Diffusion-weighted MRI for imaging cell death after cytotoxic or apoptosis-inducing therapy.

BACKGROUND: Non-invasive serial imaging is desirable to detect processes such as necrotic and apoptotic cell death in cancer patients undergoing treatment. This study investigated the use of diffusion-weighted (DW-) magnetic resonance imaging (MRI) for imaging cell death induced by either a cytotoxic drug (irinotecan), or the apoptosis-inducing agent birinapant, in human tumour xenografts in vivo. METHODS: Nude mice bearing human SW620 colon carcinoma xenografts were treated with vehicle, irinotecan (50 mg kg(-1)) or birinapant (30 mg kg(-1)) for up to 5 days. DW-MRI was performed prior to and on days 1, 3 and 5 during treatment. Assessment of tumour apoptosis and necrosis ex vivo was used to validate the imaging findings. RESULTS: Both irinotecan and birinapant induced significant tumour growth delay. Irinotecan induced a small increase in the tumour apparent diffusion coefficient (ADC) after 1 day, with a 20 and 30% increase at days 3 and 5 respectively. ADC was unchanged in the vehicle- and birinapant-treated tumours despite a growth delay in the latter. Histological analysis showed that irinotecan increased necrosis at days 3 and 5, and induced apoptosis after 1 day, compared with vehicle. Birinapant induced apoptosis after day 3, but had no effect on tumour necrosis. CONCLUSIONS: Tumour ADC changes after irinotecan treatment were associated with the induction of a mixture of necrotic and apoptotic cell death, whereas induction of apoptosis alone with birinapant was not sufficient to induce changes in tissue microstructure that were detectable with DW-MRI. ADC is a useful non-invasive biomarker for early detection of response to cytotoxic drugs, but false negatives may arise while detecting apoptotic response to birinapant.

Bronchobiliary fistula due to echinococcosis of the liver.

In Greece, which has the second highest incidence of echinococcosis in the world, there has been an overall decrease in the frequency of this disease and its complications during the past 15 years. Between 1920 and 1960, approximately 46 patients per year were operated on for echinococcosis at the Hellenic Red Cross Hospital, and 1.8% of 1037 hepatic hydatid cysts had ruptured into the bronchi. From 1960 to 1975, the number of patients requiring operation decreased to approximately 25 per year, and incidence of rupture into the bronchi declined to 1% of 288 liver cysts. The reduction has resulted from improvements in preventive medicine and surgical care and a decrease in the frequency of infected cysts. Bronchobiliary fistula is a serious complication of hydatid cyst of the liver and it must be treated surgically. A right thoracotomy or thoracoabdominal approach offers the possibility of dealing simultaneously with the hepatic cyst and the pulmonary lesions. The choice of operation depends on the findings and ranges from simple drainage of the hepatic cavity with division of the bronchobiliary communication, to resection of the lung (usually lobectomy) when a chronically infected pulmonary cavity is present. If a hydatid cyst of the liver ruptures simultaneously into the lung and the extra-hepatic biliary tree with resultant obstruction of the common bile duct, unblocking of the common duct by evacuation of cysts and debris through a laparotomy takes priority over any other surgical action. Of 3 patients with bronchobiliary fistulas treated during the past 15 years, 2 were cured by simple drainage through a transabdominal approach.