Prognostic Role of Basal Serum Alpha-Fetoprotein in Patients with Hepatocellular Carcinoma Suitable for Curative Treatment.

Background and Objectives: Serum alpha-fetoprotein (AFP) is a recognized affordable oncological marker in patients with hepatocellular carcinoma (HCC). However, AFP's prognostic role has been assessed mainly after specific treatments, and no unanimously recognized cut-offs have been identified. The aim of this study is to investigate the prognostic role of different basal AFP cut-offs on survival and HCC course. Materials and Methods: In this single-center, retrospective study, all patients newly diagnosed with HCC between January 2009 and December 2021 were prospectively enrolled. Only patients suitable for curative HCC treatments were included in the analyses. Patients were stratified according to AFP cut-offs of 20, 200, 400, and 1000 ng/mL, which were correlated with survival outcomes and clinical parameters. Results: A total of 266 patients were analyzed, with a median follow-up time of 41.5 months. Median overall survival (OS) of all cohort was 43 months. At the multivariate Cox-regression analysis, AFP value ≥ 1000 ng/mL correlated with impaired OS (1-year OS: 67% vs. 88%, 5-year OS: 1% vs. 43%; p = 0.005); other risk factors were tumor dimension ≥ 5 cm (HR 1.73; p = 0.002), Child-Pugh class B-C (HR 1.72; p = 0.002), BCLC stage A (vs. 0) (HR 2.4; p = 0.011), and malignant portal vein thrombosis (HR 2.57; p = 0.007). AFP ≥ 1000 ng/mL was also associated with a reduced recurrence-free survival (HR 2.0; p = 0.038), while starting from AFP ≥ 20 ng/mL, a correlation with development of HCC metastases over time (HR 3.5; p = 0.002) was seen. AFP values ≥ 20 ng/mL significantly correlated with tumor size and higher histological grading; starting from AFP values ≥ 400 ng/mL, a significant correlation with Child-Pugh class B-C and female gender was also observed. Conclusions: Basal AFP correlates with relevant outcomes in patients with HCC. It could help identify patients at a higher risk of worse prognosis who might benefit from personalized surveillance and treatment programs. Prospective studies are needed to confirm these results.

Superior bowel preparation quality for colonoscopy with 1L-PEG compared to 2L-PEG and picosulphate: Data from a large real-world retrospective outpatient cohort.

BACKGROUND: Several randomized clinical trials comparing different bowel preparations (BP) have shown similar efficacy; however, there is a lack of real-world studies on this topic. AIMS: This study aims to identify the most effective BP regimen in a real-world setting and any predictors of inadequate BP. METHODS: A retrospective single-center study was conducted over 14 months at an academic hospital including outpatient colonoscopies in which adult patients did not teach on how to perform BP before colonoscopy. Colonoscopies with 1L-PEG, 2L-PEG and picosulphate mixtures were considered. A multivariable analysis for factors associated to poor BP was fitted. RESULTS: Overall, 1779 patients (51 %F, 60±14) years were included. The 1L-PEG regimen provided a higher rate of BP adequacy at multivariate analysis (adjusted OR 2.30, 95 %CI 1.67-3.16,p < 0.001) and was associated with higher median Boston Bowel Preparation Scale score (p < 0.001), higher rate of right-colon cleansing (p < 0.001) and exam completion (p = 0.04). Furthermore, we identified male sex, history of constipation, active smoking, previous pelvic surgery, concomitant psychiatric/neurological or chronic kidney diseases as predictors of inadequate BP. CONCLUSIONS: This is the largest real-world study comparing 1L-PEG to other BP regimens. Our results suggest 1L-PEG provides better BP in a non-controlled setting, improving clinical practice quality and minimizing the need for repeated colonoscopies and saving healthcare resources.

A Comprehensive Review on Bariatric Endoscopy: Where We Are Now and Where We Are Going.

Background: Obesity is a chronic disease that impairs quality of life and leads to several comorbidities. When conservative therapies fail, bariatric surgical options such as Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are the most effective therapies to induce persistent weight loss. Over the last two decades, bariatric endoscopy has become a valid alternative to surgery in specific settings. Primary bariatric endoscopic therapies: Restrictive gastric procedures, such as intragastric balloons (IGBs) and endoscopic gastroplasty, have been shown to be effective in inducing weight loss compared to diet modifications alone. Endoscopic gastroplasty is usually superior to IGBs in maintaining weight loss in the long-term period, whereas IGBs have an established role as a bridge-to-surgery approach in severely obese patients. IGBs in a minority of patients could be poorly tolerated and require early removal. More recently, novel endoscopic systems have been developed with the combined purpose of inducing weight loss and improving metabolic conditions. Duodenal mucosal resurfacing demonstrated efficacy in this field in its early trials: significant reduction from baseline of HbA1c values and a modest reduction of body weight were observed. Other endoscopic malabsorptive have been developed but need more evidence. For example, a pivotal trial on duodenojejunal bypasses was stopped due to the high rate of severe adverse events (hepatic abscesses). Optimization of these more recent malabsorptive endoscopic procedures could expand the plethora of bariatric patients that could be treated with the intention of improving their metabolic conditions. Revisional bariatric therapies: Weight regain may occur in up to one third of patients after bariatric surgery. Different endoscopic procedures are currently performed after both RYGB and SG in order to modulate post-surgical anatomy. The application of argon plasma coagulation associated with endoscopic full-thickness suturing systems (APC-TORe) and Re-EndoSleeve have shown to be the most effective endoscopic treatments after RYGB and SG, respectively. Both procedures are usually well tolerated and have a very low risk of stricture. However, APC-TORe may sometimes require more than one session to obtain adequate final results. The aim of this review is to explore all the currently available primary and revisional endoscopic bariatric therapies focusing on their efficacy and safety and their potential application in clinical practice.

Challenging cases in high-risk prostate cancer patients treated with Retzius-sparing robot-assisted radical prostatectomy.

OBJECTIVE: To evaluate the relationship between enlarged prostate, bulky median lobe (BML) or prior benign prostatic hyperplasia (BPH) surgery and perioperative functional, and oncological outcomes in high-risk (HR) prostate cancer (PCa) patients treated with Retzius-sparing robot-assisted radical prostatectomy (RS-RARP). METHODS: 320 HR-PCa patients treated with RS-RARP between 2011 and 2020 at a single high-volume center. The relationship between prostate volume, BML, prior BPH surgery and perioperative outcomes, Clavien-Dindo (CD) grade ≥ 2 90-day postoperative complications, positive surgical margins (PSMs), and urinary continence (UC) recovery was evaluated respectively in multivariable linear, logistic and Cox regression models. Complications were collected according to the standardized methodology proposed by EAU guidelines. UC recovery was defined as the use of zero or one safety pad. RESULTS: Overall, 5.9% and 5.6% had respectively a BML or prior BPH surgery. Median PV was 45 g (range: 14-300). The rate of focal and non-focal PSMs was 8.4% and 17.8%. 53% and 10.9% patients had immediate UC recovery and CD ≥ 2. The 1- and 2-yr UC recovery was 84 and 85%. PV (p = 0.03) and prior BPH surgery (p = 0.02) was associated with longer operative time. BML was independent predictor of time to bladder catheter removal (p = 0.001). PV was independent predictor of PSMs (OR: 1.02; p = 0.009). Prior BPH surgery was associated with lower UC recovery (HR: 0.5; p = 0.03). CONCLUSION: HR-PCa patients with enlarged prostate have higher risk of PSMs, while patients with prior BPH surgery have suboptimal UC recovery. These findings should help physicians for accurate preoperative counseling and to improve surgical planning in case of HR-PCa patients with challenging features.

Retzius-sparing Robot-assisted Radical Prostatectomy in High-risk Prostate Cancer Patients: Results from a Large Single-institution Series.

Background: Retzius-sparing (RS) robot-assisted radical prostatectomy represents a valid surgical treatment option for prostate cancer (PCa) patients. However, the available evidence on the role of RS in high-risk (HR) PCa setting is sparse. Objective: To describe our RS technique for HR-PCa patients and to evaluate intra-, peri-, and postoperative oncological and functional outcomes. Design setting and participants: A total of 340 D'Amico HR-PCa patients underwent RS at a single high-volume centre between 2011 and 2020. Surgical procedure: Surgical procedures were performed by five experienced robotic surgeons. Measurements: Complications were collected according to the standardised methodology proposed by the European Association of Urology guidelines. Postoperative outcomes were evaluated in patients with complete follow-up data (n = 320). Biochemical recurrence (BCR) was defined as two consecutive prostate-specific antigen values of ≥0.2 ng/ml. Urinary continence (UC) recovery was defined as the use of zero or one safety pad. Kaplan-Meier and multivariable logistic and Cox regression models were performed. Results and limitations: Fourteen patients (4%) experienced intraoperative complications and 52 90-d complications occurred in 44 patients (14%), of whom 24 had Clavien-Dindo 3a/b. Final pathology reported 49% International Society of Urological Pathology (ISUP) grade 4-5, 55% ≥pT3a, and 28.8% positive surgical margins (PSMs; 9.4% focal and 19.4% extended PSMs). The median follow-up was 47 mo. Overall, 35.3% and 1.3% harboured BCR and died from PCa. At 4 yr of follow-up, BCR-free survival and additional treatment-free survival were 63.6% and 56.6%, respectively. ISUP 4-5 at biopsy (odds ratio [OR]: 2.6), prostate volume (OR: 1.03), partial or full nerve sparing (OR: 1.9), and full bladder neck preservation (OR: 2.2) were independent predictors of PSMs. Pathological ISUP 4-5 (hazard ratio [HR]: 1.5) and PSMs (HR: 2.3) were independent predictors of BCR. Pathological ISUP 4-5 (HR: 1.5), PSMs (HR: 2.4), pT ≥3b (HR: 1.8), and pN ≥1 (HR: 1.8) were independent predictors of additional treatment. Immediate UC recovery was recorded in 53% patients. The 1- and 2-yr UC recovery and erectile function recovery were, respectively, 84% and 85%, and 43% and 50%. Conclusions: RS in HR-PCa patients allows optimal intra-, peri-, and postoperative outcomes. The RS approach should be considered a valid surgical treatment option for HR-PCa patients in expert hands. Patient summary: Relying on the largest cohort of high-risk prostate cancer patients treated with Retzius sparing (RS), we observed that the RS approach is safe and allows optimal cancer control, without significantly compromising functional outcomes.

Incidence and risk factors for preneoplastic and neoplastic lesions of the colon and rectum in patients under 50 referred for colonoscopy.

BACKGROUND: Colorectal cancer (CRC) diagnosed before the age of 50, known as early-onset CRC (eoCRC), is considered uncommon. We aimed at analysing the incidence of preneoplastic and neoplastic lesions of the colon and rectum in patients under 50 years old and to identify possible predictors Methods: We retrospectively collected data from 1778 patients under 50 years old (mean age 39.9±7.8) referred for colonoscopy between 2015-2018. Cumulative incidence of adenomas and eoCRC was assessed. Multivariable regression models were fitted Results: The cumulative incidence for adenomas was 11.0% (95% CI 9-12), while it was 1.5% (95% CI 1-2) for eoCRC (metastatic disease in 13/27 patients). Age as a continuous variable was associated with the presence of adenomas (incidence rate ratio 1.06; 95% CI 1.03-1.09; p<0.001). EoCRC arose in most cases in the rectum (13/27, 48.1%). Age ≥40 was the main risk factor (OR 2.25; 95% CI 1.35-3.73; p=0.002) for both adenomas (160/196 patients, 81.6%) and eoCRC (20/27 patients, 74.1%), while smoking seemed to have no role (p=0.772). The presence of alarm symptoms was statistically significant at bivariable analysis for eoCRC only (OR 3.70; 95% CI 1.49-9.22; p=0.005), as well as having multiple gastrointestinal symptoms (OR 19.85; 95% CI 2.64-149.42; p=0.004). Only 3/27 (11.1%) patients with eoCRC had a family history for CRC Conclusions: A high cumulative incidence rate of both adenomas and eoCRC was found, this latter occurring more common in patients aged 40-49, without apparent risk factors. The presence of alarm symptoms or multiple gastrointestinal symptoms led to a late diagnosis.

Retzius-sparing Robotic Radical Prostatectomy for Surgeons in the Learning Curve: A Propensity Score-matching Analysis.

BACKGROUND: Several authors claimed that the Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) needs a prolonged learning curve, and outcomes during this phase could be suboptimal. OBJECTIVE: To verify the safety and outcomes of RS-RARP performed by young surgeons during the learning curve. DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective analysis of the pre-, intra-, and postoperative features of all the patients who underwent RS-RARP from 2013 to 2017. We divided our patients into two groups: patients operated by two experienced surgeons (ESs) with >100 procedures and patients operated on by five younger surgeons in the learning curve (LCSs). LCSs had no previous experience in radical prostatectomy, and the very first RS-RARP procedures of each LCS case are included in the analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Perioperative, oncological, and functional data were analyzed. Short-term oncological results were reported as positive surgical margins (PSMs) and 1-yr disease-free survival. Complications were graded according to the Clavien-Dindo system. Potency was defined as erections sufficient for intercourse; continence was defined as no pad or one safety liner. A propensity score-matching analysis was used to adjust the difference in baseline preoperative parameters between the groups. RESULTS AND LIMITATIONS: We obtained two homogeneous groups of 256 patients each. After the matching, preoperative variables were similar in the two groups. The mean console time was longer for younger surgeons (98 vs 122 min, p < 0.001). Postoperative course, complications, and functional results were similar in the two groups; the final pathological analysis showed a worse T stage in the ES group (p = 0.017). PSMs and 1-yr disease-free survival did not differ between the groups. CONCLUSIONS: RS-RARP can be safely performed by inexperienced surgeons who have received adequate training. PATIENT SUMMARY: Surgeons in the learning curve can perform Retzius-sparing robot-assisted radical prostatectomy safely, with similar early oncological results and functional outcomes.

Upper gastrointestinal bleeding in COVID-19 inpatients: Incidence and management in a multicenter experience from Northern Italy.

BACKGROUND: COVID-19 patients have an increased susceptibility to develop thrombotic complications, thus thromboprophylaxis is warranted which may increase risk of upper gastrointestinal bleeding (UGIB). Our aim was to evaluate incidence of UGIB and use of upper GI endoscopy in COVID-19 inpatients. METHODS: The medical and endoscopic management of UGIB in non-ICU COVID-19 patients has been retrospectively evaluated. Glasgow Blatchford score was calculated at onset of signs of GI bleeding. Timing between onset of signs of GI bleeding and execution, if performed, of upper GI endoscopy was evaluated. Endoscopic characteristics and outcome of patients were evaluated overall or according to the execution or not of an upper GI endoscopy before and after 24h. RESULTS: Out of 4871 COVID-19 positive patients, 23 presented signs of UGIB and were included in the study (incidence 0.47%). The majority (78%) were on anticoagulant therapy or thromboprophylaxis. In 11 patients (48%) upper GI endoscopy was performed within 24h, whereas it was not performed in 5. Peptic ulcer was the most common finding (8/18). Mortality rate was 21.7% for worsening of COVID-19 infection. Mortality and rebleeding were not different between patients having upper GI endoscopy before or after 24h/not performed. Glasgow Blatchford score was similar between the two groups (13;12-16 vs 12;9-15). CONCLUSION: Upper GI bleeding complicated hospital stay in almost 0.5% of COVID-19 patients and peptic ulcer disease is the most common finding. Conservative management could be an option in patients that are at high risk of respiratory complications.

Pain and discomfort after Retzius-sparing robot-assisted radical prostatectomy: a comparative study between suprapubic cystostomy and urethral catheter as urinary drainage.

BACKGROUND: The aim of this study is to evaluate differences in discomfort, complications and functional results after Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) according to different urinary drainage: suprapubic tube (SPT) and standard urethral catheter (UC). METHODS: Prospective, comparative, consecutive, non-randomized study. In all patients with a water-tight anastomosis, no hematuria, obesity, previous suprapubic surgery or history of bladder cancer, a SPT (two-way Foley 14-Fr catheter) was positioned instead of a Foley 18-Fr UC. One week after surgery, an institutional self-compiled questionnaire was administered. The patients were divided into two groups according to the presence of UC or SPT and were compared concerning pain, perioperative results, complications, functional outcomes. RESULTS: Fifty-six patients with UC and 135 with SPT agreed to participate to the study. Median postoperative pain score was 3 (IQR: 2-5) in UC and 3 (IQR: 1-5) in SPT group (P=0.324); urinary drain-related pain scores were 3 (IQR: 1-5) in UC and 1 (IQR: 0-3) in SPT groups (P<0.001); catheter removal related scores were 1 (IQR: 0-3) and 1 (IQR: 1-3) (P=0.317), respectively. Lastly, 17.8% (UC) and 31.1% (SPT) wore a protection (small or medium pad) while the urinary drainage was in place (P=0.061). No differences related to complications were found (P=0.085); 7.9% of patients in UC group and 4.2% in SPT group (P=0.178) used pads one year after surgery. CONCLUSIONS: We demonstrated suprapubic tube to be more comfortable than transurethral catheter after RARP, with a possible advantage concerning anastomotic postoperative problems.

Technical features and the demonstrated advantages of the Retzius sparing robotic prostatectomy.

OBJECTIVE: Robot-assisted laparoscopic  radical prostatectomy (RARP) is nowadays considered  the main surgical option for localized prostate cancer (PCa). We recently developed a new approach for RARP  avoiding all the Retzius structures involved in continence  and potency preservation, the so called Retzius-sparing  technique (RSP). The objective of the paper is to report technical aspects and functional results of RSP.  METHODS: We evaluated our data and available literature  regarding RSP, functional results and advantages.  RESULTS: RSP is oncologically safe and guarantee high early continence rates. CONCLUSION: Long-term, prospective, comparative,  and possibly randomized studies are needed but RSP is  now spreading all over the world thanks to the different advantages that offers to patients. The most recognized benefit is surely the achievement of early continence, as well documented in multiple studies and papers, without compromising the oncological outcomes.

ARTICULO SOLO EN INGLES. OBJETIVO: La prostatectomía radical laparoscópica  asistida por robot (PRAR) se considera hoy  en día la principal opción quirúrgica para el cáncer de próstata localizado. Recientemente desarrollamos un  nuevo abordaje para la PRAR evitando todas las estructuras  del Retzius involucradas en la conservación de la continencia y la potencia, la conocida como técnica de prostatectomía conservadora del Retzius (PCR). El objetivo  de este artículo es comunicar los aspectos técnicos  y funcionales de la PCR. MÉTODOS: Evaluamos nuestros datos y la literatura disponible  sobre PCR, resultados funcionales y ventajas. RESULTADOS: La PCR es oncológicamente segura y garantiza  unas tasas altas de continencia precoz. CONCLUSIONES: Son necesarios estudios a largo  plazo, prospectivos, comparativos y posiblemente aleatorizados pero la PCR está actualmente extendiéndose  por todo el mundo gracias a las diferentes ventajas que ofrece a los pacientes. El beneficio más reconocido es  seguramente la consecución de continencia precoz, bien documentada en múltiples estudios y artículos, sin  compromiso de los resultados oncológicos.

Technical features and the demonstrated advantages of the retzius sparing robotic prostatectomy / Aspectos técnicos y ventajas demostradas de la prostatectomía robótica con preservación de Retzius

Objective: Robot-assisted laparoscopic radical prostatectomy (RARP) is nowadays considered the main surgical option for localized prostate cancer (PCa). We recently developed a new approach for RARP avoiding all the Retzius structures involved in continence and potency preservation, the so called Retzius-sparing technique (RSP). The objective of the paper is to report technical aspects and functional results of RSP. Methods: We evaluated our data and available literature regarding RSP, functional results and advantages. Results: RSP is oncologically safe and guarantee high early continence rates. Conclusion: Long-term, prospective, comparative, and possibly randomized studies are needed but RSP is now spreading all over the world thanks to the different advantages that offers to patients. The most recognized benefit is surely the achievement of early continence, as well documented in multiple studies and papers, without compromising the oncological outcomes

Objetivo: La prostatectomía radical laparoscópica asistida por robot (PRAR) se considera hoy en día la principal opción quirúrgica para el cáncer de próstata localizado. Recientemente desarrollamos un nuevo abordaje para la PRAR evitando todas las estructuras del Retzius involucradas en la conservación de la continencia y la potencia, la conocida como técnica de prostatectomía conservadora del Retzius (PCR). El objetivo de este artículo es comunicar los aspectos técnicos y funcionales de la PCR. Métodos: Evaluamos nuestros datos y la literatura disponible sobre PCR, resultados funcionales y ventajas. Resultados: La PCR es oncológicamente segura y garantiza unas tasas altas de continencia precoz. Conclusiones: Son necesarios estudios a largo plazo, prospectivos, comparativos y posiblemente aleatorizados pero la PCR está actualmente extendiéndose por todo el mundo gracias a las diferentes ventajas que ofrece a los pacientes. El beneficio más reconocido es seguramente la consecución de continencia precoz, bien documentada en múltiples estudios y artículos, sin compromiso de los resultados oncológicos

Does prostate volume have an impact on the functional and oncological results of Retzius-sparing robot-assisted radical prostatectomy?

BACKGROUND: The objective of our study is to evaluate the effect of prostatic volume on the outcomes of Retzius-sparing robot-assisted radical prostatectomy (RSP). METHODS: All the consecutive patients undergoing RSP up to January 2015 were included. The series was divided into three groups based on prostate weight at radical prostatectomy specimen (<40 g, 40-60 g, >60 g). Perioperative, oncological and functional data were prospectively recorded. Potency was defined as erections sufficient for penetration; continence as no pad or one safety liner. Oncological results were reported as positive surgical margins (PSMs) and 1-year biochemical disease-free survival (PSA<0.2 ng/mL). RESULTS: We evaluated 750 patients (366 with <40 g prostates, 272 with 40-60 g prostates, 112 with >60 g prostates). Median follow-up was 22 months; PSA was higher in larger prostates (6.6 vs. 6.8 vs. 8 ng/mL). Nerve-sparing and bladder-neck sparing procedures were in similar percentages. Larger prostates required longer surgeries (90 vs. 100 vs. 100 minutes, P=0.002). Perioperative results were similar (blood loss, discharge, complications, catheter removal). Larger prostates had more frequently localized disease (pT2 in 49.5% vs. 60.7% vs. 68.5%; P=0.001); PSMs were similar both in pT2 (15.5% vs. 9.4% vs. 11.8%) and in pT3 cases (40.1% vs. 42% vs. 34%). In the three study groups, immediate continence was reached by 88%, 89.5% and 81.3% (P=0.045), while no differences were observed concerning continence (93.4%, 94.1%, 94.7%; P=0.892) or potency after follow-up. CONCLUSIONS: RSP is feasible in patients with prostates of any volume, with similar oncological and functional outcomes. Despite being inferior to the figures obtained in low volume prostates, the very high immediate continence rates observed in larger prostates encourage the use of this approach also in larger prostates.

Tolerogenic effect of mesenchymal stromal cells on gliadin-specific T lymphocytes in celiac disease.

BACKGROUND AIMS: Celiac disease is caused by a dysregulated immune response toward dietary gluten, whose only treatment is a lifelong gluten-free diet. We investigated the effects of mesenchymal stromal cells (MSCs) on gliadin-specific T cells, which are known to induce intestinal lesions, in view of a possible use as new therapy. METHODS: Bone marrow-derived MSCs and gliadin-specific T-cell lines were obtained from allogeneic donors and mucosal specimens of celiac patients, respectively. The immunosuppressant effect of MSCs was evaluated in terms of proliferative response and interferon (IFN)-γ production upon gliadin stimulation of long-term T-cell lines; the immunomodulant effect was assessed in terms of apoptotic rate, immunophenotype and cytokine profile of short-term T-cell lines generated in the presence of MSCs. Different MSC:T-cell ratios were applied, and statistics were performed as appropriate. RESULTS: MSCs inhibited both proliferative response and IFN-γ production of long-term T-cell lines in a dose-dependent manner while limiting the expansion of short-term T-cell lines by increasing the apoptotic rate. Moreover, a reduction of the CD4(+) population and expansion of the regulatory FoxP3+ subset were found in T-cell lines cultured with MSCs, in which a significant decrease of interleukin (IL)-21, IFN-γ and IL-10 paralleled by an upregulation of transforming growth factor-ß1, IL-6 and IL-8 were observed. Finally, an increase of the indoleamine 2,3-dioxygenase activity was found, possibly playing a key role in mediating these effects. CONCLUSIONS: MSCs exert potent immunomodulant effects on gliadin-specific T cells, which may be exploited for future therapeutic application in celiac disease.

Role of the advanced glycation end products receptor in Crohn's disease inflammation.

AIM: To investigate the level of mucosal expression and the involvement of the receptor for the advanced glycation end products (RAGE) in delayed apoptosis and tumor necrosis factor (TNF)-α production in Crohn's disease (CD). METHODS: Surgical and endoscopic specimens from both inflamed and non-inflamed areas of the ileum and/or colon were collected from 20 and 14 adult CD patients, respectively, and used for the assessment of RAGE expression by means of immunohistochemistry and western blotting analysis. Normal tissues from 21 control subjects were used for comparison. The same polyclonal anti-human RAGE antibody (R and D System) was used in all experimental conditions. RAGE staining was quantized by a score including both the amount of positive cells and intensity of immunoreactivity; cellular pattern was also described. The effects of RAGE blocking on apoptotic rate and TNF-α production were investigated on immune cells freshly isolated from CD mucosa and incubated both with and without the muramyl dipeptide used as antigenic stimulus. Statistical analysis was performed via the test for trend, with regression models to account for intra-patient correlations. A 2-sided P < 0.05 was considered significant. RESULTS: In inflamed areas, RAGE expression in both the epithelial and lamina propria compartments was higher than control tissues (P = 0.001 and 0.021, respectively), and a cluster of positive cells were usually found in proximity of ulcerative lesions. Similar results were obtained in the lamina propria compartment of non-inflamed areas (P = 0.025). The pattern of staining was membranous and granular cytosolic at the epithelial level, while in the lamina propria it was diffuse cytosolic. When evaluating the amount of protein expression by immunoblotting, a significant increase of both surface area and band intensity (P < 0.0001 for both) was observed in CD inflamed areas compared to control tissue, while in non-inflamed areas a significant increase was found only for band intensity (P < 0.005). Moreover, a significantly lower expression in non-inflamed areas in comparison with inflamed areas was found for both surface area and band intensity (P < 0.0006 for both). Finally, RAGE blocking largely affects both the apoptotic rate of mucosal cells (towards an increase in both non-inflamed and inflamed areas of P < 0.001 and < 0.0001, respectively) and TNF-α secretion (towards a decrease in both non-inflamed and inflamed areas of P < 0.05 and < 0.01, respectively), mainly in the presence of antigenic stimulation. CONCLUSION: RAGE is up-regulated in CD, especially in inflamed areas, and it appears to play a role in the mechanisms involved in chronic inflammation.

Beyond the learning curve of the Retzius-sparing approach for robot-assisted laparoscopic radical prostatectomy: oncologic and functional results of the first 200 patients with ≥ 1 year of follow-up.

BACKGROUND: Robot-assisted laparoscopic radical prostatectomy (RARP) has become the main surgical option for localized prostate cancer. We recently developed a new approach for RARP, passing through the pouch of Douglas and avoiding all the Retzius structures involved in continence and potency preservation. OBJECTIVE: To report the functional and oncologic results of our first 200 patients operated on using this new approach. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective, noncontrolled case series including the first 200 consecutive patients undergoing this kind of surgery (January the 1st, 2010 to December the 31st, 2011). SURGICAL PROCEDURE: Retzius-sparing RARP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: All perioperative, oncologic, and functional data were prospectively recorded. Potency was defined as an International Index of Erectile Function-5 questionnaire score >17; continence was defined as use of no pad or of one safety liner. Oncologic results were reported as positive surgical margins (PSM) and 1-yr biochemical disease-free survival (1y-bDFS). Recurrence was defined as a repeated prostate-specific antigen >0.2 ng/ml. Complications were graded according to the Clavien-Dindo system. The first 100 patients (group 1) were compared with the second 100 (group 2) to evaluate the learning curve effects. RESULTS AND LIMITATIONS: The median patient age was 65 yr. Comparing the two groups, transfusions were needed in 8% versus 4% of cases in groups 1 and 2, respectively (p=0.02). There was one Clavien-Dindo grade 3b in group 1 versus one grade 3a complication in group 2. In patients with pT2 disease, PSMs were recorded in 22.4% of those in group 1 versus 10.1% in group 2 (p=0.045). 1y-bDFS was 89% in group 1 versus 92% in group 2. For groups 1 and 2, respectively, immediate continence was reached in 92% versus 90% of patients, and the 1-yr continence rate was 96% versus 96%. Considering the 77 potent patients aged <65 yr who underwent bilateral intrafascial nerve-sparing surgery, 40.4% of those in group 1 versus 40% of those in group 2 reached their first intercourse within 1 mo; at 1 yr of follow-up, these figures had increased to 81% versus 71%, respectively (p=0.162). The main limitation of this study is its noncontrolled nature. CONCLUSIONS: We demonstrated Retzius-sparing RARP to be oncologically safe and to result in high early continence and potency rates. Long-term, prospective, comparative, and possibly randomized studies are needed.

Mycobacterium avium paratuberculosis in Italy: commensal or emerging human pathogen?

BACKGROUND: Specific bacterial infections or alterations of the gut microbiota likely trigger immuno-pathological phenomena associated with Crohn's disease and ulcerative colitis. Mycobacterium avium subspecies paratuberculosis is a candidate etiological agent of Crohn's disease. Definitive causal connection between Mycobacterium avium subspecies paratuberculosis infection and Crohn's disease has not been demonstrated. AIMS: To determine the circulation of Mycobacterium avium subspecies paratuberculosis in Crohn's disease patients and water supplies in an Italian region where this bacterium is endemic in cattle farms. METHODS: Mycobacterium avium subspecies paratuberculosis screening was performed on biopsies from human patients, and from water samples, using two different PCR procedures. RESULTS: In hospitals where multiple specimens were obtained from different sites in the intestine, the prevalence of Mycobacterium avium subspecies paratuberculosis infection was 82.1% and 40% respectively in Crohn's disease and ulcerative colitis patients; in another hospital, where single specimens were obtained from patients, the bacterium was not detected. Control subjects also harboured Mycobacterium avium subspecies paratuberculosis, but at a lower prevalence. Tap water samples collected in the study area contained Mycobacterium avium subspecies paratuberculosis DNA. DISCUSSION: The results of screenings for Mycobacterium avium subspecies paratuberculosis in humans are deeply influenced by both the number and location of the collected biopsies. There is a wide circulation of the organism in the study area, considering the prevalence in humans and its presence in drinking water.

Impact of venous tumour thrombus consistency (solid vs friable) on cancer-specific survival in patients with renal cell carcinoma.

BACKGROUND: To our knowledge, the impact of venous tumour thrombus (VTT) consistency in patients affected by renal cell carcinoma (RCC) has never been addressed. OBJECTIVE: To analyse the effect of VTT consistency on cancer-specific survival (CSS). DESIGN, SETTING, AND PARTICIPANTS: We retrospectively analysed 174 consecutive patients with RCC and renal vein or inferior vena cava (IVC) VTT who underwent surgical treatment between 1989 and 2007 at our institute. INTERVENTION: All patients underwent radical nephrectomy and thrombectomy. MEASUREMENTS: Pathologic specimens were reviewed by a single uropathologist. In addition to traditional pathologic features, the morphologic aspect of the tumour thrombus was evaluated to distinguish solid from friable patterns. The prognostic role of thrombus consistency (solid vs friable) on CSS was assessed by means of Cox regression models. RESULTS AND LIMITATIONS: The VTT was solid in 107 patients (61.5%) and friable in 67 patients (38.5%). The presence of a friable VTT increased the risk of having synchronous nodal or distant metastases, higher tumour grade, higher pathologic stage, and simultaneous perinephric fat invasion (all p < 0.05). The median follow-up was 24 mo. The median CSS was 33 mo; the median CSS was 8 mo in patients with a friable VTT and 55 mo in patients with a solid VTT (p < 0.001). On multivariable analyses, the presence of a friable VTT was an independent predictor of CSS (p = 0.02). The power of our conclusion may be somewhat limited by the relatively small study population and the retrospective nature of the study. CONCLUSIONS: In patients with RCC and VTT, the presence of a friable thrombus is an independent predictor of CSS. If our finding is confirmed by further studies, the consistency of the tumour thrombus should be introduced into routine pathologic reports to provide better patient risk stratification.

[From kidney disease to ischemic heart disease]. / Dall'insufficienza renale alla cardiopatia ischemica.

Chronic kidney disease is a pathology progressively increasing in the world. Patients with renal disease have an about 20 times greater chance of dying for cardiovascular disease than to reach the stage of dialysis and, compared to general population, they have a three times greater risk of developing acute myocardial infarction. Based on these considerations, we analyzed the most important metabolic changes that occur in renal failure, predisposing to ischemic heart disease. Changes in lipids and calcium-phosphorus metabolism, inflammation and oxidative stress, hyperhomocysteinemia, renin-angiotensin-aldosterone axis, anemia, left ventricular hypertrophy and albuminuria have been considered.

The extent of tumour fat invasion affects survival in patients with renal cell carcinoma and venous tumour thrombosis.

OBJECTIVE: • To investigate the effect of presence and extent of tumour fat invasion (TFI) - perinephric invasion (PFI), renal sinus fat invasion (RSFI) or both PFI and RSFI - on cancer-specific mortality (CSM) in patients with renal cell carcinoma (RCC) and venous tumour thrombus (VTT). METHODS: • We examined 184 consecutive patients with RCC with VTT treated with nephrectomy between 1987 and 2007. Associations with CSM were evaluated by univariable and multivariable Cox proportional hazard models. RESULTS: • Median follow up was 21 months. The 5-year CSM-free survival estimates were 75%, 36% and 20% in patients with VTT without TFI, those with VTT with PFI or RSFI, and those with VTT with both PFI and RSFI, respectively (P < 0.001). In multivariable analyses, presence of either PFI or RSFI was associated with a two-fold increased risk of CSM, whereas presence of both PFI and RSFI was associated with a three-fold increased risk of CSM, relative to VTT-only cases. • The inclusion of the variable describing the presence and extent of TFI in a base model including pT stage, Fuhrman grade and presence of nodal disease and metastatic disease significantly increased the accuracy in predicting CSM (+2.1%; P < 0.001) in patients with VTT. CONCLUSIONS: • Patients affected by RCC with VTT and TFI have a higher risk of CSM relative to cases with VTT only. Patients with both PFI and RSFI showed increased CSM compared with patients with either PFI or RSFI. • Our results suggest TFI should be accurately evaluated and included in routine pathological reports to provide better patient risk stratification.