Transgender Males on Gender-Affirming Hormone Therapy and Hepatobiliary Neoplasms: A Systematic Review.

OBJECTIVE: Behavioral therapy, gender-affirming hormone therapy (GAHT), and surgery are all components of a successful gender transition, but due to a historical lack of access, there is paucity of long-term data in this population. We sought to better characterize the risk of hepatobiliary neoplasms in transgender males undergoing GAHT with testosterone. METHODS: In addition to the 2 case reports, a systematic literature review of hepatobiliary neoplasms in the setting of testosterone administration or endogenous overproduction across indications was conducted. The medical librarian created search strategies using keywords and controlled vocabulary in Ovid Medline, Embase.com, Scopus, Cochrane Database of Systematic Reviews, and clinicaltrials.gov. A total of 1273 unique citations were included in the project library. All unique abstracts were reviewed, and abstracts were selected for complete review. Inclusion criteria were articles reporting cases of hepatobiliary neoplasm development in patients with exogenous testosterone administration or endogenous overproduction. Non-English language articles were excluded. Cases were collated into tables based on indication. RESULTS: Forty-nine papers had cases of hepatocellular adenoma, hepatocellular carcinoma, cholangiocarcinoma, or other biliary neoplasm in the setting of testosterone administration or endogenous overproduction. These 49 papers yielded 62 unique cases. CONCLUSION: Results of this review are not sufficient to conclude that there is an association between GAHT and hepatobiliary neoplasms. This supports current evaluation and screening guidelines for initiation and continuation of GAHT in transgender men. The heterogeneity of testosterone formulations limits the translation of risks of hepatobiliary neoplasms in other indications to GAHT.

Standardization of thyroid ultrasound reporting in the community setting decreases biopsy rates.

OBJECTIVE: With the rising incidence of thyroid cancer, a standardized approach to the evaluation of thyroid nodules is essential. Despite the presence of multiple national guidelines detailing evaluation and management of these nodules, significant variability exists in the information that is collected and reported to clinicians from diagnostic imaging. The aim of this study was to evaluate the impact of thyroid ultrasound standardization on thyroid cancer detection in a community practice setting. DESIGN: As part of a physician-driven quality improvement project, a multidisciplinary team created an electronic worksheet to be utilized by sonographers to capture suspicious findings based on societal guidelines and agreed on institutional criteria for recommending fine needle aspiration (FNA) of thyroid nodules. PATIENTS: For a one-year period prior to and after the intervention, all ultrasounds performed for suspected thyroid pathology, excluding patients undergoing follow-up imaging, were reviewed at two affiliated community hospitals served by a single radiology and pathology group. MEASUREMENTS: The number of fine needle biopsies recommended and performed, as well as the percentage of FNAs positive for malignancy were evaluated. RESULTS: A total of 608 and 675 ultrasounds were reviewed in pre- and post-standardization periods, respectively. Following standardization, there was a similar percentage of FNAs recommended (35% vs. 37%, p = .68), fewer FNAs per total ultrasounds performed (36% vs. 31%, p = .03), fewer FNAs performed when FNA was not explicitly recommended (9.9% vs. 2.8%, p = .000046) and an increased detection of cytology consistent with, or suspicious for, malignancy (5% vs. 11.5%, p = .0028). CONCLUSIONS: Standardization of thyroid imaging protocol and management recommendations can reduce the number of FNAs performed and increase the percentage of positive tests in a community setting.

A Phase Ib Study of Preoperative, Locoregional IRX-2 Cytokine Immunotherapy to Prime Immune Responses in Patients with Early-Stage Breast Cancer.

PURPOSE: To evaluate the safety and feasibility of preoperative locoregional cytokine therapy (IRX-2 regimen) in early-stage breast cancer, and to evaluate for intratumoral and peripheral immunomodulatory activity. PATIENTS AND METHODS: Sixteen patients with stage I-III early-stage breast cancer (any histology type) indicated for surgical lumpectomy or mastectomy were enrolled to receive preoperative locoregional immunotherapy with the IRX-2 cytokine biological (2 mL subcutaneous × 10 days to periareolar skin). The regimen also included single-dose cyclophosphamide (300 mg/m2) on day 1 to deplete T-regulatory cells and oral indomethacin to modulate suppressive myeloid subpopulations. The primary objective was to evaluate feasibility (i.e., receipt of therapy without surgical delays or grade 3/4 treatment-related adverse events). The secondary objective was to evaluate changes in stromal tumor-infiltrating lymphocyte score. The exploratory objective was to identify candidate pharmacodynamic changes for future study using a variety of assays, including flow cytometry, RNA and T-cell receptor DNA sequencing, and multispectral immunofluorescence. RESULTS: Preoperative locoregional cytokine administration was feasible in 100% (n = 16/16) of subjects and associated with increases in stromal tumor-infiltrating lymphocytes (P < 0.001). Programmed death ligand 1 (CD274) was upregulated at the RNA (P < 0.01) and protein level [by Ventana PD-L1 (SP142) and immunofluorescence]. Other immunomodulatory effects included upregulation of RNA signatures of T-cell activation and recruitment and cyclophosphamide-related peripheral T-regulatory cell depletion. CONCLUSIONS: IRX-2 is safe in early-stage breast cancer. Potentially favorable immunomodulatory changes were observed, supporting further study of IRX-2 in early-stage breast cancer and other malignancies.

Management of Primary Hyperparathyroidism: Can We Do Better?

The failure to follow national guidelines in management of various diseases has been previously established. We sought to quantify primary care providers' familiarity with primary hyperparathyroidism as it affects adherence to the 2009 National Institute of Health (NIH) consensus recommendations in treatment of primary hyperparathyroidism. A large primary care group was surveyed to determine their familiarity with the 2009 NIH consensus recommendations for management of primary hyperparathyroidism (PHPT). Retrospective review of the group's records (2009-2011) was performed to verify compliance. Survey responders included 109 clinicians, 31 per cent were familiar with all criteria for surgical intervention in asymptomatic patients and 34 per cent correctly identified appropriate surveillance testing for patients undergoing observation. Chart review identified 124 patients with PHPT. Of the patients who met NIH criteria, 34 per cent had a parathyroidectomy. Younger age, higher intact parathyroid hormone, hypercalciuria, and history of nephrolithiasis were associated with surgery in multivariable analysis. Of the observed patients, 16 per cent had appropriate surveillance studies. In conclusion, this study confirms suboptimal adherence with consensus recommendations in management of PHPT. A minority of clinicians demonstrated solid familiarity with management strategies, paralleling their treatment approach. Educational efforts may improve adherence with upcoming national recommendations.

Treatment strategies for primary hyperparathyroidism: what is the cost?

Primary hyperparathyroidism (HPT) contributes to the onset of many chronic conditions. Although parathyroidectomy is the only definitive treatment, observation remains a valid option. Over a 3-year span, a major health plan was queried for HPT and benign parathyroid neoplasm. Patients with secondary and tertiary HPT, Stage III to V kidney disease, and prior renal transplant were excluded. Patients were divided into: observation (Group 1), parathyroidectomy during the study period (Group 2), and parathyroidectomy before the study group (Group 3), and were compared with a control group of 27,092 adult members without HPT using analysis of variance. The 3-year mean total allowed expenditure for Group One (n = 559), Group Two (n = 93), and Group Three (n = 48) were $21,267, $37,043, and $14,702, respectively. Groups One and Two had significantly higher use than the nonparathyroid group (P < 0.0001), whereas that of Group Three was comparable. Group Two had the highest cost, whereas Group Three had a significantly lower cost than Group One (P 0.0001). Primary hyperparathyroidism is associated with a higher use of healthcare resources. Patients observed incurred a higher allowed expenditure than those with prior parathyroidectomy. Surgical treatment may represent a cost-effective strategy for treatment of hyperparathyroidism, although more comprehensive studies are needed to confirm these findings.

Subxyphoid thyroidectomy: a feasibility study.

OBJECTIVE: The cultural desire to avoid cervical incisions and increasing concern for cosmetic outcomes has motivated surgeons to develop alternative approaches to thyroid surgery. The Direct Drive Endoscopic System (DDES) platform combines a flexible endoscope with a pair of separately controlled articulating instruments through a single, flexible, access system. We hypothesized that the DDES platform would permit single-incision minimally invasive thyroid lobectomy without robotic assistance. METHODS: This is a single-cadaver feasibility study. A single, 2.2-cm subxyphoid incision was used for access. The platform's 55-cm flexible sheath was secured to the operating table rails and introduced into the subcutaneous space. A flexible pediatric endoscope was simultaneously introduced with 2 interchangeable 4-mm instruments. Blunt dissection and electrocautery were used to create the tunnel in the otherwise free central plane. The thyroid was dissected using a superior to inferior technique while maintaining the critical steps of traditional thyroid surgery. A Veress needle introduced through the lateral neck provided additional retraction. RESULTS: The total operating time was 2.5 hours. The subcutaneous tunnel was safe and accommodated the DDES well. Visualization was adequate. Graspers, scissors, and hook cautery were used to complete the lobectomy. The ergonomics, articulation, and strength of the instrumentation were sufficient. CONCLUSIONS: Subxyphoid thyroidectomy is technically possible and avoids the difficulties inherent to a transaxillary approach while still avoiding cosmetically unappealing cervical scars. Continued technological refinement will only expand the therapeutic possibilities of flexible endoscopy while minimizing the physical insult to patients and maximizing aesthetics for patients.

Randomized controlled trial comparing single-port laparoscopic cholecystectomy and four-port laparoscopic cholecystectomy.

OBJECTIVE: To compare short-term surgical outcomes and quality of life (QOL) between single-port laparoscopic cholecystectomy (SPLC) and classic 4-port laparoscopic cholecystectomy (CLC). BACKGROUND: There is significant interest in further reducing the trauma associated with surgical procedures. Although a number of observational studies have suggested that SPLC is a feasible alternative to CLC, there is a lack of data from randomized studies validating any benefit over CLC. METHODS: Eligible patients were randomized to receive SPLC or CLC. Operative and perioperative outcomes, including cosmesis and QOL were analyzed. RESULTS: Forty-three patients were randomized to SPLC (n = 21) or CLC (n = 22). There were no significant differences between groups for most preoperative demographics, American Society of Anesthesiology score, gallstone characteristics, local inflammation, blood loss, or length of stay. Patients undergoing SPLC were older than those receiving CLC (57.3 years vs. 45.8 years, P < 0.05). Operative times for SPLC were greater than CLC (88.5 minutes vs. 44.8 minutes, P < 0.05). Overall and cosmetic satisfaction, QOL as determined by the SF-36 survey, postoperative complications, and post-operative pain scores between discharge and 2-week postoperative visit were not significantly different between groups. Wound infection rates were similar in both groups. The SPLC group contained 1 retained bile duct stone, 1-port site hernia, and 1 postoperative port site hemorrhage. CONCLUSIONS: SPLC procedure time was longer and incurred more complications than CLC without significant benefits in patient satisfaction, postoperative pain and QOL. SPLC may be offered in carefully selected patients. Larger randomized trials performed later in the learning curve with SPLC may identify more subtle advantages of one method over another.

Poor knowledge of basic cancer facts of physicians-in-training.

PURPOSE: Since many physicians-in-training will play an important role in cancer screening, their understanding of cancer screening and basic cancer facts is paramount. This investigation was undertaken to determine their baseline knowledge in basic cancer facts. METHOD: A questionnaire was used to assess the knowledge of basic cancer facts of medical students, medical residents and surgical residents. Participants were asked to rank five different malignancies in their correct order for both mortality and incidence. Physicians-in-training were given separate questions for male and female patients. The questions were considered correct if at least the first three malignancies were ranked in the appropriate order. RESULTS: One-hundred-twelve second-year medical students and 78 residents were assessed. Few physicians-in-training ranked the malignancies in correct order for mortality (21% for female patients and 18% for male patients). Even fewer physicians-in-training ranked the malignancies in correct order for incidence (2% for female patients and 9% for male patients). CONCLUSION: Most physicians-in-training lack an understanding of basic cancer facts. If this poor basic cancer fact knowledge represents an overall lack of cancer knowledge, educational efforts need to be focused on cancer care for all levels and specialties of physician training.

Physicians-in-training recommendations for prophylactic bilateral mastectomies.

The decision to recommend bilateral prophylactic mastectomy (PBM), one treatment modality used to reduce the development of breast carcinoma, may be influenced by physician bias. This investigation tested the hypothesis that there are physician-in-training biases in recommendations of PBM. All second-year medical students, general surgical residents, and internal medicine residents at our institution participated in a survey in which they were asked at what percent risk of developing breast carcinoma the physicians-in-training would recommend PBM for 1) their patients, 2) themselves, and 3) their significant others, as applicable. A total of 198 physicians-in-training responded. Univariate analysis demonstrated an association between both the type of physician-in-training (p<0.03) and gender (p<0.004) with the percent risk for which respondents would recommend PBM. However, with multivariate analysis, only gender was associated with percent risk (p<0.05). Physicians-in-training also chose PBM at a lower risk for their significant others than for themselves (67.5% versus 57.2%; p<0.02). Respondents also chose PBM at a similar risk for themselves or significant others as for their patients (r=0.83, r=0.98; p<0.001). This investigation suggests that males (compared to females) are more likely to recommend PBM for the prevention of breast cancer.

Synchronous occurrence of glioblastoma multiforme and esophageal adenocarcinoma.

Synchronous malignancies are rare occurrences for which there may be a genetic link between two cancers or which may be simply coincidental. Although glioblastoma multiforme and esophageal adenocarcinoma have few clinical similarities there are no known biochemical or genetic links between the two malignancies. This case discussion details the synchronous occurrences of these two lesions and highlights possible clinical, biochemical, and genetic commonalities.

Education of medical students in clinical breast examination during surgical clerkship.

BACKGROUND: Medical student training in clinical breast examination is deficient at most medical schools. The use of silicone breast models may allow the education of abnormal and normal findings. This study examines the efficacy of silicone breast models to educate medical students in clinical breast examinations during their third-year surgical rotation. METHODS: Medical students were randomly selected to participate in formalized training sessions in clinical breast examination or as a control group. Presession and postsession testing with silicone breast models were performed. True positives (masses that were present and documented by the student) and false positives (masses that were not present but were documented by the student) were recorded. RESULTS: Medical students undergoing the training sessions demonstrated improved true positive scores (2.2 to 2.8; P <0.05) as well as improved false positive scores (3.0 to 2.0; P = 0.30) and total scores (-0.8 to 0.8; P = 0.07). Students who documented an increase in the number of breast examinations during their rotations had statistically lower false positive scores. CONCLUSIONS: Students after formalized clinical breast examination sessions do improve their ability to detect breast masses, although they continue to detect masses that are not present. Experience of actual breast examinations during their surgical rotations may refine their clinical skills.

How early is early laparoscopic treatment of acute cholecystitis?

BACKGROUND: Despite the well-accepted success of laparoscopic cholecystectomy in elective treatment of symptomatic cholelithiasis, the efficacy and timing of this technique has been subject to some debate in the setting of acute cholecystitis. This study was undertaken to evaluate our institution's experience with early cholecystectomy as a safe, effective treatment of acute cholecystitis. METHODS: Charts of all patients who had undergone laparoscopic cholecystectomy for the diagnosis of acute cholecystitis were reviewed. Patients were divided into two groups based on the length of time from onset of symptoms to surgical intervention: less than 48 hours in the early group (n = 14) and more than 48 hours in the late group (n = 31). RESULTS: Comparing the two groups, the conversion rate to an open procedure was significantly less (0 versus 29%, P <0.04) in the early treated patients. Furthermore, the operative time (73 versus 96 minutes, P <0.004), postoperative hospitalization (1.2 versus 3.9 days, P <0.001), and total hospital stay (2.1 versus 5.4 days, P <0.004) were significantly reduced in patients undergoing early laparoscopic cholecystectomy. CONCLUSIONS: Laparoscopic cholecystectomy performed by experienced surgeons is a safe, effective technique for treatment of acute cholecystitis. Patients treated within 48 hours of onset of symptoms experience a lower conversion rate to an open procedure, shorter operative time and reduced hospitalization.