Simonetta Pozzi

Best choice of central venous insertion site for the prevention of catheter-related complications in adult patients who need cancer therapy: a randomized trial

BACKGROUND Central venous access is extensively used in oncology, though practical information from randomized trials on the most convenient insertion modality and site is unavailable. METHODS Four hundred and three patients eligible for receiving i.v. chemotherapy for solid tumors were randomly assigned to implantation of a single type of port (Bard Port, Bard Inc., Salt Lake City, UT), through a percutaneous landmark access to the internal jugular, a ultrasound (US)-guided access to the subclavian or a surgical cut-down access through the cephalic vein at the deltoid-pectoralis groove. Early and late complications were prospectively recorded until removal of the device, patients death or ending of the study. RESULTS Four hundred and one patients (99.9%) were assessable: 132 with the internal jugular, 136 with the subclavian and 133 with the cephalic vein access. The median follow-up was 356.5 days (range 0-1087). No differences were found for early complication rate in the three groups {internal jugular: 0% [95% confidence interval (CI) 0.0% to 2.7%], subclavian: 0% (95% CI 0.0% to 2.7%), cephalic: 1.5% (95% CI 0.1% to 5.3%)}. US-guided subclavian insertion site had significantly lower failures (e.g. failed attempts to place the catheter in agreement with the original arm of randomization, P = 0.001). Infections occurred in one, three and one patients (internal jugular, subclavian and cephalic access, respectively, P = 0.464), whereas venous thrombosis was observed in 15, 8 and 11 patients (P = 0.272). CONCLUSIONS Central venous insertion modality and sites had no impact on either early or late complication rates, but US-guided subclavian insertion showed the lowest proportion of failures.

Full Robotic Left Colon and Rectal Cancer Resection: Technique and Early Outcome

AbstractObjectiveThe technique for robotic resection of the left colon and anterior resection of the rectum with total mesorectal excision is not well defined. In this study we describe a method that standardizes robot and trocar position, and allows for a complete mobilization of the left colon and the rectum, without repositioning of the surgical cart. Outcome and pathology findings are also reported. MethodsFrom January 2007 to May 2008 a total of 55 consecutive patients affected by rectal and left colon cancer were operated on, with full robotic technique, using the Da Vinci robot. Data regarding outcome and pathology reports were prospectively collected in a dedicated database.ResultsThe following procedures were performed 27 left colectomies, 17 anterior resections, 4 intersphincteric resections, 7 abdominoperineal resections. There were 21 female and 34 male patients with a mean age of 63 ± 9.9 years. Mean operative time was 290 ± 69 minutes, ranging from 164 to 487 min., none were converted to open surgery. The median number of lymph nodes harvested was 18.5 ± 8.3 (range 5-45), and circumferential margin was negative in all cases. Distal margin was 25.15 ± 12.9 mm (range 6-55) for patients with rectal cancer, and 31.6 ± 20 mm for all the patients in this series. Anastomotic leak rate was 12.7% (7/55); in all cases conservative treatment was successful.ConclusionsFull robotic colorectal surgery is a safe and effective technique that exploits the advantages of the Da Vinci robot during the whole intervention, without the need to make use of hybrid operations. Outcome and pathology findings are comparable with those observed in open and laparoscopy procedures.

Genetic polymorphisms and modulation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-DNA adducts in human lymphocytes.

2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) is the most abundant heterocyclic amine derived from food, possibly involved in human carcinogenesis. We evaluated the formation of PhIP‐DNA adducts in lymphocytes from 76 incident colorectal cancer patients likely to be exposed to dietary PhIP. To address the role of the metabolic polymorphisms relevant to PhIP‐DNA adduct formation, the patients were genotyped for common polymorphisms in the N‐acetyltransferase (NAT1 and NAT2), sulfotransferase (SULT1A1) and glutathione S‐transferase (GSTM1 and GSTA1) genes. PhIP released from adducted DNA after hydrolysis was quantitated by liquid chromatography‐tandem mass spectrometry. Overall, adducts were 3.24 ± 3.58/108 nucleotides (mean ± SD); they were not related to sex, smoking habits or age, though levels were not significantly higher in smokers, young subjects and high meat consumers. High vegetable intake significantly reduced PhIP‐DNA adducts (Mann‐Whitney U, p = 0.044). Individuals with the GSTM1 null genotype showed colon cancer onset at earlier age (58.8 ± 1.8 vs. 63.5 ± 1.6 years; Mann‐Whitney U, p = 0.047). None of the genetic polymorphisms studied significantly affected PhIP‐DNA adducts. However, individuals carrying 2 mutated GSTA1 alleles and younger than the median age had higher adduct levels than homozygous wild‐type and heterozygous ones (Kruskal‐Wallis p = 0.0008). In conclusion, these preliminary data indicate that PhIP‐DNA adducts are formed in people likely to be exposed to this carcinogen through the diet, suggesting this biomarker may be useful to detect human exposure and DNA damage. Overall, the genetic polymorphisms considered had limited effect on PhIP‐DNA levels, but young people with lower detoxification capacity may form a subgroup particularly susceptible to dietary carcinogen.

Impact on survival of the number of lymph nodes removed in patients with node-negative gastric cancer submitted to extended lymph node dissection

PURPOSE This study was designed to establish whether the number of lymph nodes removed has an effect on prognosis in patients with node-negative gastric cancer. PATIENTS AND METHODS We retrospectively analysed data of 114 consecutive patients who underwent gastrectomy and extended lymph node dissection for node-negative adenocarcinoma of the stomach between 2000 and 2005. Standard survival methods and restricted cubic spline multivariable Cox regression models were applied. RESULTS Median age was 63 years and 67 patients out of 114 (59%) were males. Median number of dissected LNs was 22 (range 2-73). Median follow-up was 76 months. Patients who had ≤15 nodes removed had significantly worse distant disease-free survival, disease-free survival and overall survival at multivariable analysis than other patients. The results did not change when pT1 and pT2-3 cancer patients were analysed separately. The risk of distant metastases decreased as the number of dissected lymph nodes increased (>15). CONCLUSIONS More extended lymph node resection offered survival benefit even in the subgroup of patients with early stage disease. Lymphadenectomy involving more than 15 lymph nodes should be performed for the treatment of node-negative gastric cancer. SYNOPSIS The impact on survival of the number of lymph nodes removed in patients with node-negative gastric cancer has not been established. This study suggests that more extended lymph node resection offers protection, as patients who had ≤15 nodes removed had significantly worse disease-free survival and overall survival at multivariate analysis than patients in whom >15 nodes were removed.

Surgical and pathological outcomes after right hemicolectomy: case‐matched study comparing robotic and open surgery

To compare the surgical and pathological outcomes of patients with right‐sided colon cancers operated on by means of open and robotic surgery with extracorporeal anastomosis.

Totally implantable vascular access devices 30 years after the first procedure. What has changed and what is still unsolved

The first placement of a totally implantable central venous access device (TIVAD) was performed in 1982 at the MD Anderson Cancer Center in Houston by John Niederhuber, using the cephalic vein—exposed by surgical cut-down—as route of access to central veins. After that, TIVADs proved to be safe and effective for repeated administration of drugs, blood, nutrients, and blood drawing for testing in many clinical settings, especially in the oncologic applications. They allow for administration of hyperosmolar solutions, extreme pH drugs, and vescicant chemotherapeutic agents, thus improving venous access reliability and overall patients’ quality of life. Despite the availability of a variety of devices, each showing different features and performances, many issues are still unsolved. The aim of this review article is to point out what has changed since the first implant of a TIVAD, and what it is still matter of debate, thus needing more investigation. Topics analyzed here include materials, choice of the veins and techniques of implantation, role of ultrasound (US) guidance in central venous access, position of catheter tip assessment, TIVAD-related infection and thrombosis, and quality of life issues.

Complementary molecular approaches reveal heterogeneous CDH1 germline defects in Italian patients with hereditary diffuse gastric cancer (HDGC) syndrome.

Germline inactivation of the E‐cadherin gene (CDH1) is associated with hereditary diffuse gastric cancer (HDGC), a rare autosomal dominant syndrome predisposing to both diffuse gastric cancer (DGC) and lobular breast cancer (LBC). We searched for CDH1 germline defects in 32 HDGC Italian probands selected according to international consensus criteria and in 5 selected relatives. We used a series of molecular methods, including: DNA sequencing, multiplex ligation‐dependent probe amplification, single‐nucleotide primer extension, bisulfite sequencing, reverse‐transcription PCR, and bioinformatics tools. We identified pathogenic mutations in 6 out of 32 probands (19%): one truncating and two missense mutations, one large deletion, one allelic expression imbalance and one splicing defect. Three out of six CDH1 constitutive alterations were novel. Our data support the need for a multimethod approach for CDH1 genetic testing, demonstrating that both DNA and RNA analyses are required to increase the detection rate of pathogenic mutations, thus reducing the number of patients without a clear molecular diagnosis. On the whole, our results indicate that not only DGC patients, but also subjects with personal or family history of LBC might benefit from CDH1 genetic testing. Moreover, our findings support the notion that prophylactic gastrectomy should be offered to asymptomatic CDH1 mutation carriers; indeed, while endoscopic analysis with histological examination of random gastric biopsies can miss cancer foci, gastrectomy performed in these subjects always revealed foci of cancer cells.

Preoperative versus postoperative docetaxel–cisplatin–fluorouracil (TCF) chemotherapy in locally advanced resectable gastric carcinoma: 10-year follow-up of the SAKK 43/99 phase III trial

BACKGROUND Fluorouracil-based adjuvant chemotherapy in gastric cancer has been reported to be effective by several meta-analyses. Perioperative chemotherapy in locally advanced resectable gastric cancer (RGC) has been reported improving survival by two large randomized trials and recent meta-analyses but the role of neoadjuvant chemotherapy and optimal regimen remains to be determined. We compared a neoadjuvant with adjuvant docetaxel-based regimen in a prospective randomized phase III trial, of which we present the 10-year follow-up data. PATIENTS AND METHODS Patients with cT3-4 anyN M0 or anyT cN1-3 M0 gastric carcinoma, staged with endoscopic ultrasound, computed tomography, bone scan, and laparoscopy, were assigned to receive four 21-day/cycles of docetaxel 75 mg/m(2) day 1, cisplatin 75 mg/m(2) day 1, and fluorouracil 300 mg/m(2)/day over days 1-14, either before (arm A) or after (arm B) gastrectomy. Event-free survival was the primary end point, whereas secondary end points included overall survival, toxicity, down-staging, pathological response, quality of life, and feasibility of adjuvant chemotherapy. RESULTS This trial was activated in November 1999 and closed in November 2005 due to insufficient accrual. Of the 70 enrolled patients, 69 were randomized, 34 to arm A and 35 to arm B. No difference in EFS (2.5 years in both arms) or OS (4.3 versus 3.7 years, in arms A and B, respectively) was found. A higher dose intensity of chemotherapy was observed in arm A and more frequent chemotherapy-related serious adverse events occurred in arm B. Surgery was safe after preoperative chemotherapy. A 12% pathological complete response was observed in arm A. CONCLUSION Docetaxel/cisplatin/fluorouracil chemotherapy is promising in preoperative setting of locally advanced RGC. The early stopping could mask the real effectiveness of neoadjuvant treatment. However, the complete pathological tumour responses, feasibility, and safe surgery warrant further investigation of a taxane-based regimen in the preoperative setting.

Postoperative enteral feeding improves mucosal morphometry and absorption of d-xylose by intestinal allografts in pigs

Abstract Intestinal absorption of nutrients has been reported as considerably reduced after total orthotopic small bowel transplantation (TOSBT) in pigs as well as in humans; moreover, morphological changes of mucosal structure are commonly found in intestinal allografts, even when immunological factors such as acute or chronic graft rejection or graft-versus-host disease (GVHD) are not detectable. In the clinical setting, the common policy to limit these adverse effects of TOSBT is to start an enteral feeding as soon as possible after surgery, but this impact has never been validated by controlled trials. Therefore, the aim of this study was to assess the intestinal absorption of d -xylose and the changes in villi height in pigs given either a commercial chow ad libitum or a polymeric enteral formula after TOSBT under Cyclosporin A (CyA).

Laboratory-based management of microbiological alerts: effects of an automated system on the surveillance and treatment of nosocomial infections in an oncology hospital.

Background: Prevention and surveillance programs are key to contain Nosocomial Infections (Nis). At the European Institute of Oncology, surveillance based on ex-post data collection has been done since the inception of hospital activity; laboratory-based surveillance of microbiological alert was not standardized. This study describes the issues related to the recent introduction into the hospital routine of a laboratory-based automated surveillance system and its clinical impact on monitoring and treatment of Nis. Methods: An interdisciplinary team defined the alerts and the actions to be taken in response; recipients of the alert messages were identified and software was programmed. Program features were created so their employment would generate a prompt notification of clinically critical results. After a training period, the program was introduced in the hospital routine. Results: There were a total of 150 generated alerts; the main alert related to microorganisms requiring prompt patient isolation and/or public notification. Clinical use of the program was relevant in detection and immediate notification of Cytomegalovirus active infection in stem cell recipients and central venous catheter related candidemia: the prompt administration of adequate treatment was possible hours earlier compared to the previous approach. Conclusions: A laboratory-based automated surveillance system is effective in facilitating the management of Nis; its clinical employment also leads to important clinical advantages in patient care.