Niall Mulligan

Plaque Inflammation and Unstable Morphology Are Associated With Early Stroke Recurrence in Symptomatic Carotid Stenosis

Background and Purpose— Although symptomatic carotid stenosis is associated with 3-fold increased risk of early stroke recurrence, the pathophysiologic mechanisms of high early stroke risk have not been established. We aimed to investigate the relationship between early stroke recurrence after initial symptoms and histological features of plaque inflammation and instability in resected carotid plaque. Methods— Carotid endarterectomy tissue from consecutive patients with ipsilateral stenosis ≥50% and recent symptoms were analyzed using a validated histopathologic algorithm (Oxford Plaque Study [OPS] system). Nonprocedural stroke recurrence before carotid endarterectomy was ascertained at 7, 28, and 90 days after initial symptoms. Results— Among 44 patients meeting eligibility criteria, 27.3% (12/44) had stroke recurrence after initial stroke/transient ischemic attack but before carotid endarterectomy. Compared with patients without recurrence, stroke recurrence was associated with dense macrophage infiltration (OPS grade ≥3; 91.7% versus 37.5%; P=0.002), extensive (>25%) fibrous cap disruption (90.9% versus 37%; P=0.004), neovascularization (OPS grade ≥2; 83.3% versus 43.8%; P=0.04), and low plaque fibrous content (OPS grade <2; 50% versus 6.3%; P=0.003). Early recurrence rates were 82.3% (confidence interval, 49.2%–98.8%) in patients with extensive plaque macrophage infiltration (OPS grade ≥3) compared with 22.2% (confidence interval, 3.5%–83.4%) in those with OPS grade <3 (log-rank P=0.009). On multivariable Cox regression, including OPS macrophage grade (≥3 or <3), age, and severity of stenosis (50%–69% or ≥70%), plaque inflammation was the only variable independently predicting stroke recurrence (adjusted hazard ratio, 9; confidence interval, 1.1–70.6; P=0.04). Conclusions— Plaque inflammation and other vulnerability features were associated with highest risk of stroke recurrence and may represent therapeutic targets for future stroke prevention trials.

Effects of the dual 5 α‐reductase inhibitor dutasteride on apoptosis in primary cultures of prostate cancer epithelial cells and cell lines

The profound reduction in serum dihydrotestosterone (DHT) observed with the dual 5 α‐reductase inhibitor (5ARI) dutasteride makes it an attractive agent for prostate cancer therapy. The objective of the current study was to determine whether dutasteride would induce apoptosis in a range of prostate epithelial cell lines and primary cultures.

Small-Cell Carcinoma of the Cervix at 23 Weeks Gestation

A 26-year-old primigravida with no significant past medical history presented at 23 weeks gestation with a history of a watery vaginal discharge of 1 month’s duration. Speculum examination revealed a polypoid mass in the cervix. Magnetic resonance imaging (MRI) of the lesion showed a large, exophytic, macrolobulated mass surrounding the cervix and distending the vagina measuring 9.4 4.6 9 cm. It did not appear to invade the adjacent fat or vaginal wall (Fig 1). MRI of the abdomen showed a normal liver and no evidence of retroperitoneal or paraortic lymphadenopathy. Low-dose computed tomography of the thorax showed normal lung fields and mediastinum, and no sclerotic or lytic bony lesions. After a biopsy, the mass was shown to consist of sheets of small, densely packed cells, with hyperchromatic nuclei and a high nuclear-to-cytoplasmic ratio consistent with a small-cell carcinoma (Fig 2). Neuroendocrine origin was confirmed with staining for synaptophysin (Fig 3) and chromogranin (Fig 4). A diagnosis of small-cell carcinoma of the cervix in association with pregnancy was made. As the patient wished to maintain her pregnancy and was at 23 weeks gestation, a decision was made to proceed with neoadjuvant chemotherapy with adriamycin (60 mg/m) and cyclophosphamide (600 mg/m) intravenously every 21 days, which was given for three cycles without adverse effects. Repeat MRI showed a significant decrease in tumor volume by 85% with a maximum tumor diameter of 2.8 cm (Fig 5). This was confirmed on clinical examination. A fourth cycle of chemotherapy was deferred due to the onset of mild intrauterine growth retardation in the fetus. The patient underwent delivery of a healthy 6-pound baby boy by elective Caesarian section at 35 weeks gestation. After delivery, the patient subsequently underwent four cycles of platinum and etoposide– based chemotherapy with good clinical and radiologic response in the pelvis and showing no evidence of metastatic spread. She is currently undergoing definitive local treatment with pelvic radiation.

Giant right atrial myxoma: characterization with cardiac magnetic resonance imaging☆

A 53-year-old woman presented to the emergency department with a 2-week history of dyspnoea and chest pain. Computed tomography pulmonary angiography was performed to exclude acute pulmonary embolism (PE). This demonstrated a large right atrial mass and no evidence of PE. Transthoracic echocardiography followed by cardiac magnetic resonance imaging confirmed a mobile right atrial mass. Surgical resection was then performed confirming a giant right atrial myxoma. We describe the typical clinical, radiologic, and pathologic features of right atrial myxoma.

Screening for mismatch repair deficiency in colorectal cancer: data from three academic medical centers

Reflex immunohistochemistry (rIHC) for mismatch repair (MMR) protein expression can be used as a screening tool to detect Lynch Syndrome (LS). Increasingly the mismatch repair‐deficient (dMMR) phenotype has therapeutic implications. We investigated the pattern and consequence of testing for dMMR in three Irish Cancer Centres (CCs). CRC databases were analyzed from January 2005–December 2013. CC1 performs IHC upon physician request, CC2 implemented rIHC in November 2008, and CC3 has been performing rIHC since 2004. The number of eligible patients referred to clinical genetic services (CGS), and the number of LS patients per center was determined. 3906 patients were included over a 9‐year period. dMMR CRCs were found in 32/153 (21%) of patients at CC1 and 55/536 (10%) at CC2, accounting for 3% and 5% of the CRC population, respectively. At CC3, 182/1737 patients (10%) had dMMR CRCs (P < 0.001). Additional testing for the BRAF V600E mutation, was performed in 49 patients at CC3 prior to CGS referral, of which 29 were positive and considered sporadic CRC. Referrals to CGS were made in 66%, 33%, and 30% of eligible patients at CC1, CC2, and CC3, respectively. LS accounted for CRC in eight patients (0.8%) at CC1, eight patients (0.7%) at CC2, and 20 patients (1.2%) at CC3. Cascade testing of patients with dMMR CRC was not completed in 56%. Universal screening increases the detection of dMMR tumors and LS kindreds. Successful implementation of this approach requires adequate resources for appropriate downstream management of these patients.

Prognostic significance of neuroepithelial transforming gene 1 in adenocarcinoma of the oesophagogastric junction

Neuroepithelial transforming gene 1 (NET1) mediates tumour invasion and metastasis in a number of cancers, including gastric adenocarcinoma. It is an indicator of poor prognosis in breast cancer and glioma. This study examined NET1 expression and its prognostic significance in patients with adenocarcinoma of the oesophagogastric junction (AOG).

Blistering psoriatic plaques during narrowband UVB phototherapy.

To the Editor, Narrowband UVB or TL-01 phototherapy is an effective treatment for psoriasis (1). The emitted wavelength range (311–313 nm) is optimal for antipsoriatic activity (2). A rare side effect of TL-01 phototherapy is the development of blisters on psoriatic lesions, during a treatment course. Herein, we report four such cases which were identified in our institution over a 5-month period and review all reported cases in an effort to better understand the pathogenesis of this phenomenon.

Subacute cutaneous lupus erythematosus: a paraneoplastic phenomenon in oropharyngeal squamous cell carcinoma

itching sensation without pain or tenderness (Fig. 1a,b). The patient was worried about the cosmetic appearance of her forehead. We diagnosed the patient as having a local injectionsite reaction to the filler, and we decided on prompt treatment using combination LED (Smartlux FX ; Medmix, Seoul, Korea), because she did not want to be treated with anti-inflammatory agents such as topical steroids. During treatment, the LED device delivered 635 and 830 nm light with a concomitant power density of 75 mW/cm. The recommended distance between the lesion and LED device was 150–200 mm. The patient was treated for 15 min with continuous (not pulsed) light every day for 7 days. Both the patient and operator wore safety goggles during treatment to protect their eyes. No pain or discomfort was reported by the patient during the treatment period. The inflammatory reaction gradually disappeared over the next 7 days (Fig. 1c,d). Low-intensity light therapy using light in the far-red to near-infrared region of the spectrum (630–1000 nm) can modulate numerous cellular functions. Several recent studies have demonstrated the anti-inflammatory effects of LED therapy. A study conducted with human gingival fibroblasts treated with arachidonic acid showed that 635 nm irradiation inhibits prostaglandin 2 synthesis in a manner similar to inhibition by cyclooxygenase inhibitors. Another study demonstrated that LED therapy has beneficial effects on the prevention of postinflammatory hyperpigmentation and scarring. A further recent study found that LED inhibits several inflammatory cells, improves skin barrier function, and may potentially contribute to the treatment of patients with atopic dermatitis. Furthermore, at the cellular level, LED can upregulate procollagen and collagen synthesis in human fibroblast cultures. Irradiation at 830 nm accelerates fibroblast transformation, downregulation of matrix metalloproteinases and mast cell degranulation. In addition, the chemotaxis and phagocytic activity of leucocytes and macrophages was shown to be enhanced with cellular stimulation at this wavelength. The Smartlux FX is a new LED device, which has 1200 output lamps (635 nm red: 700; 830 nm infrared: 500) and an dual-wavelength output light that produces concomitant red light at 635 nm (58%)and infrared light at 830 nm (42%). This dual-wavelength effect may be the reason why more rapid wound healing and decreased inflammation occur without side effects and patient discomfort. Although we could not histologically confirm inflammatory reaction of the injection area as the patient refused permission for a biopsy, we believe the present study supports the clinical application of LED (635 and 830 nm) as a new treatment option for local injection site reactions after HA filler. We consider that it is likely this LED technique could also be applied for various inflammatory conditions with excellent clearance in a safe manner with high patient compliance.

Two cases of dermatoses koebnerizing within fields of previous radiotherapy.

We describe two patients with newly diagnosed dermatoses localizing to the radiotherapy field following treatment for breast cancer. Patient 1 was a 53‐year‐old woman who developed bullous morphoea on her left breast two years after radiotherapy. Patient 2 was a 43‐year‐old woman who developed urticaria pigmentosa on her right breast eight months after radiotherapy and similar lesions gradually developed beyond the radiotherapy field. Both patients experienced a significant delay in diagnosis due to diagnostic confusion and concern over breast cancer recurrence. Irradiated skin demonstrates gradual and sustained alterations in fibrosis due to the production of long‐lived cytokines and chemokines. These changes can induce a koebnerizing response in conditions such as morphoea and urticaria pigmentosa. We explore the mechanisms behind radiotherapy‐induced skin changes, and highlight the potential for radiotherapy to exacerbate or unmask underlying dermatoses and systemic disease in the months and years following treatment.

Extensive warfarin-induced skin necrosis successfully treated with negative pressure wound therapy.

A 55-year-old woman presented with an extensive warfarin-induced skin necrosis while an inpatient for treatment of a pulmonary embolism and thromboembolic stroke. She had a background of diabetes mellitus, hypertension and dyslipidaemia. Her warfarin was stopped and she was anticoagulated with low-molecular weight heparin. The wound was successfully treated with a combination of antibiotic, debridement and negative pressure wound therapy.