Diagnostic Challenges and Long-term Outcomes of Neuroendocrine Carcinoma of the Cervix: A Case Series.

Neuroendocrine carcinomas (NECs) of the cervix are rare, aggressive malignancies that are challenging to diagnose and treat. They are high-grade lesions that often share features with poorly differentiated adenocarcinoma and squamous cell carcinoma. NECs are classified into large-cell or small-cell subtypes but can often have a mixed appearance or occur concurrently with a squamous or adenocarcinoma. Diagnosis is dependent on tissue sampling, histomorphology, and immunohistochemistry. Eight cases of NEC were retrieved from the Department of Pathology at our institution from 2008 to 2022. Tumor slides were reviewed and evaluated by 2 independent pathologists. Seven of 8 patients tested positive for neuroendocrine markers, including CD56, synaptophysin, and chromogranin. We discuss the diagnostic challenges, review the histopathology, and describe the treatment courses and clinical outcomes. This case series reveals that traditional markers, such as p16, p63, and p40, may be focally positive in NEC and should not be considered a confirmation of squamous cell carcinoma. Patient outcomes can be affected by delays in diagnosis, misdiagnosis, and inadequate treatment when NEC is not considered in the initial differential diagnosis.

Left-Handedness in Obstetrics and Gynecology: A Nationwide Survey of U.S. Trainees and Educators.

OBJECTIVE: This study aimed to evaluate the views and influence of left-handedness among obstetrics and gynecology (OBGYN) trainees and educators and to identify perceived obstacles in training by left-handed (LH) trainees. STUDY DESIGN: An online survey was sent to the U.S. Obstetrics and Gynecology training programs. All participants were asked questions on hand preference for various medical and nonmedical activities, as well as on demographics. Participant responses to handedness and their role as a learner or educator directed them toward further questions. Trainees were surveyed on their experience and outlook as a LH physician in OBGYN. Educators were surveyed on their experience and attitudes in working with LH trainees. LH educators were also surveyed on their experience as a LH physician, similar to the LH trainees. Chi-square or Fisher's exact analysis was used as appropriate, with p-value <0.05 considered statistically significant. RESULTS: Responses were received from 21 training programs, totaling 304 individuals. Participants included 205 learners (156 right handed and 49 left handed), and 99 faculty (82 right handed and 17 left handed). A lack of LH surgical instrument availability (93.6%) and difficulty using right-handed (RH) instruments (83%) were notable obstacles reported by LH learners. The majority of LH learners (57.4%) did not consider their handedness to be disadvantageous but did note added difficulty when training under RH mentors when compared with training under LH mentors (66%). In contrast to LH educators, RH educators endorsed added difficulty in instructing operative procedures to LH learners (32.1 vs. 13.3%, p = 0.012). CONCLUSION: LH trainees face unique challenges during their OBGYN training. Educators would benefit from guidance on how best to manage these trainees. Educators should work to adapt surgical and procedural techniques to accommodate LH trainees. KEY POINTS: · LH learners reported more difficulty in training under RH mentors.. · RH mentors reported increased difficulty in educating LH trainees.. · Neither trainees nor educators considered being LH a significant disadvantage..

The physician healer track: educating the hearts and the minds of future physicians.

Calls to reform medical education recommend explicit training in professional identity formation to promote the development of humanistic, compassionate physicians. The authors report their experience offering The Physician Healer Track, a 500-contact-hour curricula integrated over 4 years, focusing on self-awareness, reflection, being-with-suffering, communication and professional identity development. The voluntary scholarly-concentration program comprises 4 years of monthly dinner meetings with faculty mentors, a two-month preceptorship in the first year, a one-month immersion course in MS4 and one elective. Training in mindfulness, cognitive behavioral therapy, nonviolent communication, motivational interviewing, spirituality in healthcare, wellness, equanimity, and 'being with suffering' is reinforced across all 4 years. Community building and reflection are integral to the training both in the monthly sessions and the immersion courses. Enrollment has grown from 26 students in the first year (11% of class) to a total of 258 students across our first 6 years (average of 20-26% of each class). Graduates in our first two cohorts of PHT have exceeded the numbers in the eight other scholarly concentrations offered at UTMB. Among students participating in the summer preceptorship, there has been less than 1% attrition. In serial assessments, students report continued growth in personal development, professional development, and the ability to empathize. Offering PHT has resulted in the growth of training for our medical residents, faculty, physical therapy students and the creation of a student healer association. Despite the demands on student's time, they are voluntarily participating in a challenging program of integrated training with the intention of keeping them connected to their humanity during the rigors of medical school training.

Abdominal Wall Clear Cell Carcinoma: Case Report of a Rare Event with Potential Diagnostic Difficulties.

Clear cell carcinoma (CCC) is a well-known aggressive histological type of carcinoma, predominantly seen in ovary and endometrium. However, CCC arising in abdominal wall is a very rare event. We report a case of a 48-year-old woman with an abdominal wall mass at her cesarean section (c-section) scar, which increased in size and became painful in the last months. Radiology revealed a 7 cm mass in the right inferior rectus muscle sheath, suggestive of endometriosis. An irregular, firm mass was resected, densely adherent to the rectus muscle and pubic bone. Frozen section revealed a multicystic lesion with minimal cytologic atypia, and a benign cystic neoplasm was favored. However, permanent sections showed marked nuclear atypia, hobnail morphology, and areas of infiltrative growth within fibrous stroma. No benign endometrial glands were found, although fibrosis and hemorrhage were present. Napsin-A, racemase, and PAX-8 were positive, consistent with CCC, likely arising within a c-section endometriosis focus. Although CCC usually presents with moderate to marked nuclear atypia, it can be mild and, especially in cases with a predominant cystic pattern, create diagnostic difficulties. An endometriosis-associated malignancy should be considered in the differential with any enlarging nodule or increasing pain within an abdominal wall scar.

Effects of adjunct testosterone on cardiac morphology and function in advanced cancers: an ancillary analysis of a randomized controlled trial.

BACKGROUND: Adjunct testosterone therapy improves lean body mass, quality of life, and physical activity in patients with advanced cancers; however, the effects of testosterone on cardiac morphology and function are unknown. Accordingly, as an ancillary analysis of a randomized, placebo-controlled trial investigating the efficacy of testosterone supplementation on body composition in men and women with advanced cancers, we explored whether testosterone supplementation could prevent or reverse left ventricular (LV) atrophy and dysfunction. METHODS: Men and women recently diagnosed with late stage (≥IIB) or recurrent head and neck or cervical cancer who were scheduled to receive standard of care chemotherapy or concurrent chemoradiation were administered an adjunct 7 week treatment of weekly intramuscular injections of either 100 mg testosterone (T, n = 1 M/5F) or placebo (P, n = 6 M/4F) in a double-blinded randomized fashion. LV morphology (wall thickness), systolic function (ejection fraction, EF), diastolic function (E/A; E'/E), arterial elastance (Ea), end-systolic elastance (Ees), and ventricular-arterial coupling (Ea/Ees) were assessed. RESULTS: No significant differences were observed in LV posterior wall thickness in placebo (pre: 1.10 ± 0.1 cm; post: 1.16 ± 0.2 cm; p = 0.11) or testosterone groups (pre: 0.99 ± 0.1 cm; post: 1.14 ± 0.20 cm; p = 0.22). Compared with placebo, testosterone significantly improved LVEF (placebo: - 1.8 ± 4.3%; testosterone: + 6.2 ± 4.3%; p < 0.05), Ea (placebo: 0.0 ± 0.2 mmHg/mL; testosterone: - 0.3 ± 0.2 mmHg/mL; p < 0.05), and Ea/Ees (placebo: 0.0 ± 0.1; testosterone: - 0.2 ± 0.1; p < 0.05). CONCLUSIONS: In patients with advanced cancers, testosterone was associated with favorable changes in left ventricular systolic function, arterial elastance, and ventricular-arterial coupling. Given the small sample size, the promising multisystem benefits of testosterone warrants further evaluation in a definitive randomized trial. TRIAL REGISTRATION: This study was prospectively registered on ClinicalTrials.gov (NCT00878995; date of registration: April 9, 2009).

A randomized trial of adjunct testosterone for cancer-related muscle loss in men and women.

BACKGROUND: Cancer cachexia negatively impacts cancer-related treatment options, quality of life, morbidity, and mortality, yet no established therapies exist. We investigated the anabolic properties of testosterone to limit the loss of body mass in late stage cancer patients undergoing standard of care cancer treatment. METHODS: A randomized, double-blind, placebo-controlled phase II clinical trial was undertaken to assess the potential therapeutic role of adjunct testosterone to limit loss of body mass in patients with squamous cell carcinoma of the cervix or head and neck undergoing standard of care treatment including chemotherapy and chemoradiation. Patients were randomly assigned in blocks to receive weekly injections of either 100 mg testosterone enanthate or placebo for 7 weeks. The primary outcome was per cent change in lean body mass, and secondary outcomes included assessment of quality of life, tests of physical performance, muscle strength, daily activity levels, resting energy expenditure, nutritional intake, and overall survival. RESULTS: A total of 28 patients were enrolled, 22 patients were studied to completion, and 21 patients were included in the final analysis (12 placebo, nine testosterone). Adjunct testosterone increased lean body mass by 3.2% (95% confidence interval [CI], 0-7%) whereas those receiving placebo lost 3.3% (95% CI, -7% to 1%, P = 0.015). Although testosterone patients maintained more favourable body condition, sustained daily activity levels, and showed meaningful improvements in quality of life and physical performance, overall survival was similar in both treatment groups. CONCLUSIONS: In patients with advanced cancer undergoing the early phase of standard of care therapy, adjunct testosterone improved lean body mass and was also associated with increased quality of life, and physical activity compared with placebo.

Use of BRCA Mutation Test in the U.S., 2004-2014.

INTRODUCTION: BRCA mutation testing has been used for screening women at high risk of breast and ovarian cancer and for selecting the best treatment for those with breast cancer. To optimize the infrastructure and medical resources allocation for genetic testing, it is important to understand the use of BRCA mutation testing in the U.S. health system. METHODS: This retrospective cohort study included 53,254 adult women with insurance claims for BRCA mutation testing between 2004 and 2014 from ClinformaticsTM Data Mart Database. Data analysis was performed in 2016. This study assessed trends in the use of BRCA mutation testing in women with previously diagnosed breast or ovarian cancer and those without (unaffected women). RESULTS: Between 2004 and 2014, of those receiving BRCA testing, the proportion of BRCA tests performed in unaffected women increased significantly (p<0.001), from 24.3% in 2004 to 61.5% in 2014. An increase in the proportion of BRCA tests used in unaffected women was found in each characteristic subgroup. In 2014, most subgroups had a proportion surpassing 50%, except for those aged 51-65 years and those without a family history of breast cancer. There was a much lower proportion of those aged 20-40 years among tested women with previously diagnosed breast or ovarian cancer than in unaffected women (17.6% vs 41.7%, p<0.001). CONCLUSIONS: During the past decade, the role of BRCA testing has gradually shifted from being used primarily in cancer patients to being used in unaffected women in the U.S.

Should high-risk adolescents have Papanicolaou tests?

BACKGROUND: The current American College of Obstetricians and Gynecologists guidelines state that cervical cancer screening should begin at age 21 years, regardless of sexual or obstetric history. However, previous studies have demonstrated that there is a small but significant subset of high-risk adolescents with extensive sexual and obstetric history who harbor a significant squamous cervical lesion. The objective of the current study was to use histologic and demographic data from adolescents (aged <21 years) who received Papanicolaou (Pap) tests to determine whether they benefited from early cervical cancer screening. METHODS: Adolescent girls who had Pap tests between 2000 and 2010 were included in the study. Demographic data, including obstetric history, number of sexual partners, age of first coitus, age at first pregnancy, menarche, smoking history, and Chlamydia and syphilis infection, were analyzed for associations with levels of cervical dysplasia. RESULTS: Of 56,785 adolescent Pap tests, 277 (0.5%) were diagnosed as high-grade squamous HSIL, and 56 of those Pap tests (20%) were from patients who had grade 3 cervical intraepithelial neoplasia (CIN-3) on subsequent biopsy and/or excision. One patient had microinvasive cervical carcinoma identified on loop electrosurgical excision procedure at age 27 years after an HSIL Pap test. Increased parity was associated significantly with higher rates of CIN-3. CONCLUSIONS: The study findings indicated that current American College of Obstetricians and Gynecologists guidelines to begin Pap testing at age 21 years are appropriate for the majority of adolescents, because the rate of HSIL is very low, and the risk for invasive carcinoma is minimal. Although higher parity was associated with a significantly increased grade of CIN, the conclusions are questionable because of the significant amount of missing demographic data points. That being said, this study should lead to other similar studies to determine any association of higher grade CIN with adolescent sexual and obstetric history.

Cancer cachexia and anabolic interventions: a case report.

BACKGROUND: Standard-of-care (SOC) cancer treatments are primarily aimed at reducing size and progression of a tumor. There is a need for successful supplemental anabolic therapies to combat cancer cachexia in addition to these SOC treatment modalities. Anabolic interventions, including testosterone and amino acid supplements, may be beneficial in reducing and/or reversing muscle wasting in these patient populations. METHODS: A 48-year-old Caucasian female with recurrent cervical cancer was scheduled to receive three 21-day cycles of cisplatin and topetecan chemotherapy. She qualified, consented, and enrolled into a blinded interventional pilot study where she received daily whey protein (10 g, three times per day with meals) and a weekly injection of testosterone enanthate (100 mg intramuscular) before and during the SOC chemotherapy treatment period. Body composition, serum inflammatory markers, mixed muscle protein synthesis and breakdown rates, physical function, fatigue, and quality of life were assessed before and after the intervention period. RESULTS: Body composition, as assessed by an increase in body weight and lean body mass and reduction in fat mass; physical function; fatigue; and quality of life each improved across the entire intervention period despite general increases in inflammatory markers and no improvements in muscle protein turnover towards the end of the intervention. CONCLUSIONS: Concomitant treatment of oral amino acids and testosterone may be a viable therapeutic option for fighting cachexia and improving body composition and quality of life during chemotherapeutic treatment of recurrent cervical cancer. These positive outcomes may be attainable over time despite overall poor inflammatory status.

Work related stress among gynecologic oncologists.

OBJECTIVE: Up to one third of oncologists experience burnout. The objective was to determine correlates of work related stress in gynecologic oncologists (GOs). METHODS: Using an online tool, we surveyed 273 members of the International Gynecologic Cancer (IGCS) Society (60% from North America) to examine demographic, psychological and spiritual correlates of work related stress (WRS) and burnout. Measures of death anxiety (DA) and locus of control (LOC) were also administered. RESULTS: WRS did not correlate with religion, religiosity, race, or gender, but did correlate with DA (r=0.23, p=0.0006). WRS was also associated with younger age (p=0.01) and fewer years out of training (p=0.0286), higher scores on LOC Chance (r=0.18, p=0.007), higher scores on Powerful Other (r=0.30, p<0.0001), and lower scores on LOC Internality (r=-0.30, p<0.0001). CONCLUSION: Responses from younger and less experienced GOs, correlate with higher WRS scores especially if their LOC is weighted toward chance and powerful others. Responses of GO's with these two characteristics also correlate with higher DA scores and reports of difficulty talking about death.

Religious and spiritual beliefs of gynecologic oncologists may influence medical decision making.

BACKGROUND: Religious (R) and spiritual (S) beliefs often affect patients' health care decisions, particularly with regard to care at the end of life. Furthermore, patients desire more R/S involvement by the medical community; however, physicians typically do not incorporate R/S assessment into medical interviews with patients. The effects of physicians' R/S beliefs on willingness to participate in controversial clinical practices such as medical abortions and physician-assisted suicide has been evaluated, but how a physician's R/S beliefs may affect other medical decision-making is unclear. METHODS: Using SurveyMonkey, an online survey tool, we surveyed 1972 members of the International Gynecologic Oncologists Society and the Society of Gynecologic Oncologists to determine the R/S characteristics of gynecologic oncologists and whether their R/S beliefs affected their clinical practice. Demographics, religiosity, and spirituality data were collected. Physicians were also asked to evaluate 5 complex case scenarios. RESULTS: : Two hundred seventy-three (14%) physicians responded. Sixty percent "agreed" or "somewhat agreed" that their R/S beliefs were a source of personal comfort. Forty-five percent reported that their R/S beliefs ("sometimes," "frequently," or "always") play a role in the medical options they offered patients, but only 34% "frequently" or "always" take a R/S history from patients. Interestingly, 90% reported that they consider patients' R/S beliefs when discussing end-of-life issues. Responses to case scenarios largely differed by years of experience, although age and R/S beliefs also had influence. CONCLUSIONS: Our results suggest that gynecologic oncologists' R/S beliefs may affect patient care but that most physicians fail to take an R/S history from their patients. More work needs to be done to evaluate possible barriers that prevent physicians from taking a spiritual history and engaging in discussions over these matters with patients.