30-day morbidity and mortality after transoral robotic surgery for human papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma: A retrospective analysis of two prospective adjuvant de-escalation trials (MC1273 & MC1675).

OBJECTIVE: Dose de-escalation of adjuvant therapy (DART) in patients with HPV(+)OPSCC was investigated in two prospective Phase II and III clinical trials (MC1273 and MC1675). We report the 30-day morbidity and mortality associated with primary TORS resection in patients enrolled in these trials. MATERIALS AND METHODS: Patients with HPV(+)OPSCC, who underwent TORS resection between 2013 and 2020 were considered in this analysis. The severity of postoperative transoral bleeding was graded using both the Hinni Grade (HG) transoral surgery bleeding scale and the Common Terminology for Adverse Events (CTCAE) v5.0. Post-surgical complications within 30 days of surgery, as well as rates of tracheostomy, PEG and nasogastric tube placement. RESULTS: 219 patients were included. A total of 7 (3.2 %) patients had a tracheostomy placed at the time of surgery, and all were decannulated within 26 days (median: 5, range: 2-26). There were 33 (15.1 %) returns to the emergency department (ED) with 10 (4.6 %) patients requiring readmission. Using the HG scale, 10 (4.6 %) patients experienced ≥ Grade 3 bleeding with no Grade 5 or 6 bleeds. In contrast, using the CTCAE scale, 15 patients (6.8 %) experienced ≥ Grade 3 bleeding with no Grade 5 bleeds. There was one post-operative death in a patient withdrawn from the trial, and no deaths related to hemorrhage. CONCLUSION AND RELEVANCE: TORS for HPV(+)OPSCC in carefully selected patients at a high volume center was associated with low morbidity and mortality.

Atypical ductal hyperplasia and ductal carcinoma in situ as revealed by large-core needle breast biopsy: results of surgical excision.

OBJECTIVE: This investigation compares the frequency of histologic underestimation of breast carcinoma that occurs when a large-core needle biopsy reveals atypical ductal hyperplasia or ductal carcinoma in situ with the automated 14-gauge needle, the 14-gauge directional vacuum-assisted biopsy device, and the 11-gauge directional vacuum-assisted biopsy device. SUBJECTS AND METHODS: Evaluation of 428 large-core needle biopsies yielding atypical ductal hyperplasia (139 lesions) or ductal carcinoma in situ (289 lesions) was performed. The results of subsequent surgical excision were retrospectively compared with the needle biopsy results. RESULTS: For lesions initially diagnosed as ductal carcinoma in situ, underestimation of invasive ductal carcinoma was significantly less frequent using the 11-gauge directional vacuum-assisted biopsy device when compared with the automated 14-gauge needle (10% versus 21%, p < 0.05) but was not significantly less frequent when compared with the 14-gauge directional vacuum-assisted device (10% versus 17%, p > 0.1). For lesions diagnosed initially as atypical ductal hyperplasia, underestimation of ductal carcinoma in situ and invasive ductal carcinoma was significantly less frequent using the 11-gauge directional vacuum-assisted biopsy device compared with the 14-gauge directional vacuum-assisted device (19% versus 39%, p = 0. 025) and with the automated 14-gauge needle (19% versus 44%, p = 0. 01). CONCLUSION: The frequency of histologic underestimation of breast carcinoma in lesions initially diagnosed as atypical ductal hyperplasia or ductal carcinoma in situ using large-core needle biopsy is substantially lower with the 11-gauge directional vacuum-assisted device than with the automated 14-gauge needle and with the 14-gauge directional vacuum-assisted device.

Mammographic and sonographic appearances of nodular adenosis.

OBJECTIVE: We determined whether nodular adenosis of the breast possesses any pathognomonic features on imaging studies. CONCLUSION: The imaging features of nodular adenosis are often benign-appearing and can be indistinguishable from other ellipsoid, circumscribed, or hypodense masses. Occasionally, nodular adenosis may appear suggestive of malignancy. Pathologic evaluation by excisional or large core needle biopsy is necessary for diagnosis.

Gynecomastoid hyperplasia: imaging findings in six patients.

This case series describes the radiologic appearances of gynecomastoid hyperplasia of the breast in our experience. The clinical histories, breast images, and histopathologic findings in six women were reviewed. At mammography, there was no abnormality in two women, an enlarging asymmetric density in three women, and a nodule in one woman. Breast ultrasonography showed a hypoechoic nodule in one woman. Gynecomastoid hyperplasia has a varied radiologic appearance.

Large-core needle biopsy of nonpalpable breast lesions.

CONTEXT: An increasing number of nonpalpable abnormalities requiring breast biopsy are being identified due to the widespread use of screening mammography. Large-core needle biopsy (LCNB) has become an alternative to surgical excision. OBJECTIVE: To determine whether LCNB is a safe and accurate technique to evaluate nonpalpable abnormalities found on breast imaging studies. DESIGN AND SETTING: Case series at an institutional referral center from August 1, 1991, to December 31, 1997. PATIENTS: A total of 1643 women with 1 or more suspicious breast abnormalities received LCNBs (n = 1836 lesions). INTERVENTION: The LCNB of the breast uses a 14- or 11-gauge needle with stereotactic localization or ultrasound guidance. MAIN OUTCOME MEASURE: Utility and potential limitations of LCNB compared with the criterion standard, surgical excision after wire localization. RESULTS: Of the 1836 breast lesions sampled, 444 (24%) were found to be malignant. A total of 412 (22%) were found to be malignant on the initial LCNB and 202 repeat biopsies yielded 32 additional malignancies. Complications were infrequent: 1 patient experienced a superficial infection and 1 developed a pneumothorax after LCNB. CONCLUSION: Image-guided LCNB is a reliable diagnostic alternative to surgical excision of suspicious nonpalpable breast abnormalities.

Fibrous nodules found at large-core needle biopsy of the breast: imaging features.

PURPOSE: To describe the imaging and histologic features of large-core needle biopsy (LCNB) specimens of fibrous nodules. MATERIALS AND METHODS: Of 853 breast masses in which LCNB was performed, 38 (4%) revealed histologic findings of fibrous nodules. Repeat biopsy was performed in 16 lesions (surgical excision, 13 lesions; repeat LCNB, three lesions). The mammographic and ultrasonographic findings in these 16 cases, the histologic LCNB findings, and the repeat biopsy findings were retrospectively reviewed. RESULTS: Repeat biopsy findings confirmed the diagnosis of fibrous nodules in 15 of the 16 masses. In one mass, repeat LCNB findings showed a fibroadenoma. The imaging features of the fibrous nodules varied. Five nodules (33%) manifested as masses with indistinct margins; six (40%), as circumscribed masses. In four cases (27%), imaging suggested malignancy. None were calcified masses. An additional 22 masses had circumscribed or indistinct borders and were diagnosed with LCNB as fibrous nodules. None of these masses had suspicious findings, and repeat biopsy was not performed. CONCLUSION: Fibrous nodules usually manifest as masses with circumscribed or indistinct margins but can have findings suggestive of malignancy. LCNB can reveal histologic findings consistent with this diagnosis. In all masses in which repeat biopsy was performed, the diagnosis of a fibrous nodule was confirmed or another benign stromal lesion was diagnosed.

Large-needle core biopsy: nonmalignant breast abnormalities evaluated with surgical excision or repeat core biopsy.

PURPOSE: To classify lesions initially considered nonmalignant at large-needle core biopsy that were subsequently surgically excised or sampled at repeat biopsy. MATERIALS AND METHODS: From August 1, 1991, to December 31, 1996, 1,032 breast abnormalities (214 malignant and 818 nonmalignant lesions) were sampled at large-needle core biopsy. Of the nonmalignant lesions, 112 (14%) abnormalities were studied. Twenty-four abnormalities were subsequently excised because of discordant imaging and pathologic findings; 41 may have been missed at biopsy (25 were surgically excised, and 16 were sampled at repeat biopsy); 40 were surgically excised as recommended by the pathologist; and seven were excised for other indications. RESULTS: None of 24 abnormalities excised because of discordant findings was malignant. Among the 41 possibly missed lesions, infiltrating ductal carcinoma was found in one lesion that was removed surgically and in one sampled at repeat biopsy. Among the 40 lesions recommended for excision by the pathologist, 16 malignancies were found (ductal carcinoma in situ, 11; infiltrating ductal carcinoma, three; phyllodes tumor, two). None of the remaining seven lesions was malignant. CONCLUSION: Correlation of the technical quality of the biopsy, imaging features, and pathologic findings resulted in 96 surgical excisions and 16 repeat biopsies of lesions initially considered nonmalignant. Eighteen additional malignancies were identified.

Epidermal inclusion cysts of the breast: three lesions with calcifications.

PURPOSE: To determine whether there are any mammographic and ultrasonographic (US) features of epidermal inclusion cysts of the breast, including heterogeneous microcalcifications, that may be used to preclude unnecessary biopsy. MATERIALS AND METHODS: Clinical history and imaging findings in 15 patients who had undergone surgical excision of an epidermal inclusion cyst were reviewed. RESULTS: In 11 patients, imaging findings of an epidermal inclusion cyst were noted, including 10 patients with mammographic findings, one with US findings only, and seven with mammographic and US findings. The most common mammographic finding (in nine of 10 patients) was an isodense to high-density mass with a circumscribed margin; three circumscribed masses had multiple associated heterogeneous microcalcifications. In the seven patients with corresponding US findings, a circumscribed hypoechoic mass with through transmission was depicted. An additional US feature in six patients was extension of the mass into the dermis. CONCLUSION: Biopsy may be deemed unnecessary if the characteristic US and physical examination findings are present, even in the case of a cyst with heterogeneous microcalcifications.

Spindle cell lipoma of the breast. A case report.

A case of spindle cell lipoma of the breast found on mammography in a 53-year-old woman is presented. This rare type of tumor has been previously reported on only after its presentation as a palpable mass. Radiographically it appears as a well-circumscribed mass. Ultrasonographically it appears as a homogeneously hyperechoic nodule. Histologically these lesions are composed of spindle cells intermingled with adipocytes.

Evaluation of nonpalpable solid breast masses with stereotaxic large-needle core biopsy using a dedicated unit.

OBJECTIVE: In our institution for the past 4 years, stereotaxic core breast biopsy using a 14-gauge needle has been offered as an alternative to surgical excision. The purpose of this paper is to describe our protocol, results, and lessons learned from our experience. MATERIALS AND METHODS: From August 1991 to July 1995, 388 stereotaxic needle core biopsies of clinically occult, noncalcified, mammographically detected solid masses were performed. In this group, 103 patients underwent subsequent surgical excision. Another 169 have had follow-up examinations 1 year or more after their biopsies. RESULTS: Of the 61 patients diagnosed with a malignant process on core biopsy, all had confirmation on subsequent surgical excision. Forty-one of the 42 core biopsies that showed a benign process were subsequently confirmed on surgical excision. One patient with atypical ductal hyperplasia on core biopsy had ductal carcinoma in situ on surgical excision. Patients with 169 benign masses on core biopsy have been followed for at least 1 year by mammography. Of these women, 110 have been followed for at least 2 years, and no malignant lesions have been found. CONCLUSION: Stereotaxic large-needle core biopsy appears to be an accurate alternative to surgical excision for evaluating a solid breast mass. However, the mammographic appearance, technical quality of the biopsy, and pathologic findings in each patient must be correlated to ensure the highest possible accuracy when using this technique.

Clonal analysis by study of X chromosome inactivation in formalin-fixed paraffin-embedded tissue.

Analysis of clonality by X chromosome inactivation has proven to be a powerful strategy in the study of neoplastic and preneoplastic disorders (P. J. Fialkow, Biochim. Biophys. Acta, 458: 283-321, 1976; B. Vogelstein et al., Cancer Res., 47: 4806-4813, 1987). Recently, the gene for the androgen receptor has been shown to be a highly polymorphic locus in which methylation of DNA correlates with inactivation of one or the other X homologue (R. C. Allen et al., Am. J. Hum. Genet., 51: 1229-1239, 1992). Unlike other loci used for analysis of X inactivation, the methylation sites within the androgen receptor gene lie close to the region of DNA containing the polymorphism. Consequently, it should be possible to use methylation-sensitive restriction enzymes and polymerase chain reaction to study differential methylation among alleles of this gene in formalin-fixed and paraffin-embedded archival tissue specimens. To investigate this question, we performed clonal analysis on a variety of randomly selected, formalin-fixed, paraffin-embedded tumor tissues from 15 women. Thirteen of the women were found to be heterozygous for polymorphisms at the androgen receptor locus. Among these women, 11 tumors were clearly clonal in assays of methylation of the androgen receptor gene. Interpretation of results for the remaining two cases was complicated because of a skewed pattern of X chromosome inactivation found in normal control tissues. We conclude that analysis of methylation in the androgen receptor gene should allow study of clonality in most formalin-fixed, paraffin-embedded tissue specimens from women, including small preneoplastic lesions or rare conditions for which sufficient material is not available for analysis by other techniques.

Occult breast calcifications sampled with large-core biopsy: confirmation with radiography of the specimen.

In a series of nine stereotaxic large-core biopsies of calcifications, radiography of the specimen was used to ensure that appropriate tissue was removed. In eight cases, calcifications were evident at radiography as well as at histologic evaluation. Four cases were malignant and four were benign, and in one case in which calcification was not evident at either radiographic or histologic evaluation, a benign process was confirmed at surgical excision. Radiography of the specimen is a key component in diagnosis of breast calcifications sampled with large-core technique.

Lineage-restricted chromosome translocation in a benign fibrous tumor of the breast.

We describe a clonal chromosome rearrangement, t(4;14)(q24-25;q24.3), in a benign fibrous tumor of the breast. This is the first reported cytogenetic analysis of a fibrous tumor of the breast and the first evidence for clonality in these lesions. A combined immunohistochemical/cytogenetic study demonstrated that cells with the clonal translocation were mesenchymal. Epithelial cells, in contrast, had normal chromosomes.

The carriage of Escherichia coli resistant to antimicrobial agents by healthy children in Boston, in Caracas, Venezuela, and in Qin Pu, China.

BACKGROUND AND METHODS: The healthy members of a community represent its largest reservoir of bacteria resistant to antimicrobial agents. We compared the resistance to eight agents of Escherichia coli in stool samples from untreated, healthy children in cities on three continents. RESULTS: When screened by a selective method that detected 1 resistant colony in 10,000 colonies, nearly half the children in Boston (18 of 39) had no resistant colonies--a finding consistent with the findings of other surveys performed in developed countries. However, all but 1 of 41 children screened in Caracas, Venezuela, and all but 2 of 53 in Qin Pu, China, carried resistant strains. Only 1 child in Boston but 25 in Caracas and 34 in Qin Pu carried strains resistant to trimethoprim. None of the children in Boston or Caracas but 17 in Qin Pu carried strains resistant to gentamicin. Among 10 colonies selected randomly from each stool sample, the average frequency of resistance in Caracas was 3.6 times greater than in Boston, and that in Qin Pu was 5.3 times greater. There was resistance to five or more antimicrobial agents in 20 percent of the Qin Pu strains and in 6 percent of the Caracas strains but in none of the Boston strains. CONCLUSIONS: In addition to clinical isolates, as reported previously, the bacteria that colonize health children in the community may be resistant far more often in some regions than in others. A low rate of carriage of antimicrobial resistance in the community should become a public health goal.

Derepression of genes on the human inactive X chromosome: evidence for differences in locus-specific rates of derepression and rates of transfer of active and inactive genes after DNA-mediated transformation.

Mouse-human hybrid cells that contained an inactive human X chromosome were treated with agents known to alter gene expression and to perturb DNA methylation. 5-Azacytidine greatly increased the rate of derepression of HPRT on the inactive X, while butyrate and dimethyl sulfoxide had smaller effects. Ethionine did not change the rate of derepression. Derepression of two other X-chromosomal loci, PGK and GPD, was also detected. The rate of derepression of PGK was 20-fold higher than the rate for HPRT. Derepression events at the two loci appeared to be independent. Hybrids expressing derepressed X-chromosomal genes had more variable levels of human enzyme activities when compared to control hybrids. HPRT+ clones did not appear after transfer of purified DNA from a cell hybrid containing an inactive human X into HPRT- recipients, but such clones did appear after transfer of DNA from derivative cells in which HPRT had been derepressed.

Expression of human genes for adenine phosphoribosyltransferase and hypoxanthine-guanine phosphoribosyltransferase after genetic transformation of mouse cells with purified human DNA.

Human DNA purified from HeLa cells and from three strains of skin fibroblasts was precipitated with calcium phosphate and added to mouse cells that were deficient in adenine phosphoribosyltransferase (APRT) and hypoxanthine phosphoribosyltransferase (HPRT). Selection for cells possessing either of the phosphoribosyltransferases was imposed by blocking de novo synthesis of purine nucleotides with azaserine in a medium supplemented with adenine and hypoxanthine. The frequency of colony formation after selection was 1.7 x 10(-7)-3.3 x 10(-6). Excepting some azaserine-resistant colonies that appeared only in the first experiment and infrequent revertants expressing moust APRT, all characterized clones expressed the human forms of APRT or HPRT according to the criteria of specific immunoprecipitation and electrophoretic mobility. The frequency of transfer of the human APRT gene was much greater than that of HPRT. Transfer efficiency was not significantly reduced when HeLa DNA was sheared to 6.5-13.5 kb size or when the donor DNA was isolated from a transferent that expressed human APRT.