Replacement Of Parenchyma Research Articles

Cystic echinococcosis due to Echinococcus equinus in a Swiss donkey

SummaryA 22‐year‐old donkey (Equus asinus) mare was presented for investigation of a 3‐day history of lethargy and anorexia. Serum biochemistry profile revealed severe increased liver‐derived enzymes. Abdominal ultrasound demonstrated several large round cysts in the liver. Broad‐spectrum antimicrobials and anti‐inflammatory therapy were started. However, exacerbation of the clinical signs occurred, and the donkey was euthanised. Necropsy and histopathological evaluation showed multiple hydatid cysts with protoscoleces from Echinocococcus spp. in the liver with replacement of parenchyma by fibrosis accompanied by liver atrophy, severe ascites and thorax effusion. The present report describes the first case of a molecularly confirmed Echinococcus equinus infection in a donkey in northern Switzerland.

RETROSPECTIVE ASSESSMENT OF CLINICAL-MORPHOLOGICAL CHANGES OF THE HEPATOBILIARY SYSTEM IN LIVER CIRRHOSIS OF THE CHORNOBYL NPP ACCIDENT CLEAN-UP WORKERS.

to retrospectively characterize changes in the hepatobiliary system in liver cirrhosis (LC) in the clean-up workers of the Chornobyl NPP accident and to determine the factors of disease progression according to the expert materials of the Central Interagency Expert Commission on Establishing the Causal Relationship of the Diseases with the influence of factors of Chornobyl NPP accident. Based on the data of 60 cases of the Central Interagency Expert Committee on establishing the causal link of diseases with the impact of the Chornobyl NPP accident, the factors of development, concomitant pathology and indicators of the hepatobiliary system status in 49 deceased and 11 alive clean-up workers with LC were investigated. A retrospective study of the morphological changes of the hepatobiliary system in the clean-up workers with LC showed that the main pathologic anatomical diagnosis in 37.8 % of cases was small-nodal LC, in 8.9 % - micromacronodular, in 4.4 % - large-nodal, in 2.2 % - primary biliary LC, in the other 40 % of cases - LC with uncer- tain nodal structure, as well as 2 (4.4 %) cases of fatty liver and 1 case (2.2 %) of portal cirrhosis against the back- ground of fatty liver. Pathomorphological changes were characterized by expressed growth of fibrous tissue with replacement of the liver parenchyma (fields of fibrosis), increase in size and impaired structure of the liver, thick- ening and tightening of its capsule, fibrotic changes in other organs - gastric mucosa, pancreas, spleen, lungs, heart. Histological examination revealed lobe structure abnormalities, false lobules, periportal fibrosis, lymphoid-lympho- cytic infiltration, diffuse fatty small-sized and large-drop dystrophy, and hepatocyte atrophy. Common inflammato- ry processes and fibrotic changes of other organs and systems: cardiovascular, urinary, bronchopulmonary, stomach, pancreas and spleen made the course of the LC more severe. The most frequent were cardiovascular diseases, signi- ficantly more frequent among the deceased than alive patients: hypertension - 67.3 % and 45.5 %, p < 0.05, coro- nary heart disease - 57.1 % and 18 %, p < 0.05. In most cases, the cause of death in the clean-up workers with LC was hepatic and cellular failure (53.3 %), which together with hepatic-renal failure (17.8 %) made 71.1 %. Changes in the hepatobiliary system of change in in the clean-up workers with LC were characterized by marked growth of fibrotic tissue with replacement of the parenchyma and impaired liver structure, fibrotic changes in other organs, diffuse fatty small and large droplet dystrophy and atrophy of hepatocytes. The severe course of the LC with the manifestation of the disease at the stage of decompensation was due to a vague clinical picture, lack of subjective symptoms of liver disease, slow, steadily progressing development, lack of or inadequate examination and treatment, a significant number of concomitant pathology of other organs and systems. The fac- tors of the development of LC in the clean-up workers were the long course of chronic liver disease, numerous con- comitant pathology, long stay in the accident zone, the effect of ionizing radiation, as well as the lack of dispensa- ry supervision and adequate treatment.

Re-evaluation of hepatocyte replacement by recipient-derived cells after allogenic liver transplantation: Discrepancy between clinical observations and a rat model.

Reports suggest that hepatocyte replacement by recipient-derived cells is an active phenomenon after allogenic liver transplantation in rats. However, this phenomenon is rarely observed in humans, and further evaluation is necessary to bridge the gap between clinical practice and animal experiment. Fifty percent volume of the liver from green fluorescent protein (GFP) transgenic Lewis rats were transplanted into wild-type Dark Agouti (DA) rats, in which GFP negative hepatocytes were considered as host (DA rat)-derived cells. The transplanted liver was observed on whole imaging system and fluorescent microscope 7-10days after transplantation. As a different method from previous reports, hepatocytes isolated from transplanted livers were cultured, and the expression of GFP was examined. The sliced liver (2mm) after allogenic transplantation demonstrated decreased intensity of GFP signals compared with the positive control. The hematoxylin-eosin staining of the section revealed abundant infiltration of inflammatory cells, suggesting an immunological rejection reaction. Large polygonal cells with significantly decreased or negative GFP signals were also demonstrated, which was consistent with the results of previous studies. However, cell culturing demonstrated that none of the examined albumin positive large polygonal cells were host-derived cells. The same results were obtained irrespective of reconstruction of hepatic artery. Our result implies that rejection reaction does not promote parenchymal replacement by recipient-derived cells, in contrast to previous reports. If so, the phenomena occurring in rats are consistent with clinical observation of liver transplantation in humans.

Two-tier regenerative response in liver failure in humans

Acute and chronic liver failure is associated with high mortality. The enormous regenerative potential of the liver has generated a lot of attention. We undertook this work to assess the two-tier regenerative response in liver failure by immunohistochemistry and to correlate such response with liver histology in acute liver failure (ALF), acute-on-chronic liver failure (ACLF), and decompensated cirrhosis (CHD). Histological examination and immunohistochemical analysis of proliferating hepatocytes and activated hepatic progenitor cells (HPCs) were performed on the liver tissue of patients with ALF (25), ACLF (70), and CHD (70). Comparative analysis of regenerative markers and correlation with histological parameters were done in ALF, ACLF, and CHD. Hepatocytes proliferated significantly more in ALF in comparison to ACLF (p < 0.001) and CHD (p < 0.001). HPC proliferation was significantly higher in ACLF (p < 0.001) and CHD (p < 0.001) than in ALF. ACLF patients showed the highest HPC proliferation and differentiation. Significantly more intermediate hepatocytes were found in ACLF than in ALF and CHD (p < 0.001). Marked parenchymal replacement by fibrosis and/or necrosis correlated significantly with activation of HPC in ACLF (p = 0.01, odds ratio (OR) 4.95) and in CHD (p = 0.05, OR 4.19). The study of liver regeneration in human acute and chronic liver failure suggests that hepatocyte proliferation, providing the first line of regeneration response, is most active in ALF whereas HPC activation, the second line of defense, is more prominent in ACLF. More HPC differentiate to hepatocytes in ACLF than in CHD, reflecting better regenerative potential in ACLF.

Morphology and morphometry of the human sublingual glands in mouth floor enlargements of edentulous patients

Asymptomatic mouth floor enlargements may be observed in edentulous patients. These masses, which protrude from the mouth floor, may complicate the fitting of dentures and require surgery. Whether this "entity" may be considered an anatomical variation of the mouth floor or represent specific alterations in the sublingual gland is not known. ObjectiveThe aim of this work is to investigate the morphological and morphometric aspects of the sublingual glands of edentulous patients with mouth floor enlargements and compare the glands of these patients with the sublingual glands of human cadavers. Material and MethodsMicroscopic evaluation was performed on human sublingual glands from edentulous patients with mouth floor enlargements (n=20) and edentulous cadavers (n=20). The patients and cadavers were of similar ages. The data were compared using Mann-Whitney U, Fisher's exact and Student's t tests (p<0.05). ResultsAcinar atrophy, duct-like structures, mononuclear infiltrates, replacement of parenchyma with fibrous/adipose tissue, mucous extravasation and oncocytosis were similar between the groups (p>0.05). Only the variables "autolysis" and "congested blood vessels" presented statistical difference between groups (p=0.014; p=0.043). The morphometric study revealed that the volume densities of acini, ducts, stroma and adipose tissue were similar between the groups (p>0.05). ConclusionThe microscopic characteristics of the sublingual glands in mouth floor enlargements in edentulous patients correspond to characteristics associated with the normal aging process. The glands are not pathological and represent an age-related alteration that occurs with or without the presence of the mouth floor enlargements.

Liver histology as predictor of outcome in patients with acute-on-chronic liver failure (ACLF)

There is paucity of literature on liver histological spectrum of acute-on-chronic liver failure (ACLF). The aims of this study are to (a) to characterize the liver histological features in ACLF, (b) to correlate histological parameters with prognosis, and (c) to investigate whether etiology influences prognosis. We retrospectively studied liver biopsies of patients with ACLF. The histological findings were correlated with the clinical outcome. Fifty cases (median age, 39 years [10-69 years]; M/F, 3:1) were included. Etiology of acute insult was viral or alcohol in majority of the cases. Twenty-five patients survived (good outcome, 50%) and 25 died (poor outcome, 50%). On a univariate analysis, the outcome correlated with fibrosis, ballooning, eosinophilic degeneration, ductular proliferation, pericellular fibrosis, Mallory's hyaline, foci of confluent necrosis and/or bridging necrosis (CN/BN), cholestasis, apoptosis (present), and parenchyma left. However, on a multivariate analysis, only fibrosis, ballooning, ductular proliferation, apoptosis, and parenchyma left were found to be independently associated with outcome. Two distinct patterns of liver histology were observed: pattern I, observed in cases with poor outcome, showing marked ductular proliferation, coarse inspissated ductular bile plugs, eosinophilic degeneration of hepatocytes, foci of CN/BN, higher apoptosis, pericellular fibrosis, Mallory's hyaline, and higher stage of fibrosis. Pattern II is seen in cases with good outcome, show prominent hepatocyte ballooning with lesser parenchymal involvement by fibrosis and necrosis. Histological features of liver biopsy are: extent of fibrosis, ballooning, ductular proliferation, apoptosis, and lesser degree of parenchymal replacement by fibrosis or necrosis which correlates with the outcome in patients with ACLF. Two distinct patterns of liver histology are seen which help in prognostication.

Prior Biliary Tree Instrumentation Does Not Preclude Hepatic Arterial Therapy for Malignancy

Hepatic arterial therapy (HAT) has become an accepted alternative for patients with unresectable hepatic malignancies. HAT has an acceptable toxicity profile, yet its safety for use in patients who have undergone significant biliary manipulation is undocumented. A retrospective review identified 18 consecutive patients with unresectable hepatic malignancies who had undergone significant prior biliary tree manipulation. All patients received peri-HAT antibiotics. Clinicopathologic, treatment-related, and outcomes data were collected and analyzed. Eighteen patients who had HAT were analyzed; 72 per cent were men, the median age was 61 years, and 61 per cent had greater than 25 per cent hepatic parenchymal replacement by tumor. Seventy-eight per cent of patients had an indwelling biliary stent and 22 per cent had undergone a hepaticojejunostomy. Twenty-two per cent of patients developed a complication, none of which were infectious, and there were no peri-HAT deaths. The majority of patients had evidence of either a partial response (55%) or stable disease (22%) upon follow-up. One patient had a complete response to HAT. The median survival was 27 months. Hepatic arterial therapy seems to be safe for patients with unresectable hepatic malignancies and a history of significant biliary instrumentation. There is no increased risk of infectious complications in this population after HAT.

A growing transplanted kidney.

Sir, Renal sinus lipomatosis (RSL) is a rare disease, described by replacement of parenchyma by sinus and/or perirenal fat. We report here an exceptional case of RSL on kidney graft after corticosteroid treatment was stopped, leading to functional graft transplantectomy. A 74-year-old man received a first renal allograft in 2004. He was maintained on tacrolimus and mycophenolate mofetil with no rejection. Corticosteroid was stopped at the sixth month. The lowest serum creatinine level was 100 μmol/L. On February 2007, renal ultrasonography, performed for acute renal failure, showed dilatation of renal cavities. Contrast-enhanced computed tomography (CT) showed an enlarged kidney (14.3 cm) with an increased amount of fatty-like tissue in renal sinus and perirenal area (Figure 1). For 6 months, he experienced several obstructive renal failures and infections, leading to permanent nephrostomy. Biopsy of the sinus mass revealed an extensive fatty tissue with fibrosis. Finally, because of bilateral pulmonary embolism secondary to vena cava compression, persistent obstruction and continuous graft enlargement without conclusive histology, and despite good renal function, he underwent transplantectomy. Histological examination showed RSL (immunophenotypical labelling and biomolecular investigations negative for sarcoma) and atrophic chronic pyelonephritis graft. Fig. 1 Filling defects secondary to thrombosis in the right RV and VCI (white arrows) after contrast administration from vena cava superior. RSL is essentially described on native kidneys [1,2]. Possible risk factors for RSL include ageing, obesity and pathologic states that cause renal inflammation such as intense corticotherapy and/or early rejection for transplants. Often, chronic or repeat urinary tract infections have been found, and one hypothesis is that RSL may be secondary to periodic leakages of urine into the peripelvic tissues [2]. RSL can also be part of replacement of destroyed or atrophic renal tissue [3]. It has also been suggested that high-dose steroid treatment by itself, Cushing's syndrome or obesity may have contributed to the development of fibrolipomatosis [4]. Intriguingly, a very few cases of RSL have been reported in the renal transplant population [5]. This case is intriguing for several reasons: The time between transplantation and the first symptoms was quite long (3 years). The recipient of the contralateral kidney did not develop any RSL. The patient experienced his first urinary tract infection at the same time as the first acute obstructive renal failure. No history of earlier acute rejection episodes has been found. He did not have a long-term steroid treatment and was not obese. Finally, our case is also exceptional because it led to transplantectomy. Transplantectomy was decided in view of the rapidly increasing graft mass, responsible of vena cava compression and suspicion of malignity. In conclusion, our case underlines that diagnosis of RSL, although exceedingly rare, should be considered when imaging exams demonstrate a fat-containing renal sinus mass. In transplant recipients, immunosuppressive regimen and malignancy risk underline the importance to establish differential diagnosis between fibrolipomatosis and fibrosarcoma, renal tumour or post-transplant lymphoproliferative disorder. Conflict of interest statement. None declared.

Diffuse Liver Metastasis of Small Cell Lung Cancer Causing Marked Hepatomegaly and Fulminant Hepatic Failure

A 62-year-old female was admitted for examination of an abnormal liver function. Plain CT and MRI of the abdomen showed marked hepatomegaly but no visible nodular lesion in the liver. On the 3rd hospital day she had hepatic encephalopathy and was treated with a course of high-dose steroids, but ultimately died of disease progression on the 7th hospital day. An autopsy revealed a small pulmonary nodule with the histological findings showing small cell carcinoma. There was almost complete parenchymal replacement with metastatic tumor in the liver. Neoplastic involvement of the liver should be considered in the differential diagnosis of fulminant hepatic failure of unknown etiology.

Hepatic parenchymal replacement in mice by transplanted allogeneic hepatocytes is facilitated by bone marrow transplantation and mediated by CD4 cells

The lack of adequate donor organs is a major limitation to the successful widespread use of liver transplantation for numerous human hepatic diseases. A desirable alternative therapeutic option is hepatocyte transplantation (HT), but this approach is similarly restricted by a shortage of donor cells and by immunological barriers. Therefore, in vivo expansion of tolerized transplanted cells is emerging as a novel and clinically relevant potential alternative cellular therapy. Toward this aim, in the present study we established a new mouse model that combines HT with prior bone marrow transplantation (BMT). Donor hepatocytes were derived from human alpha(1)-antitrypsin (hAAT) transgenic mice of the FVB strain. Serial serum enzyme-linked immunosorbent assays for hAAT protein were used to monitor hepatocyte engraftment and expansion. In control recipient mice lacking BMT, we observed long-term yet modest hepatocyte engraftment. In contrast, animals undergoing additional syngeneic BMT prior to HT showed a 3- to 5-fold increase in serum hAAT levels after 24 weeks. Moreover, complete liver repopulation was observed in hepatocyte-transplanted Balb/C mice that had been transplanted with allogeneic FVB-derived bone marrow. These findings were validated by a comparison of hAAT levels between donor and recipient mice and by hAAT-specific immunostaining. Taken together, these findings suggest a synergistic effect of BMT on transplanted hepatocytes for expansion and tolerance induction. Livers of repopulated animals displayed substantial mononuclear infiltrates, consisting predominantly of CD4(+) cells. Blocking the latter prior to HT abrogated proliferation of transplanted hepatocytes, and this implied an essential role played by CD4(+) cells for in vivo hepatocyte selection following allogeneic BMT. The present mouse model provides a versatile platform for investigation of the mechanisms governing HT with direct relevance to the development of clinical strategies for the treatment of human hepatic failure.

Age-related changes in human sublingual glands: a post mortem study

To analyse age- and gender-related microscopic changes in sublingual glands obtained from human cadavers. One hundred eighty six human sublingual glands were obtained from 93 autopsies. Approximately five individuals of each gender per decade of life were allocated to three age groups: group I (0-30 years, n=26); group II (31-60 years, n=32) and group III (61-90 years, n=35). The specimens were fixed in 10% formalin and submitted to routine histological processing, and sections were stained with hematoxylin and eosin. Significant differences with increasing age were observed for the following microscopic aspects: acinar atrophy (r=0.26, p=0.0115); replacement of parenchyma by fibrous tissue (r=0.79, p<0.0001) and/or adipose tissue (r=0.63, p<0.0001); oncocytosis (r=0.61, p<0.0001); duct-like structures (chi(2)=14.68, p=0.0006) and congested blood vessels (chi(2)=7.18, p=0.0276). The mononuclear infiltrate changed from focal to diffuse with age (H=8.47, p=0.0144). No significant differences were observed between genders. The aging process starts with acinar atrophy, followed by the presence of duct-like structures and ends with the replacement of the parenchyma by fibrous and/or adipose tissue. The mononuclear infiltrate changes from focal to diffuse. No difference in the aging of the sublingual glands is observed between men and women.

How aggressive should we be in patients with stage IV colorectal cancer?

The prognosis for metastatic colorectal cancer is grave. Whether to perform surgical resection or palliative treatment remains controversial for this advanced disease. In this retrospective study, we collected data from patients with Stage IV colorectal cancer to identify prognostic factors for predicting selection criteria for surgical treatment in patients with metastatic disease. A retrospective chart review was performed for patients treated from 1992 to 1999 from the Koo Foundation Sun Yat-Sen Cancer Center Tumor Registry. Seventy-four patients were identified as having Stage IV disease at the time of diagnosis. Data concerning the patients' demographics, laboratory results, operative procedure, mortality, morbidity, and survival were collected. Independent variables and survival time were analyzed by the independent t-test method. The difference was considered statistically significant at P < 0.05. Overall survival time for the patients with Stage IV colorectal cancer was 16.1 months. Survival in the curative resection group was significantly longer than that in the noncurative group (31.9 vs. 12.7; P < 0.016). The operative mortality and morbidity rates were 5.6 percent (4 of 71) and 21.1 percent (15 of 71), respectively. The two most common complications were leakage at the site of anastomosis and urinary tract infection. Based on these results, we conclude that patients older than 65 years, with metastases at multiple sites, intestinal obstruction, preoperative carcinoembryonic antigen level > or =500 ng/ml, lactate dehydrogenase > or =350 units/liter, hemoglobin <10 mg/dl, or hepatic parenchymal replacement by tumor >25 percent have poor prognosis for surgical intervention. Whether to perform primary tumor resection in patients with asymptomatic Stage IV colorectal cancer remains controversial; however, the more aggressively we perform radical resection and metastasectomy to selected patients, the more survival benefits the patients obtain.

THE PATHOLOGY, DIAGNOSIS, AND TREATMENT OF HEPATIC VENO‐OCCLUSIVE DISEASE: CURRENT STATUS AND NOVEL APPROACHES

THE PATHOLOGY, DIAGNOSIS, AND TREATMENT OF HEPATIC VENO‐OCCLUSIVE DISEASE: CURRENT STATUS AND NOVEL APPROACHES

Nonoperative management of primary colorectal cancer in patients with stage IV disease.

Traditional teaching maintains that patients with primary colorectal adenocarcinoma require timely resection to prevent bleeding, perforation, or obstruction. The true benefits of primary tumor resection remain undocumented for patients presenting with metastatic disease, however. We postulated that resection of primary colorectal tumors could be avoided safely in a select population of asymptomatic colorectal cancer patients presenting with incurable stage IV disease. A retrospective review of the Vanderbilt University Hospital tumor registry was performed for the years 1985 to 1997. During this period, 955 patients presented for management of primary colorectal cancer. From this group, all patients with stage IV disease at the time of diagnosis were identified. Patients who initially underwent resection of their primary lesion were included in the resection group; those who underwent initial nonoperative primary tumor management were included in the nonresection group. Data were obtained regarding age, extent of disease, nonsurgical therapy, tumor-specific complications, and palliative surgical procedures. Surgery-free survival and overall survival were analyzed using the Kaplan-Meier method. For patients with liver metastases, hepatic tumor burden was defined as either H1 (<25% parenchymal replacement), H2 (25% to 50%), or H3 (>50%) disease. Sixty-six patients were included in the resection group, and 23 patients with intact asymptomatic primary colorectal lesions were included in the nonresection group. Among patients with hepatic metastases, most of the patients in both groups had H1 disease. Ten patients in the resection group and 3 patients in the nonresection group presented with exclusively extrahepatic metastases. In the nonresection group, primary therapy included chemotherapy in 13 patients, external beam radiation therapy in 1 patient, and combination chemoradiation in 9 patients. The median survival in the nonresection group was 16.6 months. The 2-year actuarial survival was 18%, and the surgery-free survival was 91.3%. Only 2 of 23 patients (8.7%) managed without resection eventually developed obstruction at the primary tumor site requiring emergent diversion. There were no episodes of tumor-related hemorrhage or perforation. For the resection group, the operative morbidity was 30.3%, and the perioperative mortality rate was 4.6%. The median survival in the resection group was 14.5 months (P = 0.59, log-rank test vs. nonresection group). Selected patients with asymptomatic primary colorectal tumors who present with incurable metastatic disease may safely avoid resection of their primary lesions, with an anticipated low rate of hemorrhage, perforation, or obstruction before death from systemic disease. No survival advantage is gained by resection of an asymptomatic primary lesion in the setting of incurable stage IV colorectal cancer.

Repopulation of the liver after dipin-induced damage

The alkylating preparation dipin in combination with partial hepatectomy induces genomic damage and apoptosis of hepatocytes with total replacement of parenchyma at the expense of the stem reserve cells. This model was employed to study the responses of the cell cycle to genetic damage, mechanisms of cell survival and death, and the sources of cells repopulating liver parenchyma.

Malignant mesotheliomas presenting as ovarian masses. A report of nine cases, including two primary ovarian mesotheliomas.

Nine cases of malignant mesothelioma (MM) presenting as ovarian masses occurred in female patients aged 16 to 63 (median, 52) years. In most of the cases, the referring pathologist initially misdiagnosed the neoplasm or was uncertain about its nature. In two cases, the tumors were confined to one or both ovaries, representing primary ovarian MMs; only one similar case has been previously reported. In the other cases, widespread peritoneal tumor precluded definite conclusions about the primary or secondary nature of the ovarian involvement. That at least some of the latter were also primary ovarian MMs is suggested by a degree of ovarian enlargement, the striking parenchymal replacement, or both, which are not usually seen in cases of secondary ovarian involvement by peritoneal MMs. The clinical presentation was usually that of abdominal or pelvic pain or abdominal swelling, an adnexal mass on pelvic examination or at laparotomy, or combinations thereof. One tumor was an autopsy finding. There was no history of asbestos exposure in any patient. Eight patients underwent bilateral oophorectomy, usually with hysterectomy and biopsies of extraovarian tumor. Four patients were given chemotherapy and one, radiation therapy. Follow-up in five cases revealed that three patients had died of tumor at postoperative intervals of 8 to 44 months, one was alive with persistent tumor at 18 months, and one was alive with no clinical evidence of tumor at 11 years. The ovaries were replaced by tumors 3 to 15 cm in maximum diameter; seven were bilateral. The neoplastic tissue was typically solid, but small cysts were present in two cases, and one tumor was a unilocular cyst with a solid mural nodule. On microscopic examination, tumor involved both the serosa and the parenchyma of the ovary in seven cases, the serosa only in one case, and the parenchyma only in one case. Seven tumors were exclusively epithelial, with papillary, tubular-glandular, and solid patterns, and two were biphasic. The cells in the epithelial mesotheliomas usually exhibited moderate atypicality and a low mitotic rate. The stroma was typically hyalinized, and in three of the cases with a papillary pattern papillae with hyalinized cores were a striking finding. Psammoma bodies were present in three cases. Histochemical and immunohistochemical stains confirmed the mesothelial nature of the tumor cells. Because of the wide variety of microscopic patterns in MMs, the differential diagnosis of ovarian MM includes a variety of primary and metastatic ovarian tumors as well as other peritoneal mesothelial lesions.

Computed Tomography of Renal Tuberculosis and Its Pathological Correlates

Computed tomographic studies of eight patients with proven renal tuberculosis demonstrated a spectrum of findings related to the extent and the severity of kidney involvement. In early or focal disease, obstruction of a single major calyx or a group of minor calyces was noted (four cases) with no excretion of contrast material into the affected calyces (three cases) and cortical thinning. Tuberculosis of the renal pelvis (five cases) was manifested by either pelvic dilatation secondary to ureteropelvic junction obstruction (three patients) or diffuse pelvic contraction (two patients). In far advanced disease (four cases) the kidneys were small and exhibited atrophy with replacement of parenchyma by one or more low density areas. Calcifications (37.5%) were identified in the parenchyma and within the calyces. Computed tomography may provide the first clue in suggesting the inflammatory nature of a renal mass and excluding a neoplastic process. Computed tomography is also of value in determining the full extent of extrarenal involvement and the amount of residual functioning parenchyma, both of which are critical in proper treatment planning.

Renal lymphoma: radiologic-pathologic correlation of 21 cases.

The radiologic findings in 21 cases of renal lymphoma were correlated with the gross and microscopic pathologic findings. The gross morphology and consequent radiographic images depend upon the mechanism of renal involvement (hematogenous or direct extension); the pattern of intrarenal growth (interstitial or expansile); the size, number, and distribution of lesions; and the presence of extension beyond the kidney. Initially, the lymphoma grows between nephrons that may continue to function and, because this interstitial proliferation preserves gross morphology, radiographic detection may be difficult. With continued growth, the scaffolding along which the tumor infiltrates is destroyed, growth becomes expansile, and the lymphomatous mass resembles other renal neoplasms that enlarge by appositional growth. Continued growth and coalescence of small foci result in progressive parenchymal replacement and, rarely, in destruction of the entire kidney. Perinephric extension with subsequent vascular and ureteral encasement is common.

Selected lobar injury after infusion of oleic acid.

A model of respiratory distress has been developed using sheep in which an isolated lobar injury is induced by infusion of oleic acid into a selected lobar artery. The directed insult permits acute and chronic phase study without the requirement of intensive pulmonary support. One hour after selective lobar injury the affected pulmonary venous oxygenation (Ppvo2) was reduced from greater than 310 to 66-90 Torr. Ppvo2 was most impaired at 48 h (40-55 Torr), but showed improvement by 96 h postinjury. Radionuclide estimates of lobar ventilation and perfusion demonstrated an initial fall in ventilation by 51% and corresponding 41% reduction in perfusion. By 24 h the depression of perfusion matched that of ventilation. Sequential light and scanning electron microscopy demonstrated the presence of a nonhomogeneous injury with areas of both complete parenchymal replacement by fibrous tissue and those with minimal architectural distortion. The selective injury model offers a useful methodology for the evaluation of the effects of various agents on the acute and chronic response of the lung to injury.

Histological changes in the liver and indices of drug metabolism in alcoholics.

The drug metabolizing capacity of the liver was investigated in 27 consecutive alcoholics by comparison of in vivo (antipyrine kinetics) and in vitro (cytochrome P-450) indices of drug metabolism with quantitative histological determinations of fat, trabeculae and non-fatty parenchyma in liver biopsies, and with biochemical liver function tests. The reduced amount of hepatic parenchyma in the biopsies was related to diminished drug metabolizing capacity, both in vivo and in vitro. The accumulation of fat alone did not significantly alter the kinetics of antipyrine, although it was associated with reduced cytochrome P-450 content. The replacement of parenchyma by fibrous tissue resulted in a decrease both in antipyrine clearance rate and cytochrome P-450 content. There was a logarithmic correlation between the kinetic parameters of antipyrine and cytochrome P-450 in the entire series, whereas a linear relationship was found in the alcoholic subjects in the various diagnostic groups. A non-linear relationship was also found between biochemical liver function tests and the in vivo and in vitro indices of drug metabolism. The results demonstrate that drug metabolizing capacity in alcoholics is related to ethanol-induced changes in the liver. quantitative evaluation of hepatic parenchymal changes, together with tests of the functional capacity of the liver, might be of significance value in predicting the ability of alcoholics to metabolize drugs.