A woman in her fifties with a post-operative infection, generalised rash and organ failure. / En kvinne i 50-årene med postoperativ infeksjon, generalisert utslett og organsvikt.

Background: Toxic shock syndrome (TSS) is a rare but potentially life-threatening disease caused by superantigen-producing Gram-positive bacteria such as Staphylococcus aureus and Streptococcus pyogenes. Staphylococcal TSS received special attention from 1978 to 1981, when an epidemic was observed associated with the use of hyper-absorbent tampons. Today the disease is rare and generally not related to menstruation, but can occur postpartum or in post-surgical wounds, intrauterine devices (IUDs), burns or other soft tissue injuries, mastitis or other focal infections. The annual incidence of staphylococcal TSS is around 0.5/100 000 and around 0.4/100 000 for streptococcal TSS. The mortality in menstrual-related cases is < 5 % and up to 22 % in non-menstrual related cases. Case presentation: This article presents a case of a middle-aged woman who developed symptoms of toxic shock syndrome five days after elective breast cancer surgery, with high fever, multiorgan failure and a characteristic desquamation of the palms. Interpretation: Toxic shock syndrome is a potentially lethal, toxin-mediated disease. Symptoms develop quickly, within hours. Early recognition and appropriate surgical management, intensive care and antibiotics are therefore important to reduce mortality and sequelae.

Thyroidectomy for Euthyroid Patients with Hashimoto Disease and Persistent Symptoms: An Observational, Postrandomization Study.

Background: Despite adequate hormone substitution in Hashimoto disease, some patients may have persistent symptoms with a possible autoimmune pathophysiology. A recent randomized trial (RCT) using patient-reported outcome measures as the primary endpoint showed benefit in total thyroidectomy, but at a cost of high complication rates. Objective: To verify results from the RCT in an observational study including a wider range of patients and explore means of predicting who may benefit from such surgery. Design: A total of 154 patients with Hashimoto disease, euthyroid with or without thyroid hormone substitution, and persistent Hashimoto-related symptoms were subjected to total thyroidectomy and followed for 18 months after surgery. The primary outcome was the General Health (GH) dimensional score in the Short Form-36 Health Survey (SF-36). Results: Eighteen months after surgery, a clinically significant improvement in GH was seen, similar to the findings in the previous RCT. Anti-TPO antibody titers were markedly reduced after surgery, but preoperative titers or other preoperative parameters could not predict the outcome of surgery. Three (1.9%) of 154 patients experienced permanent unilateral recurrent nerve palsy and six (3.9%) experienced hypoparathyroidism after surgery. Conclusions: Thyroidectomy had a beneficial symptom-reducing effect in euthyroid patients with Hashimoto disease and persistent symptoms. The pathophysiology of residual symptoms remains unclear, and surgical complication rates are high. If thyroidectomy is considered as a treatment option, it should be performed in dedicated centers with experienced endocrine surgeons and as part of further studies on persistent symptoms. This trial is registered with NCT-02319538.

Assessment of preoperative axillary nodal disease burden: breast MRI in locally advanced breast cancer before, during and after neoadjuvant endocrine therapy.

BACKGROUND: Axillary lymph node (LN) metastasis is one of the most important predictors of recurrence and survival in breast cancer, and accurate assessment of LN involvement is crucial. Determining extent of residual disease is key for surgical planning after neoadjuvant therapy. The aim of the study was to evaluate the diagnostic reliability of MRI for nodal disease in locally advanced breast cancer patients treated with neoadjuvant endocrine therapy (NET). METHODS: Thirty-three clinically node-positive locally advanced breast cancer patients who underwent NET and surgery were prospectively enrolled. Two radiologists reviewed the axillary nodes at 3 separate time points MRI examinations at baseline (before the first treatment regimen), interim (following at least 2 months after the first cycle and prior to crossing-over), and preoperative (after the final administration of therapy and immediately before surgery). According to LN status after surgery, imaging features and diagnostic performance were analyzed. RESULTS: All 33 patients had a target LN reduction, the greatest treatment benefit from week 8 to week 16. There was a positive correlation between the maximal diameter of the most suspicious LN measured by MRI and pathology during and after NET, being highest at therapy completion (r = 0.6, P ≤ .001). Mean and median differences of maximal diameter of the most suspicious LN were higher with MRI than with pathology. Seven of 33 patients demonstrated normal posttreatment MRI nodal status (yrN0). Of these 7 yrN0, 3 exhibited no metastasis on final pathology (ypN0), 2 ypN1 and 2 ypN2. Reciprocally, MRI diagnosed 3 cases of ypN0 as yrN + . Diffusion -weighted imaging (DWI) was the only axillary node characteristic significant when associated with pathological node status (χ2(4) = 8.118, P = .072). CONCLUSION: Performance characteristics of MRI were not completely sufficient to preclude surgical axillary staging. To our knowledge, this is the first study on MRI LN assessment following NET in locally advanced breast cancer, and further studies with larger sample sizes are required to consolidate the results of this preliminary study. TRIAL REGISTRATION: Institutional Review Board approval was obtained (this current manuscript is from a prospective, open-label, randomized single-center cohort substudy of the NEOLETEXE trial). NEOLETEXE, a phase 2 clinical trial, was registered on March 23rd, 2015 in the National trial database of Norway and approved by the Regional Ethical Committee of the South-Eastern Health Region in Norway; registration number: REK-SØ-84-2015 .

Lack of cross-resistance between non-steroidal and steroidal aromatase inhibitors in breast cancer patients: the potential role of the adipokine leptin.

PURPOSE: The aromatase inactivator exemestane may cause clinical disease stabilization following progression on non-steroidal aromatase inhibitors like letrozole in patients with metastatic breast cancer, indicating that additional therapeutic effects, not necessarily related to estrogen-suppression, may be involved in this well-known "lack of cross-resistance". METHODS: Postmenopausal women with ER positive, HER-2 negative, locally advanced breast cancer were enrolled in the NEOLETEXE-trial and randomized to sequential treatment starting with either letrozole (2.5 mg o.d.) or exemestane (25 mg o.d.) followed by the alternative aromatase inhibitor. Serum levels of 54 cytokines, including 12 adipokines were assessed using Luminex xMAP technology (multiple ELISA). RESULTS: Serum levels of leptin were significantly decreased during treatment with exemestane (p < 0.001), regardless whether exemestane was given as first or second neoadjuvant therapy. In contrast, letrozole caused a non-significant increase in serum leptin levels in vivo. CONCLUSIONS: Our findings suggest an additional and direct effect of exemestane on CYP-19 (aromatase) synthesis presumably due to effects on the CYP19 promoter use that is not present during therapy with the non-steroidal aromatase inhibitor letrozole. Our findings provide new insights into the influence of clinically important aromatase inhibitors on cytokine levels in vivo that contribute to the understanding of the clinically observed lack of cross-resistance between non-steroidal and steroidal aromatase inhibitors in breast cancer patients. TRIAL REGISTRATION: Registered on March 23rd 2015 in the National trial database of Norway (Registration number: REK-SØ-84-2015).

Thyroidectomy Versus Medical Management for Euthyroid Patients With Hashimoto Disease and Persisting Symptoms: A Randomized Trial.

Background: Hashimoto disease is a chronic autoimmune thyroiditis. Despite adequate hormone substitution, some patients have persistent symptoms that may be the result of immunologic pathophysiology. Objective: To determine whether thyroidectomy improves symptoms in patients with Hashimoto thyroiditis who still have symptoms despite having normal thyroid gland function while receiving medical therapy. Design: Randomized trial. (ClinicalTrials.gov: NCT02319538). Setting: Secondary care hospital in Norway. Patients: 150 patients aged 18 to 79 years with persistent Hashimoto-related symptoms despite euthyroid status while receiving hormone replacement therapy and with serum antithyroid peroxidase (anti-TPO) antibody titers greater than 1000 IU/mL. Intervention: Total thyroidectomy or medical management with hormone substitution to secure euthyroid status in both groups. Measurements: The primary outcome was general health score on the Short Form-36 Health Survey (SF-36) at 18 months. Secondary outcomes were adverse effects of surgery, the other 7 SF-36 subscores, fatigue questionnaire scores, and serum anti-TPO antibody titers at 6, 12, and 18 months. Results: During follow-up, only the surgical group demonstrated improvement: Mean general health score increased from 38 to 64 points, for a between-group difference of 29 points (95% CI, 22 to 35 points) at 18 months. Fatigue score decreased from 23 to 14 points, for a between-group difference of 9.3 points (CI, 7.4 to 11.2 points). Chronic fatigue frequency decreased from 82% to 35%, for a between-group difference of 39 percentage points (CI, 23 to 53 percentage points). Median serum anti-TPO antibody titers decreased from 2232 to 152 IU/mL, for a between-group difference of 1148 IU/mL (CI, 1080 to 1304 IU/mL). In multivariable regression analyses, the adjusted treatment effects remained similar to the unadjusted effects. Limitation: Results are applicable only to a subgroup of patients with Hashimoto disease, and follow-up was limited to 18 months. Conclusion: Total thyroidectomy improved health-related quality of life and fatigue, whereas medical therapy did not. This improvement, along with concomitant elimination of serum anti-TPO antibodies, may elucidate disease mechanisms. Primary Funding Source: Telemark Hospital.

Prophylactic Nipple-Sparing Mastectomy and Direct-to-Implant Reconstruction of the Large and Ptotic Breast: Is Preshaping of the Challenging Breast a Key to Success?

BACKGROUND: Nipple-sparing mastectomy with simultaneous hammock technique direct-to-implant reconstruction is increasingly offered to patients opting for risk-reducing mastectomy. Despite this promising method, patients with macromastia and ptotic breasts remain a challenging group to treat satisfactorily and more often end up undergoing a difficult corrective procedure and experience an unacceptably high rate of failed reconstruction. The authors examined whether targeted preshaping mastopexy/reduction could prepare these patients for a successful nipple-sparing mastectomy/direct-to-implant reconstruction. METHODS: Patients seeking risk-reducing nipple-sparing mastectomy/direct-to-implant reconstruction at the authors' institutions deemed unfit for a one-stage procedure based on their previous experience were offered a targeted two-stage, risk-reducing mastopexy/reduction followed by a delayed secondary nipple-sparing mastectomy and direct-to-implant reconstruction. Patients were followed up at 3 weeks and 6 or 12 months. RESULTS: Forty-four reconstructions were performed in 22 patients aged 43 years (range, 26 to 57 years). All 44 procedures were completed successfully without any failure or nipple-areola complex losses. Patients' median body mass index was 30 kg/m (range, 22 to 44 kg/m). Six patients were smokers and one had hypertension. Two patients underwent reoperation because of hematoma and fat necrosis. CONCLUSIONS: The authors' results demonstrate that a targeted preshaping mastopexy/reduction followed by nipple-sparing mastectomy/direct-to-implant reconstruction can be safely planned in women who opt for a risk-reducing mastectomy and can be performed successfully with a 3- to 4-month time span between operations. On the basis of these results and the superior cosmetic outcome, the two-stage approach has become the authors' standard of care in all such settings. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.