Acute Methamphetamine-Induced Hepatic and Pancreatic Ischemia.

Methamphetamine is a central nervous system stimulant that induces arousal, a positive mood, cardiac stimulation, and an acute improvement in cognitive domains. Its illicit exploitation is rapidly growing in North America. Typically, extended use of the drug induces organ damage via vasoconstriction and subsequent ischemia. This case specifically discusses hepatic and pancreatic pathology resulting from methamphetamine overdose alongside an unusual discovery of globally necrotic von Meyenburg complexes.

The cutaneous lesions of dioxin exposure: lessons from the poisoning of Victor Yushchenko.

Several million people are exposed to dioxin and dioxin-like compounds, primarily through food consumption. Skin lesions historically called "chloracne" are the most specific sign of abnormal dioxin exposure and classically used as a key marker in humans. We followed for 5 years a man who had been exposed to the most toxic dioxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), at a single oral dose of 5 million-fold more than the accepted daily exposure in the general population. We adopted a molecular medicine approach, aimed at identifying appropriate therapy. Skin lesions, which progressively covered up to 40% of the body surface, were found to be hamartomas, which developed parallel to a complete and sustained involution of sebaceous glands, with concurrent transcriptomic alterations pointing to the inhibition of lipid metabolism and the involvement of bone morphogenetic proteins signaling. Hamartomas created a new compartment that concentrated TCDD up to 10-fold compared with serum and strongly expressed the TCDD-metabolizing enzyme cytochrome P450 1A1, thus representing a potentially significant source of enzymatic activity, which may add to the xenobiotic metabolism potential of the classical organs such as the liver. This historical case provides a unique set of data on the human tissue response to dioxin for the identification of new markers of exposure in human populations. The herein discovered adaptive cutaneous response to TCDD also points to the potential role of the skin in the metabolism of food xenobiotics.

Retinoic acid-induced lumbosacral neural tube defects: myeloschisis and hamartoma.

OBJECTS: To observe the morphological features of the lumbosacral neural tube defects (NTDs) induced by all-trans retinoic acid (atRA) and to explore the pathogenesis of these defects. METHODS: Rat embryos with lumbosacral NTDs were obtained by treating pregnant rats with administration of atRA. Rat embryos were obtained by cesarean. Fetuses were sectioned and stained with hematoxylin-eosin (H&E). Relevant structures including caudal neural tube were examined. In the atRA-treated rats, about 48% embryos showed lumbosacral NTDs. There appeared a dorsally and rostrally situated, neural-plate-like structure (myeloschisis) and a ventrally and caudally located cell mass containing multiple canals (hamartoma) in the lumbosacral NTDs induced by atRA. CONCLUSIONS: Retinoic acid could disturb the notochord and tail bud development in the process of primary and secondary neurulation in rat embryos, which cause lumbosacral NTDs including myeloschisis and hamartoma. The morphology is very similar to that happens in humans.

[Small bowel diaphragm disease associated with NSAIDs with histology of neuromuscular and vascular hamartoma. Case report and literature review]. / Enfermedad diafragmática intestinal asociada a AINE con histología de hamartoma neuromuscular y vascular. Presentación de un caso y revisión de la bibliografía.

Diaphragm disease (DD) induced by non-steroidal anti-inflammatory drugs (NSAIDs) and neuromuscular and vascular hamartoma (NMVH) are rare entities that can be difficult to recognize clinically, radiologically and pathologically. Both may cause small bowel obstruction and both reveal annular constrictions macroscopically. However, the 2 entities differ in that the constrictions are purely fibrous in DD whereas they have a hamartomatous histopathology in NMVH. We describe the case of a 76-year-old woman with a history of prolonged NSAID use who developed clinical features and gross pathology consistent with DD and histopathology of NMVH.

Enfermedad diafragmática intestinal asociada a AINE con histología de hamartoma neuromuscular y vascular. Presentación de un caso y revisión de la bibliografía / Small bowel diaphragm disease associated with nsaids with histology of neuromuscular and vascular hamartoma. Case report and literature review

La enfermedad diafragmática intestinal (EDI) asociada a los antiinflamatorios no esteroideos (AINE) y el hamartoma neuromuscular y vascular (HNMV) son 2 entidades raras, de difícil diagnóstico clínico, radiológico y patológico. Ambas pueden ser causa de obstrucción intestinal y macroscópicamente pueden evidenciarse en forma de estenosis intestinales de tipo anular. Sin embargo, difieren en su histología: en la EDI las estenosis son fibrosas y en el HNMV son hamartomatosas. Presentamos el caso de una mujer de 76 años con antecedentes de ingesta prolongada de AINE por artropatía que presentóclínica y macroscopia compatibles con EDI e histología propia del HNMV

Diaphragm disease (DD) induced by non-steroidal anti-inflammatory drugs (NSAIDs) and neuromuscular and vascularhamartoma (NMVH) are rare entities that can be difficult to recognize clinically, radiologically and pathologically.Both may cause small bowel obstruction and both reveal anular constrictions macroscopically. However, the 2 entities differ in that the constrictions are purely fibrous in DD whereas they have a hamartomatous histopathology in NMVH. We describe the case of a 76-year-old woman with a history of prolonged NSAID use who developed clinical features and gross pathology consistent with DD and histopathology of NMVH

Diaphragm disease after use of nonsteroidal anti-inflammatory agents: first report of diagnosis with capsule endoscopy.

Diaphragm disease of the small intestine is part of the spectrum of diseases associated with injury to the gastrointestinal tract induced by nonsteroidal anti-inflammatory drugs. Standard endoscopy or contrast studies of the small intestine rarely identify these lesions. The diagnosis usually is established at the time of surgery. We report the case of a 72-year-old woman with obscure gastrointestinal bleeding and intermittent obstruction of the small intestine who had had multiple hospitalizations and extensive testing. The patient had been treated with nonsteroidal anti-inflammatory drugs for osteoarthritis. A radiograph of the small intestine with barium contrast revealed no abnormalities, so capsule endoscopy was performed. Capsule endoscopy showed multiple small intestinal strictures beyond which the capsule could not pass. After the patient experienced continued symptoms suggestive of intermittent partial obstruction of the small intestine, computed tomography showed the capsule within a dilated loop of intestine adjacent to a stricture. After 9 days of conservative medical therapy and worsening symptoms, the patient required an exploratory laparotomy. The capsule was located in a 12-cm segment of intestine with 4 diaphragm-like lesions. Pathologic study found submucosal lesions with features identical to those of neuromuscular and vascular hamartoma (eg, mature, reactive tissue elements of smooth muscle, dense fibrous tissue, and nerve tissue bundles with scattered ganglion cells and vessels). No manifestations of Crohn disease were evident. This case represents the first diagnosis with capsule endoscopy of diaphragm disease of the small intestine with pathologic features of neuromuscular and vascular hamartoma.

Clinical and pathologic overlap in nonsteroidal anti-inflammatory drug-related small bowel diaphragm disease and the neuromuscular and vascular hamartoma of the small bowel.

Diaphragm disease (DD) is a radiographically subtle cause of small bowel obstruction and is part of the spectrum of diseases associated with nonsteroidal anti-inflammatory drug injury. The neuromuscular and vascular hamartoma (NMVH) is a nonepithelial hamartomatous, submucosally based proliferation of mature submucosal elements capable of causing small bowel obstruction. The authors report two patients in whom the clinical setting and gross pathology are that of DD, but the histologic characterization is identical to that described for NMVH. It is probable that in some patients the two diseases overlap so that some patients readily fit the criteria for both entities.

Bile duct hamartoma occurring in association with long-term treatment with danazol.

We report a case of bile duct hamartoma which developed in a patient who had been on long-term danazol treatment. Such patients should be under close follow-up, preferably with periodic ultrasound examination of the liver. If the patient develops a liver mass, because of non-specific clinical features and imaging appearances, biopsy may be the only way to achieve a definitive diagnosis.

[Clinical, epidemiological, morphological and etiopathogenetic aspects of benign tumors of hepatocytic derivation, with description of a case of focal nodular hyperplasia]. / Aspetti clinici, epidemiologici, morfologici ed etiopatogenetici dei tumori benigni, di dervazione epatocitaria, con descrizione di un caso di iperplasia focale nodulare.

PIP: Since the introduction of hormonal contraception many studies have been published on the role of oral contraceptives (OCs) in causing liver neoplasms. The tumor registers established in the US, England, and France allow researchers to study the incidence of such tumors, and to better evaluate the population at risk. The most frequent types of benign hepatic tumors are adenomas, hepatocellular adenoma or biliary duct adenoma, and focal nodular hyperplasia. Although morphologically very different, such tumors have been called with a varied and confusing terminology. Liver tumors are usually discovered by chance during laparotomy, and are more numerous in women aged 20-40. Radiography, scintigram and echography and very helpful in diagnosis, but arteriography is still the best diagnostic tool. Therapy consists of simple resection or of lobectomy, when possible. Many authors, however, insist on their sponteneous regression after OC termination, if OCs are the cause. According to the most recent studies OC-caused liver tumors happen more often in patients who have taken mestranol for over 4 years; liver tumors are also more common in multiparous women and may grow very quickly during pregnancy. In recent years the association between liver tumors, benign or malignant, and treatment with androgens has often been documented. This document presents the case of a 26 year old patient hospitalized for pain and for the presence of a large abdominal mass. The patient suffered severe dysmenorrhea and serious menstruation disorders. The patient had never taken OCs but had been treated for a long time with aspirin for headache and with diazepam for a nervous breakdown during adolescence, and more recently during pregnancy. The patient underwent surgery, and a large focal nodular hyperplastic tumor was excised.^ieng

Focal nodular hyperplasia of the liver and hepatic cell adenoma in women on oral contraceptives.

The article reports on the respective occurrence of focal nodular hyperplasia and hepatic cell adenoma in the liver of two women on oral contraceptives. The hepatic cell adenoma showed serious vascular lesions, including peliosis hepatis. Both tumors were removed surgically, and the patients are well. A possible relationship between oral contraception and benign hepatic tumor genesis is discussed under consideration of the pertinent literary data.

Survey of primary liver tumors and oral contraceptive use.

The American College of Surgeons' survey data on 378 female and 165 male cases of primary liver tumors reported by 477 hospitals in the United States during 1970--1975 are presented. In males, 91.5% of the tumors were malignant, confirming the rarity of benign liver tumors in males. Among females, 43.9% were malignant and 56.1% were benign. Of the 212 benign tumors, 96 were hepatic cell adenomas and 58 were focal nodular hyperplasias. A positive history of oral contraceptive use was found in nearly half of all tumors, 65% of benign tumors, 74% of hepatic cell adenomas, and 74% of focal nodular hyperplasias. High frequencies of benign tumors were observed in the age group 20--30 yr. More than 80% of the tumors in this age group were found in oral contraceptive users. Symptomatology was more severe among users. No case of intraperitoneal bleeding was observed in nonusers. The findings confirm the suggested association between use of oral contraceptives and hepatic cell adenomas and focal nodular hyperplasias.

PIP: The American College of Surgeons conducted a survey of primary liver tumors in cancer-approved hospitals throughout the U.S. in the 6-year period, 1970-75. Of the 165 male cases identified, 91.5% were malignant, indicating the rarity of benign liver tumors in males. Of the 378 female cases located, 43.9% were malignant and 56.1% were benign. Nearly 50% of all primary liver tumors were found in women with a positive history of OC (oral contraceptive) usage, with OC history unknown in 29% of the study population. OC users accounted for 65% of all benign tumors reported, 74% of all hepatic cell adenomas, 74% of all focal nodular hyperplasias, 80% of benign tumors in the 20-30 year age group, and almost 90% of hepatic cell adenomas in the age group 26-30. This incidence survey confirms the reported association between OC usage and some types of benign liver tumors, especially hepatic cell adenomas and focal nodular hyperplasias. It is pointed out, and illustrated with graphs, that the age pattern for benign tumores corresponds to the age pattern for OC use. More of the OC users who developed benign tumors had used mestranol, results confirming earlier reported associations. However, this may simply be due to the fact of mestranol's earlier availability. Symptomatology, particularly with regard to pain and mass, was more pronounced in OC users. Results on duration of OC use and any association with tumor development were inconclusive. The incidence of benign liver tumors has increased from 1970 to 1975.

Relation of steroids to liver oncogenesis.

Experience with pathological material from 150 women with liver tumors is reviewed. The features of liver cell adenoma and focal nodular hyperplasia are sufficiently different that the vast majority of the benign tumors can be easily subclassified. Although most occurred in women ingesting steroids, the wide usage of oral contraceptives makes it difficult to prove a causative role. Nineteen of the tumors were malignant and, to date, 12 of those patients have died of their disease. Since hepatomas are much more common than benign liver tumors, one must be even more circumspect in indicting steroids in their causation. In this group of women none had cirrhosis, whereas in the general population cirrhosis is a very common precedent lesion. Further investigation of estrogens and primary liver carcinoma would be timely.

PIP: Histological specimens from 150 women with liver tumors are discussed. Of the 150 patients under consideration, 85% had ingested contraceptive steroids, most for more than 3 years. Of these 64% had taken pills containing mestranol, and 18% had used ethinyl estradiol; 18% had taken both. Average age was about 30 years, and pain was the most common presenting symptom. 19 tumors were malignant (hepatoma), 57 were adenoma, 68 were focal nodular hyperplasia, and 6 were unclassified. To date, 12 of the 19 hepatoma patients have died. In addition to presenting numerous figures depicting the pathology material and a discussion of tumor differentiation difficulties, speculation between steroid ingestation and tumor appearance is considered. Since hepatomas are much more common than benign liver tumors, circumspection is in order before indicting steroids as causative. In this group of women studied, none had cirrhosis, for example, whereas cirrhosis is very common in the general population. The authors call for further investigation of estrogens and primary liver tumores.

Role of oral contraceptive agents in the pathogenesis of liver tumors.

Since the introduction of oral contraceptive steroids in 1960 there has been a sharp increase in the incidence of benign liver tumors. Epidemiologic and other evidence links focal nodular hyperplasia and hepatic cell adenoma to the use of these agents. The risk increases with long-term exposure. The majority of patients were less than 35 years old. Most patients were exposed to mestranol (ME) alone or alternately with ethinylestradiol, both synthetic steroidal estrogens. Inability to demethylate ME in the smooth endoplasmic reticulum of hepatocytes may allow massive accumulation of oncogenic metabolites. This is probably a pharmacogenetic variable in a small number of women. Cholestasis, hypervascularity, induction of intracellular enzyme systems, thrombogenesis, and thickening of arterial and venous walls are other known effects of synthetic estrogens and progestogens. All may contribute to the pathogenesis of liver tumors. Many patients are asymptomatic until there is rapid expansion of the tumor. Pain occurs when Glisson's capsule stretches. Intrahepatic bleeding and liver rupture are common sequelae. Ligation of the hepatic artery may be lifesaving in the face of exsanguinating liver bleeding. Reports of regression with observation alone are encouraging. Instances of progression of unresected adenomas to rupture during subsequent pregnancy dictate avoidance of sex steroids in patients with hepatic neoplasia. Sonography, computerized axial tomography, radionuclide scans, and selective celiohepatic angiography are useful methods for the diagnosis of liver tumor in the symptomatic patient. There is a primary need to develop biochemical methods for detecting patients at risk for developing liver tumors. Epidemiologic research and central reporting of case histories are needed in the search for common factors.

Primary liver tumors and oral contraceptives. Results of a survey.

Data on 378 (in females) and 165 (in males) cases of primary liver tumors reported by 477 hospitals in the United States during 1970 to 1975 show that in males, 91.5% of the tumors were malignant, and in females, 43.9% were malignant and 59.1% were benign. Of the 212 benign tumors in females, 96 were hepatic cell adenomas and 58 were focal nodular hyperplasias. A history of oral contraceptive use was found in nearly half of all women: 65% with benign tumors, 74% with hepatic cell adenomas, and 74% with focal nodular hyperplasias. Symptoms were more severe among users. No case of intraperitoneal bleeding was observed in nonusers. The findings confirm the suggested association between oral contraceptive use and hepatic cell adenomas and focal nodular hyperplasias.