Microscopic colitis with granulomatous inflammation.

AIMS: To present four cases in which the clinical and endoscopic findings were consistent with microscopic colitis, but the inflammatory infiltrate included a conspicuous granulomatous reaction. Microscopic colitis is defined as a syndrome of chronic watery diarrhoea with a chronic inflammatory cell infiltrate in the colonic mucosa and without significant abnormalities at colonoscopy. It encompasses both collagenous and lymphocytic colitis. METHODS AND RESULTS: In all cases the clinical course and endoscopic findings were unlike Crohn's disease and no infectious agents were identified. In all cases the main symptom was frequent watery diarrhoea, all were female and there were no endoscopic findings apart from mild mucosal erythema. Histologically, an active chronic inflammatory infiltrate was accompanied by scattered non-necrotizing granulomas, often closely associated with crypt epithelium (cryptolytic or pericryptal granulomas). In three of the patients the symptoms began after antibiotic use or had worsened with antibiotic use. Two of the patients were on allopurinol at the time of the onset of symptoms. In two of the patients symptoms have continued for more than 10 years. One patient died as a result of medical complications relating to severe diarrhoea and dehydration. CONCLUSIONS: Microscopic colitis rarely may be characterized by granulomatous inflammation. Such patients should not be regarded as having Crohn's disease.

Aberrant p16(INK4A) and DPC4/Smad4 expression in intraductal papillary mucinous tumours of the pancreas is associated with invasive ductal adenocarcinoma.

BACKGROUND AND AIMS: Intraductal papillary mucinous tumours (IPMT) of the pancreas constitute a unique pathological entity with an overall incidence of associated invasive malignancy of 20%. The malignant potential of an individual IPMT cannot be accurately predicted. Preoperative estimation of the risk of associated invasive malignancy with IPMT would be of significant clinical benefit. As aberrations in cell cycle regulatory genes are associated with the progression of precursor pancreatic ductal lesions to invasive adenocarcinoma, we examined expression of key cell cycle regulatory genes in the cyclin D1/retinoblastoma pathway and the transforming growth factor beta/Smad4 signalling pathway in a cohort of patients with surgically resected IPMT. METHODS: Sections of formalin fixed paraffin embedded pancreatic tissue from a cohort of 18 patients with IPMT were examined using immunohistochemistry for protein expression of cell cycle regulatory genes p16(INK4A), p21(CIP1), p27(KIP1), cyclin D1, pRb, and p53, as well as the cell signalling molecule Smad4. A comparison of expression levels was made between adenoma/borderline IPMT (10 patients) and intraductal papillary mucinous carcinoma (IPMC) (eight patients, four of whom harboured invasive carcinoma). Statistical analysis was performed using the chi(2) and Fisher's exact tests. RESULTS: Aberrant expression of the proteins examined increased in frequency from adenoma/borderline IPMT to IPMC. Specifically, there was a significantly greater incidence of loss of p16(INK4A) expression in IPMC: 8/8 lesions (100%) compared with 1/10 (10%) adenoma/borderline IPMT (p<0.001). Similarly, loss of Smad4 expression was associated with IPMC: 3/8 (38%) versus adenoma/borderline IPMT 0/10 (p<0.03). Loss of Smad4 expression within the IPMT was the best marker for the presence of invasive carcinoma (p<0.001). CONCLUSIONS: These data indicate that loss of p16(INK4A) and Smad4 expression occur more frequently in IPMC alone, or with associated invasive carcinoma, compared with adenoma/borderline IPMT. Aberrant protein expression of these cell cycle regulatory genes in IPMT and pancreatic intraepithelial neoplasia in the current model of pancreatic cancer progression suggest similarities in their development and may also represent the subsequent risk of invasive carcinoma.

Renal dysfunction associated with the perioperative use of diclofenac.

UNLABELLED: Postoperative renal dysfunction in rats is induced by ketorolac dosed concurrently with gentamicin. Herein, we report the renal effects of diclofenac in four groups of rats: control (C = anesthesia, surgery); diclofenac (D = anesthesia, surgery, diclofenac 18 mg x kg(-1) x d(-1)); gentamicin (G = anesthesia, surgery, gentamicin 20 mg x kg(-1) x d(-1)); and diclofenac and gentamicin (DG = anesthesia, surgery, diclofenac, gentamicin). Renal function, after three treatment days, was assessed using histology, p-aminohippurate (PAH), and iothalamate (IOT) clearances, serum and urine electrolytes, osmolality, urea, and creatinine. Urine output was increased (from 5.2 to 12.5 mL/24 h), and urine osmolality was decreased (from 2121 to 883 mOsm/kg) in the DG group. PAH and IOT clearances were decreased in the G and DG groups (PAH by 18%, IOT by 22%; PAH by 38%, IOT by 43%, respectively); there were no changes in the C and D groups. Urea and creatinine clearances were decreased by 61% and 43%, respectively, in the DG group. Kidney sections showed the most severe pathologic changes in the DG group. Our data indicate that the perioperative combination of diclofenac and gentamicin was deleterious to renal function. IMPLICATIONS: Diclofenac alone does not result in significant perioperative renal dysfunction, but the combination of gentamicin and diclofenac is deleterious to renal function. Considering this and previous findings, the evidence suggests that treatment with aminoglycosides may be a significant risk factor for inducing perioperative renal failure during treatment with nonsteroidal antiinflammatory drugs.

Factors influencing ketorolac-associated perioperative renal dysfunction.

UNLABELLED: Nonsteroidal antiinflammatory drugs (NSAIDs) are useful for the treatment of postoperative pain, but there is continuing concern about adverse effects on renal function. We studied the renal effects of ketorolac in an animal model using Fischer 344 rats undergoing isoflurane anesthesia and laparotomy. Treatment groups--control (C), ketorolac (5 mg x kg(-1) x d(-1)) (K), large-dose ketorolac (15 mg x kg(-1) x d(-1)) (KH), dehydration-ketorolac (5 mg x kg(-1) x d(-1)) (DK), gentamicin (20 mg x kg(-1) x d(-1)) (G), and gentamicin (20 mg x kg(-1) x d(-1)) with ketorolac (5 mg x kg(-1) x d(-1)) (GK)--each comprised 10 animals. Renal function was assessed before laparotomy and after 3 treatment days using concurrent paraaminohippurate and iothalamate clearances, respectively, to estimate renal plasma flow and glomerular filtration rate, and by measuring serum and urine electrolytes, osmolality, urea, and creatinine. A significant increase in serum potassium was found in the GK and DK groups. There were no major changes in renal function in the C, K, KH, and DK groups. Mild renal dysfunction was found in the G group. We found severe and consistent changes in renal function, accompanied by severe, widespread histological changes of acute tubular necrosis, in the GK group. In this postoperative rat model, the combination of ketorolac and gentamicin was deleterious to renal function. IMPLICATIONS: We examined the renal effects of the nonsteroidal antiinflammatory drug ketorolac. Renal function was measured in rats before and after surgery and 3 days' drug administration; the kidneys studied by using microscopy. Only ketorolac plus the antibiotic gentamicin produced marked changes in kidney function and structure.

Glomerulonephritis secondary to Barmah Forest virus infection.

Clinical infection with Barmah Forest virus (BFV) is becoming increasingly recognised with serological testing. We report the first case of glomerulonephritis after BFV infection. The patient required diuretic and antihypertensive therapy, but made an almost complete recovery. BFV infection should be considered in the differential diagnosis of glomerulonephritis.

Intraductal papillary-mucinous neoplasm of the pancreas: a report of five cases with immunohistochemical findings.

Five cases of intraductal papillary-mucinous neoplasm (IPMN) of the pancreas are here described. This group of tumors represents a distinct clinicopathological entity with characteristic endoscopic, radiological, gross and microscopic appearances. Our five cases all showed marked dilatation of the main pancreatic duct which contained mucin and papillary tumor, sometimes filling and sometimes lining the lumen. The papillae were lined by columnar epithelium showing varying degrees of dysplasia. In one case there was adjacent invasive adenocarcinoma. Immunohistochemical staining for p53 protein was strongly positive in a majority of cells in the three cases with severe epithelial dysplasia and in the invasive adenocarcinoma, while weaker staining in a minority of cells was seen in the remaining two cases. A small proportion of tumor cells expressed PCNA and Ki-67 immunohistochemically in four cases, while the case with severe dysplasia and invasive carcinoma showed positivity for these proliferation markers in most cells. The four cases of exclusively intraductal tumor showed no evidence of disease recurrence at follow-up (median 55 months). The patient with IPMN and associated invasive adenocarcinoma died 21 months post-operatively. In view of its relatively favourable prognosis, it is important that IPMN is recognised.

Stromal endometriosis of the cervix simulating Kaposi's sarcoma.

Stromal endometriosis refers to the presence of endometriotic stroma without the presence of endometrial glands. We report a case in the uterine cervix in which the diagnosis of Kaposi's sarcoma was considered before being discounted on histological and immunohistochemical grounds.

Minocycline-induced liver injury.

Tetracycline may cause fatty infiltration of the liver; more recently, it has been reported to cause intrahepatic cholestasis with bile duct depletion. However, minocycline, a derivative of tetracycline, is not generally recognized to be hepatotoxic. We report a series of six cases of presumed minocycline-induced liver injury; five of these patients had acute hepatitic illness, whereas one had a more prolonged course with histological evidence of chronic hepatitis. In addition, three patients demonstrated abnormal anti-nuclear antibody levels, and one had positive double-stranded DNA.

Iron tablets cause histopathologically distinctive lesions in mucosal biopsies of the stomach and esophagus.

Iron tablets are widely used in the community. Severe, sometimes lethal, damage to the gastrointestinal tract following overdose is well known, but there is less appreciation of the damage that can be caused by therapeutic dosage. In this histological study of three esophageal lesions and six gastric lesions (including one autopsy case), heavy iron accumulation was demonstrated within ulcer granulation tissue, in connective tissue and blood vessels of the mucosal lamina propria, and within glandular and squamous epithelium. The appearance was distinctive and was similar to that seen following overdosage, although more localized. Five of the patients studied had evidence of delayed esophageal or gastric emptying which could have contributed to the damaging effect of the iron tablets. In most of the patients ulceration appeared to have preceded the commencement of iron therapy, so that the iron probably exacerbated rather than initiated ulceration and stricture formation. Histopathological reporting of iron-induced changes in endoscopic biopsies will alert clinicians to a correctable pathological process.

Pancreatic pseudotumor arising in association with Sjögren's syndrome.

A case is presented of an elderly female who was found by imaging to have an enlarged pancreas with narrowed distal common bile duct, thought to be neoplastic. Resection revealed an inflammatory and fibrosing process of the pancreas, suggestive of autoimmune disease. Subsequently she developed dry mouth, enlarged salivary glands, and an enlarged lacrimal gland with typical histology of Sjögren's syndrome. Pathological review of the contralateral lacrimal gland excised 20 years earlier showed similar histology. This case is a rare, but not unique, example of pancreatic pseudotumor associated with Sjögren's syndrome. The increasing use of sophisticated abdominal imaging may result in an increased detection of such pseudotumors. Failure to recognize their real nature can lead to inappropriate surgery.

Efficacy of cisapride therapy in functional dyspepsia.

AIM: To assess the efficacy of cisapride therapy in relieving symptoms of functional dyspepsia. METHODS: After a 2-week placebo run-in period, 61 out of 74 patients were eligible to enter a 4-week double-blind treatment phase, consisting of treatment with cisapride (10 mg) or placebo tablets t.d.s. Gastric emptying was assessed scintigraphically at entry to the study. Patients were stratified before treatment into those with or without active chronic (Helicobacter pylori) gastritis. Patients were also classified retrospectively into those with 'reflux-like' dyspepsia (n = 29) and those with 'motility-like' dyspepsia (n = 32). RESULTS: At the end of the active treatment phase, there was a similar significant (P < 0.001) reduction in total symptom score from baseline in both cisapride (8.9 +/- 0.5 to 5.8 +/- 0.6) and placebo (9.7 +/- 0.6 to 5.5 +/- 0.6) groups. Scores for heartburn and continual bloating were significantly reduced in the cisapride but not the placebo group; improvement was attributable to patients with normal, rather than delayed, rates of gastric emptying. For continual bloating, significant improvement also occurred in the cisapride subgroup without gastritis, but not in the subgroup with gastritis (mean symptom score reduction 0.48 +/- 0.18, P = 0.03). For global evaluation by the investigator and by the patient, the overall improvement rates were not statistically different between cisapride and placebo groups. In those with normal gastric emptying, however, there was a significant (P = 0.01) improvement in general well-being in the cisapride but not in the placebo group. CONCLUSIONS: We were unable to show major differences in the short-term efficacy of cisapride and placebo in functional dyspepsia. There were indications, however, of beneficial effects of cisapride over placebo in those with 'reflux-like' dyspepsia, and in those without gastroparesis.

Primary ependymoma of a cranial nerve. Case report.

Ependymomas arising from peripheral or spinal nerves are extremely rare. Other ectopic ependymomas are found mostly in the sacrococcygeal region, possibly in association with developmental anomalies. The case of an ependymoma arising from a cranial nerve in a 40-year-old man is described.

Intragastric distribution and gastric emptying of solids and liquids in functional dyspepsia. Lack of influence of symptom subgroups and H. pylori-associated gastritis.

The relative contributions of altered gastric motor function and Helicobacter pylori-associated active chronic gastritis to the pathogenesis of functional dyspepsia are controversial. We therefore evaluated scintigraphically the intragastric distribution and gastric emptying of a mixed solid-liquid meal in 75 patients with functional dyspepsia; patients were subdivided on the basis of both specific symptom clusters and the presence or absence of H. pylori gastritis. Twenty-one (28%) patients displayed abnormal solid and/or liquid gastric emptying, with prolonged solid lag time the most prominent alteration detected. The number of patients with abnormal scintigraphic patterns increased to 36 (48%) when intragastric distribution parameters (fundal half-emptying time and antral maximal fraction) were examined. Although patients with reflux-like dyspepsia (N = 36) demonstrated significantly slower rates of liquid emptying at 45 and 70 min and a higher prevalence of abnormal liquid intragastric distribution when compared to patients with motility-like dyspepsia (N = 39) or to controls (N = 34), the absolute differences were small and unlikely to be of clinical significance. Patients without H. pylori gastritis (N = 50) demonstrated a significantly more prolonged solid lag time when compared to those with H. pylori gastritis (N = 25), but the difference was small and there were no other differences between these two subgroups.(ABSTRACT TRUNCATED AT 250 WORDS)

Flucloxacillin induced liver disease: histopathological findings at biopsy and autopsy.

The histological appearances of liver biopsies of 13 patients who developed cholestasis following courses of flucloxacillin are presented. In most of the cases jaundice and pruritus were protracted and in nearly all cases liver function tests are yet to return to normal after mean follow-up of 18 mths. One patient died after 7 mths of jaundice and another shows clinical evidence of secondary biliary cirrhosis. Biopsies typically showed hepatocellular and canalicular bile stasis with minimal or no hepatitis. Mild portal fibrosis and a patchy portal lymphocytic infiltrate were usually present. In 4 cases bile ducts were reduced in number and in 6 cases reduced in size. Bile duct epithelium showed degenerative changes but only occasional infiltration by inflammatory cells. Ductular proliferation was quite variable and in some cases--most noticeably the fatal case--was inconspicuous despite depletion of bile ducts. The appearances suggested damage not only of hepatocytes but also of bile ducts and proliferating ductules. This may explain the prolonged and occasionally irreversible hepatic disease associated with the use of flucloxacillin. Flucloxacillin should be included amongst the causes of vanishing bile duct syndrome.

The acute appendicitis syndrome: psychological aspects of the inflamed and non-inflamed appendix.

The aetiological importance of stressful life events and psychological characteristics was assessed amongst 280 appendicectomy patients of whom 80% were classified with 'acutely inflamed' (organic) appendicitis and 20% with 'non-inflamed' (non-organic) appendicitis. Patients were compared with a community comparison group. Specific characteristics of life stressors, namely severe goal frustration for organic patients and severe threat for non-organic patients, were the best predictors of patient outcome. Whilst psychological characteristics were not useful in discriminating between patients, depression in particular, was clearly associated with both conditions, with 38% of non-organic and 28% of organic patients with depression scores in the clinical range. As the patient's clinical depression status failed to modify the effect of the life stress predictors, it was concluded that life stress played an important role in the development of the patients GI symptoms, irrespective of their clinical depression status.

Renal oncocytomas--an Australian experience.

A review was made of 24 cases of renal oncocytoma seen between 1978 and 1989. There was considerable overlap between the clinical presentation of renal oncocytomas and renal carcinomas. Although pre-operative radiological, cytological and pathological investigations may suggest the presence of an oncocytoma, these studies cannot make a definitive diagnosis. We recommend that these tumours be treated as potential renal carcinomas until post-operative microscopic evaluation proves otherwise.