Sergio Bertoglio

Enoxaparin for the Prevention of Venous Thromboembolism Associated With Central Vein Catheter: A Double-Blind, Placebo-Controlled, Randomized Study in Cancer Patients

PURPOSE The extent of venous thromboembolism (VTE) associated with central vein catheters (CVC) in cancer patients remains unclear. The aim of this study was to evaluate the efficacy and safety of the low molecular weight heparin, enoxaparin, in the prevention of VTE. PATIENTS AND METHODS In a multicenter, double-blind study, consecutive cancer patients scheduled for CVC insertion were randomly assigned to receive either subcutaneous enoxaparin 40 mg once a day or placebo. Treatment was started 2 hours before CVC insertion and continued for 6 weeks. The primary end points of the study were deep vein thrombosis (DVT), confirmed by venography of the CVC limb performed 6 weeks after randomization, or clinically overt pulmonary embolism, confirmed by objective testing during the study drug administration. Patients were assessed for bleeding complications. RESULTS Three hundred eighty-five patients were randomized, of which 321 (83.4%) underwent venography. A venography was adequate for adjudication in 155 patients in each treatment group. A DVT was observed in 22 patients (14.1%) treated with enoxaparin and in 28 patients (18.0%) treated with placebo, corresponding to a relative risk of 0.78 (95% CI, 0.47 to 1.31). No major bleeding occurred. Five patients (2.6%) in the enoxaparin group and two patients (1.0%) in the placebo group died during the treatment period. CONCLUSION In this study, no difference in the rate of CVC-related VTE was detected between patients receiving enoxaparin and patients receiving placebo. The dose of enoxaparin used in this study proved to be safe. Clinical trials evaluating higher enoxaparin doses could optimize the efficacy of this agent for this indication.

Sentinel lymph node mapping and biopsy for breast cancer: a review of the literature relative to 4791 procedures.

The status of axillary nodes is the most important prognostic factor in breast cancer to select patient subgroups for adjuvant chemotherapy; the current standard of care for surgical management of invasive breast cancer is complete removal of the tumor by either mastectomy or lumpectomy followed by axillary lymph node dissection (ALND). The recent introduction of intraoperative lymphatic mapping and sentinel lymph node biopsy (SLND) represents a major new opportunity for appropriate and less invasive surgical management of many tumors. There is an almost uniformly enthusiasm concerning the potential of this technique in breast carcinoma management, shown by published data. A peculiar attention to the so-called “sentinel node debate” in breast cancer surgery is a constant in the last years issues of the major medical journals. Even patients have become more aware about medical enthusiasm and their request of concise information on the topic and the possibilities of this approach is an increasing reality in medical practice. The aim of this paper is to review recent literature to offer an overview about the main controversial methodological aspects and a wide analysis of reported results. The most significative international literature papers from Medline were retrieved from 1993 to September 1999, and 4782 procedures were analysed. This extensive review of the literature has confirmed accuracy, feasibility and reliability of the SN detecting technique in axillary mapping. Provided a good proficiency in SN localisation and pathological evaluation, human resources and efforts should be mainly focused on its clinical validation as an alternative to ALND instead of on further phase I–-II clinical studies.

The Postoperative Analgesic Efficacy of Preperitoneal Continuous Wound Infusion Compared to Epidural Continuous Infusion with Local Anesthetics After Colorectal Cancer Surgery: A Randomized Controlled Multicenter Study

BACKGROUND: Open colorectal cancer (CRC) surgery induces severe and prolonged postoperative pain. The optimal method of postoperative analgesia in CRC surgery has not been established. We evaluated the efficacy of preperitoneal continuous wound infusion (CWI) of ropivacaine for postoperative analgesia after open CRC surgery in a multicenter randomized controlled trial. METHODS: Candidates for open CRC surgery randomly received preperitoneal CWI analgesia or continuous epidural infusion (CEI) analgesia with ropivacaine 0.2% 10 mL/h for 48 hours after surgery. Fifty-three patients were allocated to each group. All patients received patient-controlled IV morphine analgesia. RESULTS: Over the 72-hour period after the end of surgery, CWI analgesia was not inferior to CEI analgesia. The difference of the mean visual analog scale score between CEI and CWI patients was 1.89 (97.5% confidence interval = −0.42, 4.19) at rest and 2.76 (97.5% confidence interval = −2.28, 7.80) after coughing. Secondary end points, morphine consumption and rescue analgesia, did not differ between groups. Time to first flatus was 3.06 ± 0.77 days in the CWI group and 3.61 ± 1.41 days in the CEI group (P = 0.002). Time to first stool was shorter in the CWI than the CEI group (4.49 ± 0.99 vs 5.29 ± 1.62 days; P = 0.001). Mean time to hospital discharge was shorter in the CWI group than in the CEI group (7.4 ± 0.41 and 8.0 ± 0.38 days, respectively). More patients in the CWI group reported excellent quality of postoperative pain control (45.3% vs 7.6%). Quality of night sleep was better with CWI analgesia, particularly at the postoperative 72-hour evaluation (P = 0.009). Postoperative nausea and vomiting was significantly less frequent with CWI analgesia at 24 hours (P = 0.02), 48 hours (P = 0.01), and 72 hours (P = 0.007) after surgery evaluations. CONCLUSIONS: Preperitoneal CWI analgesia with ropivacaine 0.2% continuous infusion at 10 mL/h during 48 hours after open CRC surgery provided effective postoperative pain relief not inferior to CEI analgesia.

Efficacy of Normal Saline Versus Heparinized Saline Solution for Locking Catheters of Totally Implantable Long-Term Central Vascular Access Devices in Adult Cancer Patients

Background:Heparin solution is routinely used to maintain the patency of infusion devices. Literature supports the alternative use of normal saline solution for flushing and locking intravenous infusion devices especially for pediatric patients. There is uncertainty regarding safety and efficacy of this policy for intermittent locking of implanted ports. Objective:This study evaluates efficacy and safety of normal saline solution for intermittent locking procedures of implanted ports. Methods:This is a retrospective observational cohort study of 610 implanted ports receiving 2 different locking solutions conducted at the National Institute for Cancer Research, IST Genova, Italy, from January 2007 to August 2009. Group A (n = 297) received heparinized solution (10 mL/500 U heparin), whereas group B (n = 313), 10 mL normal saline. Primary endpoint was irreversible port occlusion. Minimum follow-up was 12 months. The role of age, type of tumor, disease stage, access site, access body side, catheter tip position, and concomitant use of parenteral nutrition and chemotherapy was evaluated in secondary aim. Results:Results fail to show statistically significant differences in implanted ports survival free from failure for occlusive events between the use of heparinized solution and that of normal saline for the maintenance of port patency, both in univariate (P = .9) and in multivariate analyses (P = .7). Conclusion:Normal saline solution seems to be as effective as heparinized solution for keeping patent implanted ports in adult cancer patients. Implications for Practice:Switching from heparinized solution to normal saline for catheter intermittent lock of ports seems a safe procedure.

Peripherally inserted central catheters (PICCs) in cancer patients under chemotherapy: A prospective study on the incidence of complications and overall failures.

The increasing use of peripherally inserted central venous catheters (PICCs) for chemotherapy has led to the observation of an elevated risk of complications and failures. This study investigates PICC failures in cancer patients.

Long-term femoral vein central venous access in cancer patients

Subclavian percutaneous access with reservoir placement has been shown to be difficult or contraindicated in some patients. Of 465 cancer patients who required a port placement between January 1992 to January 1995, 41 (8.8%) had alternative percutaneous femoral access with a totally implantable port reservoir located in the abdomen because of the inaccessibility to subclavian or jugular veins and/or the presence of massive cutaneous metastases or severe radiodermitis in the upper part of the torso. Overall implant days was 9880, with an average of 241 days (range: 65-445). Ports were alternatively used for chemotherapy and nutritional purposes in 11 of 41 patients. Late morbidity causing the removal of the implanted ports was observed in two of 41 (4.9%) and 25 of 424 (5.9%) patients in the femoral and subclavian series, respectively (P = 0.86). The femoral percutaneous access for totally implantable port devices appears to be a safe alternative for cancer patients when subclavian and/or jugular vein catheterization and reservoir in the upper part of the torso is contraindicated.

Radioimmunoguided surgery after primary treatment of locally advanced breast cancer.

PURPOSE To assess the role of radioimmunoguided surgery (RIGS) using a handheld intraoperative gamma-detecting probe (GDP) to identify neoplastic disease after primary chemotherapy in locally advanced breast cancer (LABC) patients injected with iodine 125-labeled monoclonal antibodies (MAbs). PATIENTS AND METHODS Twenty-one patients with histologically documented LABC were treated with a combined modality approach. After three courses of primary chemotherapy and before modified radical mastectomy, the 125I-radiolabeled MAbs B72.3 (anti-TAG72) and FO23C5 (anti-carcinoembryonic antigen [CEA]) were administered to 11 patients (group A) and 10 patients (group B), respectively. At surgery, a GDP was used to locate the primary tumor and to assess possible tumor multicentricity and the presence of ipsilateral axillary metastases. Routine pathologic examination was performed in neoplastic and normal tissue specimens of all 21 patients. In addition, immunohistochemical assay for TAG72 and CEA expression was performed. RESULTS In group A patients, RIGS identified primary tumor in seven of 11 patients (63.3%) and unpalpable multicentric tumor lesions were located in two of four (50%). Positive axillary lymph nodes were histologically documented in eight of 11 patients (72.7%) and RIGS identified three of eight (37.5%). In group B, RIGS located the primary tumor lesion in four of 10 patients (40%); in two cases, the tumor was not clinically evident. Multicentricity was observed in one of two patients and lymph node involvement in three of nine (33.3%). No false-positive results were observed in either group A or B. CONCLUSION RIGS appears to be a safe and reliable technique. However, the MAbs used in this study are not sufficiently specific. RIGS represents a technique for which the full potential for intraoperative assessment of breast cancer lesions can be reached when more specific antibodies become readily available.

Perilymphatic injections of recombinant interleukin‐2 (rIL‐2) partially correct the immunologic defects in patients with advanced head and neck squamous cell carcinoma

Patients with advanced head and neck squamous cell carcinoma (HNSCC) are severely immunocompromised. In virtually all such patients who have been studied, reduced numbers of circulating CD3+ T‐cell‐receptor (TCR)α/β + T lymphocytes, a reduction of natural killer (NK) activity, and a poor induction of lymphokine‐activated killer (LAK) cell activity (following in vitro treatment with recombinant interleukin‐2 [rIL‐2]) have been detected. Recently, however, it has been demonstrated that perilymphatic injections of low doses of rIL‐2 may induce a local reduction of tumor masses in these patients.

SENTINEL NODE BIOPSY IN PATIENTS WITH CUTANEOUS MELANOMA

The role of elective lymph node dissection (ELND) for treatment of cutaneous melanoma is still debated. Initially, lymphatic mapping technique was performed by an intradermic injection of vital blue dye; subsequently, it was improved by the use of radioguided surgery (RGS). Preliminary experience with this technique proved effective for detection of clinical occult lymph node metastasis; it may also enable the surgeon to perform a selective lymph node dissection (SLND) to concentrate on pathologic node-positive patients for the same potential benefits that have been provided by ELND. We performed sentinel node biopsy on 48 patients with stage pT3N0M0 melanoma. Vital blue dye mapping only was carried out on 39 patients; the remaining nine patients had a combined lymphatic mapping with both blue dye and RGS. The sentinel lymph node (SLN) was identified in 46 of 48 patients (95.8%). Ten patients (20.8%) were found to have metastatic melanoma cells in their SLN(s); all these patients underwent SLND of the affected basin. Our findings confirm that the intraoperative lymphatic mapping of the SLN using both blue dye and radiodetection is an appropriate and simple technique for selecting patients who are more likely to benefit from lymph node dissection.

A double-blind placebo-controlled randomized study on the efficacy and safety of enoxaparin for the prevention of upper limb deep vein thrombosis in cancer patients with central vein catheter

8021 Background: Efficacy of prophylaxis with fixed dose of warfarin or low molecular weight heparin (LMWH) for upper limb deep vein thrombosis (UL-DVT) related to central vein catheter (CVC) has been claimed after open studies with limited sample size. The rate of bleeding in cancer patients receiving prolonged prophylaxis with LMWH is unclear. The aim of this study was to evaluate the efficacy and safety of the LMWH enoxaparin in the prevention of UL-DVT in cancer patients with CVC. METHODS Consecutive cancer patients with CVC for chemotherapy were included in a multicenter double-blind randomized placebo-controlled study performed in 11 Italian centers. Enoxaparin, 40 mg once a day, or placebo were given subcutaneously for 6 weeks, starting 2 hours before the CVC insertion. The primary endpoint of the study was UL-DVT, as detected by venography (CVC limb) performed at 6 weeks and/or clinically overt pulmonary embolism confirmed by objective testing. The secondary endpoints of the study were death from thromboembolic disease and death from any cause at 3-month. The safety endpoint was major bleeding. RESULTS 385 patients were included in the study. 321 patients underwent venography (83.4%). The primary efficacy outcome was assessed in 310 patients with adequate venography. Enoxaparin reduced the incidence of UL-DVT from 18.1 % (28/155) to 14.2 % (22/155), a relative risk reduction of 21.4 % (95% CI: 0.47 to 1.31, p=0.35). Two patients in the enoxaparin group (1.0%) and 6 patients in the placebo group (3.1%) had a symptomatic venous thromboembolism. No major bleeding occurred in both treatment groups. Minor bleeding occurred in 6.3% of the patients (12/191) in the enoxaparin group and 3.6% of the patients (7/194) in the placebo group. CONCLUSIONS Enoxaparin, at the dose of 40 mg daily, produced a 21% non significant reduction in the incidence of CVC-related DVT in cancer patients. This dose was safe and well tolerated: this leaves open the option of increasing the dose of enoxaparin to optimize its efficacy in this clinical setting. No significant financial relationships to disclose.