Prognostic study of ovarian clear cell carcinoma

Prognostic studies were performed on 17 cases with clear cell carcinoma of the ovary. The results are follows: 1) The average age was 45.9 years and ranging from 35 to 57 years. 2) Regarding the FIGO clinical stage, all of 5 patients with stage I and 3 of 5 with stage II survived over 2 years, while all of patients with stage III and 2 with stage IV were dead within 2 years. 3) Of 9 patients who had complete resection for primary operation, 8 (89%) survived over 2 years. All of 8 patients who had incomplete resection were dead within 2 years. 4) All cases had been received various chemotherapy; CQ + 5-FU (n = 5), CPM + ADM + CDDP + 5-FU (n = 7), 5-FU + CPM + MMC (n = 2), CDDP (n = 1), CDDP + MMC + 5-FU (n = 1), MCNU + VCR + 5-FU (n = 1), but none of them improved the prognosis of this histological type. 5) With or without administration of CDDP, there was no significant difference in the prognosis. These results suggest that early diagnosis of disease, curative surgical resection and selection of effective chemotherapeutic agents are important things to improve prognosis of clear cell carcinoma of the ovary.     

Study of intermittent intra-arterial infusion chemotherapy in liver metastases from squamous cell carcinoma

There are few reports about the methods, amounts, and kinds of dosage about intermittent intra-arterial chemotherapy of liver metastases from primal pathological type's squamous cell carcinoma. Because they are less than liver metastases from adenocarcinoma of colon or stomach. Although it is important of other factors about the operative method of primary focus and metastases of the other parts, it is possible that those cases obtained the good prognosis and protected liver failure, if those liver metastases could be controlled well. In our department from January 1987 to December 1989, 9 cases of inoperative liver metastases of squamous cell carcinoma (esophagus: 4 cases, larynx: 3 cases and cervix of uterus 2 cases) were treated of intra-arterial infusion chemotherapy of FAM (5Fu 500 mg/week, ADM 30 mg/4 weeks and MMC 4 mg/2 weeks) and CDDP methods (only CDDP 10 mg/week). Cases of esophagus carcinoma were treated with FAM method. On the CT-scan one of the cases showed the reduction rate of more than 50% and was a Progressive Response (PC), and the SCC tumor marker decreased in 2 cases. However, 2 other cases died of liver failure. Cases of larynx were treated with FAM and CDDP methods. However, on the CT-scan all of the cases showed No Change (NC) nor decrease in SCC. But thinking of prognosis FAM was better than CDDP. Cases of cervix of uterus were treated with the FAM and CDDP methods. FAM was not different than the CDDP in the prognosis and effect.     

Downstaging of lymph node metastasis after neoadjuvant intraperitoneal and systemic chemotherapy in gastric carcinoma with peritoneal metastasis

PurposeThe aim of the present study was to evaluate the clinical features and prognosis of lymph node metastasis (LNM) in gastric cancer patients with peritoneal metastasis (PM) after neoadjuvant intraperitoneal and systemic chemotherapy.MethodsA total of 69 gastric cancer patients with PM and LNM who received neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) of intraperitoneal docetaxel (DXT) and cisplatin (CDDP); intravenous chemotherapy of DXT and CDDP and oral S-1in Kishiwada Tokushukai Hospital between January 2008 and February 2017. After surgical resection, the response of LNMs was studied to confirm the effect of NIPS on LNMs.ResultsAfter NIPS, 197 lymph nodes (LNs) (42.5%) were graded as G3, the progression in LNMs were significantly better than in the primary tumors. Until the last follow-up, 1-year overall survival rate was 82.6%, and the median survival period was 22.0 ± 3.7 months. In the group of patients who had achieved a more than 50% G3 grade of the response of LNMs, the median survival period is 38 months; in the less than 50% G3 grade group, it is 14 months, that is a significantly different result. Multivariate analyses showed that the factors PCI, Post-therapeutic N status and response of the LNMs were found to be as independent prognostic factors.ConclusionDownstaging of LNMs were achieved in patients of gastric cancer with PM who received NIPS. Downstaging of LNMs after NIPS is related with the prognosis of gastric cancer and should be valued in subsequent surgery for gastric cancer with peritoneal and lymph nodes metastasis.     

Effectiveness of intra-arterial infusion chemotherapy for solitary bone metastasis from lung cancer with radiotherapy--a case report

There have been few reports on intra-arterial infusion chemotherapy for metastatic bone cancer because the bone metastasis is multiple in almost all cases. However, selective intra-arterial infusion chemotherapy is thought to be more effective than systemic chemotherapy for solitary bone metastasis. The patient was a 47-year-old man who had been diagnosed with solitary metastasis of the right knee joint from lung cancer on the basis of various imaging studies and biopsy. The metastatic bone cancer showed rapid growth with systemic inflammatory response, and the patient's general condition became progressively worse. Therefore, radiotherapy alone consisting of 3 Gy of fraction x 5 fractions/week was initiated, but the metastatic lesion was a progressive disease (PD) at the middle point of radiotherapy (24 Gy), and we had no choice but to alter the therapy. Angiography showed dense tumor staining, so intra-arterial infusion chemotherapy was contemplated. Subsequently 15 mg/body of CDDP was administered persistently 5 days a week through a catheter placed in the right femoral artery that had been introduced via the left femoral artery. After 8 courses of this therapy (total dose 600 mg), the metastatic bone cancer was remarkably reduced in size and showed nearly a complete response (CR) on CT scan. This result suggests that intra-arterial infusion chemotherapy is very effective if there is only one bone metastasis lesion.     

Evaluation of intra-arterial infusion chemotherapy for liver metastasis from gastric cancer FEM--combination therapy of 5 FU,Epirubicin and MMC

OBJECTIVE: We evaluated the effectiveness of FEM (5-FU, Epirubicin, MMC) therapy. SUBJECTS: One hundred ten cases of liver metastasis from gastric cancer were collected from January, 1977 until June, 2001 (synchronous: 74 cases, asynchronous: 36 cases). Twenty-nine cases were H1, 20 cases were H2 and 61 cases were H3. METHODS: The patients were divided into the following groups: Group A: Resection of the primary lesion and hepatic resection (n = 9); Group A1: Hepatic resection only (5 cases), Group A2: Hepatic resection and intra-arterial infusion (4 cases). Group B: Resection of the primary lesion (n = 67); Group B1: Resection of the primary lesion only (46 cases), Group B2: Intra-arterial infusion (21 cases). In Groups A2 and B2, FEM therapy was applied to A2a (3 cases) and B2a (8 cases). Non-FEM therapy was applied to A2b (1 case) and B2b (13 cases). Group C consisted of 34 cases in which resection of the primary lesion was not undertaken. Survival rates were then compared. RESULTS: One-year survival rates and 50% survival period for each group were as follows: Group A: 33%, 5.9 months; Group B: 22%, 4.8 months; and Group C: 6%, 3.9 months, respectively. Five patients from Groups A2a and B2a survived for one year or longer. CONCLUSION: 1. The prognosis with liver metastasis from gastric cancer, even with a number of therapies, is not promising. 2. Resection of the primary lesion along with hepatic intra-arterial infusion therapy (in addition to hepatic resection), especially in combination with FEM therapy, provided an extended survival.     

A case of complete response in a primary lesion treated by combined chemotherapy of TS-1 and CDDP for small cell carcinoma of the stomach with liver metastasis

A 75-year-old male patient with small cell carcinoma of the stomach and liver metastasis was treated by combined chemotherapy of TS-1 and CDDP. One course consisted of TS-1 (120 mg/day) administered for 14 days followed by 14 days rest. CDDP (108 mg/day) was administered by 24-hour continuous intravenous infusion at day 8 after the start of TS-1. After 3 courses, endoscopic examination revealed complete disappearance of the primary tumor with no cancer cells detected by endoscopic biopsy. CT-scan showed that the metastasis of the left lobe of the liver had disappeared and also that the metastasis of the right lobe of the liver was remarkably reduced (75%). The primary lesion was estimated CR, the metastasis PR, and the synthesis PR. The TS-1/CDDP chemotherapy regimen is considered effective for small cell carcinoma of the stomach with liver metastasis.     

New interesting chemotherapeutic regimens in advanced gastric cancer]

We have made over view of new chemotherapeutic regimen for treatment of advanced gastric cancer 5-FU + MMC, FT + MMC and UFT + MMC therapy have been used widely for treatment of advanced gastric cancer as chemotherapeutic regimens in Japan. These regimens did not shown made than 25% in response rate as antitumor effect. Since development of CDDP, FP (5-FU + CDDP), FAP (5-FU + ADM + CDDP) and EAP (Etoposide + ADM + CDDP) is becoming gradually very important regimen for treatment of advanced stomach cancer patients. Recently, we have studied EAP therapy on 50 cases of advanced gastric cancer from January 1988 to September 1989. ADM 20 mg/m2, CDDP 40 mg/m2 and Etoposide 100 mg/m2 were administered on day 1 and 7, 2 and 8, and 4, 5 and 6, respectively, with not less than 2 courses every 3 to 4 weeks. The rate of effectiveness were obtained 43.8% with a confidence interval 95% of 30-58%. Median survival time was only 5.1 months for EAP therapy, which was highly effective but led to no prolonged survival period. Thus it is thought that good control of leukopenia, a dose-limiting factor remains to be examined. Biochemical modulation of 5-FU using such as MTX + LV and CDDP + LV (leucovorin) now under studying in the nation wide in Japan, so far it is getting better results.     

Effect of hepatic arterial infusion chemotherapy for liver metastasis from gastric cancer

We performed hepatic arterial infusion (HAI) chemotherapy for 4 patients with advanced gastric cancer who had undergone curative resection except for liver metastasis. The main antineoplastic drugs were 5-fluorouracil (5-FU), mitomycin C (MMC) and cisplatin (CDDP). A catheter was inserted into the hepatic artery by interventional radiological techniques in 3 patients and operatively in 1 patient. The response rate for 4 patients was 75% (CR2, PR1, PD1). The adverse events were Grade 3/4 nausea and/or vomiting in 2 cases. The HAI chemotherapy was effective and useful for patients with advanced gastric cancer who had no unresectable lesions except for liver metastasis.     

A case of thymic carcinoma responded to intra-arterial chemotherapy combined with radiation therapy

A 70-year-old male complained of pain in the left neck. A tumor of about 8 cm in diameter was detected by contrast CT in the region extending from the anterior to upper mediastinum. For definitive diagnosis, biopsy was performed under CT guidance, and the patient was diagnosed as having anaplastic carcinoma in the thymus (T4, N1, M0, stage IVb). Since surgical treatment was judged to be impossible because of infiltration into large blood vessels, the patient underwent chemotherapy by intra-arterial injection (CDDP, ADM) and radiotherapy (45 Gy), and obtained a CR. Metastasis to the spleen was detected during the follow-up period, but a CR was obtained by chemotherapy by intra-arterial injection (CDDP) and systemic chemotherapy (TXL). Generally, the prognosis for carcinoma in the thymus is poor, and the prognosis for anaplastic carcinoma in the thymus is considered especially poor. However, chemotherapy by intra-arterial injection of carcinostatics such as CDDP can be applied to patients in whom surgical treatment is impossible.     

Multimodality therapy for synchronous liver metastases of gastric cancer--significance of aggressive hepatic resection of liver lesions

We analyzed 15 gastric cancer patients with synchronous liver metastases, and studied the significance of hepatic resection with multimodality therapy. 1. Both gastric and hepatic resections followed by intra-arterial or systemic chemotherapy were performed for six patients, two of whom had intra-operative MCT or EIT. The survival time of four patients without recurrence was 5 Y 4 M, 4 Y 5 M, 2 Y 4 M and 11 M. Two patients died of recurrence in the retroperitoneum or residual liver 3 Y 10 M and 8 M after therapy, respectively. The three-year survival rate was 83%. 2. The longest survival among the five patients treated with gastric resection without hepatic resection followed by intra-arterial or systemic chemotherapy was 1 Y 1 M. 3. Four patients with non-curative factors (P, N, M) were treated with systemic chemotherapy only, and the longest survival was 1 Y 1 M. In conclusion, when local control is obtained during surgery in patients with gastric cancer with synchronous liver metastasis, aggressive hepatic resection supported with MCT or EIT should be performed on liver lesions to improve the prognosis.     

Pancytopenia and ARDS with high dose hepatic arterial infusion

The patient was a 74-year-old woman with gastric cancer with multiple liver metastasis. She was treated with daily oral administration of TS-1 100 mg/day (day 1-21) and systemic administration of CDDP 90 mg (day 8) as neoadjuvant chemotherapy for 2 courses. As metastatic lesions became smaller, we performed distal gastrectomy. TS-1 was started for the residual cancer lesion. However, liver metastatic lesions increased in size, so we carried out intraarterial chemotherapy (IAC), Nausea appeared at 9 days, pancytopenia at 28 days and ARDS at 78 days after IAC. She died due to ARDS.     

A case of gastric cancer associated with synchronous liver metastasis successfully treated with combination therapy of systemic and hepatic arterial infusion chemotherapy

A 56-year-old man who underwent distal gastrectomy at another hospital was admitted to our hospital because of advanced gastric cancer with synchronous liver metastasis. As we considered that the metastatic liver tumor was unresectable one, an intra-arterial catheter was inserted and weekly chemotherapy including methotrexate (MTX) (intra-venous) and 5-fluorouracil (5-FU) (intra-arterial) was started. The metastatic liver tumor was gradually reduced and resulted in partial response (PR) after 12 courses. Eight months later, the size of the metastatic liver tumor increased and lung metastasis occurred, so we started a new regimen of chemotherapy using CPT-11 (intra-venous) and CDDP (intra-arterial). After 4 courses of this regimen, we gained PR both in the metastatic liver and lung tumor. This case indicates that the combination therapy of systemic and hepatic arterial infusion chemotherapy is a treatment option in cases of advanced gastric cancer with liver metastasis.     

Usefulness of hepatic arterial infusion chemotherapy for liver metastasis in gastric cancer]

We have performed intra-hepatic arterial chemotherapy for 9 patients with liver metastasis arising from gastric cancer. We mainly used 5-FU and CDDP as antineoplastic drugs. RESULTS: The median survival after gastrectomy was 600 days. Of 9 cases, 2 showed CR, 4 PR, 2 NC, 1 PD. The response rate was 67%. The 9 cases were classified into 2 groups. One group, the short-term survival group, concised of 5 patients that had no more than 2 years survival and the other, the long-term survival group, consisted 4 patients that had more than 2 years survival. We compared these 2 groups and found no difference in the primary lesions between the 2 groups. The patients in the long-term survival group had fewer and smaller metastatic lesions in the liver than the patients of the short-term survival group. The patients in the long-term survival group had no unresectable lesions except liver metastasis when gastrectomy was performed. However, 2 patients in the short term survival group had unresectable lymphatic involvement at the time gastrectomy was performed. Of 9 patients, 6 died from the extrahepatic lesion. CONCLUSION: The intra-arterial chemotherapy was effective and useful for liver metastasis arising from gastric cancer. However, the majority of patients died from extrahepatic lesions. We should therefore consider the use of systemic chemotherapy with intra-arterial chemotherapy.     

Complete remission in a case of sigmoid colon cancer with multiple liver metastases-treatment with arterial chemotherapy and percutaneous microwave coagulation therapy

A 59-year-old man was admitted to our hospital for advanced sigmoid colon carcinoma with synchronous multiple liver metastases. The patient received sigmoidectomy with regional lymph node dissection on June 8, 1998. We started intra-arterial combination chemotherapy on July 1, 1998. MMC (4 mg/body) was administered via rapid intra-arterial infusion on day 1. After MMC administration, 5-day intra-arterial continuous infusion of 5-FU at 500 mg/body/day was performed with oral administration of LV (30 mg/body/day). The treatment cycle was defined as every three weeks. The patient was treated with 4 courses of chemotherapy. From September 30, he received intra-arterial infusion of bolus MMC 4 mg/body, LV 6 mg/body and 5-FU 1,000 mg/body/4 hrs every two weeks with oral administration of Tegafur-uracil 400 mg/day. After 4 intra-arterial chemotherapy sessions, the metastatic liver tumors disappeared except for a focus in the right lobe. Therefore we decided to give the remnant liver metastasis percutaneous microwave coagulation therapy (PMCT). He obtained a complete remission in the liver metastases after two PMCT (70 W, 60 sec) sessions. Intra-arterial chemotherapy is effective for unresectable metastatic liver tumors from colon cancer. If a patient shows a partial response on the metastatic tumors through the chemotherapy, one must consider other modalities such as PMCT.     

Preoperative adjuvant chemotherapy of skeletal and soft tissue sarcomas

Preoperative adjuvant chemotherapy for skeletal and soft tissue sarcomas requires: (1) correct identification of the effective postoperative adjuvant chemotherapy, (2) eradication of any of the micrometastatic foci that may have already occurred in many of the patients with these sarcomas, (3) easier and safer limb-salvage procedure, being clearly defined, with shrinkage of the primary lesion. For this purpose, a preoperative adjuvant chemotherapy regimen making practical use of intra-arterial CDDP (cis-dichlorodiammineplatinum II) infusion is desired in multi-drug combined chemotherapeutic treatment, including HDMTX (high-dose methotrexate), ADR (adriamycin) and CDDP. In this paper, the clinical application of preoperative adjuvant chemotherapy to skeletal and soft tissue sarcomas with combination of HDMTX and CDDP is presented in the light of the observations of tumor response to these anticancer agents, and the possibility of to establishing a new preoperative adjuvant protocol is discussed.     

Study on neoadjuvant chemotherapy of Borrmann 4 type carcinoma of stomach and its clinical significance

Considering a high potential of biological malignancies of Borrmann 4 type carcinoma (abbr., Borr. 4) of the stomach, preoperative induction (neoadjuvant) chemotherapy was applied to patients with Borr. 4 as an initial therapy. Anticancer drugs used in this study were FAM-OK432, sequential MTX-5Fu or UFT-M through aortic infusion or induced hypertension chemotherapy (IHC) in order to obtain selective enhancement of drug delivery into tumor tissue. These trials were carried out on 24 patients who had Borr. 4 type carcinoma. The response to neoadjuvant chemotherapy showed CR in 1 case, PR in 3 cases and MR in 4 cases. The objective improvement except the primary gastric lesion showed shrinking of distant metastatic lymph nodes along paraaorta or Virchow of 50% (5/10), disappearance of pleural or peritoneal fluids 85. 7% (6/7) and marked decrease of tumor marker such as CEA, CA19-9 or CA125 100% (12/12). In one of 5 cases showing morphological improvement of primary gastric lesion, no viable cancer cells were seen in the stomach associated with multiple foci of granulofibromatous lesion of regional nodes. In 17 cases of 24 total gastrectomy was done with extended lymphadenectomy (R2-R3). While there was no difference in the median survival time (MST) among curable resection group, MST of non-curable resection group with neoadjuvant chemotherapy showed a fairly good prognosis for 14 months as compared to that of 4 months without chemotherapy. As for disease-free survival, patients whose tumor showed a high response to neoadjuvant chemotherapy had a good prognosis in non-curable resection group (p less than 0.01). In conclusion our results demonstrated that patients whose tumor were effectively destroyed by neoadjuvant chemotherapy against Borr. 4 carcinoma of stomach had an improved prognosis.     

Gastric cancer with liver metastasis effectively treated by intra-hepatic arterial infusion

The prognosis of gastric cancer with liver metastasis is very poor. Because many gastric cancers with liver metastasis have multiple metastatic tumors in the liver, and the indication for surgical resection is rare. Moreover, the non-curative factors of many cases are not only liver metastasis but also are lymph node metastasis and peritoneal dissemination. However, some authors have reported gastric cancer with liver metastasis was treated effectively by intra-hepatic infusion of an anti-cancer drug. In this article, we report three cases of gastric cancer with liver metastasis that are treated effectively by intra-hepatic arterial infusion of an anti-cancer drug. There were no non-curative factors except liver metastasis. The first was a H3 case treated effectively by intra-hepatic arterial infusion of 5-fluorouracil (5-FU), mitomycin C (MMC) and peroral administration of 5-FU. The metastatic liver tumors had disappeared in 14 weeks. However, the patient eventually died of liver and brain metastases in 7 months after the therapy. The second was a H2 case treated effectively by intra-hepatic arterial infusion of CDDP and peroral administration of 5'-DFUR and PSK. The metastatic liver tumors had disappeared in 4 months, and the patient is still alive without recurrence in 35 months after surgery. The third was a H2 case treated effectively by intra-hepatic arterial infusion of cisplatin (CDDP) and peroral administration of TS-1 and PSK. The size of metastatic nodules had increased, and Virchow lymph node metastasis had appeared in 28 months after surgery. The patient eventually died in 32 months after surgery. These results suggested that intra-hepatic arterial infusion of CDDP with peroral administration of TS-1 or 5'-DFUR was an effective therapy for gastric cancer with liver metastasis.     

Phase II study with cisplatin in advanced stomach and colon carcinoma. Cooperative Study Group of Cisplatin for Stomach and Colon Carcinoma

A multicenter phase II study was performed to evaluate cisplatin (CDDP) in patients with gastric carcinoma or colon carcinoma. Ninety-nine cases of gastric carcinoma and 25 cases of colon carcinoma were entered into the study. According to the eligibility criteria prepared for the study protocol, 28 and 5 patients were excluded from the stomach and colon group, respectively. CDDP, 70-100 mg/m2, was administered intravenously with sufficient hydration. The efficacy rates evaluated by the UICC tumor reduction criteria were 19.1% (13/68 cases) in gastric carcinoma and 5.0% (1/20 cases) in colon carcinoma. Lymph node metastasis and metastatic abdominal tumor were effective targets for CDDP treatment. As side-effects of CDDP, nausea/vomiting (69.2%) and general malaise (35.2%) were observed. CDDP was thus considered to be one of the effective chemotherapeutic agents for treatment of gastric carcinoma.     

Regional treatment of esophageal liver metastasis by intra-arterial low-dose 5-FU therapy

The prognosis of esophageal liver metastasis remains poor because of the high incidence of synchronous metastasis in other area and insufficient response to systemic chemotherapy. We assessed loco-regional anticancer potential of intra-arterial 5-FU chemotherapy for esophageal liver metastasis aimed at combination with systemic chemotherapy, radiotherapy and ablation therapy as a multidisciplinary treatment. Six patients of esophageal cancer with liver metastasis and without extra-hepatic metastasis were enrolled. Intra-aortic chemotherapy consisted of 5-FU (250 mg/body) in a one-shot infusion or a continuous infusion for 7 days with 2-week intervals until failure. The responses of liver metastasis were 2 cases of CR, 3 of PR and 1 of SD. The response rate and the local control rate were 83% and 100%, respectively. The maximum time to progression was 53 months. Grade 3/4 toxicity was not observed. Two cases had catheter failure and the treatment was interrupted. Liver metastases were controlled well until death in all cases except one. Low-dose intra-aortic 5-FU chemotherapy provided a good regional response and a combination with systemic chemotherapy may prolong survival for the patients of liver metastasis of esophageal cancer.     

Evaluation of continuous intra-arterial infusion chemotherapy after hepatic resection of liver metastases in colorectal cancer

We retrospectively evaluated continuous intra-arterial infusion chemotherapy after hepatic resection for hepatic metastases of colorectal cancer. From 1982 to 1990, we treated 22 patients with continuous intra-arterial infusion chemotherapy after hepatic resection, and 43 patients with only hepatic resection. 5-FU (250 mg/day) was administered continuously through implantable reservoir immediately after hepatic resection, and continued as long as possible. The total dose of 5-FU administered was 1.75-46.0 g (mean 17.4 g). We divided the patients into three groups: the first was administered a total dose of 5-FU more than 15 g, the next with less than 15 g, and the last with only hepatic resection was not given 5-FU. The 5-FU group receiving more than 15 g showed the lowest rate of hepatic metastasis recurrence. We compared the group showing recurrence within six months after hepatic resection (early recurrent group) with the group evidencing recurrence on and after six months (late recurrent group). In the former group, extra-hepatic recurrence significantly increased, whereas in the latter group hepatic recurrence significantly increased (p less than 0.05). In the early recurrent group, moderately or poorly differentiated adenocarcinoma significantly increased (p less than 0.01). According to the pathological result of pre-operative biopsy, one should check for extra-hepatic lesion as much as possible, and choose systemic chemotherapy for the early recurrent group.