Histology in mixed germ cell tumors. Is there a favorite pairing?

PURPOSE: Mixed germ cell tumors account for approximately 30% to 50% of testicular tumors. To our knowledge a systematic review with statistical analysis of the associations of histological subtypes in mixed germ cell tumors has not been done previously. It was our impression that such associations exist. Delineating concordant histological types may provide insight into the ontogeny of testicular tumors and also have important clinical implications. MATERIALS AND METHODS: We retrospectively reviewed the testis cancer data base at our institution. The primary tumor of orchiectomy specimens was examined in 2589 patients. Of these patients mixed histology was noted in 1765 (68.2%). ORs were calculated for all possible combinations of teratoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma and seminoma. In addition, we evaluated the association of various histological types with teratoma at post-chemotherapy retroperitoneal lymph node dissection. RESULTS: Of 10 possible combinations of histological types in the primary tumor, positive correlations were noted in 4. The strongest correlation was found between teratoma and yolk sac tumor (OR 2.58, p <0.001). Teratoma or yolk sac tumor in the testis was associated with teratoma in the pathology specimen at post-chemotherapy retroperitoneal lymph node dissection. CONCLUSIONS: The strongest associations of histological subtypes in mixed germ cell tumors were seen between yolk sac tumor and teratoma. Similar associations are seen in late relapse and in some cases of prepubertal tumors. Further study of these associations may prove valuable in understanding the biology and clinical behavior of germ cell tumors.     

Nephron sparing surgery for appropriately selected renal cell carcinoma between 4 and 7 cm results in outcome similar to radical nephrectomy

PURPOSE: We compared outcomes between patients treated with nephron sparing surgery (NSS) without imperative indications for renal preservation and radical nephrectomy (RN) for 4 to 7 cm renal cell carcinoma (RCC). MATERIALS AND METHODS: We identified 91 patients treated with NSS and 841 patients treated with RN for 4 to 7 cm RCC between 1970 and 2000. Cancer specific, distant metastases-free and recurrence-free survivals were estimated using the Kaplan-Meier method. RESULTS: Cancer specific survival rates at 5 years for patients treated with NSS and RN for 4 to 7 cm RCC were 98% and 86%, respectively. On univariate analysis patients treated with RN for 4 to 7 cm RCC were more likely to die of RCC compared to patients treated with NSS. However, after adjusting for features associated with death from RCC including stage, grade, histological tumor necrosis and histological subtype, this difference was no longer statistically significant (risk ratio 1.60, 95% CI 0.50-5.12, p = 0.430). Distant metastases-free survival rates at 5 years for patients treated with NSS and RN were 94% and 83%, respectively. On univariate analysis patients treated with RN were more likely to have tumors that metastasized compared to patients treated with NSS, although this difference was no longer significant after adjusting for the features listed previously (risk ratio 1.76, 95% CI 0.64-4.83, p = 0.273). Recurrence-free survival rates at 5 years for patients treated with NSS and RN were 94% and 98%, respectively. On univariate analysis patients treated with RN were less likely to have recurrence compared to patients treated with NSS (risk ratio 0.32, 95% CI 0.12-0.85, p = 0.022). CONCLUSIONS: There were no statistically significant differences in cancer specific survival and distant metastases-free survival between patients treated with NSS and RN for 4 to 7 cm RCC after adjusting for important pathological features. NSS for 4 to 7 cm RCC results in excellent outcome in appropriately selected patients.     

Monitoring systemic donor lymphocyte macrochimerism to aid the diagnosis of graft-versus-host disease after liver transplantation

BACKGROUND: The diagnosis of graft-versus-host disease (GvHD) after liver transplantation can be difficult because early symptoms are often nonspecific. In this study, the presence of donor lymphocyte macrochimerism in recipient peripheral blood was examined as a diagnostic aid for GvHD after cadaveric donor liver transplantation. METHODS: Between 1996 and 2002, 33 liver transplant recipients with a clinical suspicion of GvHD (skin rash, diarrhea, pyrexia, pancytopenia, or anemia, without an obvious alternative cause) were investigated for peripheral blood donor lymphocyte macrochimerism. Donor macrochimerism was determined at the time of first clinical presentation by a low-sensitivity polymerase chain reaction (PCR) to detect donor human leukocyte antigen (HLA) alleles using genomic DNA extracted from recipient peripheral blood. Where donor HLA alleles were detected, the percentage of donor T cells was quantified by two-color flow cytometric analysis using antibodies specific for mismatched donor and recipient HLA alleles. The relationship between the presence or absence of donor lymphocyte macrochimerism and final diagnoses based on clinical and histological criteria was examined. RESULTS: Seven of the 33 patients were PCR positive for donor HLA alleles. All had macrochimerism, with donor T lymphocyte levels ranging from 4% to 50% of circulating lymphocytes. All seven patients had normal liver function tests, skin rash, and diagnosis of GvHD histologically confirmed by skin or gut biopsies. Twenty-six patients were PCR negative, and, in 23, an alternative diagnosis was eventually established. The remaining three patients made a rapid and spontaneous recovery with no further symptoms suggestive of GvHD. CONCLUSIONS: Donor lymphocyte macrochimerism was present in all patients in whom the diagnosis of GvHD was confirmed. In patients with symptoms consistent with GvHD and a negative PCR for donor HLA, an alternative diagnosis was eventually established or the patients recovered spontaneously. Detection of donor HLA alleles in recipient peripheral blood by PCR is a useful diagnostic tool for GvHD after liver transplantation.     

Outcome of popliteal artery aneurysms after exclusion and bypass: significance of residual patent branches mimicking type II endoleaks

PURPOSE: Popliteal aneurysms (PAs) often are treated with exclusion and bypass. However, excluded aneurysms can transmit systemic pressure from persistent flow through collateral arteries (endoleak), resulting in aneurysm growth and rupture. We used duplex ultrasound scanning for postoperative surveillance more than 2 years after PA repair with exclusion and bypass, to determine the presence of flow and aneurysm growth. METHODS: From 1995 to 2001, 23 patients with 26 PAs (mean diameter, 3.2 cm; range, 1.6-5.6 cm) underwent surgical repair and were available for more than 2 years of follow-up. The popliteal artery was ligated proximal and distal to the aneurysm, and autogenous revascularization was performed. All patients who underwent PA endoaneurysmorrhaphy through a posterior approach were excluded from the study. During long-term follow-up, aneurysm sac flow and size were evaluated with duplex ultrasound scanning, computed tomography, or magnetic resonance angiography, and standard angiography. Patients with increased PA size and persistent flow were offered repair through a posterior approach. RESULTS: Over 7 years, 26 PAs (symptomatic, 11; asymptomatic, 15) treated with aneurysm exclusion and bypass were available for more than 2 years of follow-up (mean, 38 months; range, 24-78 months). In the postoperative period 16 PAs (62%) became thrombosed, 10 (38%) had persistent collateral flow through geniculate vessels, 6 (23%) increased in size, and 3 (12%) ruptured; 1 (4%) resulted in limb loss. Operative findings for all ruptured PAs and 3 of 6 PAs with increased sac size that underwent aneurysm sac exploration and endoaneurysmorrhaphy revealed retrograde flow through geniculate vessels, mimicking type II endoleak. CONCLUSIONS: These findings question the effectiveness of PA exclusion through proximal or distal ligation and bypass. In addition, retrograde flow into the aneurysm sac (ie, type II endoleak after endovascular abdominal aortic aneurysm repair) may transmit systemic pressure that can result in aneurysm rupture. We recommend PA treatment with aneurysm sac decompression and ligation of geniculate vessels whenever possible and routine postoperative surveillance of the excluded aneurysm sac.     

Computed Tomography and Ultrasound in Follow-up of Patients after Endovascular Repair of Abdominal Aortic Aneurysm

The purpose of this study was to compare our experience with duplex ultrasonography (US) and computed tomography (CT) for the routine follow-up of patients after endovascular repair (EVAR) of abdominal aortic aneurysm (AAA). We reviewed the electronic charts and radiologic exams of the first 125 patients (113 males, 12 females, median age of 76 years, range 48-98 years) with AAA treated by EVAR from June 1996 to November 2001. Our follow-up protocol included serial CT and US at regular intervals after the procedure (before discharge, at 1 month, and then every 6 months). Adequacy of each exam, ability to detect endoleaks, measurements of AAA diameter, and ability to determine graft patency were compared. For endoleak detection, comparison between CT and US was done using CT as the gold standard. A total of 608 exams, 337 CTs and 271 US, were performed 1 day to 5 years after endovascular aneurysm repair; 98% of CT and 74% of US were technically adequate. Contrary to CT, the proportion of adequate US exam was significantly less in patients with higher body mass index (BMI 30 = 54% vs. BMI < 30 = 81%, p < 0.001) and for pre-discharge US compared to the post-discharge US (54% vs. 88%, p = 0.0005). Concurrent scan pairs were obtained in 252 instances in 107 patients (1-8 pairs per patient). Excellent correlation between AAA diameter measured on CT and US was noted (correlation coefficient of 0.9, p < 0.0001). However, agreement was poor. CT anteroposterior (AP) and transverse measurements were on average 2.9 mm (95% limits of agreement = –7 to 13 mm) and 1.8 mm (95% limits of agreement = –9 to 12 mm) greater than US. For AAA diameter change, there was no case of increase AP diameter on CT. However, in 23% (29/128 pairs of sets) of US, an increase in AAA size that could have influenced patient management (4 mm) was reported despite no change demonstrated on CT. For endoleak detection, sensitivity and specificity of US compared to that of CT was 25% and 89%. Similar sensitivity and specificity were noted when we excluded the first set (25% and 95%), sets done prior to 2000 (30% and 89%), inadequate CT or US scans (31% and 98%), or duplicate sets of results for each patient (28% and 81%). Of the 27 endoleaks missed on US in 17 patients, 2 were type I endoleaks. None of the four endoleaks seen only on US were type I endoleak. US usefulness prior to discharge was reduced by the high rate of inadequate exam, especially in obese patients. Despite the excellent correlation in AAA diameter between US and CT, there was significant disagreement in AAA diameter measurement and diameter change. Sensitivity of nonstandardized US for endoleak was low compared to CT. CT remains our primary imaging study after EVAR, but standardization of post-EVAR US technique may improve its accuracy.Presented at the Midwestern Vascular Surgical Society Annual Meeting, Madison, WI, September 12-14, 2002.     

Rhinologic pharmacotherapy in rhinoplasty

Rhinoplasty surgeons inevitably encounter therapeutic considerations in managing their patients, and a thorough understanding of nasal function, as well as of disorders of the nose and sinuses, is requisite for positive clinical outcomes. Patients suffering from allergic rhinitis are not precluded from undergoing rhinoplasty, whereas other disease processes may warrant an otolaryngologic evaluation before proceeding with surgery. A thorough medical history and examination elucidate sinonasal disease conditions that may not improve after septorhinoplasty but potentially could respond to pharmacologic therapy.     

Reduced penetrance of craniofacial anomalies as a function of deletion size and genetic background in a chromosome engineered partial mouse model for Smith-Magenis syndrome

Smith-Magenis syndrome (SMS) is a multiple congenital anomaly/mental retardation syndrome associated with del(17)(p11.2p11.2). The phenotype is variable even in patients with deletions of the same size. RAI1 has been recently suggested as a major gene for majority of the SMS phenotypes, but its role in the full spectrum of the phenotype remains unclear. Df(11)17/+ mice contain a heterozygous deletion in the mouse region syntenic to the SMS common deletion, and exhibit craniofacial abnormalities, seizures and marked obesity, partially reproducing the SMS phenotype. To further study the genetic basis for the phenotype, we constructed three lines of mice with smaller deletions [Df(11)17-1, Df(11)17-2 and Df(11)17-3] using retrovirus-mediated chromosome engineering to create nested deletions. Both craniofacial abnormalities and obesity have been observed, but the penetrance of the craniofacial phenotype was markedly reduced when compared with Df(11)17/+ mice. Overt seizures were not observed. Phenotypic variation has been observed in mice with the same deletion size in the same and in different genetic backgrounds, which may reflect the variation documented in the patients. These results indicate that the smaller deletions contain the gene(s), most likely Rai1, causing craniofacial abnormalities and obesity. However, genes or regulatory elements in the larger deletion, which are not located in the smaller deletions, as well as genes located elsewhere, also influence penetrance and expressivity of the phenotype. Our mouse models refined the genomic region important for a portion of the SMS phenotype and provided a basis for further molecular analysis of genes associated with SMS.     

Auditory neuropathy/auditory dys-synchrony in school children with hearing loss: frequency of occurrence

OBJECTIVE: The frequency of occurrence of a recently identified hearing disorder, auditory neuropathy/auditory dys-synchrony (AN/AD), was investigated in children with hearing impairment in Hong Kong. METHODS: In this study, 56 students, aged 7-18 years, attending primary divisions in schools for the hearing impaired were screened using otoacoustic emission procedures. RESULTS: One student in the study group was found to have intact outer hair cell function. A detailed diagnostic assessment of this case strongly suggested AN/AD was involved. Combining the study results with those of a previously conducted survey in Hong Kong, the frequency of occurrence of AN/AD in children attending schools for the hearing impaired was estimated to be 2.44% (3 out of 123 children screened). Estimates of the frequency of occurrence of AN/AD in various other educational settings in Hong Kong were also derived. CONCLUSIONS: The study indicates that AN/AD is not an extremely rare disorder. Educational audiologists and other health care professionals need to be actively involved in the identification and management of AN/AD. Research should be directed at technological innovations that may help to overcome the limitations of present screening procedures, in order to more accurately identify the disorder.     

BK channels mediate the voltage-dependent outward current in type I spiral ligament fibrocytes

Recent experimental and clinical studies have provided considerable evidence to support the phenomenon of K(+) recycling in the mammalian cochlea. However, the precise cellular and molecular mechanisms underlying and regulating this process remain only partially understood. Here, we report that cultured type I spiral ligament fibrocytes (SLFs), a major component of the K(+) recycling pathway, have a dominant K(+) membrane conductance that is mediated by BK channels. The averaged half-maximal voltage-dependent membrane potential for the whole-cell currents was 70+/-1.2 mV at 1 nM intracellular free Ca(2+) and shifted to 38+/-0.2 mV at 20 microM intracellular free Ca(2+) (n=4-6). The reversal potential of whole-cell tail currents against different bath K(+) concentrations was 52 mV per decade (n=3-6). The sequence of relative ion permeability of the whole-cell conductance was K(+)>Rb(+)z.Gt;Cs(+)>Na(+) (n=5-17). The whole-cell currents were inhibited by extracellular tetraethylammonium and iberiotoxin (IbTx) with IC(50) values of 0.07 mM and 0.013 microM, respectively (n=3-7). The membrane potentials of type I SLFs measured with conventional zero-current whole-cell configuration were highly K(+)-selective and sensitive to IbTx (n=4-9). In addition, the BK channels in these cells exhibited voltage-dependent and incomplete inactivation properties and the recovery time was estimated to be approximately 6 s with repetitive voltage pulses from -70 to 80 mV (n=3). These data suggest that BK channels in type I SLFs play a major role in regulating the intracellular electrochemical gradient in the lateral wall syncytium responsible for facilitating the K(+) movement from perilymph to the stria vascularis.