Douglas B. McGill

A 21-year experience with major hemorrhage after percutaneous liver biopsy

Nine thousand two hundred twelve liver biopsies were performed according to a defined protocol, and data were prospectively recorded to identify risk factors for major bleeding. There were 10 fatal and 22 nonfatal hemorrhages (0.11% and 0.24%, respectively). By comparison with a control group that did not hemorrhage, malignancy, age, sex, and the number of passes were the only predictable risk factors. The risk of fatal hemorrhage in patients with malignancy is estimated to be 0.4%; for nonfatal hemorrhage, 0.57%. In patients undergoing liver biopsy for nonmalignant disease, the risks are 0.04% and 0.16%, respectively.

Prospective Comparison of Indirect Methods for Detecting Lactase Deficiency

To compare sensitivity, specificity and convenience, four indirect methods of detecting lactase deficiency were tested prospectively in 25 subjects with biopsy-proved lactase deficiency and in 25 with normal lactase activity. After ingestion of 50 g of lactose, containing 1-14Clactose, breath hydrogen was abnormally elevated in all 25 lactase-deficient subjects (greater than 0.30 ml per minute at two hours); breath 14CO2 was below the normal range in 23, and in 19 the plasma glucose increased by less than 20 mg per deciliter. When lactose and ethanol were given together, the rise in plasma galactose remained less than 5 mg per deciliter in 24 of the lactase-deficient subjects. The specificity of the four tests was excellent, with only one false-positive plasma glucose test. Measurement of breath hydrogen is sensitive and specific, and does not require ethanol or isotopes. It is noninvasive, and is not influenced by gastric emptying or metabolic factors. We believe it to be the most suitable test for population screening for lactase deficiency.

REVIEW: Nonalcoholic steatohepatitis

Nonalcoholic steatohepatitis (NASH) is a reasonably well‐defined clinicopathological entity; it has been reported more commonly in women than in men or children of both sexes and it appears to be most closely associated with obesity, diabetes mellitus and related abnormalities, such as hyperlipidaemia and hyperglycaemia. However, the association with female gender, obesity and diabetes may not be as close as suggested by the literature and an underlying condition cannot be discerned in all cases. The natural history of the disease is poorly understood; the associated biopsy features span a wide spectrum, reaching from uncomplicated, clinically non‐progressive fatty liver (not NASH in a strict sense) to a slowly progressive fatty liver with inflammation and fibrosis, to steatohepatitis with submassive hepatic necrosis, which has a subfulminant course and is often fatal. Non‐progressive fatty liver appears to be very common but is of little clinical importance. The slowly progressive form of the disease represents NASH as encountered by most clinicians and pathologists. It is a common liver disease in current practice; patients may present with cirrhosis and even HCC arising from steatohepatitic cirrhosis. Subfulminant NASH has become exceedingly rare because many clinicians are now aware of the hazards of sudden weight loss, particularly in morbidly obese patients. Treatment options for NASH are still limited. The promotion of gradual weight loss in obese patients is the most widely recommended therapy but, unfortunately, this is very difficult to achieve. Avoidance of precipitous weight loss and careful control of diabetes mellitus are important and undisputed parts of patient management. Administration of UDCA as a treatment of NASH is still under study; it may be effective in some patients. The treatment of established steatohepatitic cirrhosis does not differ substantially from that of other types of cirrhosis and includes orthotopic liver transplantation.

Fecal blood levels in health and disease. A study using HemoQuant.

We tested HemoQuant, a quantitative assay of fecal blood based on the fluorescence of heme-derived porphyrin, in 106 healthy volunteers, 170 patients with gastrointestinal symptoms but with normal diagnostic studies, 44 patients with gastrointestinal cancer, 75 patients with benign polyps, and 374 patients with a variety of other benign gastrointestinal lesions, including ulcers and erosions. In 98 per cent of the healthy volunteers, fecal hemoglobin concentrations were less than 2 mg per gram of stool. Levels were similarly low in stools from patients with symptoms and normal studies and in patients with relatively minor benign lesions. Within these groups, levels were slightly higher in those who had ingested red meat or aspirin. The fecal hemoglobin concentration was higher in patients with gastrointestinal cancer than in any other group, and 97 per cent of those with colorectal cancer had levels above 2 mg per gram. The sensitivity of HemoQuant was significantly greater than that of the guaiac test Hemoccult, particularly when heme was degraded or stools were dry. Intestinal degradation of heme to porphyrin can be measured separately by HemoQuant, and was greater when bleeding was from proximal lesions rather than distal ones. We conclude that HemoQuant is a more sensitive measure of gastrointestinal bleeding than Hemoccult, and that its capacity to measure degraded heme may be useful in indicating the anatomic site of bleeding.

Gastrointestinal Blood Loss and Anemia in Runners

Iron deficiency, with or without anemia, occurs commonly in long-distance runners, but the cause is unknown. The recent development of a simple quantitative assay for fecal hemoglobin, HemoQuant , allowed us to study whether gastrointestinal bleeding occurs in runners. Blood and stool samples were collected from 24 runners before and after a race of 10 to 42.2 km and from age- and sex-matched, nonrunning controls. The mean blood hemoglobin level and hematocrit were significantly lower in runners than in controls. Serum ferritin levels were below normal in 4 runners but in no controls. Fecal hemoglobin levels increased in 20 of 24 runners (p less than 0.01) after a race. Mean fecal hemoglobin level was 1.08 mg/g (range, 0.11 to 2.36) in controls and 0.99 mg/g (0.18 to 2.41) in runners before a race, but peaked at 3.96 mg/g (0.37 to 43.20) after a race. Competitive long-distance running induces gastrointestinal blood loss and may contribute to iron deficiency.

Intestinal Pseudo-Obstruction as the Presenting Manifestation of Small-Cell Carcinoma of the Lung: A Paraneoplastic Neuropathy of the Gastrointestinal Tract

A 58-year-old woman who had presented with intestinal pseudo-obstruction died 9 months later from rapidly progressive neurologic symptoms and autonomic insufficiency. Her gastric emptying had been markedly delayed and transit of markers had been slowed throughout the small bowel. A 5-hour manometric recording of the antrum and duodenum had shown absence of the normal interdigestive motor complex, which was replaced by irregular contractile activity of reduced amplitude. A small-cell carcinoma of the lung was found at autopsy. Pathologic study of the gut showed widespread degeneration of the myenteric plexus, which was infiltrated by plasma cells and lymphocytes and contained significantly reduced numbers of neurons. The extra-intestinal nervous system had neuronal loss and lymphocytic infiltrates in dorsal root ganglia. Thus, a gastrointestinal neuropathy causing intestinal pseudo-obstruction may be the presenting manifestation of a paraneoplastic syndrome associated with small-cell carcinoma.

Lactase Deficiency: Prevalence in Osteoporosis

We determined the prevalence of lactase deficiency by analysis of respiratory hydrogen (H2) in 30 women with idiopathic postmenopausal osteoporosis and in 31 female control subjects without evidence of metabolic bone disease. Eight subjects with osteoporosis had breath H2 excretion greater than 0.20 ml/minute at 2 h after receiving 50 g of lactose and were considered lactase deficient; only one control subject was lactase deficient (P less than 0.05). Symptoms developed in seven of the nine lactase-deficient persons after receiving 50 g of lactose; in contrast, only three of the 52 lactase-normal subjects had symptoms. Although none of the lactase-deficient subjects was aware of milk intolerance, their intake of both lactose and calcium was significantly lower than that in the lactase-normal group. Lactase deficiency appears to be one of several factors that predispose to the development of osteoporosis, probably through diminished calcium intake and possibly through an effect on calcium absorption.

An assessment of the role of liver biopsies in asymptomatic patients with chronic liver test abnormalities

An assessment of the role of liver biopsies in asymptomatic patients with chronic liver test abnormalities

Patterns of occult bleeding in asymptomatic colorectal cancer

The assumption that asymptomatic colorectal cancers bleed provides the rationale for widespread stool screening. The authors studied 12 patients with unoperated colorectal cancer but without colorectal symptoms and six healthy volunteers as laboratory controls. All stools were collected for 2 weeks and analyzed by the HemoQuant and Hemoccult tests. In controls, the mean HemoQuant value was 0.7 mg hemoglobin (Hb)/g stool (range, 0.1–1.8) and all stools were Hemoccult‐negative. In cancer patients, the mean HemoQuant was 3.3 mg Hb/g (range, 03–13.2); stools were within the normal HemoQuant range (<2 mg Hb/g) in 38% and negative by Hemoccult in 70%. The mean cancer detection rate testing a single stool per patient was 57% for HemoQuant and 25% for Hemoccult (P < 0.001). The detection rate rose testing multiple stools and was maximal with five stools at 83% for HemoQuant compared to 31% for Hemoccult (P < 0.001). The authors conclude that fecal blood levels are commonly normal with asymptomatic colorectal cancer. Although higher with HemoQuant than Hemoccult, cancer detection rates by fecal blood testing appear to be lower than previously reported.

Hemoccult detection of fecal occult blood quantitated by radioassay

Results from the guaiac slide or Hemoccult (HO) test for fecal occult blood were compared with quantitative determinations of gastrointestinal loss after intravenous administration of51Cr-labeled red cells. Subjects were 80 consecutive patients, without dietary restriction, who were referred because of clinical suspicion of gastrointestinal blood loss or complex anemia. A total of 555 stool specimens analyzed for51Cr loss were graded negative, trace, or positive by the HO method. Of 338 specimens containing 0–2 ml/day by isotope assay, 7.4% were positive to the HO qualitative test. Loss of at least 10 ml/day in51Cr equivalent was necessary to assure that the majority of HO reactions would be positive. Of specimens containing more than 30 ml/day, 93% were positive. The ratio of51Cr-labeled red cell equivalents to stool volume and the percentage of positive HO reactions increased together. When this ratio exceeded 10%, two thirds of the HO responses were positive.