Herschel A. Carpenter

Increasing incidence of adenocarcinoma of the esophagus and esophagogastric junction

BACKGROUND The aim of this study was to determine whether the incidence of adenocarcinoma of the esophagus and esophagogastric junction in a well-defined population was higher than previously recognized. METHODS Clinical records and original histological slides from patients residing in Olmsted County, Minnesota, were reviewed and compared with a previous study in the same population. RESULTS The incidence of esophageal adenocarcinoma rose from 0.13 for 1935-1971 to 0.74 for 1974-1989, and the incidence of adenocarcinoma of the esophagogastric junction rose from 0.25 to 1.34 per 100,000 person-years. Histological review of preserved surgical specimens showed associated intestinal metaplasia (Barretts esophagus) in 2 of 2 esophageal and in 5 of 9 esophagogastric adenocarcinomas. CONCLUSIONS The incidence of adenocarcinoma in each location increased five to sixfold compared with the earlier study. This increase could not be explained by improved diagnostic methods or classification changes. The association with Barretts esophagus and the parallel increased incidence of cancer in each location is evidence that adenocarcinoma of the esophagus and of the esophagogastric junction are related disorders.

Adenocarcinoma of the esophagogastric junction and Barrett's esophagus.

BACKGROUND & AIMS Barretts esophagus is associated with adenocarcinoma of the esophagus. The aim of this study was to find the prevalence of Barretts esophagus in patients with adenocarcinoma of the esophagogastric junction. METHODS Consecutive, freshly resected surgical esophagogastrectomy specimens were examined, and multiple histological sections were made around the tumor periphery. Barretts esophagus was defined as specialized columnar epithelium above the esophagogastric junction. Tumors centered < or = 2 cm from the junction were defined as junction cancers. RESULTS Barretts esophagus was found in 9 of 9 (100%) esophageal adenocarcinomas compared with 0 of 8 (0%) squamous carcinoma controls (P < 0.001). Ten of 24 (42%) junction adenocarcinomas had a Barretts esophagus. A Barretts esophagus was found in 8 of 12 (67%) junction cancers < or = 6 cm in length but only 2 of 12 (17%) larger tumors (P < 0.05). Barretts esophagus was significantly associated with junction tumors < 6 cm compared with squamous carcinoma controls (P < 0.02). In 5 specimens with junction cancer, the length of Barretts esophagus was < 3 cm, and in 5 specimens it was > or = 3 cm. Specialized epithelium was often found below the esophagogastric junction in controls. CONCLUSIONS Adenocarcinomas of the esophagogastric junction are associated with short and long segments of Barretts esophagus. Larger cancers probably overgrow and conceal the underlying specialized columnar epithelium from which they arise.

Sensitivity, specificity, and predictability of biopsy interpretations in chronic hepatitis

BACKGROUND To determine the frequency of individual histological findings in different types of chronic hepatitis and to assess the sensitivity, specificity, and predictability of histological patterns in distinguishing these types, liver biopsy specimens were examined from 86 patients with autoimmune hepatitis (43 patients), chronic hepatitis B (11 patients), chronic hepatitis C (21 patients), and cryptogenic hepatitis (11 patients). METHODS Specimens were examined under code by a single hepatopathologist, and predefined histological features were sought. A histological diagnosis was rendered based on composite changes. RESULTS Patients with chronic hepatitis C had a higher frequency of portal lymphoid aggregates (76% vs. 42%, P = 0.02) and steatosis (52% vs. 16%, P = 0.006) than patients with autoimmune hepatitis, whereas the latter patients more commonly had severe periportal hepatitis (23% vs. 0%, P = 0.02), moderate to severe plasma cell infiltration of the portal tracts (66% vs. 21%, P = 0.005), and lobular hepatitis (47% vs. 16%, P = 0.04). Patients with chronic hepatitis B had a higher frequency of ground-glass hepatocytes (36% vs. 0%, P = 0.001) and multinucleated giant cells (54% vs. 2%, P = 0.0001) than those with autoimmune hepatitis and chronic hepatitis C. The histological diagnoses for these clinical entities had high specificity (81%-99%) and predictability (62%-91%) but low sensitivity (36%-57%). CONCLUSIONS Autoimmune hepatitis, chronic hepatitis B, and chronic hepatitis C have characteristic individual histological features. Histological patterns based on these features have high specificity and predictability but low sensitivity.

A clinicopathologic study of 34 cases of diffuse pulmonary hemorrhage with lung biopsy confirmation

Based on a clinicopathologic study of 34 patients with biopsy-confirmed diffuse pulmonary hemorrhage (DPH). we present an approach to the differential diagnosis of DPH with attention to histologic features such as capillaritis and the importance of laboratory tests such as anticytoplasmic autoantibodies (ACPA). The following DPH syndromes were encountered: antibasement membrane antibody (ABMA) disease (four cases); idiopathic pulmonary hemorrhage (four cases); Wegeners granulomatosis (WG) (five cases); probable WG (six cases); systemic necrotizing vasculitis otherwise unclassified (three cases); systemic lupus erythematosus (two cases); rheumatoid arthritis (one case); seronegative juvenile rheumatoid arhritis (one case); IgA nephropathy (one case); idiopathic glomerulonephritis (two cases—one with and one without immune complexes); and unclassified pulmonary-renal syndromes (five cases). Capillaritis was found in lung biopsy samples from 30 of the 34 patients (88%) and included patients with every type of DPH syndrome. Serologic testing for ACPA was useful in the diagnosis of WG. Identification of ABMA in the serum, kidney, or lung was the defining feature for the diagnosis of ABMA-mediated disease. Subclassification of the cases could not be done solely on histologic grounds except for cases of WG that showed granulomatous inflammation, foci of necrosis, or vasculitis. Classification of the remaining cases required correlation with (a) clinical and laboratory data; (b) biopsy samples from other sites such as the kidney, nasal sinuses, or skin; and (c) results of immunofluorescence or electron microscopy of kidney or lung biopsy samples.

Host- and disease-specific factors affecting steatosis in chronic hepatitis C

Abstract Background/Aim: Steatosis is commonly present in chronic hepatitis C. Our aim was to evaluate host- and disease-specific factors associated with its occurrence. Methods: Histologic findings in 60 patients were correlated with body mass index, human leukocyte antigens, and other conventional parameters. Comparisons were made with 41 patients who had nonalcoholic steatohepatitis and 18 patients who had chronic hepatitis B. Results: Patients with chronic hepatitis C and steatosis had lower serum concentrations of γ-globulin ( p =0.01)_and immunoglobulin G ( p =0.05) than their counterparts without steatosis, and they had a lower frequency of antinuclear antibodies (19% versus 52%, p =0.01). They also had a higher mean body mass index ( p =0.002) and a greater frequency of risk factors for steatosis (70% versus 34%, p =0.009). These risk factors, however, occurred more commonly in patients with nonalcoholic steatosis ( p =0.007). Furthermore, fat deposition occurred more often in chronic hepatitis C than in chronic hepatitis B (52% versus 22%, p =0.03), despite comparable metabolic findings. The degree of steatosis in chronic hepatitis C was not associated with individual metabolic features. Conclusions: Steatosis in chronic hepatitis C is mainly a viral effect, and host-dependent metabolic factors may potentiate the manifestation. Fat deposition is associated with less immunoreactivity and it may connote a distinctive pathogenic mechanism.

Barrett's esophagus with high-grade dysplasia: An indication for esophagectomy?

Between 1982 and 1991, 19 patients (17 men and 2 women) with Barretts esophagus, 10 of whom were in a surveillance program, were found to have high-grade dysplasia without evidence of invasive carcinoma. Median age was 66 years (range, 30 to 79 years). Heartburn was the most common presenting symptom. Esophagoscopy at the time of high-grade dysplasia diagnosis demonstrated normal Barretts mucosa in 10 patients (53%), shallow ulcers in 3, slight mucosal irregularities in 2, small mucosal nodules in 2, stricture in 1, and shallow ulcer with stricture in 1. Eighteen patients underwent esophagectomy. There were no operative deaths. Nine patients (50%) had invasive carcinoma. Postsurgical stage was stage 0 in 9 patients, stage I in 6, stage IIA in 2, and stage IIB in 1. Median follow-up was 34 months (range, 2 to 116 months). Recurrent cancer developed in 2 patients. Overall 5-year survival was 66.7%; 5-year survival for patients with stage 0 disease was 100% and for stage I and II disease, 35.7%. We conclude that high-grade dysplasia in an indication for esophageal resection because of the high rate of associated early invasive carcinoma and that resection can be done safely with the expectation of excellent long-term survival. Because of these findings, we continue to recommend endoscopic surveillance in all patients with Barretts esophagus.

Pulmonary Alveolar Phospholipoproteinosis: Experience With 34 Cases and a Review

A retrospective review of Mayo Clinic records through 1983 revealed 84 patients (24 male and 10 female; mean age, 41 years) with the diagnosis of pulmonary alveolar phospholipoproteinosis. The major clinical features were dyspnea, cough, fever, and chest pain. Chest roentgenograms usually showed bilateral symmetric alveolar infiltrates, but asymmetric, unilateral, and chronic patchy patterns were also noted. Diagnosis was established by thoracotomy-lung biopsy in 26 patients. Histologic analysis revealed uniform filling of the alveoli by periodic acid-Schiff-positive material and maintenance of normal alveolar architecture. Electron microscopy showed enlarged alveolar macrophages with lamellar osmiophilic inclusions, dense granules, and myeloid bodies. Of the 21 patients who underwent therapeutic bronchoalveolar lavage, 13 had no recurrence of the disease during a mean follow-up of 8.8 years. In patients who underwent pulmonary function testing both before and after lavage, significant restrictive dysfunctions present before the procedure were alleviated afterward. Three deaths occurred among the 34 patients. Pulmonary alveolar phospholipoproteinosis may result from defective clearance of phospholipids by the alveolar macrophages, excessive production of phospholipids by type II pneumocytes, or both. It is likely a nonspecific response to a variety of injuries to the alveolar macrophage or type II pneumocyte or both, including exposure to certain dusts and chemicals and occurrence of hematologic diseases or infections. The uncommon occurrence of this disorder suggests individual susceptibility.

Significance of HLA DR4 in type 1 autoimmune hepatitis

BACKGROUND HLA DR3 and DR4 have been recognized as independent risk factors for autoimmune hepatitis. We compared the clinical features and prognosis of patients with HLA DR4 to those with HLA DR3 and other phenotypes to determine if subclassification by HLA is a valid consideration. METHODS Forty-four patients with HLA DR4; 41 patients with HLA DR3; and 16 patients with neither allele were studied. Ninety patients were treated with corticosteroids. RESULTS Patients with HLA DR4 were older (51 +/- 2 years vs. 38 +/- 3 years, P = 0.0001) and more commonly women (89% vs. 68%, P = 0.04) than counterparts with HLA DR3. Additionally, these patients had higher serum immunoglobulin G levels (3300 +/- 216 mg/dL vs. 2732 +/- 192 mg/dL, P = 0.05) and a greater frequency of concurrent immunologic diseases (59% vs. 27%, P = 0.005). Similar differences in clinical presentation distinguished the patients with HLA DR4 from those with other phenotypes. Remission during corticosteroid therapy (85% vs. 63%, P = 0.05) occurred more commonly in the patients with HLA DR4 than in those with HLA DR3 and treatment failure (10% vs. 32%, P = 0.03) occurred less frequently. CONCLUSIONS Patients with HLA DR4 have a different clinical profile than counterparts with other phenotypes, and they have a better response to corticosteroid therapy than patients with HLA DR3. Subclassification of patients by HLA DR phenotype may have clinical and prognostic value.

Distinctive clinical phenotype and treatment outcome of type 1 autoimmune hepatitis in the elderly

Autoimmune hepatitis is classically a disease of young women. Our aims were to determine its occurrence, clinical phenotype, and outcome in elderly patients and contrast findings to young adults. Two‐hundred‐and‐five white North American adults with definite type 1 autoimmune hepatitis were grouped according to age at presentation and the groups compared. Forty‐seven patients (23%) were aged ≥60 years (median age, 68 years), and 31 patients (15%) were aged ≤30 years (median age, 25 years). The patients ≥60 years had a higher frequency of cirrhosis at presentation than the patients ≤30 years (33% versus 10%, P = .03). They also had thyroid or rheumatic diseases more commonly (42% vs. 13%, P = .006). HLA DR3 occurred more frequently in the patients ≤30 years than in those ≥60 years (58% vs. 23%, P = .004), and HLA DR4 occurred more often in the patients ≥60 years (47% vs. 13%, P = .003). Patients aged ≥60 years failed corticosteroid treatment less commonly than those aged ≤30 years (5% vs. 24%, P = .03). Autoimmune hepatitis occurred in patients aged 18‐30 years (15%), 31‐39 years (15%), 40‐49 years (21%), 50‐59 years (25%), and ≥60 years (23%). Differences in age distribution, HLA frequencies, and treatment outcome occurred after age ≥40 years. In conclusion, elderly patients have a greater frequency of cirrhosis at presentation and HLA DR4 than patients ≤30 years, and they have a lower occurrence of treatment failure. Transitions in clinical and genetic phenotypes occur after age ≥40 years. Genetic susceptibilities may favor etiologic factors that are age‐related. (HEPATOLOGY 2006;43:532–538.)

Antibodies to soluble liver antigen, P450IID6, and mitochondrial complexes in chronic hepatitis

BACKGROUND Antibodies to soluble liver antigen, P450IID6, and the E2 subunits of mitochondrial dehydrogenase complexes occur in autoimmune liver diseases, but their specificities and implications are uncertain. The aims of the present study were to assess the importance of these autoantibodies in different types of chronic hepatitis. METHODS Sera from 62 patients with autoimmune hepatitis, 37 patients with cryptogenic hepatitis, and 19 patients with chronic hepatitis C were assessed under code by enzyme immunoassay. RESULTS Antibodies to soluble liver antigen were found in 7 patients with autoimmune hepatitis (11%) and 5 patients with cryptogenic disease (14%). Patients with antibodies to soluble liver antigen were indistinguishable from seronegative counterparts with autoimmune hepatitis. Seropositive patients with cryptogenic hepatitis had autoimmune features, and they responded to corticosteroid therapy. Five patients (8%) with autoimmune hepatitis were seropositive for antibodies to mitochondrial complexes. Three lacked antimitochondrial antibodies. None of the patients had antibodies to P450IID6, and patients with chronic hepatitis C were seronegative for all markers. CONCLUSIONS Antibodies to soluble liver antigen do not define a distinct subgroup of patients with autoimmune hepatitis. They may be found in some patients with corticosteroid-responsive cryptogenic hepatitis. Antibodies to E2 subunits and P450IID6 are uncommon in adults with chronic hepatitis.