A 74-year-old man, who had mantle cell lymphoma treated with several anticancer drugs including rituximab, was admitted to our hospital because of gait disturbance and progressive paralysis of the right lower limb. T2-weighted MR image showed multiple high intensity lesions in the left parietal lobe. Suspected of being cerebral invasion of lymphoma, high-dose methotrexate was begun, but the patient died of sepsis without neurological improvement. At autopsy, it was proven that neurological symptoms had been caused by progressive multifocal leukoencephalopathy (PML). PML should be considered as a possible complication of heavily treated lymphoma.

The response criteria proposed by European Leukemia Net are useful to predict the prognosis of de novo chronic myeloid leukemia (CML) patients in the chronic phase (CP) treated with imatinib. However, the clinical significance of late suboptimal response, which is defined as the achievement of CCgR without MMR after 18 months, is controversial. In this study, we retrospectively analyzed the clinical courses of 16 CML-CP patients, who satisfied the criteria for late suboptimal response. The median duration of imatinib treatment was 62 (25∼87) months. The median starting dose of imatinib was 400 mg/day. Imatinib dose was escalated to 600∼800 mg/day in 10 patients for various reasons. Among 4 patients who continued high-dose imatinib for late suboptimal response, 2 patients subsequently achieved MMR, and BCR-ABL mRNA transcript levels were decreasing in 2 patients. However, imatinib was kept at 300 or 400 mg/day in 6 patients. Among these six patients, 4 patients achieved MMR, while 2 failed to achieve MMR. None of 16 patients progressed to the acute phase or blast phase. Imatinib dose escalation was effective for late suboptimal response. Furthermore, a second tyrosine kinase inhibitor such as nilotinib may be more potent to reduce the risk of disease progression by achieving earlier MMR.

Transcatheter arterial chemoembolization (TACE) was performed as the initial therapy for advanced hepatocellular carcinoma (HCC). However, no effective chemotherapy has been established for patients who did not respond to TACE, and for those the therapy was not suitable. Since 2004, transcatheter arterial infusion (TAI) chemotherapy using fine-powder cisplatin has been applied at our department to such cases mentioned before. This report described the therapeutic results of TAI therapy and presented a case of HCC accompanied by portal vein tumor thrombus (PVTT) for which the therapy was effective.

We evaluated the effect of sorafenib and intermittent hepatic arterial infusion chemotherapy (HAIC) using cisplatin for unresectable advanced hepatocellular carcinoma (HCC).

We analyzed the treatment outcome and effect of sorafenib in advanced hepatocellular carcinoma. Nine patients were received the therapy of sorafenib between June 2009 and October 2009. The overall incidence of treatment-related adverse events was 87.5%. Grade 3 drug-related adverse events included a hand-foot skin reaction (two patients) and fatigue (one patient). Grade 2 hypertension (three patients), grade 1 diarrhea (two patients) and anorexia (four patients) occurred at this study. The response rate was 0% (CR/PR 0, SD 2, PD 6) and median overall survival length was 101 days. Now there are two patients undergoing the therapy of sorafenib. Effect of sorafenib in advanced hepatocellular carcinoma was not good in this study, and drug-related adverse events had a high rate. However, the continuous treatment was possible with dose modified chemotherapy.

Neoadjuavnt chemotherapy for liver metastasis of colorectal cancer implies issues about timing for resection and management for adverse events due to chemotherapy.

Recent advances in chemotherapy for colorectal cancer prolonged survival. Tumor necrosis may develop as a side effect of chemotherapeutic agents. Recently, radiofrequency ablation sometimes indicated to patients with colorectal liver metastasis, when hepatectomy cannot be performed due to impaired hepatic functional reserve or general condition. We experienced hepatectomy for colorectal liver metastasis containing necrotic foci which was induced by anti-cancer drugs and radiofrequency ablation. Massive liver necrosis and abscess developed in a patient with initially unresectable large liver metastasis 6 months after induction of mFOLFOX6 and bevacizumab. Chemotherapy was discontinued due to systemic inflammatory responses. Extended right hepatectomy resulted in both resection of the tumor and significant improvement of septic condition. Chemotherapy was re-started after the operation. Bevacizumab targeted to tumor-related vascular endotherial cells might be responsible for the massive tumor necrosis. Another patient with chronic renal dysfunction underwent radiofrequency ablation for colorectal liver metastasis 2 cm in diameter in the segment 7. Three months after ablation, the tumor grew very rapidly to 6 cm in diameter. After extended posterior sectorectomy of the liver, blood CEA levels were normalized. Resected specimen showed a massive tumor growth around the necrotic foci of radiofrequency ablation. Hepatectomy played significant roles in these patients with necrotic foci of the liver. Decision and timing of hepatectomy are very important to save the patient.

Cetuximab (Erbitux) is a targeted therapy that used to treat metastatic colorectal cancer. It is classified as a "monoclonal antibody" and "signal transduction inhibitor" by binding to epidermal growth factor receptors (EGFR). We report 6 patients who responded well to cetuximab out of 8 patients with recurrent/advanced colorectal cancer who have received the drug at our hospital since November 2008. Four patients were men and 2 were women, with their ages ranging from 48 to 77 years. The primary cancers were located in the rectum (n=1), sigmoid colon (n=4), and ascending colon (n=1). Performance status (PS) was 0-1. These patients were treated with cetuximab as second-line (n=1), third-line (n=3), fifth-line (n=1), or seventh-line (n=1) therapy. Three patients received cetuximab monotherapy, while the other 3 were given CPT-11 (150 mg/m2, every 2 weeks) as concomitant therapy. Among the 3 patients receiving combination therapy, 2 patients had already received treatment with FOLFIRI. Even in the cetuximab monotherapy group, a partial response (PR) was observed in 2 patients, demonstrating a strong cytoreductive effect. Tumor markers also showed large decreases, with the percent decrease at 1 month being 31.7% and 60.8% in the monotherapy and combination therapy groups, respectively, while it was respectively 14.1% and 29.5% at 2 months. The mean progression-free survival (PFS) time and the time to treatment failure (TTF) were respectively 3.0 months and 4.5 months in the monotherapy group versus 7.3 months and 9.3 months in the combination therapy group. Acneiform rash and paronychia occurred in all 6 patients.

Although combination of S-1 and cisplatin (CDDP) is a standard therapy for advance or recurrent gastric cancer patients, there are some cases where a CDDP administration is difficult for patients. We here report three such cases of gastric cancer treated by S-1 and docetaxel (DOC) combination therapy. Based on our three cases, we believe that S-1 and DOC combination therapy could be suitable for outpatients showing safety and efficacy.

We report a successful case of chemotherapy with oral fluoropyrimidines. The patient was an 81-year-old woman who complained epigastric discomfort. Endoscopy revealed a type 3 advanced gastric cancer, and the biopsy specimen was defined histologically as poorly-differentiated adenocarcinoma. She didn't hope for an operation, but agreed to receive chemotherapy. S-1 (80 mg/day) was administered for 14 days, followed by 7 days rest. This schedule induced grade 1 thrombocytopenia and fatigue after two weeks administration. Therefore, we reduced the administration dosage to 60 mg/ day. Almost complete response (CR) was observed after 8 weeks of S-1 administration. But she was admitted urgently to other emergency hospital for stumbling due to dizziness accompanied with vomiting and anorexia. We considered it was difficult to continue S-1 administration. Therefore, we changed S-1 to UFT-E and started from 300 mg/day. One month later, as the adverse effects were not recognized, we increased a dosage of UFT-E to 400 mg/day for the purpose of more dose intensity. After 6 months, CR was confirmed continuously. We reduced UFT-E to 300 mg/day, and CR has been continued for 3 years until now without any adverse events. There was no evidence regarding the best timing to syop anticancer administration. As the adverse effect was very mild and her quality of life improved, we continued UFT-E administration for a long time.

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.

Although PSK is an antitumor drug with immunomodulating effects, it has also been shown to have a direct action on cancer cells. This study analyzed the mechanism of the direct action of PSK on cancer cells, focused on the apoptosis-inducing effect. First, the cell growth inhibitory effect of PSK was examined using seven cancer cell lines, and HL60 cells were found to be strongly inhibited. Next, using HL60 cells, the apoptosis-inducing effect of PSK was examined using Annexin-V/Propidium iodide immunostaining and DNA fragmentation. The results indicated that PSK induced the apoptosis of HL60 cells. When the effect of PSK on protein expression of apoptosis-related factors was analyzed using an apoptosis array, over-expression of pro-caspase-3 and under-expression of factors such as cIAP-1, and cIAP-2 were observed. Furthermore, FACS analysis confirmed an increase in percentage of cells expressing activated caspase-3. These findings suggest that PSK induces apoptosis of HL60 cells and inhibits cell proliferation.

We report here the experience of the treatment with cetuximab in our department. Thirteen patients were treated with cetuximab. Median age was 65-year-old including 8 males and 5 females. Six cases were treated with single administration, and seven were with CPT-11. Median number of treatment was 13 times. In evaluable 9 cases, partial response (PR) was obtained in 3 cases and stable disease (SD) and progressive disease (PD) were in 2 and 4 cases, so that the response rate and disease control rate were 33% and 56%, respectively. Median survival after initiation of cetuximab was 219 days. Skin toxicity was observed in 91% including only one case with grade 3. We think that it is important to control skin toxicity for a continuation of cetuximab.

A 53-year-old woman with left breast tumor was diagnosed as bilateral breast cancer(left; T3N3M0, Stage III C/right; T2N0M0, Stage II )in our hospital, both of which were revealed as invasive ductal carcinoma shown to be ER-negative, PgR negative and HER2-positive by core needle biopsy. In December 2004, paclitaxel and trastuzumab combination therapy was tried, but she went into shock just during administration of paclitaxel, and this therapy was discontinued. After that the triweekly CTF therapy was tried as an anthracycline containing regimen, and the lymph node metastases obtained a complete response after a month and a 38. 5% reduction of left primary breast tumor, which was the best response observed after three months. Time to progression was prolonged to 7 months(9 cycles). Although febrile neutropenia occurred in the first cycle, the therapy could be continued safely thereafter as an outpatient. Anthracycline-containing regimens are likely to be avoided because of the difficulty of combining with trastuzumab in the treatment of HER2 overexpressing advanced/metastatic breast cancer. But the CTF therapy of less cardiotoxicity and less alopecia, can expect longer use and better QOL as an alternative for HER2 overexpressing advanced/metastatic breast cancer patients.

Hyponatremia is one of the most common electrolyte disorders encountered in clinical practice of medical anticancer treatment. Cisplatin (CDDP) is a well-known chemotherapeutic agent that associates with hyponatremia. We retrospectively studied clinical features of hyponatremia CDDP administration. The incidence of hyponatremia at the first administration was 64. 1%. The significant risk factors of hyponatremia are body weight less than 60 kg, creatinin clearance less than 60mL/min, and sodium depletion and intake loss due to treatment-induced anorexia, nausea, vomiting and diarrhea. The mechanism of hyponatremia induced by CDDP is thought to be mainly renal salt wasting, and sometimes the syndrome of inappropriate secretion of antidiuretic hormone(SIADH).

The case was a man in his 60s with no past history of heart and lung. Chest tightness was felt during the first course of cetuximab therapy for recurrent colon cancer. He was diagnosed as having vasospastic angina, and administration of vasodilatation agents was done. After the therapy, no chest pain attack was seen. Chemotherapy was continued. After 3 courses, fever elevation, chest tightness and dyspnea were seen. Chest X-ray and CT revealed diffuse interstitial pneumonia in bilateral lung. Although steroid pulse therapy and intensive therapy with mandatory ventilation were performed, he died of respiratory failure. Pathological findings of autopsy revealed remarkable metastasis of cancer cells to the bilateral lungs accompanied chiefly with carcinomatous lymphangiosis. Furthermore, acute and subacute interstitial pneumonia with diffuse alveolar damage were seen in the background of the lungs. Cardiopulmonary disorder as well as skin disorder should be considered as possible adverse events of cetuximab therapy.

It is known that the serum iron level shows a transient elevation after chemotherapy in some cases; however, the cause of this phenomenon has not been clearly described. We report two cases of colorectal cancer whose serum iron level demonstrated recurrent elevation after administration of irinotecan as a second-line chemotherapy. The transferrin saturation rate showed marked elevation together with serum iron. This fact indicates that the release of non-transferrin bound iron (NTBI) occurs and then, NTBI binds with transferrin immediately thereafter. Additionally, elevation of indirect bilirubin in case 1, and mild anemia in case 2 were observed after every course of chemotherapy. All these phenomena were synchronized with the fluctuation of the serum iron level. These observations suggest that the transient elevation of the serum iron was related with the release of the NTBI from red blood cells after chemotherapy including irinotecan.

A 56-year-old man was admitted to our hospital because of increasing chest discomfort and abnormal chest shadow. Computed tomography (CT) of the chest revealed an anterior mediastinal mass, pleural dissemination and lung metastasis. Percutaneus needle biopsy guided by CT showed that the mass was advanced thymic cancer (stage IV b according to the classification proposed by Masaoka). After failure of combination chemotherapy of cisplatin, vincristine, doxorubicin and etoposide (CODE), he received 4 cycles of carboplatin plus paclitaxel and then achieved confirmed stable disease. In terms of toxicity profile, grade 4 anemia, grade 2 leucopenia and neutropenia were observed, and particularly non-severe toxicity was not observed in terms of non-hematologic toxicity. Carboplatin plus paclitaxel can be an active agent against pretreated thymic cancer.