Search

Background: We describe a multistep model of cancer genetic counselling designed to promote awareness, and disease surveillance and preventive measures for hereditary and familial breast and ovarian cancer. Patients and methods: Step T0 of the model entails information giving; this is followed by pedigree analysis and risk estimation (T1), risk communication and genetic testing (T2), and genetic test result communication (T3). User consent was required to proceed from one step to the next. Surveillance and preventive measures are proposed to at-risk users. Of the 311 subjects who requested cancer genetic counselling, consent data to each counselling step were available for 295: 93 were disease-free, 187 had breast cancer, 12 had ovarian cancer and three had breast plus ovarian cancer. Results: Consent was high at T0 (98.39%), T1 (96.40%) and T2 (99.65%). Consent decreased at the crucial points of counselling: T2 (87.71%) and T3 [genetic test result communication (85.08%), and extension of counselling to and testing of relatives (65.36%)]. Conclusions: The model fosters the user’s knowledge about cancer and favours identification of at-risk subjects. Furthermore, by promoting awareness about genetic testing and surveillance measures, the algorithm enables users to make a fully informed choice of action in case of predisposing or familial cancer risk.

Autosomal dominant polycystic kidney disease (ADPKD) is a heterogeneous genetic disorder included in ciliopathies, representing the fourth cause of end stage renal disease (ESRD), with an estimated prevalence between 1:1000 and 1:2500. It is mainly caused by mutations in the PKD1 and PKD2 genes encoding for polycystin 1 (PC1) and polycystin 2 (PC2), which regulate differentiation, proliferation, survival, apoptosis, and autophagy. The advances in the knowledge of multiple molecular pathways involved in the pathophysiology of ADPKD led to the development of several treatments which are currently under investigation. Recently, the widespread approval of tolvaptan and, in Italy, of long-acting release octreotide (octreotide-LAR), represents but the beginning of the new therapeutic management of ADPKD patients. Encouraging results are expected from ongoing randomized controlled trials (RCTs), which are investigating not only drugs acting on the calcium/cyclic adenosin monoposphate (cAMP) pathway, the most studied target so far, but also molecules targeting specific pathophysiological pathways (e.g. epidermal growth factor (EGF) receptor, AMP-activated protein kinase (AMPK) and KEAP1-Nrf2) and sphingolipids. Moreover, studies on animal models and cultured cells have also provided further promising therapeutic strategies based on the role of intracellular calcium, cell cycle regulation, MAPK pathway, epigenetic DNA, interstitial inflammation, and cell therapy. Thus, in a near future, tailored therapy could be the key to changing the natural history of ADPKD thanks to the vigorous efforts that are being made to implement clinical and preclinical studies in this field. Our review aimed to summarize the spectrum of drugs that are available in the clinical practice and the most promising molecules undergoing clinical, animal, and cultured cell studies. Graphical abstract: [Figure not available: see fulltext.]

Background Although enzyme replacement therapy with agalsidase beta resulted in a variety of clinical benefits, life‐long biweekly intravenous infusion may impact on patients’ quality of life. Moreover, regular infusions are time‐consuming: although a stepwise shortening of infusion duration is allowed up to a minimum of 1.5 hr, in most centers it remains ≥3 hr, and no data exists about the safety and tolerability of agalsidase beta administration at maximum tolerated infusion rate. Methods In this study, we reported our experience with a stepwise infusion rate escalation protocol developed in our center in a cohort of 53 Fabry patients (both already receiving and treatment‐naΪve), and explored factors predictive for the infusion rate increase tolerability. Results Fifty‐two patients (98%) reduced infusion duration ≤3 hr; of these, 38 (72%) even reached a duration ≤2 hr. We found a significant difference between the mean duration reached by already treated and naΪve patients (p, Although enzyme replacement therapy with agalsidase beta resulted in a variety of clinical benefits, life‐long biweekly intravenous infusion may impact on patients’ quality of life because regular infusions are time‐consuming. In this study, we reported our experience with a stepwise infusion rate escalation protocol developed in our center in a cohort of 53 Fabry patients (both already receiving and treatment‐naΪve), and explored factors predictive for the infusion rate increase tolerability. We showed that our infusion rate escalation protocol is safe and could improve patient compliance, satisfaction and quality of life.

Background: Fabry disease (FD) is a rare X-linked genetic disorder of glycosphingolipid catabolism caused by mutations in the GLA gene. Its heterogeneous presentation, the paucity of specific early markers, and the absence of a genotype–phenotype correlation are associated with a delayed or missed diagnosis. The true prevalence of FD remains so far unknown. Methods: A systematic search of FD screening studies in dialysis patients published from January 1995 until January 2019 was performed to reanalyze the prevalence of GLA mutations in this population after assigning their correct phenotype. Results: Twenty five screening studies involving 39,621 dialysis patients were included. Of them, 116 [91 males (0.23%) and 25 females (0.06%)] were positive to the GLA sequencing analysis. 56 (48.2%) had benign variant, 52 (44.8%) a pathogenic GLA mutation (39 classic and 13 late onset mutations) and 8 (6.9%) a mutation of uncertain significance. The overall prevalence of GLA variants was 0.24% [CI 95%, 0.17–0.32] while the overall prevalence recalculated on basis of only pathogenetic mutations was 0.14% [CI 95%, 0.08–0.20]. This difference was significant (P = 0.048). Conclusions: Although the real prevalence of classic FD is low, the screening in the high-risk renal population remains of primary interest as an early diagnosis is fundamental for a timely specific therapy; moreover, the identification of index cases could allow patients’ relatives to be investigated and promptly treated.

Progressive nephropathy is one of the main features of Fabry disease. Although some clinical signs of Fabry nephropathy are already present in childhood, patients are often diagnosed relatively late in the course of the disease due to the absence of specific clinical markers, while a timely diagnosis and the prompt start of enzyme replacement therapy may be beneficial in stabilizing renal function or slowing its decline. Proteinuria/albuminuria has been accepted as the most important marker for Fabry nephropathy; however, a large proportion of renal impairment occurs in nonalbuminuric state. Therefore, early biomarkers may be useful for early identification of kidney involvement. The aim of this article is to review the current available literature on all biomarkers of Fabry nephropathy, with a comprehensive and critical description of their utilization in early recognition of renal damage.

This is the frst record in the literature of the benefcial efect of metformin on ADPKD progression in the same family: during 10 years of follow-up, eGFR decreased in three sisters, but in one of them, it decreased slower after the introduction of metformin and without adverse event . Our results confrm the benefcial efect of metformin in delaying the progression of renal dysfunction in ADPKD patients with moderately impaired eGFR

Aim: The standard-of-care in breast cancer (BC) with positive sentinel lymph node (SLN) metastasis includes complete axillary lymph node dissection (ALND); however, almost half of such cases have no further tumor burden. This study aimed to assess the clinicopathological factors that predict non-SLN metastasis to define subgroups of SLN-positive patients in whom the axilla may be staged by SLN biopsy alone, while avoiding unnecessary overtreatment. Patients and Methods: The records of 191 patients with histologically-proven primary BC who underwent a positive (SLN) biopsy between 2005 and 2017 were reviewed. Patients with at least one tumor-involved SLN who underwent completion ALND were enrolled. Demographic and clinicopathological characteristics, including age, primary tumor size and histological grade, lymphovascular invasion, ratio of positive SLNs to the harvested SLNs, SLN metastasis size, and molecular subtype classification according to immunohistochemical biomarker status [estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)], were evaluated. Data were collected retrospectively and analyzed using the Mann-Whitney and Chi-square tests (statistical significance: p0.67 [odds ratio (OR)=2.55, p=0.032], luminal BC subtype (OR=2.67, p=0.06), HER2 overexpression (OR=0.4, p=0.016), and ER(+)PR(-)HER2(-) profile (OR=2.95, p=0.027). There was a tendency (statistically insignificant; p>0.05) toward higher incidence of non SLN metastasis with increasing age and histological grade, which could be attributed to the small sample size. Conclusion: According to this study, sentinel nodal ratio and BC subtypes as per ER, PR, and HER2 status significantly predicted the likelihood of additional lymphatic involvement. Validation of these parameters in prospective studies is indicated, and may help individualize treatment modalities.

Laparoscopic ventral mesh rectopexy (LVR) is gaining wider acceptance as the preferred procedure to correct internal as well as external rectal prolapse associated with obstructed defaecation syndrome and/or faecal incontinence. Very few reports exist on the use of biologic mesh for LVR. The aim of our study was to report the complication and recurrence rate of our first 100 cases of LVR for symptomatic internal rectal prolapse and/or rectocele using a porcine dermal collagen mesh. Prospectively collected data on LVR for internal rectal prolapse were analysed. Surgical complications and functional results in terms of faecal incontinence (measured with the Faecal Incontinence Severity Index = FISI) and constipation (measured with the Wexner Constipation Score = WCS) at 3, 6 and 12 months were analysed. It was considered an improvement if FISI or WCS scores were reduced by at least 25 % and a cure if the FISI score decreased to < 10 and the WCS decreased to < 5. Between April 2009 and April 2013, 100 consecutive female patients (mean age 63 years, range 24-88 years) underwent LVR. All patients had internal rectal prolapse (grade III [n = 25] and grade IV [n = 75] according to the Oxford classification) and rectocele. Mean operative time was 85 +/- A 40 min. Conversion rate to open technique was 1 %. There was no post-operative mortality. Overall 16 patients (16 %) experienced 18 complications, including rectal perforation (n = 1), small bowel obstruction (n = 2), urinary tract infection (n = 8), subcutaneous emphysema (n = 3), wound haematoma (n = 2), long lasting sacral pain (n = 1) and incisional hernia (1). Median post-operative length of stay was 2 days. Ninety-eight out of 100 patients completed follow-up. At the end of follow-up, the mean FISI score improved from 8.4 (+/- 4.0 standard deviation (SD) p = 0.003) to 3.3 +/- 2.3 SD (p = 0.04). Incontinence improved in 37 out of 43 patients (86 %), and 31 patients (72 %) were cured. Similarly, the mean WCS score improved from 18.4 +/- 11.6 SD to 5.4 +/- 4.1 SD (p = 0.04). Constipation improved in 82 out of 89 patients (92 %), and 70 patients (79 %) were cured. No worsening of continence status, constipation or sexual function was observed. Fourteen patients (14 %) experienced persistence or recurrence of prolapse. LVR using biologic mesh is a safe and effective procedure for improving symptoms of obstructed defaecation and faecal incontinence in patients with internal rectal prolapse associated with rectocele.

We present a modified laparoscopic ventral mesh rectopexy procedure using biological mesh and bilateral anterior mesh fixation. The rectopexy is anterior with a minimal posterior mobilization. The rectum is symmetrically suspended to the sacral promontory through a mesorectal window.

Background and Objectives: Small-bowel obstruction (SBO) is a common surgical emergency that occurs in 9% of patients after abdominal surgery. Up to 73% are caused by peritoneal adhesions. The primary purpose of this study was to compare the rate of SBOs between patients who underwent laparoscopic (LPS) and those who had open (OPS) colorectal surgery. The secondary reasons were to evaluate the rate of adhesive SBO in a cohort of patients who underwent a range of colorectal resections and to assess risk factors for the development of SBO. Method: This was a retrospective observational cohort study. Data were analyzed from a prospectively collected database and cross checked with operating theater records and hospital patient management systems. Results: During the study period, 707 patients underwent colorectal resection, 350 of whom (49.5%) were male. Median follow-up was 48.3 months. Of the patients included, 178 (25.2%) underwent LPS, whereas 529 (74.8%) had OPS. SBO occurred in 72 patients (10.2%): 20 (11.2%) in the LPS group and 52 (9.8%) in the OPS group [P = .16; hazards ratio (HR) 1.4 95% CI 0.82-2.48] within the study period. Conversion to an open procedure was associated with increased risk of SBO (P = .039; HR 2.82; 95% CI 0.78-8.51). Stoma formation was an independent risk factor for development of SBO (P = .049; HR, 0.63; 95% CI 0.39 -1.03). The presence of an incisional hernia in the OPS group was associated with SBO (P = .0003; HR, 2.85; 95% CI 1.44 -5.283). There was no difference in SBO between different types of procedures: right colon, left colon, and rectal surgery. Patients who developed early small-bowel obstruction (ESBO) were more often treated surgically compared to late SBO (P= .0001). Conclusion: The use of laparoscopy does not influence the rate of SBO, but conversion from laparoscopic to open surgery is associated with an increased risk of SBO. Stoma formation is associated with a 2-fold increase in SBO. Development of ESBO is highly associated with a need for further surgical intervention.

Neuroendocrine tumors represent a heterogeneous category of neoplasm, with conflicting diagnostic and therapeutic demands. We here describe the case of a 72-yr-old woman with evidence of a poorly differentiated small-cell neuroendocrine carcinoma (NEC) localized in different endocrine glands and other non-endocrine organs. In particular, a large ovarian mass, multi-nodular thyroid goiter, right adrenal mass, cystic liver metastases and anterior mediastinum lymph node metastasis were present. The largest thyroid nodule caused tracheal restriction and dyspnea. Diagnosis of poorly differentiated metastasized NEC of unknown origin was made on the basis of histological and immunohistochemical findings, and treatment with etoposide (100 mg/m2 in days 1, 2 and 3) and cisplatinum (45 mg/m2 in days 2 and 3) was initiated. Simultaneously, im administration of octreotide LAR 20 mg every 28 days was started, according to the presence of SS receptors at 111In-octreotide scan. Rapid improvement of dyspnea and a reduction of the largest thyroid nodule, liver metastases and adrenal mass by 50% were observed after 3 months of treatment; the dimensions remained stable thereafter, while the pericardial lymph node disappeared. In conclusion, poorly differentiated NEC of unknown primary site is a well-recognized category, usually with an aggressive behavior, rapid growth rate and wide dissemination. Median survival of these patients is 6 months if left untreated. Our patient is alive 18 months after beginning the treatment, reporting good general condition and quality of life over the whole follow-up period.