Predictors and Prevalence of Nodal Disease in Salvage Oropharyngectomy.

BACKGROUND: Patients with recurrent oropharyngeal cancer often require extensive salvage surgery. For patients with clinically N0 necks, the indication for concurrent neck dissection remains unclear. This study aimed to determine predictors, prevalence, and distribution of nodal disease in patients treated with salvage oropharyngectomy. METHODS: In a case series with data collection at a single tertiary academic National Cancer Institute (NCI)-designated comprehensive cancer center, this study analyzed patients treated with prior radiation or chemoradiation who had persistent, recurrent, or second primary squamous cell carcinoma of the oropharynx requiring oropharyngeal resection between 1998 and 2017 (n = 95). Clinical and oncologic characteristics and treatment outcomes were collected, and statistical analyses were performed. RESULTS: The overall rate of nodal positivity was 21% (24/95), and the rate of occult nodal disease was 6% (4/65). Ipsilateral and contralateral level 2 were the most common areas harboring positive nodes. Bivariate analysis showed female sex (p = 0.01), initial overall stage (p = 0.02), and N status (p = 0.03), as well as recurrent overall and T stage (p = 0.05) to be predictors of nodal disease. In the multivariate analysis, recurrent T stage continued to be significantly predictive of pathologic nodal disease. Both computed tomography (CT) and positron emission tomography-CT were moderately accurate in predicting nodal disease in the salvage setting (area under the curve, 0.79 and 0.80, respectively). CONCLUSION: Occult nodal disease is observed in few patients undergoing salvage oropharyngeal resection. This study identified factors predictive of nodal disease in patients undergoing salvage oropharyngectomy and appropriate diagnostic tests in this setting.

Unilateral submandibular gland aplasia associated with ipsilateral sublingual gland hypertrophy.

Congenital absence of the major salivary glands is an infrequent disorder. Clinically, patients may be asymptomatic or may present with dryness of the mouth, difficulty in chewing and swallowing, and dental caries. The absence of the submandibular gland may be associated with hypertrophy of the contralateral submandibular gland. We report a case of ipsilateral sublingual hypertrophy associated with unilateral submandibular aplasia.

Sympathetic paraganglioma as an unusual cause of Horner's syndrome.

BACKGROUND: Paragangliomas are rare tumors arising from paraganglionic tissue of neural crest origin. They are present in any location where autonomic ganglia are found. The most common location in the head and neck is the carotid body, followed by the jugular bulb and vagus nerve. METHODS: A 30-year-old woman with a slowly growing left neck mass, aniscoria, and left eyelid ptosis was found to have a vascular tumor consistent with a paraganglioma arising near the left carotid bifurcation. After preoperative embolization, the patient underwent resection of the tumor. RESULTS: The tumor was found to be arising from the left sympathetic trunk and did not involve any other surrounding structures. Histopathologic analysis revealed the typical findings of a paraganglioma. CONCLUSIONS: Sympathetic paragangliomas are exceedingly rare tumors in the head and neck and should be considered in the differential diagnosis when clinical and radiographic evidence suggest a paraganglioma. The presentation is typically a slow-growing neck mass with the presence of an ipsilateral Horner's syndrome.

Angiotensin-converting enzyme and male fertility.

The angiotensin-converting enzyme (ACE; EC 3.4.15.1) gene (Ace) encodes both a somatic isozyme found in blood and several other tissues, including the epididymis, and a testis-specific isozyme (testis ACE) found only in developing spermatids and mature sperm. We recently used gene targeting to disrupt the gene coding for both ACE isozymes in mice and reported that male homozygous mutants mate normally but have reduced fertility; the mutant females are fertile. Here we explore the male fertility defect. We demonstrate that ACE is important for achieving in vivo fertilization and that sperm from mice lacking both ACE isozymes show defects in transport within the oviducts and in binding to zonae pellucidae. Males generated by gene targeting that lack somatic ACE but retain testis ACE are normally fertile, establishing that somatic ACE in males is not essential for their fertility. Furthermore, male and female mice lacking angiotensinogen have normal fertility, indicating that angiotensin I is not a necessary substrate for testis ACE. Males heterozygous for the mutation inactivating both ACE isozymes sire wild-type and heterozygous offspring at an indistinguishable frequency, indicating no selection against sperm carrying the mutation.

Angiotensin-converting enzyme gene and atherosclerosis.

Common variants of the angiotensin-converting enzyme (ACE) gene (ACE ie humans, Ace in mice) associated with changes in circulating ACE activities have been suggested to confer differential risks for atherosclerosis. Using a mouse model of atherosclerosis induced by heterozygosity for apolipoprotein E gene disruption and an atherogenic diet, we have studied the impact on atherogenesis of a mutation that changes the level of function of Ace. We find that this genetically determined change does not influence the size or complexity of atherosclerotic lesions. Ace genotype was not a significant determinant of lesion size in female (+/+ = 12.9 +/- 1.5 and +/- = 11.7 +/- 1.6 microns2 x 10(4)) or male (+/+ = 0.95 +/- 0.25 and +/- = 1.83 +/- 0.59 microns2 x 10(4)) mice; however, lesions were significantly larger (P < .001) in female than male mice. Ace genotype also did not affect lesion complexity; however, lesions in females showed significantly increased frequency of cholesterol clefts, acellular cores, fibrous caps, and calcifications compared with those in males. The hypothesis that genetic variation in the level of ACE gene expression affects the development of atherosclerosis is not supported by these findings.

Angiotensin-converting enzyme gene mutations, blood pressures, and cardiovascular homeostasis.

A common polymorphism of the angiotensin-converting enzyme (ACE) gene (ACE in humans, Ace in mice) is associated with differences in circulating ACE levels that may confer a differential risk for cardiovascular diseases. To study the effects of genetically determined changes in Ace gene function within a defined genetic and environmental background, we have studied mice having one, two, or three functional copies of the Ace gene at its normal chromosomal location. ACE activities in the serum increased progressively from 62% of normal in the one-copy animals to 144% of normal in the three-copy animals (P < 10(-15), n = 132). The blood pressures of the mice having from one to three copies of the Ace gene did not differ significantly, but the heart rates, heart weights, and renal tubulointerstitial volumes decreased significantly with increasing Ace gene copy number. The level of kidney renin mRNA in the one-copy mice was increased to 129 +/- 9% relative to that of the normal two-copy mice (100 +/- 4%, P = .01, n = 16). We conclude that significant homeostatic adaptations successfully normalize the blood pressures of mice that have quantitative changes in Ace gene function. Our results suggest only that quantitative changes in expression of the Ace gene will observably affect blood pressures when accompanied by additional environmental or genetic factors that together with Ace exceed the capacity of the homeostatic mechanisms.

Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene.

Estrogen receptor and its ligand, estradiol, have long been thought to be essential for survival, fertility, and female sexual differentiation and development. Consistent with this proposed crucial role, no human estrogen receptor gene mutations are known, unlike the androgen receptor, where many loss of function mutations have been found. We have generated mutant mice lacking responsiveness to estradiol by disrupting the estrogen receptor gene by gene targeting. Both male and female animals survive to adulthood with normal gross external phenotypes. Females are infertile; males have a decreased fertility. Females have hypoplastic uteri and hyperemic ovaries with no detectable corpora lutea. In adult wild-type and heterozygous females, 3-day estradiol treatment at 40 micrograms/kg stimulates a 3- to 4-fold increase in uterine wet weight and alters vaginal cornification, but the uteri and vagina do not respond in the animals with the estrogen receptor gene disruption. Prenatal male and female reproductive tract development can therefore occur in the absence of estradiol receptor-mediated responsiveness.