Focusing on Diabetic Ulcers.

Foot ulcers associated with Diabetes mellitus require immediate attention due to risk of amputation if left untreated. Herein we focus on the mitigating risk factors and physiopathology of the diabetic foot, recounting our own surgical approach and revascularization procedures.

Acute Deep Vein Thrombosis and Pulmonary Embolism: is the Thromboaspiration Device an Appropriate Choice?

Nowadays patients affected by deep vein thrombosis (DVT) and pulmonary embolism (PE) are studied widely but the challenge for physicians is when and how they are to be treated. Most patients present serious comorbidities that can potentially make treatment difficult. An increasing cohort of patients cannot be treated with systemic fibrinolysis but fortunately today, physicians can utilize a number of different instruments to resolve acute DVT and PE.

Novel therapeutics for the treatment of familial Mediterranean fever: from colchicine to biologics.

Familial Mediterranean fever (FMF), an inherited autosomal recessive disorder, is characterized by sporadic, paroxysmal attacks of fever and serosal inflammation, lasting 1-3 days. Patients may develop renal amyloidosis, arthritis, serositis, and skin and oral lesions. Diagnosis is based on clinical features, response to treatment with colchicine, and genetic analysis. Colchicine prevents attacks and renal amyloidosis, in addition to reversing proteinuria. Nonresponders may receive novel therapy, including interleukin (IL)-1 receptor antagonists and IL-1 decoy receptor. Recently, new options have been considered.

Unexpected discovery of massive liver echinococcosis. A clinical, morphological, and functional diagnosis.

We report a case of symptomatic massive liver echinococcosis due to Echinococcus granulosus, unexpectedly found in a 34 year old woman living in Apulia, Italy. Based on size (max diameter 18 cm), clinical presentation, geographical area, and natural history of echinococcosis, we estimate that the initial infection should have occurred 9-20 yrs before. Presenting symptoms were those of typical mass effect with RUQ pain, pruritus, malaise, and recent weight loss. Abdominal ultrasound diagnosis of probable echinococcal cyst was subsequentely confirmed by positive serology and further detailed by radiological imaging. The cyst was massively occupying subdiaphragmatic liver segments and extending to the omentum and the stomach. The characteristics of the lesion were compatible with the WHO 2003 classification type CE2l, indicating a large active fertile cyst with daughter cysts. The cyst was successfully treated with medical therapy followed by surgery. The prevalence, diagnostic workup, management, and costs of echinococcosis are discussed in this case presentation.

AAA with a challenging neck: early outcomes using the Endurant stent-graft system.

OBJECTIVES: The efficacy and safety of endovascular aneurysm repair is disputable in aneurysms with a short, angulated, wide, conical, or thrombus-lined neck making a reliable seal difficult to achieve. The influence of a challenging neck on early results using the Endurant stent-graft system in high risk patients was investigated. MATERIALS AND METHODS: A retrospective study conducted on a prospectively compiled database of 72 elective patients with challenging neck treated with the Endurant system (Endurant Stent Graft, Medtronic AVE, Santa Rosa, CA, USA). These patients were compared to a control group (n = 65) without significant neck problems. Endpoints were early technical and clinical success, deployment accuracy and differences in operative details at one month follow-up. Data are reported as mean and standard deviation or as absolute frequency and percentage (%). Normality distribution and homogeneity of variances were tested by Shapiro-Wilks and Levene tests, respectively. Inter-group comparisons for each variable were made by t-test or χ2-test or Fisher exact test. A p < 0.05 was considered statistically significant. RESULTS: Mean age was 76.12 years; 76.6% were males. Risk factors and pre-operative variables did not differ significantly between the two groups. Mean neck length was 10.56 mm in patients with challenging anatomies and 22.85 mm in controls. Patients with a challenging neck differed significantly (p < 0.001) from controls in terms of mean infrarenal (37.67° vs. 20.12°) and suprarenal angle (19.63° vs. 15.57°); 82% of patients with a challenging neck were ASA III/IV (vs. 86%). Technical success was 100%, with four unplanned proximal extension in challenging group. No type I endoleaks or aneurysm-related deaths occurred in either group; major complications were 1.54% vs. 1.39% (p = 0.942). Operative details were similar in both groups. CONCLUSION: Treatment with the Endurant stent-graft is technically feasible and safe, yielding satisfactory results even in challenging anatomies. Medium- and long-term data are needed to verify durability, but early results are promising.

Benefit of revascularisation to critical limb ischaemia patients evaluated by a patient-oriented scoring system.

OBJECTIVES: The concept of patency and limb salvage are physician-oriented endpoints in critical limb ischaemia (CLI). These endpoints have failed to enhance function after revascularisation. The aim of this study was to create a scoring system to predict 1-year functional status and to assess the benefit to patients possible by revascularisation. MATERIALS AND METHODS: During the period 2007-2009, 480 consecutive patients (mean age ± SD, 83.2 ± 8.7 years) underwent repair for CLI. Preoperative, operative and functional status characteristics and post-operative outcomes were recorded. The following patient-oriented outcomes were investigated pre- and postoperatively: basic and instrumental activities of daily living (BADL and IADL) and ambulatory and living status. Statistical analysis was performed to assess predictors of functional benefit from revascularisation. The variables significant on multivariable analysis were used to generate a scoring system to pre and postoperatively grade individual patient risk of losing baseline functional status at 1 year (CLI functional score). RESULTS: Ninety-three of 480 patients (19.3%) were in Rutherford class IV, 208 (43.3%) in class V and 179 (37.4%) in class VI. Surgical, endovascular and hybrid operations were performed in 108 (22.5%), 319 (66.5%) and 53 (11%) patients, respectively; mean follow-up was 408 ± 363 days. Improved or unchanged functional status was observed in 276 patients (57.5%). Preoperative mean ± SD BADL and IADL (4.26 ± 1.98 and 3.92 ± 2.69, respectively) were modified from mean values at 1-year follow-up (4.19 ± 2.06 and 4.12 ± 3, respectively) (p = 0.401 and p < 0.05, respectively). In the same time interval, mortality was 50%, limb salvage 50.4%, CLI-related new hospitalisations 50.8%, relief of symptoms 18.5% and tissue healing 14.5%. A CLI functional score of >80% indicates that patients are likely to lose functional abilities and require assistance for ambulation or ADL, as well as risking outcomes such as major amputation, new CLI-related hospitalisation or re-operation (p < 0.001). Preoperative poor living status, dependence in daily activities, advanced local disease (lesion >2 cm, infection and poor tibial runoff), American Society of Anesthesiologists (ASA) score > II, previous cerebrovascular event and heart disease were the strongest pre-operative negative predictors of losing baseline functional status. Major amputation was the only negative post-operative predictor. CONCLUSIONS: Considering patient-oriented outcomes, our study showed that revascularisation could be worthwhile in nearly 60% of CLI patients. A non-revascularisation strategy such as primary amputation or palliation could be indicated in patients with a poor pre-operative living status, dependence for daily activities, advanced local disease, extensive comorbid conditions and a score >80%. To make our findings generalisable, the score needs to be validated in independent cohorts at different centres before it can be recommended for application.

Primary amputation: is there still a place for it?

Diabetic foot (DF) continues to present a significant challenge to the vascular surgeon. Despite great advances in the treatment of DF, including open revascularization and endovascular techniques, significant numbers of amputations are still performed. The effect of aggressive revascularization on ultimate limb salvage rates continues to be debated. In the US the amputation rate has increased from 19 to 30 per 100000 persons years over the last two decades primarily due to an increase in diabetes and advancing age. Despite advances in cardiovascular treatment, in patients over 85 year of age an amputation rate of 140 per 100000 persons/year has been reported with a primary amputation (PA) still carrying an excessively high mortality rate of 13-17%. Amputation has been historically regarded as a life saving therapeutic measure. At the time the advances of surgical techniques in revascularization, diagnostic modalities and effectiveness in antimicrobial agents have unintentionally designated amputation to be the last treatment option. Nowadays we have a variety of therapeutic options to correct, modify, or circumvent the obstructive vascular pathology, such as angioplasty, atherectomy, stenting, stent graft and the traditional open surgical approach using endarterectomy, patch angioplasty, or bypass revascularization and even sympathectomy to enhance cutaneous perfusion to the toes. However it is understandable that many older patients who have received multiple limb preservation procedures have spent most of the remaining days of their lives in and out of the hospital or in a long-term care facility where high technical and sophisticated wound care techniques can be provided.

Renal aneurysms: surgical vs. endovascular treatment.

Renal artery aneurysms (RAA) are rare (general population incidence is 0.09%). At this time, the appropriateness of the type of intervention ­ surgical or endovascular ­ is based on single center experiences rather than large randomized trials. Endovascular therapy offers less morbidity but surgery has excellent long-term results. In reality, the choice of the treatment relies on the operative risk. A patient with a RAA and good surgical risk should be offered open surgery. If the patient is deemed to be at high risk from surgery then the choice of the type of endovascular treatment (stent grafting, coil/glue embolization, multilayer stenting) should be based on the location and shape of the RAA. RAA should be treated by surgeons/interventionalists who have demonstrated expertise in renal artery procedures.

Open vascular surgery as a starting point for endovascular surgery.

What distinguishes vascular surgeons from other specialists who treat patients with vascular disease is their ability to combine skills in both open and endovascular treatments. Open vascular surgery should be considered the "starting point" for endovascular surgery, since training and practice in vascular surgery require extensive knowledge of the basic science and a thorough education in general surgical techniques. In addition, surgeons must possess detailed specialized knowledge of the anatomy and physiology of arteries, veins and lymphatics and of the pathological processes which may affect them. This scientific and technical background is also imperative for endovascular surgery. Open vascular surgery can also be considered as a potential finishing point of endovascular surgery. In fact, open surgery is still often the only solution for complex cases considered unsuitable for an endovascular approach, or for different types of complications following endovascular treatments. As endovascular surgery is increasingly considered as the initial treatment option for many patients with vascular disease, it is crucial that vascular surgery training programs develop methods to maintain the open surgical skills of their trainees. The only way for vascular surgeons to remain the premier specialists to care for patients with vascular disease is for them to combine skills in both open and endovascular treatments.

Hybrid procedures for acute limb ischemia.

The most efficient treatment for acute arterial embolism is operative embolectomy using Fogarty's balloon catheter, especially if a single large artery is involved. Unfortunately, although the early surgical success of arterial thromboembolectomy often seems acceptable, the early clinical outcome still remains unsatisfactory. This may be related to the incomplete restoration of perfusion (i.e., residual thrombus in distal vessels not reached by the balloon catheter thromboembolectomy), propagation of residual thrombi or presence of underlying steno-occlusive lesions. In such a situation a meticulous intraoperative assessment of the adequacy of clot removal is decisive. Residual thrombus, chronic atherosclerotic disease and even vessel injuries secondary to balloon catheter passage can be corrected by endovascular techniques (hybrid procedures). The combination of surgical and endovascular options may overcome the limitations that characterize the traditional approach, and it is likely that in the future many treatments will be a mix of techniques that can be performed by vascular surgeons in the operating room or in a dedicated endovascular suite. This review article summarizes the hybrid treatment options for acute arterial occlusion caused by either embolism or local thrombosis.

Endovascular approach for ruptured abdominal aortic aneursyms.

The rupture of an abdominal aortic aneurysm (rAAA) causes about 15000 deaths/year in the USA alone. Even though over the last 50 years progress in surgical techniques and in postoperative intensive care have been outstanding, the analysis of registries has shown either no decrease in the mortality rate for surgically treated rAAAs. Some reports asserted better out come for endovascular repair (EVAR) compared with surgery in case of rAAA. Despite this evidence, EVAR for rAAA remains prerogative of few centers worldwide. In conclusion only larger study or registry could assest the real role of EVAR in the management of rAAA.

Biliary proteins and their redox status changes in gallstone patients.

BACKGROUND: Proteins might act as pronucleating agents of cholesterol crystallization in bile. However, little is known about the redox status of biliary proteins in humans and their interaction with crystallization of biliary cholesterol. MATERIALS AND METHODS: Gallbladder biles were obtained at cholecystectomy from 86 symptomatic patients with either cholesterol gallstones (32 multiple and 32 solitary stones) or pigment stones (n = 22), and studied for protein redox status [carbonyl and sulfhydryl (PSH) concentrations], total lipid and protein levels and cholesterol saturation index (CSI). First appearance of cholesterol crystals in ultrafiltered bile (crystal observation time, COT) was studied with polarizing light microscopy during 21 days. RESULTS: Patients with cholesterol stones had significantly shorter COT (3 days vs. >21 days, P < 0.05), higher CSI (149 +/- 10% vs. 97 +/- 7%, P < 0.05) and higher total biliary proteins (1.96 +/- 0.1 mg mL(-1) vs. 0.55 +/- 0.1 mg mL(-1), P < 0.05) than patients with pigment stones. Patients with cholesterol stones had significantly lower (P < 0.05) level of protein sulfhydryl concentrations (18 +/- 4 nmol mg(-1) protein vs. 49 +/- 16 nmol mg(-1) protein), while total lipid and carbonyl proteins concentrations were similar between cholesterol and pigment stone patients. Crystallization probability was influenced by the number/type of gallstones (multiple > solitary > pigment stones, P = 0.009) and total protein concentration (high > low levels, P = 0.004). COT was negatively correlated with total protein content (r = -0.45, P = 0.03). CONCLUSIONS: Biles with cholesterol stones show high CSI and total protein concentration, and rapid COT, which is even faster in patients with multiple stones and high protein concentration. Low PSH levels in cholesterol stone patients point to a biochemical shift, potentially able to affect cholesterol crystallization.

Expression and localisation of insulin receptor substrate 2 in normal intestine and colorectal tumours. Regulation by intestine-specific transcription factor CDX2.

BACKGROUND AND AIMS: Self-renewal and differentiation of intestinal epithelium is a tightly regulated process, whose perturbations are implicated in human colorectal tumourigenesis. The insulin/insulin-like growth factor (IGF) signalling pathway may play an important role in intestinal epithelium homeostasis. Insulin receptor substrate 2 (IRS2) is a poorly characterised component in this pathway. METHODS: Using complementary in vitro and in vivo human and murine models, expression (mRNA and protein levels), localisation (immunohistochemistry) and regulation of IRS2 were investigated in the normal intestine and colorectal tumours. In silico analysis of the human IRS2 promoter was performed together with reporter and chromatin immunoprecipitation assays. RESULTS: Significant IRS2 expression was detected in the intestine, with specific protein localisation in the villus region of the ileum and in the surface epithelium of the colon. In human HT29 and Caco2 cells, IRS2 mRNA levels increased with spontaneous and induced differentiation, together with CDX2 (caudal-related homeobox protein 2), P21 and KLF4 (Krüppel-like factor 4). Adenoviral infection with human CDX2 induced IRS2 expression in APC- (adenomatous polyposis coli) and beta-catenin-mutated cells. On the other hand, IRS2 downregulation was observed in differentiated enterocytes after adenoviral infection with short hairpin CDX2 (shCDX2), in the intestine of CDX2 heterozygous mice and in colorectal tumours of Apc(Min/+) and patients with familial adenomatous polyposis (FAP). The human IRS2 promoter region presents several CDX2-binding sites where CDX2 immunoprecipitated in vivo. IRS2 reporters were functionally activated via CDX2 and blocked via a dominant-negative CDX2 protein. CONCLUSIONS: Combining gain- and loss-of-function approaches, an intriguing scenario is presented whereby IRS2 is significantly expressed in the apical intestinal compartment and is directly controlled by CDX2 in normal intestine and tumours.

Beneficial effects of oral tilactase on patients with hypolactasia.

BACKGROUND: A lactose-free diet is commonly prescribed to subjects with hypolactasia. We tested the effectiveness of a single ingestion of tilactase (a beta-D-galactosidase from Aspergillus oryzae) in adults with hypolactasia, previously assessed by lactose H(2)-breath test. MATERIALS AND METHODS: After measurement of orocecal transit time (OCTT, by lactulose H(2)-breath test) and lactose H(2)-breath testing plus placebo, a total of 134 subjects were positive to hypolactasia and underwent lactose H(2)-breath testing plus either low (6750 U) or standard (11,250 U) doses of tilactase. The appearance of gastrointestinal symptoms during the tests was monitored. RESULTS: OCTT was longer in malabsorbers (subjects without bloating, abdominal pain and/or diarrhoea, n = 25) than in intolerants (bloating, abdominal pain and/or diarrhoea, n = 109, P < 0.02). Malabsorbers had longer time to H(2) peak (P < 0.03), lower H(2) peak levels (P < 0.002) and smaller integrated H(2) excretion levels (P < 0.005) than intolerants. After tilactase ingestion, integrated H(2) levels were decreased by 75% (low dose) and 87% (standard dose) in malabsorbers, and by 74% (low dose) and 88% (standard dose) in intolerants. In the latter group, total symptom score were decreased by 76% (low dose) and by 88% (standard dose) (P < 0.0001). CONCLUSION: A single oral administration of tilactase is highly effective in decreasing symptoms and hydrogen excretion of hypolactasia assessed by lactose H(2)-breath test. If confirmed by long-term observations, ingestion of tilactase might be a better option than exclusion diets in intolerant subjects with hypolactasia.

Severe liver steatosis correlates with nitrosative and oxidative stress in rats.

BACKGROUND: Little is known about nitric oxide (NO) metabolism and redox changes with hepatocyte adipocytic transformation. The aims of this study were to investigate the changes occurring in plasma and hepatic NO metabolites and redox balance in a rat experimental model of simple fatty liver, and to relate plasma with hepatic and mitochondrial changes at different degrees of steatosis. MATERIALS AND METHODS: Circulating and hepatic redox active and nitrogen regulating molecules thioredoxin, glutathione, protein thiols (PSH), mixed disulfides (PSSG), NO metabolites nitrosothiols, nitrite plus nitrate (NOx), and lipid peroxides (TBARs) were measured in rats fed a choline deprived (CD) diet for 30 days. RESULTS: At histology, the CD diet resulted in hepatocellular steatosis (75% of liver weight at day 30) with no signs of necro-inflammation. In plasma, thioredoxin, nitrosothiols and NOx were unchanged, while TBARs levels increased significantly and were positively related with hepatic TBARs (r = 0.87, P < 0.001) and lipid content (r = 0.90, P < 0.001). In the liver, glutathione initially increased (day 3) and then decreased. From day 14, PSH decreased and NO derivatives increased. Thioredoxin 1 had initially increased (days 7-14) and then decreased. In the mitochondria, on day 14, nitrosothiols were inversely related to thioredoxin 2 (r = 0.988, P < 0.05); on day 30, PSH were decreased by 70%, PSSG were doubled and related with nitrosothiols levels (r = 0.925, P < 0.001). CONCLUSION: Adipocytic transformation of hepatocytes is accompanied by major interrelated modifications of redox parameters and NO metabolism especially at mitochondrial level, suggesting an early adaptive protective response but also an increased predisposition towards pro-oxidant insults.

Advential cystic disease of the popliteal artery: experience of a single vascular and endovascular center.

Adventitial cystic disease (ACD) is an uncommon condition with only around 300 cases reported in the literature. ACD consists of a collection of gelatinous material within a cyst, that is adjacent or surrounding a vessel. In the last five years three cases of ACD have been observed: the first case was a 48-year-old man, ex nicotine abuser, with a four-month history of progressive claudication; the second case was a 55-year-old man, ex nicotine abuser, with ischemic heart failure and a one-year history of progressive claudication; the third case was a 70-year-old man, with diabetes, dislipidemia and current nicotine abuser with a few-day history of acute pain in the right leg. In two cases the cysts were incised and the contents evacuated. The adventitia was repaired and the wound closed. The first patient is currently asymptomatic after four years from surgery. The second one, at 21 months, follow-up, presented newly severe claudication. Duplex ultrasound scan and computed tomography angiography demonstrated a cranial progression of the lesions. This lesion was treated with bare stent, with complete regression of the symptoms. The third patient was treated with interposition of an autogenous saphenous vein. The patient is asymptomatic at the three-month follow-up. Even if ACD is quite rare, it should be taken in consideration in young patients with severe claudication and no- or poor comorbidities. The best treatment is the incision of the cysts and the advential reconstruction. Short lesions can be treated with endovascular therapy.

Aquaporins in the hepatobiliary tract. Which, where and what they do in health and disease.

The biological importance of the aquaporin family of water channels was recently acknowledged by the 2003 Nobel Prize for Chemistry awarded to the discovering scientist Peter Agre. Among the pleiotropic roles exerted by aquaporins in nature in both health and disease, the review addresses the latest acquisitions about the expression and regulation, as well as physiology and pathophysiology of aquaporins in the hepatobiliary tract. Of note, at least seven out of the thirteen mammalian aquaporins are expressed in the liver, bile ducts and gallbladder. Aquaporins are essential for bile water secretion and reabsorption, as well as for plasma glycerol uptake by the hepatocyte and its conversion to glucose during starvation. Novel data are emerging regarding the physio-pathological involvement of aquaporins in multiple diseases such as cholestases, liver cirrhosis, obesity and insulin resistance, fatty liver, gallstone formation and even microparasite invasion of intrahepatic bile ducts. This body of knowledge represents the mainstay of present and future research in a rapidly expanding field.