Pre-operative staging of rectal cancer: MRI or ultrasound?

Optimal management of rectal cancer depends on obtaining accurate and detailed staging information at the time of diagnosis. The majority of this comes from radiological staging investigations such as computed tomography (CT), magnetic resonance imaging (MRI) and endoanal ultrasound (EAUS). Whilst there is little debate on the use of CT to assess distant spread of disease, there is still variation in the use of MRI or EAUS in the local staging of rectal cancer. Both techniques have their roles but MRI is better able to visualise the entire rectum and mesorectum as well as accurately identify the circumferential resection (CRM) margin in relation to the tumour edge. Breach of the CRM is one of the most important predictors of local recurrence and knowledge of its relationship to the tumour determines initial management. MRI has additional advantages in being able to identify other poor prognostic factors such as extramural venous invasion (EMVI) and mucin deposition, which further influence oncological treatment. It also provides the surgeon with accurate information on the relationship of the tumour to surrounding structures and the sphincter complex which is important for surgical planning. This review highlights the important determinants of local staging in rectal cancer and presents the evidence to answer the question as to which is a better imaging modality—MRI or EAUS?     

A Study of Angiotensin II Pressor Response throughout Primigravid Pregnancy

The present study was designed to ascertain sequentially the pressor response to angiotensin II in young primigravid patients throughout pregnancy in order a) to define when in pregnancy resistance to the pressor effects of angiotensin II develops; b) to define the physiologic sequence of events leading to this resistance; and c) to ascertain whether sensitivity to infused angiotensin II could be detected before the onset of clinical signs of pregnancy-induced hypertension.With this prospective approach, two separate groups of patients were defined. The first group of patients remained normal throughout pregnancy. The second group consisted of those patients who, while clinically normotensive during the initial phase of the study, ultimately developed hypertension of pregnancy.192 patients were studied; of these, 120 patients remained normotensive and 72 developed pregnancy-induced hypertension. In both groups, vascular resistance to infused angiotensin II (more than 8 ng/kg/min required to elicit a pressor response of 20 mm Hg in diastolic pressure) was demonstrated as early as the 10th wk of pregnancy. In the group that remained normotensive, maximum mean vascular resistance occurred at 18-30 wk of pregnancy, (mean pressor dose required being 13.5 to 14.9 ng/kg/min). In those subjects who developed pregnancy-induced hypertension, the mean maximum dose required was 12.9 ng/kg/min, which was observed at the 18th wk of pregnancy. By the 22nd wk there was a clear separation of the two groups, with the mean dose requirement of the subjects destined to develop hypertension being progressively less than that of those who remained normal. The difference between the two groups became significant (P < 0.01) by 23-26 wk of pregnancy.Among patients requiring more than 8 ng/kg/min on one or more tests done between wk 28-32, 91% remained normotensive. Conversely, during the same time period among patients requiring less than 8 ng/kg/min, on at least one occasion, 90% developed pregnancy-induced hypertension.     

The EMPOWER Study: Randomized, Prospective, Double-Blind, Multicenter Trial of Vagal Blockade to Induce Weight Loss in Morbid Obesity

Background

Intermittent, reversible intraabdominal vagal blockade (VBLOC? Therapy) demonstrated clinically important weight loss in feasibility trials. EMPOWER, a randomized, double-blind, prospective, controlled trial was conducted in USA and Australia.

Methods

Five hundred three subjects were enrolled at 15 centers. After informed consent, 294 subjects were implanted with the vagal blocking system and randomized to the treated (n?=?192) or control (n?=?102) group. Main outcome measures were percent excess weight loss (percent EWL) at 12?months and serious adverse events. Subjects controlled duration of therapy using an external power source; therapy involved a programmed algorithm of electrical energy delivered to the subdiaphragmatic vagal nerves to inhibit afferent/efferent vagal transmission. Devices in both groups performed regular, low-energy safety checks. Data are mean ± SEM.

Results

Study subjects consisted of 90?% females, body mass index of 41?±?1?kg/m², and age of 46?±?1?years. Device-related complications occurred in 3?% of subjects. There was no mortality. 12-month percent EWL was 17?±?2?% for the treated and 16?±?2?% for the control group. Weight loss was related linearly to hours of device use; treated and controls with ??12?h/day use achieved 30?±?4 and 22?±?8?% EWL, respectively.

Conclusions

VBLOC? therapy to treat morbid obesity was safe, but weight loss was not greater in treated compared to controls; clinically important weight loss, however, was related to hours of device use. Post-study analysis suggested that the system electrical safety checks (low charge delivered via the system for electrical impedance, safety, and diagnostic checks) may have contributed to weight loss in the control group.     

Post Roux-en-Y Gastric Bypass Biliary Dilation: Natural Process or Significant Entity?

Background

Changes in the biliary system after gastric bypass are not well defined. Dilation may be normal or due to biliary tract pathology. The purpose of this study is to review patients who underwent imaging of their biliary system both before and after Roux-en-Y gastric bypass in an effort to elucidate the effect this operation has on hepatic duct diameter.

Methods

Patients with imaging both before and at least 3?months after gastric bypass were analyzed. Hepatic duct was measured at the level of the porta hepatis to determine interval changes.

Results

Thirty-three patients had postoperative imaging at least 3?months following gastric bypass. Mean hepatic duct diameter was 5.2?±?2 and 7.1?±?2.6?mm preoperatively and postoperatively, respectively (p?<?0.01). Patients with prior cholecystectomy had hepatic duct diameters of 7.9?±?1.3 and 9.5?±?3.5?mm preoperatively and postoperatively, respectively (p?=?0.3). Patients who had not previously undergone cholecystectomy had hepatic duct diameters of 4.3?±?1.1 and 6.4?±?1.8?mm preoperatively and postoperatively, respectively (p?<?0.01).

Conclusions

Hepatic duct diameter increases after Roux-en-Y gastric bypass. A better understanding of this phenomenon may limit the need for further work-up in patients with incidentally detected biliary dilation.     

EZH2 expression in gliomas: Correlation with CDKN2A gene deletion/ p16 loss and MIB‐1 proliferation index

Enhancer of zeste homolog 2 (EZH2) mediated down‐regulation of CDKN2A/p16 has been observed in cell lines as well as in a few carcinomas. However, there is no study correlating EZH2 expression with CDKN2A/p16 status in gliomas. Hence, the present study was conducted to evaluate EZH2 expression in astrocytic and oligodendroglial tumors and correlate with CDKN2A/p16 status as well as MIB‐1 labeling index (LI). Gliomas of all grades (n = 118) were studied using immunohistochemistry to assess EZH2, p16 and MIB‐1 LI and fluorescence in situ hybrization to evaluate CDKN2A gene status. EZH2 expression and CDKN2A homozygous deletion (HD) were both significantly more frequent in high‐grade gliomas (HGG). Further, strong EZH2 expression (LI ≥ 25%) was significantly more common in HGGs without CDKN2A HD (48.7%; 19/39) as compared to cases with deletion (15.8%; 3/19). Loss of p16 expression was noted in 100% and 51.3% of CDKN2A deleted and non‐deleted tumors, respectively. Notably, 80% (16/20) of the CDKN2A non‐deleted HGGs with p16 loss had strong EZH2 expression, in contrast to only 15.8% (3/19) in the deleted group. Loss of p16 expression significantly correlated with MIB‐1 LI, irrespective of EZH2 status. Thus, this study shows that EZH2 expression correlates with tumor grade in both astrocytic and oligodendroglial tumors and hence can be used as a diagnostic marker to differentiate between low and HGGs. Further, this is the first report demonstrating an inverse correlation of strong EZH2 expression with CDKN2A HD in HGGs. Loss of p16 protein expression is mostly attributable to CDKN2A HD and correlates significantly with MIB‐1 LI. Notably, our study for the first time suggests a possible epigenetic mechanism of p16 loss in CDKN2A non‐deleted HGGs mediated by strong EZH2 expression. A hypothetical model for control of proliferative activity in low versus HGGs is therefore proposed.