Delayed L2 Vertebrae Split Fracture following Kyphoplasty

Kyphoplasty is an accepted therapeutic modality for the treatment of painful osteoporotic vertebral compression fractures. Complication rates are reported between 1% and 3% for osteoporotic fractures. Most previously reported complications, however, have occurred perioperatively. In this article, we report a case in which balloon kyphoplasty was performed as described by manufacturer guidelines. Four weeks after a successful kyphoplasty, the patient presented with a painful split vertebral fracture with anterior deformity at the same level where the kyphoplasty was initially performed. A recurrent fracture at the same level of a previous successful kyphoplasty may be considered in the differential diagnosis of a patient who presents with new pain at a similar level.     

Impact of alterations affecting the p53 pathway in bladder cancer on clinical outcome, assessed by conventional and array-based methods.

This study was designed to define the potential clinical relevance of identifying alterations affecting p53 pathway in bladder cancer and to test a new, low-cost, high-throughput, and array-based TP53 sequencing technology. Tumor samples from 140 evaluable patients with bladder cancer were analyzed with two methods to detect TP53 gene mutations, including single-stranded conformational polymorphism followed by direct sequencing and an oligonucleotide array-based sequencing method. Immunohistochemistry was used to assess patterns of expression of p53, p21/WAF1, and mdm2. Median follow-up time was 27.6 months. Results from the above analyses were correlated with clinicopathological parameters and outcome. Combining the mutation-detection assays, 79 cases (56.4%) were found to harbor TP53 gene mutations. Direct sequencing identified 66 point mutations and five frameshift mutations. The p53 oligonucleotide array detected 65 point mutations and four splice site mutations in different exons but missed all five frameshift mutations. p53 nuclear overexpression was observed in 71 cases (50.7%), lack of p21 nuclear expression was found in 81 cases (57.9%), and mdm2 nuclear overexpression was seen in 64 cases (45.7%). In multivariate analysis, 17 patients (12.1%) had an altered p53 pathway, defined by the detection of mutant TP53 and/or p53 nuclear overexpression, loss of p21 nuclear expression, and mdm2 nuclear overexpression, and exhibited the worst clinical outcome in the observation period (P = 0.015), and it appears to be a significant prognostic factor associated with patient survival.     

Phase I trial of intravesical gemcitabine in bacillus Calmette-Guérin-refractory transitional-cell carcinoma of the bladder.

PURPOSE: The aim of this phase I study was to determine the safety and toxicity profile of gemcitabine administered as an intravesical agent in patients with transitional-cell carcinoma (TCC) of the bladder. PATIENTS AND METHODS: Patients with superficial bladder cancer refractory to intravesical bacillus Calmette-Guérin (BCG) therapy and refusing a cystectomy were considered eligible for the trial. Gemcitabine was given in the bladder for 1 hour twice weekly in 100 mL sodium chloride for a total of six treatments. After a 1-week break, a second course of six treatments over 3 weeks was given, followed by response assessment. Four dose levels were explored: 500 mg, 1,000 mg, 1,500 mg, and 2,000 mg. RESULTS: Eighteen patients completed therapy: three at 500 mg, six at 1,000 mg, three at 1,500 mg, and six at 2,000 mg. No grade 3 or 4 toxicity was observed at 500 mg. At 1,000 mg, three patients developed hematuria and one had a skin reaction resembling grade 3 hand-foot syndrome. Three patients at 1,500 mg had no grade 3 or 4 toxicity. Of six patients at 2,000 mg, one had grade 3 thrombocytopenia and neutropenia without infection. Seven patients had a complete response (negative cytology and posttreatment biopsy), and four patients had a mixed response (negative bladder biopsy but positive cytology). CONCLUSION: Gemcitabine has substantial activity as an intravesical agent in BCG-refractory TCC and warrants further investigation. Therapy given twice weekly was associated with minimal bladder irritation and tolerable myelosuppression. The recommended phase II dose for twice-weekly therapy is 2,000 mg.     

Impact of nursing home deaths on life expectancy calculations in small areas

STUDY OBJECTIVE: The drive to tackle health inequalities at the local level has increased interest in mortality data for small populations. There is some concern that nursing homes may affect measures of mortality for small populations, but there has been little in depth analysis of this. DESIGN AND SETTING: Deaths between 1997 and 2001 and population figures from the GP register (Exeter) database and census 2001 were used to produce life expectancy (LE) figures for all electoral wards in West Sussex. The proportion of those dying within each ward that had been residents of nursing homes was calculated and the relation between these variables and deprivation investigated. RESULTS: There was a significant linear relation between nursing home deaths and LE (p<0.0001), which explained 36% of variation in LE between wards. Deprivation accounted for around 35% of the variation in LE (p<0.0001) but was not correlated with nursing home deaths (p> or =0.0982). Multiple linear regression shows that over 60% of the variation in LE at ward level can be explained by both nursing home deaths and deprivation (p<0.0001) and that the two variables explain similar proportions of this variation. The relation between LE and nursing home deaths within wards grouped by deprivation suggests that the impact of nursing homes is strongest in deprived wards. CONCLUSIONS: This finding has important implications for LE calculations in small populations. Further investigation is now needed to examine the impact of nursing homes in other areas, on other mortality measures, and in larger populations.     

Biochemical recurrence rate in patients with positive surgical margins at radical prostatectomy with further negative resected tissue

OBJECTIVE

To determine the biochemical recurrence (BCR) rate in patients with positive surgical margins (PSMs) on the prostate specimen who have additional negative tissue resected from that site (M+ ?), compared to patients with negative margins (M?) and those with persistent PSM (M+), as those with PSM at radical prostatectomy (RP) are at greater risk of BCR, and in some instances where suspicious tissue is noted in the prostate bed or when frozen‐section analysis shows PSM, additional tissue is resected from the suspect site of the PSM.

PATIENTS AND METHODS

Between January 1999 and June 2007, 4217 consecutive patients underwent open or laparoscopic RP with no previous radiotherapy or hormonal therapy. The median (interquartile range) follow‐up was 37.4 (21.1–60.7) months.

RESULTS

Pathological organ‐confined (OC) cancer was present in 2901 men, of whom 2659 had M?, 216 had M+, and 26 had M+ ?. Extracapsular extension (ECE) alone with no seminal vesicle or lymph node involvement was present in 843 men, of whom 657 had M?, 174 had M+ and 12 had M+ ?. For patients with OC cancer, the 36‐month actuarial BCR‐free probability was 97.9% (95% confidence interval 97.3–98.5) for M?, vs 89.0 (84.1–93.9)% for M+ vs 100% for M+ ?. For patients with ECE, the 36‐month actuarial BCR‐free probability was 83.7 (80.0–87.4)% for M? vs 73.7 (66.1–81.3)% for M+ vs 90.0 (71.4–100)% for M+ ?. The main limitation of the study was its retrospective nature, with the reason for resection of additional tissue not always well documented.

CONCLUSIONS

While the few patients with PSMs and further negative resected tissue limited the statistical analysis, it would appear that in these patients the disease behaves as in those with negative margins.     

Helminth Infection Can Reduce Insulitis and Type 1 Diabetes through CD25- and IL-10-Independent Mechanisms

Parasitic helminth infection has been shown to modulate pathological inflammatory responses in allergy and autoimmune disease. The aim of this study was to examine the effects of infection with a helminth parasite, Heligmosomoides polygyrus, on type 1 diabetes (T1D) in nonobese diabetic (NOD) mice and to elucidate the mechanisms involved in this protection. H. polygyrus inoculation at 5 weeks of age protected NOD mice from T1D until 40 weeks of age and also inhibited the more aggressive cyclophosphamide-induced T1D. Moreover, H. polygyrus inoculation as late as 12 weeks of age reduced the onset of T1D in NOD mice. Following H. polygyrus inoculation of NOD mice, pancreatic insulitis was markedly inhibited. Interleukin-4 (IL-4), IL-10, and IL-13 expression and the frequency of CD4⁺ CD25⁺ FoxP3⁺ regulatory T cells were elevated in mesenteric and pancreatic lymph nodes. Depletion of CD4⁺ CD25⁺ T cells in vivo did not abrogate H. polygyrus-induced T1D protection, nor did anti-IL-10 receptor blocking antibody. These findings suggest that infection with H. polygyrus significantly inhibits T1D in NOD mice through CD25- and IL-10-independent mechanisms and also reduces the severity of T1D when administered late after the onset of insulitis.Helminth parasites infect about 1.5 billion people worldwide, especially in developing countries, and cause chronic infection that leads to malnutrition, anemia, impaired growth, and significant mortality. Intestinal nematode parasites can produce strong polarized Th2-type responses in mice. This immune response is characterized by eosinophilia, mucosal mast cell hyperplasia, elevated immunoglobulin E (IgE) secretion, and increased production of Th2 cytokines, such as interleukin-4 (IL-4) and IL-13. Recent studies have suggested that helminth infection can regulate infectious, allergic, or autoimmune inflammatory diseases. Helminth infection enhances susceptibility to certain infectious diseases, like tuberculosis (11, 35) and viral hepatitis (10, 17). Conversely, helminth infection is protective in murine models of asthma (19), multiple sclerosis (40), and inflammatory bowel disease (42).Type 1 diabetes (T1D) is a life-threatening disease that affects approximately 1 out of 400 children in westernized societies (18). Over the past 3 decades, the rate of T1D has increased by approximately 4% per year in both Europe and the United States (8, 12, 39). This increase in disease incidence may result in part from a dysregulated immune system due to lack of exposure to certain environmental pathogens, such as helminth parasites (5, 7, 32). Studies with nonobese diabetic (NOD) mice showed that inoculation with Trichinella spiralis, Heligmosomoides polygyrus, or Schistosoma mansoni markedly reduced the rate of T1D and suppressed lymphoid infiltration in the islets (9, 37). T1D was also prevented in NOD mice by injection of whole eggs or soluble antigens from the schistosome egg antigen or the schistosome worm antigen, but only if treatment was started at 4 weeks of age (49). Moreover, the addition of oral insulin B chain to schistosome egg antigen-treated mice augmented the induction of regulatory T cells (Tregs) that secreted IL-4, IL-10, and transforming growth factor beta (TGF-β) (27).We were interested in further examining potential mechanisms contributing to the control of T1D during infection with the intestinal nematode parasite H. polygyrus. This strictly enteric parasite triggers a potent Th2-type response without eliciting an associated Th1-type response (4). We found that H. polygyrus infection exerted significant protection against T1D in NOD mice when administered at 5 and 7 weeks of age and even when given as late as 12 weeks of age (30% protection). This was associated with reduced lymphoid infiltration in the islets and an increased frequency of CD25⁺ Tregs with augmented Th2-type responses, including induction of alternatively activated macrophages (AAMΦs) and IL-10 mRNA in pancreatic lymph nodes (PLN). When H. polygyrus-inoculated NOD mice were treated with cyclophosphamide (Cyp), an agent known to accelerate T1D, T1D prevention was sustained. Similarly, when H. polygyrus-inoculated NOD mice were treated with anti-CD25 monoclonal antibody (MAb) in vivo, we observed no change in insulitis between this group and those receiving a control monoclonal Ig. Furthermore, in Cyp-treated NOD mice, administration of an anti-IL-10 receptor (IL-10R) blocking MAb did not abrogate H. polygyrus-induced protection from T1D. These findings suggest that H. polygyrus inoculation suppressed T1D even after the development of insulitis and that suppression of T1D in H. polygyrus-treated NOD mice is accomplished through CD25- and IL-10-independent mechanisms.     

Subsite Distribution of Gastric Cancer in an Area of High Prevalence—Northwest Iran

Background

The aim of the present study was to determine subsites of gastric cancer in East Azerbaijan, Iran—a high incidence region for gastric cancer and Helicobacter pylori infection.

Methods

Data were collected from 2002 through 2007 from patients who sought treatment for gastrointestinal symptoms or signs at a university clinic and subsequently underwent upper gastrointestinal endoscopy.

Results

Cancer was diagnosed and histologically confirmed in 362 patients (352 adenocarcinomas). The mean age of the patients was 64.57 ± 11.32 (range, 16–94 years) and the male-to-female ratio was 2.8:1. The gastric cardia was involved in 40.3% of patients with gastric adenocarcinoma, while the gastric fundus was involved in 3.7%, the gastric body in 49.1%, and the gastric antrum in 24.1% of patients. Complete evaluation for metastasis was possible in 144 patients; 61 were free of metastasis, and most of these patients underwent surgical therapy. Cardia involvement was not associated with the sex or age of patients.

Conclusions

Noncardia gastric cancer is still more frequent in East Azerbaijan, which is likely due to the very high prevalence of infection with Helicobacter pylori. The low rate of cancer involving the fundus is a target for further research on the etiology of gastric cancer.Key words: gastric cancer, subsite, gastric cardia, Iran