Prognostic Factors Affecting Locoregional Recurrence in Patients with Stage IIIB Noninflammatory Breast Cancer

Background The aim of the present study was to identify the clinicopathological factors affecting locoregional recurrence (LRR) in patients with clinical stage IIIB noninflammatory breast cancer (NIBC). Methods The records of 120 stage IIIB NIBC patients treated with neoadjuvant chemotherapy (NAC) and then modified radical mastectomy followed by radiotherapy were evaluated. In this retrospective cohort, the effects of age, menopausal status, clinical tumor size, clinical response to NAC, pathological axillary status, number of positive axillary lymph nodes, pathological response to NAC, grade, lymphovascular invasion, estrogen receptor status, progesterone receptor status, Her-2-neu status, and p53 status on LRR were evaluated by univariate and multivariate analyses. Results The clinical response rate of 120 patients was 79.2% (17.5% complete and 61.7% partial), with a complete pathological response rate of 12.5%. The median follow-up was 28 months (range: 10–74 months). The LRR rate was 13.3%. Based on the univariate analysis, the clinical tumor size, clinical response rate, pathological axillary status, four or more positive axillary lymph nodes, lymphovascular invasion, and estrogen receptor status were factors that significantly affected LRR. In the multivariate analysis, however, only the clinical response rate and the number of positive axillary lymph nodes were found to be statistically significant independent factors. Conclusions Effective local control of disease can be achieved in patients with stage IIIB NIBC using a combination of NAC, surgery, and radiotherapy. However, a worse clinical response after chemotherapy and four or more positive axillary lymph nodes affect LRR negatively in these patients.     

Is surgery necessary for asymptomatic tethered cord in anorectal malformation patients?

Background

Evidence supporting routine surgery for asymptomatic tethered cord in patients with anorectal malformation (ARM) is, at best, speculative. The authors therefore examined whether untethering is indicated for asymptomatic tethered cord in patients with ARM.

Methods

A retrospective analysis of all patients with ARM (n = 223) between 1992 and 2002 was conducted. During the same period, 435 patients had surgery for tethered cord.

Results

Tethered cord was detected radiologically in 22 (9.8%); 8 patients with a low conus, and 14 with a low conus with and thickened filum. Seven of 22 patients underwent untethering; 3 prophylatic (14%) and 4 for neuro/motor function deficits (18%). All 4 symptomatic patients had significant clinical improvement in their neuro/motor functions after surgery. However, bowel and urinary functions remained unchanged in all 7 patients with a mean follow-up of 6.4 years (range, 4 to 8 years). Fifteen patients with radiologically diagnosed tethered cord remain asymptomatic with a mean follow-up of 2.7 years (range, 8 months to 10 years).

Conclusions

Neuro/motor functions clearly improved with surgery in symptomatic patients. However, bowel and urinary functions remained unchanged after surgery. Only 4 ARM patients with tethered cord required surgery, whereas prophylactic surgery appears to have minimal benefit. Expectant conservative approach in the management of asymptomatic tethered cord patient appears to be safe.     

Ultraviolet carcinogenesis in nonmelanoma skin cancer. Part I: incidence rates in relation to geographic locations and in migrant populations

Over the past two decades a worldwide increase in the incidence of skin cancer to near epidemic proportions has led to increased morbidity and appreciating cost. Well known risk factors include UV radiation, x or gamma irradiation, chemical carcinogens, genetic aberrations, and immunosuppression. This article reviews and analyzes the evidence for UV radiations role in the pathogenesis of nonmelanoma skin cancer (NMSC). Observations on the incidence of NMSC among migrants to temperate regions show an increase in both basal cell carcinoma and squamous cell carcinoma. There is also an increase in NMSC in areas with lower latitudes. Irradiation of human skin grafted to animals and animal models that develop NMSC lend further support to the role of UV radiation in the pathogenesis of NMSC. In the forthcoming Part II of this review, epidemiologic evidence will be presented attesting to the relationship between UV radiation and NMSC.     

Polysialylation and lipopolysaccharide‐induced shedding of E‐selectin ligand‐1 and neuropilin‐2 by microglia and THP‐1 macrophages

Microglia are tissue macrophages and mediators of innate immune responses in the brain. The protein‐modifying glycan polysialic acid (polySia) is implicated in modulating microglia activity. Cultured murine microglia maintain a pool of Golgi‐confined polySia, which is depleted in response to lipopolysaccharide (LPS)‐induced activation. Polysialylated neuropilin‐2 (polySia‐NRP2) contributes to this pool but further polySia protein carriers have remained elusive. Here, we use organotypic brain slice cultures to demonstrate that injury‐induced activation of microglia initiates Golgi‐confined polySia expression in situ. An unbiased glycoproteomic approach with stem cell‐derived microglia identifies E‐selectin ligand‐1 (ESL‐1) as a novel polySia acceptor. Together with polySia‐NRP2, polySia‐ESL‐1 is also detected in primary cultured microglia, in brain slice cultures and in phorbol ester‐induced THP‐1 macrophages. Induction of stem cell‐derived microglia, activated microglia in brain slice cultures and THP‐1 macrophages by LPS, but not interleukin‐4, causes polySia depletion and, as shown for stem cell‐derived microglia, a metalloproteinase‐dependent release of polySia‐ESL‐1 and polySia‐NRP2. Moreover, soluble polySia attenuates LPS‐induced production of nitric oxide and proinflammatory cytokines. Thus, shedding of polySia‐ESL‐1 and polySia‐NRP2 after LPS‐induced activation of microglia and THP‐1 macrophages may constitute a mechanism for negative feedback regulation. GLIA 2016 GLIA 2016;64:1314–1330     

Reduced levels of active GLP-1 in patients with cystic fibrosis with and without diabetes mellitus

Glucagon like peptide 1 (GLP-1) is an incretin hormone released as a bioactive peptide from intestinal L-cells in response to eating. It acts on target cells and exerts several functions as stimulating insulin and inhibiting glucagon. It is quickly deactivated by the serine protease dipeptidyl peptidase IV (DPP-IV) as an important regulatory mechanism. GLP-1 analogues are used as antidiabetic drugs in patients with type 2 diabetes. We served patients with cystic fibrosis (CF, n=29), cystic fibrosis related diabetes (CFRD, n=19) and healthy controls (n=18) a standardized breakfast (23 g protein, 25 g fat and 76 g carbohydrates) after an overnight fasting. Blood samples were collected before meal as well as 15, 30, 45 and 60 min after the meal in tubes prefilled with a DPP-IV inhibitor. The aim of the study was to compare levels of GLP-1 in patients with CF, CFRD and in healthy controls. We found that active GLP-1 was significantly decreased in patients with CF and CFRD compared to in healthy controls (p<0.01). However, levels in patients with CFRD tended to be lower but were not significantly lower than in patients with CF without diabetes (p=0.06). Total GLP-1 did not differ between the groups, which points to that the inactive form of GLP-1 is more pronounced in CF patients. The endogenous insulin production (measured by C-peptide) was significantly lower in patients with CFRD as expected. However, levels in non-diabetic CF patients did not differ from the controls. We suggest that the decreased levels of GLP-1 could affect the progression toward CFRD and that more studies need to be performed in order to evaluate a possible treatment with GLP-1 analogues in CF-patients.     

Versatility of the distally based superficial sural flap for reconstruction of lower leg and foot in children

Twenty children are presented after undergoing a distally based superficial sural flap for coverage of defects at the lower leg and foot. The age of the patients was between 1 and 12 years. Fifteen patients had trauma to the lower leg, with eight of them having associated injuries. Three had postburn contracture and two had pressure sore. In 14 cases, the flap was used as a fasciocutaneous flap, whereas in six cases it was used as a fascial flap covered with a skin graft. The flaps were used to cover the defects from the dorsum of the foot distally up to the mid third of tibia proximally. The mean follow-up was for a period of 2 years. Even though free tissue transfer is reliable and safe for the reconstruction of major leg injuries in children, the distally based superficial sural flap has the advantage of being easy to perform, with short operating time, minimal donor side morbidity, and preservation of major arteries of the leg.     

The influence of rotator cuff disease on the results of shoulder arthroplasty for primary osteoarthritis: results of a multicenter study

BACKGROUND: Rotator cuff disease is uncommon in primary glenohumeral osteoarthritis. Consequently, the prognostic implications of rotator cuff disease in patients undergoing prosthetic replacement for the treatment of primary glenohumeral osteoarthritis are uncertain. The purpose of this study was to report the effects of the condition of the supraspinatus tendon and the rotator cuff musculature on the results of shoulder arthroplasty in the treatment of primary osteoarthritis. METHODS: Five hundred and fifty-five shoulders in 514 patients who had an arthroplasty for the treatment of primary glenohumeral osteoarthritis as part of a multicenter study were evaluated. Forty-one shoulders had a partial-thickness tear of the supraspinatus, and forty-two had a full-thickness tear. Ninety shoulders had moderate (stage-2) fatty degeneration of the infraspinatus, and nineteen had severe (stage-3 or 4) degeneration. Eighty-four shoulders had moderate fatty degeneration of the subscapularis, and fifteen had severe degeneration. The influence of the condition of the supraspinatus tendon and the infraspinatus and subscapularis musculature on the postoperative outcome was evaluated with respect to the scores according to the system of Constant and Murley, active mobility, subjective satisfaction, radiographic result, and rate of complications. RESULTS: The shoulders were evaluated at a mean of 43.1 months postoperatively. With the numbers available, supraspinatus tears were not found to influence the postoperative outcome with respect to the total Constant score, active mobility, subjective satisfaction, radiographic result, or rate of complications. Additionally, the treatment of these tears did not markedly influence the outcome parameters. Conversely, both shoulders with moderate fatty degeneration and those with severe degeneration of the infraspinatus were associated with poorer results than those with no degeneration with respect to the total Constant score (p < 0.0005), active external rotation (p < 0.0005), active forward flexion (p = 0.001), and subjective satisfaction (p = 0.031). Similar although less dramatic results were seen with fatty degeneration of the subscapularis. CONCLUSIONS: This study demonstrates that minimally retracted or nonretracted rotator cuff tears that are limited to the supraspinatus tendon do not appreciably affect most shoulder-specific outcome parameters in shoulder arthroplasty performed for the treatment of primary osteoarthritis. Conversely, fatty degeneration of the infraspinatus and, less importantly, subscapularis musculature adversely affects many of these parameters.     

Unplanned return to operating room after lower extremity endovascular intervention is an independent predictor for hospital readmission

Objective

Hospital readmissions after surgical operations are preventable and are now counted as a quality metric. Patients with peripheral arterial disease often have several serious medical comorbidities. With advancements in endovascular technology and increasing comfort level of vascular surgeons, more and more patients with peripheral arterial disease are being treated with endovascular therapy. Most of these interventions are done as same-day operations. This study retrospectively reviewed the factors associated with hospital readmission after lower extremity endovascular interventions.

Epithelial–mesenchymal transformation markers E-cadherin and survivin predict progression of stage pTa urothelial bladder carcinoma

Purpose

To determine whether the immunohistochemical markers survivin and E-cadherin can predict progress at initially diagnosed Ta bladder cancer.

Methods

We retrospectively searched for every initially diagnosed pTa urothelial bladder carcinoma having been treated at our single-center hospital in Germany from January 1992 up to December 2004. Follow-up was recorded up to June 2010, with recurrence or progress being the endpoints. Immunohistochemical staining and analysis of survivin and E-cadherin of the TURB specimens were performed. Outcome dependency of progression and no progression with immunohistochemical staining was analyzed using uni- and multivariate regression analysis, Kaplan–Meier analysis and uni- and multivariate Cox regression analysis.

Results

Overall, 233 patients were included. Forty-two percent of those were tumor free in their follow-up TURBs, 46 % had at least one pTa recurrence and 12 % even showed progress to at least pT1 bladder cancer. Aberrant staining of E-cadherin was found within 71 % of patients with progression in contrast to only 40 % in cases without progression (p = 0.004). Of all progressed patients, 92 % showed overexpression of survivin in their initial pTa specimen compared to 61 % without progression (p = 0.001). Kaplan–Meier analysis revealed aberrant E-cadherin staining to be associated with worse progression-free survival (PFS) (p = 0.005) as well as overexpression of survivin (p = 0.003). In multivariate Cox regression analysis, strong E-cadherin staining was an independent prognosticator for better PFS (p = 0.033) and multifocality (p = 0.046) and tumor size over 3 cm (p = 0.042) were prognosticators for worse PFS.

Conclusion

Adding the immunohistochemical markers survivin and E-cadherin could help to identify patients at risk of developing a progressive disease in initial stage pTa bladder cancer.