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Importance: Prospective trials have demonstrated sentinel lymph node (SLN) false-negative rates of less than 10% when 3 or more SLNs are retrieved in patients with clinically node-positive breast cancer rendered clinically node-negative with neoadjuvant chemotherapy (NAC). However, rates of nodal recurrence in such patients treated with SLN biopsy (SLNB) alone are unknown because axillary lymph node dissection (ALND) was performed in all patients, limiting adoption of this approach., Objective: To evaluate nodal recurrence rates in a consecutive cohort of patients with clinically node-positive (cN1) breast cancer receiving NAC, followed by a negative SLNB using a standardized technique, and no further axillary surgery., Design, Setting, and Participants: From November 2013 to February 2019, a cohort of consecutively identified patients with cT1 to cT3 biopsy-proven N1 breast cancer rendered cN0 by NAC underwent SLNB with dual tracer mapping and omission of ALND if 3 or more SLNs were identified and all were pathologically negative. Metastatic nodes were not routinely clipped, and localization of clipped nodes was not performed. The study was performed in a single tertiary cancer center., Intervention: Omission of ALND in patients with cN1 breast cancer after NAC if 3 or more SLNs were pathologically negative., Main Outcome and Measures: The primary outcome was the rate of nodal recurrence among patients with cN1 breast cancer treated with SLNB alone after NAC., Results: Of 610 patients with cN1 breast cancer treated with NAC, 555 (91%) converted to cN0 and underwent SLNB; 234 (42%) had 3 or more negative SLNs and had SLNB alone. The median (IQR) age of these 234 patients was 49 (40-58) years; median tumor size was 3 cm; 144 (62%) were ERBB2 (formerly HER2)-positive, and 43 (18%) were triple negative. Most (212 [91%]) received doxorubicin-based NAC; 205 (88%) received adjuvant radiotherapy (RT), and 164 (70%) also received nodal RT. At a median follow-up of 40 months, there was 1 axillary nodal recurrence synchronous with local recurrence in a patient who refused RT. Among patients who received RT (n = 205), there were no nodal recurrences., Conclusions and Relevance: This cohort study found that in patients with cN1 disease rendered cN0 with NAC, with 3 or more negative SLNs with SLNB alone, nodal recurrence rates were low, without routine nodal clipping. These findings potentially support omitting ALND in such patients.

Juvenile papillomatosis (JP) of the breast is a rare benign mass-forming lesion occurring in young women, which is histologically characterized by a constellation of proliferative changes and large cysts, giving it the gross appearance of Swiss cheese. A subset of patients with JP report a family history of breast carcinoma and/or coexisting or subsequent breast carcinoma. We performed whole-exome sequencing of the hyperplastic epithelial component of three JPs, including one with coexisting ductal carcinoma in situ (DCIS) and invasive ductal carcinoma of no special type (IDC-NST). JPs harbored clonal somatic PIK3CA hotspot mutations in two cases. In the JP with coexisting DCIS and IDC-NST, these lesions were clonally related to the associated JP, sharing a clonal PIK3CA E542K somatic hotspot mutation. JP showed a paucity of copy number alterations, whereas the associated DCIS and IDC-NST showed concurrent 1q gains/16q losses, hallmarks of estrogen receptor (ER)-positive breast cancers. We observed JP to harbor a dominant aging-related mutational signature, whereas coexisting DCIS and IDC-NST showed greater exposure to an APOBEC signature. Taken together, our findings suggest that, at least in a subset of cases, JP might constitute the substrate from which DCIS and invasive breast carcinomas develop., (© 2020 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland & John Wiley & Sons, Ltd.)

Significance: Standardized guidelines that are clinically practical are needed to assist the prescriber in minimizing the risk of conveying infection through multiuse diagnostic contact lens use and reuse.Contact lens prescribers face the specter of transferring potential pathogens from one patient to another when reusing diagnostic (trial) contact lenses on multiple patients because infectious organisms have been recovered from worn contact lenses, although there is no evidence of transmission through this mechanism. These pathogens can be introduced into the system from one patient to another, or they may be introduced by clinician lens handling, storage, or both. These pathogens can cause acute or chronic systemic or ocular infection that can lead to significant morbidity (temporary or permanent) that includes vision loss.

Background: Rates of mastectomy with immediate reconstruction are rising. Skin flap necrosis after this procedure is a recognized complication that can have an impact on cosmetic outcomes and patient satisfaction, and in worst cases can potentially delay adjuvant therapies. Many retrospective studies of this complication have identified variable event rates and inconsistent associated factors., Methods: A prospective study was designed to capture the rate of skin flap necrosis as well as pre-, intra-, and postoperative variables, with follow-up assessment to 8 weeks postoperatively. Uni- and multivariate analyses were performed for factors associated with skin flap necrosis., Results: Of 606 consecutive procedures, 85 (14 %) had some level of skin flap necrosis: 46 mild (8 %), 6 moderate (1 %), 31 severe (5 %), and 2 uncategorized (0.3 %). Univariate analysis for any necrosis showed smoking, history of breast augmentation, nipple-sparing mastectomy, and time from incision to specimen removal to be significant. In multivariate models, nipple-sparing, time from incision to specimen removal, sharp dissection, and previous breast reduction were significant for any necrosis. Univariate analysis of only moderate or severe necrosis showed body mass index, diabetes, nipple-sparing mastectomy, specimen size, and expander size to be significant. Multivariate analysis showed nipple-sparing mastectomy and specimen size to be significant. Nipple-sparing mastectomy was associated with higher rates of necrosis at every level of severity., Conclusions: Rates of skin flap necrosis are likely higher than reported in retrospective series. Modifiable technical variables have limited the impact on rates of necrosis. Patients with multiple risk factors should be counseled about the risks, especially if they are contemplating nipple-sparing mastectomy.

Background: For breast-conserving surgery, the method of margin assessment that most frequently achieves negative margins without increasing the volume of tissue excised is uncertain. We examined our institutional experience with three different margin assessment methods used by six experienced breast surgeons., Methods: Patients undergoing breast-conserving surgery for invasive carcinoma during July to December of a representative year during which each method was performed (perpendicular, 2003; tangential, 2004; cavity shave, 2011) were included. The effect of margin method on the positive margin rate at first excision and the total volume excised to achieve negative margins were evaluated by multivariable analysis, by surgeon, and by tumor size and presence of extensive intraductal component (EIC)., Results: A total of 555 patients were identified, as follows: perpendicular, 140; tangential, 124; and cavity shave, 291. The tangential method had a higher rate of positive margins at first excision than the perpendicular and cavity-shave methods (49, 15, 11 %, respectively; p < 0.0001). Median volumes to achieve negative margins were similar (55 ml perpendicular; 64 ml tangential; 62 ml cavity shave; p = 0.24). Four of six surgeons had the lowest rate of positive margins with the cavity-shave method, which was significant when compared to the tangential method (p < 0.0001) but not the perpendicular method (p = 0.37). The volume excised by the three methods varied by surgeon (p < 0.0001). The perpendicular method was optimal for T1 tumors without EIC; the cavity-shave method tended to be superior for T2-T3 tumors and/or EIC., Conclusions: Although the cavity-shave method may decrease the rates of positive margins, its effect on volume is variable among surgeons and may result in an increase in the total volume excised for some surgeons and for small tumors without EIC.

Background: Day-case axillary lymph node dissection (ALND) is not standard practice. Here we assess the feasibility of converting this traditional inpatient procedure to an outpatient procedure without compromising the quality or continuity of patient care, identify barriers to introducing an enhanced clinical pathway based on this conversion, and report strategies employed to overcome these barriers., Methods: Consecutive patients (n=282) undergoing ALND alone or with a concurrent breast procedure (excluding mastectomy/reconstruction) over a 12-month period were recorded in a prospective database. Assessed outcomes were successful discharge the day of surgery, early postoperative complication rates, and readmission rates., Results: From July 2009 to June 2010, 282 ALNDs were performed at Memorial Sloan-Kettering Cancer Center. 240 (85.1%) were performed as an outpatient procedure and 42 (14.9%) had inpatient ALND. The readmission rate was 0.8% (2/240), and the reoperation rate was 0.7% (2/282). Outpatient ALND procedure implementation created 240 additional beds over the 12-month study period. Identified barriers to implementing this new clinical pathway included patient expectations, reducing narcotic administration while optimizing postoperative pain control, and facilitating preoperative patient education., Conclusion: ALND may be safely performed as a day-case procedure. The key to successfully implementing ALND as a day-case procedure is a multidisciplinary team approach combined with enhanced pre and postoperative patient education. In addition, changes in the mindsets of patients and health care providers are essential., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: We hypothesized that the introduction of a short-stay pathway would result in a significant reduction in length of stay for patients undergoing unilateral mastectomy, without a negative impact on patient safety., Materials and Methods: As part of a quality improvement project, a multidisciplinary committee designed a 1-day stay program for unilateral mastectomy patients. The study period was the first year after the 1-day pathway had routinely been implemented. We report on consecutive patients undergoing unilateral mastectomy ± tissue expander at Memorial Sloan-Kettering Cancer Center from July 1, 2009 to June 30, 2010. The primary endpoint was the percentage of patients discharged on postoperative day 1. Secondary endpoints included the incidence of postoperative complications within 30 days of surgery, reoperations, readmissions, and urgent-care visits within 7 days., Results: Over a 12-month period, 537 patients underwent unilateral mastectomy. Of those, 82.7% (444/537) were performed on a 1-day hospitalization basis, compared with 9.6% in 2008, before implementation of the 1-day plan. The 30-day complication rate was 6.1% (33/537). Overall, 2.6% of all patients had reoperation for hematoma (14/537), 0.9% had to be readmitted (5/537), and 1.5% (8/537) attended the urgent-care department. If all patients had stayed in the hospital for more than 1 day, none of the readmissions and only 2 urgent-care visits would have been prevented., Conclusions: This study shows that a 1-day stay following mastectomy is easy to implement and safe for patients if a multidisciplinary team is involved in planning and implementation., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: The purpose of this study was to evaluate the influence of prosthetic reconstruction on the incidence, detection, and management of locoregional recurrence following mastectomy for invasive breast cancer., Methods: A matched retrospective cohort study was performed. Only patients with invasive breast cancer who had 2 years or more of follow-up and/or patients who had recurrence within 2 years of their primary cancer were included., Results: In total, 618 patients who underwent mastectomy for invasive breast cancer from 1995 until 1999 were evaluated. Three hundred nine patients who had immediate, tissue expander/implant reconstruction were matched to 309 women who underwent mastectomy alone on the basis of age (+/-5 years) and breast cancer stage (I, II, or III). The incidence of locoregional recurrence following mastectomy was 6.8 percent in patients who had reconstruction and 8.1 percent in patients who had mastectomy alone (log rank p = 0.6015). Median time to detection of a locoregional recurrence was 2.3 years (range, 0.1 to 7.2 years) in the reconstructed cohort and 1.9 years (range, 0.1 to 8.8 years) in the nonreconstructed cohort (p = 0.733). Permanent implants were removed following infection in one patient and patient request in two., Conclusions: These results suggest that there is no difference in the incidence of locoregional recurrence in breast cancer patients who undergo immediate, tissue expander/implant reconstruction compared with those patients who do not have reconstruction. Prosthetic breast reconstruction does not appear to hinder detection of locoregional cancer recurrence. In the majority of patients, management of locoregional recurrence does not necessitate removal of a permanent prosthesis.

Background: Risk-reducing mastectomy (RRM) remains an effective yet controversial modality for the primary prevention of breast cancer. Is the choice of RRM consistent with a generally proactive healthy lifestyle?, Methods: The National Prophylactic Mastectomy Registry is a volunteer database comprised of 460 women who have undergone bilateral RRM. Each patient received a questionnaire drawn from the Centers for Disease Control Behavioral Risk Factor Surveillance System. Their responses were compared with gender-specific national data from the Centers for Disease Control., Results: Women in the RRM group were statistically more likely to engage in risk-reducing personal health behavior including not smoking, exercising, maintaining their health, and taking advantage of screening programs., Conclusions: Women in the registry who underwent RRM practiced a more "healthy" lifestyle than gender-matched controls. Therefore, the decision to have prophylactic surgery may have been part of a proactive approach toward their overall physical well-being.

Objective: We sought to identify the rate of axillary recurrence after sentinel lymph node (SLN) biopsy for breast cancer., Summary Background Data: SLN biopsy is a new standard of care for axillary lymph node staging in breast cancer. Nevertheless, most validated series of SLN biopsy confirm that the SLN is falsely negative in 5-10% of node-positive cases, and few studies report the rate of axillary local recurrence (LR) for that subset of patients staged by SLN biopsy alone., Methods: Through December of 2002, 4008 consecutive SLN biopsy procedures were performed at Memorial Sloan-Kettering Cancer Center for unilateral invasive breast cancer. Patients were categorized in 4 groups: SLN-negative with axillary lymph node dissection (ALND; n = 326), SLN-negative without ALND (n = 2340), SLN-positive with ALND (n = 1132), and SLN-positive without ALND (n = 210). Clinical and pathologic characteristics and follow-up data for each of the 4 cohorts were evaluated with emphasis on patterns of axillary LR., Results: With a median follow-up of 31 months (range, 1-75), axillary LR occurred in 10/4008 (0.25%) patients overall. In 3 cases (0.07%) the axillary LR was the first site of treatment failure, in 4 (0.1%) it was coincident with breast LR, and in 3 (0.07%) it was coincident with distant metastases. Axillary LR was more frequent among the unconventionally treated SLN-positive/no ALND patients than in the other 3 conventionally treated cohorts (1.4% versus 0.18%, P = 0.013)., Conclusions: Axillary LR after SLN biopsy, with or without ALND, is a rare event, and this low relapse rate supports wider use of SLN biopsy for breast cancer staging. There is a low-risk subset of SLN-positive patients in whom completion ALND may not be required.

A case of primary marginal zone B-cell lymphoma in an elderly female patient is presented. Primary breast lymphomas are rare, comprising less than 1 per cent of all breast malignancies. These tumors have no clinical, pathologic, or radiologic pathognomonic features to distinguish them from breast adenocarcinoma. The diagnosis is usually made with an excisional biopsy, and more extensive surgery should be avoided. Delivery of radiation therapy and chemotherapy is tailored according to the histologic grade, stage of disease, and overall patient condition. This report summarizes the current knowledge reflected in the literature.

Background: This study examined whether the volume of isosulfan blue dye used in sentinel lymph node (SLN) mapping in breast cancer is related to the SLN identification rate or to the incidence of allergic reactions., Methods: From January 2001 to November 2002, 1728 breast cancer patients underwent 1832 SLN mapping procedures with the combined technique of intraparenchymal blue dye and intradermal radioisotope. Details of each procedure and all allergic reactions were prospectively recorded. Bilateral synchronous SLN procedures were considered as one dye exposure but as two distinct procedures for determining mapping success. Dye-only success was defined as the proportion of cases in which the SLN was identified by blue dye alone. Overall dye success was defined as the proportion of cases in which the SLN was identified by blue dye with or without isotope., Results: When stratified by volume of blue dye, there were no significant differences in dye-only successes, overall dye successes, or mapping failures. Allergic reactions were documented in 31 (1.8%) of 1728 patients. Hypotensive reactions occurred in 3 (.2%) of 1728 patients; 2 (.1%) required pressor support. There was a nonsignificant trend toward fewer allergic reactions with smaller volumes of blue dye., Conclusions: In combined-technique SLN mapping protocols for breast cancer, using smaller volumes of blue dye may represent a means of optimizing the safety of the procedure without compromising its success.

Background: We wished to determine whether transcutaneous oximetry or laser Doppler flowmetry (LDF) could identify patients at risk for wound failure after conservative, limb-sparing surgery for extremity sarcomas., Methods: Studies were performed on postoperative days (PODs) 1, 4/5, 7, and 9. Measurements of transcutaneous oxygen pressure (tcPO2) were taken at breathing room air (BL) and 100% oxygen (rate tcPO2). LDF measurements were taken at multiple sites along the wound, and a perfusion index was calculated., Results: Twenty-four patients were studied. Four (17%) had nonhealing wounds. There was no difference in tcPO2 (BL) values between healed and nonhealing wounds. Measurement of rate tcPO2 on POD 1 was significantly lower in the nonhealing wounds than in those with normal healing (28.5 +/- 12.1 mm Hg vs 14.3 +/- 16.2 mm Hg, mean +/- SD, p = 0.03). Rate tcPO2 values increased significantly in healing wounds from POD 1 to PODs 7 and 9 (p = 0.006, p = 0.009). This increase was absent in nonhealing wounds. A clear separation was noted in rate tcPO2 values between groups, with a minimum rate tcPO2 value recorded in a healed wound of 9 mm Hg/min, compared with the maximum value in a nonhealing wound of 7 mm Hg/min. The LDF perfusion index failed to predict wound healing at any of the measured time points., Conclusions: This study showed that measurement of tcPO2 during oxygen inhalation can accurately predict wound healing in patients after excision of an extremity sarcoma.

Background: Although infiltrating lobular carcinoma (ILC) is known to be associated with higher rates of bilaterality, contralateral breast biopsies are not routinely performed in such patients., Methods: The pathology reports of all patients with ILC admitted to Memorial Sloan-Kettering Cancer Center between 1970 and 1980 were retrospectively reviewed. The incidence of contralateral biopsies, random and directed, was determined. The findings on contralateral biopsy were evaluated with respect to age of the patient, nodal status of the ipsilateral cancer, and multicentricity of the primary lesion., Results: Of the 275 patients undergoing mastectomy for ILC, 130 (47%) had contralateral biopsies. Twenty-two were directed biopsies and 108 were random biopsies. On random biopsy 11 (10%) patients were found to have infiltrating carcinomas and seven (6%) were found to have intraductal cancer. Multicentric invasive disease in the ipsilateral breast was found to be predictive of a positive contralateral biopsy (p = 0.01)., Conclusions: Despite the current trend toward less extensive surgery for breast cancer, random contralateral breast biopsy is indicated in patients with ILC.

The internal mammary lymphatics are the second most common site of regional metastasis in breast carcinoma. However, because of their retrosternal location, they rarely become clinically evident. This report describes a patient with a parasternal breast carcinoma metastasis arising from internal mammary lymphatics. The metastasis caused symptoms for more than 3 years before the primary tumor was discovered. The pathologic elements underlying this unusual presentation along with the treatment options and the surgical management with extended mastectomy are discussed in detail.

While breast cancer is affecting American women at an epidemic rate, certain patients are identified as being at particularly high risk because of environmental, endocrine, genetic, and pathologic risk factors. Risk assessment, dietary, and psychological counseling, as well as breast cancer screening, are the function of a high-risk breast cancer program. Our own program is discussed.

Extraadrenal retroperitoneal paragangliomas (RP) are uncommon tumors. Because of their rarity, little is known of their natural history or response to treatment. We reviewed 22 patients with RP who were seen at our center between 1949 and 1990. The distribution of male and female patients was nearly equal, and the mean age was 42. Most patients were admitted with pain or a mass, and eight of 22 tumors were functional. No significant difference was noted in duration of symptoms, size of the tumor, or survival between functional and nonfunctional tumors. Eleven of 22 (50%) RP metastasized and were therefore classified as malignant. Five-year and 10-year disease free survival rates were 19% and 19% for tumors not resected and 75% and 45% for those completely resected. Once metastases occurred, the 5-year survival rate was 36%, but no patient survived beyond 76 months. Predictors of survival included complete resection of the tumor but not size or functional status. Although some patients who received chemotherapy or radiotherapy had clinical responses, a survival benefit could not be shown. RP have a high rate of malignant behavior and should be treated aggressively with operation. Late metastases are not uncommon, and prolonged follow-up is necessary. Once metastases have occurred, some patients may have prolonged survival.

The role of nitroethane as an intermediate in the oxidation of pyruvic oxime to nitrate by an Alcaligenes sp. was examined. Unlike pyruvic oxime, which serves as a sole source of C and N for the bacterium, nitroethane was incapable of supporting the growth of the microbe. Nitroethane was metabolized and diauxic growth did occur, however, if the nitroethane medium was amended with yeast extract. Alcaligenes sp. resting cells and cell-free extracts were prepared from nitroethane-yeast extract grown cultures and the maximum rate of nitrite synthesis when nitroethane was the substrate was 6.8 nmol min-1 mg cell protein-1, a 10-fold lower rate than that previously noted for pyruvic oxime oxidation. These cell-free extracts were unable to metabolize pyruvic oxime. Resting cells and cell-free extracts prepared from Alcaligenes sp. cells grown in a pyruvic oxime medium were, conversely, incapable of metabolizing nitroethane. Collectively, these results indicate that nitroethane is not an intermediate in the pathway of pyruvic oxime oxidation and that two separate enzyme systems exist in the Alcaligenes sp. for the metabolism of pyruvic oxime and nitroethane.

Automated methods, with and without cyanide (+CN and -CN), for whole blood hemoglobin (Hb) determination were evaluated on the Technicon H*1TM System. Both automated Hb methods were linear over the range 0-250 g/L (0-25 g/dL) and correlated well with the International Committee for Standardization of Hematology (ICSH) reference method and with the Coulter S+II. Both methods quantitatively converted whole blood containing up to 100% carboxyhemoglobin in less than 24 seconds to their respective end products. With respect to abnormal samples (sickle cell anemia, multiple myeloma, and hyperlipemia), both H*1 methods gave Hb results that were equivalent to the (postfiltration) ICSH method. For samples with white blood cell (WBC) counts less than 36 X 10(9)/L, the +CN method was equivalent to the (postfiltration) ICSH method, whereas for WBC counts greater than 20 X 10(9)/L, the -CN method showed acceptable recovery of the mean but unacceptable imprecision. For WBC counts of 36-164 X 10(9)/L, the +CN method yielded acceptable Hb recovery with unacceptable imprecision. Hyperlipemia, resulting from addition of Intralipid directly to the blood samples, caused large errors in both H*1 methods.

The Derifield-Thompson test for leg length inequality (LLI) is commonly used by chiropractors to assess a need for adjustment and to evaluate the results of adjustment. The two previous studies testing the reliability of the technique reported conflicting results. This study had two objectives: to demonstrate inter- and intraobserver reliability in detecting a LLI as little as 3 mm; and to document what effect Pierce-Stillwagon cervical adjusting has on a functional LLI. Twenty-six subjects walked into five successive examining rooms where a Derifield leg check was performed, including an estimate of the millimeters of difference in leg lengths. The subjects then entered a treatment room where they were randomly given no treatment, cervical adjusting, or gluteal massage. This process continued for 5 cycles. This study demonstrated that clinicians could reliably measure a LLI to less than 3 mm (both inter- and intraobserver), and also detect a change in LLI when the head was rotated. Neither cervical adjustment nor gluteal massage produced a significant change in observed LLI.

Whole blood hematocrit was determined by an approach which depends on the diffusion of an inert probe, to which red blood cells are impermeable, from a small agarose gel into a stirred, much larger blood sample. Blood cells influence the diffusion rate of the probe by, on the average, physically blocking a fraction of the gel surface. The blocking effect increases with the hematocrit. Cyanocobalamin (B-12) was found to be a suitable probe because it did not penetrate, bind to, or lyse blood cells and was not bound by plasma solutes. The loss of B-12 from gels in contact with blood was monitored by determination of the absorbance change at 540 nm of gels which had been quickly rinsed. The visible spectrum of B-12 in agarose gels was identical to the spectrum in water. Beer's Law was obeyed in 1-mm thick agarose gels over a concentration range of 0.1-0.8 mM. Based on the results from 48 blood samples covering the hematocrit range 25-69, a least-squares line was generated with a slope, -3.46 X 10(-3) delta A/hematocrit unit, a Y intercept of 0.295, and a correlation coefficient of 0.971. The precision of the technique was +/- 9.7%. The assay was insensitive to mean corpuscular volume and sample volume as long as the latter was 50-fold larger than the gel volume. The diffusion coefficient for B-12 in 1% agarose gels was found to be 1.4 +/- 0.2 X 10(-6) cm2 sec-1.