Clinical impact of right accessory hepatic artery injury in deceased donor livers.

BACKGROUND: Right accessory hepatic artery (RAHA) injury at retrieval is a rare complication of deceased liver procurement. Arterial reconstruction is often required under these circumstances which could potentially increase the risk of hepatic artery thrombosis (HAT). The aim of this study is to investigate whether RAHA injury affects the incidence of HAT, early biliary complications, or 3-month graft and patient survival rates. METHODS: All adult liver transplants performed between 1994 and February 2007 at Addenbrooke's Hospital, Cambridge, UK were considered for inclusion in the study. Grafts were divided into three groups depending on the presence of RAHA and injury (Group 1: normal anatomy and single hepatic artery anastomosis; Group 2: RAHA requiring reconstruction; Group 3: RAHA injury requiring reconstruction). RESULTS: Eight hundred and forty-four liver transplants were included in the study (Group 1: 654 grafts; Group 2: 63 grafts; Group 3: 14 grafts). The incidence of HAT (Group 1, 2.9%; Group 2, 6.4%; Group 3, 14.3%) was significantly different between the three groups (P = 0.01); biliary complications at 3 months (Group 1, 7.1%; Group 2, 11.1%; Group 3, 7.1%) were not significantly different. Graft and patient survival at 3 months were significantly worse in Group 3 when compared with Group 2 (61.5 vs. 88.3%, P = 0.01; 81.8 vs. 98.2%, P = 0.02). CONCLUSION: This is the first study analysing the clinical impact of RAHA injury during liver procurement. We conclude that the use of liver grafts with RAHA injury does result in a higher HAT rate and is also associated with lower graft and patient survival rates at 3 months.

The relationship between gene-specific DNA methylation in leukocytes and normal colorectal mucosa in subjects with and without colorectal tumors.

CpG island methylation in the promoter regions of tumor suppressor genes has been shown to occur in normal colonic tissue and can distinguish between subjects with and without colorectal neoplasms. It is unclear whether this relationship exists in other tissues such as blood. We report the relationship between estrogen receptor gene (estrogen receptor alpha) methylation in leukocyte and normal colonic tissue DNA in subjects with and without colorectal neoplasia. DNA was extracted from frozen stored whole blood samples of 27 subjects with cancer, 30 with adenoma, 16 with hyperplastic polyps, and 57 disease-free subjects. DNA methylation in seven CpG sites close to the transcription start of estrogen receptor alpha was quantitated using pyrosequencing and expressed as a methylation index (average methylation across all CpG sites analyzed). Estrogen receptor alpha methylation in leukocyte DNA was compared with estrogen receptor alpha methylation in normal colonic mucosa DNA that had been previously determined in the same subjects. Estrogen receptor alpha was partially methylated (median, 4.3%; range, 0.0-12.6%) in leukocyte DNA in all subjects, with no significant difference between disease groups (P>0.05). Estrogen receptor alpha methylation in leukocytes was 60% lower than estrogen receptor alpha methylation in normal colonic tissue (P<0.001). Estrogen receptor alpha methylation in colonic tissue (P<0.001) and smoking (P=0.016) were determinants of estrogen receptor alpha methylation in leukocytes, independent of age, body mass index, gender, and disease status. In conclusion, there was a positive relationship between estrogen receptor alpha methylation in leukocytes and colonic tissue in subjects with and without colorectal tumors. However, unlike in colonic tissue, estrogen receptor alpha methylation in leukocytes was unable to distinguish between disease groups.

Strategy to reduce the risk of positive pancreatic resection margin at pancreatico-duodenectomy.

BACKGROUND: The accuracy of histological assessment of frozen section (FS) of the pancreatic resection margin (PRM) at pancreatico-duodenectomy can be improved by concurrent FS examination of a sample of the suspected pancreatic lesion. METHODS: A prospective trial was conducted using archived material. FS of all the PRM and suspected pancreatic lesion of 12 patients randomly selected from a historical group who underwent pancreatico-duodenectomy for suspected malignancy were examined by five histopathologists. They were asked to examine the PRM alone and alongside the suspected lesion. The diagnosis of the PRM was 'benign', 'malignant' or 'defer to paraffin section'. All the histopathologists were blinded to the paraffin section diagnosis. RESULTS: The main outcome measures were sensitivity, specificity and the incidence of deferring to paraffin section. In this respect examination of the PRM alone had a sensitivity of 70% and a specificity of 87.5%. Concurrent FS examination of PRM with the pancreatic lesion increased the sensitivity to 90% and the specificity to 92.5%. The incidence of deferring to paraffin section was reduced from 17 to 7% (P = 0.03). CONCLUSION: This policy is recommended because it improves the diagnostic accuracy of FS evaluation of the PRM resulting in a reduction of residual pancreatic cancer at the pancreatic transection line.

Methylation of estrogen receptor alpha and mutL homolog 1 in normal colonic mucosa: association with folate and vitamin B-12 status in subjects with and without colorectal neoplasia.

BACKGROUND: Greater promoter methylation in some tumor-suppressor genes underlies most sporadic colorectal cancers and increases with age in the colon. OBJECTIVE: We tested the hypothesis that biomarkers of folate and vitamin B-12 status are associated with estrogen receptor alpha (ERalpha) and mutL homolog 1 (MLH1) promoter methylation in subjects with and without neoplasia. DESIGN: Biopsies of normal-appearing colorectal mucosa from 156 subjects with and without colorectal neoplasia (disease free, n = 76; cancer, n = 28; adenoma, n = 35; hyperplastic polyps, n = 17) were obtained at colonoscopy and used to evaluate methylation in 7 CpG sites in the ERalpha promoter and 13 CpG sites in the MLH1 promoter. Blood samples were obtained for the measurement of serum and red cell folate, serum vitamin B-12, and plasma homocysteine concentrations. Methylation indexes were generated to reflect an average methylation value across all CpG dinucleotides in both ERalpha and MLH1. RESULTS: The methylation indexes for ERalpha and MLH1 generally were significantly (P < 0.05) higher in subjects with neoplasia than in disease-free subjects. The ERalpha methylation index correlated negatively with serum vitamin B-12 (r = -0.239, P = 0.003) and positively with plasma homocysteine (r = 0.188, P = 0.021). Disease status (P < 0.005), age (P < 0.001), and serum vitamin B-12 concentrations (P = 0.006) were independent determinants of ERalpha promoter methylation. Serum and red cell folate concentrations had no influence on ERalpha promoter methylation. CONCLUSION: Serum vitamin B-12 but not folate status may be associated with ERalpha promoter methylation in normal-appearing colorectal mucosa.

Surgical dexterity after a 'night out on the town'.

BACKGROUND: This study examines the effect of alcohol intake on surgical dexterity immediately after and the morning after alcohol intake and minimal sleep deprivation by simulating a typical night out on the town. METHODS: Five surgeons (all men, aged 31-40 years) were trained on a laparoscopic surgical simulator (minimally invasive surgical trainer-virtual reality) to reach a desired standard of performance. Three experimental settings were used: (i) a control night with no alcohol and full night's sleep; (ii) a sham night out (sleep deprived) without alcohol; and (iii) a night out with alcohol ad libitum. The parameters recorded were the average time taken to carry out a task, error rate, average diathermy time and diathermy (damage) time to main object. Comparisons between baseline readings, those in the middle of the night and those of the following morning were made by applying ANOVA methods after logarithmic transformation of the data. RESULTS: The candidates consumed, on average, 10.33 units (range, 6-15 units) of alcohol and had 0.86% (range, 0.71-1.1%) of breath alcohol levels and an average of 3.75 h (range, 3-5 h) of sleep after a typical night out. The morning-after breath alcohol levels were 0%. There was significant deterioration in performance, as measured by all indicators, immediately after alcohol consumption. The adverse effects on time taken to complete the task and total diathermy time were still apparent the morning after. The sham night out appeared to affect only 'time parameters'. No significant changes in performance were seen in the control setting. CONCLUSION: Both alcohol consumption and sleep deprivation adversely affect the ability to carry out surgical procedures. Our simulation study suggests that the adverse effects of alcohol intake persist the following morning.

Transgastric surgery for posterior juxtacardial ulcers: a minimal and safe approach.

HYPOTHESIS: A transgastric approach may be used succesfully for the treatment of posterior juxtacardial ulcers presenting with massive bleeding. METHODS: Eight patients were admitted during a 6-year period with acute massive upper gastrointestinal bleeding caused by posterior juxtacardial ulcers. All patients had signs of profound hypovolemic shock, and initial endoscopic control was achieved in 3 patients. They all underwent surgery after endoscopy. At operation, the ulcer was approached through an anteromedial gastrostomy and hemostasis was achieved by transfixing stitches. Ulcers were excised whenever possible, or excluded if adherent posteriorly. Four-quadrant biopsy was taken for frozen section to exclude malignancy. Both anterior and posterior gastric walls were then closed with nonabsorbable suture material. RESULTS: There were 6 men and 2 women with a mean age of 73 years. Hemoglobin levels ranged from 5.2 to 8.0 g/dL. Five patients underwent emergency surgery within 28 hours of admission. The diameter of the ulcers ranged from 2 to 5 cm. Ulcerectomy was performed in 6 cases. In the remaining 2 patients, the crater of the ulcer was adherent to the diaphragm and required exclusion from the gastrointestinal tract. None of the ulcers proved to be malignant, and there were no operative deaths. Patients were followed up for a mean of 3 years with no complications. CONCLUSIONS: Satisfactory results can be achieved with a transgastric approach to these rare ulcers. This allows definitive treatment while avoiding major gastric resection with its potential complications.

Folate status, genomic DNA hypomethylation, and risk of colorectal adenoma and cancer: a case control study.

BACKGROUND & AIMS: Low folate intake may increase risk for colorectal cancer by inducing DNA hypomethylation. This study reports the influence of folate status, DNA methylation, and polymorphisms of methylenetetrahydrofolate reductase (MTHFR 677C-->T and 1298A-->C), methionine synthase (MS 2756A-->G), and cystathionine-beta-synthase (CBS 844ins68) on risk for developing colorectal neoplasia. METHODS: Thirty-five patients with adenoma, 28 patients with cancer, and 76 controls were recruited for a case control study. Recruitment consent rate was 98%. Blood samples were obtained for determination of blood folates, vitamin B(12), homocysteine, DNA methylation, and genotypes. Tissue biopsy samples were obtained at colonoscopy for determination of DNA methylation in colonic mucosa. Folate status was assessed by constructing a score from estimates of dietary intake and serum and erythrocyte folate. RESULTS: Cancer patients had 26% lower folate status (95% confidence interval [CI]: 6% to 44%, P = 0.01) and 21% lower serum vitamin B(12) concentration (95% CI: -38% to 1%, P = 0.06) compared with controls. [(3)H] methyl incorporation into colonic DNA was 26% higher in patients with adenoma (95% CI: 8% to 56%, P = 0.009) and 30% higher in patients with cancer (95% CI: -3% to 48%, P = 0.08) compared with controls. High folate status was associated with decreased risk for cancer (P = 0.01 for trend). Colonic and leukocyte DNA hypomethylation were associated with increased risk for adenoma (P = 0.02 and P = 0.01 for trend, respectively) and a nonsignificantly increased risk for cancer (P = 0.09 and P = 0.08 for trend, respectively). CONCLUSIONS: Low folate status and DNA hypomethylation are associated with colorectal neoplasia.

Prediction of inflammation of the appendix at open and laparoscopic appendicectomy: findings and consequences.

OBJECTIVE: To evaluate the accuracy of operative assessment of the condition of the appendix during laparoscopic and open appendicectomy, and to assess whether a normal-looking appendix should be excised routinely during a laparoscopic operation. DESIGN: Prospective study. SETTING: District general hospital, UK. SUBJECTS: 387 patients who presented with signs and symptoms of appendicitis and underwent appendicectomy. INTERVENTION: 63 patients (16%) were operated on laparoscopically, of whom 48 were female. MAIN OUTCOME MEASURES: Correlation of operative with histological findings. RESULTS: The positive predictive value of operative assessment was increased during the laparoscopic procedure in both male (94.4% to 100%) and female (78% to 88%) patients. Of 21 female patients whose appendixes looked normal at laparoscopy, 5 had other conditions (appendixes normal on histological examination) and 4 were inflamed. CONCLUSION: In women of childbearing age a normal-looking appendix should be resected during laparoscopic appendicectomy unless another condition is obviously the cause of the signs and symptoms.