The candidate tumour suppressor gene, ING1, is retained in colorectal carcinomas

ING1 plays a critical role in regulating cell cycle progression and susceptibility to apoptosis. The present study aimed to investigate allelic deletion of, and mutations within, the ING1 gene in colorectal carcinomas. Genomic DNA was extracted from 29 sporadic colorectal carcinomas and samples of adjacent normal mucosa. Losses of heterozygosity of two polymorphic dinucleotide repeat markers close to the ING1 locus at chromosome 13q32-34 were analysed. Single-stranded conformational polymorphisms of polymerase chain reaction amplified regions within the coding sequence of ING1 were examined. Microsatellite instability was noted in 5 (17%) colorectal carcinomas; this confirms selection of a subject sample representative of the population. Neither losses of heterozygosity nor changes in electrophoretic mobility of single-stranded polymerase chain reaction products were detected in any colorectal carcinoma. Thus, in common with tumour suppressor genes such as RB and BRCA2 on chromosome 13q, ING1 appears to be retained intact in colorectal carcinomas.     

Minimally invasive management of chylous fistula after esophagectomy

Chyle leak is an unwelcome complication of esophagectomy that is associated with a high mortality. The diagnosis of this condition may be difficult or delayed and requires a high index of suspicion. Management varies from conservative treatment with drainage, intravenous nutrition, treatment and prevention of septic complications, to re-operation, either by thoracotomy or laparotomy to control the fistula. To reduce the mortality, early surgical intervention is advised and a minimally invasive approach has recently been reported in several cases. From June 2002 through August 2005 we have used video-assisted thoracoscopic surgery to diagnose and treat chyle fistulas from 6/129 (5%) patients who underwent esophagectomy for resectable carcinoma of the esophagus or high-grade dysplasia. The fistula was successfully controlled in 5/6 cases by direct thoracoscopic application of a suture, clips or fibrin glue. One patient required a laparotomy and ligation of the cysterna chyli after thoracoscopy failed to identify an intrathoracic source of the leak. An early minimally invasive approach can be safely and effectively applied to the diagnosis and management of post-esophagectomy chylous fistula in the majority of cases. Open surgery may be appropriate where minimally invasive approaches fail or where the availability of such skills is limited.     

Hepatic and splanchnic nitric oxide activity in patients with cirrhosis

BACKGROUND: In animal models of cirrhosis, altered activity of nitric oxide (NO) has been implicated in the pathogenesis of increased intrahepatic portal vascular resistance and abnormal mesenteric vasodilatation. AIMS: To investigate NO activity in the liver and splanchnic vascular bed of patients with cirrhosis. METHODS: Activity of the calcium dependent constitutive and calcium independent inducible isoforms of NO synthase (cNOS and iNOS, respectively) was assayed biochemically in biopsy specimens of liver and a vascular portion of the greater omentum (representative of mesenteric vasculature) obtained from patients with cirrhosis undergoing liver transplantation (n=14) and non-cirrhotic control patients undergoing liver resection for metastases (n=9). The concentration of NO metabolites (NO2 + NO3) in portal and peripheral venous plasma was measured. RESULTS: The activity of cNOS was lower in cirrhotic compared with non-cirrhotic subjects for both liver and omentum. Hepatic and omental iNOS activities did not differ significantly between the two groups. Portal (NO2 + NO3) was threefold higher in cirrhotic than non-cirrhotic patients, but no differences were observed in systemic venous samples from the two groups. CONCLUSIONS: The activity of cNOS is diminished in the cirrhotic human liver. The resultant decrease in constitutive NO release may promote an increase in the intrahepatic portal vascular resistance. Elevated portal venous (NO2 + NO3) indicates enhanced splanchnic vascular release of NO in cirrhotic patients, but the absence of increased NOS activity in the mesenteric vasculature suggests differential regulation of NO synthesis within the splanchnic vascular bed.     

Persistent acid and bile reflux in asymptomatic patients with Barrett esophagus receiving proton pump inhibitor therapy

HYPOTHESIS: Symptom control does not reflect elimination of abnormal acid reflux or abnormal bile reflux in patients with long-segment Barrett esophagus receiving proton pump inhibitors (PPIs). DESIGN: Prospective survey. SETTING: University hospital. PATIENTS: Thirty-two patients with long-segment Barrett esophagus who were asymptomatic with PPIs. MAIN OUTCOME MEASURES: Twenty-four-hour ambulatory pH and bile reflux monitoring while continuing PPIs. RESULTS: Abnormal acid reflux (pH <4 for 11.9% [interquartile range, 6.8%-19.6%) of 24 hours] persisted in 15 patients (47%) who could not be distinguished from those with normal acid reflux (pH <4 for <4.5% of 24 hours) by any endoscopic, manometric, or therapeutic characteristic. Abnormal bile reflux (absorbance >0.14 for 8.7% [interquartile range, 3.9%-8.7%] of 24 hours) was detected in 11 (48%) of 23 patients, such that both normal bile reflux (absorbance >0.14 for <1.8% of 24 hours) and normal acid reflux were observed in only 8 patients (35%). There was no association between abnormal acid reflux and abnormal bile reflux. CONCLUSIONS: Despite symptom control with PPIs, both acid reflux and bile reflux were controlled in only one third of patients. Posttherapeutic monitoring of acid and bile reflux is recommended in future clinical trials of PPI treatment vs laparoscopic antireflux surgery.     

Hematocrit influences immunoassay performance for the measurement of tacrolimus in whole blood

The comparison between the MEIA II and the EMIT assays for tacrolimus measurement and the interference by the hematocrit were evaluated in 93 samples from routine therapeutic monitoring at tacrolimus concentrations less than 9 microg/L (group A). Additionally, the incidence of false-positive results were determined in samples (n=46) from patients who were not receiving the drug (group B). In group A, no statistical differences were observed between the mean+/-SD values obtained by MEIA II (5.14+/-2.28 microg/L) and EMIT (4.61+/-1.79 microg/L). The correlation coefficient and the regression equation (95% CI) between both assays, were 0.761 and EMIT=1.088 (0.90, 1.35) MEIA II -0.38 (-1.65, -0.46), respectively. When the samples were stratified according to the hematocrit, the median differences between the methods (MEIA II minus EMIT) were as follows: hematocrit35%, 0.25 microg/L (P=0.02). In group B, false-positive results (above the detection limit) were observed in 63.04% of samples analyzed by MEIA II and in 2.17% of samples analyzed by EMIT. The median differences in apparent tacrolimus results were significantly higher in the samples with the lowest hematocrit: 2.2 microg/L, 1.4 microg/L, and 0.0 microg/L in samples with hematocrit35%, respectively. In conclusion, the differences in the tacrolimus results obtained by MEIA and EMIT assays were higher in samples from patients with hematocrit less than 25%, and the MEIA assay demonstrated a high incidence of false-positive results.     

Metastasis to the Adrenal Gland: The Emerging Role of Laparoscopic Surgery

Background:It is unclear whether resection of clinically isolated metastasis to the adrenal gland improves survival. Also, the role of laparoscopic adrenalectomy (LA) for metastasis is controversial. This study aimed to (1) identify patients who are most likely to have prolonged survival after resection of adrenal metastasis and (2) compare oncological outcomes of LA and open adrenalectomy (OA).Methods:A retrospective review of 41 patients, who underwent either OA or LA for metastasis to the adrenal gland during 1997–2002 at a single institution, was conducted.Results:There were 20 women and 21 men, with a median age of 59 years. The most common disease was non-small-cell lung carcinoma (n = 23), followed by renal cell carcinoma (n = 6). With a median follow-up of 16 months, the overall five-year actuarial survival was 29% (median, 28 months). Four patients were actually alive at four years after adrenalectomy. Disease-free interval (DFI) > 6 months was the only significant predictor of improved survival. LA was performed for 11 patients. There was no difference in the incidence of positive resection-margins or survival between patients with OA or LA.Conclusions:Adrenalectomy for metastasis, with intent to prolong survival, should be offered to patients with favorable tumor biology, such as those with significant DFI. The oncological outcome from LA appears similar to that from OA.