Prediction of chemosensitivity of colorectal cancer to 5-fluorouracil by gene expression profiling with cDNA microarrays

5-Fluorouracil (5-FU) is the most widely used anticancer agent for gastrointestinal cancers. Because many tumors show primary resistance, it is clinically meaningful to predict tumor sensitivity to the drug before treatment. cDNA microarrays containing 21,168 clones were used to identify genes associated with sensitivity to 5-FU. Gene expression profiling of 3 colorectal cancer cell lines (DLD-1, HT-29 and NUGC-3) and the corresponding 5-FU-resistant sublines (DLD-1/FU, HT-29/FU and NUGC-3/5FU/L) showed 81 genes that were differentially expressed. The gene set thus identified successfully predicted the sensitivities of 5 other colorectal cancer cell lines and could also separate 5-FU resistant clinical samples from sensitive ones.     

Adrenomedullin causes coronary vasodilation in humans: effects of inhibition of nitric oxide synthesis

Experimental studies have shown that adrenomedullin (AM) causes vasodilation, in part, mediated by endothelium-derived nitric oxide (NO). However, it remains to be clarified how NO is involved in AM-induced coronary vasoreactivity in humans. We examined whether NO contributes to the vasodilatory effects of adrenomedullin on human coronary arteries. In 10 patients with angiographically normal coronary arteries, adrenomedullin (low dose: 1 ng/kg/min; high dose: 10 ng/kg/min) was infused into the left coronary ostium before and after an infusion of N-monomethyl-L-arginine (L-NMMA, 40 micromol/min for 5 min), an NO synthase inhibitor. Coronary diameter and coronary blood flow (CBF) were evaluated by quantitative angiography and Doppler flow velocity measurements. Changes in these parameters in response to adrenomedullin were expressed as percent changes from baseline values. Adrenomedullin at a high dose dilated coronary arteries (3.7+/-0.5%, P<0.001). Adrenomedullin increased the coronary blood flow at both doses (low: 55.7+/-13.9%, P<0.01; high: 48.8+/-9.8%, P<0.001). After the infusion of L-NMMA, adrenomedullin-induced coronary vasodilation and increase in coronary blood flow were attenuated. These findings suggest that adrenomedullin dilates human coronary arteries through an increase in NO production, at least in part.     

Usefulness of prophylactic transcatheter arterial infusion of anticancer agents with lipiodol to prevent recurrence of hepatocellular carcinoma after hepatic resection

To improve the prognosis after hepatectomy for HCC, repeated postoperative transcatheter arterial infusions of anticancer drugs and lipiodol (TAI) were given. TAI may be effective as an adjuvant therapy for prevention of residual liver recurrence after hepatectomy, probably by suppression of the development of intrahepatic micrometastases rather than of multicentric carcinogenesis.     

Effectiveness of prehepatectomy intra-arterial chemotherapy for multiple bilobar colorectal cancer metastases to the liver: a clinicopathologic study of peritumoral vasculobiliary invasion

BACKGROUND: Consensus remains to be achieved concerning prehepatectomy neoadjuvant chemotherapy as a treatment strategy for multiple bilobar colorectal liver metastases, in part because the effect of prehepatectomy neoadjuvant chemotherapy has not been determined pathologically. We investigated the efficacy of prehepatectomy intra-arterial chemotherapy for multiple bilobar colorectal cancer metastases to the liver. METHODS: Clinicopathologic data for 37 consecutive patients with > or =5 bilobar liver metastases from colorectal cancer who underwent hepatectomy were analyzed retrospectively with respect to long-term outcome and histological findings in resected liver tumors. RESULTS: In the 15 patients receiving neodadjuvant chemotherapy (NEO+ group), liver metastases progressed in 2 patients, remained stable in 8 patients, responded more than 50% in 4 patients, and responded completely in 1 patient (combined response rate, 33.3%). Overall and hepatic recurrence-free survival tended to be higher in responders than in nonresponders ( P = .053). Microscopic invasion of the portal vein, hepatic vein, and bile ducts near liver tumors was less frequent according to use of neoadjuvant chemotherapy and responsiveness to the therapy (responders, 20.0%; patients not receiving neoadjuvant therapy [NEO-], 72.7%; P < .05). Such microscopic invasion independently predicted hepatic recurrence by multivariate analysis ( P = .011). CONCLUSIONS: A neoadjuvant chemotherapy-associated decrease in microscopic vasculobiliary invasion by metastatic liver tumors was related to clinical response and favorable outcome.     

Envenomation accidents caused by snakebites in the surgical emergency unit of Gabriel-Touré Hospital, Bamako, Mali (1998-1999)

This study aimed at assessing envenomations caused by snakebite in the Gabriel Touré hospital between January 1998 and December 1999. We included in total 112 victims of snakebites proved by the identification of the snake, the fangs traces and envenomation signs. The bites concerned 34 women (30.36%) versus 78 men (69.64%) from the Bamako district, while 66.7% were from a rural environment. The farmers were the most affected category (35.1%). The bite concerned the lower limb in 83.3% of the cases. Snakes such as Echis ocellatus, Bitis arietans, Naja nigricollis and N. katiensis caused the envenomations. The viperine syndrome dominated the clinical picture; its severity depended on the bleeding stage and the delay of administration of the antivenom serum (AVS) after the envenomation: 19 hours for Echis sp. and 2 hours for Naja sp. This study shows that the envenomation accidents caused by snakes are frequent with a lethality rate of 9.8%.     

Clinical features of argyrophilic grain disease: a retrospective survey of cases with neuropsychiatric symptoms.

OBJECTIVE: Although argyrophilic grain disease (AGD) appears common in post-mortem series, its clinical features are not widely known. The aim of this study was to explore such clinical features in neuropathologically-confirmed AGD cases. METHODS: After completing a neuropathological assessment of 386 patients, 33 cases (8.5%) were diagnosed as having AGD; 10 were diagnosed as "pure" cases. These subjects had been admitted to geriatric wards of mental hospitals because of behavioral or neuropsychiatric symptoms requiring medical management. Assessment of the clinical features of the pure cases was based on the evaluations in medical records. RESULTS: The average age at onset was 82.2 years. Amnesia was the most common initial symptom; irritability and agitation were also common as initial symptoms. During the course of the illness, irritability was the most frequently observed, followed by delusions (mostly delusions of persecution), dysphoria, and then agitation, and apathy. In contrast to the severity of amnesia, other cognitive functions were relatively spared, and the sensorimotor symptoms were not remarkable. CONCLUSIONS: AGD is a late-onset dementing disorder clinically characterized by amnesia, with other cognitive functions relatively spared, and prominent neuropsychiatric features. These features may correlate with the high level of AGD seen in limbic structures. Future studies are needed to elucidate whether these features are common to all AGD patients or to a clinical subtype with neuropsychiatric symptoms.     

Dementia with Lewy bodies]

"Dementia with Lewy bodies (DLB)" was proposed at the first international workshop in 1995. It has received much attention since we had proposed "Lewy body disease" in 1980 and "diffuse Lewy body disease" in 1984. In the CDLB guidelines, which were reported in 1996, the clinical and pathological diagnostic criteria for DLB were shown for the first time. At present, DLB as well as Alzheimer's disease (AD) and vascular dementia (VD) are known as the three major dementing illnesses. The second international workshop was held in 1998, and the third in 2003. One of the authors, K. Kosaka, presented a paper on DLB at each international workshop, based on series of our papers which we had reported since 1976. The revised CDLB guidelines will be reported soon. In addition, the fourth international workshop on DLB will be held by Kosaka in Yokohama in 2007. In this article, we review the history, the clinical, therapeutic, neuropathological, neurochemical and molecular biological issues, based on our previous papers and other important reports on DLB.     

Procedures of Choice for Resection of Primary and Recurrent Liver Metastases from Colorectal Cancer

Although liver resection offers the only realistic chance of cure for patients with liver metastases from colorectal cancer, no consensus exists as to the procedure of choice for managing these tumors. Data from 193 patients who underwent hepatectomy for liver metastases from colorectal cancer and 26 of 193 patients who underwent repeat hepatectomy for recurrent metastases were collected. The suitability of resection was evaluated retrospectively based on known risk factors for recurrence and patterns of recurrence. On multivariate analysis, a positive surgical margin (SM+) was the only risk factor for recurrence after the initial resection (p < 0.01). SM+ (p < 0.01) and nonanatomic resection (p < 0·05) that was less than a sectionectomy (p < 0.05) were risk factors for recurrence after repeat hepatectomy. Multiple tumors (four or more) was the most common pattern of recurrence after initial hepatectomy, and recurrence close to the line of resection was most common after repeat hepatectomy. Based on tumor doubling times, recurrence after initial hepatectomy seemed to originate from the primary colorectal lesion, whereas recurrence after repeat hepatectomy was derived from a hepatic metastasis. Retrospective analysis suggests that hepatectomy with clear surgical margins is more important than anatomic resection for initial hepatectomy, and at least sectionectomy is necessary for repeat hepatectomy.