Gastric electrical stimulation for refractory gastroparesis: predictors of response and redefining a successful outcome.

Predictors of a favorable response and measures of success with gastric electrical stimulation (GES) for gastroparesis remain elusive. Published results remain inconsistent with respect to patient perceived benefit, despite statistical improvements in objective measures of symptom severity. We performed a retrospective analysis of 56 patients with gastroparesis who underwent insertion of a gastric electrical stimulator during the study period. Data included demographics, symptoms, total symptom severity score (TSS, range 0-24, initial and most recent), and gastric emptying times. TSS were grouped into four severity categories (0-10, 11-14, 15-18, 19-24). TSS improvement was defined as movement to a lower severity category. Perception of improvement was compared with that of TSS score improvement using χ(2) test. Etiology as a predictor of improvement was measured using logistic regression. Initial mean TSS was 21, and post-treatment TSS was 13.5. Improvement was significant for individual symptoms and in reduction of TSS for both diabetic/idiopathic etiologies (P ≤ 0.001). No correlation was noted between likelihood of success/failure and gastric emptying times (P = 0.32). Thirty-eight improved (moved to lower TSS category), whereas 18 failed (remained in same category) (P ≤ 0.001), which correlated with perception of improvement. Of 18 failures, 14 (77.7%) were idiopathic. On logistic regression, diabetics were more likely than idiopathic patients to move to a lower TSS category (odds ratio 14, P = 0.003) and even more likely to improve based on patient perception (odds ratio 45, P = 0.005). GES produces far more consistent improvement in diabetics. Further study of GES in idiopathic gastroparesis is needed. Application of the proposed TSS severity categories allowed differentiation of small, statistically significant (but clinically insignificant) reductions in TSS from larger, clinically significant reductions, thereby permitting more reliable application of TSS to the evaluation of GES efficacy.

The effect of chronic renal insufficiency by use of glomerular filtration rate versus serum creatinine level on late clinical outcome of carotid endarterectomy.

BACKGROUND: Several studies have reported mixed results after carotid endarterectomy (CEA) in patients with chronic renal insufficiency (CRI), and we previously reported the perioperative outcome in patients with CRI by use of serum creatinine (Cr) level and glomerular filtration rate (GFR). However, only a few of these studies used GFR by the Modification of Diet in Renal Disease equation in their analysis of long-term outcome. METHODS: During the study period, 1000 CEAs (926 patients) were analyzed; 940 of these CEAs had Cr levels and 925 had GFR data. Patients were classified into normal (GFR ≥60 mL/min/1.73 m(2) or Cr <1.5 mg/dL), moderate CRI (GFR ≥30-59 or Cr ≥1.5-2.9), and severe CRI (GFR <30 or Cr ≥3). RESULTS: At a mean follow-up of 34.5 months and a median of 34 months (range, 1-53 months), combined stroke and death rates for Cr levels (867 patients) were 9%, 18%, and 44% for Cr <1.5, ≥1.5 to 2.9, and ≥3 (P = .0001) in contrast to 8%, 14%, and 26% for GFR (854 patients) of >60, ≥30 to 59, and <30, respectively (P = .0003). Combined stroke and death rates for asymptomatic patients were 8%, 17%, and 44% (P = .0001) for patients with Cr levels of <1.5, ≥1.5 to 2.9, and ≥3, respectively, vs 7%, 13%, and 24% for a GFR of ≥60, ≥30 to 59, and <30 (P = .0063). By Kaplan-Meier analysis, stroke-free survival rates at 1 year, 2 years, and 3 years were 97%, 94%, and 92% for Cr <1.5; 92%, 85%, and 81% for Cr ≥1.5 to 2.9; and 56%, 56%, and 56% for Cr ≥3 (P < .0001); vs 98%, 95%, and 93% for a GFR ≥60; 93%, 90%, and 86% for a GFR of ≥30 to 59; and 86%, 77%, and 73% for a GFR <30 (P < .0001). These rates for asymptomatic patients at 1 year, 2 years, and 3 years were 97%, 95%, and 93% for Cr <1.5; 94%, 87%, and 82% for Cr ≥1.5 to 2.9; and 56%, 56%, and 56% for Cr ≥3 (P < .0001); vs 98%, 95%, and 94% for a GFR ≥60; 95%, 91%, and 86% for a GFR of ≥30 to 59; and 84%, 80%, and 75% for a GFR <30 (P = .0026). A univariate regression analysis for asymptomatic patients showed that the hazard ratio (HR) of stroke and death was 6.5 (P = .0003) for a Cr ≥3 and 3.1 for a GFR <30 (P = .0089). A multivariate analysis showed that Cr ≥3 had an HR of stroke and death of 4.7 (P = .008), and GFR <30 had an HR of 2.2 (P = .097). CONCLUSIONS: Patients with severe CRI had higher rates of combined stroke/death. Therefore, CEA for these patients (particularly in asymptomatic patients) must be considered with caution.

False-negative results with the Bethesda System of reporting thyroid cytopathology: predictors of malignancy in thyroid nodules classified as benign by cytopathologic evaluation.

The benign category of the Bethesda System for reporting thyroid cytopathology (BSRTC) predicts an incidence of malignancy from zero to three per cent. However, recent series report higher rates of malignancy ranging from eight to 14 per cent. Surgery is often performed for reasons other than their fine needle aspiration biopsy (FNAB) such as symptoms, nodule enlargement, or worrisome imaging. We hypothesized that an analysis of patients who underwent thyroidectomy despite a benign FNAB would identify predictors of malignancy, an area not currently addressed by American Thyroid Association guidelines. We performed a retrospective analysis of patients with benign FNAB results who underwent thyroidectomy from October 2007 to October 2012. Data collected included symptoms, imaging findings, FNAB results, and operative and histopathology results, all of which were obtained by chart review. Findings were compared between patients with and without a diagnosis of malignancy. Statistical significance was set as P < 0.05. Of 3839 FNABs, 2838 were benign. Of these, 180 underwent surgery for indications other than the FNAB category. Twenty-four (13.4%) malignancies were identified: 12 (6.7%) incidental microcarcinomas and 12 (6.7%) significant cancers (papillary greater than 1.0 cm, any nonpapillary histology). No patient's symptoms or signs reached significance as a predictor of malignancy. Suspicious ultrasound appearance was significantly associated with an underlying carcinoma (P = 0.004). The false-negative result with benign FNAB is higher in surgical series than suggested by the BSRTC. Patients with tolerable symptoms may be observed in the face of a benign FNAB. Additionally, despite a benign FNAB, recommendations for closer follow-up or surgical intervention are warranted if the ultrasound appearance is suspicious.

Practice patterns of carotid endarterectomy as performed by different surgical specialties at a single institution and the effect on perioperative stroke and cost of preoperative imaging.

BACKGROUND: Carotid endarterectomy (CEA) is currently performed by various surgical specialties with varying outcomes. This study analyzes different surgical practice patterns and their effect on perioperative stroke and cost. METHODS: This is a retrospective analysis of prospectively collected data of 1000 consecutive CEAs performed at our institution by three different specialties: general surgeons (GS), cardiothoracic surgeons (CTS), and vascular surgeons (VS). RESULTS: VS did 474 CEAs, CTS did 404, and GS did 122. VS tended to operate more often on symptomatic patients than CTS and GS: 40% vs 23% and 31%, respectively (P < .0001). Preoperative workups were significantly different between specialties: duplex ultrasound (DUS) only in 66%, 30%, and 18%; DUS and computed tomography angiography in 27%, 35%, and 29%; and DUS and magnetic resonance angiography in 6%, 35%, and 52% for VS, CTS, and GS, respectively (P < .001). The mean preoperative carotid stenosis was not significantly different between the specialties. The mean heparin dosage was 5168, 7522, and 5331 units (P = .0001) and protamine was used in 0.2%, 19%, and 8% (P < .0001) for VS, CTS, and GS, respectively. VS more often used postoperative drains; however, no association was found between heparin dosage, protamine, and drain use and postoperative bleeding. Patching was used in 99%, 93%, and 76% (P < .0001) for VS, CTS, and GS, respectively. Bovine pericardial patches were used more often by CTS and ACUSEAL (Gore-Tex; W. L. Gore and Associates, Flagstaff, Ariz) patches were used more often by GS (P < .0001). The perioperative stroke/death rates were 1.3% for VS and 3.1% for CTS and GS combined (P = .055); and were 0.7% for VS and 3% for CTS and GS combined for asymptomatic patients (P < .034). Perioperative stroke rates for patients who had preoperative DUS only were 0.9% vs 3.3% for patients who had extra imaging (computed tomography angiography/magnetic resonance angiography; P = .009); and were 0.9% vs 3% for asymptomatic patients (P = .05). When applying hospital billing charges for preoperative imaging workups (cost of DUS only vs DUS and other imaging), the VS practice pattern would have saved $1180 per CEA over CTS and GS practice patterns; a total savings of $1,180,000 in this series. CONCLUSIONS: CEA practice patterns differ between specialties. Although the cost was higher for non-VS practices, the perioperative stroke/death rate was somewhat higher. Therefore, educating physicians who perform CEAs on cost-saving measures may be appropriate.

The effect of surgeon's specialty and volume on the perioperative outcome of carotid endarterectomy.

BACKGROUND: Several studies have demonstrated better outcomes for carotid endarterectomy (CEA) at high-volume hospitals and providers. However, only a few studies have reported on the impact of surgeons' specialty and volume on the perioperative outcome of CEA. METHODS: This is a retrospective analysis of CEA during a recent 2-year period. Surgeons' specialties were classified according to their Board specialties into general surgeons (GS), cardiothoracic surgeons (CT), and vascular surgeons (VS). Surgeons' annual volume was categorized into low volume (<10 CEAs), medium volume (10 to <30 CEAs), and high volume (≥30 CEAs). The primary outcome was 30-day perioperative stroke and/or death; however, other perioperative complications were analyzed. Both univariate and multivariate analyses were done to predict the effect of specialty/volume and any other patient risk factors on stroke outcome. RESULTS: Nine hundred and fifty-three CEAs were performed by 24 surgeons: 122 by seven GS, 383 by 13 CT, and 448 by 4 VS. Patients' demographics/clinical characteristics were similar between specialties, except the incidence of coronary artery disease, which was higher for CT (P < .0001). The indications for CEA were symptomatic disease in 38% for VS, 31% for GS, and 23% for CT (P < .0001). The perioperative stroke and death rates were 4.1%, 2.9%, and 1.3% for GS, CT, and VS, respectively (P = .126). A subgroup analysis showed that the perioperative stroke rates for symptomatic patients were 5.3%, 2.3%, and 2.3% (P = .511) and for asymptomatic patients were 3.6%, 3%, and 0.72% (P = .099) for GS, CT, and VS, respectively. Perioperative stroke rates were significantly higher for nonvascular surgeons (GS and CT combined) vs VS in asymptomatic patients (3.2% vs 0.72%; P = .033). Perioperative stroke/death was also significantly lower for high-volume surgeons: 1.3% vs 4.1% and 4.3% for medium- and low-volume surgeons (P = .019) (1.3% vs 4.15% for high vs low/medium combined; P = .005). More CEAs were done for asymptomatic patients in the low/medium-volume surgeons (78%) vs high-volume surgeons (64%; P < .0001) with a stroke rate of 4.6% for low/medium-volume surgeons vs 0.51% for high-volume surgeons (P = .0005). A univariate logistic analysis showed that the odds ratio of having a perioperative stroke was 0.3 (95% confidence interval [CI], 0.13-0.73; P =.008) for high-volume surgeons vs low/medium-volume surgeons, 0.4 (95% CI, 0.16-1.07; P = .069) for VS vs CT/GS and 0.2 (95% CI, 0.06-0.45; P = .0004) when patching was used. A multivariate analysis showed that the odds ratio of having a perioperative stroke for CT VS was 2.1 (95% CI, 0.71-5.92; P = .183); for GS vs VS, 1.8 (95% CI, 0.49-6.90; P = .3709); for low-volume surgeons (vs high-volume) 3.4 (95% CI, 0.96-11.77; P = .0581); medium- vs high-volume surgeons 2.2 (95% CI, 0.75-6.42; P = .1509). CONCLUSIONS: High-volume surgeons had significantly better perioperative stroke/death rates for CEA than low/medium-volume surgeons. Perioperative stroke/death rates were also higher for nonvascular surgeons in asymptomatic patients.

Endovascular repair of subclavian/axillary artery injury with a covered stent. A case report and review of literature.

Experience with and acceptance of endovascular repair of arch vessel injuries continues to increase. This manuscript reports the case of a 65-year-oldman with a gunshot wound to the right supraclavicular area with a hematoma, pulsating mass and loss of neurological function of the right upper extremity. As he was hemodynamically stable, a computed tomography angiogram was performed and it demonstrated a 6 cm right subclavian/axillary artery pseudoaneurysm. The patient was taken to the angiogram/ hybrid room and an arch angiogram was performed. A selective right subclavian angiogram was performed and a covered stent was deployed across the pseudoaneurysm and a completion angiogram showed complete exclusion with normal runoff to the upper extremity. In conclusion, penetrating subclavian/axillary artery trauma can be successfully managed with minimal morbidity via early utilization of endovascular covered stent therapy. A literature review suggests that the endovascular approach will soon be the standard of care for traumatic disruption of subclavian arteries.

Impact of chronic renal insufficiency using serum creatinine vs glomerular filtration rate on perioperative clinical outcomes of carotid endarterectomy.

BACKGROUND: Several studies have reported conflicting results after carotid endarterectomy in patients with chronic renal insufficiency (CRI). However, only a few used glomerular filtration rate (GFR) (Modification of Diet in Renal Disease) in their analysis. STUDY DESIGN: Nine hundred and forty carotid endarterectomies that had serum creatinine and GFR were analyzed. Patients were classified as normal (creatinine <1.5 mg/dL or GFR ≥60 mL/min/1.73 m(2)); moderate CRI (creatinine ≥1.5 to 2.9 mg/dL or GFR ≥30 to 59 mL/min/1.73 m(2)), and severe CRI (creatinine ≥3 mg/dL or GFR <30 mL/min/1.73 m(2)). RESULTS: Using creatinine, perioperative stroke and major adverse event rates for normal, moderate CRI, and severe CRI were 2%, 3.5%, and 11.1% (p = 0.091) and 2.4%, 4.4%, and 11.1% (p = 0.089) vs 1.1%, 3.7%, and 5.4% (p = 0.018) and 1.8%, 4%, and 5.4% (p = 0.086) using GFR. Univariate logistic regression analysis showed that creatinine ≥1.5 mg/dL had an odds ratio of 2.1 for having early stroke/death vs an odds ratio of 3.5 (p = 0.009) for GFR <60 mL/min/1.73 m(2). A multivariate analysis showed that GFR <60 mL/min/1.73 m(2) had an odds ratio for early stroke/death of 3.7 (p = 0.013). Using creatinine, perioperative stroke rates for symptomatic patients were 2.8%, 2.6%, and 0% and 1.6%, 4.1%, and 11.1% (p = 0.045) for asymptomatic patients with normal, moderate CRI, and severe CRI vs 1.6%, 4.7%, and 9.1% for symptomatic patients (p = 0.09) and 1%, 3.2%, and 3.9% for asymptomatic patients (p = 0.074) using GFR. Perioperative major adverse event rates for symptomatic patients using creatinine were 3.2%, 2.6%, and 0%, and for asymptomatic patients 2.1%, 5.4%, and 11.1% (p = 0.048) vs 2.1%, 4.7%, and 9.1% for symptomatic patients and 1.7%, 3.7%, and 7.7% (p = 0.193) for asymptomatic patients using GFR. Moderate/severe CRI also had more cardiac (5.7% vs 2.4%; p = 0.072) and respiratory complications (2.5% vs 0.2%; p = 0.018). CONCLUSIONS: Glomerular filtration rate (Modification of Diet in Renal Disease) was more sensitive in detecting perioperative stroke/death after carotid endarterectomy in patients with CRI. Patients with moderate/severe CRI had more major adverse events than normal patients.

Ang II and EGF synergistically induce COX-2 expression via CREB in intestinal epithelial cells.

Cyclooxygenase (COX)-2 derived prostaglandins (PGs) play a major role in intestinal inflammation and colorectal carcinogenesis. Because COX-2 is the rate-limiting step in the production of PGs, mechanisms that regulate COX-2 expression control PG production in the cell. Using the non-tumorigenic, rat intestinal epithelial cell, IEC-18, we demonstrate that co-activation of endogenously expressed AT(1) receptor and EGFR resulted in synergistic expression of COX-2 mRNA and protein involving transcriptional and post-transcriptional mechanisms. Ang II and EGF induced transient phosphorylation of ERK, p38(MAPK) and CREB. Co-stimulation with Ang II and EGF prolonged phosphorylation of ERK, p38(MAPK), and CREB. The p38(MAPK) selective inhibitor, SB202190, but not the MEK selective inhibitor, PD98059, or the EGFR kinase inhibitor, AG1478, inhibited Ang II-dependent COX-2 expression and CREB phosphorylation. EGF-dependent COX-2 expression and CREB phosphorylation were inhibited by SB202190, PD98059, and AG1478. Inhibition of CREB expression using two separate RNAi methods blocked COX-2 expression by Ang II and EGF. Expression of a dominant negative CREB mutant inhibited Ang II- and EGF-dependent induction of the COX-2 promoter. Ang II induced luciferase expression in cells transfected with the CRE-luc reporter vector and cells co-transfected with Gal4-luc reporter vector and a Gal4-CREB expression vector. Chromatin immunoprecipitation assays demonstrated CREB binding to the proximal rat COX-2 promoter region containing a CRE cis-acting element. These results indicate that co-stimulation with Ang II and EGF synergistically induced COX-2 expression in these intestinal epithelial cells through p38(MAPK) mediated signaling cascades that converge onto CREB.

15-Hydroxyprostaglandin dehydrogenase suppresses K-RasV12-dependent tumor formation in Nu/Nu mice.

Oncogenic Ras mutations are early genetic events in colorectal cancer that induce cyclooxygenase (COX)-2 expression and prostaglandin E(2) (PGE(2)) biosynthesis. PGE(2), a downstream product of COX-2, promotes cancer progression by modulating proliferation, apoptosis and angiogenesis. 15-hydroxyprostaglandin dehydrogenase (PGDH) degrades PGE(2) and is down-regulated in colorectal cancer, suggesting that PGDH plays a role in regulating PGE(2) levels and that PGDH over-expression could attenuate Ras-mediated tumorigenesis. Lentiviral transduction was used to express GFP (18.GFP), K-Ras(V12) (18.K-Ras(V12)), PGDH (18.PGDH) or both K-Ras(V12) and PGDH (18.K-Ras(V12).PGDH) in nontumorigenic rat intestinal epithelial (IEC-18) cells. 18.K-Ras(V12) cells exhibited increased phosphorylation of MAP kinases and CREB, proliferation rates, COX-2 and microsomal prostaglandin E synthase (mPGES)-1 expression and PGE(2) and PGI(2) levels. 18.PGDH and 18.K-Ras(V12).PGDH cells had 10(4)-fold increases in PGDH activity with decreased PGE(2) and PGI(2) levels, COX-2 and mPGES-1 expression and proliferation rates. 18.GFP, 18.PGDH, and 18.K-Ras(V12).PGDH cells were unable to grow in soft agar media whereas 18.K-Ras(V12) cells exhibited anchorage-independent cell growth. Xenografts of implanted 18.K-Ras(V12) cells in nu/nu mice produced rapid (2 wk) tumors with uniform antibody staining for COX-2 and mPGES-1 throughout the tumor and elevated PGE(2) levels. Xenografts of 18.K-Ras(V12).PGDH cells exhibited delayed (8 wk) tumor formation with negligible COX-2 and mPGES-1 expression and significantly decreased PGE(2) levels. 18.K-Ras(V12).PGDH tumors had decreased staining of the proliferative marker, Ki-67, and a significant increase in apoptosis in the central region of the tumor. Based on these data, we conclude that PGDH expression suppresses K-Ras(V12)-mediated tumorigenesis in intestinal epithelial cells.