Circumferential margin involvement after total mesorectal excision for mid or low rectal cancer: are all R1 resections equal?

AIM: Our aim was to assess the prognostic influence of the circumferential resection margin (CRM) exact value after total mesorectal excision for mid or low rectal cancer. METHODS: All patients (n = 321) who underwent total mesorectal excision from 2005 to 2013 were identified from a prospective database, including 49 (15%) who presented with a CRM ≤ 1 mm. Four groups were defined: group 1, CRM = 0 mm (n = 21); group 2, 0 < CRM ≤ 0.4 mm (n = 13); group 3, 0.4 < CRM ≤ 1 mm (n = 15); group 4, CRM > 1 mm (n = 272). RESULTS: After a mean follow-up of 42 ± 26 months, locoregional recurrence rates were 8/21 (38%) in group 1, 3/13 (23%) in group 2, 0/12 (0%) in group 3 and 26/272 (10%) in group 4 (P < 0.001), leading to significantly impaired 3-year locoregional recurrence-free survival in group 1 (57% ± 13%) and group 2 (56% ± 15%) compared to group 3 (85% ± 10%, vs group 1, P = 0.021, vs group 2, P = 0.049) and to group 4 (89% ± 2%, vs group 1, P < 0.001, vs group 2, P < 0.001). In multivariate Cox analysis, a CRM ≤ 0.4 mm was identified as an independent factor impairing both locoregional recurrence-free survival (OR 3.14, 95% CI 1.53-6.46; P = 0.002) and disease-free survival (OR 2.15, 95% CI 1.28-3.63; P = 0.004). CONCLUSION: Our study suggests that the prognosis after mid or low rectal cancer surgery was worse with a CRM ≤ 0.4 mm. The prognosis was similar in patients with a CRM > 0.4 mm or ≤ 1 mm and patients with an R0 resection.

Technical difficulties of left colic artery preservation during left colectomy for colon cancer.

PURPOSE: Low-tie ligation in colorectal cancer surgery is associated with technical difficulties in left colic artery preservation. We aimed to evaluate and classify the anatomical and technical difficulties of left colic artery (LCA) preservation at its origin and along its route at the inferior border of the pancreas. METHODS: A vascular reconstruction computed tomography prospective series of 113 patients was analyzed. The inferior mesenteric artery (IMA) branching pattern according to Latarjet's classification (Type I, separate LCA origin, Type II, fan-shaped branching pattern) and the distances between the IMA and the LCA origins and between the LCA and the Inferior mesenteric vein (IMV) at the inferior border of the pancreas were measured. RESULTS: The IMA branching pattern was Type I in 80 (71 %) patients and Type II in 33 (29 %) patients. The IMA-LCA distance was 39.8 ± 12.2 mm. The LCA-IMV distance at the inferior border of the pancreas was 20.5 ± 21.7 mm. When classified based on this distance, 75 (66 %) patients were classified into the Near subgroup (<20 mm) (7.7 ± 4.1 mm) and 38 (34 %) into the Far subgroup (≥20 mm) (45.6 ± 20.4 mm, p < 0.001). A Type I subgroup F accounted for 27 % of the patients. CONCLUSIONS: Left colic artery preservation is highly feasible at its origin in more than two-thirds of cases due to the separate origin. The addition of a high IMV ligation increases the risk of damage to the LCA at the inferior border of the pancreas because the distance to the IMV is less than 20 mm in two-thirds of cases.

A survey of methicillin-resistant Staphylococcus aureus control strategies in Italy.

PURPOSE: Data regarding the implementation of state-of-the-art methicillin-resistant Staphylococcus aureus (MRSA) control procedures in Italy are lacking. There is a need to evaluate compliance with MRSA recommendations (CR) in Italian hospitals. METHODS: A 67-question closed-answer survey was sent to all Italian hospitals, in order to analyze and evaluate program consistency with CR [hand hygiene (HH), contact precautions, screening of high-risk patients, decolonization, feedback on surveillance data, and antimicrobial guidelines and education programs]. RESULTS: 205 hospitals, which account for 42 % of national admissions, returned questionnaires. 131 hospitals (64 %) did not have written MRSA control guidelines. Hospitals reported the following levels of compliance with CR: (1) HH: 67 hospitals (33 %); (2) contact precautions: 33 (16 %); (3) MRSA screening: 66 (32 %); (4) MRSA decolonization: 42 (20 %); (5) surveillance data feedback: 87 (43 %); and (6) antimicrobial guidelines and education programs: 41 (20 %). One hospital (0.5 % of responses) had implemented all recommendations and 28 hospitals (14 %) had implemented four or five recommendations. 31 % of hospitals surveyed had implemented none. Multivariate analysis showed that the only factor identified as being associated with the implementation of MRSA control recommendations was the number of meetings/year of the infection control team (ICT) (p = 0.004). CONCLUSIONS: Written MRSA control guidelines are available in only one-third of Italian facilities. An organized system, with ≥4 interventions, has been implemented in just 1 out of 7 hospitals. HH programs and ICT activity are related to better MRSA control. In Italy, there is significant opportunity for improvement in MRSA control.

Risk factors for previously unknown meticillin-resistant Staphylococcus aureus carriage on admission to 13 surgical wards in Europe.

BACKGROUND: Early identification of meticillin-resistant Staphylococcus aureus (MRSA) carriers may be helpful for clinical and epidemiological reasons. AIM: To identify and compare risk factors of previously unknown MRSA carriage on admission to 13 surgical wards in France, Greece, Italy, and Spain. METHODS: The study was a prospective observational cohort study which enrolled consecutive patients screened for MRSA on admission to surgical wards. Sociodemographic data, comorbidities and possible risk factors for MRSA were recorded. A multivariate logistic regression model was used to predict probabilities of previously unknown MRSA colonization on admission based on patient characteristics. Prediction rules for MRSA carriage were developed and evaluated using the c-statistic. FINDINGS: Of 2901 patients enrolled, admission screening identified 111 (3.8%) new MRSA carriers. Independent risk factors for MRSA carriage were urinary catheterization (odds ratio: 4.4; 95% confidence interval: 2.0-9.9), nursing home residency (3.8; 1.9-7.7), chronic skin disease (2.9; 1.5-5.8), wounds/ulcers (2.4; 1.5-4.0), recent hospitalization (2.2; 1.5-3.3), diabetes (1.6, 1.02-2.5), and age >70 years (1.5; 1.03-2.3). However, risk factors varied between centres. The c-statistic for the common prediction rule for all centres was 0.64, indicating limited predictive power. CONCLUSIONS: Risk profiles for MRSA carriers vary between surgical wards in European countries. Identifying local risk factors is important, as a common European prediction rule was found to be of limited clinical value.

Adherence to surgical site infection guidelines in Italian cardiac surgery units.

BACKGROUND: Data on the adherence to surgical site infection (SSI) prevention guidelines in Italian cardiac surgery units are lacking. METHODS: A multiple-choice questionnaire, structured into eight sections following the Centers for Disease Control 1999 (CDC) guidelines, was prepared and sent to 24 surgical units participating in a national study group (GIS-InCard); this units perform over 20% of all cardiac surgical procedures in Italy. Answers were stratified based upon the evidence of the recommendations: grade IA (ten questions), grade IB (52 questions), grade II (11 questions), and no recommendation (seven questions). RESULTS: 17 of the 24 units (72%) returned the questionnaire. Adherence to grade IA recommendations was 69 +/- 34%, with five units (29%) showing a > or =80% adherence. Adherence to grade IB and II was 65 +/- 26% and 71 +/- 28%, respectively. Adherence did not vary significantly depending on the evidence of the recommendation, i.e., grade IA, IB or II (p = 0.72). Low adherence levels to grade I recommendations were observed on hair removal: (1) it was performed systematically in all male patients (0% adherence), (2) it was performed on the morning of the intervention in 29% of centers, and (3) the method of hair removal was adequate in 41% of cases. Despite 94% of units having written guidelines on antibiotic prophylaxis, only 65% administered antibiotic prophylaxis with the correct timing - i.e., on anesthesia induction. CONCLUSIONS: Adherence to CDC SSI guidelines in Italy is fair. The evidence of the recommendation does not influence adherence. Organizational improvements, especially those regarding hair removal and the timing of antibiotic prophylaxis, should be implemented in most hospitals.

Outcome and predictive factors of mortality in hospitalized HIV-patients in Burkina Faso.

BACKGROUND: The aim of this study was to describe the clinical presentation and predictors of death in a HIV population hospitalized in Ouagadougou, Burkina Faso. MATERIALS AND METHODS: Baseline demographics, viro-immunological status, clinical presentations, and outcome have been analyzed by univariate analysis and a multivariate model. RESULTS: A total of 1,071 hospitalizations of HIV-positive patients was recorded between 1 January, 2004 and 31 August, 2006, the majority of whom were female (64.1%). The baseline CD4 cell count/microl was higher in the female patients than in the male ones (166.1 vs 110.9). Gastroenteric symptoms were the first cause of hospitalization (61.7%). The crude mortality rate was higher in males than females (38% vs 25.3%). Baseline World Health Organization clinical stage IV (OR 9.22), neurological syndrome (OR 3.04) or wasting syndrome at admission (OR 2.9), positive malaria film (OR 2.17), and an older age independently predicted death. Weight at admission > 40 kg and a higher platelet count at admission were independently associated with a better outcome. CONCLUSIONS: Females are admitted to hospital earlier than males, probably as an indirect result of the Prevention of Mother-to-Child Transmission (PMTCT) public health initiative. An active search of HIV status in other members of the family (PMTCT-plus) may result in the detection of asymptomatic HIV-infected patients as well. A Plasmodium falciparum-positive smear during admission significantly impacted on outcome as well as low platelet count.

Prevalence of drug resistance and newly recognised treatment-related substitutions in the HIV-1 reverse transcriptase and protease genes from HIV-positive patients naïve for anti-retrovirals.

The aim of this study was to assess the prevalence of genetic changes in either the HIV reverse transcriptase (RT) or protease (Pro) genes in a cohort of patients naïve for anti-retroviral therapy. Of 61 patients, 43 (70.5%) were infected with HIV strains harbouring at least one resistance-related mutation, with 41 (67.2%) harbouring newly recognised treatment-related mutations. Among the 61 patients, the prevalence of specific mutations in the RT gene was as follows: 39A, 1.6%; 43E, 1.6%; and 228H, 1.6%. The prevalence of specific mutations in the Pro gene was as follows: 11I, 1.6%; 13V, 26.2%; 35D, 19.6%; 45R, 1.6%; 58E, 1.6%; 62V, 31%; 72V, 11.4%; 72M, 6.5%; 72T, 3.2%; 75I, 1.6%; and 89M, 13%. A higher prevalence of newly recognised mutations was found in strains from patients infected through sexual practices (30/36 = 83.4% vs. 11/25 = 44%; p 0.0023; OR 10.91; 95% CI 3.14-40.39). These findings support the use of resistance testing in patients naïve for anti-retroviral therapy, and suggest that the possible impact of newly recognised treatment-related mutations on clinical outcome requires further investigation.

Lopinavir plasma levels in salvage regimes by a population of highly active antiretroviral therapy-treated HIV-1-positive patients.

Increased lopinavir (LPV) exposure obtained in vivo through combination with low-dose ritonavir may overcome a certain grade of resistance but not all. We sought to analyze LPV variability and possible risk factors. LPV trough plasma concentrations were determined by high-performance liquid chromatography after 1, 4, and 12 weeks from salvage regimens and tested in both univariate and multivariate regression analyses with age, gender, weight, risk factors for HIV acquisition, hepatitis C virus reactivity, hepatitis B surface antigen positivity, baseline aspartate transferase (AST) or alanine transferase (ALT) levels, creatinine, non-nucleoside reverse transcriptase inhibitors (NNRTIs) or tenofovir as concomitant drugs, and NNRTIs administered in the previous regimen. Fifty-six patients were included into the study. Among them, 8 of 56 (14.3%) at week 1, 12 of 56 (21.4%) at week 4, and 9 of 56 (16.1%) at week 12 had suboptimal LPV plasma concentrations, defined as trough concentration less than 4 microg/mL. No correlation was found between LPV trough concentrations and assessed variables. In conclusion, pharmacokinetic variability and low LPV concentrations have been found, supporting the use of therapeutic drug monitoring in those starting this drug.

Predictors of long-term immunological outcome in rebounding patients on protease inhibitor-based HAART after initial successful virologic suppression: implications for timing to switch.

OBJECTIVE: To assess predictive factors of long-term immune restoration in patients who started protease inhibitor (PI)-based HAART and experienced virological rebound after initial complete success. METHOD: A retrospective longitudinal analysis of all HIV-infected patients who started their first PI-based HAART and reached viral load below 500 copies/mL was carried out in a large academic center in Italy. Patients were classified either as complete virologic responder (CR) or rebounders (REB) when confirmed plasma viremia was detected thereafter. Immunological outcome was the area under the curve (AUC) of the absolute CD4+ cell count change since the 8th month after treatment initiation (CD4+ T-cell AUC). Association between baseline characteristics, virological outcome, and CD4+ T-cell AUC was assessed by univariate and multivariate analysis. RESULTS: There were 374 patients who were included in the study. Mean follow-up was 30.2 months. There were 226/374 patients (60.4%) who remained CR while 148/374 (39.6%) presented at least one rebound (REB). Among REB patients, complete viral suppression was regained in 15/42 (35.7%) and 50/106 (47.1%) patients who underwent therapy changes or not, respectively. When multiple linear regression was carried out, previous nucleoside reverse transcriptase inhibitor (NRTI) experience and baseline CD4+ cell count below 350 cells/muL did not impair long-term immune restoration. The occurrence of rebound, its duration (> 18 months), and its magnitude (peak of viral load > 10,000 copies/mL) were independent negative prognostic factors. CONCLUSION: The occurrence of viral rebound is independently associated with significantly impaired long-term immunological restoration. The magnitude of viral rebound (< 10,000 copies/mL) and its duration (< 18 months) may be useful to identify those rebounding patients who may still profit from maintaining the current failing therapy if a more aggressive approach may be expected to be deleterious for tolerability reasons or lack of options.

Analysis of HIV-1 mutation patterns in patients failing antiretroviral therapy.

The emergence of mutations encoding drug resistance is supposed to be a significant limitation to the clinical efficacy of inhibitor compounds directed against specific HIV-1 enzymatic targets. We have used a commercial test (Visible Genetics Inc., Paris, France) to study the prevalence of mutations occurred in HIV-1 protease and reverse transcriptase (RT) genes in 93 HIV-1 infected patients treated with at least one regimen containing a protease inhibitor (PI) and failing to the current therapeutic regimen. Protease mutations conferring resistance to at least one PI were detected in 46/93 (49.4%) of strains, 25 (26.8%) of which showed resistance to all PIs. Reverse transcriptase mutations conferring resistance to at least one RT inhibitor were detected in 57/93 (61.2%) of strains, 18 (19.3%) of which showed resistance to all RT inhibitors. The most frequent RT mutations were T215Y/F, M41L, and M184V (41.9, 40.8, and 40.8%, respectively), while L63P, L10R/V, and A71V/T (58, 41.9, and 34.4%, respectively) were the most represented protease substitutions. We have found no mutations encoding for multiple dideoxynucleoside resistance (Q151M or T69SS). Twelve of our patients (12.9%) had no mutation encoding drug resistance and were completely sensitive to all RT and protease inhibitors. Therefore, not all virological failures are caused by HIV-1 genomic resistance.

The human immunodeficiency virus-infected traveler.

As the number of travelers from industrialized countries who are infected with human immunodeficiency virus (HIV) increases as a consequence of the clinical benefits of highly active antiretroviral therapy (HAART), updated prophylactic knowledge is needed. Vaccine prophylaxis must balance the safety and immunogenicity of vaccines with the estimated risk of acquiring the disease. Further research is needed on antimalarial chemoprophylaxis for travelers who are HAART recipients, because of possible pharmacokinetic interactions. Safe sex practices must be adopted to avoid both spreading of the infection in the host country and superinfection with different HIV strains. Most individuals infected with HIV may travel safely, even though the infectious risk has been reported to be higher for patients with advanced infections than for the general population. These patients are also less likely to produce an effective immune response to vaccines. Migrants and refugees from poor countries are also at risk of acquiring HIV infection. Their legal-residency status may often prevent their access to adequate health services, thus necessitating urgent public health actions.