Giant extra-hepatic thrombosed portal vein aneurysm: a case report and review of the literature.

BACKGROUND: Extrahepatic Portal vein aneurysm (EPVA) is a rare finding that may be associated with different complications, e.g. thrombosis, rupture, portal hypertension and compression of adjacent structures. It is being diagnosed more frequently with the advent of modern cross-sectional imaging. Our review of the English literature disclosed 13 cases of thrombosed EPVA. CASE PRESENTATION: A 50-years-old woman presented with acute abdominal pain but no other symptom. She had no relevant medical history. Palpation of the right upper quadrant showed tenderness. Laboratory tests were unremarkable. A computed tomography showed portal vein aneurysm measuring 88 × 65 mm with thrombosis extending to the superior mesenteric and splenic vein. The patient was treated conservatively with anticoagulation therapy. She was released after two weeks and followed on an outpatient basis. At two months, she reported decreased abdominal pain and her physical examination was normal. A computed tomography was performed showing a decreased thrombosis size and extent, measuring 80 × 55 mm. CONCLUSIONS: Although rare, surgeons should be made aware of this entity. Complications are various. Conservative therapy should be chosen in first intent in most cases. We reported the case of the second largest thrombosed extra-hepatic PVA described in the literature, treated by anticoagulation therapy with a good clinical and radiological response

Photodynamic diagnosis of breast tumours after oral application of aminolevulinic acid

Photodynamic diagnosis is of increasing interest for diagnosis in oncology. It is based on a more intense incorporation of a fluorescent dye in tumours compared to normal tissue. As a feasibility study we investigated the effectiveness of oral application of 5-aminolevulinic acid for photodynamic diagnosis of human primary mammary tumours. The study included 16 patients with palpable breast tumours. Aminolevulinic acid was administered at a concentration of 40 mg kg−1bodyweight 150–420 min prior to tumourectomy. Intraoperatively blue light (405 nm) was applied to the operation site. Sections of the excised tumour and some lymph nodes were prepared and analysed with a fluorescent microscope. All primary mammary tumour tissues showed significantly higher fluorescence intensity than surrounding normal mammary tissue. Fluorescence of the mammary tumours could also be discriminated macroscopically and intraoperatively. Fluorescence intensity in nonmetastatic lymph node tissue was higher in 2 out of 3 patients than in primary tumour tissue. By photodynamic diagnosis using aminolevulinic acid we were able to reliably distinguish primary mammary tumours from normal mammary tissue microscopically and macroscopically in all our patients. We suggest that photodynamic diagnosis with aminolevulinic acid for breast tumours should be further investigated and developed for intraoperative use and may well be a simple tool for better intraoperative diagnosis and recognition of tumour margins. We hypothesize that lymph node metastasis of breast tumours will not be detectable by this method. © 2001 Cancer Research Campaign http://www.bjcancer.co

Robotic-Assisted Surgery Improves the Quality of Total Mesorectal Excision for Rectal Cancer Compared to Laparoscopy: Results of a Case-Controlled Analysis.

BACKGROUND: The use of a robotic surgical system is claimed to allow precise traction and counter-traction, especially in a narrow pelvis. Whether this translates to improvement of the quality of the resected specimen is not yet clear. The aim of the study was to compare the quality of the TME and the short-term oncological outcome between robotic and laparoscopic rectal cancer resections. METHODS: 20 consecutive robotic TME performed in a single institution for rectal cancer (Rob group) were matched 1:2 to 40 laparoscopic resections (Lap group) for gender, body mass index (BMI), and distance from anal verge on rigid proctoscopy. The quality of TME was assessed by 2 blinded and independent pathologists and reported according to international standardized guidelines. RESULTS: Both samples were well matched for gender, BMI (median 25.9 vs. 24.2 kg/m(2), p = 0.24), and level of the tumor (4.1 vs. 4.8 cm, p = 0.20). The quality of the TME was better in the Robotic group (complete TME: 95 vs. 55 %; p = 0.0003, nearly complete TME 5 vs. 37 %; p = 0.04, incomplete TME 0 vs. 8 %, p = 0.09). A trend for lower positive circumferential margin was observed in the Robotic group (10 vs. 25 %, p = 0.1). CONCLUSIONS: These results suggest that robotic-assisted surgery improves the quality of TME for rectal cancer. Whether this translates to better oncological outcome needs to be further investigated

18F- FDG PET/CT-derived parameters predict clinical stage and prognosis of esophageal cancer.

Although <sup>18</sup> F- FDG PET/CT is validated in baseline workup of esophageal cancer to detect distant metastases, it remains underused in assessing local staging and biology of the primary tumor. This study aimed to evaluate the association between <sup>18</sup> F- FDG PET/CT-derived parameters of esophageal cancer, and its clinico-pathological features and prognosis. All patients (n = 86) with esophageal adenocarcinoma or squamous cell cancer operated between 2005 and 2014 were analyzed. Linear regression was used to identify clinico-pathologic features of esophageal cancer associated with the tumor's maximal Standardized Uptake Value (SUV <sub>max</sub> ), Total Lesion Glycolysis (TLG) and Metabolic Tumor Volume (MTV). ROC curve analysis was performed to precise the optimal cutoff of each variable associated with a locally advanced (cT3/4) status, long-term survival and recurrence. Kaplan Meier curves and Cox regression were used for survival analyses. High baseline SUV <sub>max</sub> was associated with cT3/4 status and middle-third tumor location, TLG with a cT3/4 and cN+ status, whereas MTV only with active smoking. A cT3/4 status was significantly predicted by a SUV <sub>max</sub> > 8.25 g/mL (p < 0.001), TLG > 41.7 (p < 0.001) and MTV > 10.70 cm <sup>3</sup> (p < 0.01) whereas a SUV <sub>max</sub> > 12.7 g/mL was associated with an early tumor recurrence and a poor disease-free survival (median 13 versus 56 months, p = 0.030), particularly in squamous cell cancer. Baseline <sup>18</sup> F- FDG PET/CT has a high predictive value of preoperative cT stage, as its parameters SUV <sub>max</sub> , TLG and MTV can predict a locally advanced tumor with high accuracy. A SUV <sub>max</sub> > 12.7 g/mL may herald early tumor recurrence and poor disease-free survival

Drain Versus No Drain in Open Mesh Repair for Incisional Hernia, Results of a Prospective Randomized Controlled Trial.

Open mesh repair of incisional hernia is associated with different local complications, particularly bleeding and seroma formation. Traditionally, drains have been placed perioperatively to prevent these complications, despite the lack of scientific evidence or expert consensus. We formulated the hypothesis that the absence of drainage would reduce number of patients presenting collections or complications. The present study aimed to compare postoperative complication rates after open mesh repair for incisional hernia with or without prophylactic wound drainage. Prospective randomized study using standardized surgical technique and drain placement. The primary endpoint was the evaluation of residual fluid collection with ultrasound on postoperative day 30. Other complications, subdivided into medical and surgical, were analyzed as secondary endpoints. There were 144 patients randomized (70 with drain, 74 without drain). No difference was identified between both groups for fluid collection at 30 days (60.3% vs. 62%, p = 0.844). However, less surgical complications were identified in the drain group (21.7% vs. 42.7%, p = 0.007), with a lower wound dehiscence rate (1.5% vs. 9.3%, p = 0.041). Prophylactic drainage in open incisional hernia repair does not objectively reduce the rate of postoperative fluid collections. Therefore, our results do not support the use of routine drainage in incisional hernia repair. Trial registration on clinicaltrials.gov (NCT00478348)

Implementation of Enhanced Recovery (ERAS) in Colorectal Surgery Has a Positive Impact on Non-ERAS Liver Surgery Patients.

BACKGROUND: Enhanced recovery after surgery (ERAS) reduces complications and hospital stay in colorectal surgery. Thereafter, ERAS principles were extended to liver surgery. Previous implementation of an ERAS program in colorectal surgery may influence patients undergoing liver surgery in a non-ERAS setting, on the same ward. This study aimed to test this hypothesis. METHODS: Retrospective analysis based on prospective data of the adherence to the institutional ERAS-liver protocol (compliance) in three cohorts of consecutive patients undergoing elective liver surgery, between June 2010 and July 2014: before any ERAS implementation (pre-ERAS n = 50), after implementation of ERAS in colorectal (intermediate n = 50), and after implementation of ERAS in liver surgery (ERAS-liver n = 74). Outcomes were functional recovery, postoperative complications, hospital stay, and readmissions. RESULTS: The three groups were comparable for demographics; laparoscopy was more frequent in ERAS-liver (p = 0.009). Compliance with the enhanced recovery protocol increased along the three periods (pre-ERAS, intermediate, and ERAS-liver), regardless of the perioperative phase (pre-, intra-, or postoperative). ERAS-liver group displayed the highest overall compliance rate with 73.8 %, compared to 39.9 and 57.4 % for pre-ERAS and intermediate groups (p = 0.072/0.056). Overall complications were unchanged (p = 0.185), whereas intermediate and ERAS-liver groups showed decreased major complications (p = 0.034). Consistently, hospital stay was reduced by 2 days (p = 0.005) without increased readmissions (p = 0.158). CONCLUSIONS: The previous implementation of an ERAS protocol in colorectal surgery may induce a positive impact on patients undergoing non-ERAS-liver surgery on the same ward. These results suggest that ERAS is safely applicable in liver surgery and associated with benefits

QTc interval and resting heart rate as long-term predictors of mortality in type 1 and type 2 diabetes mellitus: a 23-year follow-up

Aims/hypothesis: We evaluated the association of QT interval corrected for heart rate (QTc) and resting heart rate (rHR) with mortality (all-causes, cardiovascular, cardiac, and ischaemic heart disease) in subjects with type 1 and type 2 diabetes. Methods: We followed 523 diabetic patients (221 with type 1 diabetes, 302 with type 2 diabetes) who were recruited between 1974 and 1977 in Switzerland for the WHO Multinational Study of Vascular Disease in Diabetes. Duration of follow-up was 22.6 ± 0.6years. Causes of death were obtained from death certificates, hospital records, post-mortem reports, and additional information given by treating physicians. Results: In subjects with type 1 diabetes QTc, but not rHR, was associated with an increased risk of: (1) all-cause mortality (hazard ratio [HR] 1.10 per 10ms increase in QTc, 95% CI 1.02-1.20, p = 0.011); (2) mortality due to cardiovascular (HR 1.15, 1.02-1.31, p = 0.024); and (3) mortality due to cardiac disease (HR 1.19, 1.03-1.36, p = 0.016). Findings for subjects with type 2 diabetes were different: rHR, but not QTc was associated with mortality due to: (1) all causes (HR 1.31 per 10 beats per min, 95% CI 1.15-1.50, p < 0.001); (2) cardiovascular disease (HR 1.43, 1.18-1.73, p < 0.001); (3) cardiac disease (HR 1.45, 1.19-1.76, p < 0.001); and (4) ischaemic heart disease (HR 1.52, 1.21-1.90, p < 0.001). Effect modification of QTc by type 1 and rHR by type 2 diabetes was statistically significant (p < 0.05 for all terms of interaction). Conclusions/interpretation: QTc is associated with long-term mortality in subjects with type 1 diabetes, whereas rHR is related to increased mortality risk in subjects with type 2 diabete

Loss of Hyperconjugative Effects Drives Hydride Transfer during Dihydrofolate Reductase Catalysis

Hydride transfer is widespread in nature and has an essential role in applied research. However, the mechanisms of how this transformation occurs in living organisms remain a matter of vigorous debate. Here, we examined dihydrofolate reductase (DHFR), an enzyme that catalyzes hydride from C4′ of NADPH to C6 of 7,8-dihydrofolate (H2F). Despite many investigations of the mechanism of this reaction, the contribution of polarization of the π-bond of H2F in driving hydride transfer remains unclear. H2F was stereospecifically labeled with deuterium β to the reacting center, and β-deuterium kinetic isotope effects were measured. Our experimental results combined with analysis derived from QM/MM simulations reveal that hydride transfer is triggered by polarization at the C6 of H2F. The σ Cβ–H bonds contribute to the buildup of the cationic character during the chemical transformation, and hyperconjugation influences the formation of the transition state. Our findings provide key insights into the hydride transfer mechanism of the DHFR-catalyzed reaction, which is a target for antiproliferative drugs and a paradigmatic model in mechanistic enzymology

Isotope Substitution of Promiscuous Alcohol Dehydrogenase Reveals the Origin of Substrate Preference in the Transition State

The origin of substrate preference in promiscuous enzymes was investigated by enzyme isotope labelling of the alcohol dehydrogenase from Geobacillus stearothermophilus (BsADH). At physiological temperature, protein dynamic coupling to the reaction coordinate was insignificant. However, the extent of dynamic coupling was highly substrate-dependent at lower temperatures. For benzyl alcohol, an enzyme isotope effect larger than unity was observed, whereas the enzyme isotope effect was close to unity for isopropanol. Frequency motion analysis on the transition states revealed that residues surrounding the active site undergo substantial displacement during catalysis for sterically bulky alcohols. BsADH prefers smaller substrates, which cause less protein friction along the reaction coordinate and reduced frequencies of dynamic recrossing. This hypothesis allows a prediction of the trend of enzyme isotope effects for a wide variety of substrates

Salmeterol for the prevention of high-altitude pulmonary edema.

BACKGROUND: Pulmonary edema results from a persistent imbalance between forces that drive water into the air space and the physiologic mechanisms that remove it. Among the latter, the absorption of liquid driven by active alveolar transepithelial sodium transport has an important role; a defect of this mechanism may predispose patients to pulmonary edema. Beta-adrenergic agonists up-regulate the clearance of alveolar fluid and attenuate pulmonary edema in animal models. METHODS: In a double-blind, randomized, placebo-controlled study, we assessed the effects of prophylactic inhalation of the beta-adrenergic agonist salmeterol on the incidence of pulmonary edema during exposure to high altitudes (4559 m, reached in less than 22 hours) in 37 subjects who were susceptible to high-altitude pulmonary edema. We also measured the nasal transepithelial potential difference, a marker of the transepithelial sodium and water transport in the distal airways, in 33 mountaineers who were prone to high-altitude pulmonary edema and 33 mountaineers who were resistant to this condition. RESULTS: Prophylactic inhalation of salmeterol decreased the incidence of high-altitude pulmonary edema in susceptible subjects by more than 50 percent, from 74 percent with placebo to 33 percent (P=0.02). The nasal potential-difference value under low-altitude conditions was more than 30 percent lower in the subjects who were susceptible to high-altitude pulmonary edema than in those who were not susceptible (P&lt;0.001). CONCLUSIONS: Prophylactic inhalation of a beta-adrenergic agonist reduces the risk of high-altitude pulmonary edema. Sodium-dependent absorption of liquid from the airways may be defective in patients who are susceptible to high-altitude pulmonary edema. These findings support the concept that sodium-driven clearance of alveolar fluid may have a pathogenic role in pulmonary edema in humans and therefore represent an appropriate target for therapy