Neuroendocrine tumor of the pancreas and bilateral adrenal pheochromocytomas. A rare manifestation of von Hippel-Lindau disease in childhood

Background

A 12-year-old girl presenting with intermittent epigastric pains and diarrhea was referred to our clinic. Diagnostic workup revealed nonfunctional bilateral adrenal pheochromocytomas as well as a neuroendocrine tumor of the pancreatic head. This is the first report on the combination of a neuroendocrine pancreatic tumor with adrenal pheochromocytoma in a pediatric patient with von Hippel-Lindau (VHL) disease.

Methods

von Hippel-Lindau disease was confirmed by molecular genetic analysis of peripheral blood lymphocytes, which revealed the mutation VHL c. 695 G > A. The family history showed also VHL disease in the mother who carried the same mutation.

Results and Conclusion

Open laparotomy, organ-sparing enucleation of pheochromocytoma, and pylorus-preserving resection of the pancreatic head tumor were successfully performed. After an uneventful postoperative course, the child fully recovered. She was free of further manifestations of VHL disease 30 months after surgery.     

Aromatase inhibitors as solely treatment in postmenopausal breast cancer patients

Several studies evaluating the clinical effectiveness of endocrine therapy alone in breast cancer patients aged 70 years or older reported comparable survival rates to conventional surgical therapy, although the incidence of local recurrences was higher. Primary endocrine therapy is therefore only recommended as an alternative approach in elderly woman with estrogen receptor positive tumors who are deemed inoperable or who refuse surgery. We report our experience with aromatase inhibitors as primary endocrine therapy for estrogen receptor positive breast cancer in postmenopausal woman who are impaired by other diseases, refuse surgery or are of old age. Fifty-six patients with fifty-seven ER+ operable breast cancers who refused surgery, were judged ineligible for surgery because of comorbidity, or were of old age were treated with endocrine therapy using aromatase inhibitors only. Digital mammography and high-end breast ultrasound were used to assess tumor sizes. The mean age of the patients was 74 years (range 52-102 years). All patients suffered from breast cancer. The mean follow-up interval was 40 months (range 5-92 months). Seven patients (12%) achieved complete clinical remission, 31 (57%) partial response giving an overall objective response rate of 69%. In addition, seven (12%) patients showed stable disease, giving a clinical benefit rate (complete remission + partial response + stable disease rate) of 81%. Eleven patients (19%) progressed after an initial partial response or stable disease. Only one patient (2%) progressed on endocrine therapy within the first months. Eventually, 22 (39%) patients underwent surgery after informed consent to achieve better local tumor control. Primary endocrine therapy with aromatase inhibitors may offer an effective and safe alternative to surgery giving a high local control rate in postmenopausal women who refuse surgery, who are judged ineligible for surgery, or are of old age.     

Value of comprehensive renal ultrasound in children with acute urinary tract infection for assessment of renal involvement: comparison with DMSA scintigraphy and final diagnosis

The aim of this study was to evaluate the value of comprehensive renal ultrasound (US), i.e., combining greyscale US and amplitude-coded color Doppler sonography (aCDS), for assessment of urinary tract infection (UTI) in infants and children, compared to (1) ^99mTc DMSA scintigraphy and (2) final diagnosis. Two hundred eighty-seven children with UTI underwent renal comprehensive US and DMSA scintigraphy. The results were compared with regard to their reliability to diagnose renal involvement, using (1) DMSA scintigraphy and (2) final diagnosis as the gold standard. Sixty-seven children clinically had renal involvement. Sensitivity increased from 84.1% using only aCDS to 92.1% for the combined US approach, using DMSA scintigraphy as the reference standard. When correlated with the final diagnosis, sensitivity for DMSA scintigraphy was 92.5%; sensitivity for comprehensive US was 94.0%. Our data demonstrate an increasing sensitivity using the combination of renal greyscale US supplemented by aCDS for differentiation of upper from lower UTI. Sensitivity for DMSA and comprehensive US was similar for both methods compared to the final diagnosis. Comprehensive US should gain a more important role in the imaging algorithm of children with acute UTI, thereby reducing the radiation burden.     

Identification of cyclophilin A from human decidual and placental tissue in the first trimester of pregnancy

The protein patterns of tissue homogenates from human deciduaand placenta of first trimester pregnancies were investigated.Particular attention was paid to the low molecular weight componentsof these tissues, since substantial evidence has accumulatedthat some of these smaller proteins show a characteristic cyclicand pregnancy expression. Two specific bands were purified fromhomogenates of first trimester decidua and placenta using gelfiltration and anion exchange chromatography. These bands wereseparated by gel electrophoresis and blotting onto polyvinylidendifluoridemembrane. Partial amino acid sequencing of both proteins revealedsequences identical to human cyclophilin A. One protein wassequenced V-N-P-T-V-F-F-D-I-A-V-D-G-E-P-L-G-R-(X)-S-F-E-L-F-A-D-K-V-Pand identified as the 17 kDa isoform of cyclophilin A. The otherprotein was sequenced V-N-P-T-V-F-F-D-I-A and identified asthe 18 kDa isoform of cyclophilin A. cyclophilin A/decidua/placenta/progesterone/progesterone receptor     

Influence of a mutation in IFN-γ receptor 2 (IFNGR2) in human cells on the generation of Th17 cells in memory T cells

The T cell subsets involved in inflammatory reactions are mainly the IFN-γ secreting Th1 cells and IL17-producing Th17 cells. Although Th17 cells are primed in the thymus, there is evidence that Th17 cells can be generated from effector memory CD4⁺ T cells. Cytokines as IL-6, TGF-β, IL-21 and IL-23 involved in development of Th17 cells are well described. Here we analyzed the impact of a mutation in the IFN-γ receptor 2 (IFN-γR2) on the induction of Th17 cells. By isolation of T cells and monocytes of a patient with this mutation we could demonstrate an inhibitory role of IFN-γ signaling as IFN-γR2-deficient monocytes induce a higher percentage of IL-17⁺ cells from both healthy and IFN-γR2-deficient CD4⁺ T cells. This data confirm the interference of these two T helper subsets and points to a balance of Th1 and Th17 cells obtained by their own cytokine production and their interplay with APCs.     

White matter damage precedes that in gray matter despite similar magnetic resonance imaging changes following cerebral hypoxia-ischemia in neonatal rats

We hypothesized that the cerebral injury produced by hypoxia-ischemia (HI) in neonatal rats would differ in white compared with gray matter as detected histologically or with magnetic resonance (MR) imaging methods. Maps of T₂ and the apparent diffusion coefficient (ADC) of water were acquired in 1-week-old rats at times prior to cerebral HI (right carotid artery occlusion plus 1.5 h of hypoxia), within the last 5–10 min of HI, and 1 h or 24 h after HI. Near the end of HI, ADC decreased and T₂ increased in both cortical gray and subcortical white matter within the cingulum of the HI hemisphere. One hour after HI, ADC partially recovered, but T₂ remained increased and then increased further by 24 h post-HI. In contrast to the similar MR responses in white and gray matter, histological evidence for irreversible cell damage occurred in white matter earlier than in gray matter within the HI hemisphere. At 1 h post-HI, rarefied or disrupted nerve fibers and an increase in TUNEL-positive cells were observed within white matter in the cingulum, whereas neurons within the cortical gray matter appeared normal. By 24 h post-HI, damage was apparent in both white and gray matter. Thus, MR imaging detected acute tissue edema following cerebral HI in both gray and white matter but did not distinguish between the early irreversible tissue injury detected histologically in white but not gray matter in this rather severe model of neonatal encephalopathy.