Comparison of Targeted vs Random Biopsies for Surveillance of Ulcerative Colitis-Associated Colorectal Cancer.

BACKGROUND & AIMS: A random biopsy is recommended for surveillance of ulcerative colitis (UC)-associated colorectal cancer. However, a targeted biopsy might be more effective. We conducted a randomized controlled trial to compare rates of neoplasia detection by targeted vs random biopsies in patients with UC. METHODS: We performed a study of 246 patients with UC for 7 years or more, seen at 52 institutions in Japan from October 1, 2008 through December 31, 2010. Patients were randomly assigned to the random group (4 random biopsies collected every 10 cm in addition to targeted biopsies, n = 122) or the target group (biopsies collected from locations of suspected neoplasia, n = 124). The primary end point was the number of neoplastic lesions detected in a single surveillance colonoscopy. We estimated the ratio and difference in the mean number of neoplastic lesions between the groups. We also evaluated the non-inferiority between the groups as an exploratory study. A non-inferiority margin of 0.65 (0.13 of 0.20) was considered for the ratio of the mean number of neoplastic lesions between groups. RESULTS: The mean number of biopsies found to contain neoplastic tissue per colonoscopy was 0.211 (24 of 114) in the target group and 0.168 (18 of 107) in the random group (ratio of 1.251; 95% confidence interval, 0.679-2.306). The lower limit was above the non-inferiority margin of 0.65. Neoplasias were detected in 11.4% of patients in the target group and 9.3% of patients in the random group (P = .617). Larger numbers of biopsy samples per colonoscopy were collected in the random group (34.8 vs 3.1 in the target group; P < .001), and the total examination time was longer (41.7 vs 26.6 minutes in the target group; P < .001). In the random group, all neoplastic tissues found in random biopsies were collected from areas of the mucosa with a history or presence of inflammation. CONCLUSIONS: In a randomized controlled trial, we found that targeted and random biopsies detect similar proportions of neoplasias. However, a targeted biopsy appears to be a more cost-effective method. Random biopsies from areas without any signs of present or past inflammation were not found to contain neoplastic tissues. Clinical Trial Registry: UMIN000001608.

A Phase II clinical trial of pegylated liposomal doxorubicin and carboplatin in Japanese patients with platinum-sensitive recurrent ovarian, fallopian tube or primary peritoneal cancer.

OBJECTIVE: This single-arm Phase II trial was designed to assess the safety and efficacy of pegylated liposomal doxorubicin and carboplatin combination chemotherapy in patients with platinum-sensitive recurrent ovarian cancer. METHODS: Patients with a histological diagnosis of epithelial ovarian, fallopian tube or primary peritoneal carcinoma, who were relapse-free at least 6 months after completion of first-line platinum-based chemotherapy, and who had measurable disease and gave consent to participate in this study received infusions of pegylated liposomal doxorubicin (30 mg/m(2)) at 1 mg/min, followed by carboplatin (AUC 5 mg min/ml) over 30 min every 28 days. RESULTS: Thirty-three of 35 enrolled patients were eligible for efficacy analysis. One patient (3.0%) achieved a complete response, while 16 (48.5%) achieved a partial response, with an overall objective response rate of 51.5% (95% confidence interval, 34.5-68.6%). Among the 22 patients who had evaluable CA125 levels at entry, responses were observed in 18 patients, with a response rate of 81.8% (95% confidence interval, 65.3-98.3%). The median progression-free survival and overall survival rates for all 35 patients were 10.7 months (95% confidence interval, 8.1-13.2 months) and 38.8 months (95% confidence interval, 31.0-46.7 months), respectively. The most frequent Grade 3-4 toxicities, regardless of cause, were neutropenia (82.9%), thrombocytopenia (51.4%), leukopenia (45.7%) and anemia (17.1%). CONCLUSIONS: The safety and efficacy of pegylated liposomal doxorubicin and carboplatin combination chemotherapy in patients with platinum-sensitive recurrent ovarian cancer were confirmed. Although there were concerns of severe hematological toxicity with this therapy, this potential complication was safely managed through adequate monitoring of bone marrow function.

Feasibility of regression of hypertension using contemporary antihypertensive agents.

BACKGROUND: Recently, we reported that transient treatment of genetically hypertensive rats with high-dose angiotensin receptor blocker (ARB) causes regression of established hypertension. In this study, we investigated whether treatment with candesartan or nifedipine controlled-release (CR) resulted in a sustained regression of hypertension in humans. METHODS: Patients aged 30 to 59 years with untreated stage 1 essential hypertension and a family history of hypertension were treated with the antihypertensive agents candesartan (n = 124) or nifedipine CR (n = 120). After 1 year of treatment (phase 1), the medications were tapered and discontinued (phase 2). During phase 2, home and office blood pressures were monitored for another year to assess posttreatment reoccurrence of stage 1 hypertension. RESULTS: In phase 1, after 1 year of treatment a similarly substantial BP decrease was seen in the candesartan (-24.5/16.1 mm Hg) and nifedipine (-26.8/18.0 mm Hg) groups. In phase 2 there was a substantial reoccurrence of hypertension; at the study end, only 1 patient was able to continue without antihypertensive medication. However, a Kaplan-Meier analysis revealed a significant delay of reoccurrence of hyper tension (P = 0.0001) in the candesartan group. CONCLUSIONS: One year of treatment with candesartan or nifedipine CR was not associated with marked regression of hypertension in humans at the standard doses used in this trial. However, withdrawal of candesartan was associated with a slightly longer delay before restarting medications. Further studies with larger doses of candesartan given over a longer time are required to determine whether such a regimen may induce sustainable and clinically relevant reversal of hypertension and alteration in its natural history.

Effect of lesional differences in prolapsed leaflets on clinical outcomes in patients with mitral valve prolapse.

BACKGROUND: Mitral valve prolapse (MVP) is usually benign, although serious complications may occur. It remains unclear whether the region of prolapsed mitral leaflets might affect prognosis. The aim of this study was to investigate lesional differences of clinical courses of MVP. METHODS AND RESULTS: We retrospectively investigated 128 MVP patients who had been followed up for for a mean of 56.4 months. They were classified into prolapse of the anterior mitral leaflet (AML, n = 59), posterior mitral leaflet (PML, n = 47), or both leaflets (AML & PML, n = 22). Echocardiographic and clinical data were examined from medical records. Average time to clinical events; MV surgery, new onset of atrial fibrillation (AF), echocardiographic evidence of new chordal rupture, and worsening of mitral regurgitation severity were all significantly shorter in PML prolapse than in those with AML or AML & PML prolapses. Increases in the left ventricular dimensions and estimated pulmonary arterial systolic pressures were significantly larger in PML prolapse, compared with AML or AML & PML prolapses. A subanalysis of PML prolapse revealed that new chordal rupture tended to be more frequent in middle scallop prolapse (48%) compared with lateral and medial scallops (18%). In contrast, new onset of AF tended to occur in lateral and medial scallop prolapses (44%) compared with middle scallop prolapse (20%). CONCLUSIONS: PML prolapse patients had a poor outcome, compared with AML or AML & PML prolapse patients. Precise regional evaluation of the prolapsed leaflets may predict cardiac complications in MVP.

Target biopsy or step biopsy? Optimal surveillance for ulcerative colitis: a Japanese nationwide randomized controlled trial.

Colorectal cancer is one of the complications of ulcerative colitis (UC) and the risk of cancer increases as the duration of the disease becomes longer. Surveillance colonoscopy has been considered to be important for the early detection and early treatment of colorectal cancer, especially in longstanding UC. Because it is not always easy to detect neoplastic lesions in UC endoscopically, guidelines recommend the use of step biopsy in surveillance, in which either 4 biopsy specimens for every 10 cm or a total of 33 or more biopsy specimens are obtained. However, it has been pointed out that a step biopsy obtaining several tens of biopsy specimens may not be an ideal method in terms of invasiveness to the patient or medical cost. Instead of step biopsy, recent studies report the usefulness of target biopsy, in which biopsy tissues are obtained only from regions suspected of neoplasia. Therefore, the Research Group for Intractable Inflammatory Bowel Disease of the Ministry of Health, Labour and Welfare of Japan has initiated a randomized controlled study to compare the efficacy of step biopsy and target biopsy. The present article gives an introduction to this ongoing randomized controlled trial in Japan.