Primary revision of mid-vein stenoses in venous bypass conduits: venous patch versus interposition vein

PURPOSE: Patients after infrainguinal vein bypasses are a group at risk of graft stenosis and occlusion. Revision of failing grafts has been shown to significantly improve bypass patency and limb salvage. Options for surgical revision of mid bypass stenosis includes either patch angioplasty (PA) or interposition grafting (IG). We reviewed our experience with surgical revision of vein bypass stenosis. METHODS: From April 1968 to March 2006, 7557 autogenous vein bypasses were performed at Albany Medical Center and its affiliated institutions, of these 316 required single or multiple revision of vein grafts with patch angioplasty or interposition vein grafting. Excluded were proximal and distal anastomotic revisions. Only 235 bypasses had single revisions as either patch angioplasty (n = 108) or interposition grafting (n = 127) and are the focus of this review. The initial bypass revisions in these two groups are analyzed for indications, clinical parameters, operative strategies, and long-term patencies and clinical outcomes. RESULTS: There were no significant differences in mean age, gender, or frequency of comorbid conditions (coronary artery disease, pulmonary disease, hypertension, and diabetes) between the two patient groups. Secondary patency of patch angioplasty revision at 5 years was 79%. Patencies for interposition grafting revision at 5 years were equivalent to patch angioplasty group at 75%. When bypasses were evaluated on the basis of initial reconstructions (ie, in situ vs excised vein bypass), the results showed that in situ bypasses that required initial revision had similar 5-year patencies when interposition grafting was used as the first revision strategy vs patch angioplasty (80% vs 73%). Excised vein bypasses had similar patency when patch was their first revision strategy vs interposition grafting (4 year secondary patency 92% vs 75% respectively). CONCLUSION: Autogenous vein bypasses are at risk for developing significant stenosis and occlusion with time. Bypass stenosis that develops in the main body of the graft can be effectively repaired using either patch angioplasty or interposition grafting. Depending on the host of other factors, such as availability of autogenous venous conduit, location of stenosis, accessibility for operative repair, and the patient's anatomic characteristics, either operative strategy is effective in prolonging the patency of the bypass.     

Long-term oncologic outcome following preoperative combined modality therapy and total mesorectal excision of locally advanced rectal cancer

OBJECTIVE: Our aims were to (1) determine the long-term oncologic outcome for patients with rectal cancer treated with preoperative combined modality therapy (CMT) followed by total mesorectal excision (TME), (2) identify factors predictive of oncologic outcome, and (3) determine the oncologic significance of the extent of pathologic tumor response. SUMMARY BACKGROUND DATA: Locally advanced (T3-4 and/or N1) rectal adenocarcinoma is commonly treated with preoperative CMT and TME. However, the long-term oncologic results of this approach and factors predictive of a durable outcome remain largely unknown. METHODS: Two hundred ninety-seven consecutive patients with locally advanced rectal adenocarcinoma at a median distance of 6 cm from the anal verge (range 0-15 cm) were treated with preoperative CMT (radiation: 5040 centi-Gray (cGy) and 5-fluorouracil (5-FU)-based chemotherapy) followed by TME from 1988 to 2002. A prospectively collected database was queried for long-term oncologic outcome and predictive clinicopathologic factors. RESULTS: With a median follow-up of 44 months, the estimated 10-year overall survival (OS) was 58% and 10 year recurrence-free survival (RFS) was 62%. On multivariate analysis, pathologic response >95%, lymphovascular invasion and/or perineural invasion (PNI), and positive lymph nodes were significantly associated with OS and RFS. Patients with a >95% pathologic response had a significantly improved OS (P = 0.003) and RFS (P = 0.002). CONCLUSIONS: Treatment of locally advanced rectal cancer with preoperative CMT followed by TME can provide for a durable 10-year OS of 58% and RFS of 62%. Patients who achieve a >95% response to preoperative CMT have an improved long-term oncologic outcome, a novel finding that deserves further study.     

What is the Significance of the Circumferential Margin in Locally Advanced Rectal Cancer After Neoadjuvant Chemoradiotherapy?

Background

The circumferential resection margin (CRM) is highly prognostic for local recurrence in rectal cancer surgery without neoadjuvant treatment. However, its significance in the setting of long-course neoadjuvant chemoradiotherapy (nCRT) is not well defined.

Methods

Review of a single institution’s prospectively maintained database from 1998 to 2007 identified 563 patients with locally advanced rectal cancer (T3/T4 and/or N1) receiving nCRT, followed after 6 weeks by total mesorectal excision (TME). Kaplan-Meier, Cox regression, and competing risk analysis were performed.

Results

The authors noted that 75 % of all patients had stage III disease as determined by endorectal ultrasound (ERUS) and/or magnetic resonance imaging (MRI). With median follow-up of 39 months after resection, local and distant relapse were noted in 12 (2.1 %) and 98 (17.4 %) patients, respectively. On competing risk analysis, the optimal cutoff point of CRM was 1 mm for local recurrence and 2 mm for distant metastasis. Factors independently associated with local recurrence included CRM ≤1 mm, and high-grade tumor (p = 0.012 and 0.007, respectively). CRM ≤2 mm, as well as pathological, nodal, and overall tumor stage are also significant independent risk factors for distant metastasis (p = 0.025, 0.010, and <0.001, respectively).

Conclusion

In this dataset of locally advanced rectal cancer treated with nCRT followed by TME, CRM ≤1 mm is an independent risk factor for local recurrence and is considered a positive margin. CRM ≤2 mm was associated with distant recurrence, independent of pathological tumor and nodal stage.     

Anastomotic Leak Following Low Anterior Resection in Stage IV Rectal Cancer is Associated with Poor Survival

Background

Anastomotic leak is a serious complication of low anterior resection (LAR). The risk of leak in stage IV rectal cancer patients treated with synchronous or staged resection of the primary tumour and metastatic sites has not been reported. We measured the incidence of anastomotic leak and its association with clinical outcome.

Methods

With institutional review board approval, patients undergoing LAR and resection of metastatic disease were analyzed from a prospectively collected colorectal database between 1992 and 2010. Data for use of ileostomy, clinical anastomotic leak, and clinical risk score (for liver metastases, n = 86) were collected. Categorical variables were compared with the χ² test. Estimated overall survival was compared using log-rank method and Cox regression analysis.

Results

A total of 184 patients with LAR and stage IV disease were identified. Of those, 123 had curative resection for disease at distant sites. 72 % underwent simultaneous resection, 28 % staged resection. Median follow-up was 2.9 years for survivors. Anastomotic leak occurred in 6.5 %. There was one perioperative death (not attributable to leak). Overall 3-year survival following a leak was significantly worse compared with patients without a leak (35 vs. 73 %, P = 0.01). Clinical leak was associated with worse survival when controlled for use of diverting stoma, operative year, clinical risk score, and timing of resection of metastatic disease.

Conclusions

In this series of patients with stage IV rectal cancer, anastomotic leak was uncommon. However, patients who developed a clinical leak following surgery had worse survival. This finding was independent of use of diverting stoma or staged resection.     

Immediate preoperative phlebotomy with autologous blood donation for aortic replacement

The preferential use of autologous blood provided by phlebotomy can reduce the need for homologous blood transfusion in patients undergoing extensive elective operations. This blood is usually provided either by intraoperative isovolemic hemodilution or phlebotomy one to two weeks preoperatively. To minimize the intraoperative time delay or preoperative period between phlebotomy and operation required in these patients, we performed preoperative isovolemic hemodilution in 69 patients one to two days prior to elective aortic replacement for infrarenal aneurysmal disease. Patients underwent phlebotomy a mean of 0.57 +/- 0.01 liter of whole blood; volume was replaced with lactated Ringer's solution. Hematocrit levels decreased from a mean value of 42.9 +/- 0.4 per cent to 33.7 +/- 0.3 per cent. Mean intraoperative blood loss was 1.2 +/- 0.05 liters. Hemodynamic parameters (blood pressure, cardiac output, pulmonary capillary wedge pressure, central venous pressure, oxygen delivery and systemic vascular resistance) remained stable throughout the perioperative and intraoperative time periods. In addition, we evaluated the technical modification of exclusion aneurysmorrhaphy (n = 50) versus open aneurysmorraphy (n = 19) on reduction of intraoperative homologous blood transfusion in these patients. Seventy-two per cent (36 of 50) of patients whose aneurysms were excluded received no homologous blood intraoperatively. Blood loss was decreased in the excluded versus open aneurysmorraphy group, 920 +/- 90 milliliters versus 2,030 +/- 250 milliliters, as were homologous blood transfusion requirements, 175 +/- 35 milliliters versus 570 +/- 119 milliliters. Two patients died (2.9 per cent mortality rate), and there was no increase in morbidity. Surgical treatment of large aortic aneurysms is frequently performed on an urgent basis; thus, provision of autologous blood for this operation in a short period of time may be beneficial. Isovolemic hemodilution performed during the immediate preoperative period can reduce homologous blood requirements and be safely performed without adverse effects on mortality, morbidity and myocardial performance. Exclusion aneurysmorrhaphy may further reduce dependence on homologous blood.     

改性羟基磷灰石骨修复纳米复合材料的制备及生物学评价

目的:制备羟基磷灰石/聚乳酸聚乙醇酸骨修复材料,并对其进行生物学评价。方法:实验于2006-06/2007-02在中科院长春应用化学研究所完成材料制备,在吉林大学基础医学院实验动物中心完成动物实验。将低聚乳酸的羧基与羟基磷灰石表面的钙原子用化学键连接,得到表面接枝聚左旋乳酸的羟基磷灰石,将其与聚乳酸聚乙醇酸共混,得到复合材料PLLA-g-HA/PLGA。溶于氯仿后铺膜(厚0.2mm),用DMEM培养液浸泡材料膜制备浸提液。首先,进行材料生物安全性实验:①细胞毒性实验:将浸提液与培养液混合,接种兔成骨细胞,培养24h,MTT法检测细胞增殖,计算细胞增殖率和细胞毒性级(细胞毒性级0或1级为合格)。②全身毒性实验:小鼠以50mL/kg的剂量静脉注射浸提液,观察72h内小鼠中毒症状。③皮肤刺激实验:兔脊柱两侧皮内注射材料浸提液,观察72h内皮肤有无异常反应。④热原实验:自兔耳缘静脉注入浸提液(10mL/kg)。注射后每0.5h测肛温1次,共6次,以6次中最高的1次减去正常体温,计为升高度数。其次,对复合材料进行细胞黏附性检测:将复合材料制成1%氯仿溶液,涂于硅化的盖玻片上,置于6孔板,每孔接种1×105个成骨细胞,培养3d,在2,24,72h行FITC荧光染色,数码摄像系统拍摄细胞荧光照片。结果:制备了新型PLLA-g-HA/PLGA复合材料。①生物安全性实验结果:MTT实验检测复合材料细胞增殖率为94.8%,细胞毒性级为1级;全身毒性实验中动物无死亡、惊厥、瘫痪、呼吸抑制、腹泻和体质量下降等不良反应;热原实验中兔体温最大的变化值是0.25℃(国家标准为<0.6℃);皮肤刺激实验中未见任何刺激反应,无红斑、焦痂、水肿表现。②细胞黏附性实验结果:细胞接种后2h可见少量细胞开始贴壁;24h时可见贴壁细胞明显增多,并呈聚集生长;培养3d后可见细胞逐渐融合,细胞状态良好。结论:新型PLLA-g-HA/PLGA复合材料符合生物材料细胞毒性要求,按毒性剂量分级属无毒级,无致热原性、对皮肤无刺激作用,具有良好的生物相容性和细胞黏附性。     

Impaired cell-mediated immunity in systemic lupus erythematosus (SLE). A controlled study of 23 untreated patients.

Cell-mediated immunity was evaluated in 23 patients with systemic lupus erythematosus (SLE) prior to therapy and in 23 control subjects. The patients with SLE who had moderate to severe disease activity had significantly fewer positive delayed skin tests to streptokinase-streptodornase (SK-SD) and Candida than the control subjects, and a higher frequency of anergy than either the control subjects or the patients with mild SLE. Significant impairment of lymphocyte transformation to all common antigens tested was found in patients with SLE as compared to both normal subjects and control subjects with disease. Phytohemagglutinin response was reduced in patients with SLE as compared to normal subjects but not to the control subjects with disease. Lymphocyte transformation responses to SK-SD and Candida were also significantly lower in patients with moderate to severe SLE as compared to patients with mildly active SLE. Primary immune response to keyhole limpet hemocyanin (KLH) was impaired in patients with SLE as measured by lymphocyte transformation and total KLH antibody, but not 2-mercaptoethanol resistant antibody. The data indicate defective T-cell function in SLE, and suggest that the impairment relates in part to disease activity.     

Predictive clinicopathologic factors for limited response of T3 rectal cancer to combined modality therapy

Purpose The response of T3 rectal cancer to combined modality therapy (CMT) is highly predictive of long-term outcome following surgery. The aim of this study was to identify pretreatment factors associated with poor tumor response to neoadjuvant chemoradiation. Methods A prospective institutional database at Memorial Sloan-Kettering Cancer Center was queried for endorectal ultrasound (ERUS) stage T3N0–2 rectal cancer patients, treated with CMT followed by surgical resection, between 1998 and 2003. Preoperative clinicopathologic factors determined by biopsy, ERUS, proctoscopy, and digital rectal examination were correlated with the degree of downstaging of the primary mural lesion (tumor downstaging) in response to neoadjuvant therapy. Associations were analyzed by chi-square, Kaplan–Meier, and logistic regression. Results Of 274 patients, 51% obtained tumor downstaging in response to preoperative treatment, i.e., lower pathologic T-stage compared with pretreatment ERUS. Five-year recurrence-free survival was 89% in the cohort that obtained tumor downstaging compared with only 45% in the cohort that obtained no tumor downstaging. Factors significantly associated with limited or lack of tumor downstaging after CMT included: fixed tumor on digital rectal examination (p < 0.021), near-circumferential tumor (p < 0.011), tumor stenosis (p < 0.025), metastatic disease (p < 0.012), biopsy-proven poorly differentiated pathology (p < 0.002), and radial extension >2.5 mm on ERUS (p < 0.031). On multivariate analysis, deep radial extension on ERUS, metastatic disease, and poorly differentiated pathology were in each, independently associated with limited or lack of tumor downstaging. Conclusions Pretreatment evaluation with biopsy, proctoscopy, and ERUS can identify T3 rectal cancer patients unlikely to respond well to CMT. These patients may be considered for alternative protocols and their tumors studied to ascertain the molecular events responsible for resistance to chemoradiation. Presented at Presented at the 2006 annual meeting of The American Society of Colon and Rectal Surgeons, June 3–7, 2006, Seattle, WA, USA.     

The coagulant-active phospholipid content is a major determinant of in vivo thrombogenicity of prothrombin complex (Factor IX) concentrates in rabbits

In vitro evaluation of prothrombin complex concentrates in a thrombin generation assay, using DAPA and purified components of the prothrombinase complex, demonstrated significant levels of coagulant- active "phospholipid replacing" activity. Quantification of this activity showed a significant correlation (r = 0.8747, p less than 0.01) with thrombogenicity measured in vivo in a stasis model in rabbits. Extracted lipid material retained full phospholipid replacing activity in the vitro assay. Thin-layer chromatographic characterization confirmed the presence of phospholipids with known coagulant activity in vitro. In vivo, the extracted material was nonthrombogenic but augmented the thrombogenicity of purified factor Xa. Substitution of a synthetic coagulant-active phospholipid (phosphatidylcholine-phosphatidylserine lipid vesicles) for the extracted phospholipid produced a similar augmentation of a factor-Xa- induced thrombogenicity in vivo. It is concluded that the coagulant- active phospholipid content of prothrombin complex concentrates is a major determinant of thrombogenicity but requires the presence of activated clotting factors for its expression in vivo.