[Experimental study of monopolar electrical and ultrasonic dissection]. / Etude expérimentale comparant bistouri électrique monopolaire et bistouri ultrasonique.

The aim of this experimental study was to compare the disadvantages of a monopolar electric scalpel and an ultrasonically-activated scalpel in a porcine model. Using thermal gradients, the ultrasonically-activated scalpel significantly decreased thermal energy dispersion to surrounding structures and thus decreased the risk of injuries to adjacent tissues and nerves, as opposed to the monopolar electric scalpel. Histological examination of nerves showed that necrosis was significantly less important with the use of the ultrasonically-activated scalpel. This experimental study demonstrated that the ultrasonically-activated scalpel caused less thermal and histological damage than the monopolar electric scalpel.

Longitudinal analysis of hepatitis C virus replication and liver fibrosis progression in renal transplant recipients.

The pathogenesis of hepatitis C virus (HCV) infection was investigated by analysis of changes in viral and histologic parameters in 36 renal transplant recipients who were infected with HCV before transplantation. Each patient was classified according to development of liver fibrosis as assessed by 2 liver biopsies done 45 and 81 months after transplantation: 13 had progressing liver fibrosis (fibrosers) and 23 did not (nonfibrosers). All developed high-titer posttransplant viremia with a significant increase of 1.2 log RNA copies/mL. There were no significant differences in the increases in serum HCV RNA or genotype distributions in fibrosers and nonfibrosers. The hypervariable region (HVR)-1 of the HCV genome was analyzed by cloning and sequencing 20 clones per sample from 5 fibrosers and 5 nonfibrosers. Comparison of samples revealed that liver fibrosis progression was significantly associated with slower HVR-1 quasispecies diversification, suggesting the selection of more aggressive variants in fibrosers.

[Long-term consequences of co-infection by hepatitis G virus in hepatitis c virus infected kidney transplant patients]. / Conséquences à long terme d'une surinfection par le virus de l'hépatite G chez des transplantés rénaux infectés par le virus de l'hépatite C.

The objectives of this retrospective study were to determine the prevalence of hepatitis G virus (HGV) infection in hepatitis C virus positive (HCV+ve) renal transplant (RT) patients and to evaluate the impact of HGV both on liver function tests, liver histology tests and renal parameters such as the prevalence of acute rejection and renal function. Seventy-one HCV+ve renal transplant patients with a functioning graft for whom a post renal transplant liver biopsy was available, were included. Serum HGV RNA was assessed by reverse transcription polymerase chain reaction before, at the time of, and after renal transplantation. A total of 21 (30%) of the HCV+ve RT patients had a positive HGV RNA (Group 1); seventeen of these patients (81%) were already HGV RNA+ve when the most recent renal transplantation was performed. The other 4 patients became HGV RNA+ve following renal transplantation. The mean duration of HGV infection was at least 119 +/- 64 months (18-240). Patients in group 1 did not statistically differ from the 50 HGV RNA-ve/HCV+ve RT patients (Group 2) according to sex ratio; time on dialysis; number of blood transfusions; HLA matching; the duration of HCV infection; duration and type of immunosuppression or levels of liver enzymes i.e. aspartate aminotransferase, alanine aminotransferase and gamma glutamyl transpeptidase; serum HCV RNA concentration; or frequency of genotype 1b. However, Group 1 patients were statistically younger (41 +/- 10 y compared to 47 +/- 10 y; p = 0.016) than Group 2 patients. Liver histology showed a significantly lower degree of fibrosis in Group 1 (0.4 +/- 0.5) than in Group 2 (1 +/- 1.2; p = 0.02); two patients from Group 2 but none of Group 1 had overt cirrhosis. Conversely, the extent of hepatic inflammation and hepatocellular necrosis was not statistically different between the two groups. The number of patients who experienced at least one acute rejection episode was significantly higher in Group 1 (76.2%) than in Group 2 (46%; p = 0.02), although the difference was no longer significant in the multivariate analysis. In conclusion, this study shows that: i) HGV infection was often present when the patients seroconverted for HCV; ii) HGV RNA+ve/HCV+ve RT patients experience acute rejection more frequently than HGV RNA-ve/HCV+ve RT patients; iii) HGV infection seems to have no detrimental effect upon liver enzymes or liver histology in HCV+ve RT patients.

Long-term impact of superinfection by hepatitis G virus in hepatitis C virus-positive renal transplant patients.

BACKGROUND: The hepatitis G virus (HGV) has been recently cloned. Studies in immunocompetent patients have shown that HGV superinfection in hepatitis C virus (HCV)-positive patients does not affect (i) clinical presentation, HCV RNA level, or response to interferon-alpha therapy; or (ii) the histopathologic severity and characteristics of chronic hepatitis. No data are currently available on the impact of HGV infection on liver histology of renal transplant (RT) patients although the reported prevalence of serum HGV RNA in this population is high, ranging from 14% to 55%. PATIENTS AND METHODS: We determined the prevalence of HGV infection in 103 HCV-positive RT patients for whom HGV RNA was retrospectively determined by reverse transcription-polymerase chain reaction before, at the time of, and after transplantation (last follow-up). We evaluated the impact of HGV on liver function tests, liver histology (by means of the Knodell score), and renal parameters such as the prevalence of acute rejection and renal function. RESULTS: A total of 29 (28%) of the HCV-positive RT patients had a positive HGV RNA (group 1). The mean duration of HGV infection was at least 119+/-64 months (range: 18-240 months). Group 1 patients were compared to the 74 HGV RNA-negative/HCV-positive RT patients (group 2). Liver histology showed a significantly lower degree of fibrosis in group 1 (0.4+/-0.5) than in group 2 (1+/-1.2; P=0.02); two patients from group 2 but none from group 1 had overt cirrhosis. Conversely, the extent of hepatic inflammation and hepatocellular destruction was not statistically different between the two groups. The number of patients who experienced at least one acute rejection episode was significantly higher in group 1 (69%) than in group 2 (42%; P=0.01). However, the multivariate analysis did not identify the presence of HGV RNA at the time of renal transplantation as an independent factor of acute rejection; conversely, (i) the occurrence of cytomegalovirus infection or disease and (ii) the duration of HCV infection significantly increased the likelihood of having acute rejection. CONCLUSIONS: This study shows that: (i) HGV infection was often present when the patients seroconverted for HCV, (ii) HGV RNA-positive/HCV-positive RT patients experienced acute rejection more frequently than HGV RNA-negative/HCV-positive RT patients, and (iii) HGV infection seems to have no detrimental effect upon liver enzymes or liver histology in HCV-positive RT patients.

Impact of hepatitis C virus duration and hepatitis C virus genotypes on renal transplant patients: correlation with clinicopathological features.

BACKGROUND: The aim of this study was to evaluate the long-term impact of chronic hepatitis C virus (HCV) infection on the liver in renal transplant patients. METHODS: We studied 78 patients for whom at least one posttransplant liver biopsy (LB) was available and for whom the duration of HCV infection was precisely defined. The LB were graded according to a histological activity index, i.e., the Knodell score, divided into the activity score and the fibrosis score. They were also classified as either normal or showing evidence of chronic persistent hepatitis, chronic active hepatitis (CAH), or cirrhosis. RESULTS: The study comprised 7 HCV-positive/hepatitis B surface antigen-positive patients (group 1); 4 HCV-positive/RNA-negative patients (group 2); and 67 HCV-positive/RNA-positive patients (group 3). The three groups were comparable according to demographic data and baseline immunosuppression. The median time from transplantation to LB was 38 months (range, 10-306 months). At that time, alanine aminotransferase (ALT) levels had increased in 71.4%, 0%, and 42% of patients from groups 1, 2, and 3, respectively (P=0.07). The total Knodell score showed significantly more severe lesions in group 1 patients (6.2+/-3.2) than in group 2 (1+/-1.2) or in group 3 (4.6+/-2.4) patients (P=0.007). The Knodell score also showed that the fibrosis score was significantly higher in group 1 (2.3+/-1.6) than in group 2 (0) or in group 3 (0.9+/-1.1) patients (P=0.007). Overall, there were 28 cases of CAH (36%) and 4 cases of cirrhosis (5%). We did not observe any correlation between liver histology and characteristics of HCV infection or the type of chronic immunosuppression (double-drug versus triple-drug therapy). However, liver histology (total Knodell score) and the activity score were significantly correlated with ALT levels. Multivariate analysis did identify (i) four independent variables that could explain the degree of liver fibrosis-the sex of the patient, the number of blood units received before transplantation, increased ALT levels at the time of LB, and the occurrence of at least one acute rejection episode (thus the receipt of methylprednisolone pulses); and (ii) two independent variables associated with the occurrence of CAH-the number of blood units before transplantation and increased ALT levels at the time of LB. CONCLUSION: This study showed that renal transplant patients infected by HCV for more than 10 years, with a mean posttransplant follow-up of more than 5 years, showed more severe liver lesions when coinfected by hepatitis B virus. Overall, we observed only four cases of cirrhosis (5%) and evidence of histological CAH lesions in 36% of the patients.

Follow-up of patients with hyperplastic polyps of the large bowel.

BACKGROUND: Adenomatous colonic polyps are accepted as premalignant lesions. There is controversy regarding the significance of the hyperplastic polyp. The aim of this study was to determine the incidence of further polyps in patients with only hyperplastic polyps on a first colonoscopy in comparison with patients without polyps and with adenomatous polyps. METHODS: Ninety patients had only hyperplastic polyps (group I). These patients were paired according to age and sex with subjects having no polyps (group II) and with patients having adenomas (group III). RESULTS: Fifty-six patients in group I had at least one follow-up examination. New polyps were found in 46.4% in group I versus 15.5% in group II (p < 0.001) and 50% in group III (NS). In group I, 30.7% of new polyps were hyperplastic and 69.3% were adenomas. In fact, 32.2% of group I patients developed further adenomas (mean 1.5 +/- 0.8 adenomas). These adenomas occurred 1 to 4 years after the first polypectomy (mean 2.4 +/- 0.8 years). Most of these adenomas were small and tubular, but 16.6% were villous or had severe dysplasia. CONCLUSION: Patients with hyperplastic polyps were 2.4 times more likely to have further adenomas than were those without polyps.

Histopathologic analysis of transjugular intrahepatic portosystemic shunts.

This prospective study was undertaken in 17 patients treated with 22 transjugular intrahepatic portosystemic shunt (TIPS) procedures and aimed to evaluate the nature and causes of short- and long-term shunt abnormalities. Specimens were collected after autopsy in 6 patients and after liver transplantation in 11 patients; the time from shunting ranging from 4 to 385 days. During the first 2 weeks the shunt surface was covered by poorly organized fibrin platelet clots that were mixed with inflammatory and red blood cells. Thereafter, a pseudointima developed, initially made of loose granulation tissue that was formed by edema, myofibroblasts, neo-capillaries, collagen fibers, and inflammatory cells. This pseudo-intima extended with time as the myofibroblasts increased in number, as the collagen fibers thickened, and as the inflammatory cells grew more scarce. Its thickness ranged from 50 to 3,500 microm, the maximal values being observed in the middle of the shunt. The shunt was obstructed by a clot in 4 patients (18%). In 7 shunts (31.8%) the pseudo-intima was thicker than 1,000 microm and was referred to as hyperplastic pseudo-intima. It showed more dense inflammatory infiltrate and anarchic deposition of more scarce collagen fibers. Pseudo-intima hyperplasia was associated with previously diagnosed thrombosis, which had been treated by dilatation in 2 cases and by biliary deposits in 3 cases, while it remained unexplained in 2 cases. Accordingly, this study confirms the following: 1) that early TIPS obstruction results from thrombosis; 2) that 2 weeks after insertion, the stent is covered by a smooth pseudo-intima; 3) that thereafter, pseudo-intimal hyperplasia is the main cause of TIPS stenosis or occlusion; and 4) that biliary secretions and previous thrombosis could be important triggering mechanisms for this pseudo-intima overgrowth.

Treatment of chronic hepatitis B and C with alpha interferon in a renal transplant patient.

We report the case of a 51-year-old renal transplant patient, treated by interferon alpha (5MUI, three times a week) since he presented a coinfection by hepatitis B (HBV) and hepatitis C (HCV) virus for more than 7 years, associated with a chronic increase in serum alanine aminotransferase (ALT) levels and a chronic active hepatitis. The 4-month treatment was associated with a sustained normalization of ALT, a disappearance of HBV replication and a transient clearance of HCV viremia. Side effects were moderate and included thrombopenia (90,000/mm3), leucopenia (2200/mm3), an increase in serum creatinine (178 mumol/l). The withdrawal of alpha interferon was associated with the correction of these parameters. No rejection was observed on kidney biopsy. Meanwhile, liver histology was not affected by the treatment. To date, nineteen months after the end of alpha interferon therapy HBV DNA was still negative; ALT remained normal despite the early recurrence of HCV viremia; this emphasized the fact that HBV infection was certainly the most important factor involved in the patient's chronic hepatitis. It is concluded that alpha interferon therapy is able to decline HBV replication for a prolonged period in renal transplant patient although its use should be performed with caution due to the potential renal side effects.

[Low-grade papillary adenocarcinoma of the endolymphatic sac. Report of three cases with immunohistochemical study]. / Adénocarcinome papillaire de bas grade du sac endolymphatique. A propos de trois observations avec étude immunohistochimique.

Glandular tumors involving the mastoid and the middle ear are rare, and distinguishing between adenoma and adenocarcinoma remains difficult. Among these latter lesions, two distinct patterns are accepted. One of them, the papillary form takes a more aggressive course with wider regional spread and must be separated from the other type, the middle ear carcinoma. Its microscopic appearance and clinical course have been extensively described by Heffner who considered it as "low-grade adenocarcinoma of probable endolymphatic sac origin". A few cases have been associated with von Hippel-Lindau disease. Three cases of papillary adenocarcinoma of endolymphatic sac origin are reported. One concerned an isolated tumor, the two others were associated with von Hippel-Lindau disease. Their clinical, pathological and immunohistochemical data are presented.

Identification of K-ras mutations in pancreatic juice in the early diagnosis of pancreatic cancer.

OBJECTIVE: To develop an early diagnostic test for pancreatic cancer based on the identification of K-ras mutations in pure pancreatic juice collected during endoscopic retrograde pancreatography. DESIGN: Prospective study with masked comparison. The standard criteria for the diagnosis of pancreatic cancer were pancreatography or surgery (or both) and histopathology, with follow-up ranging from 6 to 40 months. SETTING: Referral center. PATIENTS: 24 patients with no pancreatic disease (group 1); 29 patients with nontumoral pancreatic disease (group 2); and 22 patients with pancreatic tumor (group 3). Endoscopic ductal aspiration of cells or brush cytology was done on patients having endoscopic retrograde pancreatography for diagnostic or therapeutic reasons. MAIN OUTCOME MEASURE: Confirmation of mutation rates in patients with pancreatic cancer. RESULTS: K-ras gene analysis was done by polymerase chain reaction-mediated restriction fragment length polymorphism analysis and direct sequencing. All patients from groups 1 and 2 (n = 53) had a normal sequence for the K-ras 12th codon (group 1, 0% [95% CI, 0% to 14%]; group 2, 0% [CI, 0% to 12%]). Mutations were seen in 17 of the 22 patients in group 3 (77% [CI, 55% to 92%]). Two of the 17 had no evidence of pancreatic cancer when K-ras was first studied. One had chronic abdominal pain and the other presented with acute pancreatitis. Both were initially free of any pancreatic mass, but they developed tumors 18 and 40 months, respectively, after the K-ras mutations were identified. CONCLUSION: Identification of K-ras mutations in samples of pancreatic juice may be useful in differentiating between pancreatic cancer and noncancerous pancreatic diseases. K-ras mutation can precede clinical evidence of pancreatic cancer, but the clinical implications of this finding need further study.

Papillary neoplasm of the endolymphatic sac in a patient with von Hippel-Lindau disease.

Glandular tumours involving the middle ear and the mastoid are rare, and distinguishing between adenoma and adenocarcinoma is difficult. Two distinct histopathological patterns are accepted. While their clinical presentation differs, both require primary surgical treatment and both have a high rate of local recurrence. The papillary form takes a more aggressive course and wider regional spread. This pattern occurs predominantly in women. Its microscopic appearance and clinical course have been extensively described by Heffner who considered it as "low-grade adenocarcinoma of probable endolymphatic sac origin". A few cases have been associated with von Hippel-Lindau disease. The case of a 32 year old black woman is described. It is suggested that papillary adenocarcinoma of the endolymphatic sac should be considered in the spectrum of neoplasms seen in von Hippel-Lindau disease.

[Brain metastasis of a cutaneous neuroendocrine carcinoma. Apropos of a case]. / Métastase cérébrale d'un carcinome neuroendocrine cutané. A propos d'une observation.

The authors report the case of a 69-year-old woman with a brain metastasis from a cutaneous neuroendocrine carcinoma. The initial lesion was situated on the leg. No other secondary lesion was found. The cutaneous neuroendocrine carcinoma was initially considered to be a locally malignant tumor. In fact, it is frequently complicated by metastases. However, brain secondaries remain rare.

Morphological analyses of paraspinal muscles: comparison of progressive lumbar kyphosis (camptocormia) and narrowing of lumbar canal by disc protrusions.

Progressive lumbar kyphosis (camptocormia), a rare, usually familial disease in elderly patients, is characterized by inability to immobilize the lumbar spine in relation to the pelvis. CT scan reveals selective involvement of the spinal muscles with a heterogeneous appearance and is in favour of a primary disorder of these muscles. Our aim was to define the muscular lesions and clarify their nature in this particular disorder. Biopsies of the paravertebral muscles of 14 patients with lumbar kyphosis and of 20 operated on for disc herniation or narrowed lumbar canal, were studied by light microscopy, histochemistry and electron microscopy. In both groups, type 1 fibre predominance and atrophy of type 2 fibres were observed. Ragged-red fibres with abnormal mitochondria also occurred. The differential feature was increased frequency of extensive diffuse or lobulated fibrosis in camptocormia. Other features related to pathogenesis could not be determined.

Androgenic granulosa cell tumor of the ovary: in vivo hormonal studies.

Androgenic granulosa cell tumors of the ovary are rare and have not been well studied hormonally. A 20-year-old woman complaining of secondary amenorrhea with high plasma testosterone (295 ng/dl) and a right ovarian tumor was studied. Plasma testosterone levels decreased after two days of dexamethasone (36 ng/dl), increased after hCG administration (538 ng/dl) and a unilateral right ovarian gradient of testosterone was noted at the selective catheterization of ovarian veins. After removal of the granulosa cell tumor, testosterone concentration returned to normal (68 ng/dl) and the patient had resumption of normal menses.

[Creutzfeldt-Jakob disease after treatment with human extracted growth hormone. A clinicopathological study]. / Maladie de Creutzfeldt-Jakob après traitement par l'hormone de croissance extractive humaine: étude clinico-pathologique.

This report describes the pathological changes observed in the brain of a 18-year-old patient who died with Creutzfeldt-Jakob disease (CJD) of the ataxic and panencephalopathic type. Clinically, the disease began at age 17 with a rapidly progressive cerebellar syndrome, associated with myoclonus and mental deterioration. Cranial CT scan and MRI showed minor abnormalities. EEG demonstrated non specific changes. The patient became progressively demented, bedridden and died 10 months after the onset. Nine years earlier, he had been operated upon for craniopharyngioma and subsequently treated with cadaver-derived human growth hormone. Post-mortem examination of the brain revealed mild diffuse atrophy. Histology showed congophilic amyloid plaques found in both gray and white matters of the cerebrum and cerebellum, associated with spongiosis, mainly in the basal ganglia and cerebellum, and gliosis. They were immunostained with antiprion protein antibody using the immunoperoxidase method on paraffin embedded sections. The clinical findings in this case were similar to those of other cases of human growth hormone-associated CJD. However, this case is unusual because of the great number of amyloid plaques, which have been only rarely found in previous reports.

[Incidence, treatment and prognosis of cancer of the pancreas in Haute-Garonne (1982-1986)]. / Incidence, traitement et pronostic du cancer du pancréas en Haute-Garonne (1982-1986).

The characteristics of incident cases of pancreatic carcinoma found in the area of Haute-Garonne (France), as determined by the Digestive Cancer Registry, are reported. Two hundred and forty-six new cases were collected during a 5 year period in a population of 820,000 inhabitants. The annual standardized incidence rate per 100,000 inhabitants was 4.7 for men and 2.6 for women, respectively. This represents a low risk and corresponds to 7 percent of all intestinal tract tumors. The tumors were shown histologically to be adenocarcinoma in 85 percent of cases. The tumor was localized in the head of the gland in 64 percent of cases, while metastases were present at the time of diagnosis in 43 percent of cases. Ultrasonography was the initial investigation (44 percent of cases) and was performed well before endoscopic retrograde wirsungography (12.8 percent) and computed tomography (18 percent). Eighty-six percent of the patients were operated on. Curative surgery, however, was possible in only 12.5 percent of patients. The incidence of carcinoma remained stable during the observation period and no change was noticed with regard to housing conditions. During follow-up, 50 of 215 patients died within one month following the diagnosis (23 percent). Actuarial survival was 36 percent at 6 months, 17.4 percent at one year, and 3.6 percent at 3 years. These data were comparable to those observed in the Côte-d'Or and Calvados areas. These findings suggest that the French Digestive Tumor Registries should develop co-operative studies particularly in the analytic epidemiological fields.

[Anatomopathologic diagnosis of parasitosis in Congo]. / Le diagnostic anatomopathologique des parasitoses au Congo.

In the part ten years, 9,650 anatomopathologic examinations have been carried out in the National Laboratory of Histopathology for Public Health in Brazzaville: 250 cases of parasitic infestation were diagnosed. In order of frequency were noted; 144 cases of bilharzia due to Schistosoma haematobium with 75 genito-urinary localisations and 51 appendicular cases, 31 cases of onchocercosis with a majority of subcutaneous nodules (17), 17 cases of digestive helminthiasis all locate in the ileo-caecal-appendix and discovered during systematic appendicular exploration, 13 cases of colitic or recto-sigmoidal amebiasis. These results point out 68 cases of appendicular parasitism. This should be in favour of more systematic anatomopathological examination of the ileo-caecal appendix both in tropical and in temperate regions.