Dose-dense adjuvant chemotherapy in early breast cancer patients: 15-year results of the Phase 3 Mammella InterGruppo (MIG)-1 study.

BACKGROUND: Adjuvant chemotherapy is the standard of care in high-risk early breast cancer patients. Dose-dense should be the preferred schedule of administration. However, its long-term benefit is unknown. METHODS: In the Italian multicentre Phase 3 randomised MIG-1 trial, node-positive and high-risk node- negative breast cancer patients were randomised to receive six cycles of adjuvant fluorouracil, epirubicin and cyclophosphamide regimen administered every 3 (FEC21) or 2 (FEC14) weeks. The primary endpoint was overall survival (OS), and the secondary endpoint was event-free survival (EFS). RESULTS: From 1992 to 1997, 1214 patients were included. Median follow-up was 15.8 years. In all, 15-year OS was 71% and 68% in the FEC14 and FEC21 groups, respectively (HR = 0.89; p = 0.25). In all, 15-year EFS was 47% and 43% in the FEC14 and FEC21 groups, respectively (HR = 0.87; p = 0.18). In a pre-planned subgroup analysis, among patients with hormone receptor-negative tumours, 15-year OS was 70% and 65% in the FEC14 and FEC21 groups, respectively (HR = 0.73; 95% CI: 0.51-1.06); 15-year EFS was 58% and 43% in the FEC14 and FEC21 groups, respectively (HR = 0.70; 95% CI: 0.51-0.96). CONCLUSIONS: Updated results from the MIG-1 study are numerically in favour of dose-dense chemotherapy, and suggest a long-term benefit of this approach in high-risk early breast cancer patients.

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

BACKGROUND AND OBJECTIVES: 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. METHODS: A prospective study was conducted at a single cancer institution on 291 PICC placement for chemotherapy. The primary study outcome was PICC failure. RESULTS: Median follow-up was 119 days. PICC complications occurred in 72 patients (24.7%) and failures with removal in 44 (15.1%). Reasons for failures were upper extremity deep venous thrombosis (UEDVT) 12 (4.1%), central line associate bloodstream infection (CLABSI) 5 (1.7%) with an infection rate of 0.95 per 1,000 catheter days, exit site infection 9 (3.1%) with a rate of 1.46 per 1,000 catheter days, catheter dislodgment 11 (3.8%), and occlusion 7 (2.4%). Statistically significant risk factors were previous DVT (HR 2.95, 95%CI 1.33-6.53), reason for PICC implant (HR 3.65, 95%CI 1.12-10.34) and 5-fluorouracil, oxaliplatin and bevacizumab based chemotherapy (HR 3.11, 95%CI 1.17-8.26). CONCLUSIONS: PICC is a safe venous device for chemotherapy delivery. Nevertheless, a 15% rate of failure has to be taken in account when planning PICC insertion for chemotherapy purposes. J. Surg. Oncol. 2016;113:708-714. © 2016 Wiley Periodicals, Inc.

European recommendations on the proper indication and use of peripheral venous access devices (the ERPIUP consensus): A WoCoVA project.

Since several innovations have recently changed the criteria of choice and management of peripheral venous access (new devices, new techniques of insertion, new recommendations for maintenance), the WoCoVA Foundation (WoCoVA = World Conference on Vascular Access) has developed an international Consensus with the following objectives: to propose a clear and useful classification of the currently available peripheral venous access devices; to clarify the proper indication of central versus peripheral venous access; discuss the indications of the different peripheral venous access devices (short peripheral cannulas vs long peripheral cannulas vs midline catheters); to define the proper techniques of insertion and maintenance that should be recommended today. To achieve these purposes, WoCoVA have decided to adopt a European point of view, considering some relevant differences of terminology between North America and Europe in this area of venous access and the need for a common basis of understanding among the experts recruited for this project. The ERPIUP Consensus (ERPIUP = European Recommendations for Proper Indication and Use of Peripheral venous access) was designed to offer systematic recommendations for clinical practice, covering every aspect of management of peripheral venous access devices in the adult patient: indication, insertion, maintenance, prevention and treatment of complications, removal. Also, our purpose was to improve the standardization of the terminology, bringing clarity of definition, and classification.

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.

Reverse tapered versus non-tapered peripherally inserted central catheters: A narrative review.

Introduced over 20 years ago, the reverse tapering design for PICC catheters is supposed to have some benefits in terms of both efficacy and safety. In particular, it would ensure less postoperative bleeding at the exit site and greater effectiveness in preventing kinking or twisting of the same. Since its introduction, these hypothesized advantages have never been demonstrated in clinical studies, however very scarce, which have highlighted neither advantages nor disadvantages of reverse tapered catheters when compared to non-reverse tapered ones. This narrative review analyzes some aspects of the use of reverse tapered PICCs, also paying attention to some possible undesirable effects that have arisen from the introduction into clinical practice of new subcutaneous systems of securement of PICCs to the skin. Clinicians should be aware of the fact that reverse tapering design does not represents a sure improvement in terms of safety and efficacy of PICCs and its adoption should be weighed against possible clinical disadvantages.

Management of antithrombotic treatment and bleeding disorders in patients requiring venous access devices: A systematic review and a GAVeCeLT consensus statement.

Insertion of venous access devices (VAD) is usually considered a procedure with low risk of bleeding. Nonetheless, insertion of some devices is invasive enough to be associated with bleeding, especially in patients with previous coagulopathy or in treatment with antithrombotic drugs for cardiovascular disease. The current practices of platelet/plasma transfusion in coagulopathic patients and of temporary suspension of the antithrombotic treatment before VAD insertion are based on local policies and are often inadequately supported by evidence, since many of the clinical studies on this topic are not recent and are not of high quality. Furthermore, the protocols of antithrombotic treatment have changed during the last decade, after the introduction of new oral anticoagulant drugs. Though some guidelines address some of these issues in relation with specific procedures (port insertion, etc.), no evidence-based document covering all the aspects of this clinical problem is currently available. Thus, the Italian Group of Venous Access Devices (GAVeCeLT) has decided to develop a consensus on the management of antithrombotic treatment and bleeding disorders in patients requiring VADs. After a systematic review of the available evidence, the panel of the consensus (which included vascular access specialists, surgeons, intensivists, anesthetists, cardiologists, vascular medicine experts, nephrologists, infective disease specialists, and thrombotic disease specialists) has structured the final recommendations as detailed answers to three sets of questions: (1) which is an appropriate classification of VAD-related procedures based on the specific bleeding risk? (2) Which is the appropriate management of the patient with bleeding disorders candidate to VAD insertion/removal? (3) Which is the appropriate management of the patient on antithrombotic treatment candidate to VAD insertion/removal? Only statements reaching a complete agreement were included in the final recommendations, and all recommendations were offered in a clear and synthetic list, so to be easily translated into clinical practice.

A multicenter retrospective study on 4480 implanted PICC-ports: A GAVeCeLT project.

BACKGROUND: PICC-ports may be defined as totally implantable central venous devices inserted in the upper limb using the current state-of-the-art techniques of PICC insertion (ultrasound-guided venipuncture of deep veins of the arm, micro-puncture kits, proper location of the tip preferably by intracavitary ECG), with placement of the reservoir at the middle third of the arm. A previous report on breast cancer patients demonstrated the safety and efficacy of these devices, with a very low failure rate. METHODS: This retrospective multicenter cohort study-developed by GAVeCeLT (the Italian Group of Long-Term Venous Access Devices)-investigated the outcomes of PICC-ports in a large cohort of unselected patients. The study included 4480 adult patients who underwent PICC-port insertion in five Italian centers, during a period of 60 months. The primary outcome was device failure, defined as any serious adverse event (SAE) requiring removal. The secondary outcome was the incidence of temporary adverse events (TAE) not requiring removal. RESULTS: The median follow-up was 15.5 months. Device failure occurred in 52 cases (1.2%), the main causes being local infection (n = 7; 0.16%) and CRBSI (n = 19; 0.42%). Symptomatic catheter-related thrombosis occurred in 93 cases (2.1%), but removal was required only in one case (0.02%). Early/immediate and late TAE occurred in 904 cases (20.2%) and in 176 cases (3.9%), respectively. CONCLUSIONS: PICC-ports are safe venous access devices that should be considered as an alternative option to traditional arm-ports and chest-ports when planning chemotherapy or other long-term intermittent intravenous treatments.

WoCoVA consensus on the clinical use of in-line filtration during intravenous infusions: Current evidence and recommendations for future research.

The need for filtering intravenous infusions has long been recognized in the field of venous access, though hard scientific evidence about the actual indications for in-line filters has been scarce. In the last few years, several papers and a few clinical studies have raised again this issue, suggesting that the time has come for a proper definition of the type of filtration, of its potential benefit, and of its proper indications in clinical practice. The WoCoVA Foundation, whose goal is to increase the global awareness on the risk of intravenous access and on patients' safety, developed the project of a consensus on intravenous filtration. A panel of experts in different aspects of intravenous infusion was chosen to express the current state of knowledge about filtration and to indicate the direction of future research in this field. The present document reports the final conclusions of the panel.

Extending the interval of flushing procedures of totally implantable vascular access devices in cancer patients: It is time for a change.

Several recent literature reports regarding the flushing technique of TIVADs highlight how the definition of the optimal flushing interval is still a source of controversy. Several recent studies indicate more and more frequently how 4 weeks can be considered a too short interval for the flushing of a totally implantable access device (TIVAD); on the other hand most of the main guidelines and instructions for use provided by the device's manufacturers still suggest an interval between 4 weeks and 1 month as the ideal one. The recent meta-analysis by Wu et al. on this topic, promotes an important strategy change, indicating the possibility of extending the flushing intervals at least up to 8 weeks. This editorial extensively discusses the flushing methods of TIVADs highlighting the need for important and substantial changes, both in extending the range of flushes and in the solutions and methods to be used. It represents an invitation to the scientific community and device manufacturers for a complete revision of the indications on flushing techniques.

International recommendations for a vascular access minimum dataset: a Delphi consensus-building study.

BACKGROUND: Data regarding vascular access device use and outcomes are limited. In part, this gap reflects the absence of guidance on what variables should be collected to assess patient outcomes. We sought to derive international consensus on a vascular access minimum dataset. METHODS: A modified Delphi study with three rounds (two electronic surveys and a face-to-face consensus panel) was conducted involving international vascular access specialists. In Rounds 1 and 2, electronic surveys were distributed to healthcare professionals specialising in vascular access. Survey respondents were asked to rate the importance of variables, feasibility of data collection and acceptability of items, definitions and response options. In Round 3, a purposive expert panel met to review Round 1 and 2 ratings and reach consensus (defined as ≥70% agreement) on the final items to be included in a minimum dataset for vascular access devices. RESULTS: A total of 64 of 225 interdisciplinary healthcare professionals from 11 countries responded to Round 1 and 2 surveys (response rate of 34% and 29%, respectively). From the original 52 items, 50 items across five domains emerged from the Delphi procedure.Items related to demographic and clinical characteristics (n=5; eg, age), device characteristics (n=5; eg, device type), insertion (n=16; eg, indication), management (n=9; eg, dressing and securement), and complication and removal (n=15, eg, occlusion) were identified as requirements for a minimum dataset to track and evaluate vascular access device use and outcomes. CONCLUSION: We developed and internally validated a minimum dataset for vascular access device research. This study generated new knowledge to enable healthcare systems to collect relevant, useful and meaningful vascular access data. Use of this standardised approach can help benchmark clinical practice and target improvements worldwide.

Left lower limb fasciitis due to sigmoid colonic perforated diverticulitis: a rare case of colocutaneous fistula.

Up to 25% of patients with acute diverticulitis develop complicated disease. Colocutaneous fistula with lower limb fasciitis secondary to complicated diverticulitis is a rare event. A 71-year-old woman with Class 3 obesity and Type 2 diabetes was admitted to the hospital because of left lower limb fasciitis associated with acute sigmoid diverticulitis complicated by covered perforation. The fasciitis was treated with multiple fasciotomies, antibiotics and hyperbaric oxygen therapy. The patient was readmitted 25 days after discharge because of the formation of a left leg colocutaneous fistula associated with an enterocolic fistula. Patient underwent sigmoid resection with primary anastomosis and ileal loop repair. Three-month follow-up showed fistula healing and absence of symptoms. Fasciitis secondary to acute diverticulitis is a rare clinical scenario. Although our therapeutic strategy was successful, the optimal treatment timing and surgical technique for fasciotomy and colon resection remain to be assessed.

PICC-PORT totally implantable vascular access device in breast cancer patients undergoing chemotherapy.

BACKGROUND AND OBJECTIVES: The increasing use of arm totally implantable vascular access devices for breast cancer patients who require chemotherapy has led to a greater risk of complications and failures and, in particular, to upper extremity deep vein thrombosis. This study aims to investigate the outcomes of the arm peripherally inserted central catheter-PORT technique in breast cancer patients. METHODS: The peripherally inserted central catheter-PORT technique is an evolution of the standard arm-totally implantable vascular access device implant based on guided ultrasound venous access in the proximal third of the upper limb with subsequent placement of the reservoir at the middle third of the arm. A prospective study was conducted on 418 adult female breast cancer patients undergoing chemotherapy. The primary study outcome was peripherally inserted central catheter-PORT failure. RESULTS: Median follow-up was 215 days. Complications occurred in 29 patients (6.9%) and failure resulting in removal of the device in 11 patients (2.6%). The main complication we observed was upper extremity deep vein thrombosis, 10 (2.4%); all patients were rescued by anticoagulant treatment without peripherally inserted central catheter-PORT removal. The main reason for removal was reservoir pocket infection: 4 (0.9%) with an infection rate of 0.012 per 1000 catheter days. Cumulative 1-year risk of failure was 3.6% (95% confidence interval, 1.3%-7.1%). With regard to the patients' characteristics, body mass index <22.5 was the only significant risk for failure (p = 0.027). CONCLUSION: The peripherally inserted central catheter-PORT is a safe vascular device for chemotherapy delivery that achieves similar clinical results as traditional long-term vascular access devices (peripherally inserted central catheter and arm totally implantable vascular access device, in particular) in breast cancer patients.

Inferior vena cava resection without reconstruction for retroperitoneal malignancies.

Inferior vena cava (IVC) involvement in retroperitoneal malignancies is a rare occurrence and radical surgery with major vascular resection represents the only potential curative treatment. IVC replacement after resection is still controversial and only small series and few prospective data are available. We report a series of three patients affected by retroperitoneal masses involving IVC treated with vena cava resection without replacement. All patients were treated by a radical R0 surgical procedure associated with infrarenal IVC resection and no reconstruction. Based on preoperative radiologic imaging and intraoperative findings, one patient also underwent right nephrectomy, while another patient underwent left renal vein ligation without nephrectomy. Neither early nor late severe post-operative complications related to the absence of IVC outflow were observed. Resection without replacement of the infrarenal IVC results in acceptable morbidity, thus specific risks related to the use of prosthetic grafts can be avoided.

Possible role of low magnesium levels in the onset of postoperative hypoparathyroidism following thyroidectomy.

BACKGROUND: A positive correlation between calcium and magnesium serum levels is well known and depends upon various factors. This study aims at verifying the existence of this association in a retrospective series of patients who underwent thyroid surgery. METHODS: Two hundred and eighty-five consecutive patients (202 female, 83 male, mean age 57 years) who underwent at least total thyroidectomy (TT) and had a complete clinical and biochemical pre- and postoperative evaluation were included in the study. Patients were evaluated with regard to: sex, age, indications for surgery, operative time, number of accidentally removed parathyroids, extent and time of surgery, thyroiditis, final histology, pre- and postoperative levels of calcium, magnesium, vitamin D, and creatinine, presence of symptoms of hypocalcemia. Statistical analysis was performed using the R software. RESULTS: In the postoperative period, biochemical hypocalcemia (<8.5 mg/dL) was observed in 126 patients (44%) and severe hypocalcemia (<7.5 mg/dL, a level indicating the need for longer hospitalization) was seen in 40 (14%). When analyzing patients with and without postoperative hypocalcemia, the factors affecting postoperative biochemical hypocalcemia were: older age (P=0.019), longer operative time (P=0.039), and a highly significant correlation between postoperative calcium and magnesium levels (r=0.432; P<0.001). CONCLUSIONS: The only factor among the ones we analyzed in this retrospective study that would appear to be linked to the onset of clinically relevant hypocalcemia is low magnesium levels in the postoperative period. A prospective randomized study with a group of patients undergoing magnesium replacement in the postoperative period can clarify the possible role of magnesium repletion on hypocalcemia.

Sentinel lymph node biopsy in patients with malignant melanoma: analysis of post-operative complications.

BACKGROUND: This study investigates the incidence of post-operative complications and risk factors of sentinel lymph node biopsy (SLNB) in melanoma patients. METHODS: A retrospective cohort study was conducted at a single cancer institution on 408 consecutive SLNBs. RESULTS: Fifty-five post-operative complications occurred in 39 (9.5%) patients and included: wound infection in 24 (5.9%), seroma and lymphorrhea in 15 (3.7%), wound dehiscence in seven (1.7%), lymphocele in six (1.5%) and others in three (0.7%). Univariate analysis failed to identify possible risk factors (i.e. gender, age, lymph node region, number of excised lymph nodes, Breslow index, pT levels, comorbidities, length of surgery and hospital stay). Metastatic sentinel nodes occurred in four of 135 (3%) patients with thin melanoma (Breslow <1 mm) and in 68 of 262 (25.9%) patients with Breslow >1 mm. CONCLUSION: For patients with thin melanoma in whom the incidence of lymph node metastasis is low, the reported post-operative morbidity of almost 10% of SLNB highlights the need for careful patient selection.

Sentinel lymph node biopsy in porocarcinoma: A case reports.

INTRODUCTION: Eccrine porocarcinoma (EPC) is a slow-growing carcinoma arising from the eccrine sweat glands. Based on its clinical presentation it can be confused with malignant and benign skin lesions, both. Histological examination is essential to formulate a correct diagnosis. Surgical excision with clear margins is the standard therapeutic approach while the role of sentinel lymph node biopsy (SNLB) remains controversial. CASE PRESENTATION: The Authors report two cases of EPC of the lower limbs occurred in two women. Patients were treated by wide surgical excision of the lesion and SNLB. 6 months follow-up was disease free for both patients. CONCLUSION: Although a rare cutaneous tumor, EPC has to be taken into account in the differential diagnosis of malignant skin lesions because of its possible loco-regional aggressiveness and related morbidity. Among the available treatment options, surgical excision is considered the standard approach whereas the role of SNLB is controversial although the Authors discuss a possible usefulness for staging and diagnosis.

Primary osteosarcoma of the spermatic cord: case report and literature review.

Primary osteosarcoma of the spermatic cord is a rare tumour with few mentions in the literature. A 59-year-old man presented with a large painless left inguinal and scrotal mass. The patient underwent excision of the mass, which arose from the spermatic cord. A left high dissection of the spermatic cord and radical orchiectomy due to associated atrophy of the left testicle were performed. Pathological findings were suggestive of spermatic cord osteosarcoma. The patient died eleven years later of metastatic lung disease. Spermatic cord osteosarcoma is an uncommon neoplasm and its preoperative diagnosis is very difficult. Any palpable suspicious mass of the cord should be investigated with ultrasonography before excision; CT scan and magnetic resonance imaging may be helpful in defining preoperative diagnosis and the extension of the mass into the neighbouring tissues. Surgical treatment of spermatic cord sarcomas in adults is via a radical orchiectomy with high dissection of the spermatic cord and en bloc excision of involved neighbouring tissues; overall 5- and 10-year survival rates are reported in the literature to be 75% and 55%, respectively.

Improving outcomes of short peripheral vascular access in oncology and chemotherapy administration.

A short peripheral intravenous catheter or cannula (PIVC) is frequently used to deliver chemotherapy in oncology practice. Although safe and easy to insert, PIVCs do fail, leading to personal discomfort for patients and adding substantially to treatment costs. As the procedure of peripheral catheterization is invasive, there is a need for greater consistency in the choice, insertion and management of short PIVCs, particularly in the oncology setting where there is a growing trend for patients to receive many different courses of IV treatment over a number of years, sometimes with only short remissions. This article reviews best practice with respect to PIVCs in cancer patients and considers the necessity for bundling these actions. Two care bundles, addressing both insertion and ongoing care and maintenance, are proposed. These have the potential to improve outcomes with the use of short PIVCs for vascular access in oncology practice.

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.