Claudin-6 is a nonspecific marker for malignant rhabdoid and other pediatric tumors

Claudins are tight junction proteins with claudin-6 (CLDN6) expression mostly restricted to embryonic and fetal life. Previously reported gene expression microarray analysis showed an increased level of CLDN6 in atypical teratoid rhabdoid tumors (AT/RT) compared with other central nervous system (CNS) tumors and sarcomas. However, there exist conflicting data on expression of CLDN6 as assessed by immunohistochemistry in CNS tumors. We established membranous staining as a specific and reproducible method for evaluating CLDN6 expression based on fetal and adolescent controls. We then evaluated a large group (257) of pediatric tumors using tissue microarrays, including: 47 malignant rhabdoid tumors (MRTs), (31 AT/RTs and 16 non-CNS MRTs); 67 small, round, blue cell tumors (10 Wilms tumors, 10 embryonal rhabdomyosarcomas, 10 neuroblastomas (NBs), 10 synovial sarcomas (SSs), 9 hepatoblastomas (HBs), 9 alveolar rhabdomyosarcomas, and 9 Ewings sarcomas); and 143 CNS tumors (24 medulloblastomas, 21 pilocytic astrocytomas, 14 astrocytomas grade II/III, 13 gangliogliomas, 12 glioblastomas, 12 ependymal tumors, 11 choroid plexus tumors, 10 meningiomas, 8 dysembryoplastic neuroepithelial tumors, 8 oligodendrogliomas, 4 craniopharyngiomas, 2 germinomas, 2 primitive neuroectodermal tumors (PNET), and 2 central neurocytomas). CLDN6 expression was seen in 12 of 31 (39%) AT/RTs, 7 of 16 (44%) non-CNS MRTs, 5 of 10 (50%) Wilms tumors, 1 of 9 (11%) HBs, 2 of 2 (100%) germinomas, 1 of 2 (50%) CNS PNETs, 1 of 24 (4%) medulloblastomas, and 1 of 10 (10%) meningiomas. Ten of 11 (91%) choroid plexus tumors showed apical staining but no concentric membranous staining. Although CLDN6 is expressed in both AT/RTs and MRTs, it is not a specific biomarker as it is expressed in a variety of other pediatric CNS and soft tissue tumors.     

Parathyroid Autotransplantation during Total Thyroidectomy—Does the Number of Glands Transplanted Affect Outcome?

Parathyroid autotransplantation is a technique for ensuring the continued function of parathyroid tissue at the time of total thyroidectomy (TT). The aim of this study was to ascertain whether the number of parathyroids transplanted affects the incidence of temporary and permanent hypoparathyroidism. A retrospective cohort study included all patients undergoing a TT in a single unit between July 1998 and June 2003. The number of parathyroids transplanted, the final pathology, and the incidence of temporary and permanent hypoparathyroidism were documented. Fisher’s exact test was used for statistical analysis. A total of 1196 patients underwent a TT during the 5 years studied. Of these, 306 (25.6%) had no parathyroids transplanted, 650 (54.3%), 206 (17.2%), 34 (2.8%) had 1,2, or 3 glands autotransplanted, respectively. The incidence of temporary hypoparathyroidism was 9.8% for no gland transplants, 11.9%, 15.1%, and 31.4% for 1,2,and 3 gland transplants, respectively (p < 0.05). The incidence of permanent hypoparathyroidism was 0.98%, 0.77%, 0.97%, and 0%, respectively (p = NS). The incidence of temporary hypoparathyroidism was higher when surgery was performed for Graves’ disease. Temporary hypocalcemia is closely related to the number of autotransplanted parathyroids during TT. The long-term outcome is not affected by the number of parathyroids autotransplanted. A “ready selective” approach to parathyroid autotransplantation is an effective strategy for minimizing the rate of permanent hypoparathyroidism.     

Significance of Histological Response to Preoperative Chemoradiotherapy for Pancreatic Cancer

Background Neoadjuvant (preoperative) chemoradiotherapy (CRT) for pancreatic cancer offers theoretical advantages over the standard approach of surgery followed by adjuvant CRT. We hypothesized that histological responses to CRT would be significant prognostic factors in patients undergoing neoadjuvant CRT followed by resection. Methods Since 1994, 193 patients with biopsy-proven pancreatic adenocarcinoma have completed neoadjuvant CRT, and 70 patients have undergone resection. Specimens were retrospectively examined by an individual pathologist for histological responses (tumor necrosis, tumor fibrosis, and residual tumor load) and immunohistochemical staining for p53 and epidermal growth factor receptor. Factors influencing overall survival were analyzed with the Kaplan-Meier (univariate) and Cox proportional hazards (multivariate) methods.Results The estimated overall survival (median±SE) in the entire group of patients undergoing resection was 23±4.2 months, with an estimated 3-year survival of 37%±6.6% and a median follow-up of 28 months. Complete histological responses occurred in 6% of patients. Overexpression of p53 was more common in patients with large residual tumor loads. Tumor necrosis was an independent negative prognostic factor, as were positive lymph nodes, a large residual tumor load, and poor tumor differentiation.Conclusions Histological response to neoadjuvant CRT—as measured by residual tumor load—may be useful as a surrogate marker for treatment efficacy. Characterization of the tumor cells that survive neoadjuvant CRT may help us to identify new or more appropriate targets for systemic therapy.     

AneuRx Device Migration: Incidence, Risk Factors, and Consequences

Success after endovascular abdominal aortic aneurysm repair (EVAR) is dependent on device positional stability. The quest for such stability has motivated different endograft designs, and the risk factors entailed remain the subject of debate. This study aims at defining the incidence, risk factors, and clinical implications of device migration after EVAR with the AneuRx® endograft. In this study we included all consecutive 109 patients submitted to primary AneuRx placement for infrarenal aortic or aortoiliac aneurysms. Preoperative computed tomography (CT) scans were reviewed for the following anatomic characteristics: neck length, diameter, angulation, calcification, and thrombus load; and sac diameter and thrombus load. Percentage of device oversizing relative to the proximal neck diameter was determined. All postoperative CT scans were reviewed, and the distance between the lowest renal artery and the craniad end of the device was measured. A 5-mm increase in such distance was considered indicative of device migration. Migration cumulative incidence was estimated by the Kaplan-Meier method, and its association with any of the preoperative anatomical characteristics was tested using Cox proportional hazards models. Median follow-up time was 9 (range, 1-31) months. Migration occurred in nine patients, corresponding to a 15.6% estimated probability of migration at 30 months (SE=5.1%). Migration was associated with the risk of proximal type I endoleak (hazard ratio=3.39, 95% confidence interval=1.46-7.87; p=0.007). This type of endoleak occurred in three of the migration-affected patients (33.3%); all of them were resolved by additional cuff placement at the proximal landing zone. No other migration-related reinterventions were performed. The only significant associations between anatomic factors and device migration probability were the protective effects of longer necks (odds ratio [OR]=0.71 for each additional 5 mm, p=0.045) and longer overlapped portions of neck and device (OR=0.56 for each additional 5 mm, p=0.003). There was a trend toward higher probability of migration among reverse-tapered necks (OR=1.75, p=0.109). Percentage of device oversizing correlated with early neck dilation (between preoperative and first postoperative diameters, correlation coefficient=0.4, p < 0.0001), but not with late neck dilatation (between first postoperative and 1.5-year scan diameters, correlation coefficient=0.29, p=0.112). There was a trend toward higher mean percentage of late dilation among migrators (11.4%, standard error of the mean [SEM] 2.6) than nonmigrators (5.7%, SEM=1) (p=0.08), but both groups had similar mean percentages of early dilation (3%, SEM=1.6%, vs. 5.5%, SEM=0.6%; p=0.365). This result indicates that device migration is not a rare event after AneuRx implantation. This phenomenon is associated with proximal type I endoleaks. Deployment of the endograft immediately below the renal arteries might help to prevent migration, since use of greater lengths of overlapped device relative to the proximal neck has a protective effect. Migration seems to be independent of the degree of device oversizing.Presented at the 29th Annual Meeting of the Peripheral Vascular Surgery Society, Anaheim, CA, June 4-5, Sergio M. Sampaio is a recipient of the Edward S. Rogers Clinical Research Fellowship in Vascular Surgery.     

A Comparison of the Intubation Conditions between Mivacurium and Rocuronium during Balanced Anesthesia

Background: Comparisons of the intubation conditions with mivacurium and rocuronium from previous reports are confounded by the use of varied induction regimens. The authors compared intubation conditions of mivacurium, rocuronium, and a placebo at 90 s and their recovery profiles during anesthesia with nitrous oxide, oxygen, and propofol.

Methods: After induction with midazolam, fentanyl, and propofol in a randomized blinded study, 100 patients received one of the following treatments: 0.25 mg/kg mivacurium in divided doses (0.15 mg/kg followed by 0.1 mg/kg 30 s later); 0.45, 0.6, 0.9, or 1.2 mg/kg rocuronium; or placebo. Evoked thumb adduction was measured throughout. Intubation was attempted 90 s after the initial dose of mivacurium and other treatment doses by a "blinded" physician. Intubating conditions were graded as excellent, good, poor, or not possible. Spontaneous recovery was studied until a 25% initial twitch height was reached. Mean arterial blood pressure and heart rate changes between groups were determined before induction through 6 min after administration of the study drugs.

Results: There were no important changes or intergroup differences in mean arterial blood pressure and heart rate. Intubation conditions were good or excellent for both mivacurium and rocuronium at the 0.9 mg/kg dose (93%) and at the 1.2 mg/kg dose (100%). Rocuronium at the 0.6 mg/kg dose was excellent in 27% of patients, whereas rocuronium at the 0.45 mg/kg dose had the least number of excellent conditions and the most poor or not possible assessments. Patients given placebo could not be intubated. Times to maximum blockade for 0.9 and 1.2 mg/kg rocuronium were the shortest. The times to 25% recovery for 0.6 mg/kg rocuronium (mean +/- SD = 27 +/- 8.6 min), 0.9 mg/kg (43.1 +/- 10.8), and 1.2 mg/kg (62.3 +/- 17.4 min) were significantly longer than were those for mivacurium (17.4 +/- 6.2 min).     

Changes in Esophageal Function after Vertical Banded Gastroplasty as Demonstrated by Esophageal Scintigraphy

Background: The effects of surgery for morbid obesity on the function of the upper gastrointestinal (GI) tract are of interest to bariatric surgeons. This study was undertaken to determine any changes in esophageal function, following vertical banded gastroplasty (VBG) in morbidly obese patients, as detected by esophageal scintigraphy. Methods: Ten consecutive morbidly obese patients (six female and four male) underwent preoperative esophageal scintigraphy and upper GI endoscopy. These investigations were repeated 12 months after VBG to coincide with expected appreciable weight reduction. The results were tabulated together with body mass indices, crude weights and percentage excess weight lost. Results: Before VBG one patient gave a history of mild heartburn, one had mild dyspepsia and the remaining eight patients had no GI symptoms. No patient had a hiatus hernia or endoscopic evidence of reflux esophagitis. Preoperatively all patients had abnormal scintiscans. The abnormalities were esophageal retention (all) and intraesophageal reflux (five out of 10 patients). Gastroesophageal reflux was not identified in any patient. Postoperatively scintiscans were normal or improved in six out of 10 patients and unchanged in four out of 10 patients. In three patients the scans were normal and three showed overall improvement in esophageal function, although in one of these latter patients gastroesophageal reflux was observed. Conclusions: In this series of morbidly obese patients, esophageal function as assessed by scintigraphy was abnormal. Following VBG it improved in six out of 10 patients and was unchanged in four out of 10. However, in one patient, who had shown an overall improvement in esophageal function, gastroesophageal reflux was demonstrated when it had not been seen preoperatively. This was asymptomatic. Thus, adverse changes in esophageal function after VBG were uncommon.     

A dilemma for doctors

Community physicians have recently, albeit often reluctantly, been involved in preparations for nuclear war. This paper suggests an alternative: that they should use their skills in epidemiology and in preventive and social medicine in the prevention of nuclear war.