Birt‐Hogg‐Dubé syndrome‐associated renal cell carcinoma: Histopathological features and diagnostic conundrum

Birt‐Hogg‐Dubé (BHD) syndrome is associated with the development of hereditary renal cell carcinoma (RCC) and is caused by a germline mutation in the folliculin gene. Most cases of BHD syndrome‐associated RCC (BHD‐RCC) are less aggressive than sporadic clear cell RCC and multifocal. Therefore, it is critical to distinguish BHD‐RCC from its sporadic counterparts to identify and monitor affected families and to preserve renal function for as long as possible. The World Health Organization/International Society of Urological Pathology consensus classification defined distinct entities for certain hereditary RCC; however, BHD‐RCC was not included in this classification. Although the clinical features and molecular mechanisms of BHD‐RCC have been investigated intensively over the last two decades, pathologists and urologists occasionally face difficulties in the diagnosis of BHD‐RCC that require genetic testing. Affected patients usually have miscellaneous benign disorders that often precede renal carcinogenesis. In the present review, we summarize the current understanding of the histopathological features of BHD‐RCC based on our epidemiological studies of Japanese families and a literature review. Pathological diagnostic clues and differential diagnosis of BHD‐RCC from other hereditary RCC are also briefly discussed.     

Associations of soluble intercellular adhesion molecule-1 with carotid atherosclerosis progression

Our previous study demonstrated that plasma concentration of high-sensitivity C-reactive protein (hs-CRP) is a marker of carotid atherosclerosis activity. In this study, we investigated whether plasma levels of soluble cell adhesion molecules have potential value to predict atherosclerosis progression. The study included 192 outpatients 40-82 years of age who were treated for traditional risk factor for cardiovascular disease. Patients underwent repeated ultrasonographic evaluation for 53+/-11 months. Severity of atherosclerosis was evaluated by the maximal intimal-medial thickness (max-IMT), plaque number (PN) and plaque score (PS, the sum of all plaque thicknesses). Blood samples were collected for measurement of hs-CRP, soluble intercellular adhesion molecule (sICAM-1) and sP-selectin at the time of baseline examination. The development of atherosclerosis was estimated by the formula: Deltavalue/year=(last value-baseline value)/number of follow-up years. Multivariate linear regression analysis revealed that sICAM-1 was associated with DeltaIMT/year and DeltaPS/year, which was not the case for sP-selectin. sICAM-1 was closely associated with DeltaIMT/year especially in patients with apparent atheromatous plaque. Our results suggested that levels of sICAM-1 might have predictive value of progression of carotid atherosclerosis independently of traditional risk factors and hs-CRP.     

Fate of full‐house immunofluorescence staining in renal allograft: A case report

Here, we report the case of a patient with renal allograft with full‐house immunofluorescence staining in the zero‐hour biopsy. Full‐house immunofluorescence staining is a well‐known characteristic of lupus nephritis. Previous studies have reported patients with full‐house immunofluorescence staining, but without other symptoms or serological findings; this condition is referred to as full‐house nephropathy. We identified only one case out of 2203 zero‐hour biopsies over 13 years. Zero‐hour biopsy presented no glomerular changes but showed full‐house immunofluorescence staining. Electron microscopy revealed a nonorganized electron‐dense deposit mainly in the mesangial lesion. Systemic lupus erythematosus (SLE)‐associated antibodies were negative, and complement deficiency was not observed in the donor patients. Deposition of immunoglobulin and complement levels markedly decreased within 1–3 years post transplantation. Neither donor nor recipient developed clinical or biological features of SLE; they showed good renal prognosis.     

The topoisomerase II alpha gene status in primary breast cancer is a predictive marker of the response to anthracycline-based neoadjuvant chemotherapy

This study aimed at evaluating the usefulness of topoisomerase II alpha (TOP2A) for predicting the effect of anthracycline-based neoadjuvant chemotherapy in breast cancer. The TOP2A status was examined using fluorescent in situ hybridization (FISH) in 14 pre-chemotherapeutic breast cancer tissues, and was also assessed by immunohistochemistry (IHC) in 14 pairs of pre- and post-chemotherapeutic breast cancer specimens. TOP2A gene aberration by IHC tended to show a correlation with pathological responses but this was not statistically significant (p=0.060). On the other hand, the low TOP2A/CEP17 ratio correlated with good pathological responses (p=0.012). TOP2A overexpression was not significantly associated with response (p=0.580). Our results thus suggest that the TOP2A/CEP17 ratio may be a useful predictor of the effects of anthracycline-based neoadjuvant chemotherapy in breast cancer.     

Efficacy and safety of ixekizumab treatment for Japanese patients with moderate to severe plaque psoriasis,erythrodermic psoriasis and generalized pustular psoriasis: Results from a 52‐week,open‐label,phase 3 study (UNCOVER‐J)

Psoriasis, a chronic, immune‐mediated skin disease characterized by red, scaly plaques, affects approximately 0.3% of the population in Japan. The aim of this open‐label study was to evaluate the long‐term efficacy and safety of ixekizumab, a humanized, anti‐interleukin‐17A monoclonal antibody, in Japanese patients with plaque psoriasis (n = 78, including 11 psoriatic arthritis), erythrodermic psoriasis (n = 8) and generalized pustular psoriasis (n = 5). Ixekizumab was administrated s.c. at baseline (week 0, 160 mg), from weeks 2 to 12 (80 mg every 2 weeks), and from weeks 16 to 52 (80 mg every 4 weeks). At week 52, 92.3% of patients with plaque psoriasis achieved Psoriasis Area and Severity Index (PASI) 75, 80.8% achieved PASI 90, 48.7% achieved PASI 100, and 52.6% had remission of plaques (by static Physician Global Assessment, sPGA [0]). Difficult to treat areas of psoriasis (nail or scalp) also responded to ixekizumab. All patients with psoriatic arthritis who were assessed (5/5) achieved an American College of Rheumatology 20 response. Most patients with erythrodermic psoriasis or generalized pustular psoriasis responded to ixekizumab and the clinical outcome was maintained over 52 weeks (75% and 60% of patients achieved sPGA [0, 1] at week 52, respectively). Mostly mild or moderate treatment‐emergent adverse events were reported by 79 of 91 patients; the most common were nasopharyngitis, eczema, seborrheic dermatitis, urticaria and injection site reactions. In conclusion, 52‐week ixekizumab treatment was efficacious and well tolerated in Japanese patients with plaque psoriasis. Efficacy was also observed in patients with erythrodermic psoriasis, generalized pustular psoriasis and psoriatic arthritis.     

Combination therapy with estramustine and docetaxel for hormone refractory prostate cancer

Six patients with hormone refractory prostate cancer were orally administered 560 mg of Estramustine daily in 2 equally divided doses for four or five days. In addition 70 mg/m2 of Docetaxel was infused through intravenous drip from day 1, decreasing to 40-60 mg/m2 if any side effects such as bone marrow depression were observed. One cycle was three weeks in hospital and one month after discharge. Patients were treated until progression or the development of treatment-limiting toxicity. In five of the six patients (83.3%), serum prostate specific antigen (PSA) was decreased by more than 50%. Currently, this therapy is ongoing in four outpatients. A side effect of leucopenia (grade 2 or 3) was observed in all patients. Granulocyte-colony stimulating factor (G-CSF) formulation was given as treatment. One case was withdrawn due to loss of appetite after one cycle. This therapy is considered to be effective against hormone refractory prostate cancer. However, further examination is needed about dosage and dosing regimen of Estramustine and Docetaxel.     

The role of magnetic resonance cholangiopancreatography (MRCP) after resection of the pancreas

Magnetic resonance cholangiopancreatography (MRCP) was performed in 35 patients to evaluate the feasibility of its use as a postsurgical imaging technique after resection of the pancreas. The surgical procedures performed were: pancreatoduodenectomy in 22 patients, segmental pancreatectomy in 1, distal pancreatectomy in 7, and pyroluspreserving pancreatoduodenectomy in 5. The pancreatic duct was shown in its entirety in 24 of the 35 patients (68.6%) and was partially visualized in 8 patients (22.9%), but the intrahepatic and extrahepatic bile ducts were visualized completely in all patients. Furthermore, MRCP was able to demonstrate lesions in 3 of 6 patients who had shown clinical evidence of recurrence. The visualization of the pancreatic and bile duct system was satisfactory despite anatomical changes brought about by resection of the pancreas. Thus, we conclude that MRCP is an appropriate follow-up screening test for patients with suspected abnormalities of the biliary and pancreatic duct system.     

Microvascular decompression for refractory neurogenic hypertension: case report

It is noted that the increased central sympathetic nerve activity caused by neurovascular compression at the rostral ventrolateral medulla (RVLM) is closely related to the genesis of neurogenic hypertension. The authors present the case of a 49-year-old female with refractory neurogenic hypertension to be uncontrolled even with all kinds of oral antihypertensive medications. After approval by the Ethical Committee in a hospital, she had received an intravenous introduction of calcium antagonist and beta-blocker at home for three years. The subsequent examination detail showed increased sympathetic nerve activity and compression of the left vertebral artery (VA) at the left RVLM on magnetic resonance imaging, and therefore microvascular decompression (MVD) underwent through a left lateral suboccipital approach. The left VA was seen indenting the left RVLM. To ensure the complete decompression, the distal part of VA was moved away from RVLM to fix to the dura of the petrous bone with a glue. Her blood pressure became normalized afterwards without drugs and remained normotensive for 23 months after MVD. In order to decide the surgical indication for pure neurogenic hypertension due to neurovascular compression, a strict differential diagnosis is necessary.