The Voronoi theory of the normal liver lobular architecture and its applicability in hepatic zonation.

The precise characterization of the lobular architecture of the liver has been subject of investigation since the earliest historical publications, but an accurate model to describe the hepatic lobular microanatomy is yet to be proposed. Our aim was to evaluate whether Voronoi diagrams can be used to describe the classic liver lobular architecture. We examined the histology of normal porcine and human livers and analyzed the geometric relationships of various microanatomic structures utilizing digital tools. The Voronoi diagram model described the organization of the hepatic classic lobules with overall accuracy nearly 90% based on known histologic landmarks. We have also designed a Voronoi-based algorithm of hepatic zonation, which also showed an overall zonal accuracy of nearly 90%. Therefore, we have presented evidence that Voronoi diagrams represent the basis of the two-dimensional organization of the normal liver and that this concept may have wide applicability in liver pathology and research.

Chronic hepatitis. An update on terminology and reporting.

The terms chronic active hepatitis (CAH), chronic persistent hepatitis (CpH), and chronic lobular hepatitis (CLH) have become obsolete, and their use without further specifications should be discontinued. This recommendation has become necessary because these names have changed from descriptive terms, intended for grading, to terms that are used either as morphologic diagnoses or disease designations or both, depending on individual preferences. Because this practice has caused serious misunderstandings, many authors and two international groups have recommended the use of a clear etiologic terminology. For the reporting practice of pathologists, we recommend that the pathologist routinely sign out biopsy samples with features of chronic hepatitis by indicating etiology, grade, and stage. An example would be autoimmune hepatitis, severe, stage 3. The stage in this case would indicate the presence of well-developed septal fibrosis but no nodular regeneration. Obviously, for the etiologic diagnosis, morphologic findings must be integrated with clinical and laboratory data. If this information is not available, clear morphologic diagnoses should be reported. Thus, instead of CPH, the diagnosis should be portal hepatitis, cause undetermined. This reporting practice eliminates ambiguous terminology and avoids the risk of inappropriate treatment as might occur, for example, when a term such as CAH is used to describe Wilson's disease and is misunderstood to mean autoimmune hepatitis. For a transitional period and to facilitate relearning, the terms CAH, CPH, and CLH can be reported in parentheses behind the etiologic diagnosis.

Detection of albumin messenger RNA in hepatic and extrahepatic neoplasms. A marker of hepatocellular differentiation.

Albumin is a ubiquitous protein synthesized only by hepatocytes. Detection of albumin messenger RNA (mRNA) in neoplastic and non-neoplastic tissues using in situ hybridization may be useful in demonstrating hepatocellular differentiation. We investigated the presence of albumin mRNA by in situ hybridization in 69 hepatic and 29 extrahepatic tumors to determine its sensitivity and specificity for hepatocellular differentiation. Albumin mRNA was detected in 22 of 23 hepatocellular carcinomas (96%); all hepatoblastomas, hepatocellular adenomas, and focal nodular hyperplasias; and within the hepatoid areas of an extrahepatic malignant mixed germ cell tumor. All other hepatic and extrahepatic tumors were negative for albumin mRNA. The staining was intense in focal nodular hyperplasias, weak in hepatocellular adenomas, and variable in hepatocellular carcinomas and hepatoblastomas. Non-neoplastic, noncirrhotic liver was present in 50 cases; all were positive for albumin mRNA with variable staining, which was usually more intense than in the neoplasms. A zonal pattern of staining was present in 49 (98%) of these, with more intense staining within acinar zone 1 and least in zone 3. This study shows that albumin mRNA is a specific marker of hepatocellular differentiation but may be present in extrahepatic germ cell tumors with hepatoid features. For primary hepatocellular carcinomas, in situ hybridization for albumin mRNA is a useful adjunct diagnostic method.

Recent-onset autoimmune hepatitis. Biopsy findings and clinical correlations.

Whereas the histologic findings in clinically "chronic" autoimmune hepatitis have been well established, with piecemeal necrosis as a hallmark lesion, the histologic findings of clinically "acute" or recent-onset autoimmune hepatitis remain undefined. The goal of this study was to define more fully the liver histomorphology in patients with recent-onset autoimmune hepatitis. Twenty-six patients were identified at our institution who had well-characterized autoimmune hepatitis and had undergone a liver biopsy within 6 months of clinical presentation. A detailed histologic evaluation revealed evidence of chronic liver disease in 25 (of 26) patients despite the lack of correlating clinical chronicity. The histologic evidence of chronicity included, in addition to a portal lymphoplasmacytic infiltrate, bridging (septal) fibrosis (11 patients) and overt cirrhosis (four patients). Eighteen of these 25 cases with evidence of chronicity also showed zone 2 and 3 lobular hepatitis, including disarray and hepatocyte necrosis. A single case showed lobular hepatitis with confluent hepatocyte necrosis (submassive hepatocellular necrosis), but no evidence of chronic liver disease. Although autoimmune hepatitis remains in the differential diagnosis of lobular hepatitis, these data show that most patients with autoimmune hepatitis who undergo biopsy early in its clinical course will have histologic evidence of chronic liver disease. Most of these patients probably have a lobular "flare" in disease activity, which likely precipitated the clinical presentation. The findings herein reinforce the concept that autoimmune hepatitis is by definition a chronic disease and supports the proposal that the modifier "chronic" be eliminated from autoimmune hepatitis.

Chronic liver allograft rejection: a National Institute of Diabetes and Digestive and Kidney Diseases interinstitutional study analyzing the reliability of current criteria and proposal of an expanded definition. National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database.

A study was conducted to assess the inter and intrarater agreement for the histopathologic features and diagnosis of chronic rejection (CR) and several other important causes of late liver allograft dysfunction. On two occasions, five pathologists, experienced with liver transplantation, reviewed a set of 49 slides representing a range of diagnoses, without knowledge of the clinical history or liver injury test results. The readings were correlated with the original histopathologic diagnosis, liver injury tests, and clinicopathologic follow-up. Assessment of biopsy adequacy (kappa = 0.69) and portal tract counts (kappa = 0.79) showed good to excellent intrarater agreement, whereas interrater agreement for these variables was moderate to good, respectively (kappa = 0.44 and 0.65). Likewise, the intrarater agreement for the diagnosis of CR (kappa = 0.68), hepatitis (kappa = 0.77), and obstructive cholangiopathy (kappa = 0.55) showed good to excellent agreement, whereas the interrater agreement for these same diagnoses ranged from fair to good (kappa = 0.58, 0.46, and 0.25, respectively). In 18 specimens, there was a near unanimous diagnosis of CR across both readings. These biopsies were obtained at a median of 7.1 months (range, 42 days to 4.9 years) after transplantation, and the average number of portal tracts was 8.4 (range, 4-15). Interestingly, only 13 of these 18 specimens showed bile duct loss in >50% of the portal triads; the remaining cases showed atrophy/pyknosis of the biliary epithelium in a majority of small bile ducts. Clinicopathologic correlation showed that these 18 biopsies were obtained from 16 grafts from 15 patients, 14 of whom ultimately required retransplantation or died of or with CR, whereas two of the grafts/patients recovered. A high rate of sensitivity (92%) and a somewhat lower, but acceptable, rate of specificity (71% to 80%) was found for the diagnosis of CR. Chronic rejection and other causes of late liver allograft dysfunction can be diagnosed reliably by a group of pathologists experienced with liver transplantation, and the diagnosis of CR correlates with clinical course and liver function abnormalities. Expanded criteria for the diagnosis of CR are presented, and potential problem areas for practicing pathologists are discussed.

Influence of positive lymphocyte crossmatch and HLA mismatching on vanishing bile duct syndrome in human liver allografts.

Among the first 52 recipients of primary liver allografts with follow-up of 2 weeks or greater, 6 patients had biopsy-confirmed vanishing bile duct syndrome (VBDS) and required retransplantation. Five of these six patients had positive lymphocyte crossmatches. Of the 46 remaining liver transplant recipients, 11 had positive crossmatches. Thus, the incidence of VBDS was 5/16 in recipients with a positive crossmatch and 1/36 in recipients with a negative crossmatch. The positive-crossmatch group was significantly more likely to develop VBDS than the negative-crossmatch group (P less than 0.004, log rank test). Additional HLA studies comparing degree of donor-recipient mismatch at the various HLA loci showed no significant difference between the groups for class I disparity. However, class II mismatch was of borderline significance (P less than 0.056). When evaluated individually, the DQ mismatch (P less than 0.04) appeared to be more important than the DR mismatch (P = NS). Our data suggest that a positive lymphocyte crossmatch and a class II mismatch, in particular HLA DQ disparity, may play an important role in the pathogenesis of VBDS.

Relationship between hepatitis C genotype and severity of recurrent hepatitis C after liver transplantation.

BACKGROUND: Recurrence of hepatitis C virus (HCV) infection after liver transplantation is universal, but the relationship between hepatitis C genotype and posttransplant outcome has been controversial. The aim of this study was to assess the relationship between hepatitis C genotype on posttransplant frequency of recurrent hepatitis, histologic severity of recurrence, and progression to cirrhosis. METHODS: We studied 42 HCV RNA positive patients who received transplants between 1985 and 1994. Sera were tested for HCV RNA and protocol liver biopsies were in obtained the posttransplant period. Biopsies were scored according to the histologic activity index (HAI) and staged in a blinded fashion. RESULTS: The distribution of hepatitis C genotypes distribution was as follows: 1a, 19 (45%); 1b, 17 (40%); 2b, 3 (7%); and 1 each of 2a, 3a, and 4a. There was histologic evidence of hepatitis in 38 of 42 (90.4%) of patients. Hepatitis C was mild, moderate, or severe (HAI>3) in 38% of grafts and minimal (HAI 0-3) in 62%. Overall HAI scores and histologic stage were higher in the genotype 1b group. Six of 17 (35%) genotype 1b patients had cirrhosis compared with 2 of 25 (8%) in the non-1b genotype group. CONCLUSIONS: (1) Histologic evidence of recurrent hepatitis C is seen in 90% of liver allografts; (2) Histologic hepatitis C recurs with similar frequency in genotype 1b and non-1b recipients; (3) Genotype 1b is associated with more severe histologic disease recurrence than non-1b genotypes; (4) Genotype 1b appears to be associated with a higher degree of posttransplant fibrosis and cirrhosis than non-1b genotypes.

Comparative allograft histology after liver transplantation for cryptogenic cirrhosis, alcohol, hepatitis C, and cholestatic liver diseases.

BACKGROUND: End-stage liver disease for which no cause can be identified, cryptogenic cirrhosis, is a common indication for liver transplantation. Allograft inflammation and fibrosis have been reported to recur with similar frequencies after liver transplantation for cryptogenic cirrhosis and hepatitis C (HCV). METHODS: We determined sequential posttransplant allograft histology in four groups of recipients: 31 transplanted for cryptogenic cirrhosis, 70 for cholestatic etiologies, 40 for alcoholic liver disease, and 56 for HCV. Modified hepatitis activity index (HAI) and fibrosis stage were determined at 4 months, 1 year, and at most recent biopsy posttransplantation. RESULTS: The prevalence of HAI > or = 2 among cryptogenic recipients was similar to that of cholestatic and alcoholic recipients at 4 months, 1 year, and at most recent evaluation (mean 45+/-17 months posttransplantation). For HCV-infected recipients, the frequency of HAI > or = 2 was more than for cryptogenic recipients at 1 year (52 vs. 29%, P=0.04) and at most recent evaluation (64 vs. 15%, P=0.003). Fibrosis scores for cryptogenic, cholestatic, and alcoholic recipients were similar at all timepoints. The proportion of HCV-infected recipients with fibrosis stage >2 was more than that of cryptogenic recipients at 4 months (29 vs. 12%, P=0.05), 1 years (46 vs. 7%, P=0.0002), and at most recent evaluation (42 vs. 15%, P=0.06). None of the cryptogenic recipients developed cirrhosis. RESULTS: The frequency of elevated HAI and fibrosis stage in recipients who undergo transplantation for cryptogenic cirrhosis is similar to that of recipients who undergo transplantation for cholestatic etiologies and significantly less than that of HCV-infected recipients. Fibrosis stage and HAI are generally stable after transplantation for cryptogenic cirrhosis. These data do not suggest a viral etiology of liver disease in the majority of patients with cryptogenic cirrhosis.

Use of fatty donor liver is associated with diminished early patient and graft survival.

It is well known that implantation of donor livers with severe fatty infiltration (>60%) is frequently associated with early hepatic dysfunction and an increased incidence of primary nonfunction after liver transplantation. The outcome of donor livers with less fatty infiltration has not been well defined. We, therefore, studied the outcome of 59 liver transplantations in which donor livers with up to 30% fat were used. Patient outcome was compared to a time-matched control group of 57 patients. The two groups were similar in terms of age, gender, preservation time, primary diagnosis, and UNOS status. We compared both groups with regard to 4-month and 2-year patient and graft survival. We also assessed the incidence of ischemic type biliary strictures and hepatic artery thrombosis, and evaluated the causes of graft loss in both groups. We found that use of donor livers with up to 30% fatty infiltration was associated with a significant decrease in 4-month graft survival (76% vs. 89%, P<0.05) and in 2-year patient survival (77% vs. 91%, P<0.05). Primary nonfunction and primary dysfunction formed the main cause of graft loss and mortality. Multivariate analysis showed that fatty infiltration is an independent predictive factor for outcome after transplantation. We conclude that liver allografts with up to 30% fat lead to diminished outcome after liver transplantation. However, this diminished outcome should be viewed with respect to the increasing mortality on the national waiting list.

Recurrence of primary biliary cirrhosis, autoimmune cholangitis and primary sclerosing cholangitis after liver transplantation.

Given the usually prolonged natural history of primary biliary cirrhosis, autoimmune cholangitis, and primary sclerosing cholangitis, and the relatively recent introduction of orthotopic liver transplantation, our understanding of recurrence of these autoimmune diseases after orthotopic liver transplantation has been slow to evolve. Present data suggest that after orthotopic liver transplantation, patients with primary biliary cirrhosis will have persistence of serum antimitochondrial antibodies, develop histologic lesions suggestive of recurrent primary biliary cirrhosis with a frequency in the 8% to 16% range at 2 to 5 years after orthotopic liver transplantation, but will demonstrate little if any symptomatic disease as a consequence. Although data are extremely limited, autoimmune cholangitis patients will have a similar post-transplant course (without antimitochondrial antibodies). Recurrence of primary sclerosing cholangitis remains the most controversial, however, these patients probably develop nonanastomotic intrahepatic and extrahepatic strictures more frequently than patients without primary sclerosing cholangitis, with a frequency in the 20% to 25% range at 3 to 5 years. With longer patient follow-up and additional studies, it is hoped that our understanding of recurrent autoimmune biliary diseases will grow considerably in the future.

Ischemic cholangitis.

Ischemia-induced bile duct lesions have been collectively labeled as ischemic cholangitis. The biliary epithelium is dependent on arterial blood flow, unlike the hepatic parenchyma with its dual arterial and portal venous blood supply. As such, the biliary epithelium is susceptible to injury when arterial blood flow is compromised. This compromise can occur at the level of the major, named hepatic artery branches or at the microscopic, peribiliary capillary plexus level. Typically, ischemic cholangitis manifests as segmental strictures and cholangiectases with resultant mechanical impairment of bile flow and, occasionally, secondary infection of the biliary system. Ischemic cholangitis after liver transplantation is becoming an important problem and likely is attributable to numerous factors. Hepatic arterial infusion of chemotherapy and systemic vasculitis are other causes of ischemic cholangitis. The role of ischemia in other chronic biliary and ductopenic diseases remains speculative.

Ischemic cholangitis in hepatic allografts.

In this report, our objectives are to introduce the term "ischemic cholangitis" as an etiologic designation and to describe its manifestations. Herein we use the label "ischemic cholangitis" as a collective term for ischemic bile duct necrosis, cholangitis caused by ischemia but without necrosis, and biliary fibrosis as a manifestation of ischemic damage. The condition was observed in 12 allografts, either at the time of retransplantation (9 cases) or at autopsy (3 cases). Ischemic cholangitis involved primarily perihilar extrahepatic and intrahepatic bile ducts. The findings included duct necroses (eight cases), strictures (four cases), and cholangiectases (four cases); some of these features coexisted. In addition, complicating ascending cholangitis and cholangitic abscesses were noted in three cases. Ischemic cholangitis was caused by hepatic artery thrombosis (in nine patients) or stenosis (in one) or by occlusion of parabiliary arteries by fibrointimal proliferations, probably attributable to old thromboses (in two, in conjunction with associated foam cell arteriopathy in one). Biopsy specimens before retransplantation or autopsy were obtained in 11 patients, only 1 of whom had an infarct as direct evidence of ischemia. Nine patients had evidence of biliary obstruction or bile flow impairment; in two cases, specimens were normal or nondiagnostic relative to cholangitis. Features of cellular rejection associated with the manifestations of bile flow impairment and ischemia were noted in five cases. Thus, biopsy features that suggest biliary obstruction, with or without cellular rejection, may be a manifestation of ischemic cholangitis. We conclude that ischemic cholangitis is an important cause of cholestatic graft failure but that this type of cholangitis is difficult to diagnose because of its misleading biopsy manifestations.

Evidence against flat dysplasia as a regional field defect in small bowel adenocarcinoma associated with celiac sprue.

OBJECTIVE: To determine whether diffuse flat dysplasia, akin to that seen with chronic ulcerative colitis, occurs as a mucosal field defect accompanying small bowel adenocarcinoma in patients with celiac sprue. DESIGN: A pathologic investigation of archival tissue was undertaken. MATERIAL AND METHODS: From the tissue archives at Mayo Clinic Rochester for the period from January 1978 to January 1993, resected sprue-associated adenocarcinomas with adequate adjacent mucosa for study were identified. On the basis of multiple strip biopsy specimens obtained at the tumor margins and within 4 cm distal and proximal to the tumor, histologic maps were created. RESULTS: Among 94 patients with primary adenocarcinoma of the small bowel, 8 had a concurrent diagnosis of celiac sprue. Of these eight cases, six surgically resected specimens (five duodenal and one jejunal adenocarcinoma) were adequate for study. A thin rim of benign dysplasia was demonstrated at the tumor margin in three of the six specimens; however, contiguous fields of flat dysplasia were not present in any of these cases. CONCLUSION: These data support focal dysplasia (for example, adenoma) rather than sheets of flat dysplasia as the premalignant lesion in sprue-associated small bowel adenocarcinoma. Blind endoscopic biopsies of small bowel mucosa are not justified for neoplasia surveillance in patients with celiac sprue.

Carcinoma of the stomach with hepatocyte differentiation (hepatoid adenocarcinoma).

A case of hepatoid adenocarcinoma of the stomach is reported, and the literature is reviewed. The stomach is one of the most common sites in which hepatoid adenocarcinomas have been detected. Of the 59 cases reviewed from the literature (including the current case), a 2:1 male predominance was noted, and the serum alpha-fetoprotein level was almost always increased. All patients were adults, and most had evidence of metastases at the time of resection. Prognosis seems less favorable than that associated with the more common intestinal type of adenocarcinoma of the stomach. Hepatoid adenocarcinomas typically show periodic acid-Schiff-positive, diastase-resistant intracytoplasmic globules, which are demonstrated to be positive with antibodies to alpha-fetoprotein. The tumor cells resemble liver cells, and rare cases, including our own, have evidence of bile production. In our case, messenger RNA for albumin, unique to liver cells, was demonstrated by in situ hybridization of the tumor cells.

Endotheliitis in hepatic allografts.

Endotheliitis (EN) is a feature of hepatic allograft rejection, characterized by the adherence of immunocytes to the endothelium of veins, often leading to endothelial damage, endophlebitis, and, sometimes, panphlebitis. We found EN at least once in 28 of 41 allografts (68%) that had survived 6 months or longer. In approximately half the affected cases, the condition recurred. The EN was mild in most instances; moderate or severe manifestations were found in only 13% of the cases. The histologic changes were present for about 1 week in approximately half the cases; a duration of more than 2 weeks was noted in 17%, and then EN usually persisted. After retransplantation, recurrence of EN was observed in all of nine cases. We were unable to establish specific clinicopathologic and laboratory correlations for EN. The immunocytes in EN consisted mainly of helper and suppressor/cytotoxic T cells as well as natural killer cells. Sometimes, the immunocytes assumed a blastlike appearance; in these instances, the condition was severe. Such blastlike changes may be specific for EN. The immunocytes were attached to the endothelium by pseudopodia, broad bases, or both; some also were interconnected by cytoplasmic bridges. Underlying endothelial cells often showed evidence of cytoplasmic damage. The pathogenesis of EN is not completely understood; the immunocytes probably attach themselves to antigenic epitopes. Their nature, however, has not been clearly identified; HLA-A, B, and C and HLA-DR were displayed in areas of EN, but the antigens also were found in vessels without EN.

Angiotropic large cell lymphoma (intravascular lymphomatosis) occurring after follicular small cleaved cell lymphoma.

Angiotropic large cell lymphoma is a rare, aggressive type of malignant lymphoma that primarily involves intravascular spaces and most often has clinical manifestations in the skin and central nervous system. Virtually any organ can be affected, however, including the lymph nodes and spleen. Peripheral blood involvement is usually not detectable morphologically. Conventional lymphoma in association with this entity has also been described. Herein we present a case of angiotropic lymphoma of B-cell lineage that affected the liver and skin. Reanalysis of a lymph node specimen that had been excised 3 years previously demonstrated a follicular small cleaved cell lymphoma. To our knowledge, this is the first reported case of possible evolution of follicular lymphoma to large cell lymphoma of angiotropic type.

Pouchitis after ileal pouch-anal anastomosis: a Pouchitis Disease Activity Index.

OBJECTIVE: To develop a "Pouchitis Disease Activity Index" (PDAI) and to compare it with other diagnostic scoring systems for pouchitis. DESIGN: We compared patients who had an optimal outcome with those who had a poor result attributable to recurrent pouchitis after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis at the Mayo Clinic. MATERIAL AND METHODS: We evaluated the applicability of a PDAI that quantitated clinical findings and the endoscopic and histologic features of acute inflammation in four groups of patients: (1) 10 who underwent IPAA for ulcerative colitis and had symptoms compatible with a clinical diagnosis of pouchitis, (2) 5 who underwent IPAA for ulcerative colitis and did not have pouchitis, (3) 5 who underwent IPAA for familial adenomatous polyposis and had no symptoms of pouchitis, and (4) 5 who had a Brooke ileostomy for ulcerative colitis (control group). RESULTS: The PDAI was significantly greater in patients with the clinical features of pouchitis than it was for patients in the other three groups. All 10 patients with pouchitis fulfilled the PDAI criteria for a diagnosis of pouchitis; in contrast, only 1 of these 10 patients met the diagnostic criteria for pouchitis by application of previously established scoring systems. No asymptomatic patient qualified for a diagnosis of pouchitis by the PDAI criteria. CONCLUSION: The PDAI provides simple, objective, and quantitative criteria for pouch inflammation after IPAA and is more sensitive than prior scoring systems.

Update on hereditary hemochromatosis and the HFE gene.

Hereditary hemochromatosis (HHC) is the most common inherited single gene disorder in people of northern European descent. Hereditary hemochromatosis is characterized by increased intestinal absorption of iron leading to its deposition into multiple organs. The classic description of HHC is bronze diabetes in a patient with cirrhosis. Hereditary hemochromatosis is increasingly being diagnosed at an earlier, less symptomatic stage. Diagnosis is based on an elevated fasting early morning transferrin saturation. Treatment is by phlebotomy, which, if initiated before the development of cirrhosis or diabetes, is associated with a normal life expectancy. Recently, a gene associated with HHC was discovered and named HFE. Two point mutations of this gene have been referred to as C282Y and H63D. Several US and European studies have found that 60% to 93% of patients with suspected HHC are homozygous for C282Y. Positive results of HFE gene testing may eliminate the need for a liver biopsy in selected cases. The greatest utility of HFE gene testing will likely be in screening family members of an identified proband and in helping to resolve ambiguous cases.

Chronic diarrhea due to surreptitious use of bisacodyl: case reports and methods for detection.

Surreptitious abuse of laxatives is a common cause of severe chronic diarrhea. Standard laboratory screening studies of urine and stool specimens may identify phenolphthalein, diuretics, and magnesium-containing agents. An assay for bisacodyl, a commonly used over-the-counter laxative, however, is not included in routine screening tests. Herein we describe two patients with chronic watery diarrhea of large volume; analysis of stool and urine samples revealed that surreptitious use of bisacodyl was the cause. In one patient, nonspecific inflammatory changes of the colonic mucosa were noted on biopsy, and fecal leukocytes were detected in both patients. In a prospective study of eight patients who received bisacodyl as part of a preparation for colonoscopy, we analyzed serial urine samples for bisacodyl diphenol during a 48-hour period. This metabolite was found in seven of eight hydrolyzed urine samples obtained 12 hours after oral administration of bisacodyl but not in samples obtained 24 and 48 hours after ingestion of the laxative. We recommend that urinalysis and, in some cases, stool analysis for bisacodyl should be considered in the diagnostic assessment for surreptitious use of laxatives.

Liver biopsy diagnosis of homozygous hemochromatosis: a diagnostic algorithm.

The diagnosis of homozygous hemochromatosis (HH) should be based on appropriate findings on liver biopsy specimens. In cases with equivocal morphologic features, quantitative tissue iron determination and calculation of the hepatic iron index generally enable one to distinguish HH from other types of hepatic iron overload. In this article, we describe a diagnostic algorithm that is designed to avoid diagnostic errors because of histologic misinterpretation or erroneous, usually false-negative, chemical iron studies. The algorithm also delineates a cost-effective method of using quantitative tissue iron analysis. Diagnostic biopsy features of uncomplicated HH include (1) hemosiderosis that involves primarily hepatocytes, with or without inactive cirrhosis, and (2) a tissue iron index of 1.9 or higher. Findings such as prominent fatty changes or lymphocytic piecemeal necrosis indicate the presence of HH in conjunction with another complicating condition or secondary iron overload in the absence of HH.