic phase. Imatinib mesylate(IM)was initiated at 400 mg daily. She achieved complete cytogenetic response at 3 months, and major molecular response at 10 months. IM was reduced to 300 mg daily at 12 months because of grade 1 nausea. IM was reduced to 300 mg for 5 days per week by her demand at 22 months. Major molecular response was maintained with 300 mg of IM for 3 days per week at 77 months. The intermittent IM therapy might be useful for CML patients who cannot tolerate the standard dose of IM.

We report a case of a 41-year-old woman who underwent mastectomy and axillary lymph node dissection for right breast cancer(T3N3cM0) in 2004. She was treated with chemotherapy for multiple bone metastases and recurrence in the iliopsoas from January 2008. Right chest wall recurrence was observed in May 2010 and it progressed to ulcer. She was admitted to our hospital complaining of dyspnea on December 2, 2011. We diagnosed open pneumothorax and inserted a chest tube, and then packed the ulcer. No recurrence was observed in the liver and lungs. After stabilization of her general condition, we performed chest wall resection and reconstruction with a latissimus dorsi flap. She was discharged 2 weeks after surgery without severe complications. Although there were distant metastases, this surgical procedure may be effective for patients with open pneumothorax from recurrent breast cancer in order to maintain quality of life.

A 71-year-old man receiving maintenance dialysis because of diabetic nephropathy presented with hematemesis at another hospital in January 2008. A gastrointestinal endoscopy demonstrated a II a-like lesion in the angle of the stomach, and he was admitted to our hospital. A diagnosis of gastric adenocarcinoma (cT2N2M0, Stage IIIA) was made. An operation could not be performed because of the high risk, so combination chemotherapy with 5-FU and l-LV was initiated. After 3 courses of treatment, the size of the primary tumor was markedly reduced. After 6 courses, the primary lesion had changed to a scar, and an endoscopic biopsy revealed no cancer cells. His performance status did not deteriorate, and no serious adverse events occurred during the course of treatment. Chemotherapy was continued because the overall response was SD. 5-FU/l-LV therapy should be considered as a safe and useful treatment for a hemodialysis patient with advanced gastric cancer.

As an acute hospital specialized in elderly patient, we utilized an integrated function screening sheet in order for doctors and nurses to start early in the discharge support at the inpatient ward. However, due to inadequate assessment, it consumed a lot of time until the request of discharge arrangement was made. Thus, as one of activities of discharge support team within the hospital, we started the inpatient ward round by team members aiming to begin a discharge support from inpatient ward. As a result of the activity, the round seems to be effective in deciding the direction of discharge, creating co-operative framework, etc. However, it revealed several problems as well. We need to study further identifying a better way of the inpatient ward round.

We evaluated the effect of intra-arterial infusion chemotherapy associated with radiotherapy for two cases of local recurrence of rectal cancer. We performed an intra-arterial infusion chemotherapy (5-FU was injected continuously: 250 mg/day/body x 28 days, CDDP was injected weekly: 5 mg/day x 5 days) associated with radiotherapy (2-3 Gy/day x 20-30 days) for local recurrence of rectal cancer with the aim of pain-relief. Both patients markedly tended to feel less pain after the radiotherapy. Radiotherapy has been useful for pain-relief of the localized bone metastasis. The present intra-arterial infusion chemotherapy associated with radiotherapy was a possible local therapy for local recurrence of rectal cancer in the pelvis. Although the survival benefit depends on the presence of other site of recurrence, this procedure is useful for the improvement of QOL by relieving the pain of the patients.

The use of neoadjuvant chemotherapy for pancreatic cancer has been advocated for its potential ability to optimize patient selection for surgical resection and to downstage locally advanced tumors, especially for patients with Stage IV b (Japan criteria). We report our experience with a six-drug chemotherapeutic regimen that resulted in sufficient downstaging of the tumor in some patients to justify surgical resection. From Jan. 2001 through December 2003, 6 patients received 5-FU as a continuous infusion (200 mg/m2/day), calcium leucovorin weekly by intravenous bolus injection (30 mg/m2), mitomycin-C every 6 weeks (10 mg/m2 intravenously), and dipyridamole daily orally (75 mg), according to the UCLA regimen and gemcitabine weekly (600 mg/m2) and heparin as a continuous infusion (0-3,000 U/day) for locally advanced unresected pancreatic cancer. All of these patients were evaluable for response and survival. There were 5 partial responses (83% response rate) and 1 no response. Four of 5 responding patients had sufficient tumor regression to meet clinical criteria for resectability, three of whom underwent a curative resection. All patients who underwent downstage operation were still alive for the follow-up period (4-23 months).

The safety of chemotherapy combining TS-1 and pirarubicin (THP) for treatment of recurrent or locally advanced gastric cancer was evaluated. THP was administered by intravenous drip infusion at a dose of 14 mg/m2 every other week. TS-1 was administered orally at a dose of 40 mg/m2 twice a day for 2 weeks followed by 2 weeks of rest (level 1), for 3 weeks followed by 2 weeks of rest (level 2), and for 4 weeks followed by 2 weeks of rest (level 3). Three patients were treated with the level 1 schedule. One patient with peritoneal dissemination received 22 courses of the treatment, and benefited from a long-term NC. However the remaining 2 cases were diagnosed as PD after 4 courses and were withdrawn from further treatment. Two patients in this group suffered from grade 2 adverse events according to the NCI-CTC. Only 1 patient who had liver metastasis was treated at level 2. Fourteen courses were administered, and a PR was achieved while grade 2 adverse events were observed. One of 3 patients who were treated with level 3 had grade 3 adverse events. Consequently, 3 more cases were added to this dose level, and no additional grade 3 adverse events were observed, while grade 2 adverse events were seen in 4 cases. Urinary urgency had completely disappeared in 1 patient with peritoneal recurrence. Myelosuppression, which was the main observed adverse event, was well controlled and of brief duration. The response, including alleviation of clinical symptoms, was confirmed in 3 of 5 chemo-naive patients.

A 64-year-old man underwent gastrectomy and partial liver resection for gastric cancer and liver metastasis, and was administered intra-arterial infusion chemotherapy for metastases of the remnant liver. This treatment was very effective against the liver metastases, but 13 months after the operation obstructive jaundice occurred. An examination revealed obstruction of the bile duct and choledocholithiasis. The choledocholithiasis was treated using a percutaneous transhepatic cholangio-scope, and choledocho-duodenostomy was performed for the obstruction of the bile duct. Findings from the operation suggested that the obstruction was caused by the intra-arterial infusion chemotherapy. At present, 2 years after the first operation, the patient is alive without the regrowth of the liver metastasis.

We evaluated the effect of intra-arterial infusion chemotherapy for liver metastasis from colorectal cancer. Of 405 patients undergoing colectomy in our department from July 1993 to February 2002, 38 had liver metastasis. We performed catheterization intra-operatively or postoperatively, and intra-arterial infusion chemotherapy was given for liver metastasis from colorectal cancer. Thirty-eight patients were treated with four different arterial infusion courses that mainly consisted of 5-FU. The 5-year survival rate was 8%. Maximal survival period was 68 months, and mean survival was 22 months. The effective rate was 20% Intra-arterial infusion chemotherapy was a useful treatment for liver metastasis from colorectal cancer. Resection of the liver metastasis was the first choice for operative liver metastases from colorectal cancer, and we performed intra-arterial infusion chemotherapy for patients postoperatively or patients with non-operative liver metastasis.

We evaluated the effects of intra-arterial infusion chemotherapy for liver metastases and lymph node metastases of gastric cancer. Of 410 patients undergoing gastrectomy in our department from July 1993 to December 2000, 29 (7.1%) had liver metastases. Intra-arterial infusion chemotherapy was carried out for 15 patients with liver metastases and 10 patients with lymph node metastases. There were 11 patients with liver metastases evaluated as follows: PR 5, NC 2, PD 4. Two patients with lymph node metastases were PR. In a comparison between the intra-arterial and non-intra-arterial chemotherapy group, it was observed among the patients with synchronous liver metastases that the survival period of the intra-arterial group was significantly longer than that of the non-intra-arterial group (p = 0.0164 logrank test). On the supposition that the survival period is counted from the day of computed tomography metachronous liver metastases was detected, in all liver metastases patients, the survival period of the intra-arterial group was significantly longer (p = 0.0212 logrank test). These results showed that the intra-arterial infusion chemotherapy is a useful treatment for gastric cancer patients with liver metastases.

Complications of hepatic arterial infusion chemotherapy were analyzed in 30 cases with hepatic metastasis from colorectal cancer from July 1993 to February 2000 in our department. Thirty patients were treated with three kinds of arterial infusion course that mainly consisted of 5-FU. Complications resulting in interruption of therapy occurred in 10 patients (33%), and there was no difference in the incidence rate of complications among the three chemotherapy regimens. The complications with our therapy were hepatic arterial occlusion in two patients, catheter tip dislocation in four patients, fistulus between the hepatic artery and common bile duct in two patients, and fistulus between the hepatic artery and duodenal bulb in two patients. Four patients who had severe complications with fistulus all underwent hepatectomy, especially right hepatic lobectomy in two cases. Sixty percent of our patients had complications after hepatectomy, so regular GIF and DSA are necessary to prevent severe complications after hepatectomy.

The authors have performed fluorescence in situ hybridization (FISH) in tissue sections of archival paraffin-embedded blocks of seven cases in adenoma and ten cases in carcinoma in order to clarify which chromosomal aberration occurred in association with multi-step carcinogenesis in colorectal carcinomas, using alpha-satellite DNA probes to chromosome 11 and 17, D11Z1 and D17Z1, respectively. Monosomy of chromosome 11 was most frequented (5/7, 71.4%) in adenoma, and trisomy of chromosome 17 was predominant (9/10, 90.0%) in carcinoma. The numerical chromosomal aberrations can be already detected at the stage of adenoma, and monosomy of chromosome 11 was mainly observed in adenoma. Furthermore, malignant transformation arising from adenoma accounted for most of the trisomic change in chromosome 17. Consequently, applying the FISH technique to tissue sections from archival paraffin embedded specimen, it would be possible to distinguish between the cancerous and non-cancerous regions in view of chromosomal numerical aberrations. The authors emphasized that intratumoral heterogeneity could be elucidated at the chromosomal level.

We performed CHPP with concomitant use of CDDP and etoposide for prevention or treatment of peritoneal dissemination in gastric (10 cases) and colon (1 case) cancers with serosal invasion or peritoneal dissemination. The patients received intra-abdominal perfusion by saline heated to 41.5-42 degrees C dissolving CDDP and etoposide for 40-50 minutes. The blood concentrations of total CDDP and etoposide rapidly increased and reached maximum at the end of perfusion. Post-operative complications were more frequent in the group without STS than with STS. The prognosis of patients with peritoneal dissemination (P3) was poor, but ascites was observed to disappear in four of five cases. All patients with S (+) or P1 have been alive and free from disease for 1 to 12 months after CHPP. These results suggested that CHPP was effective for prevention and treatment of peritoneal dissemination.

Based on our experimental study, which indicated that simultaneous combined administration of MMC and CDDP prolonged life more significantly than individual administration, clinical application was performed on three cases of carcinomatous peritonitis from Borrmann type 4 cancer of the stomach. The dosage was 14 mg/m2 (7 mg/m2 at second and following administrations) of MMC and 35 mg/m2 of CDDP and they were repeatedly administered in the abdominal cavity via the drug delivery system. As the result, no severe toxicities were found except for two cases of leukopenia (Grade 2). Effectiveness was indicated in all cases with the negative change of cytology, whereas no improvements in prognosis were obtained. We concluded that some new devices would be necessary to increase the drug delivery to the carcinomatous wall.

Numerical aberrations of chromosomes can be detected by fluorescence in situ hybridization (FISH), using chromosome-specific probes. It is possible to observe this in solid tumors from which it is very difficult to obtain metaphase nuclei. The present study employed surgical specimens from 15 cases of colorectal carcinoma, all of which showed DNA diploidy. In the same samples, we analyzed chromosomal numerical aberration by FISH according to the method of Pinkel et al. Biotinylated DNA probes specific to chromosome #7, #11 and #17, were used. The hybridization spots were observed by fluorescent microscopy. As a result, the numerical aberrations of chromosomes detected by FISH were found in DNA diploid cases by FCM. They were trisomy and monosomy. These results indicate that FISH is useful to detect the chromosomal aberrations of DNA diploid cases.

Four patients with combined hepatocellular and cholangiocarcinoma were studied. One case received hepatic arterial infusion therapy (HAIT), 2 hepatectomy and the case with extrahepatic cholangiocarcinoma underwent enucleation. According to Allen's classification, two were combined type and the others mixed type. Tumor ploidy patterns on flow cytometric DNA analysis were aneuploid in 2 cases with curative resection, of which one is still alive 6 years and 3 months after surgery. It suggested that the patient's survival was affected by the pathological factors more than the ploidy patterns of the tumor. A case treated by HAIT improved considerably in terms of symptoms and evidenced reduction in the size of the deposits. Selection of anticancer agents sensitive to both hepatocellular and cholangiocarcinoma is required.

In order to elucidate the effect of tumor vascularity on a various regimens concentration in tumor tissue, correlation among tegafur, 5-fluorouracil (5-FU), uracil concentrations in tissue and the microangiography were examined in 27 patients with colorectal cancer after preoperative administration of UFT (400 mg/day for 7 days). The concentrations of tegafur, 5-FU and uracil in tumor were higher than those in normal tissue (p < 0.01). There was no definite correlation between tissue concentration in each regimen and the extra or intramural vascular changes. A significant high concentration of 5-FU was found in the protuberant cancer and the ulcerative cancer with horizontal growth than that in the ulcerative cancer with vertical growth (p < 0.05). The present study indicates that the vascular changes within a tumor and the vascular pattern of tumor may be a contributing factor affecting the tissue concentration in the regimens.

A 56-year-old man who had undergone curative gastrectomy for Borrmann 2 type gastric cancer 43 months before, had a cancer recurrence (liver metastasis and peritoneal dissemination). Intra-arterial hypertensive chemotherapy with MMC for liver metastasis and intra-arterial sequential MTX/5-FU chemotherapy for peritoneal dissemination were given. He died of lung cancer with brain metastasis 27 months after this therapy. But in autopsy the remarkable effects of chemotherapy were recognized in intra-abdominal recurrent sites, and in fact, microscopically no cancer cells were found in metastatic lesions. We thus concluded that intra-arterial noradrenaline-induced hypertensive MMC therapy for liver metastasis and intra-arterial sequential MTX/5-FU therapy for peritoneal dissemination were useful treatment.

To prevent dissemination to the peritoneum following surgery for gastric cancer, examinations were performed with mouse ascites cancer models and the objective of enhancing the combined effect of MMC, CDDP and 5-FU. Pharmaceutical dosage was set at approximately 30% of the increased life span (ILS) for Meth-A. The dosage was 0.2 mg/kg for MMC, 1 mg/kg for CDDP and 37.5 mg/kg for 5-FU. Results indicated that simultaneous combination of 0.2 mg/kg of MMC and 1 mg/kg of CDDP extended life significantly more than individual administration, and clinical application of this combination was considered to be possible. In contrast, simultaneous combination of 1 mg/kg of CDDP and 37.5 mg/kg of 5-FU had no clear life-extending effect compared to individual administration of each. Some biochemical modulation of the administration method was thus considered necessary.

Eighty-one cases of advanced gastric cancer, who had been treated by intra-arterial infusion chemotherapy, were examined for complications related to catheter indwelling. Subjects consisted of 46 cases of aortic cannulation (via femoral artery, 29; via subclavian artery, 17) and 35 cases of hepatic cannulation (via laparotomy, 29; via subclavian a, 6). As the result, complications were more frequent in the cases via femoral (24.1%) and via laparotomy (41.4%), whereas there was only one case in subclavian route. Six cases (67%) of dislocations developed within one month after cannulation and occlusions (8 cases) were often found in cases of one shot or non-injection. In conclusion, cannulation via subclavian artery is an excellent method.

Three cases of bile duct necrosis owing to hepatic arterial infusion chemotherapy (HAI) were reported. Regarding HAI, transcatheter hepatic arterial embolization (TAE) was applied in two cases (hepatocellular carcinoma: 1; metastasis: 1) and 5-fluorouracil (continuous) combined with leucovorin (one shot) therapy (LV + 5-FU) was given to one metastatic case. In the data of blood biochemistry, serum alkaline phosphatase, gamma-glutamyl transpeptidase, and leucine aminopeptidase values characteristically elevated without the elevation of total bilirubin value. Hepatic tumors degenerated with necrosis in all cases and no viable cells were histologically recognized. Although the destruction of bile ducts was locally detected adjacent to these tumors in TAE cases and was more widespread in the LV + 5-FU case, these lesions were very similar in each case. Therefore, we concluded that both ischemia and drug toxicity induced bile duct necrosis and the necrosis around the bile duct was the secondary change due to the leaked bile juice.

Four patients with hepatic metastasis of gastric cancer (one synchronous, three metachronous), received intraarterial noradrenaline-induced hypertensive chemotherapy. The outlet of the indwelling catheter was placed in the proper hepatic artery in two patients, in the thoracic aorta in one patient and in both places in one patient. When the systolic blood pressure rose 50 percent above the level in the untreated state, mitomycin C via the catheter was administered for 10 minutes. Partial remission was found in 2 patients, NC in one patient and PD in another. One patient showing PR died of a relapse of hepatic metastasis 8 months after treatment. Another patient with PD died of multiple bone metastases after 12 months. The two other patients are alive 19 months after treatment. Intraarterial noradrenaline-induced hypertensive chemotherapy is one of the useful treatments of choice for hepatic metastasis of gastric cancer.

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.

We used treatment with intra-arterial injection in cases of liver and peritoneal metastasis in progressive or recurrent gastric cancer patients. The investigation of the relationship between efficiency of therapy and survival period was evaluated. The effective rate of sequential treatment of peritoneal metastasis with MTX.5-FU in 34 cases was 35.3%, while that of liver metastasis with MMC combined with DSM in 12 cases was 50%. Although the effective rate among 16 cases treated with MMC.5-FU combined with Angiotensin II was 50%, no effect was recognized in the groups treated with AF and MF. In cases of peritoneal metastasis with MTX.5-FU, the prognosis PR cases was significantly better than that of NC.PD. For treatment of liver metastasis with MMC combined with DSM and MMC.5-FU combined with Angiotensin II, the PR prognosis was unsatisfactory and the survival period did not significantly improve compared with that of NC.PD. In future cases of liver metastasis, these results indicate the extreme difficulty in maintaining therapy and controlling the lesion after PR. We speculated that sequential treatment of peritoneal metastasis with MTX.5-FU was useful because it significantly extended the survival period in PR cases.

A case of metachronous lung metastasis treated by intravenous administration of VDS after esophageal cancer surgery is reported. A 63-year-old man who had undergone intrathoracic esophagectomy for cancer of the esophagus was shown to have a coin lesion in the middle lobe of the right lung on X-ray examination about one year after surgery. The schedule for intravenous administration of VDS was 5 mg/body every week. The metastatic lesion disappeared after a series VDS administrations totalling 35 mg. Major side effects such as leukopenia and fever were occasionally observed during the course of drug administration. The patient required three occasions of hospitalization for these adverse effects. It is thus emphasized that an effect of VDS may be expected for hematogenous dissemination of esophageal cancer.

From tumors obtained from 87 patients with colorectal cancer during operation, portal blood levels of carcinoembryonic antigen (CEA) in drainage vein were measured and evaluated, according to the disease stage and histology, in comparison with cancerous tissue CEA in the extracts of surgical specimens and immunohistochemical analyses graded according to localization patterns and immunoreactivity; thereby trying to clarify a mechanism for the elevation of peripheral CEA levels. Mean value of portal CEA was higher than that of peripheral CEA at each stage of diseases, with a marked elevation by operative procedures. Although no significant correlation was observed between CEA contents of cancerous tissue (ng/g wet weight) and peripheral CEA levels, a close correlation was observed between portal CEA levels and cancerous CEA contents. A high CEA value was noted in moderately differentiated adenocarcinoma, according to cell differentiation (p less than 0.05). High portal CEA level was recognized in those with stain of cytoplasm and stroma, besides cancerous tissue CEA content, by means of immunopathochemical localization pattern, but a more significantly elevated CEA level was observed in those with the cancer pathologically infiltrating over muscle layers. The present study suggests that the route of CEA transfer from tumor to portal blood can be an important contributing factor to the control of peripheral CEA level.

Fifty-five gastric cancer patients with liver metastasis received arterial infusion chemotherapy. In 14 patients who had lesions in the liver intra-hepatic artery infusion chemotherapy was performed, while in 41 patients who had lesions in the liver and other sites intra-aortic infusion chemotherapy was performed. Methods for inserting the catheter into the aorta or hepatic artery and treatment schedules were reported previously. Between 1975 to 1981, 33 gastric cancer patients with liver metastasis were treated with 5-FU only (4 cases). MMC.5-FU (18 cases) and ADM.5-FU (11 cases). No response was seen, but minor response was seen in two cases. Between 1982 to 1988, 22 gastric cancer patients with liver metastasis were treated using arterial MMC.5-FU therapy combined with angiotensin II (13 cases), arterial MMC therapy combined with degradable starch microsphere (6 cases) and sequential MTX.5-FU (3 cases). The response rate of MMC.5-FU therapy combined with angiotensin II was 5/13 (38%) including one complete response. The responders of MMC-combined DSM therapy were seen in 3 (50%) out of 6 patients. However, no response was seen in sequential MTX.5-FU therapy. In the present study, a 61-year-old patient treated with MMC.5-FU combined with angiotensin II therapy, survived for 49 months after treatment. In order to improve the prognosis of gastric cancer patients with liver metastasis, it is important to increase the delivery of anticancer drugs to the target tissues by using certain drugs like angiotensin II and DSM. In the future, further studies should be done to prolong the duration of remission by arterial chemotherapy.

For the purpose of reasonable evaluation of the cell kinetics of RNA synthesis inhibitors, the flow cytometric technique using acridine orange staining for simultaneous measurement of cellular DNA and RNA content was applied in order to analyze the effects of actinomycin D (ACT-D) on cultured cancer cells (PC1). ACT-D 0.05 microgram/ml, a dose that produced little inhibitory effect on the growth curve, led to G1 accumulation after the appearance of G2M, and a decrease in RNA content was concomitantly observed at 48-72h, although the RNA level had nearly recovered to normal at 120 h. On the other hand, ACT-D 0.1 microgram/ml, a dose that produced a significant inhibitory effect, resulted in the initiation of G1-phase accumulation, a maximal peak of G2M accumulation and a decrease in RNA content at 48 h, after which there was a tendency toward G1-phase accumulation and a marked decrease in RNA content which continued for 120 h. Such a marked decrease in RNA content coincided with high values of the G1a X G1b ratio in the G1 phase. These results suggest that ACT-D has an inhibitory action on the cell cycle between G1a and G1b, accompanying a marked decrease in RNA content.

Sialyl Lewis(x)-i (SLX) as a new tumor-associated antigen was assayed in sera of 133 gastric cancer and 62 colorectal cancer patients with preoperative state in order to elucidate the clinico-pathological features. The percent positives in sera of patients with gastric and colorectal cancer were 12.7% (17/133) and 16.1% (10/62), respectively, and there were few positive cases in the early stages. Therefore, it is suggested that the early diagnosis for gastric and colorectal cancer using SLX alone may be difficult. However, it is revealed that SLX has a high tumor-specificity in consideration of the clinico-pathological properties such as H, P, n, ly, v factors, depth of cancer invasion and operative radicality. These data suggested that SLX could be applicable as a useful tumor-marker which shows the metastasis or extension of carcinoma.