Predictive role of diffusion-weighted MRI in the assessment of response to total neoadjuvant therapy in locally advanced rectal cancer.

OBJECTIVE: To investigate the predictive role of diffusion-weighted magnetic resonance imaging (DW-MRI) in the assessment of response to total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer (LARC). METHODS: In this single-center retrospective study, patients with LARC who underwent staging MRI and TNT were enrolled. MRI-based staging, tumor volume, and DWI-ADC values were analyzed. Patients were classified as complete responders (pCR) and non-complete responders (non-pCR), according to post-surgical outcome. Pre-treatment ADC values were compared to pathological outcome, post-treatment downstaging, and reduction of tumor volume. The diagnostic accuracy of DWI-ADC in differentiating between pCR and non-pCR groups was calculated with receiver operating characteristic (ROC) analysis. RESULTS: A total of 36 patients were evaluated (pCR, n = 20; non-pCR, n = 16). Pre-treatment ADC values were significantly different between the two groups (p = 0.034), while no association was found between pre-TNT tumor volume and pathological response. ADC values showed significant correlations with loco-regional downstaging after therapy (r = -0.537, p = 0.022), and with the reduction of tumor volume (r = -0.480, p = 0.044). ADC values were able to differentiate pCR from non-pCR patients with a sensitivity of 75% and specificity of 70%. CONCLUSIONS: ADC values on pre-treatment MRI were strongly associated with the outcome in patients with LARC, both in terms of pathological response and in loco-regional downstaging after TNT, suggesting the use of DW-MRI as a potential predictive tool of response to therapy. KEY POINTS: • ADC values of pre-TNT MRI examinations of patients with LARC were significantly associated with a pathological complete response (pCR) and with post-treatment regression of TNM staging. • An ADC value of 1.042 ×10-3 mm2/s was found to be the optimal cutoff value for discriminating between pCR and non-pCR patients, with a sensitivity of 75% and specificity of 70%. • DW-MRI proved to have a potential predictive role in the assessment of response to therapy in patients with LARC, throughout the analysis of ADC map values.

Upstaging nodal status in colorectal cancer using ex vivo fluorescence sentinel lymph node mapping: preliminary results.

BACKGROUND: Sentinel lymph node (SLN) mapping using near-infrared fluorescence (NIRF) imaging is a recent technique to improve nodal staging in several tumors. The presence of colorectal cancer (CRC) micro-metastases has recently been defined as N1 disease and no longer as N1mi, determining the need for adjuvant chemotherapy. In CRC, the reported rate of SLN micro-metastases detected by ultrastaging techniques is as high as 30%. The aim of this prospective study is to report the preliminary results of the sensitivity analysis of NIRF imaging for ex vivo SLN mapping and the research of micro-metastases in CRC, in patients with node-negative disease (NND). MATERIAL AND METHODS: On the specimen of 22 CRC patients, 1 mL of ICG (5 mg/mL) was injected submucosally around the tumor to identify SLNs. NND SLNs were further investigated with ultrastaging techniques. RESULTS: Three-hundred and sixty-three lymph nodes were retrieved (59 SLNs; mean per case: 2.7). The detection, sensitivity and false-negative rate were 100%, 100% and 0% respectively. Ultrastaging investigations showed no micro-metastases in the NND SLNs. CONCLUSIONS: The ex vivo SLN fluorescence-based detection in CRC was confirmed to be easy to perform and reliable. In this preliminary results report of an ongoing study, the SLN assay was congruent with the nodal status, as confirmed by histological investigations.

Tissue Expression of Androgen Receptor Splice Variant 7 at Radical Prostatectomy Predicts Risk of Progression in Untreated Nonmetastatic Prostate Cancer.

BACKGROUND: Androgen receptor splice variant V7 (AR-V7) was recently detected in circulating tumor cells of castration-resistant prostate cancer (PC) patients and its expression correlated with resistance to new-generation androgen signaling inhibitors. OBJECTIVES: We retrospectively analyzed whether AR-V7 expression was detectable on radical prostatectomy (RP) specimens of untreated nonmetastatic PC cases, and whether it could be associated with progression after surgery. METHOD: The expression of AR-V7 and AR-FL (full length) was separately evaluated by immunohistochemistry using a streptavidin-biotin-peroxidase system with 2 anti-AR-V7 and anti-AR-FL rabbit monoclonal antibodies. RESULTS: 56 PC cases, classified by their clinical risk, were analyzed. Positive expression was found in 24/32 cases in the high-risk group, 4/13 in the intermediate-risk group, and only 2/11 in the low-risk group. We found a significant correlation between AR-V7 positivity and both risk classification (p < 0.001) and progression after surgery (p < 0.001). CONCLUSIONS: In our population of untreated nonmetastatic PC, AR-V7 is detectable by immunohistochemistry in more than 50% of cases. At this early stage, AR-V7 positivity is associated with risk classification and it can predict progression after surgery.

Prospective assessment of two-gene urinary test with multiparametric magnetic resonance imaging of the prostate for men undergoing primary prostate biopsy.

PURPOSE: To evaluate the diagnostic accuracy of SelectMDx and its association with multiparametric magnetic resonance (mpMRI) in predicting prostate cancer (PCa) and clinically significant PCa (csPCa) on prostate biopsies among men scheduled for initial prostate biopsy. METHODS: In this single-center prospective study, 52 men scheduled for initial prostate biopsy, based on elevated total PSA level (> 3 ng/ml) or abnormal digital rectal examination, were consecutively included. All subjects underwent SelectMDx, PSA determination and mpMRI. RESULTS: SelectMDx score was positive in 94.1 and 100% of PCa and csPCa, respectively, and in only 8.6% of negative cases at biopsy. The probability for a csPCa at the SelectMDx score was significantly (p = 0.002) higher in csPCa (median value 52.0%) than in all PCa (median value 30.0%). SelectMDx showed slightly lower sensitivity (94.1 versus 100.0%) but higher specificity (91.4%) than total PSA (17.1%), and the same sensitivity but higher specificity than mpMRI (80.0%) in predicting PCa at biopsy. The association of SelectMDx plus mpMRI rather than PSA density (PSAD) plus mpMRI showed higher specificity (both 91.4%) compared to the association of PSA plus mpMRI (85.7%). In terms of csPCa predictive value, SelectMDx showed higher specificity (73.3%) than PSA (13.3%) and mpMRI (64.4%); as for the association of SelectMDx plus mpMRI (75.6%) versus PSA plus mpMRI (68.9%), the association of PSAD plus mpMRI showed the highest specificity (80.0%). CONCLUSION: Our results of SelectMDx can be confirmed as significant but their impact on clinical practice together with a cost-effectiveness evaluation should be investigated in a larger prospective multicenter analysis.

Sheep in Wolf's Clothing: Pedunculated Colonic Lipoma with Overlying Hyperplastic and Ulcerated Epithelium.

INTRODUCTION: Lipomas are the most common non-epithelial benign tumors of the gastrointestinal tract with a reported incidence in the colon of 0.2-4.4%. These lesions are usually asymptomatic with a typical endoscopic finding of a smooth, slightly yellow, circular, polyp that is sessile in most cases, covered with normal colonic mucosa. AREAS COVERED: There are rare reported cases of alterations of the overlying mucosa such as hyperplasia, atrophy, adenomatous changes, and necrosis. EXPERT COMMENTARY: We report a rare case of pedunculated colonic lipoma of the transverse colon covered with hyperplastic and ulcerated epithelium easily misdiagnosed as an adenomatous lesion.

Anti-transglutaminase immunoreactivity and histological lesions of the duodenum in coeliac patients.

Coeliac disease (CD) is characterized by several markers, including anti-transglutaminase auto-antibodies (tTGAb) directed against multiple epitopes of the gliadin protein. We aimed to investigate the correlation among CD duodenal lesions, tTGAb titres and the immunoreactivity against tTG constructs. A total of 345 CD patients (209 females, 136 males, overall median age: 7.3 years) were tested for full-length (fl) tTGAb with a fluid-phase radioimmunoassay. Out of the total, 231 patients were also tested for immunoreactivity against tTG fragments (F1: a.a. 227-687 and F2: a.a. 473-687). Patients were classified according to diffuse (D), patchy (P) or bulb (B) histological lesions. All sera were found fltTGAb positive. Patients with D, P and B lesions had a mean Ab index of 0.84±0.39, 0.57±0.39 and 0.45±0.24, respectively. Mean tTGAb titre varied between D and localized (P+B) patients (0.84±0.39 versus 0.52±0.34, P < 0.0001). Overall, 86.1% of patients were F1 auto-antibody (F1Ab) positive (D: 89%, P: 75%, B: 40%; D versus P+B: P = 0.004) and 49% of patients were F2 auto-antibody (F2Ab) positive (D: 53%, P: 19%, B: 10%; D versus P+B: P = 0.0006). Of the D patients 50.7% showed combined F1Ab-F2Ab (D versus P+B: P = 0.001), whereas 60% of B patients were negative for both F1Ab and F2Ab (B versus D: P < 0.0001). Coeliac-specific tTGAb immunoreactivity correlates with the grading and extension of histological duodenal lesions in CD patients at diagnosis. The immunoreactivity against single and combined tTG fragments is significantly higher in patients with D lesions. This is the first evidence of a distinct coeliac-specific immunoreactivity in patients with different duodenal involvement.

The celiac iceberg: characterization of the disease in primary schoolchildren.

OBJECTIVE: Celiac disease (CD) has a prevalence of 0.55% to 1% in Italy. Identifying CD in schoolchildren to characterize CD iceberg and evaluate the effect of diagnosis in screening-detected children. METHODS: A total of 7377 5- to 8-year-old children were invited to participate. A total of 5733 salivary samples were collected and tested for anti-transglutaminase antibodies (tTGAb), using a fluid-phase radioimmunoassay. Salivary tTGAb-positive children were analyzed for serum antibodies (anti-endomysium antibodies, radioimmunoassay, and enzyme-linked immunosorbent assay tTGAb). Positive children underwent endoscopy and then started gluten-free diet (GFD) and periodical follow-up. RESULTS: Forty-six subjects were found salivary tTGAb-positive and 16 border-line. Forty-five of 46 and 5 of 15 of them were also serum antibody-positive. Forty-two children showed duodenal villous atrophy and 1 had only type 1 lesions. Three children started GFD without performing endoscopy. CD prevalence (including 23 previously diagnosed children with CD) was 1.2%. Considering all 65 celiacs in our sample, a silent CD was found in 64%, typical in 28%, atypical in 7%, and potential in 1%. All patients showed strict adherence to GFD, weight and stature increase, and well-being improvement. Eighty-five percent and all but 2 screening-detected children with CD had Italian parents. CONCLUSIONS: Our sample size, representative of primary schoolchildren of our region, demonstrated that CD prevalence is growing in Italy, with a modified clinical spectrum and iceberg deepness.

Performance of Node-RADS Scoring System for a Standardized Assessment of Regional Lymph Nodes in Bladder Cancer Patients.

BACKGROUND: Current cross-sectional imaging modalities exhibit heterogenous diagnostic performances for the detection of a lymph node invasion (LNI) in bladder cancer (BCa) patients. Recently, the Node-RADS score was introduced to provide a standardized comprehensive evaluation of LNI, based on a five-item Likert scale accounting for both size and configuration criteria. In the current study, we hypothesized that the Node-RADS score accurately predicts the LNI and tested its diagnostic performance. METHODS: We retrospectively reviewed BCa patients treated with radical cystectomy (RC) and bilateral extended pelvic lymph node dissection, from January 2019 to June 2022. Patients receiving preoperative systemic chemotherapy were excluded. A logistic regression analysis tested the correlation between the Node-RADS score and LNI both at patient and lymph-node level. The ROC curves and the AUC depicted the overall diagnostic performance. In addition, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for different cut-off values (>1, >2, >3, >4). RESULTS: Overall, data from 49 patients were collected. Node-RADS assigned on CT scans images, was found to independently predict the LNI after an adjusted multivariable regression analysis, both at the patient (OR 3.36, 95%CI 1.68-9.40, p = 0.004) and lymph node (OR 5.18, 95%CI 3.39-8.64, p < 0.001) levels. Node-RADS exhibited an AUC of 0.87 and 0.91 at the patient and lymph node levels, respectively. With increasing Node-RADS cut-off values, the specificity and PPV increased from 57.1 to 97.1% and from 48.3 to 83.3%, respectively. Conversely, the sensitivity and NPV decreased from 100 to 35.7% and from 100 to 79.1%, respectively. Similar trends were recorded at the lymph node level. Potentially, Node-RADS > 2 could be considered as the best cut-off value due to balanced values at both the patient (77.1 and 78.6%, respectively) and lymph node levels (82.4 and 93.4%, respectively). CONCLUSIONS: The current study lays the foundation for the introduction of Node-RADS for the regional lymph-node evaluation in BCa patients. Interestingly, the Node-RADS score exhibited a moderate-to-high overall accuracy for the identification of LNI, with the possibility of setting different cut-off values according to specific clinical scenarios. However, these results need to be validated on larger cohorts before drawing definitive conclusions.

The management of oligometastatic disease in colorectal cancer: Present strategies and future perspectives.

Oligometastatic disease has been described as an intermediate clinical state between localized cancer and systemically metastasized disease. Recent clinical studies have shown prolonged survival when aggressive locoregional approaches are added to systemic therapies in patients with oligometastases. The aim of this review is to outline the newest options to treat oligometastatic colorectal cancer (CRC), also considering its molecular patterns. We present an overview of the available local treatment strategies, including surgical procedures, stereotactic body radiation therapy (SBRT), thermal ablation, as well as trans-arterial chemoembolization (TACE) and selective internal radiotherapy (SIRT). Moreover, since imaging methods provide crucial information for the early diagnosis and management of oligometastatic CRC, we discuss the role of modern radiologic techniques in selecting patients that are amenable to potentially curative locoregional treatments.

Duodenal bulb in celiac adults: the "whether biopsying" dilemma.

BACKGROUND: Celiac disease (CD)-related lesions were described in duodenal bulb of celiac patients. GOAL: Our aim was to evaluate the morphology of bulb mucosa in adult celiac patients and in controls to evaluate its usefulness for CD diagnosis. STUDY: We studied 43 celiac patients (10 male, median age: 35.2 y) at diagnosis and 43 gastroenterological controls (10 male, median age: 37.8 y), submitted to upper endoscopy for gastroenterological complaints. Histologic lesions were assayed by an experienced pathologist according to the Marsh modified classification. Antiendomysium antibodies and antitransglutaminase antibodies-tTGAb (ELISA and/or RIA) have been tested. In selected patients, DNA was typed for DRB1, DQA1, and DQB1 genes by sequence-specific primer polymerase chain reaction. RESULTS: In all celiac patients lesions were present in the bulb mucosa. One female with thyroiditis, who had a CD daughter, showed lesions only in the duodenal bulb. Patchy villous atrophy was found in another patient. All celiacs were antiendomysium and/or tTGAb positive. DQ2 heterodimer was present in 5 CD patients. The gastroenterological controls showed normal mucosa in the duodenum. CONCLUSIONS: This study demonstrates that CD-related histologic lesions are present in duodenal bulb of adult patients. Moreover, the normal aspect of this mucosa in gastroenterological controls implies the high negative predictive value of this finding. Therefore, we suggest taking at least 1 biopsy on the bulb area and 1 from the distal duodenum for CD diagnosis, in all the patients submitted to upper endoscopy, to avoid missed or delayed diagnosis.

Endoscopic and histological gastric lesions in children with celiac disease: mucosal involvement is not only confined to the duodenum.

OBJECTIVES: Lymphocytic gastritis (LG) has been reported in patients with celiac disease (CD). The aim of the present study was to evaluate gastric mucosa involvement in celiac children and gastroenterological controls (GC). METHODS: In a retrospective study on 226 patients with CD (82  M; median age: 5.7 years) at diagnosis and 154 GC (66  M; median age: 7.4 years), the evaluation of gastric and duodenal mucosa was performed. CD was diagnosed according to the North America Society for Pediatric Gastroenterology, Hepatology, and Nutrition criteria. Gastric lesions were classified according to Updated Sydney System. Anti-gastric parietal cell antibodies (GPCA) were assayed by enzyme-linked immunosorbent assay. RESULTS: A total of 21.2% and 7% of patients with CD showed chronic superficial gastritis (CSG) and LG, respectively. Helicobacter pylori (Hp) infection was found in 6 (2.7%) children with CD (66.7% had CSG, 16.7% LG, and 16.7% interstitial gastritis). CSG was present in 21.4% of controls. No control subject showed LG. Hp infection was found in 24 (15.6%) children with GC (91.7% had CSG). Among patients with CSG, Hp infection was more frequent in controls than in celiac children (P < 0.0001). Ten of 90 patients with CD and 1 of 29 controls were positive for GPCA. CONCLUSIONS: Gastritis is a common finding in children with CD and adolescents. In celiac subjects, CSG is the most frequently detected. Our data suggest the hypothesis that LG may be related to a longer exposure to gluten. The presence of GPCA may suggest the presence of an underlying autoimmune process.

Intensified Total Neoadjuvant Therapy Versus Intensified Concurrent Chemoradiotherapy in Locally Advanced Rectal Cancer: A Propensity Score Matching Analysis.

BACKGROUND/AIM: To compare clinical outcomes following intensified total neoadjuvant therapy (TNT) and intensified neoadjuvant chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (LARC). PATIENTS AND METHODS: Of the 79 patients with LARC admitted to our department, 51 received intensified neoadjuvant CRT (CRT group) and 28 received intensified TNT (TNT group). Intensified TNT was defined as multi-agent chemotherapy, including FOLFOXIRI regimen plus bevacizumab (mutated Ras-BRAF) or panitumumab/cetuximab (wild-type Ras-BRAF) followed by oxaliplatin-5-fluorouracil-based CRT and surgery. Kaplan-Meier and Log rank test were used for survival analysis. Survival rates of the two groups were compared using propensity score matching. RESULTS: Data from 28 TNT patients and 28 CRT patients were analyzed after a 1:1 propensity matching with replacement. Kaplan-Meier curve showed that overall survival (OS), disease-free survival (DFS) and distant metastasis-free survival (DMFS) rates with TNT were comparable to those with CRT. The 5-year DMFS rates for TNT and CRT were 61.5% versus 63.0% (p=0.82), respectively. In the TNT group, 32.1% patients (n=9) achieved pathological complete response (pCR), whereas 21.4% patients (n=6) achieved pCR with CRT (p=0.37). CONCLUSION: Intensified TNT and CRT resulted in similar survival outcomes, while intensified TNT led to higher pCR, albeit not statistically significant.

First salivary screening of celiac disease by detection of anti-transglutaminase autoantibody radioimmunoassay in 5000 Italian primary schoolchildren.

OBJECTIVE: The high prevalence of celiac disease (CD) prompted us to evaluate a new, noninvasive disease screening strategy. The aim was to identify CD in 6- to 8-year-old children for a timely diagnosis, start gluten-free diet (GFD) in compliant subjects, achieve the growth target, and prevent CD complications. METHODS: Five thousand subjects were invited to participate in the study. Four thousand forty-eight saliva samples were tested for anti-tissue transglutaminase (tTG) immunoglobulin (Ig)A using a fluid-phase radioimmunoprecipitation method. Positive children were tested for serum radioimmunoassay tTG IgA, enzyme-linked immunosorbent assay tTG IgA, and anti-endomysium IgA. Children confirmed as positive by serum assays underwent endoscopy with duodenal biopsies and, at the diagnosis of CD, were suggested to start GFD. RESULTS: Consent was obtained from 4242 parents (84.8%) for the screening to be performed, and adequate saliva samples were collected from 4048 children (95.4%). Thirty-two children were found to be salivary tTG IgA positive and 9 with borderline autoantibody levels. Thirty-one of the 32 and 3 of the 9 subjects were also serum positive. Twenty-eight children showed villous atrophy when undergoing intestinal biopsy, whereas 1 had Marsh 1 lesions; 3 children were suggested to start GFD without performing endoscopy. CD prevalence in the population investigated (including 19 CD known cases) was 1.16%. The ratio between screening-detected patients and those diagnosed before the screening was 3:2. The ratio between symptomatic and asymptomatic patients was 1:1.6. CONCLUSIONS: We demonstrated that it is possible to perform a powerful, simple, well-accepted, and sensitive CD screening using saliva. Until now, the compliance with GFD in children with CD has been optimal.

Prospective comparative trial on nerve-sparing radical prostatectomy using a robot-assisted versus laparoscopic technique: expectation versus satisfaction and impact on surgical margins.

INTRODUCTION: The aim of this study was to analyze whether differences exist in a population selected for a nerve-sparing (NS) procedure between robot-assisted (RARP) and laparoscopic radical prostatectomy (LRP), and whether they can have an impact on surgical margins (SM) status. MATERIAL AND METHODS: This is a single center prospective comparative trial on prostate cancer patients submitted to a RARP-NS or LRP-NS. A self-administered questionnaire on expectations before surgery, and level of satisfaction after surgery was used. RESULTS: A total of 134 cases were included in our analysis. A higher percentage of capsular bulging was found in the RARP group, compared to the LRP group (p = 0.077). At biopsy, the percentage of positive cores and multifocality were higher in the RARP group (p = 0.005). Positive SM (SM+) rate was higher in the RARP, than in LRP group (p = 0.046). On univariable analysis, the risk of SM+ increased 1.95 times using RARP when compared with LRP. On multivariable analysis, the surgical approach did not maintain a significant predictive role in terms of risk for SM+. Expectations before surgery were mainly focused on oncological radicality, however in the RARP group a higher percentage of cases focused on sexual function recovery. Satisfaction after surgery was lower in the RARP than in the LRP group. CONCLUSIONS: Comparing LRP-NS with RARP-NS in a high-volume single center, the expectation/satisfaction ratio is in favor of LRP. Worse oncologic preoperative characteristics in the RARP group may influence the higher incidence of SM+. However, the surgical approach does not result as a significant and independent factor able to influence SM positivity.

Impact of uni- or multifocal perineural invasion in prostate cancer at radical prostatectomy.

BACKGROUND: Aim of this study was to correlate perineural invasion (PNI) with other clinical-pathological parameters in terms of prognostic indicators in prostate cancer (PC) cases at the time of radical prostatectomy (RP). METHODS: Prospective study of 288 consecutive PC cases undergoing RP. PNI determination was performed either in biopsy or in RP specimens classifying as uni- and multifocal PNI. The median follow-up time was 22 (range, 6-36) months. RESULTS: At biopsy PNI was found in 34 (11.8%) cases and in 202 (70.1%) cases at the time of surgery. Among those identified at RP 133 (46.1%) and 69 (23.9%) cases had uni- and multi-PNI, respectively. Presence of PNI was significantly (P<0.05) correlated with unfavorable pathological parameters such higher stage and grade. The percentage of extracapsular extension in PNI negative RP specimens was 18.6% vs. 60.4% of PNI positive specimens. However, the distribution of pathological staging and International Society of Urological Pathology (ISUP) grading did not vary according to whether PNI was uni- or multifocal. The risk of biochemical progression increased 2.3 times in PNI positive cases was significantly associated with the risk of biochemical progression (r=0.136; P=0.04). However, at multivariate analysis PNI was not significantly associated with biochemical progression [hazard ratio (HR): 1.87, 95% confidence interval (CI): 0.68-3.12; P=0.089]. Within patients with intermediate risk disease, multifocal PNI was able to predict cases with lower mean time to biochemical and progression free survival (chi-square 5.95; P=0.04). CONCLUSIONS: PNI at biopsy is not a good predictor of the PNI incidence at the time of RP. PNI detection in surgical specimens may help stratify intermediate risk cases for the risk of biochemical progression.

Influence of operative time and blood loss on surgical margins and functional outcomes for laparoscopic versus robotic-assisted radical prostatectomy: a prospective analysis.

INTRODUCTION: The aim of this article was to analyze whether operative time and blood loss during radical prostatectomy (RP) can significantly influence surgical margins (SM) status and post-operative functional outcomes. MATERIAL AND METHODS: We prospectively analyzed prostate cancer (PC) patients undergoing RP, using robot-assisted (RARP) or laparoscopic (LRP) procedures. Blood loss was defined using the variation in hemoglobin (Hb, g/dl) values from the day before surgery and no later than 4 hours after surgery. RESULTS: From a whole population of 413 cases considered for RP, 67% underwent LRP and 33.0% RARP. Positive SM (SM+) were found in 33.9% of cases. Mean surgical operative time was 172.3 ±76 min (range 49-485), whereas blood loss was 2.3 ±1.2 g/dl (range 0.3-7.6). Operative time and blood loss at RP were not significantly correlated (r = -0.028275; p = 0.684). SM+ rates significantly (p = 0.002) varied by operative time; a higher SM+ rate was found in cases with an operative time <120 min (41.2%) and >240 min (53.4%). The risk of SM+ significantly increased 1.70 and 1.94 times in cases with an operative time <120 min and >240 min, respectively, independently to the surgical approach. The rate of erectile disfunction (ED) varied from 22.4% to 60.3% between <120 min and >240 min procedures (p = 0.001). According to blood loss, SM+ rates slightly but significantly (p = 0.032) varied; a higher rate of SM+ was found in cases with a Hb variation between 2-4 g/dl (35.9%). CONCLUSIONS: Independently to the surgical approach, operative time, more than blood loss at RP, represents a significant variable able to influence SM status and post-operative ED.

Cribriform pattern does not have a significant impact in Gleason Score ≥7/ISUP Grade ≥2 prostate cancers submitted to radical prostatectomy.

INTRODUCTION: The aim of this study was to correlate cribriform pattern (CP) with other parameters in a large prospective series of Gleason score ≥7/ISUP grade ≥2 prostate cancer (PC) cases undergoing radical prostatectomy (RP). METHODS: This is a prospective single-center study on 210 consecutive patients. Gleason pattern 4 and individual tumor growth patterns determination were performed either in biopsy or in surgical specimens for all patients. RESULTS: At multiparametric magnetic resonance, a higher percentage of PI-RADS 5 was associated to CP (53.3% vs 17.7%, P = .038). CP was significantly and inversely (r = -0.261; P = .001) correlated with perineural invasion (PNI) but not with other pathological parameters. Kaplan-Meier analysis showed that mean biochemical (Bp) and radiological (Rp) progression-free survival were similar (Bp = χ 0.906; P = .341; Rp = χ 1.880; P = .170) independently to CP. In PNI positive cases, Bp-free survival was higher (χ = 3.617; P = .057) in cases without CP. CONCLUSIONS: In a homogeneous population excluding ISUP 1 cases, CP showed limited prognostic value. We first described an association with PNI and a prognostic value influenced by PNI status.

Shmt2: A Stat3 Signaling New Player in Prostate Cancer Energy Metabolism.

Prostate cancer (PCa) is a multifactorial disease characterized by the aberrant activity of different regulatory pathways. STAT3 protein mediates some of these pathways and its activation is implicated in the modulation of several metabolic enzymes. A bioinformatic analysis indicated a STAT3 binding site in the upstream region of SHMT2 gene. We demonstrated that in LNCaP, PCa cells' SHMT2 expression is upregulated by the JAK2/STAT3 canonical pathway upon IL-6 stimulation. Activation of SHTM2 leads to a decrease in serine levels, pushing PKM2 towards the nuclear compartment where it can activate STAT3 in a non-canonical fashion that in turn promotes a transient shift toward anaerobic metabolism. These results were also confirmed on FFPE prostate tissue sections at different Gleason scores. STAT3/SHMT2/PKM2 loop in LNCaP cells can modulate a metabolic shift in response to inflammation at early stages of cancer progression, whereas a non-canonical STAT3 activation involving the STAT3/HIF-1α/PKM2 loop is responsible for the maintenance of Warburg effect distinctive of more aggressive PCa cells. Chronic inflammation might thus prime the transition of PCa cells towards more advanced stages, and SHMT2 could represent a missing factor to further understand the molecular mechanisms responsible for the transition of prostate cancer towards a more aggressive phenotype.

HLA-DQB1*02 dose effect on RIA anti-tissue transglutaminase autoantibody levels and clinicopathological expressivity of celiac disease.

OBJECTIVES: Celiac disease is an autoimmune enteropathy caused by gluten ingestion in genetically susceptible individuals. Anti-transglutaminase autoantibody (tTGAb) assay is useful to detect candidates undergoing intestinal biopsy. Our aim was to investigate whether the DQB1*02 allele could influence tTGAb titers and the clinicopathological expressivity of the disease. METHODS: A total of 124 patients with celiac disease, tested for RIA tTGAb at diagnosis, were typed for HLA-DRB1, -DQA1, and -DQB1 genes and divided according to the number of DQB1*02 alleles: group 1, homozygous; group 2, heterozygous; group 3, negative. RESULTS: The mean of tTGAb indexes was significantly higher in group 1 patients than in group 2 (P < 0.02) and group 3 patients (P < 0.01). Patients with at least 1 DQB1*02 allele showed more often a typical CD and diffuse histological lesions than did patients in the other groups. CONCLUSIONS: The study demonstrates that tTGAb titers are HLA-DQB1*02 dose dependent, with significantly higher levels in homozygous individuals. Moreover, individuals with at least 1 HLA-DQB1*02 allele tend to have a more expressed clinical and histological form of celiac disease.

Duodenal bulb biopsies in celiac disease: a multicenter study.

OBJECTIVES: Celiac disease (CD)-related lesions have been reported in duodenal bulb biopsies, sometimes the bulb mucosa being the only one affected. The aim was to verify in a significant series whether histological lesions are always present in the bulb of celiac patients, what is the prevalence of lesions when isolated to the bulb, and if similar lesions are present in nonceliac subjects. METHODS: We studied 665 children with CD (241 males, range 9 months-15 years, 8 months), at diagnosis on a gluten-containing diet, and 348 age- and sex-matched gastroenterological controls submitted to upper endoscopy for gastroenterological complaints. During endoscopy, multiple biopsies (1 bulb and 4 distal duodenum samples) were taken. Anti-endomysium antibodies were evaluated by immunofluorescence method, anti-human tissue-transglutaminase antibodies by an enzyme-linked immunosorbent assay or radioimmunoassay. Human leukocyte antigen-DRB1, -DQA1, and -DQB1 genes were typed by polymerase chain reaction sequence-specific primers repeat method. RESULTS: In all of the patients with CD, histological lesions were present in the bulb sample; in 16 of them, the lesions were present only in the bulb. Patchy villous atrophy was found in 20 children. All of the patients with CD were anti-endomysium and/or antitransglutaminase positive. The controls showed neither autoantibody positivity nor mucosal changes compatible with CD. CONCLUSIONS: This study demonstrated that CD-related histological lesions are always present in the bulb; sometimes this specific site is the only one affected. Therefore, we suggest taking 2 biopsies from the bulb and 2 from the distal duodenum for CD diagnosis.