Gastrointestinal Uses of Botulinum Toxin.

Botulinum toxin (BT), one of the most powerful inhibitors that prevents the release of acetylcholine from nerve endings, represents an alternative therapeutic approach for "spastic" disorders of the gastrointestinal tract such as achalasia, gastroparesis, sphincter of Oddi dysfunction, chronic anal fissures, and pelvic floor dyssynergia.BT has proven to be safe and this allows it to be a valid alternative in patients at high risk of invasive procedures but long-term efficacy in many disorders has not been observed, primarily due to its relatively short duration of action. Administration of BT has a low rate of adverse reactions and complications. However, not all patients respond to BT therapy, and large randomized controlled trials are lacking for many conditions commonly treated with BT.The local injection of BT in some conditions becomes a useful tool to decide to switch to more invasive therapies. Since 1980, the toxin has rapidly transformed from lethal poison to a safe therapeutic agent, with a significant impact on the quality of life.

True aneurysm of the proximal occipital artery: Case report.

INTRODUCTION: True aneurysms of the proximal occipital artery are rare, may cause neurological symptoms due to compression of the hypoglossal nerve and their resection may be technically demanding. PRESENTATION OF CASE: The case of an aneurysm of the proximal occipital artery causing discomfort and tongue deviation by compression on the hypoglossal nerve is reported. Postoperative course after resection was followed by complete regression of symptoms. CONCLUSION: Surgical resection, as standard treatment of aneurysms of the occipital artery, with the eventual technical adjunct of intubation by the nose is effective in durably relieving symptoms and preventing aneurysm-related complication.

Liver resection for metastases from colorectal cancer in very elderly patients: New surgical horizons.

INTRODUCTION AND AIM: Patients with colorectal cancer (CRC) may develop liver metastases. Surgical resection remains the best treatment of choice for colorectal liver metastases (CRLM) according to resectability criteria, with a long-term survival of 25% up to 41% after 5 years. Advanced age is associated with a higher incidence and co-morbidity, particularly cardiovascular disease, as well as deteriorating physiological reserves. The aim of this study was to analyse the overall and disease-free survival for patients with CRLM according to their chronological age. METHODS: Patients with CRLM were enrolled in the study. Data on gender, age, co-morbidity, metastasis characteristics (number, size and total metastatic volume (TMV)), use of perioperative chemotherapy and operative and post-operative complications were collected. Then, according to recent World Health Organization (WHO) guidelines, the patients were grouped by age. Statistical analysis was performed using the software R (ver. 2.14.1). RESULTS: Hepatic resection was performed in 149 patients (21 patients in the very elderly group, 79 in the elderly group and 49 in the younger group). The three groups were comparable in terms of operative duration, transfusion rate, length of high-dependency unit (HDU) stay and post-operative hospital stay. The very elderly group showed a non-significant increase in post-operative morbidity. The 30-day and 60-day/inpatient mortality rates increased with age without any significant statistically difference between the three groups (very elderly group 4.8% and 4.8%; elderly group: 2.5% and 3.8%; and younger group 0% and 2%). At 5 years, the overall survival was 28.6% for very elderly patients (≥75 years), 33.3% for elderly patients (≥65 to <75 years) and 43.5% for younger patients (≤65 years). The 1-, 3- and 5-year disease-free survival was similar across the groups. CONCLUSIONS: Liver resection for CRLM in carefully selected patients above the age of 75 can be performed with acceptable morbidity and mortality rates, similar to those in younger patients. Moreover, the severity of CRLM in elderly patients is proven to be lesser than in younger patients. Thus, we can conclude that advanced chronological age cannot be considered a contraindication to hepatic resection for CRLM.

Resection of hepatocellular carcinoma in elderly patients and the role of energy balance.

INTRODUCTION: Progressive functional impairment with age has a significant impact on perioperative risk management. Chronic liver diseases induce a strong oxidative stress; in the elderly, in particular, impaired elimination of free radicals leads to insufficient DNA repair. The events associated with a weak response to growth factors after hepatectomy leads to a decline in liver regeneration. Hypercholesterolemia is highly prevalent in the elderly, which may alter the coenzyme Q10 (CoQ) levels and in turn the cellular energy balance. This condition is commonly treated with statins. The aim of this study is to investigate the role of preoperative cellular energy balance in predicting hepatocellular carcinoma (HCC) postresection outcomes. MATERIALS AND METHODS: In a 5-year period (2009-2013), elderly patients with hypercholesterolemia, cardiovascular disease, and diabetes mellitus, undergoing HCC resection, were recruited and grouped by age (<75 and ≥ 75 years old). All patients were previously treated with statins. The risk factors associated with hospital morbidity/mortality and prolonged length of stay (LOS) were evaluated. RESULTS: Forty-five elderly patients were recruited and grouped according to their treatment: Group 1 (n = 23) was treated with statins alone (control group), whereas Group 2 (n = 22) was treated with statins and a CoQ analogue, 3 weeks from the surgery and at least a month later (experimental group). The majority of our patients were treated with atorvastatin [n = 28 (53.84%)] and the minority with simvastatin [n = 17 (32.69%)], 20 mg/day, for at least 3 years before the surgery. Perioperative mortality was observed in one patient of Group 1 (4.3%). Morbidities were noted in 13 patients of Group 1 (56.5%) and four patients of Group 2 (18.2%). The control group showed delayed functional recovery, muscle weakness, increased infection rate, and pleural effusion due to prolonged bed rest (hospital stay 13 days (7-19) vs. 8.5 days (5-12)), compared with the experimental group. The overall survival at 5 years was similar for both groups (n = 10 patients (43%) in Group 1 vs. n = 10 patients (45%) in Group 2). CONCLUSION: In the elderly population, survival is closely linked to postoperative morbidity and mortality. In our study, prolonged LOS was found to be related to delayed bioenergetic recovery. When limited, risk factors such as infections, neutropenia, and red blood cell transfusions could lower LOS and mortality of elderly patients with HCC. Higher age was associated with greater postoperative morbidity and successful hospital stay.

Hepatic ischemia reperfusion injury: A systematic review of literature and the role of current drugs and biomarkers.

Hepatic ischemia reperfusion injury (IRI) is not only a pathophysiological process involving the liver, but also a complex systemic process affecting multiple tissues and organs. Hepatic IRI can seriously impair liver function, even producing irreversible damage, which causes a cascade of multiple organ dysfunction. Many factors, including anaerobic metabolism, mitochondrial damage, oxidative stress and secretion of ROS, intracellular Ca(2+) overload, cytokines and chemokines produced by KCs and neutrophils, and NO, are involved in the regulation of hepatic IRI processes. Matrix Metalloproteinases (MMPs) can be an important mediator of early leukocyte recruitment and target in acute and chronic liver injury associated to ischemia. MMPs and neutrophil gelatinase-associated lipocalin (NGAL) could be used as markers of I-R injury severity stages. This review explores the relationship between factors and inflammatory pathways that characterize hepatic IRI, MMPs and current pharmacological approaches to this disease.

The impact of BMI on early colorectal neoplastic lesions and the role of endoscopic diagnosis:. An Italian observational study.

INTRODUCTION: CRC often arises from polyps: an early detection and resection are effective in decreasing both incidence and mortality rate. Relation between risk factors, adenomas and CRC have been showed, but there is little evidence for overweight association with preneoplastic lesions. This study analyzed the correlation between body mass index (BMI) and primitive site of polyps. METHODS: We performed a retrospective study, in a period between January 2010 and October 2014. Subjects aged 50 years and older who underwent their first-time screening colonoscopy were included. Reports regarding characteristic of the polyps were collected. RESULTS: 142 patients were enrolled and they were divided into two groups: group I - patients with left sided colonic polyps, and group II - patients who right sided colonic polyps. The ANOVA test-one way, documents a difference between the BMI and the colon localization of polyps. CONCLUSIONS: Patients with overweight had a higher risk to develop lesions in the left colon compared to patients with normal weight. Despite the fact that Italian epidemiological studies have found a prevalence of polyps of 44-53% in rectal-sigmoid segment, 32-36% in transverse segment and of 14-20% in right segment, we showed an incidence of 26.05% for right sided polyps, which maybe related with the eating habits of the territory.

Study on the efficacy of surgery of the superficial venous system and of compression therapy at early stages of chronic venous disease for the prevention of chronic venous ulceration.

The mainstay of treatment of chronic venous ulceration (CVU), as also suggested by current treatment guidelines for chronic venous disease (CVD), is represented by surgery and compression therapy for which there is strong evidence of their role in clinically relevant improvement in wound healing and also in the reduction of CVU recurrence, but no information is available as to whether or not these treatments provide effective protection from the onset of CVU. In our study, we have followed, for a median time of 13 years, a total of 3947 patients with CVD at classes C2-C3 of CEAP classification, treated with our treatment protocol (surgery and compression therapy) in order to track the natural history of these patients with regards to CVU development. We identified four groups of patients: 2354 patients (59·64%) (Group A) fully adherent to protocols; 848 patients (21·48%) (Group B) fully adherent to surgery and non-compliant to compression therapy; 432 patients (10·95%) (Group C) fully adherent to compression therapy and non-compliant to surgery; and 313 patients (7·93%) (Group D) non-compliant to either treatments. Regardless of compliance to treatments, the ulcer development rates were very similar between groups (range: 3·23-4.79%), with no statistical significance (P = 0·1522). Currents treatments used in the early stages of CVD appear to have no effects to progression to CVU. Additional longitudinal studies are required to confirm these findings.

Updates in Pathophysiology, Diagnosis and Management of Takayasu Arteritis.

BACKGROUND: Takayasu arteritis (TA) is a rare, systemic, inflammatory vasculitis of granulomatous nature, and still of unknown etiology. It mainly involves the aorta and its major branches and is more commonly seen in women of childbearing age and Asians. TA leads to stenosis, occlusion, or aneurysmal degeneration of large arteries, and its pathogenesis seems to be mainly due to an abnormal cell-mediated immunity, although other molecular and genetic abnormalities may contribute. The diagnosis and treatments lie on clinical and arteriographic findings. Because of its fluctuating course, both clinical scores and biomarkers are currently evaluated. The aim of this review is to report a comprehensive and methodologically robust state of the art about Takayasu arteritis, including the latest data and evidences in the definition, epidemiology, pathogenesis and etiology, clinical manifestations and classification, diagnosis, assessment of disease activity and progression, biomarkers, and treatment. METHODS: We searched all publications addressing definition, epidemiology, pathogenesis, etiology, classification, diagnosis, biomarkers, and treatment of TA. Randomized trials, cohort studies, and reviews were contemplated to give a breadth of clinical data. PubMed and Scopus were searched from August 2010 to November 2015. RESULTS: Of the 3,056 records found, 267 matched our inclusion criteria. After reading the full-text articles, we decided to exclude 169 articles because of the following reasons: (1) no innovative or important content; (2) no multivariable analysis; (3) insufficient data; (4) no clear potential biases or strategies to solve them; (5) no clear end-points; and (6) inconsistent or arbitrary conclusions. The final set included 98 articles. CONCLUSIONS: This review presents the last updates in all fields of Takayasu arteritis. Still today, large areas of TA pathogenesis and disease-activity assessment need to be further investigated to better treat patients with TA.

Optimizing Patient Surgical Management Using WhatsApp Application in the Italian Healthcare System.

INTRODUCTION: Smartphones changed the method by which doctors communicate with each other, offer modern functionalities sensitive to the context of use, and can represent a valuable ally in the healthcare system. Studies have shown that WhatsApp™ application can facilitate communication within the healthcare team and provide the attending physician a constant oversight of activities performed by junior team members. The aim of the study was to use WhatsApp between two distant surgical teams involved in a program of elective surgery to verify if it facilitates communication, enhances learning, and improves patient care preserving their privacy. METHODS: We conducted a focused group of surgeons over a 28-month period (from March 2013 to July 2015), and from September 2014 to July 2015, a group of selected specialists communicated healthcare matters through the newly founded "WhatsApp Surgery Group." Each patient enrolled in the study signed a consent form to let the team communicate his/her clinical data using WhatsApp. Communication between team members, response times, and types of messages were evaluated. RESULTS: Forty six (n = 46) patients were enrolled in the study. A total of 1,053 images were used with an average of 78 images for each patient (range 41-143). 125 h of communication were recorded, generating 354 communication events. The expert surgeon had received the highest number of questions (P, 0.001), while the residents asked clinical questions (P, 0.001) and were the fastest responders to communications (P, 0.001). CONCLUSION: Our study investigated how two distant clinical teams may exploit such a communication system and quantifies both the direction and type of communication between surgeons. WhatsApp is a low cost, secure, and fast technology and it offers the opportunity to facilitate clinical and nonclinical communications, enhance learning, and improve patient care preserving their privacy.

The role of adult tissue-derived stem cells in chronic leg ulcers: a systematic review focused on tissue regeneration medicine.

Wound healing is an articulated process that can be impaired in different steps in chronic wounds. Chronic leg ulcers are a special type of non-healing wounds that represent an important cause of morbidity and public cost in western countries. Because of their common recurrence after conventional managements and increasing prevalence due to an ageing population, newer approaches are needed. Over the last decade, the research has been focused on innovative treatment strategies, including stem-cell-based therapies. After the initial interest in embryonic pluripotent cells, several different types of adult stem cells have been studied because of ethical issues. Specific types of adult stem cells have shown a high potentiality in tissue healing, in both in vitro and in vivo studies. Aim of this review is to clearly report the newest insights on tissue regeneration medicine, with particular regard for chronic leg ulcers.

Symptoms in patients with skin changes due to chronic venous insufficiency often lead to emergency care service: an Italian observational study.

Chronic venous insufficiency (CVI) is the most advanced form of chronic venous disease (CVD), and is often associated with skin changes such as hyperpigmentation, eczema, lipodermatosclerosis and venous skin ulceration that cause discomfort, pain, sleep disturbances, absenteeism in the workplace, disability and deteriorated quality of life (QoL). The purpose of this study is to evaluate the prevalence of CVI and skin changes in patients who turn to Continuous Assistance Services due to the presence of disturbing symptoms of their condition. Data were evaluated by consulting the medical records, during a 16-month period, available with three Continuous Assistance Services of the Italian territory. The overall population of the referring centres consisted of 1186 patients [739 females (62·31%) and 447 males (37·69%)]. Seventy-nine patients (6·66%) consulted the emergency unit for venous symptoms related to CVD. Patients with more severe disease (CVI, categories C4-C6) represented the majority accounting for 60·75%, while patients with moderate disease (C3) accounted for 35·44% and patients with mild disease (C1-C2 stages) accounted for 3·79%. The main finding of this study is that despite CVI not being a disease that commonly requires medical emergency/urgency intervention, patients with CVI, especially in advanced stage with skin changes, may turn to Continuous Assistance Service for treating bothersome symptoms related to their condition.

Metastases of pancreatic adenocarcinoma: A systematic review of literature and a new functional concept.

INTRODUCTION: Pancreatic cancer, especially Pancreatic Adenocarcinoma, is still associated with a high mortality and morbidity for affected patients notwithstanding considerable progresses in diagnosis and both surgical pharmacological therapy. Despite metastases from colorectal, gastric and neuroendocrine primary tumor and their treatment are widely reported, the literature has been rarely investigated the impact of localization and numbers of pancreatic metastases. This study performed a systematic analysis of the most recent scientific literature on the natural history of Pancreatic Adenocarcinoma focusing attention on the role that the "M" parameter has on a possible prognostic stratification of these patients. MATERIAL AND METHODS: PubMed and Science Direct databases were searched for relevant articles on these issue. RESULTS: Initial database searches yielded 7231 studies from PubMed and 29101 from Science Direct. We evaluated 1031 eligible full text articles. CONCLUSIONS: An updated insight into the world of Pancreatic Tumors might help physicians in better evaluating mechanisms of metastases, patients selection and survival and in programming appropriate interventions to modify the worst outcomes of advanced disease.

Surgical resection of synchronous and metachronous metastases from pancreatic adenocarcinoma. Two case reports in the light of recent evidences.

UNLABELLED: Pancreatic ductal adenocarcinoma is the fourth leading cause of cancer-related mortality in the western countries for both men and women. Until in 2015, it remains one of the most challenging malignancies with a dismal prognosis and limited therapeutic options. The 5-year survival rate for pancreatic cancer is around 5%, which is the lowest among all different cancer sites. The poor prognosis of PDAC is largely attributed to delayed diagnosis due to nonspecific symptoms in the early stages of the disease, biological aggressiveness leading to rapid metastases, lack of effective screening methods, and resistance to radiation and chemotherapies. In the event of metastases, patients were traditionally referred to palliative treatments. Thanks to continuous progresses in the surgical expertise, synchronous and metachronous metastases resections seem technically feasible nowadays. These reports describe 2 several clinical cases in which patients with Pancreatic Adenocarcinoma, and synchronous and metachronous liver metastases respectively, were treated with a surgical approach. Patients showed a better survival rate compared current data in the literature. Our results, often in conflict with the guidelines and recent evidences, confirm the need for a new vision of the metastases "problem" in patients with Pancreatic Adenocarcinoma. KEY WORDS: Metastases, Pancreatic Adenocarcinoma, Surgical resection.

Seven-year survival after pancreaticoduodenectomy for early recurrent renal cell carcinoma involving the duodenum A case report.

UNLABELLED: RCC has a range of clinical manifestations including vague abdominal symptoms, haematuria, flank pain and a palpable abdominal mass. Generally, 25-30% of patients are found to have metastases at diagnosis but a further 30-50% of patients with local disease will develop metastases during the course of their illness. Spread in RCC is lymphatic, haematogenous, transcoelomic or by direct invasion and the most common sites of metastasis in RCC are the lung, lymph nodes, bones and liver. Metastasis to the small intestine is rare and the duodenum is the segment least often affected. RCC metastasis to the duodenum occurs most commonly in the periampullary region, followed by the bulband usually manifest as gastrointestinal bleeding or obstruction. Bleeding may be the first symptom of metastatic disease in patients who have previously undergone nephrectomy for RCC. Survival is better for patients with localized disease compared with those with regional and distant metastases. This report describes a case of duodenal metastasis from RCC in which the patient presented with upper gastrointestinal bleeding and duodenal obstruction and was treated with pancreaticoduodenectomy with an excellent long-term outcome. Long-term survival was better than survival data reported in the current literature. . KEY WORDS: Duodenal metastasis, Gastrointestinal bleeding, Renal cell carcinoma, Pancreaticoduodenectomy.

Portal blood arterialization with an extracorporeal device to treat toxic acute hepatic failure in a swine model.

PURPOSE: This study aimed to determine whether a controlled portal blood arterialization by a liver extracorporeal device (L.E.O2 NARDO) is effective in treating acute hepatic failure (AHF) induced through CCl4 administration in a swine model. METHODS: 20 swine with AHF induced by intraperitoneal injection of carbon tetrachloride (CCl4) in oil solution, were randomly divided into two groups: animals receiving L.E.O2 NARDO treatment 48 h after the intoxication (study group); animals sham operated 48 h after the intoxication (control group). Blood was withdrawn from the iliac artery and reversed in the portal venous system by an interposed extracorporeal device. Each treatment lasted 6 h. The survival was assessed at 5 days after L.E.O2 NARDO treatment or sham operation. In both groups blood samples were collected for biochemical analysis at different time points and liver biopsies were collected 48 h after intoxication and at sacrifice. RESULTS: We observed decreased transaminases levels and a more rapid INR recovery in the study group, as compared to the control group. Eight animals of the study group vs. two animals of the control group survived at five days after surgery with a statistically significant difference (p<0.05). Liver biopsies performed at sacrifice showed a reduction of the damaged hepatic areas in the study group as compared to the control group. CONCLUSIONS: Arterial blood supply in the portal system through the L.E.O2 NARDO device is easily applicable, efficacious, and safe in a swine model of AHF induced by CCl4 intoxication.