[A Case of Intestinal Fistula Associated with Small Intestinal Metastasis from Small Cell Lung Carcinoma].

A 53-year-old man who complained of dyspnea and prolonged cough visited to our hospital. Computed tomography (CT)revealed massive tumors of right lung and small intestine. CT-guided fine-needle aspiration(FNA)on lung lesion was performed and the lung tumor was diagnosed as small cell carcinoma. We subsequently performed surgical resection for the tumor of small intestine, but part of tumor lesion remained due to pelvic wall invasion. The resected tumor was diagnosed as metastasis from lung carcinoma by histopathological examination. After surgery the patient was treated with atezolizumab and carboplatin-etoposide chemotherapy, but the remnant metastasis caused intestinal fistula. Treatment was continued carefully with fistula management using pouches. Although the fistula was closed during chemotherapy response, it recurred after discontinuation of treatment due to severe adverse events. The patient died 325 days after the surgery.

[A Case of Severe Hyperammonemic Encephalopathy in a Dialysis Patient Following mFOLFOX6 Therapy].

A 69-year-old man on hemodialysis for chronic renal failure was diagnosed with ascending colon cancer, and received surgical resection. Multiple liver metastases were detected after surgery. He was administered modified FOLFOX6 therapy (reducing the dose to 50%), and showed severe disturbance of consciousness due to hyperammonemia on treatment day 6. After treatment with daily hemodialysis, branched-chain amino acid solutions, lactulose and rifaximin, his conscious level improved on day 9. Intensive chemotherapy in dialysis patients should be carefully performed considering the serious adverse events including hyperammonemia.

[A case of peritoneal dissemination caused by recurrent hilar cholangiocarcinoma treated with intraperitoneal infusion of cisplatin (CDDP) and systemic chemotherapy].

Six years and 9 months ago, a 72-year-old man underwent left hepatectomy for a hilar cholangiocarcinoma(T2N0M0: Stage II A). At 3 years and 2 months after surgery, he was admitted for rectal tumor and reoperation. From surgery, it was diagnosed as peritoneal metastases of the cholangiocarcinoma, and an intraperitoneal infusion port was placed. He was treated with gemcitabine administered iv at day 1 and CDDP ip at day 8 every 3 or 4 weeks for 2 years. Then, gemcitabine was changed to docetaxel because of elevation of CA19-9. Both docetaxel iv and CDDP ip were administered for one and half years. For 3 years and 4 months, 12.2 g of CDDP, 28.0 g of gemcitabine and 920 mg of docetaxel were administered. As serum CA19-9 elevated again, he has been treated with S-1 and docetaxel ip for 3 months. This case indicates that intraperitoneal application of CDDP with systematic chemotherapy was effective for carcinomatous peritonitis without serious side effects.

Single-injection ornithine decarboxylase-directed antisense therapy using atelocollagen to suppress human cancer growth.

BACKGROUND: Substantial evidence supports a direct role of ornithine decarboxylase (ODC) in the development and maintenance of human tumors. Although antisense oligonucleotide therapy targeting various genes are useful for cancer treatment, 1 of the major limitations is the problem of delivery. A novel antisense oligonucleotide delivery method is described that allows prolonged sustainment and release of ODC antisense oligonucleotides in vivo using atelocollagen. METHODS: The effect of ODC antisense oligonucleotides in the atelocollagen on cell growth of gastrointestinal cancer (MKN 45 and COLO201) and rhabdomyosarcoma (RD) was studied in vitro using a cell-counting method with a hemocytometer. In vivo, the effect of intratumoral, intramuscular, and intraperitoneal single administration of ODC antisense oligonucleotides in the atelocollagen on tumor growth of MKN45, COLO201, and RD cells was studied. ODC activity and polyamine contents were measured. RESULTS: In vitro, ODC antisense oligonucleotides in the atelocollagen remarkably suppressed MKN45, COLO201, and RD cell growth. A single administration of antisense oligonucleotides in the atelocollagen via 3 routes remarkably suppressed the growth of MKN45, COLO201, and RD tumor over a period of 35-42 days. CONCLUSIONS: As various human cancers significantly express ODC, the results strongly suggest that this new antisense method may be of considerable value for treatment of human cancers.

[A case of pericardial tamponade caused by recurrent breast cancer treated with intrapericardial and intrapleural infusion of cisplatin (CDDP)].

Breast cancer rarely metastasizes to the pericardial cavity to cause cardiac tamponade. We have recently experienced a case of pericardial tamponade due to recurrent breast cancer. A 41-year-old woman who underwent modified radical mastectomy for a right breast cancer (T(1)N(3)M(0), Stage IIIA) 8 years and 8 months ago, was admitted for dyspnea and cough. Chest X-ray and CT scan revealed cardiomegaly and right pleural effusion, and cardiac echogram showed marked retention of pericardial effusion. A diagnosis of cardiac tamponade was made, and pericardiocentesis and thoracentesis were carried out immediately. Based on cytodiagnosis of pericardial and pleural effusion, the diagnosis was pericardial and intrapleural metastases of the breast cancer. Dyspnea was improved by pericardiocentesis and thocacentesis. Both intrapericardiac and intrathoracic instillation of CDDP prevented reaccumulation of pericardial and pleural effusion. After local chemotherapy with CDDP, systemic chemotherapy of CPT-11 was started. Thereafter the patient was discharged from the hospital and recovered her daily activities. This case indicates that intrapericardiac application of CDDP was effective for carcinomatous cardiac tamponade without serious side effects.

5'-,3'-inverted thymidine-modified antisense oligodeoxynucleotide targeting midkine. Its design and application for cancer therapy.

Oligodeoxynucleotides modified at both 5'- and 3'-ends with inverted thymidine (5'-,3'-inverted T) were introduced as new reagents for antisense strategies. These modifications were performed to make the oligodeoxynucleotides resistant to nucleases. The effectiveness of these oligodeoxynucleotides was evaluated in terms of inhibition of synthesis of midkine (MK), a heparin-binding growth factor, and consequent inhibition of growth of CMT-93 mouse rectal carcinoma cells. 5'-,3'-Inverted T antisense MK suppressed synthesis of MK by CMT-93 cells and their growth in culture. Furthermore, 5'-,3'-inverted T oligodeoxynucleotides exhibited less cytotoxicity and better stability than phosphorothioate oligodeoxynucleotides. When 5'-,3'-inverted T antisense MK was mixed with atelocollagen, and injected into CMT-93 tumors pregrown in nude mice, tumor growth was markedly suppressed as compared with tumors injected with sense controls. The suppressive effect of 5'-,3'-inverted T antisense MK on tumor growth was stronger than that of phosphorothioate antisense MK. These findings indicated the usefulness of inverted thymidine-modified antisense oligodeoxynucleotides as a new reagent instead of phosphorothioate-modified oligodeoxynucleotides.