Robert M. Mitchell

Endoscopic Retrograde Cholangiopancreatography Is Safe and Effective in Patients 90 Years of Age and Older

Goals To review our experience of endoscopic retrograde cholangiopancreatography (ERCP) in patients 90 years and older. Background ERCP is effective in the investigation and treatment of biliary disease; however, in the very elderly, a perception of high procedural risk and lack of efficacy may limit its use. Study Retrospective analysis of ERCPs performed on patients 90 years of age and older from one institution. Results Between 1987–2000, 23 ERCPs were performed on patients 90 years of age and more (16 women; age range, 90–96 years). The primary indications were obstructive jaundice (16 patients), pancreatitis (2), cholangitis (1), unexplained abdominal pain (1), and planned follow-up (3). The main endoscopic findings were common bile duct (CBD) stone (15 patients), pancreatic carcinoma (2), cholangiocarcinoma (2), and dilated duct (only 1). Sixteen sphincterotomies were performed, with successful common duct clearance in 10 patients. Seven biliary stents were inserted for benign disease and three, for malignancy. In two patients, CBD cannulation was unsuccessful. Three minor hemorrhages were controlled endoscopically. Three patients died of nonprocedural causes. Conclusions ERCP is safe and effective in the very elderly. The decision to undergo ERCP should be determined by clinical need.

Flexible sigmoidoscopy and the changing distribution of colorectal cancer: implications for screening.

BACKGROUND AND AIMS There has been a significant proximal shift in the distribution of colorectal cancer (CRC) in Northern Ireland over recent decades. The aim of this study was to investigate the potential implications of this proximal shift in CRC distribution on the efficacy of flexible sigmoidoscopy (FS) as a screening tool. PATIENTS AND METHODS The site distribution of 5153 CRCs was available from the Northern Ireland Colorectal Cancer Register for the period 1990–1997. Similar data on 1241 CRCs between 1976 and 1978 were available from a previous study. Data on the site reached by FS were obtained from a prospectively collected endoscopy database at one of Northern Irelands main teaching hospitals for the period 1993–1998. RESULTS There was a significant proximal shift in CRC distribution between the two periods (23.5% proximal to the splenic flexure between 1976 and 1978v 36.7% between 1990 and 1997; p<0.001). The descending colon was visualised during 74.4% of FS examinations. By combining the observed extent of FS examination with CRC site distribution, it was calculated that FS could have visualised 68.8% of CRCs between 1976 and 1978 but only 56.0% between 1990 and 1997. Extrapolating these data to a Northern Ireland screening programme involving FS and faecal occult blood testing suggests that significantly more CRCs could have been detected between 1976 and 1978 than between 1990 and 1997 (51.7% v 48.2%, respectively; p=0.03). CONCLUSIONS This study confirms the previously documented left to right shift in CRC distribution in Northern Ireland and demonstrates that if this shift continues, FS will become less successful as a screening tool than is currently predicted.

Extensive investigation of patients with mild elevations of serum amylase and/or lipase is 'low yield'.

BACKGROUND Serum amylase and lipase levels are widely used as markers of pancreatic inflammation. However, it would seem that mild elevations of amylase and lipase rarely predict significant pancreatic pathology. Pancreatic imaging tests are expensive. The gold standard, endoscopic retrograde cholangiopancreatography, carries risk of morbidity and mortality. OBJECTIVE To determine whether extensive investigation of patients with mild, nonspecific abdominal symptoms and mild elevations of amylase and/or lipase results in a significant diagnostic yield. METHODS Outpatient evaluations were retrospectively analyzed over 12 months. Inclusion criteria were nonspecific abdominal pain, and mild elevations (less than three times the upper limit of normal) of serum amylase or lipase, or both. Exclusion criteria included a history of chronic pancreatitis, elevation of liver tests and acute pain syndromes. RESULTS Nineteen patients over the study period met the criteria. Of the nineteen patients, 58% had elevation of lipase alone, 21% amylase alone and 21% had elevations of both. In addition, 89.5% of the patients had nonspecific abdominal pain. After imaging with one or more of ultrasound, computed tomography, magnetic resonance cholangiopancreatography, endoscopic ultrasound and endoscopic retrograde cholangiopancreatography, small bowel follow through or hepatobiliary scanning, 78.9% patients were thought to have a normal pancreas. Of the remaining patients, 15.8% had mild or equivocal changes of chronic pancreatitis, and one patient was found to have a pancreatic tail pseudocyst. The average cost of investigation was US

The need for caution with topical anesthesia during endoscopic procedures, as liberal use may result in methemoglobinemia.

2,255, taking only direct procedural costs into account. No patient was found to have malignancy. CONCLUSIONS The majority of patients with nonspecific abdominal pain and isolated elevations of amylase and/or lipase (less than three times the upper limit of normal) had no identifiable pancreatic pathology. The diagnostic yield in patients with mild elevations of lipase alone was particularly poor. The cost effectiveness and risk-benefit ratio of extensive investigation of this group of patients warrants further study.

The fate of patients who undergo "preoperative" ERCP to clear known or suspected bile duct stones.

During upper gastrointestinal endoscopy, topical oropharyngeal anesthesia with lidocaine and/or benzocaine is used routinely by many endodscopists. Although such a practice is usually safe, there have been a number of reports of methemoglobinemia induced by topical anesthesia. Early treatment is extremely important as the development of methemoglobinemia is potentially fatal. Methemoglobinemia should be considered when oxygen desaturation occurs without another explanation. In this case series, we report 4 cases of methemoglobinemia that followed the liberal application of Cetacaine for ERCP. All patients recovered after appropriate treatment but these cases serve to highlight the potential problem, the importance of early recognition and treatment, and the most appropriate treatment options.

Changing patterns of colorectal cancer.

BackgroundThere is debate as to whether recurrent biliary complications are more common in patients who do not have elective cholecystectomy after endoscopic retrograde cholangiopancreatography (ERCP) management of common bile duct (CBD) stones. The aim of this study was to determine the fate of patients with intact gallbladders who have had CBD stones removed at ERCP, and to assess their risk of recurrent biliary symptoms.MethodsWe retrospectively identified all patients in our large tertiary center population with intact gallbladders who had an ERCP for CBD stones from December 1999 to March 2002. We determined which patients had subsequent elective cholecystectomy, and the outcomes of patients who did not have elective surgery.Results309 patients had CBD stones at ERCP during the study period, of which 139 had intact gallbladders at the time of ERCP. Of these 139 patients 59 had subsequent elective cholecystectomy, 11 by open operation and 48 laparoscopically. Of these 139 patients, 27 had cholecystectomy planned; 47 patients were managed with a wait-and-see strategy, 30 of whom were poor surgical candidates. Of these 47 patients in whom a wait-and-see policy was adopted, 9 (19%) developed complications including recurrent pain and/or abnormal liver function tests (LFTs), recurrent biliary colic, and pancreatitis. Eight of these nine patients were from the poor surgical candidate group. Sphincterotomy had been performed at initial ERCP in all patients.ConclusionsOver half of our population of 139 patients with CBD stones at ERCP and intact gallbladders had actual or planned elective cholecystectomy. For those patients in whom a decision to wait-and-see was made, almost 20% developed complications. Elective cholecystectomy after a finding of choledocholithiasis is supported by many and is a common strategy in our experience. Recurrent biliary complications are relatively common in those who do not undergo elective cholecystectomy, especially those patients who represent a high operative risk.

The changing scope of colorectal cancer

TO THE EDITOR: We read with great interest the report in a recent issue of this journal by Rabeneck et al. (1). This large study confirms that the proportion of colorectal cancer (CRC) located in the right colon has indeed increased over the last 20 yr in the United States, as has been previously noted in other geographical regions in the same period. The authors demonstrate that this increase has taken place without a corresponding rise in the incidence of right-sided CRC. They also show that the proportion of right-sided CRC diagnosed has increased as the age of the population increases. Our published data comparing CRC diagnosed in 1976– 1978 and in 1995–1997 in Northern Ireland show the same pattern of an increasing proportion of right-sided CRC over two decades (23.6% in 1976–1978 vs 35.1% in 1995–1997) (2, 3). Further data from the 1995–1997 period confirm that the proportion of right-sided CRC in Northern Ireland increases with age (34% for 41–50 yr of age vs 46% for >80 yr of age). However, our data also demonstrate that the agestandardized incidence of right-sided CRC has increased in both sexes over this period in Northern Ireland (rates per 100,000: males: 4.7 in 1976–1978 vs 9.5 in 1995–1997; females: 4.7 in 1976–1978 vs 8.7 in 1995–1997), although the incidence of CRC at other sites has not changed. Census data also show that the proportion of the Northern Ireland population over 80 yr of age has almost doubled in the period 1977–1996 (from 1.6% to 2.7%). These data suggest that the increased incidence of rightsided CRC in Northern Ireland may be related to aging of the population. These results also suggest that different mechanisms are responsible for similar changes observed in CRC distribution in different geographical regions. Local data collection and the maintenance of local cancer registries remain important to determine these underlying patterns in CRC distribution.

Spontaneous resolution of a pancreatic–colonic fistula after acute pancreatitis

The nature and significance of the relationship between vitamin K status and bone health has been debated for some years. Vitamin K is required for the gamma carboxylation of glutamic acid residues in three bone proteins, namely osteocalcin, matrix Gla protein, and protein S. Although the roles of these proteins have not been clearly defined, there is evidence that osteocalcin, which is produced by cells of the osteocyte/osteoblast lineage and has three vitamin K dependent gamma carboxyglutamic acid (Gla) residues, may be involved in the mineralisation of bone matrix; in addition, it may function as a negative regulator of bone formation, deletion of the osteocalcin gene in mice resulting in increased bone mass. Approximately 30% of synthesised osteocalcin is released into the circulation and serum levels of the protein are widely used as an indicator of bone formation. Vitamin K deficiency is associated with a reduction in circulating osteocalcin concentrations and a decrease in the gamma carboxylated fraction, the latter being associated with reduced binding of the protein to bone mineral. Despite this theoretical basis for adverse eVects of vitamin K deficiency in the skeleton, however, direct evidence is lacking. Thus although low vitamin K levels and undercarboxylation of osteocalcin have been described in patients with osteoporosis, 6 these findings may reflect poor nutritional status rather than a specific eVect of vitamin K deficiency on bone. Similarly, there is currently no direct evidence that therapy with warfarin, which inhibits the secretion by osteoblasts of osteocalcin, increases the risk of osteoporosis, and although increased fracture risk has been reported in patients receiving oral anticoagulants, this finding has not been universal. Malabsorption of fat soluble vitamins is a recognised complication of Crohn’s disease and, in particular, an increased prevalence of vitamin D deficiency has been reported in many studies. In rare cases this results in osteomalacia but more importantly it contributes to the increased prevalence of osteoporosis associated with Crohn’s disease as a consequence of secondary hyperparathyroidism and the resulting increase in bone turnover. In contrast, vitamin K status has been less well studied although in one study a high prevalence of deficiency of the vitamin was found in patients with ileal Crohn’s disease. The study by Schoon et al in this issue of Gut, performed in a cohort of patients with small intestinal Crohn’s disease, provides some evidence, albeit indirect, that there may be an inverse association between vitamin K status and bone mineral density of the spine (see page 473). Thus undercarboxylation of osteocalcin was higher and binding of circulating osteocalcin to hydroxyapatite lower in patients with Crohn’s disease compared with controls, indicating reduced vitamin K status. Furthermore, serum levels of undercarboxylated osteocalcin were inversely related to bone mineral density in the spine, although this relationship was not observed for proximal femur or total body bone mineral density. Interestingly, although there was a significant correlation between serum levels of the major circulating metabolite of vitamin D, 25hydroxyvitamin D, and serum vitamin K, no correlation was observed between vitamin D status and bone mineral density at any of the sites assessed. The results of this study would thus be consistent with a role for vitamin K deficiency in the pathogenesis of osteoporosis associated with Crohn’s disease. Nevertheless, further studies are required in view of the relatively small sample size in this study (n=32) and lack of a statistically significant correlation between serum vitamin K levels and bone mineral density. In addition, the reduction in bone mineral density was relatively modest in this cohort, with mean z scores higher than −0.5 at all sites, and in this respect it would be of interest to investigate the relationship between vitamin K status and bone mass across a wider spectrum of bone disease. Failure to demonstrate a correlation between the serum “free” (undercarboxylated) osteocalcin and bone mineral density in the femoral neck and total body may reflect inadequate statistical power or alternatively might indicate diVerential eVects on cancellous and cortical bone. The pathogenesis of osteoporosis in patients with Crohn’s disease is multifactorial, glucocorticoid therapy, hypogonadism, vitamin D deficiency, and malnutrition all being potential contributory factors. In the study of Schoon et al, patients were in remission at the time of assessment and were treated with no more than 5 mg of oral prednisolone daily. Nevertheless, bone mineral density values assessed at one point in time reflect multiple past and present influences and thus the eVects of glucocorticoids and disease activity could not be excluded completely, as the authors claimed. The question of whether vitamin K supplementation prevents or reduces bone loss in patients with Crohn’s disease (or in other populations) has not been established and this will be an important area for future research if an association between vitamin K status and bone mineral density is confirmed in subsequent studies.

The importance of ileoscopy in patients with suspected small bowel disease.

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Colonoscopy or barium enema for population colorectal cancer screening

We read with great interest the article by Eliakim and colleagues [1]. In 20 patients with suspected Crohn’s disease, capsule endoscopy and entero-computed tomography (CT) were performed and findings were correlated with initial small-bowel follow-through. Interestingly, capsule endoscopy detected additional lesions that were not detected by radiological studies in 47% of cases and was deemed a ‘superior and more sensitive procedure than barium follow-through and entero-CT’.