Successful use of biliary accessories in antegrade dilation of complex upper esophageal stricture due to chemoradiation and surgery.

Endoscopic management of complete or near complete upper esophageal strictures is challenging. Current methods such as retrograde esophageal access are high risk and may require additional abdominal surgery. A biliary cannulation technique with a 0.035 inch guidewire was utilized to obtain antegrade esophageal access in a patient with near complete high esophageal stricture due to chemo radiation and surgery for head and neck cancer. Biliary accessories including bougie and balloon dilators were used for the initial dilation of the esophageal stricture, followed by the traditional approach of stricture dilation using over-the-wire dilators. The procedure was successfully performed in a patient with near complete upper esophageal stricture due to chemo radiation and surgery for recurrent laryngeal cancer. The dysphagia of this patient was resolved following serial esophageal dilations and his esophageal stricture was wide open on the last upper endoscopy. Biliary accessories can be safely used for obtaining antegrade esophageal access and dilation of near complete upper esophageal strictures. This approach should be considered in patients with complex esophageal strictures, especially after chemo radiation or surgery for head and neck cancer and prior to seeking other more complex alternatives involving retrograde esophageal access.

Total and free estrogens and androgens in postmenopausal women with hip fractures.

Hip fracture constitutes the most serious complication of postmenopausal osteoporosis. To examine the possible role of circulating estrogen or androgen levels in the development of this type of fracture, 25 patients with hip fractures after minimal trauma were compared to an equal number of controls, matched for age and years since menopause. All were from a retirement community, had intact ovaries, and had not taken estrogen replacement for longer than 3 months during their entire lifetime. Hip fracture patients were found to have a significantly lower (P = 0.031) mean (+/-SE) percent ideal weight (89.4 +/- 2.9%) than controls (100.0 +/- 2.5%). Sex hormone-binding globulin levels were significantly higher (P = 0.004) in patients (6.7 +/- 0.4 X 10-8 M) than in controls (4.9 +/- 0.3 X 10-8 M), resulting in lower concentrations of biologically available estradiol and testosterone. In a subgroup of 12 patients and controls matched for percent ideal weight, differences in sex hormone binding globulin and free testosterone and estradiol levels were no longer statistically significant; however, the difference in the percentage of free testosterone persisted. These data suggest that endogenous sex steroids in their unbound form may play a role in the pathogenesis of postmenopausal hip fractures. The differences in free hormone levels appeared to be influenced by the differences in mean body size of the 2 groups. This factor is known to have an important negative effect on the concentration of sex hormone-binding globulin.

Free estradiol in postmenopausal women with and without endometrial cancer.

To assess the role of biologically active estradiol in the development of endometrial cancer, 25 patients with endometrial tumors and a similar number of control subjects matched for age and body size were studied. No differences between the 2 groups were found for levels of total estradiol, sex hormone-binding globulin (SHBG), non-SHBG-bound estradiol, and absolute free estradiol. Body size correlated positively with levels of total, non-SHBG-bound, and absolute estradiol and negatively with SHBG levels. The obese postmenopausal women had higher total circulating levels and proportionally greater concentrations of free estradiol than nonobese subjects, suggesting a dual risk for the cellular action of circulating estradiol. These factors could contribute to the association of obesity and the occurrence of this tumor in susceptible women.

Relationship of glutathione and glutathione-S-transferase to cisplatin sensitivity in human head and neck squamous carcinoma cell lines.

Factors controlling glutathione metabolism may govern sensitivity to chemotherapeutic agents such as cisplatin. Using a battery of cell lines derived from previously untreated head and neck squamous cell carcinomas, we examined cisplatin resistance relative to (a) glutathione-S-transferase (GST)-pi gene amplification and expression, (b) basal and inducible GST-total and GST-pi enzymatic activity, and (c) cellular levels of reduced glutathione (GSH). Using Southern blot analysis and northern blot hybridization, no relationship between GST-pi gene amplification, mRNA expression and drug resistance could be identified. Despite the capacity of cisplatin to induce GST enzyme activity, the response was variable and unrelated to cisplatin responsiveness. However, an inverse relationship between GSH levels and cisplatin sensitivity was identified. To further clarify these effects, cells were treated with S-allyl cysteine (SAC), a thioallyl derivative isolated from garlic (Allium sativum), which altered cellular GSH in a biphasic manner. Pretreatment with SAC to lower cellular GSH levels followed by exposure to cisplatin significantly enhanced the cytotoxic effects of cisplatin, while SAC alone had no effect on cell growth.

Long-standing virilism in a woman with hyperplasia and neoplasia of ovarian lipidic cells.

A woman with bilateral hyperplasia of ovarian hilar cells, stromal lipidic cells (hyperthecosis), and unilateral adenoma of Leydig cells is described. Her clinical course was characterized by long-standing virilism with a recent exacerbation suggesting growth of a tumor from the hyperplastic stromal lipidic cells. Evidence for this hypothesis included similar light and electron microscopic features of the hyperplastic and neoplastic cells and identical patterns of secretion of steroid hormones. Comparison of the in vivo steroid biosynthesis of the hyperplastic lipidic cells with that of testicular Leydig cells showed several similarities. These included 1) secretion of 5 and delta 4 steroids; 2) greater secretion of the delta 4 hormones, progesterone and 17-hydroxyprogesterone, than of the delta 5 steroids, pregnenolone and 17-hydroxypregnenolone; 3) prominent secretion of testosterone but not androstenedione; and 4) limited secretion of estrogens, with estradiol as the principal estrogen. These findings support prior microscopic evidence that ovarian lipidic cells and testicular Leydig cells represent cells of common function and, likely, common origin.

Endogenous cortisol and sex steroids in patients with osteoporotic spinal fractures.

Vertebral fractures due to osteoporosis commonly occur in postmenopausal women. Levels of cortisol and sex steroids in the circulation vary among older women. It has been suggested that this variation may contribute to the occurrence of osteoporotic fractures in some subjects but not others. To examine this, 30 patients with osteoporotic spinal fractures were compared to an equal number of controls matched to the patients for age and years since menopause. All subjects had intact ovaries and had not taken estrogen replacement therapy for more than 3 months during their entire lifetime. Spinal bone mineral density determined by dual photon absorptiometry was significantly lower (P less than .01) in the fraction group (0.75 +/- 0.03 g/cm2) than in the controls (1.0 +/- 0.03 g/cm2). No significant differences in body habitus or cortisol and sex steroid levels (both total and free) were found, with the exception of total estradiol levels, which were 16% higher in the fracture patients. This difference was presumably coincidental as there was no difference of free estradiol levels between groups. It is concluded that factors other than the differences of endogenous cortisol and sex steroid levels present in these postmenopausal women were responsible for the reduced bone mineral density of the spine observed in the fracture patients.

Changes in circulating steroids with aging in postmenopausal women.

to examine the possible effects of aging on circulating steroid hormones in postmenopausal women, blood samples were drawn from 155 women, aged 34 to 83 years, with spontaneous ovarian failure. The C-21 steroids, pregnenolone and 17-hydroxypregnenolone; the delta 4 progestins, progesterone and 17-hydroxyprogesterone; and cortisol did not change with age and were similar in concentration to the levels measured during the follicular phase of premenopausal women. The delta 5 androgens, dehydropiandrosterone and dehydroepiandrosterone sulfate, declined significantly (P less than .001) with age, whereas no change was noted in the delta 4 androgens, androstenedione and testosterone. The levels of estradiol (E2) and estrone (E1) were strongly correlated with percent ideal weight but did not change with age. The authors conclude that 1) The production of progestins does not change with age in normal adult women, other than that resulting from the loss of secretion associated with ovarian corpus luteum function. 2) The decline of delta 5 androgens without corresponding changes in their precursors suggests an age-related change of adrenal 17,20 desmolase activity. 3) The levels of E2 and E1 reflect an effect of body size but not of age on peripheral aromatization of precursor androgens.

Sperm hyperactivation as quality control for sperm penetration assay.

The sperm penetration assay (SPA) is subject to considerable variation, and controls are needed to verify the accuracy of the results. It is proposed that sperm hyperactivation (HA) can serve as a quality control check for the SPA. The objective was to determine if there was an association between the SPA outcome and sperm HA measured at various times during the SPA procedure. The data showed a significant correlation between percent sperm HA and percent zona-free oocyte penetration by sperm preincubated for three hours prior to sperm-oocyte interaction (short preincubation). Some sperm hyperactivity was observed in liquefied raw semen samples, but this was insignificantly related to SPA results. Low correlation was observed between SPA results and sperm HA determined immediately after centrifuge washing of sperm. The results suggest that it is possible to utilize sperm HA measured immediately after the sperm-oocyte interaction period as a quality control check of SPA results.

Urinary pregnandiol-3-glucuronide and estrone conjugates to creatinine ratios in early pregnancies complicated by vaginal bleeding.

There is no simple and rapid test available to predict the outcome of an early pregnancy complicated by vaginal bleeding. In this prospective study, 15 women with normal pregnancies collected a weekly urine sample between 6 and 13 weeks' gestation. A single random urine sample was obtained from 15 women with bleeding who continued to carry their child and 50 women who proceeded to have a spontaneous abortion (SAB). Pregnandiol-3-glucuronide (PDG) was determined with the use of enzyme-multiplied immunoassay technique (EMIT) and estrone conjugates (E1C) were measured by radioimmunoassay (RIA). The ratios of these metabolites to creatinine (C) were calculated. PDG/C ratios in normal women rose gradually from 6 weeks on. All women with bleeding during a normal pregnancy had ratios in the normal range, but 94% of women with a SAB had ratios below the normal range. The E1C/C ratio remained unchanged from 6 to 11 weeks and then rose rapidly. Until 11 weeks, there was no clear separation between the E1C/C ratios of the women with a SAB and the women with bleeding who continued their pregnancies. The prognosis of threatened abortion can be made by a urinary PDG/C ratio but not by an E1C/C ratio. EMIT is simple and quick and uses technology present in many laboratories.

An analysis of endometrial biopsies performed for infertility.

The authors evaluated 774 endometrial biopsies that were performed for infertility. Complications arose in 3.6%. Lag of more than 2 days was found in 19%; luteal phase defect (LPD) was diagnosed in 5.7%. Most of the incidence of LPD can be predicted from chance occurrence. There was no association between abnormal biopsies and basal body temperature patterns, or between pathology, pregnancy outcome, and treatment. Exceptions included women with multiple spontaneous abortions and patients treated with clomiphene citrate (CC). An endometrial biopsy was performed in a pregnancy cycle in 4.0%, with an abortion rate not significantly different from the total study group. The authors conclude that an endometrial biopsy is relatively safe; however, the diagnostic and therapeutic consequences are limited. Endometrial biopsies may be useful only if performed in cases of habitual abortion or ovulation induction with CC.

Atrial natriuretic peptide, plasma renin activity, and aldosterone in women on estrogen therapy and with premenstrual syndrome.

Estrogens are known to increase the renin-angiotensin-aldosterone system and to produce fluid retention, while atrial natriuretic peptide (ANP) induces an increase of the urinary output and tends to return the fluid balance to normal. The aim of this study was to test whether the levels of ANP were decreased during chronic estrogen and progestin administration, thereby possibly decreasing the amount of fluid excreted. The authors also studied women with premenstrual syndrome (PMS), because of the associated fluid retention often described with this syndrome. Levels of ANP, plasma renin activity (PRA), and aldosterone were determined in premenopausal women in the early follicular phase (EFP) and on low-dose oral contraceptives (OC), in postmenopausal patients with and without estrogen replacement therapy (ERT), and in women with PMS associated with fluid retention. The concentrations of ANP and PRA were enhanced in the women on OC, but those of aldosterone were unchanged. No differences were observed in the women on ERT or with PMS. It is concluded that the levels of PRA and ANP are affected by estrogen or progesterone therapy or the combination of the two and this response is dose dependent or additive. Furthermore, ANP and PRA do not seem to play a direct role in PMS.

Thyroid cancer.

Management of thyroid cancer varies somewhat between communities and institutions depending on tumor type and individual treatment philosophy. The differentiated thyroid cancers have a significantly better outlook than the medullary and anaplastic. This article provides an overview of the literature that describes pathogenesis, diagnosis, and treatment currently recommended for these thyroid cancers.

Dyslexic and normal readers' eye movements.

Dyslexic and normal readers' eye movements were compared while tracking a moving fixation point and in reading. Contrary to previous reports, the dyslexic and normal readers did not differ in their number of saccades, percentage of regressions, or stability of fixations in the tracking task. Thus, defective oculomotor control was not associated with or a causal factor in dyslexia, and the dyslexics' abnormal eye movements in reading must be related to differences in higher cognitive processes. However, individual differences in oculmotor efficiency, independent of reading ability, were found within both the dyslexic and normal groups, and these differences were correlated in reading and tracking tasks.

Perceptual flexibility in word recognition: strategies affect orthographic computation but not lexical access.

Four tachistoscopic forced-choice recognition experiments explored the flexibility of processes underlying word perception. Stimuli were words, orthographically regular but unfamiliar pseudowords, and orthographically irregular nonsense strings. In the first two experiments, subjects knew that several different kinds of stimuli would occur in each block of trials and that one kind would occur much more often than the others. No matter which stimulus subjects expected to see most often, accuracy on words and pseudowords differed little, and both were identified considerably better than nonsense. In the third and fourth experiments, subjects were led to believe that only on stimulus type would occur but were surreptitiously shown another type on a small number of trials. Words were again identified more accurately than nonsense, and the size of the effect was independent of expectations. However, when either words or nonsense strings were expected exclusively, pseudoword accuracy did not differ from nonsense accuracy. Only when subjects knew that pseudowords would occur did they identify pseudowords more accurately than nonsense. This dissociation between word and pseudoword identification indicates the operation of two independent encoding mechanisms during tachistoscopic recognition, a stimulus-specific or logogenlike system sensitive to particular familiar strings and an orthographic mechanism sensitive to generally applicable constraints on letter sequencing. The stimulus-specific mechanism appears to be utilized automatically, but use of the orthographic mechanism is under strategic control. As shown in the first two experiments, however, rather extraordinary measures were required to demonstrate the flexibility of the orthographic processes used in this task.

Posterior triangle metastases of squamous cell carcinoma of the upper aerodigestive tract.

The trend toward function-conserving surgery in the treatment of squamous cell carcinoma of the head and neck has led to a progression from radical neck dissection to modified neck dissection and selective neck dissection has growing support. These surgical modifications have resulted from an effort to spare structures uninvolved with malignancy. Level V dissection can be associated with spinal accessory dysfunction in some patients even when the nerve remains intact. In this study, we have attempted to address the need for level V dissection by determining the prevalence of level V metastases in a large series of patients undergoing radical neck dissection. There were 1,123 patients who underwent 1,277 neck dissections between 1965 and 1986. A review of pathologic and clinical records revealed 40 patients (3%) with positive nodes at level V. The prevalence of level V metastases was greatest with hypopharynx and oropharynx primary tumors (7% and 6%, respectively). Level V metastases were found in 1% of patients with oral cancers and 2% of those with larynx cancers. Groups were divided into N0 (282), N+ (719), and subsequent N+ (276), depending on the clinical status at the time of surgery. Thirty-seven of 40 patients with posterior triangle metastases were clinically N+. The prevalence of metastases at level V was 1% for N0, 5% for N+, and 0% for subsequent N+. This large series shows minimal involvement of metastases at level V. The low likelihood of metastases at level V, even in N+ disease, should be considered when performing lymphadenectomy for squamous cell carcinoma of the upper aerodigestive tract.

Cervical metastases of occult origin: the impact of combined modality therapy.

BACKGROUND: We have updated our experience with metastatic carcinoma to the neck of occult origin to assess whether increasing use of adjunctive radiation therapy has had a significant impact. METHODS: This retrospective review of 115 patients treated between 1977 and 1990 includes 73 (63%) with squamous cell carcinoma. These 73 patients were analyzed for survival, control of disease in the neck, and incidence of subsequent primary tumors. RESULTS: There has been no change in the proportion of patients with advanced neck disease (N2/N3 = 52; 71%) when compared to our last report. Surgery included comprehensive neck dissection in 59 (81%) and adjunctive radiotherapy was employed in 54 (83% of surgically treated patients). Primary carcinomas within the head and neck were identified subsequently in 9 (12%) patients, including 4 of 11 (36%) who did not have adjunctive radiotherapy and 5 of 54 (9%) who did (P = 0.038). Control of the treated neck (54/73; 74%) has improved significantly (P = 0.005) when compared to our earlier experience (37/74; 50%), and this was most apparent in those with extensive neck disease. However, cumulative survival at 5 years (45%) was not significantly different from that previously reported. CONCLUSION: Our data support the increased use of adjunctive radiation therapy for metastatic squamous cell carcinoma in the neck of occult origin. Control of neck disease has improved and the likelihood that a primary will be identified has been reduced, but there has been no improvement in survival when compared to historical controls.

The relationship of loss of heterozygosity to tobacco exposure and early recurrence in head and neck squamous cell carcinoma.

BACKGROUND: Tobacco usage contributes to carcinomas of the lung, bladder, esophagus, uterine cervix, and head and neck, and can induce specific genetic lesions. Studies of the above tumor types have documented allelic deletions affecting 3p, 5q, 9p, 9q, 10q, 11p, 13q, 17p, and 18q. Relationships between genetic loss, tobacco exposure, and patient outcome have not been described. PATIENTS AND METHODS: To confirm and further define loss of heterozygosity in head and neck squamous cell carcinoma (HNSCC), and to examine relationships between loss of heterozygosity and both tobacco exposure and early recurrence, we undertook this study on previously untreated patients with HNSCC. We performed a Southern blot analysis using 11 probes specific for loci deleted in tobacco-associated cancers. We have investigated 42 prospectively collected, paired samples of HNSCC and peripheral blood. Demographic and follow-up data were collected on these patients. RESULTS: Significant loss of heterozygosity was observed in descending order of frequency at 11p, 9p, 17p, 3p, 10q, and 13q. All nonsmokers showed loss of heterozygosity on one or more loci compared with only 53% of smokers (P < 0.05). Furthermore, patients with multiple deletions had a significantly higher rate of early recurrence than those with fewer deletions (P < 0.05). CONCLUSION: Multiple deletions occurred more frequently in nonsmokers and predicted a higher risk of early recurrence.

Supraspinal accessory lymph node metastases in supraomohyoid neck dissection.

BACKGROUND: Some patients undergoing surgical resection of primary squamous cell carcinoma of the oral cavity and oropharynx also undergo supraomohyoid neck dissection for staging of the negative (N(o)) neck. Dissection of the supraspinal accessory lymph node pad requires significant traction of the spinal accessory nerve. There are currently no data to indicate the incidence of metastases to this site and thus the necessity of performing dissection of these nodes. METHODS: A prospective analysis of a consecutive series of 44 patients with newly diagnosed squamous carcinoma of the oral cavity or oropharynx undergoing surgical management of the primary lesion with staging neck dissection was performed. Patients underwent unilateral (41) or bilateral (3) supraomohyoid neck dissection with separate submission of the supraspinal accessory lymph node pad for pathologic evaluation to determine the incidence of nodal metastases. RESULTS: A total of 15 patients (32%) had microscopic metastatic squamous cell carcinoma involving the supraomohyoid neck dissection specimen. Only 1 patient had a metastatic deposit involving the supraspinal accessory lymph node pad. This patient also had metastases in additional lymph nodes at level II. There was an equal incidence of metastases for all patients when stratifying by T stage. CONCLUSION: This preliminary report reveals a small incidence of supraspinal accessory lymph node metastases in patients with T + NO squamous cell carcinoma of the oral cavity and oropharynx. We continue to accrue patients to determine if the incidence of supraspinal accessory lymph node metastases varies with an increased number of patients.

Activation of semantic and phonological codes during reading.

Three experiments used a new paradigm to examine word-coding processes during reading. Subjects read text passages and occasionally responded to lexical-decision probes. Experiment 1 focused on semantic and surface codes. The activation of semantic codes appeared to increase over time, whereas surface codes did not. In addition, subjects who were instructed to remember the exact wording of the passages showed stronger activation of surface codes than did subjects who read for comprehension. Experiments 2 and 3 explored the role of phonological codes. Experiment 2 showed that phonological codes were activated by specific words in a passage. In contrast, Experiment 3 found no evidence that phonological codes were activated by the more general passage context. Taken together, the experiments suggest some of the roles semantic and phonological codes may play during reading.

The genetics of tobacco-induced malignancy.

OBJECTIVE: Several areas of investigation contribute to an increasing understanding of the genetics of malignancies associated with tobacco use. While the strong influence of tobacco exposure on cancer development obscures genetic influences, there are indications that aspects of cancer susceptibility may have a heritable basis. In addition, specific sites within the genome appear to be commonly involved in these malignancies. This review describes research relevant to investigation of the genetics of tobacco-induced malignancy. DATA SOURCES: A review of the pertinent literature covered the past 20 years. References were gleaned from a variety of sources including manual review of the most recent journals, a computerized database (Mini-MEDLINE), references cited in previous works, and our own ongoing research in cancer genetics and molecular biology. STUDY SELECTION AND DATA EXTRACTION: Whenever possible, controlled studies from peer-reviewed journals were used. Where studies have shown conflicting results, the possible confounding factors are discussed. DATA SYNTHESIS: From a broad array of research areas, a view of the genetic aspects of tobacco carcinogenesis emerges. This includes syndromic and nonsyndromic susceptibility, genetic determinants of carcinogen metabolism, DNA adduct formation, and site-specific genetic alterations in tobacco-induced malignancy. In addition to specific gene alterations commonly seen in tobacco-induced malignancy, viral infections may contribute to cancer development through pathways related to tobacco carcinogenesis. CONCLUSION: Further research on many aspects of tobacco-induced carcinogenesis is warranted. Investigation of cancer susceptibility may contribute to understanding DNA surveillance and repair pathways. Carcinogen metabolism investigations have application in cancer detection and prevention schemes. Further understanding of tumor suppressor gene function and the role of gene amplification in carcinogenesis may allow design of gene-specific strategies in cancer treatment.