Smoothened is a master regulator of adult liver repair

When regenerative processes cannot keep pace with cell death, functional epithelia are replaced by scar. Scarring is characterized by both excessive accumulation of fibrous matrix and persistent outgrowth of cell types that accumulate transiently during successful wound healing, including myofibroblasts (MFs) and progenitors. This suggests that signaling that normally directs these cells to repair injured epithelia is deregulated. To evaluate this possibility, we examined liver repair during different types of liver injury after Smoothened (SMO), an obligate intermediate in the Hedgehog (Hh) signaling pathway, was conditionally deleted in cells expressing the MF-associated gene, αSMA. Surprisingly, blocking canonical Hh signaling in MFs not only inhibited liver fibrosis but also prevented accumulation of liver progenitors. Hh-sensitive, hepatic stellate cells (HSCs) were identified as the source of both MFs and progenitors by lineage-tracing studies in 3 other strains of mice, coupled with analysis of highly pure HSC preparations using flow cytometry, immunofluorescence confocal microscopy, RT-PCR, and in situ hybridization. The results identify SMO as a master regulator of hepatic epithelial regeneration based on its ability to promote mesenchymal-to-epithelial transitions in a subpopulation of HSC-derived MFs with features of multipotent progenitors.     

The coracoacromial arch: MR evaluation and correlation with rotator cuff pathology

The relative prevalence of various acromial shapes, appearance of the coracoacromial ligament and enthesophytes along the inferior aspect of the acromioclavicular joint in patients with and without rotator cuff tears were evaluated. Of 76 patients with clinical instability and impingement, 31 had a normal rotator cuff and 45 demonstrated a partial or full tear of the supraspinatus tendon at surgery. Results were compared with those from magnetic resonance (MR) scans of 57 asymptomatic volunteers. Of the 45 patients with a supraspinatus tear, 38% (17) had a flat acromial undersurface (type I), 40% (18) had a concave acromial undersurface (type II), 18% (8) had an anteriorly hooked acromion (type III), and 4% (2) had an inferiorly convex acromion (type IV). Among the 31 patients with a normal rotator cuff at surgery and the 57 asymptomatic volunteers, the respective prevalences of the type I acromion were 39% (12) and 44% (25), of type II 48% (15) and 35% (20), type III 3% (1) and 12% (7), and type IV 10% (3) and 9% (5). Shoulders with surgically proven rotator cuff tears showed a tendential association with a type III acromion (8/45) and statistically significant associations with a thickened coracoacromial ligament (17/45) and acromioclavicular enthesophytes (18/45). For the association between inferiorly directed acromioclavicular joint enthesophytes and rotator cuff tears, age appears to be a confounding factor. The type IV acromion, newly classified by this study, does not have a recognizable association with rotator cuff tears. Assessment of the osseous-ligamentous coracoacromial outlet by may prove helpful to the orthopedic surgeon in patients for whom surgical decompression is contemplated.     

Exercise & Sports Science Australia (ESSA) position statement on exercise and chronic kidney disease

ObjectivesChronic kidney disease (CKD) is prevalent, affecting 13% of adult Australians and poses increased risk for cardiovascular morbidity and mortality. This position article provides evidence-based guidelines on the role of exercise training for CKD patients and provides recommendations for prescribing and delivering exercise training.DesignPosition stand.MethodsSynthesis of published work within the field of exercise training and chronic kidney disease.ResultsExercise training likely to provide benefits to CKD patients, including improvements in cardio-respiratory fitness, quality of life, sympatho-adrenal activity, muscle strength and increased energy intake and possible reduction in inflammatory biomarkers. Existing studies generally report small sample sizes, brief training periods and relatively high attrition rates. Exercise training appears to be safe for CKD patients with no deaths directly related to exercise training in over 30,000 patient-hours, although strict medical exclusion criteria in previous studies resulted in 25% of patients being excluded potentially impacting the generalisability of the findings.ConclusionsAerobic exercise at an intensity of >60% of maximum capacity is recommended to improve cardio-respiratory fitness. Few data are available on resistance training and it is unclear whether this form of training retards catabolic/inflammatory processes typical of CKD. However, it should be considered important due to its proven beneficial effects on bone density and muscle mass. Due to the high prevalence and incidence of co-morbidities in CKD patients, exercise training programs should be prescribed and delivered by individuals with appropriate qualifications and experience to recognise and accommodate co-morbidities and associated complications.     

Robotic-Assisted Minimally Invasive Central Pancreatectomy: Technique and Outcomes

Background

Central pancreatectomy is a definitive treatment for low-grade tumors of the pancreatic neck that preserves pancreatic and splenic function at the potential expense of postoperative pancreatic fistula. We analyzed outcomes after robot-assisted central pancreatectomy (RACP) to reexamine the risk–benefit profile in the era of minimally invasive surgery.

Methods

Retrospective analysis of nine RACP performed between August 2009 through June 2010 at a single institution.

Results

The average age of the cohort was 64 (range 18–75 years) with six women (67 %). Indications for surgery included: five benign cystic neoplasm and four pancreatic neuroendocrine tumor. Median operative time was 425 min (range 305–506 min) with 190 ml median blood loss (range 50–350 ml) and one conversion to open due to poor visualization. Median tumor size was 3.0 cm (range 1.9–6.0 cm); all patients achieved R0 status. Pancreaticogastrostomy was performed in seven cases and pancreaticojejunostomy in two. The median length of hospital stay was 10 days (range 7–19). Two clinically significant pancreatic fistulae occurred with one requiring percutaneous drainage. No patients exhibited worsening diabetes or exocrine insufficiency at the 30-day postoperative visit.

Conclusions

RACP can be performed with safety and oncologic outcomes equivalent to published open series. Although the rate of pancreatic fistula was high, only 22 % had clinically significant events, and none developed worsening pancreatic endocrine or exocrine dysfunction.     

Endoscopic Duodenal–Jejunal Bypass Liner Rapidly Improves Type 2 Diabetes

Background

Bariatric procedures excluding the proximal small intestine improve glycemic control in type 2 diabetes within days. To gain insight into the mediators involved, we investigated factors regulating glucose homeostasis in patients with type 2 diabetes treated with the novel endoscopic duodenal–jejunal bypass liner (DJBL).

Methods

Seventeen obese patients (BMI 30–50 kg/m²) with type 2 diabetes received the DJBL for 24 weeks. Body weight and type 2 diabetes parameters, including HbA_1c and plasma levels of glucose, insulin, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon, were analyzed after a standard meal before, during, and 1 week after DJBL treatment.

Results

At 24 weeks after implantation, patients had lost 12.7?±?1.3 kg (p?<?0.01), while HbA_1c had improved from 8.4?±?0.2 to 7.0?±?0.2 % (p?<?0.01). Both fasting glucose levels and the postprandial glucose response were decreased at 1 week after implantation and remained decreased at 24 weeks (baseline vs. week 1 vs. week 24: 11.6?±?0.5 vs. 9.0?±?0.5 vs. 8.6?±?0.5 mmol/L and 1,999?±?85 vs. 1,536?±?51 vs. 1,538?±?72 mmol/L/min, both p?<?0.01). In parallel, the glucagon response decreased (23,762?±?4,732 vs. 15,989?±?3,193 vs. 13,1207?±?1,946 pg/mL/min, p?<?0.05) and the GLP-1 response increased (4,440?±?249 vs. 6,407?±?480 vs. 6,008?±?429 pmol/L/min, p?<?0.01). The GIP response was decreased at week 24 (baseline—115,272?±?10,971 vs. week 24—88,499?±?10,971 pg/mL/min, p?<?0.05). Insulin levels did not change significantly. Glycemic control was still improved 1 week after explantation.

Conclusions

The data indicate DJBL to be a promising treatment for obesity and type 2 diabetes, causing rapid improvement of glycemic control paralleled by changes in gut hormones.     

Treatment of acute thoracic aortic injury with commercially available abdominal aortic stent-grafts

Traumatic rupture of the thoracic aorta is a common cause of death after vehicle collisions. Associated injuries are common, and patients with lung injury, cardiac contusion, abdominal bleeding, and head injury comprise a group at high risk for conventional surgical or medical therapy. In this particular population, existing commercially available stent-grafts may provide a life-saving repair option. The Ancure and AneuRx stent-grafts, designed for abdominal aortic aneurysm application, were successfully placed in three patients. Accommodation for the short length of the delivery device was achieved by retroperitoneal iliac artery access. All patients had follow-up computed tomography (CT) without evidence of endoleak and were doing well with respect to their chest trauma after 5-9 months of follow-up.     

A method for the direct electrical stimulation of the auditory system in deaf subjects: a functional magnetic resonance imaging study

PURPOSE: To develop a safe functional magnetic resonance imaging (fMRI) procedure for auditory assessment of deaf subjects. MATERIALS AND METHODS: A gold-plated tungsten electrode has been developed which has zero magnetic susceptibility. Used with carbon leads and a carbon reference pad, it enables safe, distortion-free fMRI studies of deaf subjects following direct electrical stimulation of the acoustic nerve. Minor pickup of the radio frequency (RF) pulses by the electrode assembly is difficult to eliminate, and a SPARSE acquisition sequence is used to avoid any effects of unintentional auditory nerve stimulation. RESULTS: The procedure is demonstrated in a deaf volunteer. Activation is observed in the contralateral but not the ipsilateral primary auditory cortex. This is in sharp contrast to studies of auditory processing in hearing subjects, but consistent with the small number of previous positron emission tomography (PET) and MR studies on adult deaf subjects. CONCLUSION: The fMRI procedure is able to demonstrate whether the auditory pathway is fully intact, and may provide a useful method for preoperative assessment of candidates for cochlear implantation.     

Early and late complications following laparoscopic adjustable gastric banding

There is limited U.S. data on short- and long-term complications of laparoscopic adjustable gastric banding (LAGB) as a treatment option for morbid obesity. Hereafter, we present our experience with the first 154 consecutive LAGBs performed at Loyola University Medical Center. Inpatient and outpatient charts were reviewed retrospectively for all patients undergoing LAGB between November 2001 and February 2003 for perioperative morbidity and mortality and repeat operations. Thirty-seven men (24%) and 117 women (76%) underwent LAGB in a 16-month period. There was one (0.6%) death from postoperative myocardial infarction (MI) and one (0.6%) pulmonary embolism. Six (3.9%) patients required readmission to the hospital for dehydration. During a mean follow-up of 33 weeks (range, 4-69 weeks), 14 (9%) patients required repeat operations. There were five (3.2%) band slippages and one (0.6%) gastric erosion. Three bands were removed laparoscopically. Three slippages were revised laparoscopically. One patient underwent laparoscopic cholecystectomy. Seven patients (4.5%) required port revisions for catheter disconnection (4), leak at port site (2), or flipped port (1). LAGB is a safe operative approach for the management of morbid obesity. The incidence of postoperative complications can be minimal with application of a standardized technique. LAGB should be strongly considered for morbidly obese patients who have failed nonoperative management.     

Predictors of survival after liver transplantation for hepatocellular carcinoma associated with Hepatitis C.

The efficacy of orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) is not well defined. This study examines the variables that may determine the outcome of OLT for HCC in HCV patients. From 1990 to 1999, 463 OLTs were performed for HCV cirrhosis. Of these patients, 67 with concurrent HCC were included in the study. Univariate and multivariate analyses considered the following variables: gender, pTNM stage, tumor size, number of nodules, vascular invasion, incidental tumors, adjuvant chemotherapy, preoperative chemoembolization, alpha-fetoprotein (AFP) tumor marker, lobar distribution, and histological grade. Overall OLT survival of HCV patients diagnosed with concomitant HCC was significantly lower when compared to patients who underwent OLT for HCV alone at 1, 3, and 5 years (75%, 71%, and 55% versus 84%, 76%, and 75%, respectively; P < 0.01). Overall survival of patients with stage I HCC was significantly better than patients with stage II, III, or IV (P < .05). Eleven of 67 patients developed tumor recurrence. Sites of recurrence included transplanted liver (5), lung (5), and bone (1). Twenty-four of 67 patients (36%) died during the follow-up time. Causes of deaths included recurrent HCC in 8 of 24 patients (12%) and recurrent HCV in 3 of 24 patients (4.5%), whereas 13 (19.5%) patients died from causes that were unrelated to HCV or HCC. Both univariate and multivariate analysis demonstrated that pTNM status (I versus II, III, and IV; P < .05) was a reliable prognostic indicator for patient survival. Presence of vascular invasion (P = .0001) and advanced pTNM staging (P = .038) increased risk of recurrence. Multivariate analysis showed that pretransplant chemoembolization and adjuvant chemotherapy reduced risk of death after OLT in HCC recipients. In conclusion, this study demonstrates the effectiveness of OLT for patients with HCC in a large cohort of chronic HCV patients. Advanced tumor stage, and particularly vascular invasion, are poor prognostic indicators for tumor recurrence. Early pTNM stage, adjuvant chemotherapy, and preoperative chemoembolization were associated with positive outcomes for patients who underwent OLT for concomitant HCV and HCC.