Disease-based mortality after percutaneous endoscopic gastrostomy: utility of the enterprise data warehouse

Background

Percutaneous endoscopic gastrostomy (PEG) remains a mainstay of enteral access. Thirty-day mortality for PEG has ranged from 16 to 43 %. This study aims to discern patient groups that demonstrate limited survival after PEG placement. The Enterprise Data Warehouse (EDW) concept allows an efficient means of integrating administrative, clinical, and quality-of-life data. On the basis of this concept, we developed the Vanderbilt Procedural Outcomes Database (VPOD) and analyzed these data for evaluation of post-PEG mortality over time.

Methods

Patients were identified using the VPOD from 2008 to 2010 and followed for 1 year after the procedure. Patients were categorized according to common clinical groups for PEG placement: stroke/CNS tumors, neuromuscular disorders, head and neck cancers, other malignancies, trauma, cerebral palsy, gastroparesis, or other indications for PEG. All-cause mortality at 30, 60, 90, 180, and 360 days was determined by linking VPOD information with the Social Security Death Index. Chi-square analysis was used to determine significance across groups.

Results

Nine hundred fifty-three patients underwent PEG placement during the study period. Mortality over time (30-, 60-, 90-, 180-, and 360-day mortality) was greatest for patients with malignancies other than head and neck cancer (29, 45, 57, 66, and 72 %) and least for cerebral palsy or patients with gastroparesis (7 % at all time points). Patients with neuromuscular disorders had a similar mortality curve as head and neck cancer patients. Stroke/CNS tumor patients and patients with other indications had the second highest mortality, while trauma patients had low mortality.

Conclusions

PEG mortality was much higher in patients with malignancies other than head and neck cancer compared to previously published rates. PEG should be used with great caution in this and other high-risk patient groups. This study demonstrates the power of an EDW-based database to evaluate large numbers of patients with clinically meaningful results.     

Causes of dissatisfaction after laparoscopic fundoplication: the impact of new symptoms, recurrent symptoms, and the patient experience

Background

Although laparoscopic fundoplication effectively alleviates gastroesophageal reflux disease (GERD) in the great majority of patients, some patients remain dissatisfied after the operation. This study was undertaken to report the outcomes of these patients and to determine the causes of dissatisfaction after laparoscopic fundoplication.

Methods

All patients undergoing laparoscopic fundoplication in the authors’ series from 1992 to 2010 were evaluated for frequency and severity of symptoms before and after laparoscopic fundoplication, and their experiences were graded from “very satisfying” to “very unsatisfying.” Objective outcomes were determined by endoscopy, barium swallow, and pH monitoring. Primary complaints were derived from postoperative surveys. Median data are reported.

Results

Of the 1,063 patients undergoing laparoscopic fundoplication, 101 patients reported dissatisfaction after the procedure. The follow-up period was 33 months. The dissatisfied patients (n = 101) were more likely than the satisfied patients to have postoperative complications (9 vs 4 %; p < 0.05) and to have undergone a prior fundoplication (22 vs 11 %; p < 0.05). For the dissatisfied patients, heartburn decreased in frequency and severity after fundoplication (p < 0.05) but remained notable. Also for the dissatisfied patients, new symptoms (gas bloat/dysphagia) were the most prominent postoperative complaint (59 %), followed by symptom recurrence (23 %), symptom persistence (4 %), and the overall experience (14 %). Primary complaints of new symptoms were most common within the first year of follow-up assessment and less frequent thereafter. Primary complaints of recurrent symptoms generally occurred more than 1 year after fundoplication.

Conclusions

Dissatisfaction is uncommon after laparoscopic fundoplication. New symptoms, such as dysphagia and gas/bloating, are primary causes of dissatisfaction despite general reflux alleviation among these patients. New symptoms occur sooner after fundoplication than recurrent symptoms and may become less common with time.     

Retrograde Versus Antegrade Nerve Sparing During Robot-assisted Radical Prostatectomy: Which Is Better for Achieving Early Functional Recovery?

Background

Although the retrograde approach to nerve sparing (NS) aimed at maximizing NS during robot-assisted radical prostatectomy (RARP) has been described, its significant benefits compared to the antegrade approach have not yet been investigated.

Objective

To evaluate the impact of NS approaches on perioperative, pathologic, and functional outcomes.

Design, setting, and participants

Five hundred one potent (Sexual Health Inventory for Men [SHIM] score >21) men underwent bilateral full NS and were followed up for a minimum of 1 yr. After propensity score matching, 344 patients were selected and were then categorized into two groups.

Surgical procedure

RARP with antegrade NS (n = 172) or RARP with retrograde NS (n = 172).

Outcome measurements and statistical analysis

Functional outcomes were assessed using validated questionnaires. Multivariable logistic regression models were applied.

Results and limitations

Positive margin rates were similar (11.1% vs 6.9%; p = 0.192), and no correlation with the NS approach was found on regression analysis. At 3, 6, and 9 mo, the potency rate was significantly higher in the retrograde approach (65% vs 80.8% and 72.1% vs 90.1% and 85.3% vs 92.9%, respectively). The multivariable model indicated that the NS approach was an independent predictor for potency recovery at 3, 6, and 9 mo, along with age, gland size, and hyperlipidemia. After adjusting for these predictors, the hazard ratio (HR) for the retrograde relative to the antegrade approach was 2.462 (95% confidence interval [CI], 1.482–4.089; p = 0.001) at 3, 4.024 (95% CI, 2.171–7.457; p < 0.001) at 6, and 2.145 (95% CI, 1.019–4.514; p = 0.044) at 9 mo. Regarding continence, the recovery rates at each time point and the mean time to regaining it were similar, and the method of NS had no effect on multivariable analysis. The absence of randomization is a major limitation of this study.

Conclusions

In patients with normal erectile function who underwent bilateral full NS, a retrograde NS approach facilitated early recovery of potency compared to that with an antegrade NS approach without compromising cancer control.     

High reliability of an algorithm for choice of implants in hip fracture patients

Purpose

Hip fracture treatment is controversial, with high complication rates. An algorithm for hip fracture surgery has shown reduced reoperation rates, but choice of implant is based on the commonly used fracture classifications, which were previously evaluated to be unreliable. The purpose of this study was to investigate the reliability of the algorithm.

Methods

From two hospitals, four observers (orthopaedic consultant, fellow, resident and intern) used the algorithm to classify into 15 hip fracture types [Garden type I–IV femoral neck including posterior tilt, vertical femoral neck, basocervical and Arbeitsgemeinschaft für Osteosynthesefragen (AO)-31 A1.1 to A3.3 trochanteric fractures] and to choose between five surgical procedures [parallel implants, prosthesis, two-or four-hole sliding hip screw (SHS) and intermedullary (IM) nail]. After individual assessment, each hospital made a consensus decision. Observations were performed twice, ten weeks apart, on pelvic, anteroposterior (AP) and axial X-rays from 100 consecutive patients.

Results

For fracture classification, mean kappa values were 0.60 for intra and 0.62 for interobserver variation, with interobserver variation between hospitals at 0.65. For posterior tilt, mean intraclass correlation coefficient was 0.91 for intra and 0.87 for interobserver variation. For choice of implant type, mean kappa values were 0.86 for both intra and interobserver variation. The two hospital consensus decisions chose same implant in 91 of 100 patients, giving a kappa value at 0.88.

Conclusion

Although hip fracture classification confirmed to be somewhat unreliable in this study, posterior tilt measurement and subsequent choice of implant type by the algorithm was found to be reliable, which opens up the possibility for a more standardized treatment of hip fracture patients between hospitals.     

Sclerostin antibody improves skeletal parameters in a Brtl/+ mouse model of osteogenesis imperfecta

Osteogenesis imperfecta (OI) is a genetic bone dysplasia characterized by osteopenia and easy susceptibility to fracture. Symptoms are most prominent during childhood. Although antiresorptive bisphosphonates have been widely used to treat pediatric OI, controlled trials show improved vertebral parameters but equivocal effects on long‐bone fracture rates. New treatments for OI are needed to increase bone mass throughout the skeleton. Sclerostin antibody (Scl‐Ab) therapy is potently anabolic in the skeleton by stimulating osteoblasts via the canonical wnt signaling pathway, and may be beneficial for treating OI. In this study, Scl‐Ab therapy was investigated in mice heterozygous for a typical OI‐causing Gly→Cys substitution in col1a1. Two weeks of Scl‐Ab successfully stimulated osteoblast bone formation in a knock‐in model for moderately severe OI (Brtl/+) and in WT mice, leading to improved bone mass and reduced long‐bone fragility. Image‐guided nanoindentation revealed no alteration in local tissue mineralization dynamics with Scl‐Ab. These results contrast with previous findings of antiresorptive efficacy in OI both in mechanism and potency of effects on fragility. In conclusion, short‐term Scl‐Ab was successfully anabolic in osteoblasts harboring a typical OI‐causing collagen mutation and represents a potential new therapy to improve bone mass and reduce fractures in pediatric OI. © 2013 American Society for Bone and Mineral Research     

Enhancement of hepatic 4‐hydroxylation of 25‐hydroxyvitamin D3 through CYP3A4 induction in vitro and in vivo: Implications for drug‐induced osteomalacia

Long‐term therapy with certain drugs, especially cytochrome P450 (P450; CYP)‐inducing agents, confers an increased risk of osteomalacia that is attributed to vitamin D deficiency. Human CYP24A1, CYP3A4, and CYP27B1 catalyze the inactivation and activation of vitamin D and have been implicated in the adverse drug response. In this study, the inducibility of these enzymes and monohydroxylation of 25‐hydroxyvitamin D₃ (25OHD₃) were evaluated after exposure to P450‐inducing drugs. With human hepatocytes, treatment with phenobarbital, hyperforin, carbamazepine, and rifampin significantly increased the levels of CYP3A4, but not CYP24A1 or CYP27B1 mRNA. In addition, rifampin pretreatment resulted in an 8‐fold increase in formation of the major metabolite of 25OHD₃, 4β,25(OH)₂D₃. This inductive effect was blocked by the addition of 6′,7′‐dihydroxybergamottin, a selective CYP3A4 inhibitor. With human renal proximal tubular HK‐2 cells, treatment with the same inducers did not alter CYP3A4, CYP24A1, or CYP27B1 expression. 24R,25(OH)₂D₃ was the predominant monohydroxy metabolite produced from 25OHD₃, but its formation was unaffected by the inducers. With healthy volunteers, the mean plasma concentration of 4β,25(OH)₂D₃ was increased 60% (p < 0.01) after short‐term rifampin administration. This was accompanied by a statistically significant reduction in plasma 1α,25(OH)₂D₃ (?10%; p = 0.03), and a nonsignificant change in 24R,25(OH)₂D₃ (?8%; p = 0.09) levels. Further analysis revealed a negative correlation between the increase in 4β,25(OH)₂D₃ and decrease in 1α,25(OH)₂D₃ levels. Examination of the plasma monohydroxy metabolite/25OHD₃ ratios indicated selective induction of the CYP3A4‐dependent 4β‐hydroxylation pathway of 25OHD₃ elimination. These results suggest that induction of hepatic CYP3A4 may be important in the etiology of drug‐induced osteomalacia. © 2013 American Society for Bone and Mineral Research.     

Benchtop evaluation of pressure barrier insufflator and standard insufflator systems

Background

Previous experimental research has reported minimal differences in pressure maintenance between different versions of standard insufflators (SI). However, a recent report identified potential clinical benefits with a valveless pressure barrier insufflator (PBI). We sought to perform a benchtop objective evaluation of SI and PBI systems.

Methods

A rigid box system with continuous pressure manometry was used to evaluate a PBI (Surgiquest Airseal) and two SIs (SI1 = Stryker PneumoSure High Flow Insufflator and SI2 = Storz SCB Thermoflator). Pressure maintenance of 15 mmHg was evaluated during experimental conditions of leakage from a 5 mm port site, leakage from a 12 mm port site, and continuous suction.

Results

With leakage from the 5 mm port site, the PBI maintained pressure of >13 mmHg whereas the pressures dropped moderately with the SI1 (7–13 mmHg) and SI2 insufflators (3–7 mmHg) and did not regain goal pressure until leakage was stopped. With leakage from 12 mm port site, the PBI pressure decreased to 9–11 mmHg, whereas the SI1 and SI2 lost insufflation pressures completely. The PBI maintained pressure of >11 mmHg during continuous suction while the SI1 and SI2 lost pressure entirely, and actually showed negative pressure from air suction into the rigid box system. When evaluated statistically with the mixed model repeated measures ANOVA, the SI1 and SI2 performed similarly while the PBI maintained increased pressure.

Conclusions

In the experimental rigid box system, the PBI more successfully maintained pressure in response to leakage and suction than SIs.     

Early Assessment of Axillary Response with 18F-FDG PET/CT during Neoadjuvant Chemotherapy in Stage II–III Breast Cancer: Implications for Surgical Management of the Axilla

Background

If all initially node-positive patients undergo axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NAC), overtreatment may occur in patients with complete response. Positron emission tomography–computed tomography (PET/CT) during NAC may predict axillary response and select patients appropriate for less invasive treatment after NAC. We evaluated the value of sequential ¹⁸F fluorodeoxyglucose (FDG) PET/CTs during NAC for axillary response monitoring in stage II–III breast cancer.

Methods

A total of 219 PET/CTs were performed in 80 patients with cytology-proven, node-positive disease at baseline (PET/CT1, n = 80) and twice during NAC (PET/CT2 n = 62, PET/CT3, n = 77). The relative changes in maximum standardized uptake value (SUV_max) of axillary nodes were examined for their ability to assess pathological response. All patients underwent ALND after chemotherapy, and complete axillary response (pCR), defined as absence of isolated tumor cells and of micro- and macrometastases, served as the reference standard.

Results

A total of 32 (40 %) patients experienced axillary pCR. The relative decrease in SUV_max was significantly higher in patients with pCR than in those without, both on PET/CT2 (p < 0.001) and PET/CT3 (p = 0.025). The area under the receiver operating characteristic curve values for PET/CT2 and PET/CT3 were 0.80 (95 % confidence interval 0.68–0.92) and 0.65 (95 % confidence interval 0.52–0.79), respectively. A relative decrease of ≥60 % on PET/CT2 had an excellent specificity (35 of 37, 95 %), a high positive predictive value (12 of 14, 86 %), and a sensitivity of 48 %—that is, it accurately identified histologic pCR in 12 of 25 patients with disease that responded to therapy.

Conclusions

¹⁸F-FDG PET/CT early during NAC is useful for axillary response monitoring in cytology-proven node-positive breast cancer because it identifies pathological response, thus permitting ALND to be spared.