Recent Publications by CFE Educators

PURPOSE

The rectal sphincter preserving transperineal approach has been increasingly used successfully. We analyzed our experience with this surgical approach. A secondary aim was to evaluate the surgical outcome of energy ablative rectourethral fistulas without a concomitant interposition muscle flap.

MATERIALS AND METHODS

We identified all patients with rectourethral fistula who underwent rectal sphincter preserving transperineal repair from 1998 to 2011. Re-approximation of the urethral mucosa, posterior anastomotic urethroplasty or partial/total prostatectomy with urethrovesical anastomosis was performed for urinary closure. The fistula cohort was divided into 2 groups, including postoperative and energy ablative fistulas, respectively. Success after perineal rectourethral fistula repair was defined as resolution after the first attempt at repair.

RESULTS

A total of 23 patients underwent rectal sphincter preserving, transperineal rectourethral fistula repair. In the postoperative fistula cohort the fistula was successfully resolved in all 10 patients. A dartos interposition muscle flap was used in 2 of 10 patients. In the energy ablative cohort the fistula was successfully closed in 8 of 13 patients. An interposition muscle flap was not placed in 8 patients with an energy ablative fistula, of whom success was achieved in 5. Two of the 5 patients with an energy ablative fistula and a successful outcome without a concomitant interposition muscle flap had urinary extravasation, necessitating temporary catheterization.

CONCLUSIONS

Rectal sphincter preserving transperineal repair is a successful surgical method to repair postoperative and energy ablative rectourethral fistulas. An interposition muscle flap should be considered in the setting of energy ablative rectourethral fistulas to increase successful outcomes.

The Reelin-signaling pathway regulates neuronal positioning during embryonic development. Reelin, the extracellular matrix protein missing in reeler mutants, is secreted by neurons in laminae I, II and V, binds to Vldl and Apoer2 receptors on nearby neurons, and tyrosine phosphorylates the adaptor protein Disabled-1 (Dab1), which activates downstream signaling. We previously reported that reeler and dab1 mutants had significantly reduced mechanical and increased heat nociception. Here we extend our analysis to chemical, visceral, and cold pain and importantly, used Fos expression to relate positioning errors in mutant mouse dorsal horn to changes in neuronal activity. We found that noxious mechanical stimulation-induced Fos expression is reduced in reeler and dab1 laminae I-II, compared to wild-type mice. Additionally, mutants had fewer Fos-immunoreactive neurons in the lateral-reticulated area of the deep dorsal horn than wild-type mice, a finding that correlates with a 50% reduction and subsequent mispositioning of the large Dab1-positive cells in the mutant lateral-reticulated area. Furthermore, several of these Dab1 cells expressed Fos in wild-type mice but rarely in reeler mutants. By contrast, paralleling the behavioral observations, noxious heat stimulation evoked significantly greater Fos expression in laminae I-II of reeler and dab1 mutants. We then used the formalin test to show that chemical nociception is reduced in reeler and dab1 mutants and that there is a corresponding decrease in formalin-induced Fos expression. Finally, neither visceral pain nor cold-pain sensitivity differed between wild-type and mutant mice. As differences in the nociceptor distribution within reeler and dab1 mutant dorsal horn were not detected, these differential effects observed on distinct pain modalities suggest that dorsal horn circuits are organized along modality-specific lines.

BACKGROUND

To compare outcomes for patients with recurrent or persistent papillary thyroid cancer (PTC) who had metastatic tumors that were fluorodeoxyglucose-positron emission tomography (FDG-PET) positive or negative, and to determine whether the FDG-PET scan findings changed the outcome of medical and surgical management.

METHODS

From a prospective thyroid cancer database, we retrospectively identified patients with recurrent or persistent PTC and reviewed data on demographics, initial stage, location and extent of persistent or recurrent disease, clinical management, disease-free survival and outcome. We further identified subsets of patients who had an FDG-PET scan or an FDG-PET/CT scan and whole-body radioactive iodine scans and categorized them by whether they had one or more FDG-PET-avid (PET-positive) lesions or PET-negative lesions. The medical and surgical treatments and outcome of these patients were compared.

RESULTS

Between 1984 and 2008, 41 of 141 patients who had recurrent or persistent PTC underwent FDG-PET (n = 11) or FDG-PET/CT scans (n = 30); 22 patients (54%) had one or more PET-positive lesion(s), 17 (41%) had PET-negative lesions, and two had indeterminate lesions. Most PET-positive lesions were located in the neck (55%). Patients who had a PET-positive lesion had a significantly higher TNM stage (P = 0.01), higher age (P = 0.03), and higher thyroglobulin (P = 0.024). Only patients who had PET-positive lesions died (5/22 vs. 0/17 for PET-negative lesions; P = 0.04). In two of the seven patients who underwent surgical resection of their PET-positive lesions, loco-regional control was obtained without evidence of residual disease.

CONCLUSION

Patients with recurrent or persistent PTC and FDG-PET-positive lesions have a worse prognosis. In some patients loco-regional control can be obtained without evidence of residual disease by reoperation if the lesion is localized in the neck or mediastinum.

BACKGROUND

Adrenocortical carcinoma (ACC) is a rare, but aggressive, malignancy. Current American Association of Clinical Endocrinologists (AACE)/American Association of Endocrine Surgeons (AAES) guidelines recommend resection of nonfunctional adrenal neoplasms ≥ 4 cm. This study evaluates the cost-effectiveness of this approach.

METHODS

A decision tree was constructed for patients with a nonfunctional, 4-cm adrenal incidentaloma with no radiographic suspicion for ACC. Patients were randomized to adrenalectomy, surveillance per AACE/AAES guidelines, or no follow-up ("sign-off"). Incremental cost-effectiveness ratio (ICER) includes health care costs, including missed ACC. ICER (dollar/life-year-saved [LYS]) was determined from the societal perspective. Sensitivity analyses were performed.

RESULTS

In the base-case analysis, assuming a 2.0% probability of ACC for a 4-cm tumor, surgery was more cost-effective than surveillance (ICER $25,843/LYS). Both surgery and surveillance were incrementally more cost-effective than sign-off ($35/LYS and $8/LYS, respectively). Sensitivity analysis demonstrated that the model was sensitive to patient age, tumor size, probability of ACC, mortality of ACC, and cost of hospitalization. The results of the model were stable across different cost and complications related to adrenalectomy, regardless of operative approach.

CONCLUSION

In our model, adrenalectomy was cost-effective for neoplasms >4 cm and in patients 65 years, primarily owing to the aggressiveness of ACC. Current AACE/AAES guideline recommendations for the resection of adrenal incidentalomas ≥ 4 cm seem to be cost-effective.

We analyzed associations of dissatisfaction with sexual life and desire for change in female medical students. Students enrolled in medical schools in North America between February and July 2008 were invited to participate in an internet-based survey of sexual function. The principle outcome measure was a single item question on sexual life satisfaction and desire for change. Women who reported dissatisfaction and desire for change were classified as 'sexually bothered'. The survey also assessed ethnodemographic factors, student status, sexual history and depressive symptoms. Respondents completed the Female Sexual Function Index (FSFI) and the Index of Sexual Life. Descriptive statistics, analysis of variance and multivariable logistic regression were utilized to analyze responses. There were 661 non-virgin female subjects with data adequate for analysis. Whereas 281 (43%) of these met criteria for high risk of female sexual dysfunction (HRFSD) based on FSFI scoring, just 173 (26%) reported sexual bother. Among women with HRFSD, 126 (45%) reported sexual bother; in women without HRFSD, 362 (95%) were not sexually bothered. Interference in sexual life from tiredness and stress were associated with sexual bother. Progressively better scores on the FSFI desire, orgasm and satisfaction domains were significantly associated with lower odds of sexual bother. Few women in this cohort with FSFI score >26.55 reported sexual bother. Women with FSFI 26.55 had greater odds of sexual bother but this criterion alone was not pathognomonic for sexual concerns. Issues of sexual desire and orgasm appear to have a more important role than lubrication, arousal and sexual pain issues in this population.

Invasive lobular carcinoma (ILC) has been reported to be less responsive to neoadjuvant chemotherapy (NAC) than invasive ductal carcinoma (IDC). We sought to determine whether ILC histology indeed predicts poor response to NAC by analyzing tumor characteristics such as protein expression, gene expression, and imaging features, and by comparing NAC response rates to those seen in IDC after adjustment for these factors. We combined datasets from two large prospective NAC trials, including in total 676 patients, of which 75 were of lobular histology. Eligible patients had tumors ≥3 cm in diameter or pathologic documentation of positive nodes, and underwent serial biopsies, expression microarray analysis, and MRI imaging. We compared pathologic complete response (pCR) rates and breast conservation surgery (BCS) rates between ILC and IDC, adjusted for clinicopathologic factors. On univariate analysis, ILCs were significantly less likely to have a pCR after NAC than IDCs (11 vs. 25 %, p = 0.01). However, the known differences in tumor characteristics between the two histologic types, including hormone receptor (HR) status, HER2 status, histological grade, and p53 expression, accounted for this difference with the lowest pCR rates among HR+/HER2- tumors in both ILC and IDC (7 and 5 %, respectively). ILC which were HR- and/or HER2+ had a pCR rate of 25 %. Expression subtyping, particularly the NKI 70-gene signature, was correlated with pCR, although the small numbers of ILC in each group precluded significant associations. BCS rate did not differ between IDC and ILC after adjusting for molecular characteristics. We conclude that ILC represents a heterogeneous group of tumors which are less responsive to NAC than IDC. However, this difference is explained by differences in molecular characteristics, particularly HR and HER2, and independent of lobular histology.

Lichen sclerosus is a commonly misdiagnosed disease that is characterized by thinned, hypopigmented, crinkled skin that often forms a figure-eight shape around the vaginal and anal openings. We present a case of advanced lichen sclerosus in a 53-year-old female patient prescribed a nonsteroidal aromatase inhibitor after the excision of a breast cancer tumor. We present a diagnostic approach to lichen sclerosus by recognizing its common figure-eight pattern, and we review the known causes and treatment of lichen sclerosus. Research has shown that lichen sclerosus is more common in low estrogen states, and thus it is logical that aromatase inhibitors could increase a patient's risk for developing this disease. We therefore propose that all patients prescribed aromatase inhibitors undergo regular vulvo-vaginal exams to rule out lichen sclerosus and other hypoestrogen-related vulvo-vaginal problems.