Pietro Forestieri

Epigenetic modifications alter transcriptional activity and contribute to the effects of environment on the individual risk of obesity and Type 2 Diabetes (T2D). Here, we have estimated the in vivo effect of a fat-enriched diet (HFD) on the expression and the epigenetic regulation of the Ankyrin repeat domain 26 (Ankrd26) gene, which is associated with the onset of these disorders. In visceral adipose tissue (VAT), HFD exposure determined a specific hyper-methylation of Ankrd26 promoter at the −436 and −431 bp CpG sites (CpGs) and impaired its expression. Methylation of these 2 CpGs impaired binding of the histone acetyltransferase/transcriptional coactivator p300 to this same region, causing hypo-acetylation of histone H4 at the Ankrd26 promoter and loss of binding of RNA Pol II at the Ankrd26 Transcription Start Site (TSS). In addition, HFD increased binding of DNA methyl-transferases (DNMTs) 3a and 3b and methyl-CpG-binding domain protein 2 (MBD2) to the Ankrd26 promoter. More importantly, Ankrd26 down-regulation enhanced secretion of pro-inflammatory mediators by 3T3-L1 adipocytes as well as in human sera. Thus, in mice, the exposure to HFD induces epigenetic silencing of the Ankrd26 gene, which contributes to the adipose tissue inflammatory secretion profile induced by high-fat regimens.

Sentinel lymph node biopsy (SLNB) is a minimally invasive technique to stage the axillary lymph node status. The burden of nodal metastasis is of great concern, as the clinical relevance and therapeutic implications of pN1mi and pN0(i+) in the sentinel lymph node (SLN) remain a matter of debate. We examined the pathological features of 901 patients above the age of 65 presenting with clinical T1-T2 N0M0 breast tumours (<3 cm), detecting tumours related to llary non-sentinel node (NSN) metastases when the SLN was minimally involved. A total of 270 patients underwent complete axillary lymph node dissection (cALND) after their SLNB specimen tested positive for macrometastasis, micrometastasis and isolated tumour cells (ITCs). Seventy-six patients were diagnosed with micrometastatic disease pN1mi (27.5%), whilst ITCs (pN0i+) were detected in seven patients (2.5%). NSNs were found to be involved in two patients (2.6%) with micrometastases at the SLN. No further metastatic disease was detected in NSNs when the SLN contained ITCs. At a median follow-up period of 5.8 years, no axillary recurrence was observed among pN1mi and pN0(i+) patients. Lobular histotype, multicentricity and lymphovascular invasion were found to be associated with NSN involvement. The results from our case series are supported by IBCSG 23-01 level 1 evidence, which demonstrated a local recurrence rate of 1% in 'minimally involved not-surgical treated axilla'. Based on current evidence, we spare well-informed and consenting patients from further axillary surgery when the SLN is minimally involved in early breast cancer within an agreed protocol, whilst scheduling adjuvant treatment based on the patients' primary tumour characteristics.

Laparoscopic adjustable gastric banding (LAGB) is a well-established and effective bariatric procedure, whose outcomes can be compromised by the slippage and the following removal of the band; the association between LAGB and gastric plication has recently been proved as a successful treatment for morbid obesity. The aim of this prospective randomized study was to compare weight loss and slippage rate between LAGB and LAGB plus anterior fundoplication.From January 2012 to May 2012, a total of 40 patients were allocated to undergo either LAGB (group A, n=20) or LAGB plus anterior fundoplication (group B, n=20). Data on the operative time, complications, hospital stay, total weight loss percentage (%TWL), percentage of excess weight loss (%EWL), and improvement of comorbidities were collected at 6, 12, and 36 months of follow-up.All procedures were completed laparoscopically, and no significant difference of mean operative time was found between the 2 groups. The mean hospital stay was longer in group B than in group A (2.3±0.8 vs. 1.4±0.7 d, P<0.005). Greater weight loss was found in group B rather than in group A at 6, 12, and 36 months. Obesity related comorbidities improved in both groups. Number of band regulations and slippage rate were lower in group B.Our experience shows that 36 months after surgery LAGB plus anterior fundoplication increases weight loss and reduces the slippage rate.

Recent reports have demonstrated improvement in the 5-years serviva with resecate ductal adenocarcinoma. The aim of study is to determinate the factor influencing long-term survival after DCP. We have critically reviewed a group of 85 patients how were admitted to our department with diagnosis of ductal adenocarcinoma of the head of pancreas between January 1974 and January 1998. Patients were stratified according to stage using TNM classification; in stage I 31 patients with 5 T1aN0M0 disease, 11 patients with T1bN0M0 and 15 patients T2N0M0 disease. By contrast, in stage III 54 patients with 48 patients T2N1M0 and 6 patients with T3N1M0. Tumour size was recorded for 72 patients with a median of 3.8 cm. The R1 dissection was performed in 67 patients. The R2 resection was performed in 18 patients. In our series we verified and analysed the histopathologic features of 5 patients with 15-years survival (5.8%). The features regard age, male or female, tumours size, stage and positive lymph node resection. We found a specifically subset of patients where the combination of prognostic factors, in particular, negative surgical margins R0, tumour size ≤ 30 mm and the absence of lymph node metastasis independently reduced the mortality indicating that earlier tumour detection and histologically curative resection are important factors contributing to long term survival and healing of ductal adenocarcinoma of the head of the pancreas.

Breast neoplasms include different histopathological entities, varying from benign tumors to highly aggressive cancers. Despite the key role of imaging, traditional histology is still required for a definitive diagnosis. Confocal Laser Endomicroscopy (CLE) is a new technique, which enables to obtain histopathological images in vivo, currently used in the diagnosis of gastrointestinal diseases. This is a single-center pilot feasibility study; the main aim is to describe the basic morphological patterns of Confocal Laser Endomicroscopy in normal breast tissue besides benign and malignant lesions. Thirteen female patients (mean age 52.7, range from 22 to 86) who underwent surgical resection for a palpable breast nodule were enrolled. CLE was performed soon after resection with the Cellvizio® Endomicroscopy System (Mauna Kea Technologies, Paris, France), by using a Coloflex UHD-type probe; intravenous fluorescein was used as contrast-enhancing agent. The surgical specimen was cut along the main axis; dynamic images were obtained and recorded using a hand-held probe directly applied both to the internal part of the lesion and to several areas of surrounding normal tissue. Each specimen was then sent for definitive histologic examination. Histopathology revealed a benign lesion in six patients (46%), while a breast cancer was diagnosed in seven women (54%). Confocal laser endomicroscopy showed some peculiar morphological patterns. Normal breast tissue was characterized by a honeycomb appearance with regular, dark, round or hexagonal glandular lobules on a bright stroma background; tubular structures, representing ducts or blood vessels, were also visible in some frames. Benign lesions were characterized by a well-demarcated “slit-like” structure or by lobular structures in abundant bright stroma. Finally, breast cancer was characterized by a complete architectural subversion: ductal carcinoma was characterized by ill-defined structures, with dark borders and irregular ductal shape, formingribbons, tubules or nests; mucinous carcinoma showed smaller cells organized in clusters, floating in an amorphous extracellular matrix. This is the first pilot study to investigate the potential role of confocal laser imaging as a diagnostic tool in breast diseases. Further studies are required to validate these results and establish the clinical impact of this technique.

Indications for endoscopic snare papillectomy (ESP) remain controversial. Main concerns with ESP are related to the incomplete removal of the lesion, high recurrence rates and inadequate oncological resection. Aim of the study is to report short and long term outcomes after endoscopic papillectomy in a single institutional series with strict inclusion criteria and a standardized technique. Patients with ampullary tumors who underwent endoscopic papillectomy over a 5 year period were reviewed. Inclusion criteria for endoscopic resection were: tumor diameter less than 3 cm, no endoscopic evidence of malignancy, absence of infiltration of biliary and pancreatic duct at pre-operative ERCP and tumor confined to the submucosa at EUS. An en-block resection was attempted in all cases, followed by a pancreatic stent insertion whenever possible. Twenty-seven patients (10 female, mean age 68 y) have been identified. Ampullectomy was successfully performed in all the cases. En bloc resection was completed in 24 patients (88.8%), while 3 patients had a piecemeal resection. A pancreatic stent was successfully placed in all the patients. Five patients experienced complications, including bleeding (2 cases, 7.4%) and acute pancreatitis (3 cases, 11.1%). There was no procedure-related mortality. Histology revealed a poor prognosis in two patients, which were subsequently treated by duodenopancreatectomy. Over a long-term follow-up (median 18 months), one patient developed local recurrence, which was successfully treated with further endoscopic resection. Overall curative resection rate was 92.6%. Endoscopic ampullectomy allows resection of benign tumors and in situ carcinoma. Strict indications and a proper standardized technique seem to be key factors in order to achieve excellent short and long-term results.

Obesity is a major risk factor for several chronic diseases. The BioEnterics^® Intragastric Balloon (BIB^®) is used worldwide as a short-term (6 months) treatment in morbid obese patients. However, removal of BIB^® past 6 months is a common occurrence in clinical practice often as a result of patient factors. The aim of the present Italian multicentre cohort study was to evaluate the safety and efficacy of the BIB^® left in situ for more than 6 months. A total of eight Italian centres participated in the study. Participating centres received a standardised questionnaire designed to capture safety and efficacy data. Weight loss data, as well as date, and reason for removal of the BIB^® after 6 months were recorded. Adverse events, including mortality and complications, operators’ subjective technical notes and findings, and difficulties during removal procedure were also collected. Six hundred and eleven patients were included. In the majority of cases, patient extended BIB^® treatment due to satisfactory weight loss (44 %). At 6 months, all patients achieved a BMI statistically lower than the initial BMI (p < 0.001). There was a non-significant trend towards greater BMIL % in patients who underwent removal up to 15 months versus the results achieved up to 6 months. No major complications were recorded. Extending the duration of BIB^® use up to 14 months safely maintains weight loss and satiety with greater results than that up to 6 months, without complications.

The serum collection under the abdominal flap is the most common complication after a lipo-abdominoplasty. The frequency of seroma increases further among obese patients, who have achieved massive weight loss after bariatric surgery. The purpose of this study is to demonstrate the effectiveness of fibrin glues with a low concentration of thrombin in reducing seroma formation after a lipo-abdominoplasty. Thirty patients, that had achieved a significant weight loss after an intervention of laparoscopic adjustable gastric banding (LAGB), underwent a circular lipo-abdominoplasty at our bariatric surgery department. Patients were divided into two groups of 15 subjects each: group A underwent traditional surgery; in group B, we applied a slow-clotting variant of fibrin glue (ARTISS, Baxter) under the abdominal flap. All subjects were evaluated clinically using an ultrasound device on postoperative day 15. We considered positive for seroma, those cases with a liquid collection greater than 20 cc. The groups were homogeneous for age, BMI, male/female ratio, and diabetic or smoker patients. The mean hospital stay was significantly longer in group A than in group B. We found eight cases of serum collection >20 cc in group A and only one case in group B. Hematoma, umbilicus necrosis, and surgical site infection occurred in both groups, but overall complication rate was lower in group B. The use of a fibrin glue with a low concentration of thrombin could be useful during wound closure and may decrease seroma formation in postbariatric patients undergoing lipo-abdominoplasty.

Laparoscopic Adjustable Gastric Banding (LAGB) is a safe and effective treatment for obesity. A strong evidence links weight loss with improved fertility outcomes and reduced gestational complications in subsequent pregnancies. Our aim is to describe the impact of LAGB on maternal and neonatal outcomes. Data were collected retrospectively from the database of our University Center for the Multicentric Treatment of Severe Obesity. From January 2006 to December 2011, 438 patients underwent LAGB. Of these, 140 women of reproductive age (18-46 years old) were included in our study. The following parameters were registered during follow-up: number of pregnancies, delivery and miscarriage, time from LAGB to pregnancy, band adjustments, weight gain during pregnancy, gestational and obstetrical complications (gestational diabetes mellitus, hypertensive disorders, prolonged labor), mode of delivery, neonatal birth weight and complications (low birth weight, IUGR, prematurity, macrosomy). We registered 26 pregnancies with a total of 22 babies born and 4 miscarriages. The mean time from LAGB to pregnancy was 15.8 months. Band adjustments were performed in 100% of patients during the first trimester; the average weight gain at the end of pregnancy was 14.66 kg. None presented gestational or obstetrical complications. One patient presented band slippage, which required surgery, and one patient presented iron-deficiency anemia. 100% of deliveries were by cesarean section. No perinatal complications or malformations were recorded, and the average baby weight was 3027 g. LAGB is a safe procedure, well tolerated during pregnancy and without negative implications on both the mother and the baby. According to our experience and recent studies, band loosening should be reserved to symptomatic patients to avoid unhealthy weight gain.