Determining Pattern of Recurrence Following Pancreaticoduodenectomy and Adjuvant 5-Flurouracil-Based Chemoradiation Therapy: Effect of Number of Metastatic Lymph Nodes and Lymph Node Ratio

Background  There are limited data on patterns of recurrence and factors associated with local recurrence following pancreaticoduodenectomy for pancreatic adenocarcinoma and adjuvant 5-flurouracil-based chemoradiation therapy. Methods and Materials  Between 1995 and 2005, 905 patients underwent pancreaticoduodenectomy for pancreatic adenocarcinoma; 154 patients had complete pattern of recurrence data available. Results  At median follow-up of 20.2 months, 103 (66.9%) patients recurred with median time to recurrence of 16.2 months. Most patients recurred with distant disease only (68.9%), while 21.4% patients recurred with local disease only; ten (9.7%) patients recurred with local and distant disease. Several factors were associated with local recurrence: poor tumor differentiation (hazards ration [HR] 2.39) and presence of metastatic lymph nodes (HR 1.89, both p < 0.05). Among N1 patients, poor tumor differentiation (HR 3.92), >5 metastatic LN (HR 3.75), and lymph node ratio (LNR) >0.4 (HR 2.96) had the highest risk of local recurrence (all p < 0.05). Increasing LNR was associated with an incremental increased risk of local recurrence (LNR <0.2, 21.3% versus LNR ≥0.2 to 0.4, 25.2% versus LNR >0.4, 40.4%; p < 0.05). Conclusions  Although most patients who receive standard 5-flurouracil-based chemoradiation therapy will ultimately succumb to distant disease, about 30% recur locally. Poor tumor differentiation, a high number of metastatic LN (>5), and LNR >0.4 are associated with the highest risk of local failure. In these patients, radiation dose escalation and/or a combination of radiation with novel chemotherapeutic agents may be necessary to improve outcomes. Presented at the American Hepato-Pancreato-Biliary Association Annual Meeting, Ft. Lauderdale, Florida, March 29th, 2008     

DXA-based hip structural analysis of once-weekly bisphosphonate-treated postmenopausal women with low bone mass

Summary  DXA-based hip structural analysis from 947 individuals completing two large osteoporosis clinical trials was pooled and analyzed. Treatment with once-weekly (OW) ALN or OW RIS resulted in significant improvements from baseline in geometric parameters at all three HSA ROIs. Improvements were generally greater with OW ALN than OW RIS. Introduction  BMD can be altered by changes in distribution and quantity of bone and changes in mineralization. These effects cannot be distinguished with conventional measurements of BMD. Currently, tissue composition is evaluated only by invasive means. Structural geometry of the proximal femur, however, can be measured in vivo by several methods, including dual energy X-ray absorptiometry (DXA) using specialized hip structure analysis (HSA) software. Methods  DXA-based HSA was obtained and analyzed in a subset of 947 subjects participating in the Fosamax Actonel Comparison Trials. Data were pooled to evaluate treatment effects on the structural geometry of the proximal femur by once-weekly alendronate (ALN) 70 mg and risedronate (RIS) 35 mg in postmenopausal women with low bone mass. Results  Both ALN and RIS treatment over 2 years resulted in improvements in HSA-derived geometry at all three HSA regions of interest (ROI). The largest treatment effects were seen at the intertrochanteric ROI. Consistently greater treatment effects were seen with ALN compared with RIS at all three HSA-ROIs. Conclusions  HSA offers insight into the potential mechanisms of fracture risk reduction from pharmacologic intervention. In the current study, treatment with once-weekly bisphosphonates resulted in significant improvements in hip geometric parameters.     

Biochemical and histological assessment of Alkali therapy during high animal protein intake in the rat

The Westernized diet is acidogenic due to the high content of sulfur-containing amino acids and relative deficiency of potassium organic anions. Chronic acid loads result in hypercalciuria and negative calcium balance often associated with loss of bone mineral. Alkali therapy tends to reverse the hypercalciuria but little is known regarding its effect on bone as assessed by bone histomorphometry. The present study utilized dynamic bone histomorphometry to evaluate the effects of alkali therapy on acid-induced changes in bone turnover. Serum and urine analyses and bone histomorphometry were assessed in adult rats after 2 months of either a low casein (LC) or high casein (HC) diet supplemented with either potassium chloride (KCl) or potassium citrate (KCit). Compared to animals on LC-KCl diet, HC-KCl diet delivered a substantial acid load as shown by significant increases in urinary sulfate, ammonium, and net acid excretion, and a lower urinary pH and citrate excretion without detectable changes in serum parameters. The acid load also resulted in hypercalciuria. Dynamic and static bone histomorphometry disclosed a significant reduction in cancellous bone volume and trabecular number associated with a 2.5-fold increase in eroded and a 3.5-fold increase in osteoclastic surfaces. There was also a near 2-fold increase in bone formation rate in rats on the HC-KCl diet. When animals on the HC diet were given KCit instead of KCl, all of the aforementioned changes in urine biochemistry and bone turnover were significantly attenuated or entirely prevented. These findings underscore the deleterious effects of high animal protein intake in promoting hypercalciuria and increasing bone turnover. Co-administration of potassium alkali attenuates or prevents these changes. In this animal model of high dietary animal protein intake, the major skeletal effect of alkali therapy is to reduce bone resorption, with little or no effect on bone formation.     

A multidisciplinary protocol improves electrolyte replacement and its effectiveness

Background

We implemented a multidisciplinary electrolyte replacement protocol in a tertiary referral center surgical intensive care unit. The purpose of this study was to evaluate its efficacy.

Methods

This was a retrospective study. The electrolyte replacement protocol was designed for the replacement of potassium, magnesium, and phosphorous and was nurse driven. Data evaluated included patient demographics and details specific to electrolyte replacement. Univariate analyses were performed by using the Student t test and the Fisher exact test. A P value of <.05 was considered significant.

Results

After implementation of the protocol, overall electrolyte replacement improved from 70% to 79% (P = .03), and its overall effectiveness increased from 50% to 65% (P = .01). Individual electrolyte replacement, effectiveness, and dosing varied.

Conclusions

The implementation of a multidisciplinary electrolyte replacement protocol in a tertiary referral center surgical intensive care unit significantly improved both overall electrolyte replacement and its effectiveness.     

The use of RhBMP-2 in single-level transforaminal lumbar interbody fusion: a clinical and radiographic analysis

The “off label” use of rhBMP-2 in the transforaminal lumbar interbody fusion (TLIF) procedure has become increasingly popular. Although several studies have demonstrated the successful use of rhBMP-2 for this indication, uncertainties remain regarding its safety and efficacy. The purpose of this study is to evaluate the clinical and radiographic outcomes of the single-level TLIF procedure using rhBMP-2. Patients who underwent a single-level TLIF between January 2004 and May 2006 with rhBMP-2 were identified. A retrospective evaluation of these patients included operative report(s), pre- and postoperative medical records, and dynamic and static lumbar radiographs. Patient-reported clinical outcome measures were obtained from a telephone questionnaire and included a modification of the Odom’s criteria, a patient satisfaction score, and back and leg pain numeric rating scale scores. Forty-eight patients met the study criteria and were available for follow-up (avg. radiographic and clinical follow-up of 19.4 and 27.4 months, respectively). Radiographic fusion was achieved in 95.8% of patients. Good to excellent results were achieved in 71% of patients. On most recent clinical follow-up, 83% of patients reported improvement in their symptoms and 84% reported satisfaction with their surgery. Twenty-nine patients (60.4%) reported that they still had some back pain, with an average back pain numeric rating score of 2.8. Twenty patients (41.7%) reported that they still had some leg pain, with an average leg pain numeric rating score was 2.4. Thirteen patients (27.1%) had one or more complications, including transient postoperative radiculitis (8/48), vertebral osteolysis (3/48), nonunion (2/48), and symptomatic ectopic bone formation (1/48). The use of rhBMP-2 in the TLIF procedure produces a high rate of fusion, symptomatic improvement and patient satisfaction. Although its use eliminates the risk of harvesting autograft, rhBMP-2 is associated with other complications that raise concern, including a high rate of postoperative radiculitis.     

Hypocitraturia as a risk factor for nephrocalcinosis after kidney transplantation

Calcium-oxalate crystal deposition in kidney transplant biopsy specimen led us to investigate the impact of calcineurin inhibitor treatment on urinary excretion of lithogenic and stone inhibitory substances in 53 children after successful kidney transplantation (KTx) receiving cyclosporine A (CsA) or tacrolimus. We compared the values obtained with those of 12 patients with recurrent nephrotic syndrome under CsA and of 6 patients with Rasmussen encephalitis (RE) under tacrolimus therapy. Renal ultrasound examinations were repeatedly performed. Hypocitraturia was found in 69% of patients, with KTx patients having a significantly lower urinary citrate excretion than those receiving calcineurin inhibitors for other reasons. Secondly, we found hyperoxaluria in 35% of patients, again especially in those after KTx. No significant difference in urinary substances was seen comparing CsA with tacrolimus treatment. Urolithiasis was found in one and calcium-oxalate crystal deposition in biopsy specimen of three KTx patients. Calcineurin inhibitor treatment can lead to significant hypocitraturia, especially in patients after KTx receiving the highest dose of medication. Hyperoxaluria is primarily the result of a removal of significant body oxalate stores, deposited during dialysis, but may not be suspected as a specific side effect of calcineurin inhibitor therapy. Both findings can increase the risk for urolithiasis or nephrocalcinosis.     

Positive evidence against human hippocampal involvement in working memory maintenance of familiar stimuli

Subjects (n = 40) performed a delayed item recognition task for visually presented letters with three set sizes (1, 3 or 6 letters). Accuracy was close to ceiling at all set sizes, so we took set size as a proxy for WM load (i.e. the amount of information being maintained in WM). Functional magnetic resonance imaging (fMRI) signal associated with the delay period increased in a nearly linear fashion with WM load in the left inferior frontal gyrus/anterior insula (possibly Broca's area, BA 44/45), right anterior insula, bilateral caudate, bilateral precentral gyrus (BA 6), bilateral middle frontal gyrus (BA 9/46), bilateral inferior parietal lobule (with foci in both BA 39 and 40), left superior parietal lobule (BA 7), medial frontal gyrus (BA 6), anterior cingulate gyrus (BA 32) and bilateral superior frontal gyrus (BA 8). These results lend support to the idea that at least some of the cortical mechanisms of WM maintenance, potentially rehearsal, exhibit a scaling with WM load. In contrast, the delay-related fMRI signal in hippocampus followed an inverted U-shape, being greatest during the intermediate level of WM load, with relatively lower values at the lowest and highest levels of WM load. This pattern of delay-related fMRI activity, orthogonal to WM load, is seemingly not consonant with a role for hippocampus in WM maintenance of phonologically codable stimuli. This finding could possibly be related more to the general familiarity of the letter stimuli than their phonological codability per se.     

Cervical degenerative index: a new quantitative radiographic scoring system for cervical spondylosis with interobserver and intraobserver reliability testing

Background  The lack of a widely available scoring system for cervical degenerative spondylosis encouraged the authors to establish and validate a systematic quantitative radiographic index. Materials and methods  This study included intraobserver and interobserver reliability testing among three reviewers with different years of experience. Each observer independently scored four cervical radiographs of 48 patients at separate intervals, and statistical analysis of the grading was performed. Results  There was high intraobserver and interobserver reliability between the two experienced observers. There was fair reliability between the less experienced observer and the more experienced observers. Conclusions  The cervical degenerative index appears to be a reliable and reproducible radiographic assessment of cervical spondylosis. The index will have direct applicability for longitudinal study of cervical spondylosis and may be clinically relevant as well.