Efficacy of High-dose Liraglutide 3.0 mg in Patients with Poor Response to Bariatric Surgery: Real-world Experience and Updated Meta-analysis.

PURPOSE: Poor response to bariatric surgery, characterized by insufficient weight loss (IWL) or weight regain (WR), poses a significant challenge in obesity treatment. This study aims to assess the effectiveness of liraglutide in addressing this issue. MATERIALS AND METHODS: A retrospective, multicenter cohort study investigated the impact of liraglutide 3 mg on weight loss in adults with suboptimal responses or weight regain after bariatric surgery (BS). Additionally, a systematic review and meta-analysis were conducted for a comprehensive evaluation. RESULTS: A total of 119 patients (mean age 41.03 ± 11.2 years, 71.4% female) who experienced IWL or WR after BS received pharmacologic therapy with liraglutide 3 mg. Mean percent weight loss in the entire cohort was 5.6 ± 2.6% at 12 weeks and 9.3 ± 3.6% at 24 weeks with a significant reduction in waist circumference (p < 0.0001). No serious side effects were reported. A meta-analysis, utilizing the fixed effect model with the metafor package in R, included 6 and 5 papers for the change in body weight and BMI after liraglutide treatment, respectively. The analysis demonstrated a considerable reduction in body weight (7.9; CI - 10.4; - 5.4, p < 0.0001) and BMI (3.09; CI 3.89; - 2.28, p < 0.0001). CONCLUSION: Liraglutide 3 mg emerges as a viable option for significant weight loss in patients experiencing IWL or WR after BS. Its inclusion in a multimodal, sequential obesity treatment approach proves promising.

Colo-colic intussusception in an adult caused by lipoma: Case report of a rare condition.

This report describes the case of a 56-year-old woman who presented at the emergency room with a 3-week history of severe, intermittent abdominal pain. A CT scan revealed colo-colic intussusception caused by a large, substenosing mass with predominant adipose density. Subsequent endoscopic examination with biopsy revealed a necrotic tissue covering the mass, without definitive histological characterization. A second biopsy led to the extremely rare diagnosis of colo-colic lipoma. While intussusception is rare in adults, it's important to consider it as a differential diagnosis, especially when presenting with abdominal pain and signs of bowel obstruction. Timely diagnosis and appropriate treatment are essential to prevent complications.

High-dose liraglutide improves metabolic syndrome in poor responders to bariatric surgery.

Background: Bariatric surgery (BS) represents the most effective therapy for obesity class III, or class II with at least one weight-related comorbidity. However, some patients have insufficient weight loss or clinically relevant weight regain after a successful primary procedure. This study aimed to assess the efficacy of liraglutide treatment on weight loss, body composition and improvement of metabolic syndrome (MS) in patients defined as poor responders after BS. Methods: The study involved 59 non-diabetic adults with obesity (M/F: 17/42, age: 38.6 ± 11.8 years, BMI 38.3 ± 5.5 kg/m2) who had been treated with BS and experienced a poor response, categorized as either IWL (insufficient weight loss) or WR (weight regain). All patients were prescribed pharmacological therapy with liraglutide and attended nutritional counseling. Anthropometric and clinical measurements, body composition and the presence of MS defined according to the ATP-III classification were evaluated before starting liraglutide and after 24 weeks of treatment. Results: After 24 weeks of treatment with liraglutide, the mean weight loss was 8.4% ± 3.6% with no difference between gender, bariatric procedure, or type of poor response (IWL or WR). A significant decrease in fat mass, free-fat mass and total body water was documented. After 24 weeks, patients presented significantly lowered fasting glucose, total cholesterol, triglycerides, AST and ALT. The prevalence of MS was reduced from 35% at baseline to 1.6% after 24 weeks. No patients discontinued the treatment during the study. Conclusion: In patients who experience poor response after BS, liraglutide is well tolerated and promotes significant weight loss, ameliorates cardiometabolic comorbidities, and reduces the prevalence of MS.

Jejunal volvulus within an inguinal hernia sac like as an extremely rare cause of acute mechanical gastrointestinal obstruction in adults: First literature report.

INTRODUCTION AND IMPORTANCE: Small bowel volvulus (SBV) represents a rare and life-threatening cause of gastrointestinal obstruction among adults. SBV can be classified as primary and secondary subtypes. Preoperative diagnosis of SBV is a challenge because of the absence of pathognomonic clinical, radiographic and laboratory findings. Surgery represents the correct treatment of SBV. CASE PRESENTATION: A 69-year-old Caucasian male presented to the Emergency Department with a two-day history of abdominal pain, inability to pass gas or stool, nausea, vomiting. Physical examination revealed abdominal distension, generalized abdominal pain without guarding or rebound tenderness, a partially reducible and painless right inguinal hernia. Laboratory tests reported neutrophilic leukocytosis. Abdominal computed tomography revealed massive gastroduodenal dilatation with pneumoperitoneum and small bowel loops in the right inguinal sac. The patient underwent exploratory laparotomy: a jejunal volvulus (JV) located within the right inguinal hernia sac, causing gastrointestinal obstruction, was devolvulated and a right prosthetic inguinal hernia repair was also performed. The patient was discharged on the 10th postoperative day. CLINICAL DISCUSSION: Secondary SBV is due to any congenital or acquired lesions and rarely occurs among adults in Western countries. This is the first literature report of a JV located within an inguinal hernia sac causing gastrointestinal obstruction. CONCLUSION: Secondary JV represents an extremely rare abdominal emergency necessitating early diagnosis to prevent the development of intestinal ischemia, bowel necrosis and peritonitis. Diagnosis of JV needs a high index of suspicion and may be facilitated by imaging, often it is made intraoperatively. Surgery represents the appropriate treatment of JV.

Granular cell tumor of the cecum: Case report of mini invasive surgical resection and review of the literature.

INTRODUCTION AND IMPORTANCE: Granular Cell Tumor (GCT) is a rare lesion with unclear histogenesis, predominantly described as a skin lesion. Visceral localization of GCT is even more rare with few cases reported in the literature. Nowadays GCT guidelines are not available. CASE PRESENTATION: A 45-year-old Caucasian woman was visited in our surgical department for significant weight loss (about 30 kg) during the previous 6 months. Colonoscopy showed a caecal polypoid lesion that was resected with a diatermic loop and classified as GCT. Microscopically, the neoplasm partially involved the mucosa and diffusely the submucosa, extending to the endoscopic resection margins. Because of the high risk of perforation during endoscopic radicalisation attempt, the patient underwent ileocecal resection. The postoperative course was uneventful. CLINICAL DISCUSSION: GCT is a rare soft tissue neoplasm probably deriving from Schwann cells. The main treatment for GCT is an endoscopic mucosal/submucosal resection. Nevertheless, a radicalization of the lesion through a surgical attempt should be preferred when the endoscopic procedure is linked to a high risk of perforation. It is important to distinguish GCT from other polypoid lesions of the colon, due to its malignant potential (about 2%) and its relapsing capacity when margins are involved. CONCLUSION: GTC is a rare neoplasm and as its diagnosis is made only histologically, it should be included in differential diagnosis of colonic polypoid lesions. Surgery can be considered the best choice when an endoscopic attempt of GCT lesions is linked to a high risk of colon perforation.

Complicated Littre's umbilical hernia with normal Meckel's diverticulum: A case report and review of the literature.

INTRODUCTION AND IMPORTANCE: A Littre's hernia (LH) is defined by the presence of Meckel's diverticulum (MD) in any kind of hernia sac. Preoperative diagnosis of LH is a challenge because of its rarity and the absence of specific radiological findings and clinical presentation. Surgery is the appropriate treatment of complicated LH that is an extremely rare condition with approximately 50 cases reported in the literature over the past 300 years. CASE PRESENTATION: A 46-year-old Caucasian female was admitted to the Emergency Department with a two-day history of abdominal pain. Physical examination revealed an irreducible and painfull mass in umbilical region. Abdominal computed tomography scan showed the protrusion of greater omentum and small bowel loop through the umbilical ring. Laboratory tests were unremarkable. After diagnosis of strangulated umbilical hernia, the patient underwent exploratory laparotomy: the irreducible umbilical hernial sac was opened with presence of incarcerated and strangulated omentum and uncomplicated MD. Resection of incarcerated and ischemic greater omentum alone was performed. The postoperative course of patient was uneventful. CLINICAL DISCUSSION: Meckel's diverticulum (MD) is a vestigial remnant of the omphalomesenteric duct, representing the most common congenital malformation of the gastrointestinal tract. Preoperative diagnosis of LH is very difficult and surgery represents the correct treatment of complicated LH. CONCLUSION: LH represents an extremely rare complication of MD difficult to diagnose and suspect because of the lack of specific radiological findings and clinical presentation. Surgery represents the appropriate treatment of abdominal wall hernias and complicated MD.

MR imaging-guided vacuum assisted breast biopsy: Radiological-pathological correlation and underestimation rate in pre-surgical assessment.

BACKGROUND: Magnetic Resonance(MR) guided percutaneous procedures(MRgVABB) have been developed and largely employed to reduce the need of surgical biopsies for suspicious lesions which can be detected only by MR(MR-only lesion). The present study aims to investigate correlation between imaging, histological features of MRgVABB and surgical specimens of MR-only lesions. METHODS: We retrospectively enrolled 56 patients with a total of 61 lesions. Each finding was defined as Mass-Enhancement(ME) or Non-ME(NME) and classified according to BI-RADS. MRgVABB and surgical data were collected. Concordance between MR, MRgVABB and open biopsy was calculated. Underestimation Rate(UR) of MRgVABB with surgery was obtained. RESULTS: B2 and B5b lesions were statistically associated with NME and ME, respectively. No statistical association was found to B3 nor to B5a with radiological features. UR was 10 %; underestimated lesions were strongly associated with the presence of a ME on MR imaging. Moreover, B3 lesions are associated with higher UR. CONCLUSION: Radiological features should influence patient management aiming to construct a correct diagnostic and therapeutic plan. When MR is prescribed for breast cancer staging for ME-MR-only lesions, we suggest surgical open biopsy instead of MRgVABB when upfront surgery is the treatment of choice.

Evaluation of Ultrasound-guided 8-Gauge Vacuum-assisted Excision System for the Removal of US-detectable Breast Lesions.

AIM: To assess the ability of ultrasound (US)-guided vacuum-assisted breast excision (VAE) to remove Breast Imaging Reporting and Data System (BI-RADS) ≥3 breast lesions in order to analyze US features most frequently associated with complete excision. MATERIALS AND METHODS: A total of 266 BI-RADS ≥3 lesions without microcalcifications underwent US-VAE. US-VAE and gold standard pathological results were compared. US features of lesions were analyzed. RESULTS: The complete excision rate was 93.61%; the VAE agreement rate was 99.62%. Circumscribed margins, regular shape, parallel orientation, and the absence of posterior features were favorable US features associated with complete excision. Lesions completely excised were: BI-RADS 3 ≤21.10 mm and BI-RADS 4 ≤18.70 mm with one unfavorable US characteristic, and BI-RADS 4 lesions ≤13.5 mm with two unfavorable US features hindered complete removal. Two atypical ductal hyperplasias (<10 mm, one unfavorable feature) and eight ductal carcinomas in situ (≤8.7 mm, one/two unfavorable features) were completely removed. CONCLUSION: US-VAE is highly accurate for diagnostic purpose and, in some cases, highly successful for complete lesion excision. This success also depends on the US characteristics and size of the lesion.

Right-sided aortic arch with mirror image branching and situs solitus: a case of a 79 years old woman.

Right aortic arch with mirror image branching (RAMI) is a rare congenital defect of the aorta. The exact incidence of RAMI in the general population is unclear. In RAMI the first branch arising from the arch is the left innominate artery, followed by the right carotid artery and right subclavian arteries. We report a case of an adult female patient with RAMI discovered as an incidental finding during radiological investigations for suspected pulmonary embolism in emergency department. No other congenital malformations were reported. It is important to recognize congenital variants of the aortic arch, as they can have relevant implications for patients' prognosis and management. Therefore, being aware of these conditions is key to avoid any mistakes or surgical and endovascular complications.

Internal jugular vein agenesis: a rare vascular abnormality and incidental finding. A case of internal jugular vein agenesis in a 52-years old male.

We report a case of vascular malformation arising from internal jugular vein discovered during radiological investigations for restaging of metastatic colon carcinoma of an adult male patient. Congenital absence of internal jugular vein is extremely uncommon. These developmental anomalies in general population are seen in about 0.05%-0.25%. The awareness of these vascular anomalies is extremely important to avoid unsafe complications, primarily in oncological patients, whom usually require the incannulation of neck veins for diagnostic procedures or intravenous therapy administration.

Probably Benign Breast Nodular Lesions (BI-RADS 3): Correlation between Ultrasound Features and Histologic Findings.

The purpose of this retrospective study was to determine the validity of the BI-RADS system in ultrasound findings assigned to BI-RADS 3 category, using cytologic and histologic results as a benchmark. Our study population consisted of 122 ultrasound nodular lesions in 122 women who underwent fine-needle aspiration cytology and biopsy for probably benign lesions (Breast Imaging Reporting and Data System [BI-RADS] category 3). Contrary to what was previously reported in the literature (risk of malignancy of BI-RADS 3 <2%), malignancy was the outcome in seven of 122 cases (5.7%). Our study also found that the presence of a cellular component with a mobile fluid-fluid level in a cystic lesion and small (<3 mm) anechoic components in solid lesions is not always an indication of benignity. Our experience seems to indicate the need to consider the presence of non-homogeneous echoes in the corpuscular cyst and solid nodular lesions with cystic components as suspicious, especially in lesions with large dimensions. Therefore it would be necessary to conduct further studies to establish a dimensional criterion in the assessment of the malignant nature of the mentioned lesions. The management of probably benign nodular lesions should not only be guided by BI-RADS classification; it is also necessary to include clinical and anamnestic data and apply a multidisciplinary approach to select cases that require histologic verification instead of the usual follow-up.

Laparoscopic versus open appendectomy: a retrospective cohort study assessing outcomes and cost-effectiveness.

BACKGROUND: Appendectomy is the most common surgical procedure performed in emergency surgery. Because of lack of consensus about the most appropriate technique, appendectomy is still being performed by both open (OA) and laparoscopic (LA) methods. In this retrospective analysis, we aimed to compare the laparoscopic approach and the conventional technique in the treatment of acute appendicitis. METHODS: Retrospectively collected data from 593 consecutive patients with acute appendicitis were studied. These comprised 310 patients who underwent conventional appendectomy and 283 patients treated laparoscopically. The two groups were compared for operative time, length of hospital stay, postoperative pain, complication rate, return to normal activity and cost. RESULTS: Laparoscopic appendectomy was associated with a shorter hospital stay (2.7 ± 2.5 days in LA and 1.4 ± 0.6 days in OA), with a less need for analgesia and with a faster return to daily activities (11.5 ± 3.1 days in LA and 16.1 ± 3.3 in OA). Operative time was significantly shorter in the open group (31.36 ± 11.13 min in OA and 54.9 ± 14.2 in LA). Total number of complications was less in the LA group with a significantly lower incidence of wound infection (1.4 % vs 10.6 %, P <0.001). The total cost of treatment was higher by 150 € in the laparoscopic group. CONCLUSION: The laparoscopic approach is a safe and efficient operative procedure in appendectomy and it provides clinically beneficial advantages over open method (including shorter hospital stay, decreased need for postoperative analgesia, early food tolerance, earlier return to work, lower rate of wound infection) against only marginally higher hospital costs. TRIAL REGISTRATION: NCT02867072 Registered 10 August 2016. Retrospectively registered.

The evidence of toxic wastes dumping in Campania, Italy.

The region of Campania (particularly Naples and Caserta) were subjected to extensive illegal dumping operations of toxic and radioactive wastes since the 1980s. The highly toxic wastes (HTW) dumping operations that have taken place both along the coast and the hinterland, have extremely adverse effects on health, livelihoods and the future prospect of sustainable development of the local population. The toxic wastes dumping in Campania is real and it has compromised (irreversibly) the human health, natural environment, food security and the long-term development prospects of the affected population. To reverse this tragic trend, it is necessery the identification, isolation and reclamation of the polluted sites and full assessment of the nature and the scale of the polluting chemicals and other hazardous wastes. The purpose of this review is to contribute significantly to the available evidence of the long-running toxic waste dumping in Campania and its negative impact on the health of population.

The roles of microRNAs in the pathogenesis and drug resistance of chronic myelogenous leukemia (Review).

Chronic myeloid leukemia (CML) is characterized by the accumulation of Philadelphia chromosome-positive (Ph+) myeloid cells. Ph+ cells occur via a reciprocal translocation between the long arms of chromosomes 9 and 22 resulting in constitutively active BCR-ABL fusion protein. Tyrosine kinase inhibitors (TKIs) are used against the kinase activity of BCR-ABL protein for the effective treatment of CML. However, the development of drug resistance, caused by different genetic mechanisms, is the major issue in the clinical application of TKIs. These mechanisms include changes in expression levels of microRNAs (miRNAs). miRNAs are short non-coding regulatory RNAs that control gene expression and play an important role in cancer development and progression. In the present review, we highlight the roles of miRNAs both in the progression and chemotherapy-resistance of CML. Our understanding of these mechanisms may lead to the use of this knowledge not only in the treatment of patients with CML, but also in other type of cancers.

Efficacy of Bariatric Surgery in Type 2 Diabetes Mellitus Remission: the Role of Mini Gastric Bypass/One Anastomosis Gastric Bypass and Sleeve Gastrectomy at 1 Year of Follow-up. A European survey.

BACKGROUND: A retrospective study was undertaken to define the efficacy of both mini gastric bypass or one anastomosis gastric bypass (MGB/OAGB) and sleeve gastrectomy (SG) in type 2 diabetes mellitus (T2DM) remission in morbidly obese patients (pts). METHODS: Eight European centers were involved in this survey. T2DM was preoperatively diagnosed in 313/3252 pts (9.62%). In 175/313 patients, 55.9% underwent MGB/OAGB, while in 138/313 patients, 44.1% received SG between January 2006 and December 2014. RESULTS: Two hundred six out of 313 (63.7 %) pts reached 1 year of follow-up. The mean body mass index (BMI) for MGB/OAGB pts was 33.1 ± 6.6, and the mean BMI for SG pts was 35.9 ± 5.9 (p < 0.001). Eighty-two out of 96 (85.4%) MGB/OAGB pts vs. 67/110 (60.9%) SG pts are in remission (p < 0.001). No correlation was found in the % change vs. baseline values for hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) in relation to BMI reduction, for both MGB/OAGB or SG (ΔFPG 0.7 and ΔHbA1c 0.4 for MGB/OAGB; ΔFPG 0.7 and ΔHbA1c 0.1 for SG). At multivariate analysis, high baseline HbA1c [odds ratio (OR) = 0.623, 95% confidence interval (CI) 0.419-0.925, p = 0.01], preoperative consumption of insulin or oral antidiabetic agents (OR = 0.256, 95% CI 0.137-0.478, p = <0.001), and T2DM duration >10 years (OR = 0.752, 95% CI 0.512-0.976, p = 0.01) were negative predictors whereas MGB/OAGB resulted as a positive predictor (OR = 3.888, 95% CI 1.654-9.143, p = 0.002) of diabetes remission. CONCLUSIONS: A significant BMI decrease and T2DM remission unrelated from weight loss were recorded for both procedures if compared to baseline values. At univariate and multivariate analyses, MGB/OAGB seems to outperform significantly SG. Four independent variables able to influence T2DM remission at 12 months have been identified.

Revision of failed primary adjustable gastric banding to mini-gastric bypass: results in 48 consecutive patients.

Although laparoscopic adjustable gastric banding (LAGB) has been found to be a generally successful weight loss operation, many patients require revision for weight regain, mechanical complications or intolerance to restriction. We report our experience with laparoscopic mini-gastric bypass (LMGB) as a revisional procedure for failed primary LAGB. From June 2007 to November 2012, 48 patients, who had undergone LAGB, underwent revisional surgery to LMGB. Patient demographics, reasons for band removal, interval between removal and LMGB, operative times, complications, change in comorbidities, and weight loss were collected. The revisions to a mini-gastric bypass (MGB) were completed laparoscopically in all cases except in four, when the MGB was deferred because of gastric tube damage. Mean age was 38 years (range 20-59) and BMI was 43.4 ± 4.2 kg/m(2); 82 % of patients were females. Revision was performed after a mean of 28.6 months. The mean hospital stay was 3.25 days. Within 60 days of the MGB, mortality and morbidity were nil. We observed a significant difference in mean BMI after 6 months' follow-up (P < 0.001). Diabetes remission was observed in 88 % of patients, apnea remission in 66 %, and hypertension remission in 66 % after LMGB (p < 0.001). Moreover, four patients with GERD were cured. All LAGB patients had positive outcomes after the conversion to MGB, with a mean gain of 1.7 points in the bariatric analysis and reporting outcome system questionnaire. Our results suggested that LMGB is a safe, feasible, effective and easy-to-perform revisional procedure for failed LAGB.

Sphingosine kinases signalling in carcinogenesis.

Sphingosine kinases (Sphk1 and 2) regulate the prodution of sphingosine-1-phosphate (S1P), that is key molecule in cancer development. SphK1, which is commonly overexpressed in malignant tumours, significantly contributes to the pathogenesis of various types of cancer as well as to resistance to different Tyrosine Kinase inibitors (TKIs). Even, SphK2 may promote apoptosis and inhibit cell growth but its role has not yet been fully understood in pathologic conditions. Different growth factorsinduced activation of receptor tyrosine kinases (RTKs) results in production of Sphk1 which catalyzes the phosphorylation of sphingosine. Such enzyme, in turn, is involved in many cellular processes by its five receptors. These are able to transactivate RTKs through amplification of a positive-feedback signaling loop. In conclusion, development of pharmacological inhibitors of SphK1 has been limited by the lack of completely understanding of the enzymatic activation mechanisms of SphK1.

The effects of pyrrolo[1,2-b][1,2,5]benzothiadiazepines in MEC1 cells.

Chronic Lymphocytic Leukemia (CLL) is the most common adult leukemia and is currently incurable. To expand the therapeutic armamentarium, we investigated antitumor activity of pyrrolo[1,2-b][1,2,5]benzothiadiazepine (PBTDs) in MEC1 cells. We found that PBTD (RS2778) treatment enhanced the activation of pro-apoptotic members, such as caspase-9, 3, poly (ADP-ribose) polymerase (PARP), and bax, but suppressed the activation of anti-apoptotic molecule BCL-2 in these cells. Furthermore, PBTD (RS2778)-induced autophagic cell death was verified by LC3-II conversion, and upregulation of Beclin-1 and ATG5. In addition, such compound impeded hyper phosphorylation of AKT as were determined by Western blot. In summary, PBTD (RS2778) inhibited viability and induced multiple cellular events including apoptosis, autophagic cell death, in human MEC1 cells. This distinct activity of PBTD (RS2778) against these cells suggests potential for PBTDs as a therapeutic agent for treatment of CLL.

Bypass mechanisms of resistance to tyrosine kinase inhibition in chronic myelogenous leukaemia.

Chronic myeloid leukaemia (CML) is a disease induced by the BCR-ABL oncogene. Tyrosine kinase inhibitors (TKIs) were introduced in the late 1990s and have revolutionized the management of CML. The majority of such patients can now expect to live a normal life providing they continue to comply with TKI treatment. However, in a significant proportion of cases, TKI resistance develops over time, requiring a change of therapy. Over the past few years, multiple molecular mechanisms of resistance have been identified and some common themes have emerged. One is the development of resistance mutations in the drug target that prevent the drug from effectively inhibiting the respective TK domain. The second is activation of alternative molecules that maintain the signalling of key downstream pathways despite sustained inhibition of the original drug target. In this mini-review, we summarize the concepts underlying resistance, the specific examples known to date and the challenges of applying this knowledge to develop improved therapeutic strategies to prevent or overcome resistance.