Choice of hemostatic agent influences adhesion formation in a rat cecal adhesion model.

INTRODUCTION: Hemostatic agents are frequently used during abdominal surgery and some are linked to adhesion formation. We sought to evaluate the impact of several commonly used hemostatic agents on adhesion formation in a rat peritoneal model. METHODS: In our study, Wister outbred rats underwent laparotomy and excision of a portion of their peritoneum to initiate adhesion formation process. One of six different hemostatic agents, namely, activated starch microspheres (Arista AH; Medafor Inc., Minneapolis, MN), glutaraldehyde activated collagen (BioGlue; Cryolife Inc., Kennesaw, GA), thrombin coated collagen microspheres (FloSeal; Baxter Inc., Deerfield, IL), thrombin activated fibrin polymer (Tisseel, Baxter), polyethylene glycol polymer (CoSeal, Baxter), or oxidized cellulose (Surgicel; Ethicon Inc., Somerville, NJ), was placed in the area of peritoneal defect. All animals were sacrificed on post-op day 7 and strength and extent of adhesion formation was determined. Histopathological examination of rat caecum was also performed. RESULTS: Arista and CoSeal showed significantly lower adhesion formation than controls (P < 0.05). Higher adhesion scores were seen in BioGlue (P < 0.05) treated rats. Additionally, histopathologic examination showed that BioGlue caused statistically more inflammation and necrosis than controls (P < 0.05). Total adhesion score increased with residual amount of agent present at 7 d. CONCLUSIONS: Use of Arista and CoSeal may help in reducing peritoneal adhesions after intra-abdominal surgeries. Furthermore, there appears to be a relationship between the creation of inflammation and necrosis in tissues and the eventual formation of adhesions. This could aid in improving the design of these agents in the future.

External validation of IMP3 expression as an independent prognostic marker for metastatic progression and death for patients with clear cell renal cell carcinoma.

BACKGROUND: High-quality external validation studies have recently been highlighted to be of paramount importance for proper translation of prognostic markers into the clinical setting. To that end, the authors examined associations of the insulin-like growth factor-II mRNA binding protein, IMP3, with clinical and pathologic features of clear cell renal cell carcinoma (ccRCC) in an independent cohort of patients to validate recent work showing IMP3 as a prognostic marker for RCC progression and death. METHODS: The authors studied 716 consecutive tumor specimens from patients treated with surgery at the study institution for unilateral, sporadic, noncystic ccRCC between 1990 and 1999. Tissues were stained and scored for IMP3 expression and these expression levels were correlated with clinical and pathologic features as well as clinical outcomes including progression to distant metastases and death from RCC. RESULTS: It was observed that 213 ccRCC specimens (29.8%) expressed tumor cell IMP3. IMP3 expression was associated with advanced stage and grade of primary tumors as well as other adverse features including coagulative tumor necrosis and sarcomatoid differentiation. After multivariate adjustment for ccRCC prognostic features, positive IMP3 expression was still found to be associated with a 42% increase in the risk of death from RCC (hazards ratio [HR], 1.42; P= .024). Among the subset of patients with clinically localized disease, positive IMP3 expression was associated with a nearly 5-fold increased risk of distant metastases (HR, 4.71; P< .001). CONCLUSIONS: Using a large and independent cohort of ccRCC patients, the authors confirmed that tumor cell IMP3 expression represents an independent predictor of aggressive ccRCC tumor behavior.

Differences in organ system of distant metastasis by renal cell carcinoma subtype.

PURPOSE: The majority of the published data regarding the rates of renal cell carcinoma metastasis to specific locations has examined renal cell carcinoma as a whole. We evaluated site of distant metastasis by renal cell carcinoma histological subtype. MATERIALS AND METHODS: We studied 910 patients treated with radical nephrectomy for clear cell, papillary or chromophobe renal cell carcinoma at the Mayo Clinic between 1970 and 2000 who had distant metastasis at nephrectomy or who had metastasis during followup. The sites of metastases were compared by histological subtype using the chi-square and Fisher exact tests. RESULTS: There were 853 (94%) patients with clear cell, 39 (4%) with papillary and 18 (2%) with chromophobe renal cell carcinoma. Median followup for the 65 patients who were still alive at last followup was 11.6 years. Patients with clear cell renal cell carcinoma were more likely to have metastasis to the lungs (53.6%) compared to those with papillary (33.3%) and chromophobe (33.3%) renal cell carcinoma (p = 0.012). Patients with chromophobe renal cell carcinoma were more likely to have metastasis to the liver compared to those with clear cell renal cell carcinoma (33.3% vs 9.7%, p = 0.007), but there was not a statistically significantly difference in the incidence of liver metastases between patients with chromophobe and papillary renal cell carcinoma (33.3% vs 18.0%, p = 0.308). CONCLUSIONS: Site of distant metastasis varies significantly by renal cell carcinoma histological subtype. Patients with clear cell renal cell carcinoma are more likely to have metastasis to the lungs while patients with chromophobe renal cell carcinoma are more likely to experience liver metastasis.

Treatment of prostate cancer local recurrence after radical retropubic prostatectomy with 17-gauge interstitial transperineal cryoablation: initial experience.

OBJECTIVES: Interstitial transperineal cryoablation with 17-gauge cryoprobes is an accepted treatment modality for localized prostate cancer. The effectiveness of cryoablation in the treatment of local prostate cancer recurrence after radical retropubic prostatectomy (RRP) is unknown. METHODS: We reviewed the outcome of cryoablative treatment in 15 patients for biopsy-proven locally recurrent prostate cancer after RRP. The follow-up data included prostate-specific antigen (PSA) level, imaging findings, side effects, and an assessment of voiding habits. RESULTS: The mean follow-up time for the entire group was 20 months (range 4 to 32). Of the 15 patients, 6 (40%) had sustained declines in the PSA level (cryoablation success group) and 9 (60%) had disease progression (cryoablation failure group), defined as a PSA increase greater than 0.1 ng/mL from the PSA nadir, or the addition of external beam radiotherapy or androgen deprivation therapy. The pre-RRP PSA level and pre-cryoablation PSA level were similar for both groups. The pre-RRP biopsy Gleason scores (P = 0.03), RRP Gleason scores (P = 0.03), and lesion size on magnetic resonance imaging (P = 0.001) were lower in the success group than in the failure group. All patients who were recurrence free after cryotherapy had a biopsy and Gleason score of 6 or less. Of the 15 patients, 3 (20%) developed worsening of post-RRP incontinence. CONCLUSIONS: Our preliminary results suggest that salvage cryoablation can be an effective and safe treatment modality and a possible alternative to external beam radiotherapy for targeted control of confirmed local recurrences after RRP, especially in those with favorable biopsy or pathologic Gleason scores before cryotherapy. Larger cohorts and longer follow-up are needed to assess the viability of this treatment.

Cryosurgical changes in the porcine kidney: histologic analysis with thermal history correlation.

Advances in minimally invasive renal cryosurgery have renewed interest in the relative contributions of direct cryothermic and secondary vascular injury-associated ischemic cell injury. Prior studies have evaluated renal cryolesions seven or more days post-ablation and postulated that vascular injury is the primary cell injury mechanism; however, the contributions of direct versus secondary cell injury are not morphologically distinguishable during the healing/repair stage of a cryolesion. While more optimal to evaluate this issue, minimal acute (< or = 3 days) post-ablation histologic data with thermal history correlation exists. This study evaluates three groups of porcine renal cryolesions: Group (1) in vitro non-perfused (n = 5); Group (2) in vivo 2-h post-ablation perfused (n = 5); and Group (3) in vivo 3-day post-ablation perfused (n = 6). The 3.4 mm argon-cooled cryoprobe's thermal history included a 75 degrees C/min cooling rate, -130 degrees C end temperature, 60 degrees C/min thawing rate, and 15-min freeze time. An enthalpy-based mathematical model with a 2-D transient axisymmetric numerical solution with blood flow consideration was used to determine the thermal history within the ice ball. All three groups of cryolesions showed histologically similar central regions of complete cell death (CD) and transition zones of incomplete cell death (TZ). The CD had radii of 1.4, 1.1, and 1.0 cm in the non-perfused, 2-h and 3-day lesions, respectively. Capillary thrombosis was present in the 2-h perfused cryolesions with the addition of TZ arteriolar/venous thrombosis in the 3-day perfused lesions. Thermal modeling revealed the outer CD boundary in all three groups experienced similar thermal histories with an approximately -20 degrees C end temperature and 2 degrees C/min cooling and thawing rates. The presence of similar CD histology and in vitro/in vivo thermal histories in each group suggests that direct cryothermic cell injury, prior to or synchronous with vascular thrombosis, is a primary mediator of cell death in renal cryolesions.

The cryobiology of cryosurgical injury.

Cryosurgery, or tissue destruction by controlled freezing, has been investigated as a possible alternative to surgical intervention in the treatment of many diseases. This technique, which is under the larger category of thermal therapy, has its origins in the 1800s when advanced carcinomas of the breast and uterine cervix were treated with iced saline solutions. Since those early times, this technique has been used routinely to treat malignancies on the surface of the body (ie, dermatologic tumors) and has gained some acceptance as a clinical tool for the management of internal malignancies, including carcinoma of the prostate and kidney. The main advantages of the technique are the potential for less invasiveness and lower morbidity compared with surgical excision. The study of the destructive process of freezing is the focus of this article and is divided into 2 main areas: (1) understanding the mechanism by which freezing destroys tissue, and (2) understanding the thermal history that causes tissue destruction. The term "thermal history," as used in this article, will mean the time-temperature history experienced by the tissue during a thermal insult.