Graft-vs-host disease after small bowel transplantation in children

Purpose

Graft-vs-host disease (GVHD) is a rare complication of transplantation of organs rich in immunocompetent cells. The goal of this study was to report the features of GVHD after small bowel transplantation (SBTx) in children.

Methods

The study involved a retrospective review of patients undergoing SBTx between 1999 and 2009 who had GVHD.

Results

Of 46 children receiving 52 intestinal grafts (2 liver-intestine and 3 multivisceral), 5 (10%) developed GVHD. Median age at transplant was 42 (19-204) months. Baseline immunosupression consisted of tacrolimus and steroids supplemented with thymoglobulin (n = 2) or basiliximab (n = 3) for induction. Median time between transplantation and GVHD was 47 (16-333) days. All patients had generalized rash, 2 had diarrhea, and 2 had respiratory symptoms. Other symptoms were glomerulonephritis (n = 1) and conjunctivitis (n = 1). Four developed severe hematologic disorders. The diagnosis was confirmed by skin biopsy in 4 patients and supported by chimerism studies in two. Colonoscopy and opthalmoscopic findings were also suggestive in one. Treatment consisted of steroids and decrease of tacrolimus, with partial response in four. Other immunosuppressants were used in refractory or recurrent cases. Three patients died within 4 months after diagnosis.

Conclusion

Graft-vs-host disease is a devastating complication of SBTx, with high mortality probably associated with severe immunologic dysregulation.     

Patient risk stratification using Gleason score concordance and upgrading among men with prostate biopsy Gleason score 6 or 7

PurposeTo define the impact of discordant Gleason sum (GS) between prostate biopsy (Pbx) tissue and radical prostatectomy (RP) specimen among men initially diagnosed with Gleason 6 or 7 prostate adenocarcinoma.Materials and methodsWe evaluated patients diagnosed with GS 6 or 7 and treated primarily with RP. We defined the frequency of GS discordance between Pbx and RP pathology reports. We analyzed pretreatment parameters associated with GS discordance and compared immediate postprostatectomy outcome variables across patient groups defined by their GS and concordance. We then conducted survival analysis for biochemical recurrence across patient groups defined by their GS and concordance status.ResultsAmong patients with GS 6 on Pbx, 681/1,847 (36.86%) patients were upgraded to GS 7 or higher after RP. Surgical margin, capsular involvement, seminal vesicle, and nodal involvement status were more favorable in patients with concordant Pbx and RP specimen with GS 6 (P < 0.0001). Patients with smaller transrectal ultrasound (TRUS) prostate volume were found to have higher PSA densities and were more likely to be upgraded at RP. Multivariate survival analysis also predicted fewer biochemical recurrence events over time in men with concordant Pbx tissue and RP specimen of GS 6 vs. 6/7 or 7/7 (P = 0.0025) controlling for other relevant covariates.ConclusionsGS discordance between Pbx tissue and RP specimens among prostate cancer patients initially diagnosed with either GS 6 or 7 adenocarcinoma of the prostate is substantial. This discordance has potential clinical significance in predicting oncologic outcomes.     

Local Lymphocytes and Nitric Oxide Synthase in the Uterine Cervical Stroma of Patients with Grade III Cervical Intraepithelial Neoplasia

OBJECTIVES:

Precancerous and cancerous cells can trigger an immune response that may limit tumor development and can be used as a prognostic marker. The aims of the present study were to quantify the presence of B and T lymphocytes, macrophages and cells expressing inducible nitric oxide synthase (iNOS) in the cervical stroma of women with grade III cervical intraepithelial neoplasia (CIN III) or in the intratumoral and peritumoral tissue of women with stage I invasive carcinoma.

METHODS:

Cervical tissue specimens were obtained from 60 women (20 each from control tissues, CIN III and invasive carcinomas). The average ages in the control, CIN III and invasive groups were 43.9 (± 4.3), 35.5 (± 9.5), and 50 (± 11.2) years, respectively. The specimens were immunohistochemically labeled with antibodies to identify T lymphocytes (CD3), cytotoxic lymphocytes (CD8), B lymphocytes (CD20), macrophages (CD68) and iNOS. We evaluated the markers in the stroma above the squamocolumnar junction (control), at the intraepithelial lesion (CIN cases), and in the nfiltrating tumor. Two independent observers performed the immunohistochemical analysis.

RESULTS:

T lymphocytes, B lymphocytes, macrophages and iNOS were present more frequently (P<0.05) in the stroma of peritumoral invasive tumors compared to the controls and intratumoral invasive cancer samples. CD3+ and CD20+ lymphocytes were present more frequently in CIN III patients compared to samples from patients with intratumoral invasive cancer (P<0.05).

CONCLUSION:

High numbers of T and B lymphocytes, macrophages and iNOS-expressing cells in the peritumoral stroma of the invasive tumors were observed. Cell migration appeared to be proportional to the progression of the lesion.     

Effect of pulsed estrogen therapy on hemostatic markers in comparison with oral estrogen regimen in postmenopausal women

BACKGROUND/AIMS: Hormone replacement therapy (HRT) is associated with an increased risk of thromboembolism dependent on the type of HRT; therefore, we compared therapy effects of intranasal with oral estrogens on coagulation and fibrinolysis markers in postmenopausal women. METHODS: A randomized study in which 29 healthy hysterectomized women received intranasal 17beta-estradiol or oral estrogens for 3 months. RESULTS: There were no significant differences in the baseline characteristics between groups. Those women receiving intranasal estradiol showed a mild increment in plasminogen activator inhibitor-1 (PAI-I) (from 6.8 +/- 3.5 to 9.6 +/- 3.9 U/ml, p < 0.01); however, fibrinogen, factor VII-tissue factor complex (VIIa-rTF), antithrombin III (ATIII), protein C (PC) activity, protein S (PS) activity, plasminogen (PLG), and tissue-type plasminogen activator antigen (t-PA) were unchanged. In contrast, oral unopposed estrogens elevated t-PA (from 4.9 +/- 2.9 to 9.6 +/- 5.1 ng/ml, p < 0.01) in parallel with a decrement in PAI-I (from 5.2 +/- 4.0 to 2.7 +/- 1.7 U/ml, p < 0.05) and VIIa-rTF (from 201.2 +/- 181.0 to 140.6 +/- 108.7 mU/ml, p < 0.05). Fibrinogen, ATIII, PC, PS, and PLG were unchanged. CONCLUSIONS: Nasal 17beta-estradiol had no effect on the coagulation markers, except a moderate increment in PAI-1. In contrast, oral estrogens elicited a decrement in both VIIa-rTF and PAI-1; however, those changes did not surpass normal limits.     

Shoulder dystocia at noninstrumental vaginal delivery

This study examines the relationship between episiotomy and the occurrence of shoulder dystocia among noninstrumental vaginal deliveries. Analysis of data from a retrospective database was used to study noninstrumental vaginal deliveries in New Jersey during the years 1996 to 2001. The episiotomy group and nonepisiotomy group were analyzed separately using univariate and multivariate analysis. Among 358,664 deliveries, rate of shoulder dystocia was 1.0% (n = 3596). Thirty-five percent of deliveries were assisted by episiotomy. Rate of dystocia was 1.42% with the use of episiotomy, and 0.81% when episiotomy was not used. This increased rate with episiotomy was noted across all of the racial groups, all birthweight categories, and all of the risk factor subgroups analyzed. There was a gradual decrease in the use of episiotomy from 37.30 to 26.03% without a corresponding increase in the rate of dystocia. Among noninstrumental deliveries, the rate of shoulder dystocia is higher in the episiotomy group. Decrease in the use of episiotomy has not resulted in an increase in the occurrence of dystocia.     

Bioluminescence imaging correlates with tumor progression in an orthotopic mouse model of lung cancer

Background and ObjectivesTo determine whether bioluminescence imaging of human lung cancer cells growing in an orthotopic murine model provides a sensitive tool for monitoring tumor progression in athymic nude mice.MethodsHuman lung cancer (A549) cells were stably transfected with the firefly luciferase gene and inoculated into the right lung of athymic nude mice. Seven days after inoculation tumor growth was evaluated using the Kodak in-vivo Imaging System FX and continued to be monitored on a weekly basis.ResultsIn duplicate experiments, human lung cancer tumors formed in 90% of animal’s injected orthotopically. The mean intensity of the bioluminescence signal emitted from the lung cancer cells increased logarithmically during the course of study. Mice with positive bioluminescence signaling had confirmed tumors by microscopic histological analysis. Bioluminescence activity had a strong correlation with the tumor volume as determined histologically.ConclusionsBioluminescence intensity directly correlates with tumor volume and therefore offers a reliable approach for detecting and monitoring the growth of human lung cancer cells in orthotopic murine models.     

Plasma matrix metalloproteinases and postmenopausal breast cancer risk: a nested case–control study in the Multiethnic Cohort study

The survival of malignant breast cells depends upon the remodeling of the extracellular matrix, including complex interactions with matrix metalloproteinases (MMPs). It has been hypothesized that circulating MMPs may serve as early indicators of breast cancer development in hospital-based case–control studies. A nested case–control study of the association of pre-diagnostic plasma levels of MMPs with the subsequent risk of postmenopausal breast cancer was conducted within the Multiethnic Cohort. During the follow-up period, 713 women with incident invasive breast cancer were identified and individually (1:1) matched to controls. Four types of MMPs (1, 2, 3, and 7) were analyzed by microsphere immunofluorescence assay. Mean plasma levels of MMPs did not differ significantly between cases and controls; nor were there differences in breast cancer risk by MMP level. No difference in the risk of breast cancer by plasma level of the MMPs was found within strata of age, or ethnicity, although MMP-1 levels were positively associated with breast cancer risk in obese women and women by hormone replacement medications (P values for interaction <0.05). Few significant differences in risk by levels of the MMPs were found by any of the clinical variables. Circulating MMPs were not associated with postmenopausal breast cancer risk.