Long term results of video-assisted anal fistula treatment for complex anal fistula: another shattered dream?

AIM: Complex anal fistula represents a burden for patients, and its management is a challenge for surgeons. Video-assisted anal fistula treatment (VAAFT) is one sphincter-sparing technique. However, data on its long-term effectiveness are scant. We aimed to explore the outcomes of VAAFT in a retrospective cohort of patients referred to a tertiary centre. METHOD: Consecutive adult patients with a minimum of 2 years' follow-up after VAAFT were reviewed. Patients were followed up to 5 years postoperatively. Failure was defined as incomplete healing of the external orifice(s) during the first 6 months. Recurrence was defined as new radiologically and/or clinically confirmed onset of the fistula after primary healing. A generalized linear model was fitted to evaluate the association between failure and sociodemographic characteristics. Predictors of recurrence were determined in a subgroup analysis of patients found to be free from disease at 6 months postoperatively. RESULTS: Overall, 106 patients (70% male; mean age 41 years) were reviewed. Of these 86% had a previous seton placement. Fistulas were either high trans-sphincteric (74%), suprasphincteric (12%) or extrasphincteric (13%). Eight (7%) patients experienced postoperative complications, none of which required reintervention. Mean follow-up was 53 ± 13.2 months. VAAFT failed in 14 (13%) patients. The overall recurrence rate ranged from 29% at 1 year to 63% at 5 years. Multiple external orifices, suprasphincteric fistula, younger age, previous surgery and higher complexity of the fistulous tract were independent risk factors for recurrence. CONCLUSION: VAAFT is a safe sphincter-sparing technique. The initially high success rate decreases over time and relates to a higher degree of complexity.

A pilot study on staged surgery by delta video-assisted anal fistula treatment (dVAAFT) for complex anal fistula.

Complex anal fistulas (CAF) present a challenge in achieving healing while preserving anal sphincter function. This study aims to introduce a novel staged approach for CAF treatment, combining video-assisted anal fistula treatment (VAAFT), seton placement, and other staged approaches. Consecutive patients with CAF underwent the staged approach involving VAAFT and seton placement. Data on patient demographics, fistula characteristics, and operative findings were collected. Pre-operative work-up included clinical evaluation, endoanal ultrasonography (EAUS), and magnetic resonance imaging (MRI). Surgical techniques and outcomes were evaluated. Eighteen patients (median age 38 years) were included. Misplacement of a previously placed seton was observed in 64% of cases. VAAFT combined with seton placement achieved simplification and healing of secondary tracts in 66% of cases. Operative times significantly decreased across interventions. At a median follow-up of 14 months, complete healing was achieved in 2 patients, with 1 patient demonstrating persistence of the fistula. Post-operative complications were observed in 11% of patients, with no deterioration in continence. The staged approach combining VAAFT, seton placement, and staged procedures offers a potential solution for treating CAF. VAAFT provides diagnostic and therapeutic benefits, simplifying the fistula anatomy and optimizing seton placement. The approach allows subsequent procedures based on individual fistula characteristics.

Efficacy and safety of Propionibacterium extract gel versus glyceryl trinitrate ointment in the treatment of chronic anal fissure: a randomized controlled trial.

AIM: Chronic anal fissure (CAF) is an extremely frequent finding in clinical practice. Several topical agents have been proposed for its treatment with the common goal of increasing anodermal blood flow to promote healing. The aim of this study was to compare the efficacy and safety of a Propionibacterium extract gel (PeG) and 0.4% glyceryl trinitrate ointment (GTN) in patients with CAF. METHOD: Patients were randomly allocated to a PeG or GTN group and medication was administered every 12 h for 40 days. The primary outcome was the success rate, as measured by a decrease in the REALISE scoring system for anal fissure at 10, 20 and 40 days after initiating either treatment. The secondary outcomes recorded at the same time points were healing rate, visual analogue scales for itching and burning, rate of complications and adverse events, patient quality of life and satisfaction, and cost analysis. RESULTS: A total of 120 patients were enrolled, and 96 patients (PeG, n = 53; GTN, n = 43) completed the primary outcomes. A significant decrease over time in the REALISE score was observed in both groups. Adverse events occurred more frequently in the GTN group than in the PeG group, peaking at visit 1 [37 (63.8%) vs. 2 (3.4%), respectively], with headache being the most prevalent. The between-treatment cumulative average costs per patient were significantly higher for GTN than that for PeG at each follow-up visit. There were no other significant differences between the two groups for any of the other outcomes. CONCLUSION: While there was no difference in healing rates between the two treatments, PeG was more cost-effective and associated with fewer adverse events.

Endoscopic sinusectomy: 'a rose by any other name'. A systematic review of different endoscopic procedures to treat pilonidal disease.

AIM: Pilonidal sinus or Pilonidal Disease (PD) is a relatively common, benign but challenging condition. Although commonly encountered in practice, its ideal treatment is controversial. One of the most validated treatments is video-assisted surgery. In this context, very similar endoscopic techniques have been published under different names. The aim of this systematic review is to assess the differences among these proposed techniques and their outcomes. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed during all stages of this systematic review. A systematic search of the English literature was performed on multiple databases from 1 January 2014 to 3 April 2022. The primary outcome measure was the IDEAL framework stage of innovation. The key secondary outcome measures were the adherence to the IDEAL reporting guidelines, the Blencowe framework and the core outcome set (COS) for studies evaluating the introduction and evaluation of novel surgical techniques, the qualitative assessment using appropriate tools, the procedural variations and outcomes of each technique. RESULTS: A total of 38 articles were included reporting a very similar technique under eight different acronyms. The number of patients varied from 9 to 250. Mean follow-up ranged from 1 to 60 months. There was only one published study of IDEAL 3. The majority (58%) were IDEAL 2a studies. Reporting of domains in the IDEAL reporting guidelines and Blencowe framework was poor, with most studies not reporting the component steps of procedures or efforts to standardize them. Half of COS domains were markedly underreported. The quality of the evidence was categorized as having a risk of bias from moderate to critical level in all nine comparative non-randomized series. Postoperative complications occurred in 0%-6% of cases, including surgical site infection, poor or failed wound healing bleeding, granuloma, haematoma, and pain requiring intervention. The recurrence rate varied from 0% to 22%. CONCLUSION: The study demonstrates that reporting on technical aspects of interventions for PD is poor, thus warranting a better-quality control of surgical techniques. It is advisable to group all endoscopic procedures under the umbrella term of 'endoscopic sinusectomy', thus embracing the two main principles of this technique, that is, video assistance and PD ablation.

Alternative detection of SARS-CoV-2 RNA by a new assay based on mass spectrometry.

OBJECTIVES: Accurate detection of SARS-CoV-2 RNA is essential to stopping the spread of SARS-CoV-2. The aim of this study was to evaluate the performance of the recently introduced MassARRAY® SARS-CoV-2 Panel and to compare it to the cobas® SARS-CoV-2 Test. METHODS: The MassARRAY® SARS-CoV-2 Panel consists of five assays targeting different sequences of the SARS-CoV-2 genome. Accuracy was determined using national and international proficiency panels including 27 samples. For clinical evaluation, 101 residual clinical samples were analyzed and results compared. Samples had been tested for SARS-CoV-2 RNA with the cobas® SARS-CoV-2 Test. RESULTS: When accuracy was tested with the MassARRAY® SARS-CoV-2 Panel, 25 of 27 (92.6%) samples revealed correct results. When clinical samples were analyzed with the MassARRAY® SARS-CoV-2 Panel and compared to the cobas® SARS-CoV-2 Test, 100 samples showed concordant results. One sample was found to be inconclusive with the MassARRAY® SARS-CoV-2 Panel. When time-to-results were compared, the new assay showed longer total and hands-on times. CONCLUSIONS: The MassARRAY® SARS-CoV-2 Panel showed a good performance and proved to be suitable for use in the routine diagnostic laboratory. Especially during phases of shortage of reagents and/or disposables, the new test system appears as beneficial alternative to standard assays used for detection of SARS-CoV-2 RNA.

Mechanosynthesis and Thermoelectric Properties of Fe, Zn, and Cd-Doped P-Type Tetrahedrite: Cu12-xMxSb4S13.

This contribution deals with the mechanochemical synthesis, characterization, and thermoelectric properties of tetrahedrite-based materials, Cu12-xMxSb4S13 (M = Fe2+, Zn2+, Cd2+; x = 0, 1.5, 2). High-energy mechanical milling allows obtaining pristine and substituted tetrahedrites, after short milling under ambient conditions, of stoichiometric mixtures of the corresponding commercially available binary sulfides, i.e., Cu2S, CuS, Sb2S3, and MS (M = Fe2+, Zn2+, Cd2+). All the target materials but those containing Cd were obtained as single-phase products; some admixture of a hydrated cadmium sulfate was also identified by XRD as a by-product when synthesizing Cu10Cd2Sb4S13. The as-obtained products were thermally stable when firing in argon up to a temperature of 350-400 °C. Overall, the substitution of Cu(II) by Fe(II), Zn(II), or Cd(II) reduces tetrahedrites' thermal and electrical conductivities but increases the Seebeck coefficient. Unfortunately, the values of the thermoelectric figure of merit obtained in this study are in general lower than those found in the literature for similar samples obtained by other powder processing methods; slight compositional changes, undetected secondary phases, and/or deficient sintering might account for some of these discrepancies.

FISSIT (Fistula Surgery in Italy) study: A retrospective survey on the surgical management of anal fistulas in Italy over the last 15 years.

BACKGROUND: Surgical treatment of anal fistulas is still a challenge. The aims of this study were to evaluate the adoption and healing rates for the different surgical techniques used in Italy over the past 15 years. METHODS: This was a multicenter retrospective observational study of patients affected by simple and complex anal fistulas of cryptoglandular origin who were surgically treated in the period 2003-2017. Surgical techniques were grouped as sphincter-cutting or sphincter-sparing and as technology-assisted or techno-free. All patients included in the study were followed for at least 12 months. RESULTS: A total of 9,536 patients (5,520 simple; 4,016 complex fistulas) entered the study. For simple fistulas, fistulotomy was the most frequently used procedure, although its adoption significantly decreased over the years (P < .0005), with an increase in sphincter-sparing approaches; the overall healing rate in simple fistulas was 81.1%, with a significant difference between sphincter-cutting (91.9%) and sphincter-sparing (65.1%) techniques (P = .001). For complex fistulas, the adoption of sphincter-cutting approaches decreased, while sphincter-sparing techniques were mildly preferred (P < .0005). Moreover, there was a significant trend toward the use of technology-assisted procedures. The overall healing rate for complex fistulas was 69.0%, with a measurable difference between sphincter-cutting (81.1%) and sphincter-sparing (61.4%; P = .001) techniques and between techno-free and technology-assisted techniques (72.5% and 55.0%, respectively; P = .001). CONCLUSION: Surgical treatment of anal fistulas has changed, with a trend toward the use of sphincter-sparing techniques. The overall cure rate has remained stable, even if the most innovative procedures have achieved a lower success rate.

Substrate-Induced Strain Effect on Structural and Magnetic Properties of La0.5Sr0.5CoO3 Films.

We present a detailed study about the substrate-induced strain and thickness effects on the structure and magnetic properties of La0.5Sr0.5CoO3 films. The in-plane tensile or compressive strain imposed by four different substrates configures an in-plane or out-of-plane easy axis, respectively. The presence of a soft magnetic phase at the interface is also conditioned by the type of strain. The obtained results are discussed in terms of the different anisotropies that participate and control the final magnetic behavior. The relevance of these results lies in the feasibility of La0.5Sr0.5CoO3 in memory applications and spintronic devices.

Deadlock of proctologic practice in Italy during COVID-19 pandemic: a national report from ProctoLock2020.

Proctology is one of the surgical specialties that suffered the most during COVID-19 pandemic. Using data from a cross-sectional worldwide web survey, we aimed to snapshot the current status of proctologic practice in Italy with differences between three macro areas (North, Centre, South). Specialists affiliated to renowned scientific societies with an interest in coloproctology were invited to join a 27-item survey. Predictive power of respondents' and hospitals' demographics on the change of status of surgical activities was calculated. The study was registered at ClinicalTrials.gov (NCT04392245). Of 299 respondents from Italy, 94 (40%) practiced in the North, 60 (25%) in the Centrer and 82 (35%) in the South and Islands. The majority were men (79%), at consultant level (70%), with a mean age of 46.5 years, practicing in academic hospitals (39%), where a dedicated proctologist was readily available (68%). Southern respondents were more at risk of infection compared to those from the Center (OR, 3.30; 95%CI 1.46; 7.47, P = 0.004), as were males (OR, 2.64; 95%CI 1.09; 6.37, P = 0.031) and those who routinely tested patients prior to surgery (OR, 3.02; 95%CI 1.39; 6.53, P = 0.005). The likelihood of ongoing surgical practice was higher in the South (OR 1.36, 95%CI 0.75; 2.46, P = 0.304) and in centers that were not fully dedicated to COVID-19 care (OR 4.00, 95%CI 1.88; 8.50, P < 0.001). The results of this survey highlight important factors contributing to the deadlock of proctologic practice in Italy and may inform the development of future management strategies.

Differences between computed tomoghaphy and surgical findings in acute complicated diverticulitis.

BACKGROUND/OBJECTIVE: A preoperative reliable classification system between clinical and computed tomography (CT) findings to better plan surgery in acute complicated diverticulitis (ACD) is lacking. We studied the inter-observer agreement of CT scan data and their concordance with the preoperative clinical findings and the adherence with the intraoperative status using a new classification of diverticular disease (CDD). METHODS: 152 patients operated on for acute complicated diverticulitis (ACD) were retrospectively enrolled. All patients were studied with CT scan within 24 h before surgery and CT images were blinded reanalyzed by 2 couples of radiologists (A/B). Kappa value evaluated the inter-observer agreement between radiologists and the concordance between CDD, preoperative clinical findings and findings at operation. Univariate and multivariate analysis were used to evaluate the predicting values of CT classification and CDD stage at surgery on postoperative outcomes. RESULTS: Overall inter-observer agreement for the CDD was high, with a kappa value of 0.905 (95% CI = 0.850-0.960) for observers A and B, while the concordance between radiological and surgical findings was weak (kappa values = 0.213 and 0,248, respectively and 95% CI = 0.106 to 0.319 and 95% CI = 0.142 to 0.355, respectively). When overall morbidity, mortality and the need of a terminal colostomy were considered as main endpoints no concordance was observed between surgical and radiological findings and the CDD (P=NS). CONCLUSIONS: The need for a more accurate classification of ACD, able to better stage this emergency, and to provide surgeons with reliable information for the best treatment is advocated.

Endoscopic pilonidal sinus treatment (EPSiT) in recurrent pilonidal disease: a prospective international multicenter study.

BACKGROUND: Pilonidal disease (PD) is a common disease of the natal cleft, which can lead to complications including infection and abscess formation. Various operative management options are available, but the ideal technique is still debatable. Recurrent PD after surgical treatment is frequent event for the 25-30% of cases. The present study evaluated endoscopic pilonidal sinus treatment (EPSiT) in recurrent and multi-recurrent PD. METHODS: Of the consecutive prospective patients with recurrent PD, 122 were enrolled in a prospective international multicenter study conducted at a secondary and tertiary colorectal surgery centers. Primary endpoint was to evaluate short- and long-term outcomes: healing rate/time, morbidity rate, re-recurrence rate, and patient's quality of life (QoL). RESULTS: Complete wound healing rate was occurred in 95% of the patient, with a mean complete wound healing time of 29 ± 12 days. The incomplete healing rate (5%) was significantly related to the number of external openings (p = 0.008), and recurrence was reported in six cases (5.1%). Normal daily activity was established on the first postoperative day, and the mean duration before patients returned to work was 3 days. QoL significantly increased between the preoperative stage and 30 days after the EPSiT procedure (45.3 vs. 7.9; p < 0.0001). CONCLUSIONS: The EPSiT procedure seems to be a safe and effective technique in treating even complex recurrent PD. It enables excellent short- and long-term outcomes than various other techniques that are more invasive.

Hollow viscus injuries: predictors of outcome and role of diagnostic delay.

INTRODUCTION: Hollow viscus injuries (HVIs) are uncommon but potentially catastrophic conditions with high mortality and morbidity rates. The aim of this study was to analyze our 16-year experience with patients undergoing surgery for blunt or penetrating bowel trauma to identify prognostic factors with particular attention to the influence of diagnostic delay on outcome. METHODS: From our multicenter trauma registry, we selected 169 consecutive patients with an HVI, enrolled from 2000 to 2016. Preoperative, intraoperative, and postoperative data were analyzed to assess determinants of mortality, morbidity, and length of stay by univariate and multivariate analysis models. RESULTS: Overall mortality and morbidity rates were 15.9% and 36.1%, respectively. The mean length of hospital stay was 23±7 days. Morbidity was independently related to an increase of white blood cells (P=0.01), and to delay of treatment >6 hours (P=0.033), while Injury Severity Score (ISS) (P=0.01), presence of shock (P=0.01), and a low diastolic arterial pressure registered at emergency room admission (P=0.02) significantly affected postoperative mortality. CONCLUSION: There is evidence that patients with clinical signs of shock, low diastolic pressure at admission, and high ISS are at increased risk of postoperative mortality. Leukocytosis and delayed treatment (>6 hours) were independent predictors of postoperative morbidity. More effort should be made to increase the preoperative detection rate of HVI and reduce the delay of treatment.

Operative and nonoperative management for renal trauma: comparison of outcomes. A systematic review and meta-analysis.

INTRODUCTION: Preservation of kidney and renal function is the goal of nonoperative management (NOM) of renal trauma (RT). The advantages of NOM for minor blunt RT have already been clearly described, but its value for major blunt and penetrating RT is still under debate. We present a systematic review and meta-analysis on NOM for RT, which was compared with the operative management (OM) with respect to mortality, morbidity, and length of hospital stay (LOS). METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-analyses statement was followed for this study. A systematic search was performed on Embase, Medline, Cochrane, and PubMed for studies published up to December 2015, without language restrictions, which compared NOM versus OM for renal injuries. RESULTS: Twenty nonrandomized retrospective cohort studies comprising 13,824 patients with blunt (2,998) or penetrating (10,826) RT were identified. When all RT were considered (American Association for the Surgery of Trauma grades 1-5), NOM was associated with lower mortality and morbidity rates compared to OM (8.3% vs 17.1%, odds ratio [OR] 0.471; 95% confidence interval [CI] 0.404-0.548; P<0.001 and 2% vs 53.3%, OR 0.0484; 95% CI 0.0279-0.0839, P<0.001). Likewise, NOM represented the gold standard treatment resulting in a lower mortality rate compared to OM even when only high-grade RT was considered (9.1% vs 17.9%, OR 0.332; 95% CI 0.155-0.708; P=0.004), be they blunt (4.1% vs 8.1%, OR 0.275; 95% CI 0.0957-0.788; P=0.016) or penetrating (9.1% vs 18.1%, OR 0.468; 95% CI 0.398-0.0552; P<0.001). CONCLUSION: Our meta-analysis demonstrated that NOM for RT is the treatment of choice not only for AAST grades 1 and 2, but also for higher grade blunt and penetrating RT.

An Alternative Surgery for an Atypical Kind of Grade C Postoperative Pancreatic Fistula Following Pancreaticoduodenectomy.

BACKGROUND/AIM: Grade C postoperative pancreatic fistula (POPF) is a life-threatening complication of pancreaticoduodenectomy (PD), with its surgical management remaining under debate. Occasionally, POPF is associated with a compromised anastomotic Roux-limb. Our series focused to this sort of grade C mixed fistula. PATIENTS AND METHODS: Between April 2004 and March 2014, 5 out of 12 patients with grade C POPF were classified as grade C mixed POPFs. Surgery consisted of associating resection of the anastomotic jejunal segment with resection and closure of the pancreatic stump. RESULTS: Four patients suffered from a grade C mixed POPF discharging into a single dehiscent site; 1 patient was found with two dehiscent points in all (pancreatic anastomosis and jejunal rim). For all of them, the described surgical procedure resulted in complete recovery. CONCLUSION: For grade C pancreatico-digestive POPF, resecting anastomotic jejunal segment during dismantling of the pancreatico-digestive anastomosis appears a very promising surgical technique.

5-Fluorouracil degradation rate could predict toxicity in stages II-III colorectal cancer patients undergoing adjuvant FOLFOX.

5-Fluorouracil is commonly used for gastrointestinal cancer treatment in an adjuvant setting; however, the toxicity can lead to a reduction, delay, or discontinuation of treatment. We retrospectively investigated the association between the 5-fluorouracil degradation rate (5-FUDR) and genetic polymorphisms of TSER, DPYD, and MHTFR with toxicity in colorectal cancer patients treated with adjuvant FOLFOX. Pretreatment 5-FUDR and MTHFR A1298T or C677T, TSER, and DPYD gene polymorphisms were characterized in stages II-III colorectal cancer patients. Patients were classified into three metabolic classes according to the 5-FUDR value. Association with toxicities was evaluated retrospectively using logistic regression analysis. Overall, 126 patients were selected (35 women, 91 men). Seven patients were poor metabolizers, 116 patients were normal metabolizers and three patients were ultra-rapid metabolizers. The median 5-FUDR was 1.53 ng/ml/10 cells/min (range: 0.42-2.57 ng/ml/10 cells/min). Severe, rate-limiting toxicities (grades 3-4) were encountered in 22.2% of patients. No associations between MTHFR or TSER polymorphisms and toxicity were detected, whereas 5-FUDR showed a statistically significant association with toxicity (P=0.0047). The DPYD heterozygous mutation was detected in only one patient, who showed grade 4 hematological toxicity and a lower 5-FUDR value. The 5-FUDR value seems not to be affected by MTHFR and TSER polymorphisms. Compared with the available pharmacogenomics tests, the pretreatment evaluation of 5-FUDR increases the proportion of identified colorectal patients at high risk for severe toxicity. Thus, it appears to be a suitable pretreatment toxicity biomarker in a subgroup of patients in whom dose-intensity maintenance is the key factor.

Transanal Minimally Invasive Surgery for Rectal Lesions.

BACKGROUND AND OBJECTIVES: Transanal minimally invasive surgery (TAMIS) has emerged as an alternative to transanal endoscopic microsurgery (TEM). The authors report their experience with TAMIS for the treatment of mid and high rectal tumors. METHODS: From November 2011 through May 2016, 31 patients (21 females, 68%), with a median age of 65 years who underwent single-port TAMIS were prospectively enrolled. Mean distance from the anal verge of the rectal tumors was 9.5 cm. Seventeen patients presented with T1 cancer, 10 with large adenoma, 2 with gastrointestinal stromal tumor (GIST) and 2 with carcinoid tumor. Data concerning demographics, operative procedure and pathologic results were analyzed. RESULTS: TAMIS was successfully completed in all cases. In 4 (13%) TAMIS was converted to standard Park's transanal technique. Median postoperative stay was 3 days. The overall complication rate was 9.6%, including 1 urinary tract infection, 1 subcutaneous emphysema, and 1 hemorrhoidal thrombosis. TAMIS allowed an R0 resection in 96.8% of cases (30/31 cases) and a single case of local recurrence after a large adenoma resection was encountered. CONCLUSION: TAMIS is a safe technique, with a short learning curve for laparoscopic surgeons already proficient in single-port procedures, and provides effective oncological outcomes compared to other techniques.

CYP19A1 Genetic Polymorphisms rs4646 and Osteoporosis in Patients Treated with Aromatase Inhibitor-Based Adjuvant Therapy.

OBJECTIVE: Third-generation aromatase inhibitors (AI) are potent suppressors of aromatase activity. The aim of this study was to measure the incidence of adverse effects in breast cancer patients treated with AI-based adjuvant therapy and the relationship with the CYP19A1 genotypes. MATERIALS AND METHODS: Forty-five postmenopausal breast cancer patients (46-85 yrs) in AI adjuvant treatment were genotyped for the rs4646 polymorphisms of CYP19A1 gene and three variations were identified. Toxicities were registered at each follow-up medical examination, and classified in accord with the Common Terminology Criteria for Adverse Events. RESULTS: Twenty-four (53.3%) patients presented the GG genotype; 19 (42.2%) the GT, and 2 (4.4%) the TT. The AI treatment was Anastrazole for 35 patients (77.8%) and Letrozole for the others (n=10; 22.2%). Osteoporosis was significantly associated with the GG genotype (p=0.001). Treatment discontinuation (TD) was observed in 6 cases (13.3%). The only parameter able to predict TD was the appearance of severe arthralgia/myalgia (Odds Ratio, OR=23.75; p=0.009), when adjusted for age and AI treatment. CONCLUSION: Our results suggest that CYP19A1 polymorphic variants may influence susceptibility to develop AI-related side effects. Further prospective studies are needed to confirm the role of the aromatase gene (CYP19A1) polymorphisms in predicting adverse effects to AI-based therapy.

Pre-treatment evaluation of 5-fluorouracil degradation rate: association of poor and ultra-rapid metabolism with severe toxicity in a colorectal cancer patients cohort.

Despite the wide use of 5-fluorouracil-based chemotherapy, development of severe toxicity that follow the treatment is not a rare event. The efforts to establish pretreatment tools for toxicity prediction, led to the development of various pharmacogenetic and biochemical assays, mainly targeted to assess the activity level of dihydropyrimidine dehydrogenase (DPD), the main metabolizing enzyme for 5-fluorouracil. Using peripheral blood mononuclear cells, we developed a biochemical assay, that is not limited to the evaluation of DPD activity, but determines the net result of all the enzymatic transformation of 5FU, in terms of the amount of drug consumed by the cells in a time unit. This parameter, named 5-fluorauracil degradation rate, presents a normal distribution inside the population and highlight the presence of an ultra-rapid metabolizers class of subjects, besides the expected poor metabolizers class. Here we will show that, in a colorectal cancer patient cohort, both poor and ultra-rapid metabolizers have significantly increased the risk of developing severe toxicity (grade3-4). Patient stratification depending on the individual 5-fluorouracil degradation rate allows to identify a 10% of the overall population at high risk of developing severe toxicity, compared to the 1.3% (as assessed in the Italian population) identified by the most commonly employed pharmacogenetic test, including the DPD polymorphism IVS14+1G>A.