[Evaluation of peritoneal cytology in colorectal carcinoma].

We investigated the incidence of free cancer cells in the peritoneal washings of 278 patients who had undergone surgery for colorectal cancer to evaluate its influence as a prognostic factor of the disease. Twenty-two cases (7.9%) were found to have malignant positive cytology (CY(+)). The rate of CY(+) in the cases with peritoneal dissemination (P(+)) was significantly higher than that in P(-) (66.7% vs 3.8%). In 244 cases, those who had tumors exposing to the peritoneum, both CY(+) and P(+) were observed highly in poorly differentiated adenocarcinoma. Among 18 P(+) cases, the rates of CY(+) were higher in both P3 and cur C than in P1, 2 and cur B. When restricted to 260 P(-) cases, CY(+) was observed more often in stage IV cases (14.3% vs 1.8%). Rate was significantly high in M+ (66.7%). Prognosis of 4 P(-) CY(+) cur A cases was as follows; 2 survived for a long time with no recurrence (20 and 60 months), 1 had curable liver metastases after half a year and obtained a 2 year disease free period after surgery, and another one died with brain, liver, and peritoneal recurrence one year later. The incidence of CY(+) is correlated with P(+); CY(+) increased when P(+) is extended more highly and incurable. CY(+) alone doesn't become a prognostic factor for peritoneal recurrences, because CY(+) is found rarely in curable P(-) cases. However, CY(+) is also associated with far advanced cancer with remote metastases, therefore we should consider the risk of such metastases for CY(+) cases with curable colorectal cancer.

[The docetaxel radiosensitization experience for the treatment of unresectable esophageal cancer].

BACKGROUND: Docetaxel is an increasingly important drug for the treatment of esophageal cancer. The docetaxel radiosensitization has been established in cancer cell lines. The therapeutic response and toxicity of a weekly docetaxel in combination with radiotherapy for unresectable esophageal cancer were examined. METHODS: Ten patients with locally advanced or metastatic squamous cell esophageal cancer were recruited in the following protocol. The median age was 65.7 years. Patients received radiation in 2 Gy single daily fractions to a total dose of 60 Gy. Docetaxel (10 mg/m2) was administered weekly for 6 consecutive weeks. RESULTS: One patient could not be evaluated. The overall response rate was 77% with 11% CR and 66% PRs. Mild grade 2 leukocytes toxicity was observed in 2/10 patients, which enforced the treatment absence for 7-14 days. Grade 2 stomatitis was noted in one patient. No severe grade 3 adverse effects were observed. CONCLUSION: It is concluded that low dose docetaxel with radiotherapy is feasible and, a high response rate can be expected. Toxicity is modest, and this protocol may be useful for the outpatients or neoadjuvant chemotherapy.

[A case of intraperitoneal paclitaxel administration in a gastric cancer patient with severely impaired renal function].

This study was designed to evaluate the pharmacokinetics and toxicity of paclitaxel, administered via an intraperitoneal route for a gastric cancer patient with renal dysfunction. The patient was a woman in her 50's, who had been diagnosed with severe renal dysfunction but no treatment history was known. She complained of dyspnea for a large quantity of ascites and was urgently hospitalized. It was diagnosed as gastric cancer with peritoneal dissemination. At this hospital, PTX was administered weekly intraperitoneally through an infusion port without complication. This result suggested that intraperitoneal PTX chemotherapy for a patient with renal dysfunction was a safe treatment.

[An effective weekly paclitaxel administration for gastric cancer with malignant ascites--a case report].

A 71 year-old woman underwent total gastrectomy for advanced gastric cancer of p stage IV (pathological findings: por1 type 3 pT3, pN3 (12p: 1/1, 16b1 int: 3/3, 16b1 lat: 2/2), P1, CY1, H0) in March 2002. She was treated with the double modulation therapy of MTX/CDDP/5-FU intraperitoneally after the surgery. After leaving the hospital, she was carrying out the chemotherapy with MTX/5-FU continually. In August 2002, she became hospitalized once again because an appetite decrease and diarrhea appeared. CT of abdomen showed that malignant ascites had obviously accumulated, and she was admitted. Because it was conceivable in all cases of an inflammation by the chemical stimulation that originated in an anticancer drug, we suspended the intraperitoneal chemotherapy. Paclitaxel 90 mg/body administration was started intravenously on a weekly basis from the end of the same month. Those symptoms improved and she was discharged from the hospital, and was continued the paclitaxel administration. In CT of the abdomen that was taken in November in 2002, malignant ascites had obviously been decreasing and disappeared completely after that.

[A case of gastric cancer with extraordinary liver metastasis effectively treated by adjuvant chemotherapy].

This was an extraordinary liver metastasis case with complication when the patient, a 70-year-old male, was diagnosed with stomach cancer for the first time. However, the patient has been in remission and is a long-term survivor due to an active chemotherapy after the operation. His chief complaints were stomachache and a loss of weight. He was diagnosed with stomach cancer by endoscopy. During the surgery, the mass was found to be 3 QFB palpable caused from hepatomegaly. The liver dysfunction was revealed in the blood biochemistry inspection. The abdominal CT revealed that the stomach cancer had spread to the whole liver. Distal gastrectomy was performed on May 22, 1997. In pathological findings, the tumor was diagnosed as a well-differentiated adenocarcinoma. Final findings: M, type3, T3 (SE), N2, H3, P0, CY0, and Stage IVb. The 5-FU based chemotherapy was performed and a complete response was temporarily obtained. However, it has recurred one year later and two or more kinds of chemotherapy have continued. He is alive for more than 7 years and comes to our hospital as an outpatient.

[The 5-fluorouracil hepato-arterial infusion with oral UFT therapy for the hepatic and extra hepatic metastases of colorectal cancer].

BACKGROUND: The 5 fluorouracil hepato-arterial infusion (5-FU HAI) therapy has a good effect on the liver metastases of colorectal cancer. To gain the antitumor effect of the extra-hepatic lesion, an oral UFT was combined with 5-FU HAI (pharmacokinetic modulating chemotherapy, PMC) to enhance the plasma 5-FU concentration. METHODS: UFT (200-400 mg/day) was orally administered daily and a continuous infusion of 5-FU (1,000-1,500 mg/5 h) was given once a week. Eight patients were treated with this regimen. Five of the eight have extra-hepatic lesions with liver metastases when this treatment was started. The response, time to progression, survival, and toxicity were detected. RESULTS: Four of the five patients with extra-hepatic lesion were evaluated. The response rate was 50% (1 CR, 1 PR, and 2 SD). For the liver metastases, the response rate was 62.5% (1 CR, 4 PR, 2 SD, and 1 PD). Grade 2 leukopenia was found in 1 patient. CONCLUSIONS: The 5-FU HAI with an oral UFT therapy had a good effect on the extra-hepatic lesions as well as hepatic metastases of colorectal cancer.

[A case of gastric cancer with peritoneal dissemination which shows a remarkable efficacy by a weekly administration of paclitaxel intraperitoneally].

We treated a 65-year-old female with gastric cancer who underwent peritoneal dissemination after 6 successive weeks of paclitaxel intraperitoneal therapy (90 mg/body), and obtained a disappearance of ascites and a reduction of the primary carcinoma. Operative findings: U ant, type 5, 26x20 mm, por, T2, n1(+), H0, P0, CY0, M0, stage II, and grade 2. A weekly paclitaxel intraperitoneal therapy could be a useful for both peritoneal dissemination and the primary carcinoma of advanced gastric carcinoma.

[A case of gastric endocrine cell carcinoma with neck lymph node metastasis resected after neoadjuvant chemotherapy].

A relatively rare case of gastric endocrine cell carcinoma was reported. The prognosis of this disease appears to be very poor due to its rapid rate of growth and invasiveness. A 75-year-old woman underwent a gastric endoscopy because the patient complained of an appetite loss. A gross Borrmann 3 type lesion in the greater curvature of the fornix was found. Biopsy specimens showed endocrine cell carcinoma. Abdominal CT examination revealed metastases in left neck and paraaortic lymph nodes. The serum sample showed an elevation of NSE level to be 53. A combination chemotherapy was performed using cisplatin and etoposide, which resulted in remarkable reduction of the main tumor two months later. The total gastrectomy associated with D2 lymph node dissection was performed. However, abdominal tumor was observed again in a month and it progressed rapidly. No clear response to the chemotherapies with cisplatin/etoposide or paclitaxel was found. The patient died 5 months after the operation.

[Experimental study on intraperitoneal versus intravenous CPT-11 for peritoneal seeding and liver metastasis].

Paclitaxel is an effective antitumor agent that shows ideal pharmacological characteristics for intraperitoneal chemotherapy. Intraperitoneal administration of this agent was compared with intravenous administration in mouse models of peritoneal seeding and liver metastasis. The peritoneal seeding model and liver metastasis model were established by inoculation of Colon 26 tumor cells into the peritoneal cavity and spleen of female BALB/c mice, respectively. Paclitaxel (20 mg/kg) was injected into the peritoneal seeding model intraperitoneally or intravenously on day 2 and 4 after inoculation of tumor cells. Paclitaxel (30 mg/kg) was injected into the liver metastasis model intraperitoneally and intravenously on days 4 and 8 after inoculation of tumor cells. Median survival time for intraperitoneal administration (17.50 +/- 0.86 days) was longer than that for intravenous administration (13.70 +/- 0.47 days) in the peritoneal seeding model experiment. Median survival time for intraperitoneal administration (19.78 +/- 0.74 days) was longer than that for intravenous administration (17.50 +/- 0.54 days) in the liver metastasis model experiment. Intraperitoneal administration of paclitaxel may be a more efficient form of adjuvant chemotherapy for prevention of both peritoneal seeding and liver metastasis in patients with gastrointestinal cancer.

[A case of liver and lung metastases of rectal cancer responding well to 5-FU hepato-arterial infusion (HAI) with combined use of oral UFT].

We have studied the pharmacokinetics of 5-FU hepato-arterial infusion (HAI) with combined use of oral UFT for colorectal cancer cases previously. The plasma 5-FU concentration in cases of 5-FU HAI plus UFT is 1.5-6 times as high as with 5-FU HAI only. We report a rectal cancer case with liver and lung metastases treated successfully with this protocol. A 75-year-male underwent low anterior resection for rectal cancer as Rab, 3.5 x 3 cm, well, ai, n2, P0, H3, M1 on March 26, 2002. For synchronous hepatic and lung metastases, he received weekly 5-FU 1,000 mg HAI, UFT 4T 2 x postoperatively. As a result, liver and lung metastases disappeared over 6 months. We recommend weekly 5-FU HAI with combined use of UFT, which can be more effective not only for liver metastases but also for extra-hepatic lesion of colorectal cancer.

[Complication after self expandable metallic stent for esophageal cancer].

Major complications after placement of esophageal stent and airway stent were reviewed and evaluated. Four patients, including two patients with perforations and two patients with fistula formation, developed major complications after placement of a self expandable metallic stent. Two patients underwent additional radiation to improve stricture after stent placement. In one patient, stent placement was selected to improve esophageal stricture that occurred after radical radiation therapy. In one patient, migration of stent into the lesion caused a perforation. It can be concluded that additional radiation after stent placement increases the risk of complication. Stent migration also can lead to the risk of perforation.

[A case report of intra-hepatic arterial infusion of mitomycin C with degradable starch microspheres for liver metastases of sigmoid colon carcinoma].

A 46-year-old man underwent polypectomy of sigmoid colon in January 1996. The adenocarcinoma invaded the submucosal layer, and sigmoidectomy and D2 lymph node dissection were performed one month later. Follow-up CT revealed liver metastases, and partial hepatectomy was performed in January 1998. Afterward, weekly high dose intra-hepatic arterial chemotherapy (5-FU: 1,000 mg/body) was performed 41 times, but CT revealed multiple liver metastases in October 1998. Therefore, intra-hepatic arterial infusion of mitomycin C (MMC) with degradable starch microspheres (DSM) was given in November 1998. As follow-up CT revealed that the liver metastases were growing, partial hepatectomy was performed again in March 1999. No carcinoma was seen in the resected liver. After the second hepatectomy, intra-hepatic arterial infusion of MMC with DSM was performed five times. No evidence of recurrence has been seen. Intra-hepatic arterial infusion of MMC with DSM is recommended for liver metastases of colorectal cancer as a second line treatment.

[5-FU pharmacokinetic study of 5-FU hepato-arterial infusion with oral UFT].

5-FU hepato-arterial infusion (HAI) is powerful chemotherapy for liver metastases of colorectal cancers. Event though hepatic lesions are controlled by 5-FU HAI, we have found that extra-hepatic lesions are the limiting factor for colorectal cancer patients. General chemotherapy is necessary in addition to 5-FU HAI. The chemotherapy of 5-FU venous infusion plus oral UFT is called "pharmacokinetic modulating chemotherapy (PMC)." This protocol is very effective for colorectal cancers, because UFT reduces the rate of metabolism of infused 5-FU. We studied the plasma 5-FU concentration at the time of weekly high dose 5-FU HAI plus oral UFT. The plasma concentration of 5-FU in 5-FU HAI plus UFT is 1.5-6 times as high as with 5-FU HAI only. 5-FU concentration in the liver tissue is likely to be much higher at the time of 5-FU HAI. 5-FU HAI plus oral UFT can be more effective for not only liver metastases but also for extra-hepatic lesions than 5-FU HAI alone.

[Pharmacokinetic study of CPT-11, SN-38 and SN-38 glucuronide in the ascites, plasma and bile after intraperitoneal administration of CPT-11].

We studied the pharmacokinetics of CPT-11 with intraperitoneal administration in a patient with a PTCD tube. The patient had advanced gastric cancer with peritoneal metastasis. CPT-11 was administrated in a dose of 40 mg and the intraperitoneal, plasma and bile levels of CPT-11, SN-38 and SN-38 glucuronide (SN-38 GLU) were measured periodically. The results showed that the periodical concentration pattern of CPT-11, SN-38 and SN-38 GLU in the bile was closely related to that of CPT-11 in the abdominal cavity.

[Pharmacological study on levofolinate in intraperitoneal leucovorin-5-FU chemotherapy].

We report the pharmacological findings on levofolinate after the intraperitoneal administration of leucovorin-5-FU. Levofolinate 300 mg/saline 500 ml and 5-FU 750 mg/saline 500 ml were administered intraperitoneally over 1.5 h. The plasma and intraperitoneal concentrations of levofolinate at 0, 0.5, 1, 2, 4, 8, 22(20) h after the administration were evaluated at 6 points with HPLC analysis. The intraperitoneal levofolinate concentration went up as high as 100 micrograms/ml and remained above 10 micrograms/ml over 8 hours. This suggested that intraperitoneal administration elevated the portal vein and abdominal lymphatic levofolinate levels. Intraperitoneal levofolinate-5-FU is a promising protocol for gastro-intestinal cancers.

[Staging laparoscopy for advanced gastric cancer].

Staging laparoscopy was carried out for 12 cases of advanced primary gastric cancer to evaluate the condition of peritoneal seeding. Peritoneal seeding was indicated in five cases. Abdominal lavage sampling was positive in six cases. Among six cases with positive cytology, surgery was adopted in three cases to lessen bleeding or stricture. Chemotherapy were carried out for the other three cases. Radical lymph node resection was carried out in six cases without peritoneal seeding. Laparoscopic observation was easier and more feasible under general anesthesia than local anesthesia. Preoperative staging laparoscopy for advanced gastric carcinoma can evaluate the condition of peritoneal seeding. Based on the results, a suitable treatment plan for each patient can be determined.

[Airway stent for airway obstruction caused by esophageal carcinoma].

The result of airway stent and adjuvant therapy for airway obstruction caused by advanced esophageal carcinoma was evaluated. In Tokyo Metropolitan Ohkubo Hospital, four cases of esophageal carcinoma with airway obstruction were treated by tracheo-bronchial stent. Two were primary cases and the others were recurrent cases. Three of the patients demonstrated progressive dyspnea due to airway obstruction, and the other complained of bloody discharge. An ultraflex non-covered stent was used cases. After insertion of the airway stent. The patients' dyspnea improved immediately. One patient was discharged without adjuvant treatment, and died of the cancer one month later. Adjuvant treatment was adopted in the other three cases. The size of the tumor decreased, but fistula formation was observed in two cases. An airway stent is an effective treatment with immediate results for dyspnea caused by airway obstruction. Adjuvant treatment after stent placement is often associated with fistula formation. It should be considered carefully.