Concomitant CIS on TURBT does not impact oncological outcomes in patients treated with neoadjuvant or induction chemotherapy followed by radical cystectomy.

BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle invasive bladder cancer improves all-cause and cancer specific survival. We aimed to evaluate whether the detection of carcinoma in situ (CIS) at the time of initial transurethral resection of bladder tumor (TURBT) has an oncological impact on the response to NAC prior to radical cystectomy. PATIENTS AND METHODS: Patients were identified retrospectively from 19 centers who received at least three cycles of NAC or induction chemotherapy for cT2-T4aN0-3M0 urothelial carcinoma of the bladder followed by radical cystectomy between 2000 and 2013. The primary and secondary outcomes were pathological response and overall survival, respectively. Multivariable analysis was performed to determine the independent predictive value of CIS on these outcomes. RESULTS: Of 1213 patients included in the analysis, 21.8% had concomitant CIS. Baseline clinical and pathologic characteristics of the 'CIS' versus 'no-CIS' groups were similar. The pathological response did not differ between the two arms when response was defined as pT0N0 (17.9% with CIS vs 21.9% without CIS; p = 0.16) which may indicate that patients with CIS may be less sensitive to NAC or ≤ pT1N0 (42.8% with CIS vs 37.8% without CIS; p = 0.15). On Cox regression model for overall survival for the cN0 cohort, the presence of CIS was not associated with survival (HR 0.86 (95% CI 0.63-1.18; p = 0.35). The presence of LVI (HR 1.41, 95% CI 1.01-1.96; p = 0.04), hydronephrosis (HR 1.63, 95% CI 1.23-2.16; p = 0.001) and use of chemotherapy other than ddMVAC (HR 0.57, 95% CI 0.34-0.94; p = 0.03) were associated with shorter overall survival. For the whole cohort, the presence of CIS was also not associated with survival (HR 1.05 (95% CI 0.82-1.35; p = 0.70). CONCLUSION: In this multicenter, real-world cohort, CIS status at TURBT did not affect pathologic response to neoadjuvant or induction chemotherapy. This study is limited by its retrospective nature as well as variability in chemotherapy regimens and surveillance regimens.

Biogenesis of L-glyceric aciduria, oxalosis and renal injury in rats simulating type II primary hyperoxaluria.

Tracer experiments in rats mimicking type II primary hyperoxaluria, with an expanded intracellular pool of hydroxypyruvate, showed that the excess formation of oxalate did not originate from its immediate precursor glyoxylate. In these animals, the hepatic and kidney activities of oxalate synthesising enzymes such as lactate dehydrogenase and glycolate oxidase were normal, but tissue lipid peroxidation was significantly higher. In vitro experiments established that in a mild alkaline solution, hydroxypyruvate underwent auto-oxidation to form oxalate and H2O2 and also inhibited lactate dehydrogenase and glycolate oxidase from oxidising glyoxylate to oxalate. On the basis of the experimental evidence, we suggest that in type II primary hyperoxaluria, the accumulating hydroxypyruvate could reduce the intracellular pool of glyoxylate and on ageing, give rise to excess oxalate and H2O2, to cause oxalosis in the former and free radical mediated-cell injuries in the latter.

'Cold hand, ischemic heart': treatment by stenting of the left subclavian artery.

A 59-year-old man presented with worsening angina and a cold, painful left hand, eight years after coronary artery bypass surgery. Coronary angiography showed extensive coronary atherosclerosis with blocked vein grafts to his left circumflex and right coronary arteries. There was a severe narrowing in the left subclavian artery before the origin of the left internal mammary artery (LIMA) which appeared patent. PTCA and stent implantation to the left subclavian artery stenosis restored normal flow to the left hand and the LIMA with abolition of his ischemic hand symptoms and marked improvement of his angina.

Cutaneous vasculitis secondary to ramipril.

A 61-year-old patient who had been treated with lisinopril in the past without any problems was commenced on ramipril for left ventricular dysfunction. He developed a painful symmetrical purpuric eruption over both feet after three days. A full vasculitis screen was negative. Ramipril was stopped and he required a course of steroids after which the rash improved slowly. The ACE inhibitors can cause various skin side effects; however, it rarely causes cutaneous vasculitis. Ramipril-induced cutaneous vasculitis is particularly rare and our case was atypical because the patient had tolerated lisinopril before. Previous successful treatment with one ACE inhibitor does not rule out the vasculitis caused by the drug from the same group. Here we report ramipril-induced cutaneous vasculitis in a patient who required steroid therapy to control it.

Malignant vasovagal syndrome in two patients with Wolff-Parkinson-White syndrome.

The presence of Wolff-Parkinson-White (WPW) syndrome in patients presenting with syncope suggests that tachyarrhythmia may be the cause. However, the symptoms require careful evaluation. Two young patients presented with syncope and were found to have WPW syndrome on their ECG. In both patients symptoms were suggestive of vasovagal syncope. During tilt testing, both the patients developed their typical symptoms with a fall in blood pressure and heart rate confirming the diagnosis of malignant vasovagal syndrome.

Rare case of heart failure caused by compression of the left atrium by a thoracic aortic aneurysm.

A 61 year old patient was found to have an aneurysm extending from the aortic root to the suprarenal region. He underwent first stage surgery with aortic root and arch replacement, prosthetic aortic valve replacement, and coronary artery bypass grafting. Four weeks later, he presented with breathlessness and signs of heart failure and pleural effusion. Computed tomography showed that the left atrium was compressed between the aortic aneurysm posteriorly and the left ventricle and sternum anteriorly. Obstruction of the superior vena cava, bronchus, oesophagus, and rarely right atrium by an aortic aneurysm has been described before but presentation with left atrial compression has not been reported.