Citations

Purpose Intensive postoperative surveillance is associated with improved survival and recommended for patients with late stage (stage IIB and III) colon cancer. We hypothesized that stage I and IIA colon cancer patients would experience similar benefits. Patients and Methods Secondary analysis of data from the Clinical Outcomes of Surgical Therapy trial was performed by analyzing results according to TNM stage; early (stage I and IIA, 537 patients) and late (stage IIB and III, 254 patients) stage disease. Five-year recurrence rates were higher in patients with late (35.7%) versus early stage disease (9.5%). Early and late stage salvage rates, recurrence patterns and methods of first detection were compared by χ2 test. Results Salvage rates for early- and late-stage disease patients with recurrence were the same (35.9% v 37%; P = .9, respectively). Median survival after second surgery after recurrence was 51.2 and 35.8 months for early- and late-stage patients, respectively. Single sites of first recurrence did not significantly differ between early and late stage, but multiple sites of recurrence occurred less often in early-stage patients (3.6% v 28.6%, for early v late, respectively; P < .001). Methods of first detection of recurrence were not significantly different: carcinoembryonic antigen (29.1% v 37.4%), computed tomography scan (23.6% v 26.4%), chest x-ray (7.3% v 12.1%), and colonoscopy (12.7% v 8.8%), for early versus late stage disease, respectively. Conclusion Patients with early-stage colon cancer have similar sites of recurrence, and receive similar benefit from postrecurrence therapy as late-stage patients; implementation of surveillance guidelines for early-stage patients is appropriate.

The past decade has witnessed a paradigm shift in the initial treatment of multiple myeloma with the introduction of novel agents such as thalidomide, lenalidomide, and bortezomib, leading to improved outcomes. High-dose therapy and autologous stem cell transplantation remains an important therapeutic option for patients with multiple myeloma eligible for the procedure. Before the advent of the novel agents, patients underwent stem cell collection prior to significant alkylating agent exposure, given its potential deleterious effect on stem cell collection. With increasing use of the novel agents in the upfront setting, several reports have emerged raising concerns about their impact on the ability to collect stem cells. An expert panel of the International Myeloma Working Group (IMWG) was convened to examine the implications of these therapies on stem collection in patients with myeloma and to develop recommendations for addressing these issues. Here we summarize the currently available data and present our perspective on the problem and potential options to overcome this problem. Specifically, we recommend early mobilization of stem cells, preferably within the first 4 cycles of initial therapy, in patients treated with novel agents and encourage participation in clinical trials evaluating novel approaches to stem cell mobilization.

Objective: Endoleaks are critical complications of endovascular abdominal aortic aneurysm repair (EVAR). This study sought to determine the frequency and nature of intraoperative endoleaks and their impact on postoperative endoleak-related events. Methods: A retrospective chart review was performed of all patients who underwent EVAR at our institution. The impact of intraoperative endoleaks on postoperative endoleak rates and endoleak-related reintervention rates were assessed. Results: From December 18, 1996, to May 21, 2003, 241 patients underwent EVAR. An endoleak was observed during 126 (52.3%) procedures. Type I endoleaks were observed in 63 (26.1%) cases: 35 proximal and 31 distal endoleaks (3 cases at both attachments). Angioplasty, additional cuff placement, or stenting corrected 59 (89.4%) of these endoleaks. A total of 71 type II intraoperative endoleaks (29.5%) and 8 type IV endoleaks (3.3%) were observed without any attempted corrective maneuvers. Ten type III endoleaks (4.2%) occurred but all resolved with angioplasty or additional cuff placement. In all, 86 (35.7%) endoleaks persisted on completion angiogram. Patients with a type I or type II intraoperative endoleak were more likely to have an endoleak at 1.5 years (31.4% vs. 21.6%, P = .018). Reinterventions were required more often after an intraoperative type I endoleak (10% vs. 4%, P = .003). Patients with intraoperative endoleaks demonstrated a trend toward less postoperative aneurysm diameter reduction at 2 years (43.8% vs. 74.5%, P = .104). Conclusion: The presence of a type I or a type II endoleak during EVAR significantly increases the likelihood of a postoperative endoleak and should prompt a high degree of suspicion during follow-up.

Dural arteriovenous fistulas (DAVFs) with pure leptomeningeal drainage may be cured by simple interruption of their venous side. This report illustrates the cases of 3 patients undergoing surgery for fistulas classified as Borden Type III, involving the posterior cranial fossa. Preoperatively, the surgical anatomy of these lesions was investigated with 3D reformatting of multislice CT angiography, in addition to conventional angiography. Reformatted images clarified the surgical anatomy of the malformation. Reconstructing both the osseous and the vascular structures and simulating the surgical orientation allowed localization of the dural takeoff point of the DAVF's drainage, showing its relationship with osseous landmarks. Precise localization of the DAVF's drainage may help in choosing the most direct and effective approach to treat the malformation. The reported cases could be treated with a standard retrosigmoid exposure, avoiding the need for more complex cranial base approaches.

AbstractImatinib mesylate (IM, Gleevec) has largely supplanted allogeneic hematopoietic cell transplantation (HCT) as first line therapy for chronic myeloid leukemia (CML). Nevertheless, many people with CML eventually undergo HCT, raising the question of whether prior IM therapy impacts HCT success. Data from the Center for International Blood and Marrow Transplant Research on 409 subjects treated with IM before HCT (IM+) and 900 subjects who did not receive IM before HCT (IM−) were analyzed. Among patients in first chronic phase, IM therapy before HCT was associated with better survival but no statistically significant differences in treatment-related mortality, relapse, and leukemia-free survival. Better HLA-matched donors, use of bone marrow, and transplantation within one year of diagnosis were also associated with better survival. A matched-pairs analysis was performed and confirmed a higher survival rate among first chronic phase patients receiving IM. Among patients transplanted with advanced CML, use of IM before HCT was not associated with treatment-related mortality, relapse, leukemia-free survival, or survival. Acute graft-versus-host disease rates were similar between IM+ and IM− groups regardless of leukemia phase. These results should be reassuring to patients receiving IM before HCT.

Cholangiocytes, epithelial cells lining the biliary tree, have primary cilia extending from their apical membrane into the ductal lumen. Although important in disease, cilia also play a vital role in normal cellular functions. We reported that cholangiocyte cilia are sensory organelles responding to mechanical stimuli (i.e., luminal fluid flow) by alterations in intracellular Ca 2+ and cAMP. Because cholangiocyte cilia are also ideally positioned to detect changes in composition and tonicity of bile, we hypothesized that cilia also function as osmosensors. TRPV4, a Ca 2+ -permeable ion channel, has been implicated in signal transduction of osmotic stimuli. Using purified rat cholangiocytes and perfused intrahepatic bile duct units (IBDUs), we found that TRPV4 is expressed on cholangiocyte cilia, and that hypotonicity induces an increase in intracellular Ca 2+ in a TRPV4-, ciliary-, and extracellular calcium-dependent manner. The osmosensation of luminal tonicity by ciliary TRPV4 induces bicarbonate secretion, the main determinant of ductal bile formation, by a mechanism involving apical ATP release. Furthermore, the activation of TRPV4 in vivo , by its specific agonist, 4αPDD, induces an increase in bile flow as well as ATP release and bicarbonate secretion. Our results suggest that cholangiocyte primary cilia play an important role in ductal bile formation by acting as osmosensors.

As endografting technology advances, anatomical constraints limiting access and deployment have become less of a burden. While unsuitable candidates for endografting exist, these patients are becoming less frequent. To broaden the applicability of endovascular abdominal aortic aneurysm repair (EVAR), we have modified the bifurcated AneuRx™ device into a unilimb modular prosthesis, by placing an aortic extender cuff across the flow divider, thus excluding its contralateral limb. This technique was used with success in 3 groups of patients: with occlusion of 1 iliac artery, with a nontraversable iliac stenosis, or with a small calcific aortic bifurcation. In these patients, anatomy can make it difficult, if not impossible, to place a bifurcated stent graft. Whether as a planned preoperative procedure or as a ‘bail-out’ maneuver, this procedure has been successful in avoiding open surgical conversion.

Background— Despite routine use of coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI), no conclusive evidence exists that either modality is superior to medical therapy (MT) alone for treating multivessel coronary artery disease with stable angina and preserved ventricular function. Methods and Results— The primary end points were total mortality, Q-wave myocardial infarction, or refractory angina requiring revascularization. The study comprised 611 patients randomly assigned to undergo CABG (n=203), PCI (n=205), or MT (n=203). At the 5-year follow-up, the primary end points occurred in 21.2% of patients who underwent CABG compared with 32.7% treated with PCI and 36% receiving MT alone ( P =0.0026). No statistical differences were observed in overall mortality among the 3 groups. In addition, 9.4% of MT and 11.2% of PCI patients underwent repeat revascularization procedures compared with 3.9% of CABG patients ( P =0.021). Moreover, 15.3%, 11.2%, and 8.3% of patients experienced nonfatal myocardial infarction in the MT, PCI, and CABG groups, respectively ( P <0.001). The pairwise treatment comparisons of the primary end points showed no difference between PCI and MT (relative risk, 0.93; 95% confidence interval, 0.67 to 1.30) and a significant protective effect of CABG compared with MT (relative risk, 0.53; 95% confidence interval, 0.36 to 0.77). Conclusions— All 3 treatment regimens yielded comparable, relatively low rates of death. MT was associated with an incidence of long-term events and rate of additional revascularization similar to those for PCI. CABG was superior to MT in terms of the primary end points, reaching a significant 44% reduction in primary end points at the 5-year follow-up of patients with stable multivessel coronary artery disease.