A case of advanced esophageal cancer with liver metastases: efficacy of combination therapy of docetaxel/cisplatin/5-FU

The combination chemotherapy with docetaxel/CDDP/5-FU(DCF)for head and neck squamous carcinoma(SCC) has been widely accepted. It seems quite natural that DCF therapy is expected to be equally effective against esophageal SCC because of their histological similarity. In this report, we present a case of unresectable advanced esophageal SCC with multiple liver metastases which showed remarkable regression by DCF therapy, with relatively slight adverse effects. The patient was a 46-year-old female, who underwent upper gastrointestinal fiber-optic endoscopy for dysphasia and was diagnosed to have upper middle thoracic esophageal SCC. Abdominal CT scan showed multiple liver metastases with para-aortic lymph node involvement. The clinical stage diagnosis was T3N4M1, Stage IVB, obviously non-resectable far-advanced esophageal SCC. Systemic chemotherapy with DCF was started as the initial treatment. The chemotherapy regimen was as follows. 5-FU 500 mg/m(2) was administered as continuous intravenous infusion through day 1 to 5, while docetaxl 60 mg/m(2) and cisplatin 50 mg/m(2) were given intravenously on day 2. Each course was followed by a 23-day drug-free period, and the entire course was repeated every 28 days. Ten cycles of this DCF chemotherapy were carried out. After 4 cycles, primary lesion was judged as complete response(CR)by endoscopy. After 8 cycles, the liver metastases were judged as CR and para-aortic lymph nodes showed a partial response(PR)by CT scan. After 10 cycles, all we could detect was a small local recurrence of the primary tumor, which was then treated with chemoradiotherapy at the outpatient clinic. Until this writing, we added 2 more cycles of DCF therapy for the recurrent para-aortic and inguinal lymph node metastasis. Three years have passed from her first visit, and the patient is still in a stable disease state. The adverse effects were grade 3 at most in both hematological and non-hematological toxicity. We conclude that DCF therapy is potentially very effective for advanced esophageal SCC.     

Lymph node excision with laparotomy and chemo-radiation therapy for a hepatocellular carcinoma patient with multiple lymph node metastases]

We reported a case of hepatocellular carcinoma (HCC) with multiple lymph node metastases. The patient was a 67-year-old male with C type liver cirrhosis. He underwent microwave coagulation therapy (MCT) for HCC (5 cm and 1.5 cm) 1.5 years before admission. Abdominal CT scan revealed a well-enhanced tumor (2 cm) in caudate lobe of the liver and excessive lymph node metastases, locating in the inferior phrenic, periportal and para-aortic area. The preoperative serum AFP and AFP-L3 levels were 41.9 ng/ml and 93.1%, respectively. At laparotomy, systematic dissection of the enlarged lymph nodes and MCT of the hepatic tumor was performed. After operation, residual inferior phrenic lymph node was treated with irradiation therapy (total 50.4 Gy). The lymph node showed complete response (CR) for about a year and the AFP-L3 level returned to the normal range. After 9 months, a supra-clavicular lymph node was detected on abdominal CT scan. Irradiation therapy (total 45 Gy) in combination with CDDP (100 mg) and 5-FU (4,000 mg) was applied. The lymph node had been assessed as partial response for 6 months. The patient lived quite well after these therapies, but died of hepatic failure 32 months after the initial operation. In conclusion, we recommend this therapeutic strategy using operative excision and chemo-radiation therapy for HCC with multiple lymph node metastases.     

A case of sigmoid colon cancer with metastases of para-aortic lymph nodes treated with curative resection after irinotecan plus 5-fluorouracil and l-leucovorin combination chemotherapy

A 54-year-old woman visited our hospital with a chief complaint of lower abdominal pain and melena. The patient was diagnosed with sigmoid colon cancer using colonoscopy. Abdominal CT revealed metastases to para-aortic lymph node, so our diagnosis was unresectable sigmoid colon cancer. She underwent a transverse colostomy to avoid stenosis. Two weeks after surgery, she underwent a 1-week chemotherapy regimen (CPT-11 80 mg/m(2)/week+5-FU 2,000 mg/m(2)/week+l-LV 250 mg/m(2)/week) modified AIO regimen combined irinotecan for 3 weeks, followed by a 1-week rest interval as one course. Throughout the period of treatment, there was no adverse event, and this regimen has been maintained for 5 courses. After 5 courses of chemotherapy, primary tumor and metastases to para-aortic lymph nodes were remarkably reduced on colonoscopy and abdominal CT. So, she could undergo curative resection. Pathological efficacy was Grade 3, a complete response. This combination therapy may well be useful for advanced colon cancer patients.     

A patient with gastric cancer with para-aortic lymph node metastases surviving for 9 years after effective preoperative chemotherapy and radical operation

A 63-year-old male patient with type 3 advanced gastric cancer was referred to our hospital. Preoperative examination by CT-scan revealed swollen para-aortic lymph nodes and cancer invasion to the pancreas. The patient was treated pre-operatively with intravenous 5-FU, 500 mg/body/day, continuous infusion for 1 week. Immediately after the chemotherapy, the patient underwent total gastrectomy, splenctomy, left-adrenectomy and resection of the body and tail of the pancreas, along with para-aortic lymph node dissection. Microscopic examination revealed that the tumor was a moderately differentiated tubular adenocarcinoma, which displayed invasion to the pancreas with lymph node metastasis up to the level 3 lymph node. Histologically, the effect of preoperative chemotherapy showed a grade 2 effect on the main tumor, but a grade 3 chemotherapeutic effect was observed at the para-aortic lymph nodes. The patient has subsequently remained disease free for 9 years. In this case, it is considered that the preoperative chemotherapy by 5-FU and potentially curative radical operation yielded a good outcome.     

A case of rectal cancer with multiple liver and peritoneal metastases that responded dramatically to low-dose 5-FU plus LV and CDDP combination chemotherapy

We have experienced successful treatment of a multiple hepatic metastasis of rectal cancer with combination chemotherapy. The patient is a 57-year-old male with bowel obstruction accompanied by rectal cancer (SE, N3, P1, H3, M (-) stage IV) who underwent a Hartmann operation with D3 lymph node dissection on July 6, 2000. The histopathological findings revealed a well-differentiated adenocarcinoma (se, INFbeta, n3, ly2, v2, p1). From the 11th postoperative day, combination chemotherapy using 5-FU 750 mg/day and LV 300 mg/day was performed once a week. When he underwent 5 combination chemotherapy treatments, adverse effects of grade 3 occurred, and the serum CEA level rose rapidly. We changed his regimen at that time. He underwent 2 courses of combination chemotherapy with 5-FU 500 mg/day and CDDP 10 mg/day for 5 days. Additional courses of combination chemotherapy with 5-FU 500 mg/day, LV 25 mg/day and CDDP 10 mg/day were performed weekly in the outpatient department. The treatment was effective, and a complete response (CR) was noted 4 months after the chemotherapy. The same combination chemotherapy was performed biweekly for one year after CR. The patient has been receiving a subsequent single administration of UFT and has remained in remission for 3 years and 7 months after surgery.     

A case of advanced gastric cancer with paraaortic lymph node metastasis reaching long-term survival by TS-1 treatment

A 62-year-old male patient with paraaortic lymph node metastasis of type 2 gastric cancer underwent distal gastrectomy with partial resection of transverse colon. MTX/5-FU sequential therapy was performed 5 times as adjuvant chemotherapy. After that TS-1 was administered on a 4-week dosing regimen with a 2-week interval between sessions. The patient regimen was discontinued temporarily because of thrombocytopenia. Therefore the schedule was changed to a 2-week dosing regimen with a 1-week interval between sessions at 2 years after operation. Paraaortic lymph node size was then checked by abdominal CT one or two times a year. The size showed no change for 3 years after operation. Then, 3 years and 3.5 years later, CT follow-up did not show paraaortic lymph node or other organ metastasis. We judged the effect of TS-1 was CR. Now the patient is disease-free at 4 years after operation.     

A preliminary study of preoperative chemotherapy combining irinotecan and cisplatin in patients with gastric cancer with unresectable para-aortic lymph node metastases

BACKGROUND: A high response rate has been reported for chemotherapy combining irinotecan (CPT-11) and cisplatin (CDDP) against advanced gastric cancer. The strong anti-tumor activity of this regimen makes it very attractive as a preoperative chemotherapy. We conducted a preliminary study on preoperative chemotherapy with this regimen in patients with unresectable gastric cancer with para-aortic lymph node metastases to evaluate the feasibility of it as a treatment strategy. METHODS: Patients with unresectable para-aortic lymph node metastasis without distant hematogenous metastasis (H0, M0 and M1 LYM) and peritoneal dissemination (P0) were eligible for entry. The preoperative chemotherapy consisted of at least three cycles of CPT-11 (70 mg/m(2)) on days 1 and 15 and CDDP (80 mg/m(2)) on day 15, repeated every 4-6 weeks. Chemotherapy was followed by surgery with extended lymph node dissection in patients who achieved complete or partial responses and whose cancers were judged to be resectable. RESULTS: Six patients were entered into the study. In total, 18 cycles of chemotherapy were performed and five patients received at least three cycles. Objective partial responses were achieved in four patients. The major toxicities in the chemotherapy were neutropenia and diarrhea, but these were clinically acceptable. Four patients underwent surgery after the chemotherapy, and macroscopically complete resections with extended lymph node dissection were achieved in two patients. There were no therapy-related deaths. We found no pathological complete responses, but observed a definite histopathological effect caused by the chemotherapy in surgical specimens. The median survival time of all patients was 12 months. The longest survival without relapse is >6 years from the start of therapy. CONCLUSIONS: We conclude that preoperative chemotherapy with CPT-11/CDDP therapy is feasible in patients with advanced gastric cancer and that the regimen is safe when followed by surgery. Further clinical studies with larger numbers of patients are warranted to evaluate the efficacy of this strategy.     

Stage IV gastric cancer patient who underwent palliative gastrectomy showing complete response to induction therapy with methotrexate plus 5-fluorouracil and secondary treatment with oral TS-1

We describe our experience with a patient who had undifferentiated gastric carcinoma with extensive lymph node metastasis, including para-aortic lymph-node metastasis, and had a complete response to induction therapy with methotrexate plus 5-fluorouracil (sequential therapy with MTX, 5-FU, and Leucovorin) and secondary treatment with oral TS-1. The patient was a 71-year-old woman with a massive gastric tumor (signet ring cell carcinoma), occupying most of the stomach. A computed tomographic (CT) scan revealed para-aortic, celiac, and common hepatic lymph-node metastases. Stage IV disease was diagnosed. Palliative total gastrectomy was performed to control bleeding and to improve oral intake of food. Two courses of induction therapy with MTX, 5-FU, and Leucovorin were started 3 weeks after surgery. A CT scan revealed residual lymph node metastasis. The response was assessed to be no change, but the levels of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 improved from 7,028 ng/ml and 726 U/ml 3 weeks after surgery to 2,832 ng/ml and 281 U/ml, respectively. Secondary treatment with oral TS-1 was begun, and a CT scan showed distinct shrinkage of lymph-node metastases. There was no serious toxicity. The levels of CEA and CA19-9 decreased markedly to 2.9 ng/ml and 16 U/ml, respectively, about 6 months after surgery and remained at 3.7 ng/ml and 16 U/ml, respectively, about 1 year after surgery.     

A case of recurrent sigmoid colon cancer with adrenal and para-aortic lymph node metastasis successfully treated by operation and chemotherapy

We report a case of 57-year-old woman suffering from advanced sigmoid colon cancer with adrenal and para-aortic lymph node recurrence. Sigmoidectomy was performed for sigmoid colon cancer in January 2002. Pathological staging was Stage II (pT3, pN0, pM0, Cur A). She received a UFT + CPT-11 regimen as preoperative chemotherapy for liver metastasis (S2, S7) from December 2002. A partial liver resection (S2, S7) was performed for liver metastasis in July 2003, and the UFT + CPT-11 was introduced as adjuvant chemotherapy. However, adrenal and para-aortic lymph node recurrence was detected in February 2007, and mFOLFOX6 was performed as preoperative chemotherapy. Right adrenalectomy and para-aortic lymph node dissection was performed in July 2007. mFOLFOX6 as postoperative chemotherapy was done, mFOLFOX6 + bevacizumab was started because of CEA increase. The chemotherapy was performed for 23 courses and temporarily stopped due to adverse reactions, such as peripheral neuropathy (grade 2), general fatigue (grade 1), and nausea (grade 1). She had no recurrence for almost 3 years after a resection of adrenal and para-aortic lymph node metastasis.     

A case of multiple liver metastases from colon cancer successfully treated with pharmacokinetic modulating chemotherapy

The present patient was a 54-year-old woman with anemia. After examination to identify the cause of anemia, she was diagnosed with sigmoid colon cancer and multiple liver metastasis. Sigmoid colectomy and insertion of an intra-hepatic arterial catheter were carried out. Histopathological examination of the resection specimen revealed well-differentiated adenocarcinoma, with a depth of tumor invasion of ss and positive lymph node metastasis. Pharmacokinetic modulating chemotherapy (PMC) was performed after the operation. The PMC consisted of oral UFT 300 to 400 mg/day every day and continuous arterial infusion of 5-FU 750 to 1,000 mg/24 h once a week. On a CT scan of the abdomen performed 6 months after the operation, the liver metastasis had disappeared and the patient was in complete remission (CR). PMC was continued, but the hepatic artery became occluded 1 year and 11 months after the operation, and so PMC was replaced by systemic chemotherapy of 5-FU plus levofolinate at 2 years after the operation. This chemotherapy was discontinued after 3 courses. At present, 2 years and 10 months after the operation, the patient remains in CR and is followed as an outpatient.     

Salvage combination chemotherapy with docetaxel, ifosfamide and cisplatin (DIP): successful treatment of a case with metastatic testicular immature teratoma

We present a case of metastatic testicular immature teratomathat was successfully treated despite resistance to standardchemotherapy and unsuccessful salvage surgery. At first, BEP(bleomycin, etoposide and cisplatin) treatment was performedbut failed. The patient underwent incomplete retroperitoneallymph node dissection. He was then referred to us. By the timeof the referral lung and mediastinal lymph node metastasis hadappeared and para-aortic lymph node metastasis had grown larger.We administered the DIP (docetaxel, ifosfamide and cisplatin)regimen as a second line chemotherapy, which was effective with82% reduction of para-aortic lymph nodes, 88% of mediastinallymph nodes and 85% of lung metastasis. We performed para-aorticlymph node dissection followed by resection of lung metastasisand mediastinal lymph node dissection. The patient is now followed-upat the outpatient clinic without evidence of recurrent disease3.5 years after the last surgery.     

Two cases of stage IV gastric cancer undergoing adjuvant surgery after down staging by chemotherapy

CASE 1: A 72-year-old man with epigastralgia was diagnosed with gastric cancer and referred to our hospital. An abdominal CT scan revealed liver metastasis and para-aortic lymph node metastasis. He was treated with S-1+CDDP. After 4 courses of this treatment, the liver metastasis and para-aortic lymph node metastasis disappeared, and adjuvant surgery was performed. There has been no recurrence for 16 months postoperatively. CASE 2: A 66-year-old man with anorexia was diagnosed with gastric cancer and referred to our hospital. An abdominal CT scan revealed para-aortic lymph node metastasis. He was treated with S-1+CDDP. After 9 courses of this treatment, para-aortic lymph node metastasis disappeared, and adjuvant surgery was performed. Eight months after the operation, lymph node metastases were confirmed by abdominal CT scan, and he was treated with chemotherapy as an outpatient as of 13 months after the operation. We experienced two cases of Stage IV gastric cancer undergoing adjuvant surgery after down staging by chemotherapy. It was suggested that adjuvant surgery to highly advanced gastric cancer could improve the prognosis of patients.     

Two patients with recurrent colon cancer who underwent surgery following a combination of irinotecan and UFT

One patient with pulmonary metastasis from colon cancer and one with para-aortic lymph node metastasis were treated with a combination of irinotecan and UFT. Irinotecan (100 mg/m2) was given by 24-hour intravenous infusion on day 1, and UFT (600 mg/day) was given orally on days 3 to 7 and days 10 to 14 of a 2-week course, which was then repeated. In the patient with pulmonary metastasis, the lesions in the lung resolved after 7 courses of chemotherapy. Surgery was performed after 10 courses. The patient with para-aortic lymph node metastasis had a partial response after 4 courses of chemotherapy, and underwent surgery after 6 courses. The only adverse effects were grade 2 myelosuppression and hair loss, none of which were severe enough to require treatment. With this chemotherapy regimen, patients are admitted for two days biweekly for 24-hour intravenous infusion of CPT-11. Thus, most of the treatment can be performed on an outpatient basis. The combination of irinotecan and UFT is expected to be useful for metastatic or recurrent colon cancer.     

A case of unresectable rectal cancer with liver and pulmonary metastases that responded remarkably to pharmacokinetic modulating chemotherapy

We treated a patient with unresectable rectal cancer with multiple liver, pulmonary and lymph node metastases that responded remarkably to pharmacokinetic modulating chemotherapy (PMC). The patient was a 63-year-old male. Colonoscopy showed a type 3 advanced lower rectal cancer. Examinations by computed tomography and chest X-ray revealed unresectable rectal cancer invading the sacrum and bladder with multiple liver and pulmonary metastases and swollen para-aortic lymph nodes. The patient was treated by colostomy and postoperative PMC. UFT (400 mg/day) was orally administered daily and a continuous infusion of 5-FU (1,000 mg/24 h) was given once a week. After 10 courses of treatment with PMC, the primary lesion was remarkably reduced. This chemotherapy also produced partial responses in the pulmonary metastases and para-aortic lymph node swelling. The patient experienced few side effects and had good QOL in the terminal stage. This chemotherapy regimen appears to be an effective and promising therapy with few side effects, even for patients with unresectable advanced colorectal cancer.     

A case of gastric cancer with abdominal para-aortic lymph node metastases responding to TS-1 + CDDP neoadjuvant chemotherapy

The patient was a 54-year-old woman with extremely advanced gastric cancer of type 3. A CT scan of the abdomen showed enlargement of many huge abdominal para-aortic lymph nodes. Combined chemotherapy of TS-1 and CDDP was planned in order to reduce the tumor. TS-1 (100 mg/body/day) was administered for 21 days followed by 14 days rest as one course. CDDP (96 mg/body) was administered 8 days after the start of TS-1. After 2 courses of treatment, a CT scan showed complete disappearance of lymph node metastasis, and no high grade toxicities. Therefore, one month after the completion of the chemotherapy, total gastrectomy and D2 lymph node dissection were performed. The histological effect was judged to be grade 1a-1b. There were no viable cancer cells in any lymph nodes. One year after surgery, the patient is still alive without recurrence. Neoadjuvant chemotherapy with TS-1 and CDDP is so effective that can it be adapted for advanced gastric cancer with para-aortic lymph node enlargement for downstaging.     

A case of the 5-year survivor of ascending colon cancer associated with synchronous multiple liver metastasis and peritoneal dissemination successfully treated with combination therapy of systemic and hepatic arterial infusion chemotherapy

A 67-year-old woman was diagnosed by a series of examinations as having ascending colon cancer with synchronous multiple liver metastasis. She underwent an operation after the PTPE (percutaneous transhepatic portal vein embolization) to the right lobe of the liver, as we considered that the metastatic liver tumors were all resectable. In the surgery, we identified seven peritoneal tumors and a lymph node swelling. We then pathologically diagnosed them as being peritoneal dissemination (p3) and lymph node metastasis (n2(+)). Therefore, hepatectomy was not performed, but the right hemicolectomy (D2) and insertion of an arterial infusion catheter into the hepatic artery were performed. In addition, all seven peritoneal tumors were resected. After being discharged from hospital, she was treated as an outpatient with the combination chemotherapy of systemic intravenous administration (5-fluorouracil or 5-FU, 2,500 mg/month) and hepatic arterial infusion (5-FU, 1,500 mg/week) for 16 months. Then, she continued to take tegafur uracil (300 mg/day) by mouth for 39 months. The metastatic liver tumors were gradually reduced and resulted in complete response (CR) for 20 months after the operation. She has been in remission for the past 5 years without recurrence. During the treatment, we noticed a complete atrophy that was sustained in the right lobe of the liver to which PTPE was performed. As far as hepatic arterial infusion chemotherapy is concerned, our case study was interesting and effective.     

A case of advanced colon cancer with para-aortic lymph node metastasis responding greatly to treatment by adjuvant chemotherapy of low-dose CPT-11 on an outpatient basis

We administered an adjuvant chemotherapy of a bi-weekly low-dose CPT-11 + 5-FU on an outpatient basis to a patient with advanced sigmoid colon cancer and para-aortic lymph node metastasis. After 3 months, tumor markers fell to normal levels and the regression rate in the lymph node was over 80%. Throughout the period of treatment, there were no side effects, and there was no sign of recurrence for 6 months. In conclusion, we consider that with low-dose CPT-11 + 5-FU chemotherapy on an outpatient basis, the patient can maintain a high quality of life and show a massive effect, and that this regimen can be used as a first-line chemotherapy for advanced colon cancer.     

A case of AFP producing early gastric cancer successfully treated with small dose CDDP and 5-FU (PF) therapy]

A case of AFP producing early gastric cancer successfully treated with a small dose of CDDP and 5-FU therapy administered intermittedly is reported with a review of the literature. A 63-year-old male was admitted to our hospital because of liver metastasis with a high level of serum AFP (185.8 ng/ml) three months after gastrectomy. Systemic chemotherapy was performed twice with a regimen of CDDP 20 mg and 5-FU 750 mg/day in 5 days. After hepatic arterial infusion chemotherapy (HAIC) was performed once, the patient obtained partial response according to CT scan and was discharged. After he underwent HAIC once as an outpatient, liver metastasis completely disappeared 5 months after surgery. He was administered oral 5-FU, 150 mg and Krestin 3.0 g/day and underwent HAIC with CDDP 20 mg and 5-FU 750 mg/day every 2 weeks. After serum AFP level was returned to the normal range 7 months after surgery; HAIC was performed every 4 weeks and continued until one year after surgery. One year and 11 months after surgery, serum AFP remains within the normal limit and there is no evidence of recurrence.     

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.     

Combination chemotherapy with methotrexate and 5-Fluorouracil and surgery for advanced gastric-cancer with liver and lymph-node metastases - a case-report

We report on a case of advanced gastric cancer with multiple liver metastasis and lymph node metastases in a 65-year-old Japanese man. He was treated with sequential intravenous administration of moderate-dose methotrexate 1 (MTX) and 5-fluorouracil (5-FU) preoperatively. After eleven cycles of the combination chemotherapy, the findings of liver and lymph node metastases diminished dramatically and the tumor could be resected for a potential cure, using a total gastrectomy and combined hepatectomy. The resected specimen revealed a slightly elevated lesion and a somewhat shallow ulceration due to chemotherapy. Histologically, there was an infiltration of poorly differentiated adenocarcinomas with medullary structure in the muscularis mucosae with fibrous change. The liver was metastasized, but there was no evidence-of lymph node metastasis. We believe that combination chemotherapy of MTX and 5-FU can be effective against gastric cancer.