Diagnosis and treatment of mediastinal teratoid tumors

Among anterior mediastinal tumors affecting male patients of around 20 years old, mediastinal malignant teratoid tumor must be considered as one of the possibilities. Malignant teratoid tumor can be classified as seminoma, non-seminoma or mixed, according to clinical behavior. In the non-seminoma group, AFP and/or HCG can be the specific markers in the diagnosis or assessment of the effect of treatment. Chemotherapy with CDDP must be the first choice of treatment in these types of tumor, just as chemotherapy is the first choice of therapy in the treatment of small cell lung cancer, and surgery must be the adjuvant treatment to chemotherapy. On the other hand, seminoma can be treated by surgery and radiation, which has been proven to yield a good prognosis. In cases of seminoma which produces HCG and/or AFP, chemotherapy with CDDP must be added to surgery and radiation as in non-seminomatous mediastinal teratoid tumors, because the production of such markers in seminoma is considered to be one of the poor prognostic factors in the treatment of seminomatous mediastinal teratoid tumors.     

纵隔生殖细胞瘤临床分析

目的:分析生殖器外纵隔生殖细胞瘤诊断和影响预后的因素。方法:65例纵隔生殖细胞瘤均行开胸手术治疗。单纯完全摘除肿瘤59例;姑息性切除1例;肿瘤摘除联合肺叶切除或胸膜纤维板剥脱术3例;开胸探查2例。恶性生殖细胞瘤术后均行辅助放、化疗。结果:良性畸胎类肿瘤手术摘除或合并肺、胸膜切除后效果良好。恶性生殖细胞瘤,尤其是精原细胞瘤切除后,辅助放、化疗仍可获得较好的远期生存。3年生存率66.7%。结论:纵隔生殖细胞瘤是常见的纵隔肿瘤,诊断后积极手术治疗可获得较好的结果。     

Multidisciplinary treatment for advanced bladder cancer--a case report

The patient was a 63-year-old woman who had been diagnosed with advanced bladder cancer with renal dysfunction and bilateral bulky pulmonary metastasis. Initially, the primary lesion was resected and the implantation of an infusion catheter and port system was performed. Following surgery, she received intermittent intra-arterial (IA) low-dose CDDP chemotherapy via the infusion port and concurrent bronchial arterial infusion and radiation (40 Gy for the left lung). About 3 months later, the right and left lung metastases were reduced 63% and 91%, respectively, and a right lower lobectomy was performed. CDDP was administered through the outpatient clinic ever since. From January 2001, we began to use docetaxel (TXT) for CDDP because of continuous grade 2 nausea and appetite loss. There were no adverse effects by TXT. Repeated IA chemotherapy was discontinued from June 2001 because of neurological symptoms. In September 2001, a left skull base metastasis was detected and was treated by radiation 40 Gy. In November 2002, a left patella metastasis appeared and was treated by IA chemotherapy with angiotensin II and radiation 30 Gy. We confirmed that multidisciplinary treatment contributed to her approximately 3-year survival with good QOL. The cancers in both lungs could be kept under control until her death.     

Successful treatment of a pretreated elderly case of small-cell lung carcinoma with continuous five-day intravenous infusion of cisplatin plus etoposide]

A 78-year-old man was admitted to our hospital with dyspnea in June 1988, and diagnosed as having small-cell lung carcinoma by cytological findings of pleural effusion. He was treated three times with CAV (cyclophosphamide, doxorubicin, vincristine) therapy and a partial response was achieved. In March 1989, he was again admitted complaining of right dull hypochondralgia accompanied by enlargement of primary tumor in the right lower lobe of the lung and metastases to mediastinal and intraabdominal lymph nodes. Because it was an aged and recurrent case, he was treated with continuous five-day infusion of etoposide, 30 mg/m2/day and CDDP, 18.5 mg/m2/day. After the second course, subjective symptoms clearly disappeared and swelling of mediastinal and intraabdominal lymph nodes was markedly reduced on computed tomography. No severe side effects except for moderate myelosuppression, alopecia and nausea were observed. This regimen appears useful in the treatment of small-cell lung carcinoma in elderly patients.     

Regional immunochemotherapy for liver metastasis of esophageal cancer in a patient with variant hepatic artery

A patient with metastatic liver tumor from esophageal cancer having an anomaly of the hepatic artery was treated by regional immunochemotherapy using two infuserports, which were implanted transfemoral to the right and the left hepatic artery, respectively. The schedule of this therapy was as follows: CDDP (30 mg/m2) on day 1 and 8, 5-FU (1,000 mg/m2) on day 1, 2, 8, 9, 15 and 22, and OK-432 (1 KE/body) on day 3-6, 10-13 and 16-20 were administered via the hepatic artery; and OK-432 (5 KE/body) was also injected intramuscularly three times a week. After the first course of this therapy was performed via the left hepatic artery, metastatic foci in the left lobe regressed, while those in the right lobe progressed markedly. Thereafter, the second course was performed via the right hepatic artery, and then the third course was via both right and left hepatic artery. Following these trials, metastatic foci of the right and the left lobes showed remarkable regression. These results suggest that the effect of immunochemotherapy is closely related with the local concentration of anti-cancer agents.     

Successful treatment of mediastinal seminoma with combination chemotherapy of cis-diamminedichloroplatinum (CDDP), vinblastine (VBL), and bleomycin (BLM)

Complete response (CR) has been achieved in a case of advanced mediastinal seminoma using PVB therapy (CDDP, VBL, BLM). A 21-year-old man visited our department with the complaint of superior vena cava syndrome. Chest X-ray film, ultrasonography and CT scan revealed a large anterior mediastinal mass. Histological proof of mediastinal seminoma was obtained by needle biopsy. The patient was treated with a combination chemotherapy, consisting of CDDP, VBL and BLM according to Einhorn's PVB regimen. After three courses of this regimen, complete disappearance of the tumor was obtained. The patient underwent further radiation treatment (Linac: 4,000 rad), as a salvage therapy, at the anterior mediastinum, and has since been doing well without any sign of recurrence for a follow-up period of nine months.     

Successful hepatic arterial infusion therapy of CDDP/5-FU/IFN-beta3 for recurrent hepatocellular carcinoma

A 52-year-old male patient was admitted to our hospital for a further examination of liver tumor. He was positive for hepatitis C virus antibody. CT scanning revealed two hyper vascular tumors at the lateral segment of the liver and another one located at segment 8, an indication of hepatocellular carcinoma (HCC). Ascites were not detected and major serological findings were T-Bil 1.1 mg/dl, Alb 3.5 g/dl, ICG R15 12% and PT 88%. Lateral segmentectomy and a partial resection of the segment 8 were performed at the same time. An insertion of catheter in hepatic artery via gastroduodenal artery was carried out. Dehydropyrimidine dehydrogenase (DPD) activity of the tumor was 157 pmol/min/mg proteins. Recurrence was detected one year after the operation at segments 4 and 8. Arterial infusion chemotherapy using CDDP (10 mg), 5-FU (1,000 mg) and IFN-beta 3MU (continuous infusion for 5 days) was started two months later, and a complete response was achieved. The chemotherapy continued as long as severe adverse effects were not observed. However, two months after the tumor disappearance, the treatment discontinued due to occlusion of the infusion system. Recurrence occurred in two months at the same location where the previous tumor was. In conclusion, these results suggest that arterial chemotherapy using CDDP/5-FU/IFN-beta against HCC may be beneficial.     

A case report of inflammatory breast cancer effectively treated with cis-platinum

A 50-year-old woman with bilateral inflammatory breast cancer (T4, N1b, M1, Stage IV) underwent right extended radical mastectomy and left modified radical mastectomy following pre-operative administration of carcinostatics (ADM, 5-FU) and irradiation. However, tumor recurrence was observed at the skin and right pleural cavity after the operation. Adriamycin-containing combination chemotherapy and radiation therapy were performed, but no significant response was obtained. CDDP was then administered intravenously at a daily dose of 62.5 mg/m2 at intervals of 60 days. The pleural effusion disappeared and the extent of skin metastasis was reduced, resulting in partial response which lasted for 90 days. The serum CEA level decreased from 13.1 ng/ml to 2.3 ng/ml. As the side effects of this therapy, slight nausea, vomiting and general fatigue were observed. This result suggested that CDDP is an effective drug for inflammatory breast cancer.     

High-dose chemotherapy with peripheral blood stem cell auto transplantation for an intractable case of mediastinal seminoma

HDC with PBSCT is effective for some intractable cases with malignant neoplasma. We encountered an intractable case of mediastinal seminoma treated by HDC with PBSCT. The patient was a 25-year-old man with mediastinal seminoma. He had undergone chemo-radiotherapy several times and salvage surgery for the mediastinal tumor and chest wall recurrence since September 2001. He was referred to our clinic for management of recurrent seminoma in the chest wall in January 2004. In our clinic, chemo-radiotherapy consisting of cisplatin and etoposide was performed. The tumor size decreased transiently, but re-growth was observed 2 months after chemo-radiotherapy. We then performed HDC with PBSCT twice without any lethal complication. Now, the patient is well and disease-free 1 year after HDC with PBSCT.     

A case of unresectable cholangiocellular carcinoma treated with surgery followed by combination chemotherapy

The patient was a 44-year-old man, who was investigated for lateral abdominal pain and liver dysfunction, and subsequently referred to our department with a diagnosis of unresectable intrahepatic cholangiocellular carcinoma (CCC). Radiological examinations revealed the huge mass in the right lobe of the liver with intrahepatic metastasis in the left lobe. The main tumor was surgically removed, but the metastases were not removed. A month after the operation, a subcutaneous implant reservoir was indwelled for repeated transcatheter hepatic arterial chemo infusion therapy (5-fluorouracil 500 mg/day continuous infusion, day 1-5, and CDDP 10 mg/day, day 1) from the right femoral artery. After 15 courses of home anti-cancer chemotherapy, abdominal CT revealed that the size of intrahepatic metastasis in the left lobe of the liver had not shown growth, whereas other metastitic sites popped up in the caudate lobe, which were free of chemical agent flow. There was no major complication related to the chemotherapy throughout the post-treatment course. Although he maintained a good level of QOL, he refused further chemotherapy due to depression. He died of liver failure 7 months after the operation. In conclusion, volume reduction surgery followed by transcatheter hepatic arterial chemo infusion might be promising as an effective therapy for non resectable CCC.     

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.     

A case of Vp4 hepatocellular carcinoma treated with surgical resection and continuous intrahepatic artery infusion chemotherapy of low-dose cisplatin and 5-fluorouracil

A 49-year-old woman was admitted to our hospital because of hepatocellular carcinoma (HCC). She had no hepatitis virus. Serum AFP and PIVKA-II levels were as high as AFP 329.4 ng/ml (AFP-L3% 73.1%) and 281 AU, respectively. Portal venous thrombus was observed from the right portal branch to left portal branch and superior mesenteric vein. An extended right hemihepatectomy with extraction of portal venous thrombus was performed. On postoperative day 8, low-dose cisplatin (10 mg/day for 5 days/week) and 5-fluorouracil (250 mg/day for 5 days/week) were administered through the hepatic artery for 4 weeks. After chemotherapy, one intrahepatic metastasis appeared and RFA was performed for this tumor. At 16 months after surgery, she had multiple lymph node metastases and died at 20 months after the surgery without intrahepatic metastasis. Low-dose CDDP/5-FU intra-hepatic artery infusion chemotherapy was effective for prevention of intrahepatic recurrence after resection of HCC with portal venous thrombus.     

A case of local recurrence of rectal cancer responding to local intraarterial infusion therapy]

A 42-year-old male developed pain in the right gluteal region due to local recurrence after curative resection of advanced lower rectal cancer. Radiotherapy (60 Gy) was performed, but satisfactory results were not obtained. Therefore, a reservoir was placed lowing cannulation of the internal iliac artery. The chemotherapy, in addition to intravenous administration of low dose CDDP (20 mg), included local intraarterial infusion therapy with 5-FU (1,500 mg/5 hour) once per week. After 10 courses of this chemotherapy (total dose: CDDP, 200 mg; 5-FU, 15,000 mg), the pain decreased, and the tumor size was reduced without side effects, improving the patient's QOL. At present, multidisciplinary treatments including such chemotherapy and radiotherapy is performed for local recurrence of rectal cancer, but adequate results are often not obtained. Local intraarterial infusion chemotherapy via the internal iliac artery accompanied by changes in blood flow can be safely performed on an outpatient basis, and appears to be effective for local recurrence of rectal cancer.     

A case of gastric cancer with multiple liver metastases responding to combined hepatic arterial and aortic infusion chemotherapy with cisplatinum, 5-fluorouracil,and levofolinate calcium

A 64-year-old man who had type IIc-like advanced gastric cancer with multiple liver metastases was admitted to our hospital. He underwent combined hepatic arterial and aortic infusion chemotherapy with cisplatinum (CDDP), 5-fluorouracil (5-FU), and levofolinate calcium (l-LV). After 4 weeks (2 courses) of chemotherapy, a partial response was achieved for the hepatic metastasis. Therefore, distal gastrectomy, right hepatectomy combined with caudate lobectomy, partial resection of the hepatic right lobe, and microwave coagulation therapy of the residual tumor of the hepatic right lobe were performed. With this operation, all tumor cells were removed or killed. Histopathologically, almost all of the primary tumor was fibrous tissue, and only a few sections of moderately differentiated adenocarcinoma observed in the subserosal layer. In the periphery of the metastatic lesion, residual well to moderately differentiated adenocarcinomas were observed, and in the center, only necrotic tissue was seen. The postoperative course was uneventful. Now, one year and seven months after the operation, he is followed as an outpatient. Combined hepatic arterial and aortic infusion chemotherapy with CDDP, 5-FU, and l-LV is thought to be an effective regimen for advanced gastric cancer with multiple liver metastases.     

A case report--intrahepatic arterial infusion with CDDP and S-1 administration can elicit long-term survival for the patient with recurrenced intrahepatic cholangiocarcinoma after resection

To cure intrahepatic cholangiocarcinoma (ICC), only a surgical resection is the potential treatment at present. However, recurrence tumors in residual liver and/or distant organs even after curative surgery are commonly experienced in clinical course. Unfortunately the potential treatment for this recurrent disease is not established at present. Accordingly, the prognosis of this recurrent ICC is extremely poor. Here, we report the prolonged survival case with recurrent ICC after hepatic resection followed by combined therapy of intrahepatic arterial infusion with CDDP and S-1 administration. The patient was a 71-year-old female. She had been treated for hepatitis B for last 5 years. After that, liver tumor of 30 mm in diameter was detected in S1/8 by abdominal CT examination. Subsequently, caudate lobectomy and partial resection of Segment 8 were performed under the diagnosis of Hepatocellular carcinoma in Osaka university hospital. The pathological stage was T2N0M0, Stage II with moderately differentiated intrahepatic cholangiocarcinoma. As the recurrence tumor was found in Segment 4 of residual liver, we started a treatment with intrahepatic arterial infusion with CDDP and S-1 administration, immediately. These combined therapy displayed beneficial effects and a recurrent liver tumor was well controlled. At present, this patient is still survived for over 5 years after the operation.     

Treatment of advanced and recurrent squamous carcinoma of the uterine cervix with constant intraarterial infusion of cisplatin

Twelve patients with primary or locally recurrent squamous carcinoma of the cervix were treated with constant internal iliac artery infusion of cisplatin (CDDP) via a totally implantable chemotherapy pump. Seven previously untreated patients received standard external and interstitial radiotherapy (RT) in conjunction with CDDP infusion. Five patients with isolated pelvic recurrences received CDDP therapy only. The chemotherapy pump was refilled weekly on an outpatient basis. All nine evaluable patients developed unilateral or bilateral lower extremity pain which responded to dosage reduction. No renal or marrow toxicity was seen. Both of the evaluable patients treated for recurrent tumor died 32 and 60 weeks after initiation of treatment. The seven patients treated primarily with RT + CDDP infusion include one who expired with persistent tumor and one with no evidence of disease (NED) after exenteration for a pelvic recurrence at 48 and 85 weeks respectively. The five remaining patients are NED at 12 to 60 weeks. Constant internal iliac artery infusion of CDDP via an implantable chemotherapy pump can be performed with acceptable toxicity. The preliminary results suggest that further study in previously untreated undergoing concurrent radiotherapy is warranted.     

Intra-arterial chemotherapy for head and neck cancer

There are historically speaking, three methods of intra-arterial infusion for head and neck cancer. Recently, daily concurrent chemoradiotherapy using new superselective intra-arterial infusion via superficial temporal arterial artery is noted. A catheter with a curved tip is inserted superselectively to the feeding artery of the tumor via the superficial temporal artery. Long-term catheterization is possible in this method. Thirty-five patients with stage III or IV oral cancer were treated. Radiotherapy (total dose:40 Gy/4 weeks) and superselective intra-arterial infusion chemotherapy using DOC (total dose: 60 mg/m2, 15 mg/m2/week) and CDDP total dose: 100 mg/m2, 5 mg/m2/day) were concurrently performed daily, followed by surgery. In 31 patients, intra-arterial infusion was successful(successful rate: 88.6%), and no major complication was observed. The clinical effects were CR in 25 patients(80.6%), and pathological effects of resected tumor after surgery were pathological CR in 28 (90.3%). This method promises to be new strategy of choice for the treatment of head and neck cancer.     

Successful treatment of multiple pulmonary and peritoneal recurrence of hepatocellular carcinoma with bronchial artery infusion therapy and PEIT followed by surgery--a case report

A case of hepatocellular carcinoma, successfully treated with multimodal loco-regional treatments, is reported. An 80-year-old male presented with multiple pulmonary and peritoneal metastases 4 months after right heimihepatectomy for ruptured HCC. Bronchial artery infusion of mitomycin C induced pulmonary tumor regression and stabilization. Peritoneal tumor was treated by arterial infusion of SMANCS, followed by percutaneous injection of absolute ethanol, which ended in surgical removal in 28-postoperative month due to abscess formation. He had been well until right adrenal and left pulmonary metastases appeared. Resection of both metastases was carried out in 39-post hepatectomy month. Recurrent left pulmonary metastasis was treated with two sessions of bronchial artery infusion with no effect this time. Video-assisted partial resection of the left lung was performed in 54 post-hepatectomy month. But his AFP level kept rising. Eventually pulmonary metastasis recurred and tumor thrombus reached the left atrium 58 months after hepatectomy. He wanted no more treatment. He died of cerebral infarction caused by tumor thrombus. He enjoyed a good QOL for five years through multimodal loco-regional treatments.     

Consecutive intra-arterial infusion of cis-diamminedichloroplatinum with continuous intra-arterial infusion of 5-fluorouracil in locally advanced ovarian cancer

Consecutive intraarterial infusion of cis-diamminedichloroplatinum (CDDP) with continuous intraarterial infusion of 5-fluorouracil (5-FU) (250 mg/day) was administered to 10 patients with locally advanced (peritonitis carcinomatosa) ovarian cancer. The dose of CDDP was 10 mg/5 min/body/day and it was administered for about 10-20 consecutive days per one course. Each course was repeated at about 3-week intervals. The main dose-limiting factor was the number of peripheral leucocytes. The results were 6 PR, 1 MR and 2 NC out of 9 evaluable cases, all of whom had had previous therapy. The antitumor effect needed over 200 mg of intraarterial CDDP and the response lasted from 2 to more than 9 months. Among 6 patients who obtained PR, 4 had failed to respond to intravenous or intraperitoneal infusion of CDDP, which suggested that a high concentration and a critical drug gradient across the tumor cell membrane were more essential for a significant tumor cell kill, with CDDP, than the time of exposure. The toxic effects of intraarterial infusion of CDDP were almost absent as compared with those of intravenous infusion, which consisted of nausea and vomiting. Renal dysfunction was also mild. Other toxic effects were not different from those observed in intravenous infusion. Our results with intraarterial infusion of CDDP clearly indicate that this approach can deliver a high therapeutic efficacy in patients with advanced ovarian cancer with markedly less toxic effects.     

Anaplastic sarcoma arising in a mature metachronous bilateral Wilms' tumor after irradiation and chemotherapy. Spontaneous versus induced malignant change

A 1-year-old male infant developed a classic Wilms' tumor of the left kidney. Treatment consisted of a left nephrectomy, chemotherapy, and irradiation to the left flank and associated abdomen. Two years later, a mass in the right kidney was discovered; open renal biopsy demonstrated a mature Wilms' tumor consisting entirely of rhabdomyomatous elements in the biopsy specimen. The patient was given a second course of chemotherapy and 2000 rad to the right flank. Over the next 8 years, the mass continued to grow without evidence of metastatic spread. Renal function deteriorated secondary to compression of the surrounding normal renal parenchyma by the enlarging tumor; creatinine clearance from the solitary kidney decreased from 120 ml/min to 40 ml/min during the 12 months prior to removal of the lesion. Via a nephron-sparing procedure, the 3400 g tumor measuring 19 cm X 16 cm X 9 cm was enucleated from the right kidney without compromise to the remaining normal tissue. Pathologic examination of the surgical specimen revealed a mature Wilms' tumor with a malignant anaplastic sarcoma arising in the central portion. Postoperatively, the patient received a third course of chemotherapy with no irradiation to the tumor bed. Currently, he is disease-free with normal renal function more than 20 years after diagnosis of the metachronous bilateral Wilms' tumor. This is the first reported case of an anaplastic sarcoma arising within a Wilms' tumor; this individual also is the longest surviving patient with metachronous Wilms' tumor. The various possibilities regarding the development of the anaplastic sarcoma within the Wilms' tumor of the right kidney are discussed, including the possible role of chemotherapy and irradiation in the development of a second malignancy.