Stage II endometrial cancer: The diagnostic power of hysteroscopic excisional biopsy and MRI in the pre-operative cervical stroma assessment.

INTRODUCTION/BACKGROUND: Stage II Endometrial cancer (EC) accounts only for 12% of cases. Recent evidences redraw the weight of radicality in this stage as it would seem to have no impact on survival outcomes claiming for radicality when free surgical margins are not ensured to be achieved by simple hysterectomy. Thus, an accurate pre-operative evaluation might be crucial. This study aims to estimate the diagnostic power of Hysteroscopic excisional biopsy (HEB) of cervical stroma alone and combined with Magnetic resonance imaging (MRI) to predict the stage and concealed parametrial invasion in patients with preoperative stage II EC. METHODOLOGY: From January 2019 to November 2023, all patients evaluated at the Department of Gynaecology Oncology of Humanitas, Istituto Clinico Catanese, Catania, Italy, with a diagnosis of EC and evidence of cervical stromal diffusion on preoperative MRI and/or office hysteroscopy evaluation, considered suitable for laparoscopic modified type B hysterectomy, were consecutively included in the study. These underwent endometrial and cervical hysteroscopy excisional biopsy (HEB) for histological evaluation before definitive surgery. The data obtained were compared with the definitive histological examination (reference standard). RESULTS: Sixteen patients met the including/excluding criteria and were considered into the study. Stage II endometrial cancer were confirmed in 3 cases (18.7%). We reported 2 (12,5%) parametrial involvement (IIIB), 4 (25%) cases of lymph nodes metastasis (IIIc), 7 (43,7%) cases of I stage. MRI had a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy (95% CIs) of 71%, 44%, 50%, 66% and 56.2 % respectively. HEB showed sensitivity, specificity, PPV, NPV and accuracy (95 % CI) of 85 %, 89 %, 85 %, 88 % and 87 % respectively. Comparing HEB + MRI to HEB alone, no statistical differences were noted in all fields. Considering parametrial invasion, MRI had better sensitivity but there were no statistical differences to HEB in other fields, showing both a worthy NPV. CONCLUSION: HEB was accurate in all fields for cervical stroma assessment and had a fine NPV to exclude massive cervical involvement up to parametrial. Considering the new FIGO staging a preoperative molecular and histological evaluation of the cervical stroma may be useful. Operative hysteroscopy seems to be a feasible and accurate method for this purpose.

Predictivity of early and late assessment for post-surgical recurrence of Crohn's disease: Data from a single-center retrospective series.

BACKGROUND AND AIMS: Post-surgical recurrence of Crohn's disease (CD) after ileocolonic resection is common. Early identification of features associated with recurrence is a standard procedure of postoperative management, but the prognostic role of such features when detected at later time points is unclear. We compared the predictivity for Crohn's disease recurrence of common clinical-instrumental variables when assessed early (<12 months) or late (>36 months) after surgery. METHODS: This retrospective study considered CD patients who had ileocolonic resection and were followed for a median of 7.6 years. Clinical characteristics, post-surgical therapy, endoscopy recurrence (Rutgeerts' score ≥i2) and ultrasound features were compared between subgroups who had a early or late post-surgical assessment. Univariate and multivariate analyses were done to identify variables associated with recurrence (clinical and surgical). RESULTS: Of 201 patients, 70 (32%) had a early and 39 (19%) had a late post-surgical assessment. The Early and Late subgroups had similar clinical characteristics. Overall, clinical relapse was observed in 131 patients (66%), surgical relapse in 31 (16%), endoscopic recurrence in 149 (75%) and ultrasonographic recurrence in 132 (66%), without significant differences in frequencies between subgroups. By Cox proportional hazard regression, endoscopic recurrence was a significant predictor of clinical recurrence overall (HR=2.31, P = 0.002) and in the Early (HR=3.85, P = 0.002) but not Late subgroup. DISCUSSION: The most informative postoperative CD assessment is the one done within the first year of surgery. Later endoscopic evaluations have no prognostic value and should be done only for clinical needs or for research purposes.

Correlation of neonatal weight with maternal serum levels of pregnancy-associated plasma protein-A during the first trimester of pregnancy: a retrospective study.

AIM: Evaluate the relationship between neonatal weight and pregnancy-associated plasma protein-A. METHODS: Retrospective study on 2564 singleton pregnancies with healthy term neonates in three groups of women with different values of pregnancy-associated plasma protein-A who underwent the combined test during the first trimester. Non-parametric test and correlation analysis for statistical elaboration were carried out. RESULTS: There exists a correlation between the serum levels of pregnancy-associated plasma protein-A in the first trimester of pregnancy and neonatal weight. Values of pregnancy-associated plasma protein-A lower than the 25th percentile are associated with neonatal weight in a significant way. There was no significant association between pregnancy-associated plasma protein-A values above 1.50 MoM and neonatal weight. CONCLUSION: This study confirms the positive correlation between circulating concentrations of pregnancy-associated plasma protein-A and fetal growth. Low neonatal weight and factors that can cause this could be determined from the first trimester by measuring the concentrations of pregnancy-associated plasma protein-A in maternal serum. Even if the association between the levels of pregnancy-associated plasma protein-A and a low neonatal weight has been demonstrated, however, we have to say that the sensitivity of a such screening method for the prediction of low birth weight and perinatal complications seems to be rather low. The variations of pregnancy-associated plasma protein-A during the first trimester cannot be used as a marker of excessive fetal growth.

Liver Function Test Abnormalities in Patients with Inflammatory Bowel Diseases: A Hospital-based Survey.

BACKGROUND AND AIMS: Inflammatory bowel diseases (IBD) are frequently associated with altered liver function tests (LFTs). The causal relationship between abnormal LFTs and IBD is unclear. The aim of our study was to evaluate the prevalence and etiology of LFTs abnormalities and their association with clinical variables in a cohort of IBD patients followed up in a single center. MATERIALS AND METHODS: A retrospective review was undertaken of all consecutive IBD in- and outpatients routinely followed up at a single referral center. Clinical and demographic parameters were recorded. Subjects were excluded if they had a previous diagnosis of chronic liver disease. LFT abnormality was defined as an increase in aspartate aminotransferase, (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), or total bilirubin. RESULTS: A cohort of 335 patients (179 males, mean age 46.0 ± 15.6 years) was analyzed. Abnormal LFTs were detected in 70 patients (20.9%). In most cases, the alterations were mild and spontaneously returned to normal values in about 60% of patients. Patients with abnormal LFTs were less frequently on treatment with aminosalicylates (22.8 vs. 36.6%, P = 0.04). The most frequent cause for transient abnormal LFTs was drug-induced cholestasis (34.1%), whereas fatty liver was the most frequent cause of persistent liver damage (65.4%). A cholestatic pattern was found in 60.0% of patients and was mainly related to older age, longer duration of disease, and hypertension. CONCLUSIONS: The prevalence of LFT abnormalities is relatively high in IBD patients, but the development of severe liver injury is exceptional. Moreover, most alterations of LFTs are mild and spontaneously return to normal values. Drug-induced hepatotoxicity and fatty liver are the most relevant causes of abnormal LFTs in patients with IBD.

CT enterography as a powerful tool for the evaluation of inflammatory activity in Crohn's disease: relationship of CT findings with CDAI and acute-phase reactants.

PURPOSE: Few studies have correlated computed tomography enterography (CTE) findings with Crohn's disease (CD) clinical and biochemical activity. The aim of this study was to evaluate correlations between CTE findings with CD activity. MATERIALS AND METHODS: The CTE datasets from 62 patients were retrospectively reviewed for different parameters: bowel wall thickening and hyperenhancement, mesenteric alterations, abdominal free fluid and complications related to the disease (fistulas, strictures, abscesses). Activity was assessed using the Crohn's Disease Activity Index (CDAI) and some biochemical markers (C-reactive protein, erythrocyte sedimentation rate, alpha 2-globulins, fibrinogen, platelets, haemoglobin). Correlations between CTE parameters, clinical activity score and laboratory parameters were assessed by logistic regression. RESULTS: CDAI was significantly correlated with increased fat density (p = 0.03) and intestinal strictures (p = 0.04). Platelet counts were elevated in patients with enlarged mesenteric lymph nodes (p = 0.009) and the comb sign (p = 0.05). Serum alpha 2-globulins were higher in the presence of the comb sign (p = 0.03). CONCLUSION: The CTE finding of perienteric inflammation (increased fat density) and vascular engorgement of the vasa recta in CD patients suggest that the disease is clinically active and that these patients may require more aggressive treatment than patients without these findings.

Randomized controlled clinical trials in mild-moderate ulcerative colitis.

The Authors review and critically discuss the most recent published evidence on treatment of mild-moderate ulcerative colitis both in the induction and maintenance of remission. Evidence on each drug is introduced by the related statement of ECCO guidelines. A brief introduction on disease classification and the need of standardizing indexes of clinical and endoscopic activity is also provided. Concluding remarks stress the heterogeneity of available studies both in the selection of patients and the outcomes evaluated and suggest the development of an international consensus in setting standards which will allow studies' results to be compared and combined to produce high quality clinical recommendations.

Fecal calprotectin in clinical practice: a noninvasive screening tool for patients with chronic diarrhea.

BACKGROUND: Surrogate markers of colorectal inflammation are increasingly being recognized as important in differentiating organic from functional intestinal disorders. Fecal calprotectin (FC) can be easily measured in the stool, being released by leukocytes in inflammatory conditions. AIM: We evaluated FC as an index of inflammation in consecutive outpatients referred for colonoscopy for chronic, nonbloody diarrhea. METHODS: Stool specimens of 346 outpatients with chronic, nonbloody diarrhea, referred for colonoscopy, were measured for FC levels. The proportion of patients correctly diagnosed with the test and the relationship with endoscopic and histologic findings were measured. RESULTS: Abnormal endoscopic findings were detected in 104 patients (30.1%). Histologic findings included 142 patients (41.0%) with inflammation and 204 (59.0%) without inflammation. Fecal excretion of calprotectin significantly correlated with the finding of inflammation at endoscopy and histology (P<0.0001). When 150 mcg/g of stool was used as the upper reference limit, FC showed 75.4% sensitivity and 88.3% specificity, with 81.7% positive and 83.7% negative predictive values for histologic inflammation. CONCLUSIONS: In outpatients referred for colonoscopy a measurement of FC is accurate to identify those with histologic inflammation. Assay of FC may be a reliable and noninvasive screening tool to identify inflammatory causes of chronic, nonbloody diarrhea.

Fluoroquinolone-induced liver injury: three new cases and a review of the literature.

PURPOSE: Fluoroquinolones are popular and widely used in primary care and hospital settings. Premarketing studies showed a favourable side-effect profile. However, significant morbidity and the need for liver transplantation for acute liver failure have been reported. We reviewed the available data on liver damage linked to fluoroquinolones. METHODS: A systematic search of case reports on the MEDLINE database encompassing the years 2000-2011 was carried out. Additional references were found by a manual search of the retrieved paper. We also describe three new cases of hepatotoxicity attributable to fluoroquinolones seen at our Unit. RESULTS: Thirty-five cases were retrieved from MEDLINE (51.4% male). According to the RUCAM scale, liver injury was classified as hepatocellular (51.4%), cholestatic (28.6%) or mixed (20.0%). Older age (≥ 65 years) was present in 42.8%. The time between initiation of treatment and hepatic injury ranged from 1 to 39 days (median 8 days). According to the RUCAM score, our cases were classified to be "highly probable" or "probable". Only one patient underwent liver biopsy, which showed the features of liver damage linked to drug exposure. Liver enzymes from all patients return to normal range within 4 weeks of withdrawal. Only one patient showed a renal failure, associated with liver injury, with a need for haemodialysis for 3 weeks. CONCLUSIONS: Fluoroquinolones are substantially safe antibiotics. Although fluoroquinolone-related hepatic injury occurs infrequently, its consequences can be severe. Patients should also be cautioned to avoid re-exposure to other members of the fluoroquinolone class.

Serology in adults with celiac disease: limited accuracy in patients with mild histological lesions.

Celiac disease (CD) is a gluten-triggered enteropathy, presenting with insidious clinical patterns. It can occasionally be diagnosed in asymptomatic subjects. Our aim was to define the relationship among symptoms at diagnosis, serological markers [tissue transglutaminase antibodies (tTGA), anti-endomysium antibodies (EMA) anti-actin antibodies (AAA)] and degree of mucosal damage. A total of 68 consecutive adult patients with CD were enrolled. Intestinal biopsies were scored according to the Marsh classification modified by Oberhuber: I-II minimal lesions or absent villous atrophy; IIIA partial villous atrophy; IIIB-C total villous atrophy (TVA). HLA-typing was done for all patients. No association between clinical presentation and severity of mucosal damage was found. Presence of EMA or tTGA was significantly associated with more severe mucosal damage (P < 0.001). Of 12 patients, 11 with AAA were also positive for TVA. The severity of mucosal damage is the main factor governing the detectability of serological markers of CD. The sensitivity of serological testing is questionable in patients with minimal lesions.

Adalimumab in steroid-dependent Crohn's disease patients: prognostic factors for clinical benefit.

BACKGROUND: Corticosteroids are effective in the treatment of Crohn's disease but some patients relapse during tapering or after discontinuation. We report data on efficacy and prognostic factors of response of adalimumab in steroid-dependent patients. METHODS: In all, 110 steroid-dependent patients were treated with adalimumab (80/40 or 160/80 mg every other week followed by 40 mg every other week). Clinical remission was defined as steroid discontinuation without symptomatic recurrence and clinical response as the reduction or maintenance of the initial Crohn's Disease Activity Index (CDAI) value reducing steroid dosage but without its discontinuation at week 6 and at the end of follow-up. RESULTS: At week 6, 91% of patients had a clinical benefit (remission: 45.5%, response: 45.5%). At the end of the follow-up (mean 14.6 months), 80.9% of responders maintained the clinical benefit (remission: 64.5%, response: 16.4%). At univariate analysis four variables were associated with remission at week 6: age of patients <40 years at baseline, no previous history of surgery, inflammatory pattern, and higher induction regimen. At multivariate analysis only higher induction regimen was related to remission at week 6. At the end of the follow-up, none of the variables were associated with remission. None of the variables were related to response at 6 weeks and at the end of follow-up. Adalimumab was well tolerated. CONCLUSIONS: This study shows that adalimumab is a powerful and safe weapon for steroid discontinuation in patients with steroid-dependent Crohn's disease. Higher induction regimen dosage is the better therapeutic choice for achieving clinical remission with low risk of clinical relapse.

Genetic predisposition to thrombophilia in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) is linked to a definite risk of thromboembolic events (TE), but data on the role of prothrombotic genetic mutations are conflicting. STUDY: Fourteen genetic factors involved in TE pathogenesis were investigated in a homogeneous cohort of Sicilian patients with IBD with and without history of TE and in healthy controls. Forty IBD patients (21 CD, 19 UC) and 20 healthy individuals were enrolled. Genetic testing was based on the reverse hybridization principle by a commercial assay that analyzes 14 polymorphisms involved in thrombophilia and cholesterol metabolism. The rate of genetic polymorphisms and mutations was compared between IBD patients and healthy controls. RESULTS: No significant difference in allelic frequency was found between IBD patients and controls except AGT T/T, though a trend toward significance was found also for ACE D/D. Eight out of 9 patients with earlier history of TE had more than 1 polymorphism, compared with 12 out of 31 without TE. In patients with IBD the mutation AGT T/T was related to male sex (P<0.0259) and, marginally, to arterial hypertension (P<0.06) and diabetes (P<0.09). CONCLUSIONS: Our data confirm a definite risk of TE in IBD (22.5% of our series). An increased frequency of the genotypes ACE D/D and AGT T/T, never reported so far, was found. In IBD patients TE has a multifactorial genesis with involvement of several genes as well and acquired factors. Genetic screening for prothrombotic factors could help segregate IBD patients at higher risk of TE.