The State of the World's Midwifery 2021 report: findings to drive global policy and practice.

The third global State of the World's Midwifery report (SoWMy 2021) provides an updated evidence base on the sexual, reproductive, maternal, newborn and adolescent health (SRMNAH) workforce. For the first time, SoWMy includes high-income countries (HICs) as well as low- and middle-income countries. This paper describes the similarities and differences between regions and income groups, and discusses the policy implications of these variations. SoWMy 2021 estimates a global shortage of 900,000 midwives, which is particularly acute in low-income countries (LICs) and in Africa. The shortage is projected to improve only slightly by 2030 unless additional investments are made. The evidence suggests that these investments would yield important returns, including: more positive birth experiences, improved health outcomes, and inclusive and equitable economic growth. Most HICs have sufficient SRMNAH workers to meet the need for essential interventions, and their education and regulatory environments tend to be strong. Upper-middle-income countries also tend to have strong policy environments. LICs and lower-middle-income countries tend to have a broader scope of practice for midwives, and many also have midwives in leadership positions within national government. Key regional variations include: major midwife shortages in Africa and South-East Asia but more promising signs of growth in South-East Asia than in Africa; a strong focus in Africa on professional midwives (rather than associate professionals: the norm in many South-East Asian countries); heavy reliance on medical doctors rather than midwives in the Americas and Eastern Mediterranean regions and parts of the Western Pacific; and a strong educational and regulatory environment in Europe but a lack of midwife leaders at national level. SoWMy 2021 provides stakeholders with the latest data and information to inform their efforts to build back better and fairer after COVID-19. This paper provides a number of policy responses to SoWMy 2021 that are tailored to different contexts, and suggests a variety of issues to consider in these contexts. These suggestions are supported by the inclusion of all countries in the report, because it is clear which countries have strong SRMNAH workforces and enabling environments and can be viewed as exemplars within regions and income groups.

Practice Patterns and Outcomes of Pediatric Thyroid Surgery: An NSQIP Analysis.

BACKGROUND: Pediatric thyroid cancer rates are rising. The aim of this study was to determine the state of current practice and outcomes for pediatric thyroidectomies using the pediatric National Surgical Quality Improvement Program (NSQIP-P) with specific attention to differences based on surgeon type/specialty. METHODS: All cases of pediatric thyroidectomies and neck dissections within the NSQIP-P database were identified from 2015 to 2017. Patient, disease, and treatment-related factors affecting 30-day outcomes were analyzed using univariate and multivariate analyses. RESULTS: A total of 1300 cases were identified. Mean age at time of surgery was 14.0 (SD 3.5) years. The majority of patients were female (78%) and Caucasian (72%). Pediatric general surgeons performed the largest proportion of cases (42%) followed by pediatric otolaryngologists (33%). Malignancies were present in 29% of cases. The overall rate of complications was 3.0%. On multivariate analysis, non-pediatric surgeons were more likely to operate on Caucasian children, malignant pathology, and perform modified radical neck dissections. Pediatric surgeons were more likely to have longer operative times, have specialized in otolaryngology, and operate on sicker children (ASA>2). There were no differences in length of stay or overall complications rates. CONCLUSIONS: This study shows that pediatric surgeons currently perform the majority of thyroid surgeries in children. While unable to assess surgeon volume, our data show that thyroid surgery is being safely performed at NSQIP-affiliated hospitals by both non-pediatric and pediatric surgeons. Further studies are needed to determine if there are differences in specific procedure-related complications and long-term outcomes between surgeon types.

Overcoming Barriers: Sex Disparity in Surgeon Ergonomics.

BACKGROUND: Musculoskeletal discomfort is widely experienced by surgeons across multiple surgical specialties. Developing technologies and new minimally invasive techniques add further complexity and ergonomic stressors. These stressors differentially affect male and female surgeons, but little is known about the role these sex disparities play in surgical ergonomic stress. We reviewed existing literature to better understand how ergonomic stress varies between male and female surgeons. STUDY DESIGN: A literature search was performed via PubMed including but not limited to the following topics: ergonomics, surgeons, female surgeons, women surgeons, pregnancy, and operating room. A review of available quantitative data was performed. RESULTS: Female surgeons endure more pronounced ergonomic discomfort than their male counterparts, with added ergonomic stress associated with pregnancy. CONCLUSIONS: A 4-fold method is proposed to overcome ergonomic barriers, including (1) improved education on prevention and treatment of ergonomic injury for active surgeons and trainees, (2) increased departmental and institutional support for ergonomic solutions for surgeons, (3) partnerships with industry to study innovative ergonomic solutions, and (4) additional research on the nature of surgical ergonomic challenges and the differential effects of surgical ergonomics on female surgeons.

Discriminating pheochromocytomas from other adrenal lesions: the dilemma of elevated catecholamines.

BACKGROUND: Screening tests for pheochromocytoma involve measuring levels of catecholamines in the urine or plasma, which have significant false-positive rates. We reviewed patients with adrenal masses and elevated levels of catecholamines to determine the value of different preoperative tests in diagnosing pheochromocytomas. METHODS: A retrospective chart review identified patients who underwent adrenalectomy between 1997 and 2011 with elevation of urine or serum catecholamines. A database of clinicopathologic factors was created including preoperative urine and plasma metanephrines, normetanephrines, vanillylmandelic acid, and fractionated catecholamines, and tumor dimensions on imaging and pathology. RESULTS: A total of 70 patients underwent adrenalectomy because of presence of an adrenal mass and elevation of catecholamines or normetanephrines or metanephrines. Of these, 46 had pathologically confirmed pheochromocytomas. To improve our ability to discriminate between pheochromocytoma and other pathology, we examined different combinations of clinicopathologic factors and catecholamine levels and found the best test was a scoring system. Points are awarded for a hierarchy of elevated normetanephrine, norepinephrine, metanephrines, with additional points received for age <50 and size on imaging >3.3 cm. A score of 2 is suggestive of pheochromocytoma, with a positive predictive value of 86-87%, while a score of 4 is diagnostic with positive predictive value of 100%. CONCLUSION: We found that urine/serum normetanephrine levels were the most valuable screening tool; however, a score examining the size of adrenal mass on preoperative CT, age, and either plasma or urine norepinephrine, metanephrine, and normetanephrine values leads to a higher positive predictive value, making this scoring system superior to individual lab tests.

Metastatic Disease to a Concurrent Thyroid Neoplasm: A Case Series and Review of the Literature.

BACKGROUND: Metastatic disease to the thyroid gland is uncommon but well-described. Metastatic disease to a concurrent primary thyroid neoplasm is a rare phenomenon. We sought to study patients with metastasis to the thyroid with a focus on the histopathologic and clinical features in tumor-to-tumor metastasis. METHODS: We identified a series of patients with metastatic disease to the thyroid, with or without a concurrent primary neoplasm, through a search of the files of the Department of Pathology. All relevant slides were retrieved and reviewed, including routine HE and immunohistochemical stains. We performed a detailed English language literature search (1962-2022) and review to identify tumor-to-tumor metastasis involving the thyroid. RESULTS: We identified 14 patients with metastasis to the thyroid over a 22-year period. Four patients exhibited papillary thyroid carcinoma, with metastatic spread of a different malignancy seeding into the thyroid cancer. We describe the histopathologic diagnostic process and findings, clinical management, and the clinical course of tumor-to-tumor metastasis in greater detail for these 4 patients. CONCLUSION: Tumor-to-tumor metastasis to the thyroid is a rare event with unique histopathologic features. Our findings suggest that the phenomenon of tumor-to-tumor metastasis serves to highlight broader mechanisms of metastatic disease in general. We provide the largest-to-date and comprehensive review of the literature to identify all previous reported instances of tumor-to-tumor metastasis involving the thyroid.

Indian surgery Trainee's perspective on surgical ergonomics principles and education: A long road ahead.

INTRODUCTION: This study aimed to determine the baseline knowledge and beliefs, along with the impact of incorporating surgical ergonomics lectures during a residency. METHODS: A cohort of 123 Indian surgical residents participated in this educational intervention, which consisted of two educational webinars on ergonomics. Both pre- and post-intervention surveys were electronically sent to the participants. These included questions related to their demographics, prevalence of musculoskeletal (MSK) symptoms, and factors affecting participant awareness of ergonomic recommendations. RESULTS: Seventy-one residents responded to the pre-webinar survey. Eighty-five percent of respondents reported MSK symptoms, with the most common being pain (70%) and stiffness (40%), which the residents attributed to their surgical training. Forty-six residents completed the post-webinar survey. The majority of respondents strongly agreed or agreed that surgical ergonomic educational sessions improved their understanding of the fundamental causes of MSK symptoms and increased their awareness of options available for prevention MSK injuries. CONCLUSION: The rate of MSK symptoms and/or injury was high among this cohort of surgical residents. These surveys and educational session demonstrated there is limited awareness of the comprehension of ergonomics related to surgical procedures. Our study shows that a simple surgical ergonomic educational intervention can lead to improved understanding of prevention and ergonomic changes.

Optimizing ergonomics during open, laparoscopic, and robotic-assisted surgery: A review of surgical ergonomics literature and development of educational illustrations.

BACKGROUND: The surgical profession is plagued with a high prevalence of work-related musculoskeletal disorders. While numerous interventions have been tested over the years, surgical ergonomics education is still uncommon. METHODS: The available literature on surgical ergonomics was reviewed, and with input from surgeons, recommendations from the review were used to create pictorial reminders for open, laparoscopic, and robot-assisted surgical modalities. These simple pictorial ergonomic recommendations were then assessed for practicality by residents and surgeons. RESULTS: A review of the current literature on surgical ergonomics covered evidence-based ergonomic recommendations on equipment during open and laparoscopic surgery, as well as proper adjustment of the surgical robot for robot-assisted surgeries. Ergonomic operative postures for the three modalities were examined, illustrated, and assessed. CONCLUSIONS: The resulting illustrations of ergonomic guidelines across surgical modalities may be employed in developing ergonomic education materials and improving the identification and mitigation of ergonomic risks in the operating room.

Risk of subsequent primary thyroid cancer after another malignancy: latency trends in a population-based study.

PURPOSE: To evaluate the risk of a subsequent primary thyroid cancer (SPTC) in patients with common invasive cancers, with attention to latency trends and histology associations. METHODS: Patients with one of 10 common invasive cancers were followed from 1975 to 2008 in 9 registries participating in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. Standardized incidence ratios (SIRs) for SPTC were determined by the multiple primary-SIR program in SEER*Stat. RESULTS: A total of 2502 SPTCs were observed. Greatly elevated SIRs for SPTC were noted for 9 of 10 evaluated cancers in the 12 months after initial diagnosis. The SIRs remained elevated 12-59 months after diagnosis for all cancers except leukemia, uterine, and bladder cancers. Increased risks persisted 60-119 months beyond diagnosis for renal (SIR 2.56) and breast cancer (SIR 1.16); and 120+ months for renal cancer (SIR 2.46). Increased SPTC risk after renal and female breast cancers was mostly seen in nonirradiated patients. The principal histology association was between papillary thyroid cancer and renal cell carcinomas. CONCLUSIONS: Many common cancers are associated with increased risk of SPTC beyond 12 months of initial diagnosis. Although this can be explained partly by continued surveillance bias, radiation effects, and known rare familial associations for some tumors, these factors alone are unlikely to explain the persistent, significant two-way association with renal and breast cancers. Additional research is needed to further define the biological and environmental mechanisms underlying these associations.

Endocrine surgeons have high rates of work-related musculoskeletal (MSK) injury and symptoms.

BACKGROUND: Work-related injury and musculoskeletal (MSK) symptoms are common among surgeons, however data for endocrine surgeons (ES) are lacking. METHODS: A survey was distributed to American Association of Endocrine Surgeons (AAES) and Endocrine section of American Head and Neck Society (AHNS) members. RESULTS: MSK symptoms were present in 199 (90%) of 220 respondents, most notably pain (91%) and stiffness (81%). The most common locations were neck (87%) and shoulders (55%). Women were more likely to be symptomatic (98.6% versus 86.4%, p = 0.004). Although 67% of respondents reported awareness of ergonomic principles, only 19% had learned about them during training. The most common ergonomic adjustments were stretching, use of microbreaks and headlight/loupe adjustments. CONCLUSION: The vast majority of ES surgeons suffer MSK symptoms that could potentially impact their quality of life and career length. Effective strategies are needed to protect this highly trained workforce.

Influence of endocrine multidisciplinary tumor board on patient management and treatment decision making.

BACKGROUND: Multidisciplinary Tumor Boards (MDT) are used to obtain input regarding cancer management. This study assessed the impact of our institutional Endocrine MDT. METHODS: MDT notes on patients with thyroid cancer treated during 2012-2018 were abstracted retrospectively from the electronic medical record. Management change (MC) was prospectively collected by the MDT coordinator. Biannual evaluations reviewed the impact of the MDT as observed by attendees. RESULTS: MC was recommended in 47 (15%) of 286 presentations, with additional imaging being the most frequent (43%). Presentation of recurrences were more likely to result in MC (24% vs. 13% initial, p = 0.03). Overall, 98% of attendees found the conference exceeded educational expectations. About 24% reported intending to use a more evidence/guideline-based approach after attending and this trend increased over time (p = 0.002). CONCLUSION: MDT presentations led to a higher rate of MC particularly in recurrent TC patients and increased evidenced-based practice for attendees.

Expression of cancer stem cell markers in tall cell variant papillary thyroid cancer identifies a molecular profile predictive of recurrence in classic papillary thyroid cancer.

BACKGROUND: Tall cell variant of papillary thyroid carcinoma is an aggressive subtype of papillary thyroid carcinoma. We examined expression of cancer stem cell markers in tall cell variant compared with other well-differentiated thyroid cancers. METHODS: Expression of cancer stem cell markers was examined in 572 thyroid tumors from The Cancer Genome Atlas Thyroid Cancer database and tall cell variant and papillary thyroid carcinoma tumors by immunohistochemistry. RESULTS: Expression of the PROM1 gene, encoding the cancer stem cell marker CD133, was elevated in tall cell variant compared to classic papillary thyroid carcinoma in a large cohort of unmatched samples from The Cancer Genome Atlas Thyroid Cancer database (P < .001). By immunohistochemistry in age and stage matched samples, CD133 protein was confirmed to be significantly increased in tall cell variant versus classic papillary thyroid carcinoma (P = .006). Analyzing all thyroid cancers, high PROM1 expression was associated with worse disease-specific survival. Optimal cutoffs were determined to define a tall cell variant-like cancer stem cell signature characterized by high PROM1, high ALDH1A3, and low CD24 expression. Classic papillary thyroid carcinoma with a tall cell variant-like gene signature had worse recurrence disease-free survival compared to classic papillary thyroid carcinoma with a non-tall cell variant signature (P = .02). CONCLUSION: Tall cell variant of papillary thyroid carcinoma has increased expression of cancer stem cell markers compared to classic papillary thyroid carcinoma. The tall cell variant-like cancer stem cell gene signature identified a molecular subtype of classic papillary thyroid carcinoma that has a worse recurrence-free survival.

Surveillance and intervention after thyroid lobectomy.

BACKGROUND: After thyroid lobectomy, many patients require ongoing care. This study sought to quantify the rates of surveillance and intervention after thyroid lobectomy. METHODS: One hundred one consecutive patients who underwent a thyroid lobectomy for nodular disease were evaluated. Clinical and follow-up data were obtained by a review of patient charts and included an evaluation of resource utilization related to thyroid disease. RESULTS: Nineteen patients required completion thyroidectomy for thyroid cancer, and 11 had hypothyroidism before lobectomy. Of the remaining evaluable patients, 30 (42.2%) of 71 required thyroid hormone replacement after lobectomy, with 24 patients having elevated thyroid-stimulating hormone and 6 suppression of nodules in the contralateral lobe. The likelihood of thyroid hormone replacement demonstrated a trend with a contralateral nodule (9 of 14 vs. 21 of 57, P = 0.06) and a significant association with thyroiditis on surgical pathology (10 of 11 vs. 20 of 60, P < 0.001). Of the 82 patients who did not undergo completion lobectomy, 10 (12%) of 82 underwent postoperative fine-needle aspiration of the contralateral lobe, and 25 (30%) of 82 were followed with ultrasound surveillance. Only 27% of patients treated with lobectomy required no further surveillance or intervention. There were no instances of permanent recurrent laryngeal nerve injury. CONCLUSIONS: After thyroid lobectomy, most patients require continued surveillance and intervention. With a near-zero complication rate, total thyroidectomy may be a more effective and efficient option for management of nodular thyroid disease.

Racial disparities in comorbid conditions among patients undergoing thyroidectomy for Graves' disease: An ACS-NSQIP analysis.

BACKGROUND: Studies indicate that racial disparities exist in the presentation and outcomes of patients undergoing thyroidectomy for cancer and benign disease. We examined the relationship between race, pre-operative characteristics and outcomes in patients undergoing thyroidectomy for GD. METHODS: Patients were identified from the 2013-2016 American College of Surgeons NSQIP database using ICD-9/10 codes consistent with diffuse toxic goiter. RESULTS: AA patients were more likely to have an ASA classification of ≥3 (41% vs 30%, p < 0.001), a higher rate of CHF (2.1% vs 0.5%, p = 0.01), hypertension (46% vs 32%, p < 0.001) and dyspnea (10% vs 5%, p < 0.001) compared to Non-Hispanic Caucasians (NH-C) patients. Complications were higher in patients with ASA≥3 and CHF but not affected by race. CONCLUSIONS: Analysis of a national database of thyroidectomy for GD revealed a higher burden of preoperative comorbidities in AA patients compared to other races, although race was not an independent predictor of outcomes.

Incorporating Surgical Ergonomics Education into Surgical Residency Curriculum.

BACKGROUND: Education on surgical ergonomics during residency training is lacking. This study aimed to determine the feasibility and impact of incorporating surgical ergonomics lectures into residency curriculum. METHODS: A survey was distributed to 42 residents with questions regarding demographics, surgical factors, prevalence of musculoskeletal (MSK) symptoms, and awareness of ergonomic recommendations. The residents then received 2 lectures on ergonomics in surgery. A follow up survey was distributed to evaluate the impact of the lectures. RESULTS: Twenty-two residents completed the presession survey. Ninety-one percent reported MSK symptoms attributed to their training. Seventeen residents completed the follow up survey. All reported increased awareness of their own habits while operating and improved understanding of methods to prevent and/or treat work-related injuries. All residents recommended incorporating the lectures as an adjunct to their regular curriculum. CONCLUSIONS: The rates of MSK symptoms and/or injury are high among surgeon trainees. Residency is an opportune time to educate on principles of ergonomics and may prevent future injuries.

Expansion of a cell population expressing stem cell markers in parathyroid glands from patients with hyperparathyroidism.

OBJECTIVE: We sought to examine abnormal parathyroid glands for the presence of stem cells. SUMMARY BACKGROUND DATA: Cancer stem cells have been identified in cancers from a variety of tissues as a CD44/CD24 cell population. We hypothesize that stem cells (SC) may also be involved in the pathogenesis of benign clonal expansion characteristic of hyperparathyroidism (HPT). METHODS: Under institutional review board approval, parathyroid tissue was obtained from 20 patients with HPT and analyzed by fluorescence-activated cell sorting (FACS) for the CD44/CD24 cell population. Immunohistochemistry (IHC) with CD44 antibody was correlated with FACS results. RESULTS: Parathyroid tissue was obtained for FACS analysis from 25 enlarged parathyroid glands from 20 patients, 17 with primary HPT, and 3 with secondary HPT. The average percent of SC defined as CD44/CD24 population was 10.93% for enlarged parathyroid glands. IHC using CD44 antibody was performed on 27 abnormal parathyroid glands and 7 normal parathyroid gland biopsies from the same patients. Although IHC was not as sensitive as FACS, comparison of IHC and FACS results for 24 abnormal glands gave a correlation coefficient of 0.52, which was statistically significant (P = 0.01, Spearman rank). By IHC, 13 of 27 abnormal glands stained 1+ to 3+ (average, 0.93) compared with no CD44 staining in normal glands, which was statistically different (mean IHC of 0 vs. 0.93, P = 0.03, Wilcoxon). CONCLUSIONS: These novel findings demonstrate expansion of a resident cell population that expresses SC markers in abnormal parathyroid glands from patients with HPT. Our results suggest that clonal expansion of a resident SC population occurs in the pathogenesis not only of cancer, but also in benign parathyroid tumors occurring in HPT.

Leaving no one behind: Is the achievement of the Sustainable Development Goals possible without securing the dignity, rights, and well-being of those who are "invisible"?

The persistence of obstetric fistula-a devastating childbirth injury occurring largely among poor, marginalized women and girls-constitutes a human rights violation and a public health crisis. The Sustainable Development Goals (SDGs) aim to "leave no one behind." Failing to eliminate fistula jeopardizes attainment of several of the SDGs. Member States of the United Nations adopted a UN Resolution on ending fistula in 2018, calling for an end to fistula within a decade. Building upon recommendations of the UN Secretary General's 2018 Report on Obstetric Fistula, the Resolution calls for significantly increased commitments and investments to end fistula. Crucial interventions for eliminating fistula include high-quality, equitable, accessible health systems; implementing costed national strategies for eliminating fistula; integrating fistula into national plans to achieve the SDGs; strengthening national fistula task forces; and significantly increased, sustained financial support. Fistula elimination necessitates protecting women's/girls' human rights and addressing social determinants that affect women's/girls' ability to "survive, thrive and transform," including social and economic inequities; gender-based violence; child marriage and early childbearing; and access to education. Enhanced awareness-raising and advocacy; improved research, data, monitoring and evaluation; holistic social reintegration and survivor empowerment; and community engagement are additional key strategies for realizing this ambitious goal.

The Association of Women Surgeons research grant: An analysis of the first 25 years.

BACKGROUND: The impact of the Association of Women Surgeons (AWS) Research Grant on academic productivity is unknown. METHODS: Grant applications were obtained from AWS archives. Applicant bibliometrics and National Institutes of Health (NIH) grants were identified via public databases. RESULTS: Twenty-four recipients between 1996 and 2020 and 68 nonrecipients between 2012 and 2017 were identified. $596,700 was awarded over the 25 years. Twenty-five percent of recipients subsequently acquired NIH funding amounting to $6,611,927.00, an 885-1008% return on investment. Compared to nonrecipients, grant recipients produced a greater mean number of publications (50.6 versus 36.4; p = 0.05), had a higher h-index (15.92 versus 10.7; p = 0.01), and were cited in higher impact factor journals (6.32 versus 3.9; p = 0.02). CONCLUSIONS: Overall, previous AWS Research Grant recipients were more likely to become more impactful surgeon-scientists, as indicated by a higher post-award rate of NIH funding, total number of publications, and h-index than nonrecipients.

Evaluation of switch from satellite laboratory to central laboratory for testing of intraoperative parathyroid hormone.

OBJECTIVES: The aim of this study was to evaluate testing turnaround time (TAT) and incision to close time in parathyroid surgeries before and after switching intraoperative parathyroid hormone (PTH) testing from a near point of care location to a central clinical laboratory. DESIGN AND METHODS: This retrospective study covered a ten-year period. Both testing locations used the same Roche Diagnostics PTH immunoassay but on different analyzers. The predominant site for surgeries was the main operating rooms (ORs) in an adjacent building, with a limited number of parathyroid surgeries performed at a more distant ambulatory surgery center (ASC). Under ideal conditions, TAT for near point-of-care testing was 20 â€‹min, although multiple factors could increase TAT. Incision to close time from the electronic health record was used to define time of surgery. RESULTS: A total of 897 unique patients were identified for which 3031 orders for intraoperative PTH were placed (383 unique patients and 1244 orders after switch in testing site). The average total TAT times for testing (mean â€‹± â€‹SD) in the central laboratory were 23.9 â€‹± â€‹16.0 â€‹min (median, 22 â€‹min) for all specimens, 22.8 â€‹± â€‹7.9 â€‹min (median, 21 â€‹min) for main OR specimens, and 26.4 â€‹± â€‹7.1 â€‹min (median, 25 â€‹min) for ASC specimens. Incision to close time for parathyroidectomies showed decreases in mean, median, and standard deviation following testing change. CONCLUSIONS: Surgery time for parathyroidectomies may remain consistent or decrease if intraoperative PTH testing is moved from a near point of care to a central laboratory.

Extracellular matrix 1 (ECM1) expression is a novel prognostic marker for poor long-term survival in breast cancer: a Hospital-based Cohort Study in Iowa.

INTRODUCTION: Previous work in a small, unselected series showed that up to 83% of breast carcinomas overexpress ECM1 by immunohistochemistry (IHC) and that tumors with lymph node metastases are more likely to be ECM1-positive. We sought to further evaluate ECM1 expression and its effect on prognosis in an unselected cohort of patients with breast cancer. METHODS: ECM1 expression was examined by IHC in 134 women diagnosed with invasive breast cancer between 1986 and 1989 and correlated with clinical parameters and outcomes, including disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS) using Cox proportional hazards regression. RESULTS: During follow-up, 83 of 134 (66%) patients died. The median follow-up was 211 (range, 183-245) months for surviving patients. Based on a previously described cutoff of 10% staining, 47% of breast cancers were ECM1-positive. ECM1-positive tumors were associated with increasing patient age (P = 0.01). In multivariate analyses, while controlling for age, ER status, tumor grade, stage, and treatment, ECM1 expression emerged as a significant predictor of DSS (hazard ratios, 4.16 (P = 0.009) and 11.6 (P = 0.01) at 10 and 15 years, respectively) and DFS (hazard ratio, 3.08 (P = 0.03) at 15 years) with ECM1 overexpression predicting poorer survival. CONCLUSIONS: ECM1 was overexpressed in approximately half of invasive breast carcinomas and is an important prognostic marker, particularly for predicting poorer DSS, with its predictive value increasing with time from diagnosis. Further work is needed to confirm these findings and determine whether ECM1 expression is predictive of response to specific therapy.

When is prophylactic thyroidectomy indicated for patients with the RET codon 609 mutation?

BACKGROUND: Mutations in the RET proto-oncogene cause multiple endocrine neoplasia type 2A (MEN2A), and prophylactic thyroidectomy has generally been recommended before the age of 5 years. Patients with codon 609 mutations develop MTC at a later age and therefore the timing of prophylactic thyroidectomy is less clear. We report a three-generation family with C609Y RET mutation where members having prophylactic or therapeutic thyroidectomy call the current recommendations for age at thyroidectomy into question. METHODS: Sixteen family members underwent thyroidectomy, for which clinical, laboratory, and pathological data were analyzed. A literature review of RET codon 609 mutations was carried out. RESULTS: Data were collected from 16 patients from this 38-member kindred. None of these affected members had pheochromocytoma, and one had a parathyroid adenoma. Nine of 16 patients had MTC (mean age 44.7 years, range 29-59 years) and elevated basal calcitonin levels; 6 of these 9 had lymph node metastases. Two patients had C-cell hyperplasia (CCH) at ages 18 and 37 years, and five patients had normal thyroid pathology (mean age 16 years, range 5-37 years). In the literature, a family with C609Y mutation was reported, with 15 members having MTC (mean age 42 years, range 21-59 years), and 6 with CCH (mean age 24 years, range 15-37 years). CONCLUSION: The youngest patient with C609Y RET mutation and MTC was 21 years old, and the youngest patient with CCH was 15 years old at diagnosis. These data suggest that patients with RET C609Y mutations can delay thyroidectomy until 10-15 years of age, with annual calcitonin screening prior to thyroidectomy.