Schmorl's nodes: current pathophysiological, diagnostic, and therapeutic paradigms

Schmorl's nodes were first described by the pathologist Christian Schmorl in 1927 as a herniation of the nucleus pulposus through the cartilaginous and bony endplate into the vertebral body. Although such lesions present most commonly as incidental findings in asymptomatic patients (or in patients with back or radicular pain due to other etiology), there have been several reports emphasizing the deleterious effects of the inflammatory response and endplate changes elicited by the herniation of for such reasons, Schmorl's nodes have been occasionally implicated in the etiology of chronic axial pain as well as in pathological osteoporotic fractures. In this article, a thorough literature review about the most relevant historical studies on Schmorl's nodes previously published is performed. Furthermore, the authors provide an overview about the recent advances in basic science research on the pathophysiology of such lesions, as well as on current diagnostic and therapeutic paradigms.     

The Role of Radical Prostatectomy and Lymph Node Dissection in Lymph Node–Positive Prostate Cancer: A Systematic Review of the Literature

Context

Because pelvic lymph node (LN)-positive prostate cancer (PCa) is generally considered a regionally metastatic disease, surgery needs to be better defined.

Objective

To review the impact of radical prostatectomy (RP) and pelvic lymph node dissection (PLND), possibly in conjunction with a multimodal approach using local radiotherapy and/or androgen-deprivation therapy (ADT), in LN-positive PCa.

Evidence acquisition

A systematic Medline search for studies reporting on treatment regimens and outcomes in patients with LN-positive PCa undergoing RP between 1993 and 2012 was performed.

Evidence synthesis

RP can improve progression-free and overall survival in LN-positive PCa, although there is a lack of high-level evidence. Therefore, the former practice of aborting surgery in the presence of positive nodes might no longer be supported by current evidence, especially in those patients with a limited LN tumor burden. Current data demonstrate that the lymphatic spread takes an ascending pathway from the pelvis to the retroperitoneum, in which the internal and the common iliac nodes represent critical landmarks in the metastatic distribution. Sophisticated imaging technologies are still under investigation to improve the prediction of LN-positive PCa. Nonetheless, extended PLND including the common iliac arteries should be offered to intermediate- and high-risk patients to improve nodal staging with a possible benefit in prostate-specific antigen progression-free survival by removing significant metastatic load. Adjuvant ADT has the potential to improve overall survival after RP; the therapeutic role of a trimodal approach with adjuvant local radiotherapy awaits further elucidation. Age is a critical parameter for survival because cancer-specific mortality exceeds overall mortality in younger patients (<60 yr) with high-risk PCa and should be an impetus to treat as thoroughly as possible.

Conclusions

Increasing evidence suggests that RP and extended PLND improve survival in LN-positive PCa. Our understanding of surgery of the primary tumor in LN-positive PCa needs a conceptual change from a palliative option to the first step in a multimodal approach with a significant improvement of long-term survival and cure in selected patients.     

A pilot study of blood epinephrine levels and CREB phosphorylation in men undergoing prostate biopsies

Purpose

In mouse models of prostate cancer, increased epinephrine levels accelerated tumor growth via the beta2-adrenoreceptor/PKA signaling pathway. It is unknown, however, whether men experience increased epinephrine levels sufficient to activate the beta2-adrenoreceptor/PKA pathway in the prostate gland. We measured epinephrine levels in blood samples collected immediately prior to prostate biopsies and measured phosphorylation of S133CREB (PKA site), S112BAD, T202/Y204ERK, and S473 Akt in prostate biopsy tissue samples.

Methods

Tissue samples and 3 ml of blood were obtained from men (n = 20) recruited from the patients scheduled for prostate biopsies. Epinephrine levels were measured by ELISA. Proteins were extracted from biopsied tissue, and protein phosphorylation was measured by Western blotting with phospho-specific antibodies. Pearson and Spearman’s rank correlations were analyzed to assess relationships between blood epinephrine levels and phosphorylation of CREB, BAD, AKT, and ERK.

Results

Epinephrine levels above 1 nM were detected in 5 of 20 patients. A strong positive correlation was observed between increased epinephrine levels and CREB phosphorylation. In contrast, no correlation was observed between epinephrine levels and phosphorylation of ERK, BAD, or AKT.

Conclusion

Our results suggest that increased blood epinephrine levels activate the beta2-adrenoreceptor/PKA signaling pathway in human prostate glands. These results will inform future studies to examine whether beta2-selective blockers can inhibit activation of the epinephrine/ADRB2/PKA pathway in prostate tumors of men with increased epinephrine levels and explore the use of beta2-selective blockers as adjuvant therapy for prostate cancer.     

Loco-regional treatment of hepatocellular carcinoma: Role of contrast-enhanced ultrasonography

Hepatocellular carcinoma (HCC) is one of the few cancers for which locoregional treatments (LRTs) are included in international guidelines and are considered as a valid alternative to conventional surgery. According to Barcelona Clinic Liver Cancer classification, percutaneous treatments such as percutaneous ethanol injection, radiofrequency ablation and microwave ablation are the therapy of choice among curative treatments in patients categorized as very early and early stage, while transcatheter arterial chemoembolization is considered the better option for intermediate stage HCC. A precise assessment of treatment efficacy and surveillance is essential to optimize survival rate, whereas residual tumor requires additional treatment. Imaging modalities play a key role in this task. Currently, contrast-enhanced computed tomography/magnetic resonance imaging are considered the standard imaging modalities for this purpose. Contrast enhanced ultrasound (CEUS), using second generation contrast agents, plays an increasingly important role in detecting residual disease after LRTs. CEUS is a straightforward to perform, repeatable and cost-effective imaging modality for patients with renal failure or iodine allergies. Due to the ability to focus on single regions, CEUS can also provide high temporal resolution. Moreover, several studies have reported the same or better diagnostic accuracy as contrast-enhanced computed tomography for assessing tumor vascularity 1 mo after LRTs, and recently three-dimensional (3D)-CEUS has been reported as a promising technique to improve the evaluation of tumor response to therapy. Furthermore, CEUS could be used early after procedures in monitoring HCC treatments, but nowadays this indication is still debated, and data from literature are conflicting, especially after transcatheter arterial chemoembolization procedure.     

The ringed esophagus

Abdominal Radiology -     

Accuracy of a predictive model for severe hepatic fibrosis or cirrhosis in chronic hepatitis C

AIM: To assess the accuracy of a model in diagnosing severe fibrosis/cirrhosis in chronic hepatitis C virus (HCV) infection. METHODS: The model, based on the sequential combination of the Bonacini score (BS: ALT/AST ratio, platelet count and INR) and ultrasonography liver surface characteristics, was applied to 176 patients with chronic HCV infection. Assuming a pre-test probability of 35%, the model defined four levels of post-test probability of severe fibrosis/cirrhosis: <10% (low), 10-74% (not diagnostic), 75-90% (high) and >90% (almost absolute). The predicted probabilities were compared with the observed patients' distribution according to the histology (METAVIR). RESULTS: Severe fibrosis/cirrhosis was found in 67 patients (38%). The model discriminated patients in three comparable groups: 34% with a very high (>90%) or low (<10%) probability of severe fibrosis, 33% with a probability ranging from 75% to 90%, and 33% with an uncertain diagnosis (i.e., a probability ranging from 10% to 74%). The observed frequency of severe fibrosis/ cirrhosis was within the predefined ranges. CONCLUSION: The model can correctly identify 67% of patients with a high (>75%) or low (<10%) probability of cirrhosis, leaving only 33% of the patients still requiring liver biopsy.     

Effect of oral contraceptives on endothelial function in the peripheral microcirculation of healthy women

OBJECTIVES: We assessed whether third-generation oral contraceptive (OC) treatment (30 microg ethinylestradiol + 75 microg gestodene daily) could affect the endothelial function of healthy women. METHODS: In 20 young healthy women (HW) and 10 hypercholesterolemic women (CW) we assessed forearm blood flow (strain-gauge plethysmography) changes induced by the intrabrachial infusion of acetylcholine (ACH) (0.15-15 microg/100 ml forearm tissue/min) and sodium nitroprusside (SNP) (1-4 microg/100 ml forearm tissue/min). ACH was repeated during the nitric oxide synthase inhibitor intra-arterial NG-monomethyl-L-arginine (L-NMMA) (100 microg/100 ml forearm tissue/min) or the antioxidant vitamin C (8 mg/100 ml forearm tissue/min). HW repeated the protocol after 6-month OC (n = 10) or placebo (n = 10) treatment. RESULTS: In HW the maximal vasodilation to ACH, similar between placebo and OC subgroups, was significantly reduced in CW (P < 0.01). Vasodilation to ACH was blunted (P < 0.01) by L-NMMA and unaffected by vitamin C, in both OC and placebo groups. In CW the vasodilation to ACH, not modified by L-NMMA, was improved by vitamin C (P < 0.01). OC treatment raised (P < 0.01) plasma total and low-density lipoprotein cholesterol, and values were similar to those shown by CW. Both OC and placebo intake did not change the response to ACH and the modulation induced by L-NMMA or vitamin C. Vasodilation to SNP was similar in all groups. CONCLUSIONS: In HW 6-month treatment with third-generation OC, although associated with an abnormal lipid profile, does not adversely affect endothelium-dependent vasodilation. This neutral effect could be the balance between a deleterious effect of hypercholesterolemia and a protective effect of OC on endothelial function.     

Enhancement of Gallbladder Emptying in Gallstone Patients after Oral Cholestyramine

Objective: To evaluate whether a low dose of oral cholestyramine improves gallbladder emptying in gallstone patients. Methods: Gallbladder volumes were assessed by sonography in 36 patients with cholesterol gallstones and 18 healthy controls. On three different days subjects ingested: 1 ) test meal alone, 2 ) test meal plus cholestyramine (4 g), and 3 ) cholestyramine alone (4 g). Results: Fasting gallbladder volume (mean ± SE, 25.9 ± 1.8 ml and 19.2 ± 1.3 ml for patients and controls, respectively, p < 0.05) and postprandial gallbladder residual volume (48.7 ± 3.9% and 21.6 ± 2.8% of fasting volume in patients and controls, respectively, p < 0.001) were larger in patients than controls, indicating impaired gallbladder emptying. Gallstone patients were divided into 19 "contractors" and 17 "hypocontractors" (residual gallbladder volume smaller or greater than mean ± 2 SD of controls). Compared with the test meal alone, the addition of cholestyramine induced a further decrease of residual volume in contractors (from 30.4 ± 2.1% to 19.8 ± 1.9%, p < 0.001), hypocontractors (from 69.3 ± 3.9% to 56.7 ± 7.4%, p < 0.05), and controls (from 21.6 ± 2.8% to 5.0 ± 1.0%, p < 0.0004). Two hours after test meal plus cholestyramine, gallbladder volume was still markedly reduced in both patients and controls. Fasting gallbladder volume 24 h after test meal plus cholestyramine was decreased in patients and in controls. The ingestion of cholestyramine alone initiated gallbladder evacuation comparable to that of test meal in both contractors and hypocontractors. Conclusions: A low dose of cholestyramine in combination with test meal induces a considerable decrement of gallbladder volume compared with test meal alone in gallstone patients. Cholestyramine alone causes a decrease of gallbladder volume which is comparable to that observed in response to test meal alone.     

Fast-track management is safe and effective after bowel resection in children with Crohn's disease

Background

“Fast-track” management (FT) challenges traditional postoperative tenets in order to minimize discomfort and optimize inpatient care. We examined the outcomes of consecutively performed laparoscopic-assisted ileocecectomy for Crohn's disease (CD), with particular focus on FT's effects in patients with underlying bowel inflammation.

Methods

We retrospectively reviewed all patients undergoing isolated laparoscopic-assisted ileocecectomy for CD at our institution between 12/2000 and 12/2010, excluding patients with multiple areas of surgical CD, bladder involvement, or age > 18 years.

Results

Seventy-one patients aged 8–18 years underwent isolated laparoscopic-assisted ileocecectomy for CD, of which 45 met FT criteria. Individual practice patterns primarily determined which patients were FT-managed. FT management led to decreased length of stay (LOS), time to first stool, time to full diet, and intravenous narcotic use. No significant difference in complications or disease progression was observed between the two groups during 2-year follow up.

Conclusions

Our results suggest that FT is safe and effective in patients with CD. In a chronically ill population, counseling patients and families to expect early discharge is critical to the success of this strategy. Despite CD-related GI pathology, FT patients realized benefits in terms of LOS, time to bowel function, and narcotic use without any increase in complications.