B. Andreoni

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.

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.

Recurrence and prognostic factors in patients with aggressive fibromatosis. The role of radical surgery and its limitations

BackgroundSurgery is still the standard treatment for aggressive fibromatosis (AF); however, local control remains a significant problem and the impact of R0 surgery on cumulative recurrence (CR) is objective of contradictory reports.MethodsThis is a single-institution study of 62 consecutive patients affected by extra-abdominal and intra-abdominal AF who received macroscopically radical surgery within a time period of 15 years.ResultsDefinitive pathology examination confirmed an R0 situation in 49 patients and an R1 in 13 patients. Five-year CR for patients who underwent R0 vs R1 surgery was 7.1% vs 46.4% (P = 0.04) and for limbs vs other localizations 33.3% vs 9.9% (P = 0.02) respectively. In 17 patients who had intraoperative frozen section (IFS) margin evaluation R0 surgery was more common (17 of 17 vs 32 of 45, P = 0.01) and CR lower (five-year CR 0% vs 19.1%, respectively, P = 0.04). However, in multivariate analysis only limb localization showed a negative impact on CR (HR: 1.708, 95% CI 1.03 to 2.84, P = 0.04).ConclusionsIFS evaluation could help the surgeon to achieve R0 surgery in AF. Non-surgical treatment, including watchful follow-up, could be indicated for patients with limb AF localization, because of their high risk of recurrence even after R0 surgery.

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.

Comparison of oral polyethylene glycol plus a large volume glycerine enema with a large volume glycerine enema alone in patients undergoing colorectal surgery for malignancy: a randomized clinical trial

Aim  Recent meta‐analyses and randomized clinical trials have concluded that mechanical bowel preparation (MBP) before elective colorectal surgery is not associated with a reduction of surgical site infection (SSI). The aim of this randomized clinical trial was to evaluate the impact of preoperative MBP for colon and rectal cancer surgery in comparison with a single glycerine enema.

Prognostic factors affecting survival after surgical resection of gastrointestinal stromal tumours: a two-unit experience over 10 years

BackgroundGastrointestinal stromal tumours (GISTs) are the most common mesenchymal neoplasm of the gastrointestinal (GI) tract which has only been recently described based on their specific immunohistochemistry and the presence of particular KIT-related mutations which potentially make them targets for tyrosine kinase inhibition.MethodsSixty-one patients (29 M; 32 F, median age 60 years; range: 23–86 years) between June 1994 and March 2005, were analyzed from two allied institutions. Patient, tumour, and treatment variables were analyzed to identify factors affecting survival.ResultsOf the 61 patients, 55 (90%) underwent complete surgical resection of macroscopic disease. The 5-year overall survival (OS) rate in the 61 patients was 88% and the 5-year disease-free survival (DFS) in the 55 cases completely resected was 75%. Univariate analysis revealed that R0 resection was strongly associated with a better OSrate (p < 0.0001). Likewise, univariate analysis also showed high mitotic count of > 10 mitoses/per 50 HPF was a significant variable in worse prognosis for OS (≤ 10 mitoses/per 50 HPF 95% 5-year OS vs. > 10 mitoses/per 50 HPF 74% 5-year OS, respectively; p = 0.013). On subsequent multivariate analysis, only high mitotic count remained as a significant negative prognostic variable for OS (p = 0.029). Among patients resected for cure, there were 8 recurrences during follow-up. The mean time to recurrence was 21 ± 10 months (range: 4–36 months). Univariate analysis revealed that mitotic count of > 10 mitoses per 50 high power fields, intratumoural necrosis, and pathological tumour size (> 10 cm in maximal diameter) significantly correlated with DFS (p = 0.006, 0.002 and 0.02, respectively), with tumour necrosis and high mitotic count remaining as independent predictive variables affecting prognosis on subsequent multivariate analysis.ConclusionMost GISTs are resectable with survival principally dependent upon mitotic count and completeness of resection. Future metabolic and genetic analyses will define the role of and resistance to induction or postoperative adjuvant targeted kinase inhibition therapy.

Retroperitoneal pararenal isolated neurofibroma: report of a case and review of literature

The neurofibroma is a tumour of neural origin. This kind of neoplasm, though, is generally skin located. Rare cases in deep organs or in the peritoneal cavity are also reported in the literature. There are two types of neurofibromas, localized and diffuse; the latter is associated with von Recklinghausen disease and always occurs together with skin neurofibromas. Here we report the case of a 47-year-old man affected by retroperitoneal neurofibroma, but not associated with von Recklinghausen disease. A computed tomography (CT) scan described a retroperitoneal pararenal lesion with no clear involvement of adjacent viscera. We describe the diagnostic modality, treatment planning and the timing of treatment of this neoplasm, reviewing also the literature.

Sonographic diagnosis of superior mesenteric artery syndrome

Two cases of superior mesenteric artery syndrome are presented. In both, conclusive diagnosis was made noninvasively in the presence of acute symptoms by obtaining details of the duodenum and vessels

Glucose-clamp by artificial pancreas in the study and management of a patient with insulinoma

SummaryFour euglycemic glucose-clamp studies by artificial pancreas (Biostator, Miles) have been performed during prolonged fast before and after pharmacological treatment in a patient with insulinoma. In the basal state a high glucose infusion rate (8.9 g/h) was unable to achieve the preselected blood glucose plateau of 80 mg/100 ml. The plasma insulin levels during this first glucose-clamp were comprised between 18 and 50 μU/ml. On the first day of diazoxide treatment (300 mg/die),. the glucose infusion rate decreased to 6.4 g/h, without variation in plasma insulin level, thus suggesting a diazoxide effect independent of the inhibition of insulin secretion. After 7 days of diazoxide treatment, a further reduction of glucose infusion (5.8 g/h), together with a lowering of plasma insulin levels (7–18 μU/ml) was observed. Both in the basal state and during diazoxide treatment a circadian pattern of glucose requirement was noted, with lower glucose need and plasma insulin levels during the night. Surgery was undertaken with glucose-clamp by artificial pancreas; blood glucose level being higher than the preselected value of 80 mg/100 ml, simple monitoring of glycemia was performed. The excision of a single adenoma was followed by a substantial rise in blood glucose 20 min later. An additional glucose-clamp, performed 3 months after surgery showed a dramatic fall of the glucose infusion rate (2.9 g/h) needed to achieve the preselected blood glucose plateau, confirming the completeness of the intervention. This experience shows that glucose-clamp by artificial pancreas may be of great value in the study as well as in the pharmacological and surgical treatment of patients with insulinoma.

Reliability and validity assessment of administrative databases in measuring the quality of rectal cancer management

Purpose: Measurement and monitoring of the quality of care using a core set of quality measures are increasing in health service research. Although administrative databases include limited clinical data, they offer an attractive source for quality measurement. The purpose of this study, therefore, was to evaluate the completeness of different administrative data sources compared to a clinical survey in evaluating rectal cancer cases. Methods: Between May 2012 and November 2014, a clinical survey was done on 498 Lombardy patients who had rectal cancer and underwent surgical resection. These collected data were compared with the information extracted from administrative sources including Hospital Discharge Dataset, drug database, daycare activity data, fee-exemption database, and regional screening program database. The agreement evaluation was performed using a set of 12 quality indicators. Results: Patient complexity was a difficult indicator to measure for lack of clinical data. Preoperative staging was another suboptimal indicator due to the frequent missing administrative registration of tests performed. The agreement between the 2 data sources regarding chemoradiotherapy treatments was high. Screening detection, minimally invasive techniques, length of stay, and unpreventable readmissions were detected as reliable quality indicators. Postoperative morbidity could be a useful indicator but its agreement was lower, as expected. Conclusions: Healthcare administrative databases are large and real-time collected repositories of data useful in measuring quality in a healthcare system. Our investigation reveals that the reliability of indicators varies between them. Ideally, a combination of data from both sources could be used in order to improve usefulness of less reliable indicators.