Citations

AbstractBackgroundNeuroblastomas and ganglioneuroblastomas (NB/GNB) are malignant tumors that rarely occur in adults. Their disease progression and appropriate treatment are unclear.MethodsAll adults (age ≥18 years) were evaluated for histologically confirmed NB/GNB within our institution. Data were collected via chart review and direct patient contact.ResultsFrom 1980 to 2009, a total of 15 adult patients with NB/GNB were evaluated: six men (mean age 23 years, range 19–33 years) and nine women (mean 34 years, range 20–66 years). Their overall average age at diagnosis was 30 years. Tumor‐related symptoms occurred in ten patients: Pain (abdominal 3, back 2, pelvic 1, groin 1) was more common than a mass (abdominal 2) or dysmenorrhea (1). Five patients had tumors found incidentally by computed tomography (4) or chest radiography (1). Primary tumor origins were in the pelvis (4), mediastinum (3), abdomen (2), adrenal gland (2), retroperitoneum (2), and mixed locations (2). Altogether, 12 patients underwent surgical resection (biopsy in 3; resections of R0 in 5, R1 in 3, R2 in 4). Ten underwent chemotherapy. Histology showed four GNBs and 11 NBs. Five patients with stage I disease survived a mean of 21 years (range 10–40 years). Two are alive today. Three stage III patients died at 2, 6, and 9 years after diagnosis (mean 5.7 years). Six of seven patients (one was lost to follow‐up) with initial stage IV neuroblastoma died within 5 years (mean 2.7 years). NB and GNB patients had similar survivals.ConclusionsAdult‐onset NB/GNB is rare. Symptoms appear to occur later when incurable stage IV disease is detected. Complete surgical resection can lead to long‐term, disease‐free survival in stage I patients.

Dorsal root ganglia (DRG) are critical anatomical structures involved in nociception. Intraganglionic (IG) drug delivery is therefore an important route of administration for novel analgesic therapies. Although IG injection in large animal models is highly desirable for preclinical biodistribution and toxicology studies of new drugs, no method to deliver pharmaceutical agents into the DRG has been reported in any large species. The present study describes a minimally invasive technique of IG agent delivery in domestic swine, one of the most common large animal models. The technique utilizes CT guidance for DRG targeting and a custom-made injection assembly for convectionenhanced delivery (CED) of therapeutic agents directly into DRG parenchyma. The DRG were initially visualized by CT myelography to determine the optimal access route to the DRG. The subsequent IG injection consisted of 3 steps. First, a commercially available guide needle was advanced to a position dorsolateral to the DRG, and the dural root sleeve was punctured, leaving the guide needle contiguous with, but not penetrating, the DRG. Second, the custom-made stepped stylet was inserted through the guide needle into the DRG parenchyma. Third, the stepped stylet was replaced by the custom-made stepped needle, which was used for the IG CED. Initial dye injections performed in pig cadavers confirmed the accuracy of DRG targeting under CT guidance. Intraganglionic administration of adeno-associated virus in vivo resulted in a unilateral transduction of the injected DRG, with 33.5% DRG neurons transduced. Transgene expression was also found in the dorsal root entry zones at the corresponding spinal levels. The results thereby confirm the efficacy of CED by the stepped needle and a selectivity of DRG targeting. Imaging-based modeling of the procedure in humans suggests that IG CED may be translatable to the clinical setting.

Background Debate surrounds the validity of patch testing for allergic contact dermatitis in patients taking immunosuppressants and the extent to which these medications suppress patch test reactions. Previous studies have demonstrated that corticosteroids can suppress immune reactions measured in patch testing. Because immunomodulators are increasingly used, their impact on patch testing also requires evaluation. Objectives This study aimed to report patch test results in patients taking specific immunosuppressants and to review relevant literature. Methods A retrospective review of patients patch tested with the standard series at Mayo Clinic in Rochester, Minnesota, between January 1, 2008, and December 31, 2011, was conducted. Conclusions Positive patch test results occur during methotrexate therapy. How reactions would differ with no immunosuppression is unclear.

A broadening of the clinical and imaging features of the spontaneous cerebrospinal fluid ( CSF ) leaks is now well recognized, far beyond what was thought only two decades ago. This has resulted in increasing number of patients with atypical and unusual features who, not unexpectedly, are directed to headache specialists and tertiary referral centers. In many cases, obviously the fundamental question of presence or absence of CSF leak will need to be addressed prior to proceeding with further and often more involved, more invasive, and more costly diagnostic and therapeutic considerations. Radioisotope cisternography often proves to be very helpful in these situations by demonstrating reliable, although indirect, evidences of CSF leak while it is less helpful in directly identifying the exact site of the CSF leakage. In this overview article, the expectations from and the limitations of this diagnostic method are described along with some personal observations in the past 25 years.

SummaryReliable clinical or molecular predictors of benefit from azacitidine therapy in patients with myelodysplastic syndromes (MDS) are not defined. Doubling of platelet count at start of second cycle of azacitidine therapy compared to baseline was associated with achieving response and survival advantage in a Dutch cohort. To validate this observation, we analysed a larger cohort of North American patients, whose data was collected in a prospective clinical trial with a longer median follow‐up. We found a significant association between platelet count doubling after first cycle of azacitidine therapy and probability of achieving objective response. Among patients with MDS or oligoblastic acute myeloid leukaemia (<30% bone marrow blasts, n = 102), there was a statistically significant reduction in risk of death for patients who achieved platelet count doubling (n = 23, median OS, 21·0 months) compared to those who did not (n = 79, median OS, 16·7 months, adjusted hazard ratio (no/yes)=1·88, 95% confidence interval, 1·03–3·40, P = 0·04). Nonetheless, the addition of this platelet count doubling variable did not improve the survival prediction provided by the revised International Prognostic Scoring System or the French Prognostic Scoring System. Identification of reliable and consistent predictors for clinical benefit for azacitidine therapy remains an unmet medical need and a top research priority.