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Chicago classification version 4.0 (CCv4.0) introduced stringent diagnostic criteria for oesophagogastric junction outflow obstruction (EGJOO), in order to increase the clinical relevance of the diagnosis, although this has not yet been demonstrated.To determine the prevalence of EGJOO using CCv4.0 criteria in patients with CCv3.0-based EGJOO, and to assess if provocative manoeuvres can predict a conclusive CCv4.0 diagnosis of EGJOO.Clinical presentation, high resolution manometry (HRM) with rapid drink challenge (RDC), and timed barium oesophagogram (TBE) data were extracted for patients diagnosed with EGJOO as per CCv3.0 between 2018 and 2020. Patients were then re-classified according to CCv4.0 criteria, using clinically relevant symptoms (dysphagia and/or chest pain), and abnormal barium emptying at 5 min on TBE. Receiver operating characteristic (ROC) analyses identified HRM predictors of EGJOO.Of 2010 HRM studies, 144 (7.2%) fulfilled CCv3.0 criteria for EGJOO (median age 61 years, 56.9% female). Upon applying CCv4.0 criteria, EGJOO prevalence decreased to 1.2%. On ROC analysis, integrated relaxation pressure during RDC (RDC-IRP) was a significant predictor of a conclusive EGJOO diagnosis by CCv4.0 criteria (area under the curve: 96.1%). The optimal RDC-IRP threshold of 16.7 mm Hg had 87% sensitivity, 97.1% specificity, 95.7% negative predictive value and 91.3% positive predictive value for a conclusive EGJOO diagnosis; lower thresholds (10 mmHg, 12 mmHg) had better sensitivity but lower specificity.CCv4.0 criteria reduced the prevalence of EGJOO by 80%, thereby refining the diagnosis and identifying clinically relevant outflow obstruction. Elevated RDC-IRP can predict conclusive EGJOO per CCv4.0.

The Core Outcome Set for Therapeutic Studies in Eosinophilic Esophagitis (COREOS) collaborators are a group of more than 70 gastroenterologists, pathologists, allergists, researchers, dietitians, psychologists, and methodologists who convened in a series of in-person and virtual meetings between 2018 and 2020 with the aim of developing a core outcome set (COS) for use in therapeutic studies of pharmacologic and dietary therapies for the treatment of eosinophilic esophagitis (EoE). Given heterogeneity in reported outcomes and uncertainties regarding the most appropriate end points for use in both randomized controlled trials (RCTs) and observational studies involving EoE patients, the EoE experts launched the COREOS exercise in 2018 to standardize outcome definitions using methods established by the Core Outcome Measures in Effectiveness Trials (COMET) initiative.1,2 The COS was developed using a multiphase approach, which is summarized in Figure 1. In the first phase, systematic reviews of the literature and patient engagement surveys were conducted to identify candidate outcomes that have been previously measured and are important to patients with EoE. Next, this information was used to build a framework of different outcome domains, and working groups for each domain were assembled to review the literature for relevant end points.3–6 The relative importance of these domains was categorized in a Delphi survey as core, important, and research agenda domains, and discussed in a moderated in-person meeting on May 17, 2019 at Digestive Disease Week (San Diego, CA). In phase 3, a comprehensive list of outcome measures within each of the core domains was evaluated by the COREOS collaborators in a 2-round Delphi survey and, finally, outcomes were ratified in a virtual meeting on December 8, 2020. In this meeting summary, we highlight the major points of discussion that occurred during the development of the EoE COS.

Background Anti-programmed death-1 (PD-1) drugs have been associated with immune-mediated gastrointestinal adverse events in 0.5-9% of the cases. The aim of this study was to investigate the characteristics of colitis occurring in oncological patients treated with anti-PD-1 drugs. Methods This is a prospective cohort study including patients referred for new onset colitis at Azienda Ospedaliera of Padua between 2020 and 2022. All patients were treated with anti-PD-1 drugs at Istituto Oncologico Veneto due to oncological disease [n=2 melanoma, n=1 colorectal cancer, n=1 pleural mesothelioma, n=14 non-small-cell lung cancer (NSCLC)]. Median duration of follow up was 10 months. Results Eighteen patients who developed diarrhea (≥G2, CTCAE) following treatment with anti-PD-1 were included (n=12 males, median age 70 years). The diarrhea began after a mean of seven months of therapy and after two to six months its discontinuation in 3/18 patients. The mean fecal calprotectin values at diarrhea onset was 1063 ug/g. Most of the patients (14/18) had their immunotherapy suspended, among them four required hospitalization. All patients were initially treated with systemic steroids (1 mg/kg). Seven patients had ulcerative colitis (UC)-like colitis (n=5 pancolitis, n=2 left colitis) while the others (60%) had microscopic colitis (MC, n=9 collagenous, n=1 lymphocytic) with unspecific inflammatory mucosal abnormalities in half of the cases. Among patients with UC-like colitis, two were hospitalized and treated with anti-TNFα because of steroid refractoriness; all remaining patients with UC-like colitis are maintaining remission with oral mesalamine or with budesonide non-MMX or low-dose systemic steroid (0.1 mg/kg). Two patients restarted anti-PD-1 drugs with no colitis relapse in the following three months, with mesalamine as maintenance therapy. Among patients who developed a MC, one required Vedolizumab as maintenance therapy, while 8/10 achieved partial or complete remission with oral budesonide non-MMX or low-dose systemic steroid. Three patients restarted anti-PD-1 drugs with no colitis relapse in the following three months, taking budesonide non-MMX as maintenance therapy. In our cohort of study all patients with MC were previously treated with anti-PD-1 drugs for NSCLC, while those with UC-like colitis were treated for NSCLC (n=4), melanoma (n=2) and colorectal cancer (n=1). Conclusion We observed a significant proportion of microscopic colitis in patients with NSCLC, while UC-like colitis was equally distributed in the other forms of neoplasia. Men are at higher risk to develop anti-PD-1 induced MC in NSCLC, rather than women. Anti-PD-1 induced microscopic colitis presents more frequently endoscopic signs of inflammation.

Background Prevention of postoperative recurrence (POR) in Crohn’s disease (CD) after ileo-colonic (IC) resection is still a highly debated topic. Prophylactic immunosuppression after surgery is currently recommended in presence of at least one clinical risk factor (RF). Due to drug-related adverse events and the relative high cost of biologics, we aimed to determine whether prevention of POR can be postponed and guided by endoscopy in CD patients with only one RF. Methods A multicentre retrospective study was conducted in 12 IG-IBD Italian centres. CD patients with only one RF for POR, including previous intestinal resection, extensive small intestine resection (>50 cm), fistulising phenotype, history of perianal disease, or active smoking were considered. Patients who performed a colonoscopy between 6 to 12 months after curative IC resection were included. Two groups were formed based on whether immunosuppressive therapy was started immediately after surgery (prophylaxis group) or guided by endoscopy (observation group). Primary endpoints were the rates of any endoscopic recurrence (Rutgeerts ≥i2a) and severe endoscopic recurrence (i4) within 12 months after surgery. Secondary outcomes were clinical recurrence (HBI≥5) rates at 6, 12 and 24 months after surgery. Results A total of 195 patients were enrolled. Out of all, 61 (31.3%) received immunoprophylaxis at a median time of 32 days [IQR 26-55] after surgery (n=14 infliximab, n=37 adalimumab, n=7 azathioprine, n=3 ustekinumab). Baseline patient characteristics are detailed in Table 1. Particularly, risk factors for POR were homogeneously distributed between the 2 groups. Colonoscopy was performed after a median time of 8 months [IQR 6-11]. No differences between immunoprophylaxis and endoscopy-driven approach was found regarding any endoscopic recurrence (36.1% in prophylaxis group vs 45.5% in observation group, p=0.10) and severe endoscopic recurrence (9.8% in prophylaxis group vs 15.7% in observation group, p=0.15). In 32 patients with a second colonoscopy at a median time of 30.5 months [IQR 22-43.75] after surgery, any recurrence and severe recurrence rates were also similar (p=0.55 and p=0.43, respectively). Early clinical recurrence at 6 months was reported in 23.4% of patients on immunoprophylaxis vs 31.5% who were not (p=0.43). Clinical recurrence rates between prophylaxis and observation group were also similar at 12 months (17.9% vs 34.8%, respectively, p=0.09) and at 24 months (17.9% vs 24.1%, respectively, p=0.63). Conclusion In CD patients with only one RF for POR, immediate immunoprophylaxis after curative IC resection does not decrease the rate of early clinical and endoscopic recurrence. Prospective and larger studies are needed to confirm our results.

Background Tofacitinib is a small oral molecule approved to treat moderate to severe ulcerative colitis (UC), which effectiveness and safety is still poorly known in UC patients. Recent concerns have been raised regarding its administration at high dosage in UC patients because of a likely higher incidence of drug-related thromboembolic events. Methods The aim of this study was to evaluate short-term effectiveness and safety of tofacitinib. As secondary aim, we analyzed the state of blood coagulation at baseline in order to evaluate whether it could predict thromboembolic events in relation to demographic, clinical and biochemical characteristics. A multicenter, retrospective, observational study was conducted, including patients from March 2021 to October 2022; a prospective single-centre sub-study concerning the thromboembolic risk was performed. At baseline, demographic, clinical, biochemical and endoscopic data, and previous therapies were recorded; quality of life was evaluated through IBD-Disability Index (IBD-DI) and Pittsburgh Sleep Quality Index (PSQI). In a subgroup of patients, a thrombophilic screening and a Rotational Thromboelastometry (ROTEM) were performed at baseline. Patients were reassessed after 8 weeks, 6 months and 1 year, evaluating for each timepoint clinical and biochemical characteristics, IBD-DI and PSQI, and reporting adverse events (AEs) and discontinuation of therapy. The following clinical outcomes were considered: benefit, steroid-free remission and response. Results 44 adult patients were enrolled. The overall clinical benefit was 54.2%, summing up 45.8% of subjects in steroid-free clinical remission and 8.3% with clinical response; significant short-term improvement of IBD-DI and PSQI scores (p=0.000 in both cases after 6 months of therapy) was observed. Patients previously treated with less than two different biological therapies had major rates of clinical benefit at 6 months (p=0.045). Ten AEs, including one venous thrombosis, were reported; global therapy failure rate was 31.4%. In the subgroup with additional data on coagulation (17 patients), we did not observe significant alterations of coagulating factors or inhibitors, nor of ROTEM parameters, although some coagulation features were significantly increased in obese patients (FII, p=0.030; FIX, p=0.000; FX, p=0.000; fibrinogen blood levels, p=0.030) and subjects older than 40 years old (FVIII, p=0.020). We did not find significant correlation with gender, smoking habit, concomitant steroid therapy, CRP, fecal calprotectin. Conclusion Our data confirm literature ones on effectiveness and safety of tofacitinib in UC patients, while the risk of thrombosis needs to be better evaluated in larger longitudinal studies.

Laryngopharyngeal reflux (LPR) is a common otolaryngologic diagnosis. Treatment of presumed LPR remains challenging, and limited frameworks exist to guide treatment.Using RAND/University of California, Los Angeles (UCLA) Appropriateness Methods, a modified Delphi approach identified consensus statements to guide LPR treatment. Experts independently and blindly scored proposed statements on importance, scientific acceptability, usability, and feasibility in a four-round iterative process. Accepted measures reached scores with ≥ 80% agreement in the 7-9 range (on a 9-point Likert scale) across all four categories.Fifteen experts rated 36 proposed initial statements. In round one, 10 (27.8%) statements were rated as valid. In round two, 8 statements were modified based on panel suggestions, and experts subsequently rated 5 of these statements as valid. Round three's discussion refined statements not yet accepted, and in round four, additional voting identified 2 additional statements as valid. In total, 17 (47.2%) best practice statements reached consensus, touching on topics as varied as role of empiric treatment, medication use, lifestyle modifications, and indications for laryngoscopy.Using a well-tested methodology, best practice statements in the treatment of LPR were identified. The statements serve to guide physicians on LPR treatment considerations.

Contains fulltext : 252197.pdf (Publisher’s version ) (Closed access) GASTROSWOT is a strategic analysis of the current and projected states of the different subspecialties in gastroenterology that aims to provide guidance for research, clinical, and financial planning in gastroenterology. We executed a consensus-based international strengths, weaknesses, opportunities, and threats (SWOT) analysis. Four general coordinators, six field coordinators, and 12 experts participated in the study. SWOTs were provided for the following fields: neurogastroenterology, functional gastrointestinal disorders, and upper gastrointestinal diseases; inflammatory bowel disease; pancreatology and biliary diseases; endoscopy; gastrointestinal oncology; and hepatology. The GASTROSWOT analysis highlights the following in the current state of the field of gastroenterology: the incidence and complexity of several gastrointestinal diseases, including malignancies, are increasing; the COVID-19 pandemic has affected patient care on several levels; and with the advent of technical innovations in gastroenterology, a well trained workforce and strategic planning are required to optimise health-care utilisation. The analysis calls attention to the following in the future of gastroenterology: artificial intelligence and the use of big data will speed up discovery and smarter health-care provision in the field; the growth and diversification of gastroenterological specialties will improve specialised care for patients, but could promote fragmentation of care and health system inefficiencies; and furthermore, thoughtful planning is needed to reach an effective balance between the need for subspecialists and the value of general gastroenterology services.

The clinical diagnosis of gastro-esophageal reflux disease (GERD) is based on the presence of typical esophageal troublesome symptoms. In clinical practice, heartburn relief following a proton pump inhibitor (PPI) trial or endoscopy can confirm a diagnosis of GERD. In cases of diagnostic uncertainty or before anti-reflux interventions, combined impedance-pH monitoring (MII-pH) provides a comprehensive assessment of both physical and chemical properties of the refluxate, allowing to achieve a conclusive diagnosis of GERD. Recently, the Lyon Consensus proposed the use of mean nocturnal baseline impedance (MNBI) and post-reflux swallow-induced peristaltic wave index (PSPW-I) as novel MII-pH metrics to support the diagnosis of GERD. The calculation of MNBI and PSPW-I currently needs to be performed manually, but artificial intelligence systems for the automated analysis of MII-pH tracings are being developed. Several studies demonstrated the increased diagnostic yield MNBI and PSPW-I for the categorization of patients with GERD at both on- and off-PPI MII-pH monitoring. Accordingly, we performed a narrative review on the clinical use and diagnostic yield of MNBI and PSPW-I when the diagnosis of GERD is uncertain. Based on currently available evidence, we strongly support the evaluation of PSPW-I and MNBI as part of the standard assessment of MII-pH tracings for the evaluation of GERD, especially in patients with endoscopy-negative heartburn.

BackgroundDirect comparisons of childhood- and adulthood-onset eosinophilic esophagitis (EoE) are scarce.AimTo compare disease characteristics, endoscopic and histological features, allergic concomitances and therapeutic choices across ages.MethodsCross-sectional analysis of the EoE CONNECT registry.ResultsThe adulthood-onset cohort (those diagnosed at ≥18y) comprised 1044 patients and the childhood‐onset cohort (patients diagnosed at ConclusionsChildhood‐onset EoE has differential characteristics compared with adulthood-onset, but similar response to treatment.

Background Changes in dopamine beta-hydroxylase (DBH) and anomalies in dopaminergic machinery have been shown in inflammatory bowel disease (IBD) patients and related animal models. Thus, we aimed to evaluate the dopaminergic pathways in IBD patients as well as in a mouse model of dextran sodium sulphate (DSS)-induced ileitis. Methods Colon biopsies (CB) obtained from healthy volunteers (N=3) and matched-IBD patients (N=3), were used to evaluate DBH immunoreactivity by confocal microscopy. Male C57/Bl6 (8±2 weeks old; N=16 mice) received 1.5% DSS in drinking water for 5 days, then switched to regular drinking water for 3 days. Inflammatory cytokines (IL-1β, TNFα, IL-6) were measured to assess ileitis severity. Changes in ileal muscle tension were isometrically recorded following 30 μM dopamine or 30 μM SKF38393 (a dopamine receptor 1 (D1R) agonist) or 30 μM bromocriptine (a D2R agonist). Immunofluorescence distribution of Iba1 (a macrophage specific marker), D1R, DBH and dopamine transporter (DAT) were determined in longitudinal muscle-myenteric plexus whole-mount preparations (LMMPs) by confocal microscopy. D1R and D2R mRNA transcripts were evaluated by qRT-PCR. Results CB from IBD patients and LMMPs from DSS mice showed a significant increase of DBH immunoreactivity compared to healthy patients and sham mice (+25% [p Conclusion Human colitis and mouse ileitis affect dopamine machinery in the enteric nervous system. Experimentally induced ileitis impairs dopaminergic neurotransmission altering D1R-mediated responses. These findings provide novel information on the involvement of dopaminergic pathways in IBD.

Background Adalimumab (ADL) is a therapeutic monoclonal antibody that targets the proinflammatory cytokine tumor necrosis factor-alpha (TNF-α) and has been shown to effectively induce and maintain disease remission in patients with Inflammatory Bowel Disease (IBD). However, some patients fail to respond to this treatment, experiencing primary failure (no response to induction therapy), while others initially respond but lose efficacy over time (secondary failure). Therapeutic Drug Monitoring (TDM), in clinical practice, may lead to maintain therapeutic drug concentration thereby optimizing individual dosage regimen and improving treatment response. Recently, a point of care testing (POCT) has been developed to rapidly measure trough levels in patients taking ADL. Comparative data with current gold standard are lacking. Aim To determine the degree of analytical correlation between a recently developed POCT (ProciseDx) ADL assay which analyze capillary whole blood and the comparative enzyme linked immunosorbent assays (ELISA) from serum samples. Methods From December 2020 to February 2021, consecutive patients (aged ≥ 18 years) taking ADA (Humira, Amgevita, Imraldi) were recruited at Gastroenterology Unit, Padua University Hospital, during outpatient visits. In each patient, ADL levels from capillary whole blood collected by finger stick were performed using the ProciseDx ADL assay with reportable range between 1.3 µg/mL - 51.5 µg/mL; at the same time, a serum sample from venous blood was collected to carry out Grifols’ Promonitor ELISA test (range ≤ 0.024 – 12 µg/mL). A Deming regression test was used to identify the correlation between the two methods. Results Sixty patients were enrolled (67% males with mean age of 3±14), with 80% of them having CD, 17% UC and 3% an undetermined-Inflammatory Bowel Disease (IBD-U). The assessment with ProciseDx POCT was feasible and required a turnaround time of 3±0.2 minutes while serum ELISA analysis required the collection of at least 40 samples (around three weeks at our centre) and 3 hours to be performed. Thirty patients (63% males with mean age of 41±14) had therapeutic levels as assessed by ProciseDx ADL assay lower than 1.3 or greater than 12 µg/mL, in accordance with ELISA assessment. Among the remaining 30 patients (70% males with mean age of 43±15), the correlation between the two tests was high (r of 0.858 (95% CI 0.720 – 0.930)). Conclusion The ProciseDx POCT has similar accuracy but was more rapid and easy to be performed in providing the results of TDM in outpatients taking ADL. This could lead to a more rapid and effective optimization of the biological drug, thus avoiding treatment failure.

Background The most commonly recognized clinical feature of hypogammaglobulinemia is recurrent infections with high prevalence of gastrointestinal manifestations. In some cases, clinical and endoscopic features are indistinguishable from those of inflammatory bowel disease (IBD). Methods This was a multicenter case series performed as a part of the Collaborative Network of Exceptionally Rare case reports (CONFER) project. Results This report includes 25 patients with primary hypogammaglobinemia and IBD-like features [20 males and 5 females, mean age 50 years (±21.7 SD)]. Crohn’s disease-like features were noted in 22 patients, three patients had ulcerative colitis-like features. The diagnosis of hypogammaglobulinemia preceded IBD-like features diagnosis in 20 patients (mean of 7.7 years prior, range 0.3–35 years), and followed IBD-like features appearance in 5 cases (mean of one year after, 0.4- 9.1 years). Hypogammaglobinemia etiologies were common variable immunodeficiency (72%), Agammaglobulinemia (8%), selective IgA-deficiency (8%), Goods syndrome (8%), IgG subclass deficiency with IgA deficiency (4%). In addition to antibiotics and intravenous immunoglobulin (IVIG) as a treatment for hypogammaglobinemia, fifteen patients received IBD treatment during the follow-up period, of whom two were on 5-aminosalicylic acid, five on corticosteroids, three on immunomodulatory, four on anti-tumor necrosis factor, and one on vedolizumab. By the end of the follow-up [35.5 months (Interquartile range 18–75)], 20 of 25 (80%) patients were in clinical remission. Conclusion This case series illustrates a strong male and CD-like features predilection. The diagnosis of IBD-like features mainly occurs after that of hypogammaglobulinemia, the majority of cases successfully recovered after appropriate treatment.

Gastroesophageal reflux disease (GERD) is nowadays a highly prevalent, chronic condition, with 10% to 30% of Western populations affected by weekly symptoms. Many patients with mild reflux symptoms are treated adequately with lifestyle modifications, dietary changes, and low-dose proton pump inhibitors (PPIs). For those with refractory GERD poorly controlled with daily PPIs, numerous treatment options exist. Fundoplication is currently the most commonly performed antireflux operation for management of GERD. Outcomes described in current literature following laparoscopic fundoplication indicate that it is highly effective for treatment of GERD; early clinical studies demonstrate relief of symptoms in approximately 85%-90% of patients. However it is still unclear which factors, clinical or instrumental, are able to predict a good outcome after surgery. Virtually all demographic, esophagogastric junction anatomic conditions, as well as instrumental (such as presence of esophagitis at endoscopy, or motility patterns determined by esophageal high resolution manometry or reflux patterns determined by means of pH/impedance-pH monitoring) and clinical features (such as typical or atypical symptoms presence) of patients undergoing laparoscopic fundoplication for GERD can be factors associated with symptomatic relief. With this in mind, we sought to review studies that identified the factors that predict outcome after laparoscopic total fundoplication.

Multichannel impedance pH monitoring has shown that weakly acidic refluxes are able to generate heartburn. However, data on the role of different pH values, ranging between 4 and 7, in the generation of them are lacking. The aim of this study was to evaluate whether different pH values of weakly acidic refluxes play a differential role in provoking reflux symptoms in endoscopy-negative patients with physiological esophageal acid exposure time and positive symptom index and symptom association probability for weakly acidic refluxes. One hundred and forty-three consecutive patients with gastroesophageal reflux disease, nonresponders to proton pump inhibitors (PPIs), were allowed a washout from PPIs before undergoing: upper endoscopy, esophageal manometry, and multichannel impedance pH monitoring. In patients with both symptom index and symptom association probability positive for weakly acidic reflux, each weakly acidic reflux was evaluated considering exact pH value, extension, physical characteristics, and correlation with heartburn. Forty-five patients with normal acid exposure time and positive symptom association probability for weakly acidic reflux were identified. The number of refluxes not heartburn related was higher than those heartburn related. In all distal and proximal liquid refluxes, as well as in distal mixed refluxes, the mean pH value of reflux events associated with heartburn was significantly lower than that not associated. This condition was not confirmed for proximal mixed refluxes. Overall, a low pH of weakly acidic reflux represents a determinant factor in provoking heartburn. This observation contributes to better understand the pathophysiology of symptoms generated by weakly acidic refluxes, paving the way toward the search for different therapeutic approaches to this peculiar condition of esophageal hypersensitivity.

Gastroesophageal reflux disease (GERD) is a common disorder of the gastrointestinal tract. In the last few decades, new technologies have evolved and have been applied to the functional study of the esophagus, allowing for the improvement of our knowledge of the pathophysiology of GERD. High-resolution manometry (HRM) permits greater understanding of the function of the esophagogastric junction and the risks associated with hiatal hernia. Moreover, HRM has been found to be more reproducible and sensitive than conventional water-perfused manometry to detect the presence of transient lower esophageal sphincter relaxation. Esophageal 24-h pH-metry with or without combined impedance is usually performed in patients with negative endoscopy and reflux symptoms who have a poor response to anti-reflux medical therapy to assess esophageal acid exposure and symptom-reflux correlations. In particular, esophageal 24-h impedance and pH monitoring can detect acid and non-acid reflux events. EndoFLIP is a recent technique poorly applied in clinical practice, although it provides a large amount of information about the esophagogastric junction. In the coming years, laryngopharyngeal symptoms could be evaluated with up and coming non-invasive or minimally invasive techniques, such as pepsin detection in saliva or pharyngeal pH-metry. Future studies are required of these techniques to evaluate their diagnostic accuracy and usefulness, although the available data are promising.

Pancreatic adenocarcinoma (PC) is the third most common cancer associated with BRCA mutations. Most notice has been given to BRCA2, while the association between BRCA1 and PC is less widely reported. Recently, PALB2 has been implicated in both PC and breast cancer (BC) susceptibility. We selected 29 Italian PC patients from a case-control study of PC according to their personal and family history of both PC and breast/ovarian cancer (BC/OC) and tested them for presence of germline mutations in BRCA1, BRCA2 and PALB2. We identified no germline mutations or deletions in PALB2, but detected 7 BRCA mutations (4 in BRCA1 and 3 in BRCA2). These findings suggest that PALB2 does not play a major role in PC susceptibility in our population. As we found an almost equal frequency of germline mutations in BRCA1 and BRCA2, germline alterations in either of these genes may explain a subset of Italian families presenting both PC and BC/OC. Moreover, as we began the observation of these families from probands who are affected by PC, we provide here a direct assessment of the role of PALB2 and BRCA mutations in PC susceptibility. © 2011 Springer Science+Business Media B.V.