Biomedical subjects

U Khettry

Publications and source records attributed to U Khettry.

At least 19 recordsLinked to original sources

PubMed1999

Fibrosis/cirrhosis after orthotopic liver transplantation.

The causes and pathologic changes leading to fibrosis and cirrhosis after orthotopic liver transplantation (OLT) are not fully defined. The computerized pathology files were searched for cases of fibrosis/cirrhosis after OLT. Of 493 grafts from 435 patients, 35 grafts from 32 patients of posttransplantation liver fibrosis/cirrhosis were identified and retrieved (7%). Detailed histopathologic examinations of all post-OLT liver biopsy specimens were performed in conjunction with clinical, virologic, serologic, and molecular diagnostics information. Two cases with subcapsular septa and fibrous tissue close to hilum were excluded as false positives. Fibrosis/cirrhosis was confirmed in the remaining 33 grafts. In 20, the underlying cause was recurrent viral hepatitis, including eight with hepatitis C, 10 with hepatitis B, and two with combined hepatitis C and B. Another two with pretransplantation chronic hepatitis B developed cirrhosis without detectable virologic markers after OLT; these were biliary type secondary to obstruction in one, and chronic changes due to severe graft ischemia in one. Three patients acquired hepatitis C after OLT, with molecular confirmation available in two. In five patients, the underlying causes were Budd-Chiari syndrome and autoimmune hepatitis, recurrent autoimmune hepatitis, recurrent primary biliary cirrhosis, alcohol-induced liver disease, and recurrent bile duct carcinoma. Three cases had centrilobular fibrosis but without bridging septa or cirrhosis as a result of chronic rejection. It was concluded that (1) Cirrhosis after OLT is uncommon (7%). (2) Chronic rejection does not lead to cirrhosis, but it may result in centrilobular fibrosis. (3) In most (70%) cases, cirrhosis after OLT is attributed to recurrent or acquired viral hepatitis.

Biopsy↗

PubMed1999

Nodular lymphoid lesion of the liver: an immune-mediated disorder mimicking low-grade malignant lymphoma.

Three cases of unusual lymphoid infiltrate forming nodular macroscopic masses in the liver were studied in the authors' surgical pathology laboratory. These lesions posed difficulty in diagnosis, and their differentiation from low-grade lymphoma was not possible on histopathologic evaluation alone. The liver masses were analyzed histologically and immunohistochemically as well as for clonal immunoglobulin heavy chain (IgH) and T-cell receptor gamma (TCR-gamma) gene rearrangements. The lesions were seen as solitary grossly distinct firm nodules in all three patients, measuring 0.4, 0.7, and 1.5 cm, respectively, in their greatest dimensions. Two were found in livers removed because of end-stage primary biliary cirrhosis at the time of orthotopic liver transplantation, and the third was an incidental finding during laparotomy. Microscopically, these were nodules composed of small lymphocytes, plasma cells, and immunoblasts, with varying degrees of admixed acute inflammatory cells and scattered lymphoid follicles. By immunohistochemistry and molecular studies, these were found to be reactive lymphoid proliferations. All patients are alive and well at 2, 4, and 13 years, respectively. It is concluded that these cases represent a unique type of nodular lymphoid lesion, which is probably an immune-mediated benign reactive hyperplasia. It constitutes an entity by itself and must be distinguished from low-grade lymphoma. For a definitive diagnosis, immunohistochemistry and molecular studies are required.

Diagnosis, Differential↗

PubMed1999

Sarcoidosis with selective involvement of a second liver allograft: report of a case and review of the literature.

A case of sarcoidosis recurrent in a patient's second liver allograft is described. There was no granulomatous disease seen in the patient's first liver allograft. After the second orthotopic liver transplantation (OLT), the patient was successfully treated for acute rejection, aspergillus infection, and cytomegalovirus viremia. Approximately 2 months after the second OLT, the patient was treated with long-term interferon-alpha for recurrent hepatitis C. Five years after the operation, he experienced liver failure secondary to recurrent hepatitis and underwent a third OLT. This is only the second reported case of sarcoidosis recurrent in the liver parenchyma of a transplanted organ and the first in which interferon-alpha might have played a role.

Abscess↗

PubMed1998

Inflammatory myofibroblastic tumor of the pancreaticobiliary region: morphologic and immunocytochemical study of three cases.

Inflammatory myofibroblastic tumor (IMT) is a rare tumor of the pancreaticobiliary region. The etiology and biologic behavior of IMTs at this site are unknown. We present three patients with IMT of the pancreaticobiliary region, each with long-term follow-up. In all three cases a second tumor developed. Grossly these tumors mimicked a malignant process. Microscopically, all were composed of an admixture of spindle cells and chronic inflammatory cells, including plasma cells, lymphocytes, eosinophils, and macrophages. The spindle cells stained positively for smooth muscle actin and vimentin but were negative for S-100, cytokeratin, CD35, and latent membrane protein. Results of in situ hybridization with EBER probes were negative in all cases. In addition to carcinoma, the differential diagnosis of these tumors includes follicular dendritic cell tumor and inflammatory fibrosarcoma. The importance of extensive pathologic examination to prevent misdiagnosis and the need for long-term follow-up are emphasized. This subset of IMT does not appear to be related to Epstein-Barr virus.

Actins↗

PubMed1997

Allelic deletion and mutation of the von Hippel-Lindau (VHL) tumor suppressor gene in pancreatic microcystic adenomas.

An association between pancreatic microcystic (serous) adenomas (MCAs) and von Hippel-Lindau (VHL) disease has been suggested. However, genetic alterations of the VHL gene in MCAs of the pancreas have never been reported. In this study, we performed genetic analysis of 12 pancreatic MCAs. In 2 cases, VHL disease was documented clinically, and 10 cases were sporadic. For LOH analysis, tumor and normal pancreatic cells were procured from formalin-fixed, paraffin-embedded material using tissue microdissection. After DNA extraction, the samples were amplified by polymerase chain reaction using the polymorphic markers D3S2452, D3S1110, D3S192, and D3S656. In addition, the sporadic tumors were analyzed for VHL gene mutations using probes 3b/10b and K55/K56. Both MCAs associated with VHL disease showed LOH with at least one of the microsatellite markers tested. Among the 10 sporadic cases, 7 tumors showed LOH at the VHL gene locus. A somatic VHL gene mutation on exon 2 was documented in one sporadic case. The study provides the first direct genetic evidence for the role of the VHL gene in MCA tumorigenesis. Furthermore, VHL gene alterations may be detected in both VHL-associated and sporadic pancreatic MCAs.

Adenoma↗

PubMed1996

Hepatitis C virus reinfection in orthotopic liver transplant patients with or without concomitant hepatitis B infection.

Although recurrence of hepatitis C virus (HCV) in orthotopic liver transplant (OLT) patients is frequent, the relationship between HCV recurrence and graft pathology, particularly in patients who also have a history of hepatitis B virus (HBV), is unclear. The recurrence of HCV after OLT was determined by reverse transcriptase-nested polymerase chain reaction (RT-PCR) in the sera and livers of 41 patients with OLT, 32 of whom underwent transplants for HCV or HBV-related disease. Results were compared with liver function tests, liver histology (including HBV immunohistochemistry), and antibody status. HCV PCR was more frequently positive in OLT patients with a history of HCV only (59%) than in those with a history of both HCV and HBV (41%) or no history of viral infection (2%). Recurrent HCV (60% overall) was associated with mild elevation of liver function tests and mild to moderate hepatitis. In patients who underwent transplants for both HCV and HBV disease, hepatitis on biopsy was more frequently associated with recurrent HBV than with recurrent HCV. We conclude that graft reinfection with HCV, which is frequent in OLT patients with or without HBV recurrence, is usually associated with only mild to moderate hepatitic changes compatible with graft survival.

Base Sequence↗

PubMed1995

High-dose vitamin E supplementation has no effect on ethanol-induced pathological liver injury.

The effect of alpha-tocopherol (alpha-T) supplementation on ethanol-induced liver damage was studied. The intragastric feeding rat model was used in this study. Both normal and alpha-T supplemented animals (3125 IU/kg body weight) were fed liquid diet and ethanol for 1 mo. In pair-fed animals, ethanol was isocalorically replaced by dextrose. The blood ethanol level in the ethanol-fed groups was between 150 to 350 mg/dl. Lipid peroxidation was assessed by measuring liver thiobarbituric acid reactive substances (TBARS) and conjugated dienes. Liver damage was assessed by light microscopy. Overall, chronic ethanol treatment resulted in increase in TBARS and conjugated dienes in both normal (60% and 35%, P < .01, respectively) and alpha-T-supplemented groups (50% and 47%, P < .01, respectively). In animals receiving either dextrose or ethanol and regular diet, there was a significant inverse correlation between liver alpha-T and TBARS (r = 0.88, P < 0.01) and conjugated dienes (r = -0.75, P < .05). In contrast, in the vitamin E-supplemented rats, a significant positive correlation was observed between liver alpha-T, TBARS (r = 0.78, P < .01) and conjugated dienes (r = 0.87, P < .01). Of major significance is that alpha-T supplementation had no effect on ethanol-induced pathological changes in the liver. In conclusion, these results show that in the intragastric feeding model, alpha-T supplementation had no protective effect on ethanol-induced liver damage.

Animals↗

PubMed1995

Hepatitis C infection: a rare cause of fulminant hepatic failure.

Fulminant hepatic failure is caused by a variety of viruses, toxins, and metabolic derangements. The hepatitis C virus (HCV) causes indolent development of cirrhosis and has not been associated with fulminant hepatic failure. We report the first documented case of fulminant hepatitis C in the United States. The patient developed jaundice and stage IV encephalopathy. Initial laboratory evaluation did not reveal the etiology. The patient survived without liver transplantation. Three wk later he was found to have a positive HCV RNA and anti-HCV antibody seroconversion. He continued to improve with alpha-interferon treatment and has normal liver function and a negative HCV RNA 15 months later.

Adult↗

PubMed1994

Terminal duct carcinoma. Recognition of a low-grade salivary adenocarcinoma.

We describe six cases of terminal duct carcinoma of the minor salivary glands. All were localized to the oral cavity, without regional nodal or distant metastases. Histologically, five were originally mistaken for adenoid cystic carcinoma; one was interpreted as monomorphic adenoma with areas of adenoid cystic carcinoma. Treatment consisted of wide resection with or without radiation therapy, with no incidence of recurrence or metastasis. The characteristics of this recently described pathologic entity are reviewed. The less aggressive behavior of this tumor compared with adenoid cystic carcinoma should call for less radical therapy, with a favorable prognosis in most cases. Recognition of this tumor as a distinct clinical and pathologic entity is therefore important.

Adenocarcinoma↗

PubMed1994

Shifting proportions of gastric adenocarcinomas.

OBJECTIVES: To substantiate reports of increasing proportions of gastric adenocarcinoma of diffuse histologic type and in the proximal portion of the stomach, to better understand the prognostic features that govern survival, and to determine whether alterations of operative strategy might improve the surgical results. DESIGN: Retrospective analysis of 289 consecutive patients with gastric adenocarcinoma operated on by general surgeons over a 26-year period. Records were reviewed for location, histologic type, resection, operative mortality, lymph node status, and outcome. SETTING: The Section of Surgical Oncology, the New England Deaconess Hospital, Boston, Mass. MAIN OUTCOME MEASURES: Survival rate, length of life of the patients who died, and operative mortality. RESULTS: A marked and significant shift of gastric adenocarcinoma to a proximal location (54% between 1985 and 1990) occurred over 26 years (P = .0075) with a significant stage improvement at presentation (P = .0235). Percentages of cancers that were of the diffuse, poorly differentiated histologic type increased to 48%. More curative operations were performed in the last period (61%), and this upward trend from 37% was significant. Proximal gastric cancers had a poorer prognosis with more operative deaths, more lymph node metastases, and worse survival rates than distal cancers. Poor survival rates occurred even when comparing patients with negative lymph nodes or favorable histologic features with patients with similar distal cancers. CONCLUSIONS: Despite significant increases in the proportion of proximal cancers, survival rates have improved only slightly. Nodal status plays a less prognostic role than does location or histologic type but does provide prognostic information for individual locations. Survival rates for diffuse histologic cancer were consistently worse than those for intestinal histologic cancer, which emphasizes the underlying disease biology controlling outcome. Radical lymphadenectomy for gastric adenocarcinoma would not improve surgical outcome in the United States.

Actuarial Analysis↗

PubMed1994

Clear cell carcinoma of the liver with spontaneous regression of metastases.

The purpose of this report is to establish in some detail a case of spontaneous regression of metastases secondary to a clear cell hepatocellular carcinoma. A review of the hepatocellular carcinomas from this department has been previously reported, and this particular study focuses on the two lesions that have the microscopic classification referred to above. One young female patient was 23 at the time of resection of the clear cell carcinoma of the liver plus diffuse intrahepatic metastases. She has been followed carefully over the years and has been seen as recently as June 1993. At that time, studies including ultrasonic and CT scan examinations of liver were carried out, all of which were negative for any evidence of residual disease. The evidence presented in this report would seem to establish conclusively that a spontaneous regression of the metastases from a clear cell carcinoma of the liver had occurred without any medication and without any obvious alteration in diet or state of health.

Adenocarcinoma, Clear Cell↗

PubMed1994

Plasma endothelin levels in chronic ethanol fed rats: relationship to pathologic liver injury.

We used the intragastric feeding rat model for alcohol liver disease to investigate the relationship between endothelin and pathologic liver injury. Rats were fed the following diets for periods of 1, 2 and 4 weeks: corn oil plus ethanol (CE), corn oil plus dextrose (CD) and saturated fat plus ethanol (SE). Plasma endothelin levels were significantly higher in the CE group compared to the other groups at all time periods studied. The CE animals, also, developed pathologic liver injury which is in contrast to the SE and CD animals which showed no pathologic changes. We propose that endothelin, because of its powerful vasoconstrictive effects, leads to a reduction in hepatic blood flow which is important in the pathogenesis of alcoholic liver disease.

Animals↗

PubMed1994

Lactobacillus feeding reduces endotoxemia and severity of experimental alcoholic liver (disease).

We have previously shown a relationship between plasma endotoxin levels and severity of alcoholic liver injury in the intragastric feeding rat model. We attempted to reduce both circulating endotoxin and liver injury in this model by administering a lactobacillus strain (species GG) which survives for prolonged periods in the gastrointestinal tract. Male Wistar rats were fed ethanol and liquid diet containing corn oil (CO+E). Another group of animals (CO+E+L) received the diet containing ethanol plus a daily bolus of lactobacilli GG concentrate (10(10) CFU). All animals were sacrificed after one month. All animals had plasma endotoxin measurements and evaluation of severity of pathologic changes in the liver. The weight gain and blood alcohol levels were similar in both groups. The mean +/- SE of the pathology score was significantly higher (3.4 +/- 0.85) in the CO+E group compared to the CO+E+L group (0.5 +/- 0.3, P < 0.01). The virtual absence of pathologic changes in the latter group was accompanied by significantly lower endotoxin levels (8.4 +/- 2.9 pg/ml in CO+E+L group vs 48.3 +/- 7.8 pg/ml in CO+E group, P < 0.01). Feeding of strains of lactobacilli that survive in the gastrointestinal tract reduces endotoxemia and alcohol-induced liver injury in the rat. Lactobacillus species GG provides a potential nontoxic form of therapy for both endotoxemia and alcoholic liver disease.

Animals↗

PubMed1993

A rat fatty liver transplant model.

A rat model of fatty liver transplantation has been developed to study primary nonfunction in fatty liver grafts. ACI rats were fed with a diet deficient in choline and methionine for 7, 14, 28, and 42 days. Fat content in the pretransplant livers was examined by gas chromatography and histology. The main constituent of the fatty droplets was determined to be triglyceride. The triglyceride concentration reached a maximum by day 14 and remained constant for an additional 28 days. Histology revealed an absence of necrosis in 14- and 28-day fatty livers but scattered hepatocytic necrosis and inflammation in 42-day fatty livers. After being given cold (UW stored, 4 degrees C) or warm (37 degrees C) ischemia, the fatty liver was orthotopically transplanted into normal ACI rats. The one-week survival of fatty liver grafts after 6, 12, 18, and 24 hr cold preservation was 5/5, 5/6, 3/8, 0/6 for 14-day fatty liver and 5/5, 4/6, 0/8, 0/6 for 42-day fatty livers. The survival of normal liver grafts was 5/5, 6/6, 5/9, 2/8, respectively. Increased survival rate was correlated with the absence of hepatocytic necrosis. The survival after 15 and 30 min warm ischemia prior to transplant was 5/5, 2/6 for normal liver grafts and 4/7, 0/6 for 28-day fatty liver graft, respectively. Fatty livers were less resistant to damage induced by cold or warm ischemia.

Animals↗

PubMed1993

Severity of liver injury in experimental alcoholic liver disease. Correlation with plasma endotoxin, prostaglandin E2, leukotriene B4, and thromboxane B2.

The purpose of our study is to determine if a relationship exists between the severity of injury in experimental alcoholic liver disease and plasma levels of endotoxin, prostaglandin E2, leukotriene B4, and thromboxane B2. Four groups of animals (n = 4 to 8 in each group) were fed a liquid diet with corn oil (25% of calories) and ethanol over various time periods: 1 week, 2 weeks, 1 month, and 2 months. At sacrifice, liver pathology scores and plasma levels of the above were determined. Plasma levels of endotoxin were already increased after 1 week (26.6 +/- 18.6 pg/ml) and continued to increase over time, with the highest levels at 2 months (69.5 +/- 24.5 pg/ml). A strong positive correlation (r = 0.84, P < 0.001) was seen between plasma endotoxin levels and severity of liver injury. The pathology score also correlated positively with leukotriene B4 (r = 0.47, P < 0.05) and thromboxane B2 (0.66, P < 0.01). A negative correlation was obtained with prostaglandin E2 levels (r = -0.44, P < 0.05). A positive correlation was also seen between endotoxin levels and leukotriene B4 (r = 0.57, P < 0.02) and thromboxane B2 (0.64, P < 0.01); a negative correlation was obtained with prostaglandin E2 levels (r = -0.55, P < 0.02). Each metabolite was also correlated with each of the features of alcoholic liver injury, i.e., fatty liver, necrosis, and inflammation. With prostaglandin E2, the most marked decrease was seen in association with severe fatty liver (3 to 4+). Thromboxane B2 correlated best with presence of inflammation and necrosis. Our study shows the importance of endotoxin in the pathogenesis of experimental alcoholic liver disease and suggests that endotoxin modulates production of eicosanoids that contribute to the severity of liver injury.

Animals↗

PubMed1993

Protective effects of a novel quinone derivative, (2E)-3-[5-(2,3 dimethoxy-6-methyl-1,4-benzoquinoyl)]-2-nonyl-2-propanoic acid on experimental alcoholic liver injury.

The present study evaluated the possible protective effect of ((2E)-3-[5-(2,3 dimethoxy-6-methyl-1,4-benzoquinoyl)]-2-nonyl-2-propanoic acid) (E3330), a newly synthesized hepatoprotective-quinone derivative, on experimental alcoholic liver injury. The intragastric feeding rat model for alcoholic liver disease was used. Eight sets of experiments were performed in which animals fed either corn oil and ethanol or corn oil, ethanol and E3330 were sacrificed at intervals of 1 week, 2 weeks, 1 month and 2 months. Nonparenchymal cell supernatant (NPCS) and plasma measurements of tumor necrosis factor, prostaglandin E2, leukotriene B4 and thromboxane B2 were evaluated in relation to the development of pathologic liver injury. Oral treatment with E3330 reduced the severity of liver injury; this was accompanied by a reduction in thromboxane B2 and leukotriene B4 levels in both NPCS and plasma and a reduction in tumor necrosis factor levels in NPCS. The difference in pathologic severity between drug- and nondrug-treated groups correlated well with the changes in the NPCS and plasma thromboxane B2/prostaglandin E2 ratio. These findings suggest that E3330 has multiple actions, such as inhibition of thromboxane, leukotriene and tumor necrosis factor generation, which contribute to its protective effect in alcoholic liver injury.

Animals↗

PubMed1992

31P NMR assessment of orthotopic rat liver transplant viability. The effect of warm ischemia.

The relationship between NMR visible high energy phosphates and transplant outcome for the case of liver damage by warm ischemia was investigated. In vivo 31P nuclear magnetic resonance (NMR) spectroscopy of rat liver was performed before the induction of warm ischemia in the donor and 20 min after reestablishment of portal blood flow in the recipient. Pretransplant damage was varied by subjecting the livers to 0, 15, 30, or 60 min of warm ischemia prior to harvesting. In the controls (0 min warm ischemia), 4 of 4 rats survived transplantation (one week survival end-point) and the mean NTP recovery was 94 +/- 8%; 3 of 6 rats survived in the 15 min warm ischemia group. Mean NTP recovery was 77 +/- 20% in the 15 min survival subgroup and 32 +/- 20% in the nonsurvival subgroup. Of 6 rats, 1 survived in the 30 min group. NTP recovery was 44% for the 30 min survivor and 37 +/- 5% in the nonsurvival subgroup. Of 4 rats, 1 survived in the 60 min warm ischemia group. NTP recovery was 56% for the 60 min survivor and 28 +/- 7% in the nonsurvival subgroup. Overall, there was a significant difference between the mean NTP recovery of the survival and nonsurvival subgroups (78 +/- 21% versus 31 +/- 18%, P < 0.001). The dividing line between the survival and nonsurvival groups was approximately 50% NTP recovery. Of 9 rats with liver NTP recovery greater than 50%, 8 survived while 10 of 11 rats with less than 50% recovery died. NMR visible NTP recovery 20 min after the reestablishment of portal blood flow was a good indicator of transplant outcome in the case of rat liver damage by warm ischemia.

Animals↗

PubMed1992

23Na- and 31P-NMR studies of perfused mouse liver during nitrogen hypoxia.

The effects of nitrogen hypoxia on isolated perfused mouse livers from fed mice were studied at 37 degrees C using 23Na and 31P nuclear magnetic resonance (NMR) spectroscopy. The paramagnetic shift reagent, dysprosium-triethylenetetraminehexaacetic acid, was used to distinguish intracellular from extracellular sodium. The area of the intracellular sodium resonance remained relatively constant over the first 30 min of hypoxia and then increased by a factor of approximately 2 relative to controls over the next 30 min. High-energy phosphate metabolites were measured using 31P-NMR. The beta-ATP resonance decreased to zero, and the intracellular pH decreased from 7.3 to 6.9 during 60 min of hypoxia. Liver enzyme activity in the effluent exiting the liver increased in direct proportion to the length of hypoxia up to 56 min. The sodium, ATP, and enzyme changes during hypoxia were correlated with histological and electron-microscopic findings. The morphology of liver specimens exposed to 30 min of hypoxia was close to normal, whereas extensive centrilobular and midlobular necrosis was seen in specimens subjected to 60 and 90 min of hypoxia. The effect of 30 min of reoxygenation after 15, 30, 45, 60, and 90 min of hypoxia was also studied. The level of beta-ATP recovery depended on the duration of hypoxia. For 60 min of hypoxia followed by reoxygenation, beta-ATP recovered to only 20% of control values. The morphology of hypoxic livers after 30 min of reoxygenation was similar to livers subjected to hypoxia alone.

Animals↗