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Background: Retrocecal hamartomas are rare cystic lesions due to the persistence of the tailgut. Sometimes the epithelial or mesenchymal components of the cyst wall undergo neoplastic transformation, and, within them, carcinomas and sarcomas can develop. Case Presentation: We present the case of a multicystic lesion, discovered in a patient with perineal pain, which the imaging investigations have localized in the retrocecal space. The histological evaluation performed on his excisional biopsy demonstrates a retrocecal hamartoma harboring a neuroendocrine neoplasm. Conclusion: Tailgut cysts (TGC) are quite rare, only sometimes symptomatic, and infrequently, they also undergo a malignant transformation; in particular, the literature reviews report a higher frequency of adenocarcinomas. The differential diagnosis between lesions with different prognoses and pathogenesis that can develop in the retrocecal space requires a histological examination, which in some cases, becomes essential if we consider the potential for metastatic and local recurrence of any malignant neoplasm that arose in this site.

Increasing evidence suggests that maternal cholesterol represents an important risk factor for atherosclerotic disease in offspring already during pregnancy, although the underlying mechanisms have not yet been elucidated. Eighteen human fetal aorta samples were collected from the spontaneously aborted fetuses of normal cholesterolemic and hypercholesterolemic mothers. Maternal total cholesterol levels were assessed during hospitalization. DNA methylation profiling of the whole SREBF2 gene CpG island was performed (p value SREBF2 gene shows 4 significant differentially hypermethylated sites in the 5′UTR-CpG island. This finding indicates that more effective long-term primary cardiovascular prevention programs need to be designed for the offspring of mothers with hypercholesterolemia. Further studies should be conducted to clarify the epigenetic mechanisms underlying the association between early atherogenesis and maternal hypercholesterolemia during pregnancy.

To investigate the use of computerized cardiotocography (cCTG) parameters in Intrauterine Growth Restriction (IUGR) pregnancies for the prediction of 1) complication with preeclampsia; 2) placental histological abnormalities, and 3) neonatal outcomes. A single-center observational retrospective case-control study was performed by reviewing medical records, cCTG databases and pathological reports of women with singleton pregnancy and IUGR uncomplicated (controls) and complicated by preeclampsia (cases). Primary endpoint was the association between cCTG parameters and preeclampsia in IUGR. Secondary endpoints were the association between cCTG parameters and 1) placental abnormalities, and 2) neonatal outcomes. The one-way ANOVA test was used to compare cCTG parameters in cases and controls. t-test was applied to compare neonatal outcomes and placental abnormalities in both groups. The Spearman Test value Correlation coefficients between the cCTG parameters and neonatal outcome in the two groups. A p value < .05 was considered significant for all analyses. Among all cCTG parameters, a significant association with preeclampsia in IUGR was found for Fetal Heart Rate (FHR, p = .008), Delta (p = .018), Short Term Variability (STV, p = .021), Long Term Variability (LTV, p = .028), Acceleration Phase Rectified Slope (APRS, p = .018) and Deceleration Phase Rectified Slope (DPRS, p = .038). Of all placental histologic abnormalities, only vascular alterations at least moderate were significantly associated with increased FHR (p = .02). About neonatal outcomes, all cCTG parameters were significantly associated with birth weight, Apgar index at 1 and 5 min, pH and pCO2. FHR, LTI, Delta, Approximate Entropy (ApEn) and LF were significantly associated with pO2; LTI, Interval Index (II) and ApEn with base excess. Among controls, Delta, ApEn, Low Frequency (LF) and High Frequency (HF) were significantly associated with pCO2, while among cases, STV and Delta were significantly associated with pH; STV, LTI, Delta, ApEn, LF and HF with pCO2; STV, LTI, Delta and ApEn with pO2; HF with base excess; FHR and LF with lactates. cCTG parameters may be useful to detect complication with preeclampsia in IUGR pregnancies. Regarding placental status, cCTG parameters may detect overall circulation alterations, but not specific histological abnormalities. Lastly, all cCTG parameters may predict neonatal outcomes, helping to tailor the patients’ management.

Background and Purpose: Transient receptor potential melastatin type-8 (TRPM8) is a cold-sensitive cation channel protein belonging to the TRP superfamily of ion channels. Here, we reveal the molecular mechanism of TRPM8 and its clinical relevance in colorectal cancer (CRC). Experimental Approach: TRPM8 expression and its correlation with the survival rate of CRC patients was analysed. To identify the key pathways and genes related to TRPM8 high expression, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were conducted in CRC patients. TRPM8 functional role was assessed by using Trpm8−/− mice in models of sporadic and colitis-associated colon cancer. TRPM8 pharmacological targeting by WS12 was evaluated in murine models of CRC. Key Results: TRPM8 is overexpressed in colon primary tumours and in CD326+ tumour cell fraction. TRPM8 high expression was related to lower survival rate of CRC patients, Wnt–Frizzled signalling hyperactivation and adenomatous polyposis coli down-regulation. In sporadic and colitis-associated models of colon cancer, either absence or pharmacological desensitization of TRPM8 reduced tumour development via inhibition of the oncogenic Wnt/β-catenin signalling. TRPM8 pharmacological blockade reduced tumour growth in CRC xenograft mice by reducing the transcription of Wnt signalling regulators and the activation of β-catenin and its target oncogenes such as C-Myc and Cyclin D1. Conclusion and Implications: Human data provide valuable insights to propose TRPM8 as a prognostic marker with a negative predictive value for CRC patient survival. Animal experiments demonstrate TRPM8 involvement in colon cancer pathophysiology and its potential as a drug target for CRC.

Sclerosing mesenteritis (SM) is an idiopathic disorder affecting mesentery, characterized by fat necrosis, chronic inflammation and fibrosis. The clinical presentation varies from asymptomatic cases to acute abdomen. The diagnosis is suggested by imaging but can be definitely established only by biopsies. In this paper, we discuss ultrasonography-based management of SM.

Background: The injection of tissue adhesives has been proposed as an alternative to standard laparoscopic inguinal hernia repair but no evidence is available in the pediatric population. This study aimed to evaluate safety, efficacy, and feasibility of injection of tissue adhesives for inguinal hernia repair in a rabbit model. Materials and Methods: Thirty-six New Zealand White male rabbits underwent laparoscopic inguinal hernia repair. In each animal, the hernia defect was repaired using glue on the right side and purse-string suture on the left side. The animals were divided in 3 groups, each 1 of 12 animals, according to the glue used: Glubran 2® (cyanoacrylate), Histoacryl® (cyanoacrylate), and BioGlue® (bovine serum albumin-based). For each group, 6 animals were sacrificed at 7 days postoperatively, and 6 animals at 90 days postoperatively. Histopathological exam of testis and spermatic bundle was performed. Results: The hernia defect was successfully closed on both sides in all cases. The injection of glue was faster than suture repair (P = .001). Postoperative complications (epiploon-parietal adhesions, spermatic vessel ectasia, and hydrocele) rate was significantly higher on the right side compared to the left side at both short- and long-term follow-up (P = .001). Furthermore, a lower maturity of testicles treated by adhesive compared with suture was histologically demonstrated at both short- and long-term follow-up (P = .001). Conclusions: The present experimental study confirmed the feasibility and efficacy of inguinal hernia repair by injection of tissue adhesive. However, several critical issues emerged about the safety of this technique. The use of glue was associated with higher incidence of postoperative complications and significant decrease of testicular maturity compared with standard suture repair. Based upon these preliminary results, repair using suture remains the standard of care for inguinal hernia in children. Further experimental studies are needed to assess the safety of injection of tissue adhesives for pediatric inguinal hernia repair.

IntroductionAlthough carcinomatous degeneration is a rare occurrence, some authors support the need for a histopathological examination after pilonidal cyst excision. Today, minimally invasive techniques are widely spread for the treatment of pilonidal sinus disease but opposed to standard procedures, these techniques could not allow to perform a histopathological examination because of the absence of a specimen. The aim of this two-institutions study is to evaluate whether histopathological examination of the pilonidal sinus excision material can be successfully performed after an endoscopic ablation of the cyst.Materials and MethodsWe identified all consecutive patients from January 2021 to September 2021 with diagnosis of pilonidal sinus disease who underwent Video Assisted Ablation of Pilonidal Sinus (VAAPS) followed by histopathological examination.ResultsA total of 45 patients were included in the study. All patients were Caucasians and aged below 50 years. Nine of them underwent surgery due to recurrence of PSD. No evidence of malignancy was detected in the histopathological examination of the pilonidal sinus sampling material.DiscussionWe were able to send pilonidal sinus sampling material for a histopathological examination in all patients who underwent minimally invasive technique for the treatment of pilonidal sinus disease. No evidence of malignancy was found in any of the 45 samples. Our findings prove that minimally invasive ablation of pilonidal sinus does not preclude histopathological examination of the cysts.

Background and purpose N-acylethanolamine acid amidase (NAAA) is a lysosomal enzyme accountable for the breakdown of N-acylethanolamides (NAEs) and its pharmacological inhibition determines beneficial effects in inflammatory conditions. The knowledge of NAAA in cancer is fragmentary with an unclarified mechanism whereas its contribution to colorectal cancer (CRC) is unknown to date. Experimental approach CRC xenograft and azoxymethane models assessed the in vivo pharmacological effect of NAAA inhibition; tumor secretome was evaluated by an oncogenic array; CRC cell lines were used for in vitro studies; cell cycle was analyzed by cytofluorimetry; NAAA was knocked down with siRNA; human biopsies were obtained from surgically resected CRC patients; gene expression was revealed by RT-PCR; NAEs were measured by LC-MS. Key results The NAAA inhibitor AM9053 reduced CRC xenograft tumor growth and counteracted tumor development in the azoxymethane model. NAAA inhibition impacted the composition of the tumor secretome that negatively affected the expression of epidermal growth factor family members. In CRC cells, AM9053 reduced proliferation with a mechanism mediated by PPAR-α and TRPV1 and induced cell cycle arrest in the S phase with cyclin A2/CDK2 downregulation. NAAA knock-down mirrored the effects of NAAA pharmacological inhibition. NAAA expression was downregulated in human CRC tissues, with a consequential augmentation of NAEs levels and dysregulation of some of their targets. Conclusions and implications Our results provide unprecedented data on the functional importance of NAAA in CRC progression and its mechanism. We propose this enzyme as a valid drug target for the treatment of CRC growth and development.

Antiphospholipid Antibody Syndrome (APS) is a systemic autoimmune disease characterized by acquired hypercoagulability with the possible development of venous, arterial, and microvascular thrombosis. We report a rare case of Libman–Sacks tricuspid valve endocarditis in a 38-year-old pregnant woman at 15 weeks gestation with unknown primary antiphospholipid syndrome. During a routine cardiac examination and echocardiography performed for a previous episode of pleuropericarditis, a large, mobile mass with irregular edges was found at the level of the tricuspid valve. Three main differential diagnoses for intramyocardial mass were examined: tumor, infective endocarditis, and nonbacterial thrombotic endocarditis (NTBE). Cardiac magnetic resonance imaging (CMR) with contrast raised the suspicion of a thrombus. The woman was hospitalized urgently at the Cardiac Intensive Care Unit of the Federico II University Hospital, and anticoagulant and antiplatelet therapy were started. The thrombophilic screening performed and medical history confirmed the diagnosis of primary antibody syndrome (APS). A multidisciplinary consultation with obstetricians, cardiologists, anesthetists, and cardiac surgeons was required. The patient decided not to terminate the pregnancy despite the risk to her health and to undergo cardiac surgery during pregnancy. Histological examination confirmed the presence of nonbacterial thrombotic endocarditis. Weekly obstetric scans were performed after surgery to verify fetal well-being. An emergency cesarean section was performed at the 35th week of gestation due to repeated deceleration and abnormal short-term variability on c-CTG in a pregnancy complicated by fetal growth restriction and gestational hypertension. A newborn weighing 1290 g was born. She was hospitalized in Neonatal Intensive Care and discharged after two months; currently, she enjoys good health. The management of patients with antiphospholipid antibody syndrome has not yet been standardized, but there is a general consensus that patients who do not have thrombocytopenia, thromboembolic phenomena, or pregnancy should not undergo any treatment or should take only low doses of acetylsalicylic acid. In the presence of any of the above conditions, various treatment regimens have been used based on the severity and individuality of the case.

Background Besides major clinical/biochemical features, neutropenia and inflammatory bowel disease (IBD) constitute common complications of Glycogen storage disease type Ib (GSD Ib). However, their management is still challenging. Although previous reports have shown benefit of empagliflozin administration on neutropenia, no follow-up data on bowel (macro/microscopic) morphology are available. We herein present for the first time longitudinal assessment of bowel morphology in a GSD Ib child suffering from Crohn disease-like enterocolitis treated with empagliflozin. Case presentation A 14-year-old boy with GSD Ib and severe IBD was (off-label) treated with empagliflozin (20 mg/day) after informed oral and written consent was obtained from the patient’s parents. No adverse events were noted. Clinical symptoms and stool frequency improved within the first week of treatment. Pediatric Crohn disease activity index (PCDAI) normalised within the first month of treatment. Abdomen magnetic resonance imaging (MRI) performed 3 months after treatment initiation showed dramatic decrease in disease activity and length. Similar findings were reported on histology at 5.5 months. At 7.5 months hemoglobin levels normalised and fecal calprotectin almost normalised. Improved neutrophil count, metabolic control and quality of life were also noted. G-CSF dose was decreased by 33% and the patient was partly weaned from tube feeding. Conclusions This is the first report presenting extensive gastrointestinal morphology follow-up in a GSD Ib patient receiving empagliflozin. The present case suggests that empagliflozin can be safe and effective in inducing IBD remission in GSD Ib patients and can even postpone surgery. Future studies are required to confirm its effect over time and assess its benefit in various disease stages. The development of an international collaborating networks for systematic data collection is worthy.

Background Krukenberg tumor (KT) is defined as a secondary neoplasm of the ovary. While ovarian metastases account for about 30% of ovarian tumors, KTs are rare, accounting for about 1-2% of the total. The rarity of KT is at least in part responsible for the lack of a precise clinic-pathological characterization of these tumors. Clinically, KT may have a subtle clinical presentation, with few symptomatic manifestations and nonspecific clinical signs, even though in Literature there is disagreement about the clinical presentation of these patients; such difficulties in the diagnostic framework often leads to a delayed diagnosis with serious consequences on the patient outcome. Objectives We aimed to provide a clinico-pathological characterization of Krukenberg Tumor (KT) through a systematic review and meta-analysis. Methods Electronic databases were searched for all studies assessing clinicopathological features of KT series. Pooled prevalence of each clinical or pathological factor was calculated according to the random-effect model. Results Forty-eight studies with 3025 KT patients were included; 39.7% of patients were ≥50 and 39.8% were postmenopausal. The most common primary tumor sites were stomach (42.5%), colon-rectum (26.1%), breast (9.3%), and appendix (5%); 48.7% of KTs were synchronous with the primary tumor, 64.3% were bilateral, 40.5% had a diameter ≥10 cm; 55.3% showed extraovarian extent and 49% showed peritoneal involvement. The most common presenting symptoms were ascites (51.7%), palpable mass (31.3%), pain (29.3%), abdominal distention (28.7%), irregular bleeding (9.1%), asymptomatic (11.2%); 27.5% of patients showed increased serum level of CA125, while 29.4% showed increased CEA levels. Cytokeratin-7 was positive in 34.5% of cases and cytokeratin-20 in 34.3%. Conclusions KT shows a highly variable presentation. Understanding the prevalence of clinico-pathological factors may be helpful to improve the diagnosis and management of KT.

Malignant gastrointestinal neuroectodermal tumour is an extremely rare neoplasm that arises in the wall of the small bowel, stomach or large bowel in youngaged and middle-aged adults. Histologically, it is generally characterized by monomorphic cells with clear cytoplasma, S-100 protein expression, and EWSR1 gene translocation. To the best of our knowledge, we describe for the first time, the case of a young woman with a diagnosis of metastatic gastrointestinal neuroectodermal tumour arising from ileum, who had a childhood adrenal neuroblastoma with liver, bone and lymph nodes metastasis, treated with four cycles of chemotherapy with the schedule CADO-CVP (CADO: cyclophosphamide 300 mg/m2/day on days 1–5, vincristine 1,5 mg/m2/ day on days 1 and 5, and doxorubicin 60 mg/m2/day on day 5; CVP: cisplatin 40 mg/m2/day on days 1–5 and etoposide 100 mg/m2/day on days 1–5) followed by right adrenal, kidney, lymph nodes and liver lesion resection, conditioning chemotherapy (melphalan-carmustineteniposide), stem cells autologous transplantation and consecutively radiotherapy on the spine (T9 to L3) for a total of 30 Gy. For the second diagnosis of gastrointestinal neuroectodermal tumour with liver metastasis, she underwent ileal tumour resection and platinum-anthracycline based chemotherapy with initial shrinkage of liver metastasis. Unfortunately, despite the initial response and the following delivered therapies, she died for rapid progressive disease. Taking into account the late effects of past therapeutic modalities, a long-term surveillance of young child treated for neuroblastoma, is required to appreciate their overall risks of second malignancies.

BACKGROUND: Krukenberg tumor (KT) is a rare secondary ovarian tumor. Little is known about clinicopathologic factors affecting prognosis in KT. OBJECTIVE: To assess the prognostic value of clinicopathologic factors in KT through a systematic review and meta-analysis. METHODS: Electronic databases were searched from their inception to February 2019 for studies assessing the association of clinicopathologic factors with overall survival in KT. Pooled hazard ratio (HR) was calculated for each factor; a p value 50 (HR 0.946; p = 0.743), menopausal status (HR 1.565; p = 0.204), gastric origin (HR 1.600; p = 0.201), size > 5 cm (HR 1.292; p = 0.119), size > 10 cm (HR 0.925; p = 0.714), bilateral ovarian involvement (HR 1.113; p = 0.347), non-peritoneal extaovarian metastases (HR 1.648; p = 0.237), liver metastases (HR 1.118, p = 0.555), predominant signet ring cell morphology (HR 1.322; p = 0.208) and levels of CA125 (HR 0.933; p = 0.828) and CA19.9 (HR 0.996; p = 0.992). CONCLUSION: Peritoneal involvement, synchronous presentation, ascites and increased serum CEA levels appear as unfavorable prognostic factors in KT and might affect the patient management.

Background The current study evaluates the application of histology and in situ proteomics (MALDI-MSI) in Fabry nephropathy (FN), showing investigative and classification role for this coupled approach. Methods A retrospective series of 14 formalin fixed paraffin embedded (FFPE) renal biopsies with diagnosis of FN and 1 biopsy from a patient bearing a galactosidase-alpha (GLA) genetic variant of unknown significance (GVUS, c.376A>G) have been classified for clinical characteristics. Groups were compared for histological differences (following the ISGFN scoring system). Moreover, renal biopsies from these cases have been analyzed with MALDI-MSI as previously described to find proteomic signatures among different mutations and phenotypes. Results Comparison of clinical features revealed lower mean 24 h proteinuria in females (225 mg/24 h) than in males (1477.5 mg/24 h, p = 0.006). As for clinical characteristics, females significantly differed from males only for lower arterial sclerosis, with a mean value of 0.82 vs. 1.05 (p = 0.001). Proteomic analysis demonstrated specific signatures in different subgroups of FN patients. Moreover, MALDI correctly classified cases with undetermined mutation or GVUS. Conclusions The present study demonstrated the feasible application of MALDI-MSI in the analysis of FN FFPE renal biopsies, allowing the detection of putative signatures for phenotypic distinction and demonstrating genetic classification capabilities.

Background: Stillbirth is defined by the WHO as birth of a fetus with no vital signs, at or over 28 weeks of pregnancy age. The estimation of time of death in stillbirth appears crucial in forensic pathology. However, there are no validated methods for this purpose. Objective: To perform a systematic review of the available literature regarding the estimation of the time of death in stillborn fetuses, in terms of hours or days. Methods: Electronic databases were searched from their inception to August 2018 for relevant articles. Macroscopic, histologic, and radiologic parameters were evaluated. Results: Nine studies with 664 stillborns were included. The evaluation of extent and location of fetal maceration signs showed good accuracy in estimating the time of death; by contrast, a dichotomous assessment of maceration (present vs absent) was found to be unreliable in a subsequent study. Histologic assessment of the loss of nuclear basophilia in fetal and placental tissues showed excellent accuracy; an “autolysis equation” was proposed to achieve an even higher accuracy in fetuses who had been dead for

Background Small bowel adenocarcinoma is a relatively rare cancer, often diagnosed in an advanced stage. In localized and resectable disease, surgery alone or in combination with adjuvant chemotherapy is the mainstay of treatment. In the recently published National Comprehensive Cancer Network Clinical Practice guidelines, criteria for selecting patients with stage II small bowel adenocarcinoma to receive adjuvant chemotherapy are provided, and they are mainly extrapolated from studies on colorectal cancer. Patients and Methods In the present study, we aimed to verify whether mismatch repair deficiency phenotype, high-risk pathologic features (including T4, positive resection margins and a low number of lymph nodes harvested), as well as tumor histologic subtype, were associated with cancer-specific survival in 66 stage II non-ampullary small bowel adenocarcinoma patients, collected through the Small Bowel Cancer Italian Consortium. A central histopathology review was performed. Mismatch repair deficiency was tested by immunohistochemistry for MLH1, MSH2, MSH6 and PMS2, and confirmed by polymerase chain reaction for microsatellite instability. Results We identified mismatch repair deficiency, glandular/medullary histologic subtype, and celiac disease as significant predictors of favorable cancer-specific survival using univariable analysis with retained significance in bivariable models adjusted for pT stage. Among the high-risk features, only T4 showed a significant association with an increased risk of death; however, its prognostic value was not independent of mismatch repair status. Conclusions Mismatch repair protein expression, histologic subtype, association with celiac disease, and, in the mismatch repair proficient subset only, T stage, may help identify patients who may benefit from adjuvant chemotherapy. Graphic Abstract

Background and purpose: N-acylethanolamine acid amidase (NAAA) is a lysosomal enzyme accountable for the breakdown of N-acylethanolamides (NAEs) and its pharmacological inhibition determines beneficial effects in inflammatory conditions. The knowledge of NAAA in cancer is fragmentary with an unclarified mechanism whereas its contribution to colorectal cancer (CRC) is unknown to date. Experimental approach: CRC xenograft and azoxymethane models assessed the in vivo pharmacological effect of NAAA inhibition; tumor secretome was evaluated by an oncogenic array; CRC cell lines were used for in vitro studies; cell cycle was analyzed by cytofluorimetry; NAAA was knocked down with siRNA; human biopsies were obtained from surgically resected CRC patients; gene expression was revealed by RT-PCR; NAEs were measured by LC-MS. Key results: The NAAA inhibitor AM9053 reduced CRC xenograft tumor growth and counteracted tumor development in the azoxymethane model. NAAA inhibition impacted the composition of the tumor secretome that negatively affected the expression of epidermal growth factor family members. In CRC cells, AM9053 reduced proliferation with a mechanism mediated by PPAR-? and TRPV1 and induced cell cycle arrest in the S phase with cyclin A2/CDK2 downregulation. NAAA knock-down mirrored the effects of NAAA pharmacological inhibition. NAAA expression was downregulated in human CRC tissues, with a consequential augmentation of NAEs levels and dysregulation of some of their targets. Conclusions and implications: Our results provide unprecedented data on the functional importance of NAAA in CRC progression and its mechanism. We propose this enzyme as a valid drug target for the treatment of CRC growth and development.

Placenta previa (PP) and Placenta Accreta Spectrum (PAS) are obstetric pathologies whose early detection is fundamental for an appropriate patient management. In this paper, ultrasonography (US) is performed on 53 patients and from the images a texture analysis feature extraction is performed through PyRadiomics. The US images were acquired with 3 different resampling resolutions: 1 × 1, 2 × 2 and 3 × 3. The features extracted from the images at each resolution were used to investigate which one is the best to make the correct diagnosis by employing machine learning techniques. Knime analytics platform was employed to implement decision tree, k nearest neighbor and naive Bayes. Synthetic minority oversampling technique was used to balance the dataset and some evaluation metrics were computed after a leave one out cross-validation. Averaging all the metrics among all the algorithms, 1 × 1 resolution achieved the best mean accuracy (75.97%), sensitivity (83.33%), specificity (68.50%) and Area Under the Curve Receiver Operating Characteristics (0.81). Moreover, k nearest neighbor was the algorithm with the highest metrics (greater than 80%). Despite using also artificial data to balance the dataset (less than 30% of total analysed sample), this study provides researchers with the idea that employing a 1 × 1 resolution could be the best option when analysing images with machine learning algorithms on texture analysis features US-derived.

Objectives: To predict placental accreta spectrum (PAS) in patients with placenta previa (PP) evaluating clinical risk factors (CRF), ultrasound (US) and magnetic resonance imaging (MRI) findings. Methods: Seventy patients with PP were retrospectively selected. CRF were retrieved from medical records. US and MRI images were evaluated to detect imaging signs suggestive of PAS. Univariable analysis was performed to identify CRF, US and MRI signs associated with PAS considering histology as standard of reference. Receiver operating characteristic curve (ROC) analysis was performed, and the area under the curve (AUC) was calculated. Multivariable analysis was also performed. Results: At univariable analysis, the number of previous cesarean section, smoking, loss of the retroplacental clear space, myometrial thinning < 1 mm, placental lacunae, intraplacental dark bands (IDB), focal interruption of myometrial border (FIMB) and abnormal vascularity were statistically significant. The AUC in predicting PAS progressively increased using CRF, US and MRI signs (0.69, 0.79 and 0.94, respectively; p < 0.05); the accuracy of MRI alone was similar to that obtained combining CRF, US and MRI variables (AUC = 0.97) and was significantly higher (p < 0.05) than that combining CRF and US (AUC = 0.83). Multivariable analysis showed that only IDB (p = 0.012) and FIMB (p = 0.029) were independently associated with PAS. Conclusions: MRI is the best modality to predict PAS in patients with PP independently from CRF and/or US finding. It is reasonable to propose the combined assessment of CRF and US as the first diagnostic level to predict PAS, sparing MRI for selected cases in which US findings are uncertain for PAS.

BACKGROUND Venous aneurysms are long-term complications of arteriovenous fistula (AVF) for hemodialysis with an estimated incidence rate of around 5-6%. The purpose of our study is to investigate the role of immunosuppressive therapy in the development of AVF aneurysms in renal transplant patients, and to determine whether AVF closure following transplantation is necessary. METHODS Forty-six patients with symptomatic venous AVF aneurysms underwent ligation and resection of their fistulas between January 2013 and January 2020. Immunohistochemical expression of CD3, CD4, and CD8 was assessed on the surgical specimens to characterize lymphocytic infiltrate in the aneurysm wall. Patients were subdivided into "Group A"-kidney transplant patients undergoing immunosuppressive therapy which was comprised of 39 patients and "Group B"-patients who had not undergone kidney transplant which was comprised of 7 patients. The 2 groups did not significantly differ in age, sex nor risk factors for aneurysms. RESULTS Group A showed a significantly higher aneurysm diameter (P < 0.0001), mean flow (P < 0.0001) and required a longer duration of surgery (P = 0.0007). A CD3+ lymphocytic infiltrate was significantly more common in Group A than in the Group B (90% vs 29%; P < 0.001). No significant differences in localization (adventitia, media or intima) and type (CD4+ vs CD8+) of lymphocytes were found between the 2 groups. CONCLUSION AVF venous aneurysms were significantly larger and with a more intense T-lymphocytic infiltrate in patients undergoing immunosuppressive therapy. This finding suggests that immunosuppressive therapy plays a role in aneurysm formation, supporting the need for AVF closure in patients with an estimated low risk of rejection.

Immunohistochemistry (IHC) and polymerase chain reaction (PCR) and fragment separation by capillary electrophoresis represent the current clinical laboratory standard for the evaluation of microsatellite instability (MSI) status. The importance of reporting MSI status in colorectal cancer is based on its potential for guiding treatment and as a prognostic indicator. It is also used to identify patients for Lynch syndrome testing. Our aim was to evaluate pre-analytical factors, such as age of formalin-fixed and paraffin-embedded (FFPE) block, neoplastic cell percentage, mucinous component, and DNA integrity, that may influence the accuracy of MSI testing and assess the concordance between three different MSI evaluation approaches. We selected the mucinous colorectal cancer (CRC) histotype for this study as it may possibly represent an intrinsic diagnostic issue due to its low tumor cellularity. Seventy-five cases of mucinous CRC and corresponding normal colon tissue samples were retrospectively selected. MMR proteins were evaluated by IHC. After DNA quality and quantity evaluation, the Idylla&trade, and TapeStation 4200 platforms were adopted for the evaluation of MSI status. Seventy-three (97.3%) cases were successfully analyzed by the three methodologies. Overall, the Idylla&trade, platform showed a concordance rate with IHC of 98.0% for microsatellite stable (MSS)/proficient MMR (pMMR) cases and 81.8% for MSI/deficient MMR (dMMR) cases. The TapeStation 4200 system showed a concordance rate with IHC of 96.0% for MSS/pMMR cases and 45.4% for MSI/dMMR cases. The concordance rates of the TapeStation 4200 system with respect to the Idylla&trade, platform were 98.1% for MSS profile and 57.8% for MSI profile. Discordant cases were analyzed using the Titano MSI kit. Considering pre-analytical factors, no significant variation in concordance rate among IHC analyses and molecular systems was observed by considering the presence of an acellular mucus cut-off &gt, 50% of the tumor area, FFPE year preparation, and DNA concentration. Conversely, the Idylla&trade, platform showed a significant variation in concordance rate with the IHC approach by considering a neoplastic cell percentage &gt, 50% (p-value = 0.002), and the TapeStation 4200 system showed a significant variation in concordance rate with the IHC approach by considering a DNA integrity number (DIN) &ge, 4 as cut-off (p-value = 0.009). Our data pinpoint a central role of the pre-analytical phase in the diagnostic outcome of MSI testing in CRC.

Small bowel adenocarcinomas (SBAs) are often associated with poor prognosis and have limited therapeutic options. Programmed cell death protein-1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway blockade is an effective treatment in many microsatellite instability-high (MSI-H) solid tumors. We aimed at investigating PD-L1 and PD-1 expression in non-hereditary, non-ampullary SBAs, associated with celiac disease (CeD), Crohn’s disease (CrD), or sporadic, recruited through the Small Bowel Cancer Italian Consortium. We assessed PD-L1 and PD-1 by immunohistochemistry in a series of 121 surgically resected SBAs, including 34 CeD-SBAs, 49 CrD-SBAs, and 38 sporadic SBAs. PD-L1 and PD-1 expression was correlated with several clinico-pathological features, such as the etiology, microsatellite instability status, and tumor-infiltrating lymphocyte (TIL) density. The prevalence of PD-L1 positivity according to combined positive score (CPS) was 26% in the whole cohort of SBAs, with significantly (p = 0.001) higher percentage (35%) in both CeD-SBAs and CrD-SBAs in comparison with sporadic SBAs (5%). CPS ≥ 1 SBAs were significantly (p = 0.013) more frequent in MSI-H cases (41%) than in non-MSI-H ones (18%); however, 15 CPS ≥ 1 microsatellite stable SBAs were also identified. CPS ≥ 1 SBAs showed higher TIL and PD-1+ immune cell density, more frequently medullary histotype, as well as a better outcome in comparison with CPS < 1 cases. This study demonstrates an increased proportion of PD-L1+ cases in both CeD-SBAs and CrD-SBAs in comparison with sporadic SBAs. In addition, the identification of a subset of PD-L1+ microsatellite stable SBAs supports the need to ascertain additional biomarkers of response to immune checkpoint inhibitors along with MSI-H.

International audience; The response to neoadjuvant chemoradiation (nCRT) is a critical step in the management of locally advanced rectal cancer (LARC) patients. Only a minority of LARC patients responds completely to neoadjuvant treatments, thus avoiding invasive radical surgical resection. Moreover, toxic side effects can adversely affect patients’ survival. The difficulty in separating in advances responder from non-responder patients affected by LARC highlights the need for valid biomarkers that guide clinical decision-making. In this context, microRNAs (miRNAs) seem to be promising candidates for predicting LARC prognosis and/or therapy response, particularly due to their stability, facile detection, and disease-specific expression in human tissues, blood, serum, or urine. Although a considerable number of studies involving potential miRNA predictors to nCRT have been conducted over the years, to date, the identification of the perfect miRNA signatures or single miRNA, as well as their use in the clinical practice, is still representing a challenge for the management of LARC patients. In this review, we will first introduce LARC and its difficult management. Then, we will trace the scientific history and the key obstacles for the identification of specific miRNAs that predict responsiveness to nCRT. There is a high potential to identify non-invasive biomarkers that circulate in the human bloodstream and that might indicate the LARC patients who benefit from the watch-and-wait approach. For this, we will critically evaluate recent advances dealing with cell-free nucleic acids including miRNAs and circulating tumor cells as prognostic or predictive biomarkers.

The western diet high in fat and fructose may cause metabolic disorders and cardiovascular diseases.To evaluate whether long-term daily vitamin DThree groups of rats were fed for 6 months with standard diet (SD), western diet (WD) or WD containing 23 IU/day/rat vitamin DSixty-one per cent of hepatocytes in WD rats had steatotic vacuoles compared with just 27% in rats on a WD plus vitamin DIn animal models of liver and cardiovascular metabolic damage, the supplementation of vitamin D

Background: The new concept of disease remission for pediatric inflammatory bowel diseases (IBD) implies the achievement of mucosal healing. Aims: We aimed to evaluate endoscopic and histologic healing in children with Ulcerative Colitis (UC) and Crohn's disease (CD) in clinical remission after 52 weeks of Azathioprine. Methods: From December 2012 to July 2015 we prospectively enrolled IBD children starting Azathioprine. Enrolled patients in clinical remission underwent colonoscopy after 52 weeks. Macroscopic assessment was described with Mayo score and the simplified endoscopic score for UC and CD, respectively. For microscopic assessment, an average histology score was used. Data on inflammatory markers and fecal calprotectin were also collected. Results: Fourty-seven patients were included in the analysis. Endoscopic healing was detected in 20/26 (76.9%) UC children and 10/21 (47.6%) CD patients. Median Mayo score and simplified endoscopic score were significantly decreased at week 52 (p < 0.001; p = 0.005). Median average histology score was not significantly different at week 52 in both diseases. Fecal calprotectin was directly correlated with simplified endoscopic score (T0: r = 0.4, p = 0.05; T52: r = 0.5, p = 0.01), but not with Mayo score. No correlation was found between endoscopic and histologic scores. Conclusions: IBD children under Azathioprine reach endoscopic healing, but not histological remission.

The main functions of the testis are sex hormone and sperm cell production. Steroidogenesis occurs in the Leydig interstitial cells and spermatogenesis in the seminiferous tubules. Male gonad morphogenesis is a finely orchestrated process, mainly coordinated by hormones, whose actions can significantly affect post-pubertal testicular function. Calcium is a key intracellular messenger, which regulates many signal transduction pathways, and is also implicated in steroidogenesis. Calcium homeostasis and signaling rely on many calcium-binding proteins including calretinin, of the "EF-hand" protein family. Calretinin is a highly conserved protein mainly expressed in the nervous system but also detected in rat and human adult and fetal testis as well as in pathological conditions. Calretinin expression in the fetal testis, however, has not been thoroughly analyzed probably owing to limited availability and paucity of tissues. Here, we examined by immunocytochemistry the expression of calretinin in human fetal testis specimens, obtained from natural and therapeutic abortions, at various developmental ages. We found that calretinin-immunoreactive Leydig cells were visible throughout the timeframe studied (14th-27th week). Immunoreactivity was also observed in Sertoli cells and in the germ cells of the immature seminiferous tubules. Overall our data indicate that calretinin expression parallels the decline in Leydig cell number, suggesting that its presence is indeed correlated to their steroidogenic activity. They also suggest that the intratubular positivity of calretinin could be linked to the ability of Sertoli cells to produce locally acting hormones contributing to the histodifferentiation of the male genital tract. J. Cell. Physiol. 232: 1872-1878, 2017. © 2016 Wiley Periodicals, Inc.

Introduction: Ectopic pregnancy is the most common cause of mortality during the first trimester of pregnancy, and intrauterine ectopic pregnancies show significantly higher morbidity and mortality than extrauterine ones. Despite being less invasive, safety and effectiveness of the hysteroscopic treatment are still unclear. Moreover, such approach is not standardized. We aimed to evaluate safety and effectiveness of hysteroscopic intact removal of angular or cesarean section scar pregnancies, defining a novel and markedly less invasive hysteroscopic technique with a 5-mm Bettocchi hysteroscope or a 3.5-mm Versascope hysteroscope. Materials and Methods: Medical records and video archives were reviewed for all the patients with angular or caesarean scar pregnancies treated with hysteroscopic intact removal technique from January 2000 to December 2018 at our Department. Success and complication rates were assessed. Results: Four patients with angular (n = 1) or cesarean scar pregnancy (n = 3) met inclusion criteria. Case #1 was treated with bipolar resectoscope, cases #2 and #3 with 5-mm Bettocchi hysteroscope, and case #4 with 3.5-mm Versascope hysteroscope. Cases #2–4 did not require cervical dilatation. Before hysteroscopic treatment, cases #2–4 underwent unsuccessful medical therapy with multiple-dose methotrexate. Hysteroscopic treatment success rate was 100%, while complication rate was 0%. All patients were treated with a novel technique: hysteroscopic intact removal of angular or cesarean scar pregnancies. Such technique was described step-by-step. Conclusions: Hysteroscopic treatment of angular and cesarean scar pregnancies may be a safe and effective minimally invasive option. The novel technique of hysteroscopic intact removal technique may allow a markedly less invasive approach.

BACKGROUND: Krukenberg tumor (KT) is a rare secondary ovarian tumor, primarily localized at the gastrointestinal tract in most cases. KT is related to severe prognosis due to its aggressiveness, diagnostic difficulties and poor treatment efficacy. Several treatments have been used, such as cytoreductive surgery (CRS), adjuvant chemotherapy (CT) and/or hyperthermic intraperitoneal chemotherapy (HIPEC). To date, it is still unclear which treatment or combination of treatments is related to better survival. OBJECTIVE: To assess the most effective therapeutic protocol in terms of overall survival (OS). METHODS: A systematic review of the literature was performed by searching MEDLINE, Scopus, EMBASE, ClinicalTrial.gov, OVID, Web of Sciences, Cochrane Library, and Google Scholar for all studies assessing the association of treatments with OS in KTs. The effectiveness of each treatment protocol was evaluated by comparing the OS between patients treated with different treatment protocols. RESULTS: Twenty retrospective studies, with a total sample size of 1533 KTs, were included in the systematic review. Therapeutic protocols used were CRS in 18 studies, CT in 13 studies, HIPEC in 7 studies, neoadjuvant CT in 2 studies, and some combinations of these in 6 studies. Seven studies showed that CRS significantly improved OS compared to other treatments or association of treatments without it. 11 studies showed that CRS without residual (R0 CRS) had a significantly better OS than CRS with residual (R + CRS). Five studies showed that CT significantly improved OS, but other five showed it did not. Two studies showed that HIPEC in association with CRS improved OS, while another study showed that efficacy of HIPEC was comparable to CT. Two studies evaluated neoadjuvant CT, but results were conflicting. CONCLUSION: CRS and in particular R0 CRS are the treatments showing the clearest results in improving OS in KT patients. Results about CT are conflicting. HIPEC appears effective both alone and in combination with CRS, and also related to fewer adverse effect than CT. The usefulness of neoadjuvant CT is still unclear. The association of R0 CRS with HIPEC seems to be the most effective and safe therapeutic protocol for KT patients.

Patients with ulcerative colitis (UC) using marijuana have been reported to experience symptomatic benefit. Cannabidivarin (CBDV) is a safe non-psychoactive phytocannabinoid able to activate and desensitize TRPA1, a member of the TRP channels superfamily, which plays a pivotal role in intestinal inflammation. Here, we have investigated the potential intestinal anti-inflammatory effect of CBDV in mice and in biopsies from pediatric patients with active UC. Colonic inflammation was induced in mice by dinitrobenzenesulfonic acid (DNBS). The effect of orally administered CBDV on macroscopic and microscopic damage, inflammatory parameters (i.e. myeloperoxidase activity, intestinal permeability and cytokine production) and faecal microbiota composition, was evaluated 3 days after DNBS administration. TRPA1 expression was studied by RT-PCR in inflamed colons of mice as well as in mucosal colonic biopsies of children with active UC, whose response to incubation with CBDV was also investigated. CBDV attenuates, in a TRPA1-antagonist sensitive manner, DNBS-induced signs of inflammation including neutrophil infiltration, intestinal permeability, and cytokine (i.e. IL-1β, IL-6 and the chemokine MCP-1) production. CBDV also alters the dysregulation of gut microbiota associated to colitis. Finally, CBDV lessens cytokine expression in colonic biopsies from pediatric patients with ulcerative colitis, a condition in which TRPA1 was up-regulated. Our preclinical study shows that CBDV exerts intestinal anti-inflammatory effects in mice via TRPA1, and in children with active UC. Since CBDV has a favorable safety profile in humans, it may be considered for possible clinical trials in patients with UC.

Purpose To evaluate whether a machine learning (ML) analysis employing MRI-derived texture analysis (TA) features could be useful in assessing the presence of placenta accreta spectrum (PAS) in patients with placenta previa (PP). The hypothesis is that TA features may reflect histological abnormalities underlying PAS in patients with PP thus helping in differentiating positive from negative cases. Materials and methods Pre-operative MRI examinations of 64 patients with PP of which 20 positive (12 accreta, 7 increta and 1 percreta) and 44 negative for PAS were retrospectively selected. Multiple (n = 3) rounded regions of interest (ROIs) were manually positioned on sagittal or coronal T2-weighted images over homogeneous placental tissue close to the placental-myometrial interface for each patient to extract TA features. After balancing the dataset with the Synthetic Minority Over-sampling Technique, training and testing sets were obtained using Hold-out with a 75/25% split. Different algorithms were applied on the training set using the wrapper method, which looks for the best combination of features based on the optimization of a heuristic function in order to get the highest accuracy, and a 10-fold Cross-validation. The accuracy of the best models was also assessed on the test set. Histology was used as the standard of reference. Results A total of 192 ROIs were positioned and a ROI-based analysis was then conducted. Among the different algorithms, k-nearest neighbors obtained the highest accuracy (98.1%), precision (98.7%), sensitivity (97.5%) and specificity (98.7%) while exploiting the lowest number of features (n = 26); conversely, the Naive Bayes algorithm got the lowest scores showing an accuracy of 80.5%. Conclusion ML analysis using MRI-derived TA features could be a feasible tool in the identification of placental tissue abnormalities underlying PAS in patients with PP. This approach might represent an additional tool in the clinical practice, thus expanding the application field of artificial intelligence to medical images.

Serrated adenomas are genetically heterogeneous, and the histological classification into sessile serrated (SSA) adenoma and traditional serrated adenoma (TSA) does not reflect the molecular landscape. The objective of this study was to assess clinical or pathological factors associated with BRAF-V600E mutation in serrated adenomas. Systematic review and meta-analysis was performed by searching electronic databases from January 2011 to January 2019 for studies assessing the association of BRAF-V600E mutation with clinical or pathological features of serrated adenomas. Odds ratio (OR) was calculated for each factor; a P-value

Purpose: To compare the performance US and MR in identifying placental adhesion spectrum (PAS) in placenta previa (PP) and to establish a potential method of image interpretation. Methods: US and MR examinations of 51 patients with PP were selected. The presence of imaging signs commonly used to detect PAS was assessed. Penalized logistic regression was performed considering histology as standard of reference; only signs statistically significant (p < 0.05) were considered for ROC and multivariate analysis. The probability of PAS according to the presence of US and/or MR signs was then assessed. Results: At univariate analysis, loss of retroplacental clear space, myometrial thinning (MT) and placenta lacunar spaces on US, intraplacental dark bands (IDBs), focal interruption of myometrial border (FIMB) and abnormal vascularity (AV) on MR were statistically significant (p < 0.01). Three diagnostic methods for PAS were then developed for both US and MR when at least one (Method 1), two (Method 2) or three (Method 3) imaging signs occurred, respectively. Method 2 for MR showed a significantly (p < 0.05) higher accuracy (91%) compared to the other methods. When MR IDBs and AV as well as IDBs and FIMB were present in combination with US MT the probability of PAS increased from 75 to 90% and from 80 to 91%, respectively. Conclusion: MR demonstrated a higher diagnostic accuracy than US to detect PAS. However, since the combination of MR and US signs could improve the probability to detect PAS, a complementary diagnostic role of these techniques could be considered.

Since the first edition of this book, the impressive development of neuroendoscopy has dramatically changed the surgical approach to hydrocephalus, the main pathology pediatric neurosurgeons worldwide have to deal with. This revised and updated second edition, written by worldwide leaders in the field, fully reflects this progress: not only existing chapters have been reviewed whenever required, but new ones have been added thus taking into consideration every aspect of hydrocephalus, even when associated with the rarest pathologies. The general part include now more data on history, biomechanics, circulation and molecular basis. Special consideration for fetal surgery has been added, whereas the section on neonatal hydrocephalus has been further developed. Section 4, on the different pathologies associated with hydrocephalus, has been significantly expanded. and is now amazingly detailed, as well as the section on shunt treatment. Infections are now dealt with in two different chapters, and special attention to shunt complications (the nightmare of every Pediatric Neurosurgeon.) is paid in five different chapters. A very complete overview of the endoscopic treatment, that will surely draw the reader’s attention thanks to the wonderful full color images, is also included. Written by acknowledged experts in the field, this title is an indispensable tool for all those facing this pathology in their daily practice.

OBJECTIVES: Early-onset preeclampsia is a form of preeclampsia requiring delivery before 34 weeks of gestation. The etiology is unknown, but placental dysfunction appears crucial. We evaluated the immunohistochemical expression of the antiapoptotic protein Bcl-2, the angiogenetic factors VEGF and PlGF, and the epithelial factors HGF, c-Met and STAT3 in placental samples of pregnancies complicated by early-onset preeclampsia. MATERIALS AND METHODS: Placental sections were obtained from 41 women with early-onset preeclampsia (cases) and from 31 uncomplicated pregnancies (controls). A standard haematoxylin and eosin stain was used to assess histological structure. Immunohistochemical expression of Bcl-2, VEGF, PlGF, HGF, c-Met and STAT3 was analyzed. RESULTS: Mean gestational age was 32 weeks in cases and 39 weeks in controls. Microscopically, sections from women with preeclampsia showed a disorder of villous development as a distal villous hypoplasia with placental undergrowth. The immunoistochemical expression of Bcl-2 (p

Objective: To evaluate MRI accuracy in assessing placental adhesion disorders (PAD) in patients with placenta previa correlating imaging results with histological findings. Materials and methods: Sixty-one patients who underwent abdomino-pelvic magnetic resonance imaging (MRI) for ultrasound suspicion of PAD were prospectively evaluated. T1- and T2-weighted images, with and without fat suppression, were obtained in the three conventional planes using a 1.5 T MRI scanner. MRI accuracy to evaluate the presence of PAD was assessed on the basis of the occurrence of the following abnormal MRI signs: 1) intraplacental dark bands; 2) focal interruption of myometrial border; 3) intraplacental abnormal vascularity; 4) uterine bulging; 5) tenting of the bladder and/or 6) direct visualization of adjacent tissues invasion only in case of percretism. Imaging results were classified as suggestive or not of PAD using histological data as standard of reference; two methods of imaging analysis were used represented by the presence of at least one (Method A) or two (Method B) abnormal MRI signs; the correlation between the presence of each abnormal MRI sign of PAD and the corresponding histological finding was also assessed. Results: The accuracy, as the area under the receiver operating characteristic curve, was significantly (p = 0.001) higher for Method B (0.92, C.I. 95%: 0.82–0.97) compared to Method A (0.764, C.I. 95%: 0.64–0.86). Among the abnormal MRI signs, intraplacental dark bands and focal interruption of myometrial border were those highly correlated with histological proof of PAD (ρ > 0.71, p < 0.001, for both); as result, a modified version of Method B (Method C) was identified considering as criterion for PAD the combined presence of the two abnormal MRI signs highly correlated with histologically proven PAD; however, the accuracy of Method C was significantly (p = 0.005) lower (0.80, C.I. 95%: 0.67–0.89) than Method B and comparable to Method A. Conclusions: MRI is a useful imaging technique to assess PAD in patients with placenta previa; in particular, the presence of at least two among all the abnormal MRI signs represents the most accurate criterion (Method B) to identify PAD. Although intraplacental dark bands and focal interruption of myometrial border showed the highest correlation with histological proof of PAD as well as this association was the most frequent in PAD, the combination of these latter MRI signs along with other abnormal signs should be considered diagnostic for PAD.

BACKGROUND: To understand the role of ghrelin in the mechanism of action of laparoscopic sleeve gastrectomy (LSG), a prospective cohort case-control study to assess the expression of ghrelin-producing cells (GPC) in two groups of patients was designed. METHODS: Specimens of resected stomach from 26 obese patients who underwent LSG (group A), were compared by immunohistochemistry to control stomach samples from 26 non-obese patients (group B) resected for other pathologies or during autopsy; (GIST: 6 cases, inflammatory diseases: 4 cases, post-mortem autopsy cases with stomachs from healthy persons victims of traumatic accidents: 16 cases). Immunohistochemistry investigation was performed with the use of Ventana Benchmark ultra, anti-ghrelin antibody NOVUS, mouse monoclonal 2F4, diluted at 1:100. RESULTS: No significant difference in the expression of GPC number between group A and B was found (p = 0.87). No significant correlation between patients presenting a GPC number above (subgroup 1) or below (subgroup 2) the average, and EWL% changes, both at 1 and 6 years of follow-up, was recorded. CONCLUSIONS: Our study has shown that the expression of GPC is similar in the stomach of obese and non-obese controls, being mostly influenced by the inflammatory status of the gastric mucosa. A variation in the preoperative number of GPC has not influenced the weight loss in patients who underwent LSG.

Hiatal hernia (HH) affects from 10% to 50% of adult population. The correlation between HH, gastroesophageal reflux disease, dyspeptic symptoms, and esophagitis has long been known in adults. The primary objective of our prospective observational study was to estimate the prevalence of HH in children undergoing esophagogastroduodenoscopy (EGD), irrespective of their symptoms. METHODS: We prospectively enrolled 111 consecutive children (48 boys and 63 girls; mean age 94.9 ± 52.3 months) referred for EGD. In all of the patients a asymptomatic score assessment based on the Rome III criteria was used to measure frequency, severity, and duration of gastrointestinal symptoms. HH presence was endoscopically defined; esophagitis presence was evaluated either endoscopically and histologically. Children were divided in 2 age-range groups: 48 months (group 2). RESULTS: Twenty-three patients of 111 (20.7%) had evidence of a sliding HH at EGD. In children from group 2, we found a statistically significant association of HH with heartburn (P = 0.03, 95% confidence interval 1-9.3, r = 0.1) and regurgitation (P = 0.003, 95% confidence interval 1.7-20.4, r = 0.3). Regarding esophagitis presence, no association was found at any age either with defined esophagitis or with dilated intercellular spaces. CONCLUSIONS: Prevalence of HH in our study population was 20.7%. According to our data, HH correlates with the presence of heartburn and regurgitation in children, but not in toddlers. No association was found with esophagitis at any age.