Non-functioning pituitary microadenoma in children and adolescents: Is follow-up with diagnostic imaging necessary?

PURPOSE: No consensus exists regarding follow-up recommendations for suspected pituitary microadenoma in children. To address this knowledge gap, we investigated the growth potential of pituitary solid and cystic lesions <10 mm in children and evaluated the accuracy of magnetic resonance imaging (MRI) measurements. METHODS: The children included were <18 years at first pituitary MRI and radiologically diagnosed with a non-functioning microadenoma or cyst <10 mm. Lesion size at first and latest MRI as well as all individual MRI examinations were re-evaluated. RESULTS: In total, 74 children, median age 12 years (range 3-17), had a non-functioning microadenoma, probable microadenoma, or cyst. Of these, 55 underwent repeated MRI (median 3, range 2-7) with a median follow-up of 37 months (range 4-189). None of the pituitary lesions without hormonal disturbances increased significantly during follow-up. Two radiologists agreed that no lesion could be identified in 38/269 (14%) MRI examinations, and in 51/231 (22%) they disagreed about lesion location. In 34/460 (7%) MRI measurements size differed >2 mm, which had been considered significant progression. CONCLUSION: Non-functioning pituitary microadenoma in children has small size variations, often below the spatial resolution of the scanners. We suggest lesions <4 mm only for clinical follow-up, lesions 4-6 mm for MRI after 2 years and ≥7 mm MRI after 1 and 3 years, with clinical follow-up in between. If no progression, further MRI should only be performed after new clinical symptoms or hormonal disturbances.

Mohs micrographic surgery revisited: A multidisciplinary, collaborative approach for the treatment of aggressive and recurrent basal cell carcinoma on the head and neck.

Mohs micrographic surgery is the preferred surgical option for high-risk basal cell carcinomas. In our institution, the method is exclusively used for the treatment of aggressive and recurrent facial tumours selected via multidisciplinary team meetings and consistently managed using a multidisciplinary approach. The aim of this retrospective patient-record study was to examine the outcomes for basal cell carcinomas managed with Mohs micrographic surgery and to present our experience from multidisciplinary team meetings and interdisciplinary collaborations. All patients treated between September 2009 and March 2019 at Karolinska University hospital were included. In a total of 143 facial basal cell carcinomas in 138 patients, 86 primary and 57 recurrent, the recurrence rate was 4.9% after a median follow-up of 24 months. In regions, where highly specialised Mohs surgeons performing all the steps of the procedure are limited, interdisciplinary collaboration can be an effective strategy for appropriate patient selection and for performing all steps of Mohs surgery with dermatosurgeons eradicating the tumour, pathologists evaluating the histopathology, followed by reconstructive surgery by plastic surgeons. The approach we present here provides a robust and functioning Mohs surgical service during the build-up of the organisation, while providing the opportunity to train new surgeons. Once the clinic has been set up, the multidisciplinary approach should always be considered and applied when dealing with complex cases.

Correction: Differences in cutaneous melanoma treatment and patient satisfaction.

[This corrects the article DOI: 10.1371/journal.pone.0205517.].

Ten-year Follow-up Study of Grenz Ray Treatment for Lentigo Maligna and Early Lentigo Maligna Melanoma.

Radiotherapy is often used to treat lentigo maligna. However, the long-term efficacy and safety of radiotherapy approaches have not been thoroughly evaluated. We aimed to evaluate the long-term efficacy and safety of ultrasoft X-ray/Grenz ray treatment in those patients. A total of 161 lesions from 159 patients received treatment with Grenz ray between 2005 and 2007. Follow-up of recurrence was performed 10 years after the final treatment. In the study setting, the cure rates were 97% for primary therapy with Grenz ray alone and 100% when Grenz ray was combined with partial or radical excision. The treatment is well tolerated, simple to perform, and has an excellent cosmetic outcome, with 94% of patients pleased with the results. Grenz ray is painless, effective, and safe for use when surgery is not feasible. Thus, Grenz ray can be considered as a standard treatment option for lentigo maligna.

Patients with cutaneous head and neck melanoma, particularly elderly with more advanced primary tumors, seem to benefit from initial CT staging before considering a sentinel lymph node biopsy.

Background: The role of CT scanning at the time of diagnosis for patients with primary cutaneous head and neck melanoma (cHNM) clinically asymptomatic for metastatic disease remains unclear.Aim: To determine the positive yield of initial CT scanning before considering sentinel lymph node biopsy (SLNB) staging.Materials and methods: A retrospective review was performed on 170 consecutive patients with cHNM referred to a tertiary head and neck academic center for SLNBs from 2014 through 2018.Results: Initial CTs identified occult melanoma metastases in 7.1% and other advanced malignancies in 4.7%. The overall CT yield for patients >65 years (n = 115) was 13.9%, and 5.5% for patients <65 (only occult melanoma metastases). The SLNB yield did not differ between older (11.5%) and younger patients (10.2%). Patients with more advanced primary tumors were upstaged more often by both staging procedures. Multivariate analysis indicated a true-positive CT finding as the strongest prognostic factor for OS (p<.001).Conclusions and significance: The CT yield was >11% and higher for older than for younger patients. The findings suggest that CT imaging may be considered before SLNB staging, potentially identifying metastatic melanoma disease as well as other occult malignancies, enabling especially older patients to bypass the SLNB procedure.

Pituitary Metastases: A Nationwide Study on Current Characteristics With Special Reference to Breast Cancer.

OBJECTIVE: To investigate the contemporary presentation of pituitary metastases. PATIENTS: Thirty-eight patients diagnosed with pituitary metastases from 1996 to 2018 in Sweden. METHODS: Pituitary metastases were confirmed by histopathology (n = 27) or considered highly likely according to radiological findings, including rapid tumor progression (n = 11). Medical records were reviewed and sellar images reexamined centrally. RESULTS: Breast and lung cancers were the most common primary tumors, in 45% and 21% of patients, respectively. Sixty-seven percent of breast cancers overexpressed human epidermal growth factor receptor 2 (HER2); 53% of pituitary metastases from breast cancers appeared ≥10 years after diagnosis of the primary tumor. At presentation, 71% appeared to have ACTH deficiency, 65% had TSH deficiency, and 26% had diabetes insipidus. Fatigue, nausea/vomiting, loss of appetite, weight loss, myalgia, and/or arthralgia were reported in 47% of patients with morning cortisol <100 nmol/L vs 23% with cortisol ≥200 nmol/L. Sixteen patients had visual field defects, and eight had diplopia. Intrasellar and suprasellar tumor growth was the most frequent finding. Initially, a pituitary adenoma was considered the etiology in 18% of patients.Radiotherapy, pituitary surgery, and chemotherapy were used in 68%, 68%, and 11% of patients, respectively. One and 2 years after diagnosis of pituitary metastases, 50% and 26% of patients were alive. CONCLUSION: Pituitary metastases may be mistaken for pituitary adenomas and can appear late, especially in breast cancer. Breast cancers overexpressing HER2 seem prone to metastasize to the pituitary. Hypocortisolism may be misdiagnosed as cancer-related malaise. An increased awareness of pituitary metastases and undiagnosed pituitary failure can improve management in these patients.

Differences in cutaneous melanoma treatment and patient satisfaction.

Although clinical guidelines exist, the management of patients with cutaneous melanoma (CM) is a complex process that may vary between different care providers with potential dysfunctions ultimately mirrored in the overall patient satisfaction. The aim of the present study was to investigate the CM management as related to lead times, surgical quality and diagnosis communication with the hypothesis that the care may differ between providers and disparities may impact patient satisfaction. Medical records of 181 patients were retrospectively analyzed with parallel patient satisfaction evaluation by telephone interviews. Overall mean lead times from initial diagnosis until completion of all surgery and histopathology reports were 80-100 days and delays occurred at every step of the process. General practitioners performed excision biopsies faster however this was mitigated by slower histopathology processing. University level CM care showed less lag time between excision biopsy, wide local excision for thick melanomas and histopathology confirmation. University level care operated with twice the surgical margin as compared to general practitioners and non-university level specialists. Male patients had larger excision biopsy margins and significantly shorter lead times than female patients. Patient satisfaction rates were generally higher in the academic hospitals as compared to general practitioners and non-university dermatology clinics. Surprisingly, there was no correlation between lead times and patient satisfaction. Taken together, CM show substantial variation and caution should be practiced when using patient satisfaction as a quality indicator.

Prognostic factors and disease-specific survival among immigrants diagnosed with cutaneous malignant melanoma in Sweden.

Little is known about cutaneous malignant melanoma (CMM) among immigrants in Europe. We aimed to investigate clinical characteristics and disease-specific survival among first- and second-generation immigrants in Sweden. This nationwide population-based study included 27,235 patients from the Swedish Melanoma Register diagnosed with primary invasive CMM, 1990-2007. Data were linked to nationwide, population-based registers followed up through 2013. Logistic regression and Cox regression models were used to determine the association between immigrant status, stage and CMM prognosis, respectively. After adjustments for confounders, first generation immigrants from Southern Europe were associated with significantly more advanced stages of disease compared to Swedish-born patients [Stage II vs. I: Odds ratio (OR) = 2.37, 95% CI = 1.61-3.50. Stage III-IV vs I: OR = 2.40, 95% CI = 1.08-5.37]. The ORs of stage II-IV versus stage I disease were increased among men (OR = 1.9; 95% CI = 1.1-3.3; p = 0.020), and women (OR = 4.8; 95% CI = 2.6-9.1; p < 0.001) in a subgroup of immigrants from former Yugoslavia compared to Swedish-born patients. The CMM-specific survival was significantly decreased among women from former Yugoslavia versus Swedish-born women [hazard ratio (HR)=2.2; 95% CI = 1.1-4.2; p = 0.043]. After additional adjustments including stage, the survival difference was no longer significant. No survival difference between the second generation immigrant group and Swedish-born patients were observed. In conclusion, a worse CMM-specific survival in women from former Yugoslavia was associated with more advanced stages of CMM at diagnosis. Secondary prevention efforts focusing on specific groups may be needed to further improve the CMM prognosis.

Later stage at diagnosis and worse survival in cutaneous malignant melanoma among men living alone: a nationwide population-based study from Sweden.

PURPOSE: To investigate the association between cohabitation status, clinical stage at diagnosis, and disease-specific survival in cutaneous malignant melanoma (CMM). METHODS: This nationwide population-based study included 27,235 patients from the Swedish Melanoma Register diagnosed with a primary invasive CMM between 1990 and 2007 and linked data to nationwide, population-based registers followed up through 2012. RESULTS: After adjustment for age at diagnosis, level of education, living area, period of diagnosis, and tumor site, the odds ratios (ORs) of higher stage at diagnosis were significantly increased among men living alone versus men living with a partner (stage II v stage I: OR, 1.42; 95% CI, 1.29 to 1.57; stage III or IV v stage I: OR, 1.43; 95% CI, 1.14 to 1.79). The OR for stage II versus stage I disease was also increased among women living alone (OR, 1.15; 95% CI, 1.04 to 1.28). After adjustments for the factors listed earlier, the CMM-specific survival was significantly decreased among men living alone (hazard ratio [HR] for death, 1.48; 95% CI, 1.33 to 1.65; P < .001). After additional adjustments for all potential and established prognostic factors, CMM-specific survival among men living alone versus men living with a partner remained significantly decreased (HR, 1.31; 95% CI, 1.18 to 1.46; P < .001), suggesting a residual adverse effect on survival not accounted for by these parameters. CONCLUSION: In all age groups among men, living alone is significantly associated with reduced CMM-specific survival, partially attributed to a more advanced stage at diagnosis. This emphasizes the need for improved prevention and early detection strategies for this group.

Electrical impedance spectroscopy as a potential adjunct diagnostic tool for cutaneous melanoma.

BACKGROUND: Previous studies have shown statistically significant differences in electrical impedance between various cutaneous lesions. Electrical impedance spectroscopy (EIS) may therefore be able to aid clinicians in differentiating between benign and malignant skin lesions. OBJECTIVES: The aim of the study was to develop a classification algorithm to distinguish between melanoma and benign lesions of the skin with a sensitivity of at least 98% and a specificity approximately 20 per cent higher than the diagnostic accuracy of dermatologists. PATIENTS/METHODS: A total of 1300 lesions were collected in a multicentre, prospective, non-randomized clinical trial from 19 centres around Europe. All lesions were excised and subsequently evaluated independently by a panel of three expert dermatopathologists. From the data two classification algorithms were developed and verified. RESULTS: For the first classification algorithm, approximately 40% of the data were used for calibration and 60% for testing. The observed sensitivity for melanoma was 98.1% (101/103), non-melanoma skin cancer 100% (25/25) and dysplastic nevus with severe atypia 84.2% (32/38). The overall observed specificity was 23.6% (66/280). For the second classification algorithm, approximately 55% of the data were used for calibration. The observed sensitivity for melanoma was 99.4% (161/162), for non-melanoma skin cancer was 98.0% (49/50) and dysplastic nevus with severe atypia was 93.8% (60/64). The overall observed specificity was 24.5% (116/474). CONCLUSION: EIS has the potential to be an adjunct diagnostic tool to help clinicians differentiate between benign and malignant (melanocytic and non-melanocytic) skin lesions. Further studies are needed to confirm the validity of the automatic assessment algorithm.

Interobserver variability of histopathological prognostic parameters in cutaneous malignant melanoma: impact on patient management.

Clinical management of primary cutaneous melanomas is based on histopathological staging of the tumour. The aim of this study was to investigate, in a non-selected population in clinical practice, the agreement rate between general pathologists and pathologists experienced in melanoma in terms of the evaluation of histopathological prognostic parameters in cutaneous malignant melanomas, and to what extent the putative variability affected clinical management. A total of 234 cases of invasive cutaneous malignant melanoma were included in the study from the Stockholm-Gotland Healthcare Region in Sweden. Overall interobserver variability between a general pathologist and an expert review was 68.8-84.8%. Approximately 15.5% of melanomas ≤1 mm were re-classified either as melanoma in situ or melanomas >1 mm after review. In conclusion, review by a pathologist experienced in melanoma resulted in a change in recommendations about surgical excision margins and/or sentinel node biopsy in subgroups of T1 melanomas.

Female urinary incontinence: patient-reported outcomes 1 year after midurethral sling operations.

INTRODUCTION AND HYPOTHESIS: Although midurethral slings have become standard surgical methods to treat stress urinary incontinence (SUI), little is known about women who still have urinary incontinence (UI) after surgery. This study assesses and compares the patient-reported outcome 12 months after tension-free vaginal tape (TVT), tension-free vaginal tape-obturator (TVT-O), and transobturator tape (TOT), with a special focus on women who still have urinary leakage postoperatively. METHODS: This study analyzed preoperative and 12-month postoperative data from 3,334 women registered in the Swedish National Quality Register for Gynecological Surgery. RESULTS: Among the women operated with TVT (n = 2,059), TVT-O (n = 797), and TOT (n = 478), 67 %, 62 %, and 61 %, respectively, were very satisfied with the result at the 1-year follow-up. There was a significantly higher chance of becoming continent after TVT compared with TOT. In total, 977 women (29 %) still had some form of urinary leakage postoperatively. Among the postoperatively incontinent women who expressed a negative impact of UI on family, social, work, and sexual life preoperatively, considerably fewer reported a negative impact in all domains after surgery. Of those in the postoperatively incontinent group who had coital incontinence preoperatively, 63 % reported a cure of coital incontinence. CONCLUSIONS: The proportion of women very satisfied with the result of the operation did not differ between the three groups. TVT had a higher SUI cure rate than did TOT. Despite urinary leakage 1-year postoperatively, half of the women were satisfied with the result of the operation.

Antimicrobial protein hCAP18/LL-37 is highly expressed in breast cancer and is a putative growth factor for epithelial cells.

Human cathelicidin antimicrobial protein hCAP18/LL-37 is an effector molecule of the nonspecific innate immune system. hCAP18/LL-37 is present in leukocytes and is expressed in skin and other epithelia, where it is upregulated in association with inflammation and injury. In addition, antimicrobial proteins including cathelicidins have been proposed to play a role in the nonspecific defense against tumors. To assess its potential role in tumor host defense, we investigated the expression of hCAP18/LL-37 in a series of breast carcinomas. Unexpectedly, we found that hCAP18/LL-37 was strongly expressed in the tumor cells and not in the adjacent stroma. To test the hypothesis that hCAP18/LL-37 may provide a growth advantage for the tumor cells, we treated human epithelial cell lines with synthetic biologically active LL-37 peptide and found a significant increase in cell proliferation. In addition, transgenic expression of hCAP18 in 2 different human epithelial cell lines resulted in increased proliferation of both cell types. These findings do not support the hypothesis that LL-37 has an antitumor effect, but rather suggest that hCAP18/LL-37 may promote tumor cell growth in breast cancer.