Cell proliferation in colorectal adenocarcinomas: comparison between Ki-67 immunostaining and bromodeoxyuridine uptake detected by immunohistochemistry and flow cytometry.

We compared three different means of assaying tumor proliferative activity in 30 human colorectal adenocarcinomas labeled in vivo with bromodeoxyuridine (BrdUrd). The labeling indices (LI) of BrdUrd obtained both by flow cytometry (FCM) and immunohistochemistry (IH) were also compared with the labeling index of Ki-67. These methods were then related to tumor ploidy and pathological features. Flow cytometry was performed in accordance with Begg's method after intravenous infusion of BrdUrd four hours before surgery. Immunohistology was carried out on paraffin-embedded sections with monoclonal antibodies against BrdUrd and Ki-67. A positive correlation was found between BrdUrd LI obtained by both FMC and IH (p<0.0001), a finding that complies with the literature. However, we report on a correlation between Ki-67 LI and BrdUrd LIs in colorectal tumors (p=0.012). The results were valid for all tumors when they were subdivided into diploid and aneuploid groups. The labeling indices were significantly higher in the aneuploid tumor group than in the diploid group (p=0.047). No relationship between proliferation parameters and tumor stage or grade was found. To our knowledge, this is the first report on a positive correlation between tumor proliferation indices in BrdUrd LIs and Ki-67 in colorectal carcinomas. This finding validates the value of Ki-67 immunostaining, which, however, should be confirmed in a larger series under the same technical conditions.

An isochromosome 6p in a primary meningeal malignant melanoma.

The rearrangement of chromosome 6, particularly the deletion of 6q, has been observed in human malignant melanoma with or without brain metastases. The isochromosome 6p has also been described. In this study, we report the cytogenetic analysis of a primary malignant melanoma of the central nervous system. Its dominating karyotype was 47,XX,+i(6)(p10). Fluorescence in situ hybridization (FISH), using a 6p chromosome arm probe, confirmed the structure of the isochromosome. To our knowledge, this is the first report of this type of chromosomal aberration in an uncommon neoplasm of leptomeningeal melanocytic origin.

Pre-operative kinetic parameter determination of colorectal adenocarcinomas. Prognostic significance.

BACKGROUND: The aim of this study was to test the prognostic value of pre-operative assessment of tumour kinetics in colorectal adenocarcinoma. METHODS: The study of tumour kinetics was performed using an in vivo injection of bromodeoxyuridine. Endoscopic biopsies were obtained from the tumour and analysed using flow cytometry. This procedure enables calculation of the in vivo S-phase fraction labelling index (LI), the duration of S-phase (Ts) and the potential tumour doubling time (Tpot). Disease-free survival curves were calculated by a Kaplan-Meier method. The statistical significance between curves was tested by the log rank test. A multivariate analysis was performed using the Cox's proportional hazards model to determine the effect of pathological staging (lymph node involvement), ploidy and kinetic parameters. RESULTS: Thirty-eight colorectal carcinomas were studied without prior chemotherapy or radiation therapy. In univariate analysis, lymph node involvement, labelling index > 10% and Tpot < 5 days were associated with poor prognosis, with P= 0.0006, 0.049 and 0.029 respectively; no significant differences were found in Ts (P = 0.214), and ploidy (P= 0.095). In multivariate analysis, lymph node involvement, ploidy and Tpot were found to be independent factors of colorectal cancer prognosis (P= 0.028, 0.032 and 0.035 respectively) in all tumours. Tpot was considered a independent prognostic factor in diploid tumours (P= 0.047) but not in aneuploid tumours (P= 0.345). CONCLUSIONS: These results suggest that kinetic parameters determined by pre-operative biopsies of colorectal adenocarcinoma represent a prognosis factor, independent of pathological staging, particularly in diploid tumours.

Low sensitivity of invasive tests for the detection of Helicobacter pylori infection in patients with bleeding ulcer.

BACKGROUND: A high false negative rate for antral infection with Helicobacter pylori when assessed by rapid urease test has recently been reported in patients with bleeding ulcer. This result could partly explain the differing prevalence of H. pylori infection in bleeding and non-bleeding ulcers. AIMS: To evaluate the accuracy of a rapid urease test (UT), histology and culture for detection of H. pylori in antral biopsies from acute bleeding peptic ulcer patients using a serological test as reference. PATIENTS AND METHODS: All consecutive patients with active bleeding gastric or duodenal ulcer at endoscopic examination admitted in six university hospitals in France were considered for inclusion. Five antral biopsies were taken during the diagnostic endoscopy for UT, culture and histology. A blood sample was taken for H. pylori serology. RESULTS: One hundred and eighty one patients were included and 129 (71%) had a positive serology. The sensitivity of UT, histology and culture for detection of H. pylori infection were 41%, 33% and 34%, respectively. The sensitivity and specificity of the combination of the three invasive tests were 48.8% (95% CI: 40.2-57.4) and 90.6% (95% CI: 82. 6-99) respectively. In the 52 serologically negative patients, only 5 had at least one invasive positive test. The sensitivity of the invasive tests decreased significantly with age but was not influenced by NSAIDs intake. Of 80 patients with a positive serological test and negative histological evaluation for H. pylori, chronic antral inflammation was found in 70 patients (87%). In 46 patients with both negative serological test and H. pylori negative test according to histology, only 13 (28%) had chronic antral inflammation. CONCLUSIONS: The sensitivity of invasive tests for detection of H. pylori is low during acute ulcer bleeding, and they should be used with caution in this condition. A serological test is recommended to identify patients with H. pylori infection in spite of negative invasive tests.

Type 1-primary cutaneous meningioma of the scalp.

Type 1-primary cutaneous meningioma is a rare and often clinically unsuspected lesion of the scalp, forehead or paravertebral region which occurs at birth or during childhood. The pathogenesis of these lesions still remains uncertain. Several authors have emphasized that type 1-cutaneous meningiomas are not real tumors but sequestrated meningoceles or heterotopic meningeal nodules of the skin. Nevertheless, the search for an intracranial or intravertebral connection should be carried out. We describe the clinical and pathological features of a congenital type 1-meningioma of the vertex. No cranial defect or intracranial tumor was found. However, the cutaneous lesion was directly linked to a large cranial vein. The purpose of this study was to illustrate this rare lesion and to indicate the possible surgical risks and the pathological characteristics.

[Epidermal nevus associated with a type I neurofibromatosis and a nephroblastoma: a new epidermal nevus syndrome?]. / Association d'un naevus épidermique, d'une neurofibromatose de type I et d'un néphroblastome: un nouveau syndrome du naevus épidermique?

We report the case of a 6-year-old boy who showed a large epidermal nevus mixed with a plexiform neurofibroma, which was associated with "café au lait" macules and a nephroblastoma. This association could not be classified in one of the five well defined epidermal nevus syndrome. To our knowledge this is the first time that this type of epidermal nevus syndrome has been described, which raises the question of the relationship between neurofibromatosis 1, nephroblastoma and epidermal nevus.

Effect of radiation therapy on the potential doubling time of tumours in colorectal cancers.

OBJECTIVE: The aim of the present study was to investigate the effects of standard fractionated radiation therapy on the kinetic parameters of colorectal adenocarcinomas. METHODS: The study of tumour kinetics involved in vivo injection of bromodeoxyuridine. Endoscopic biopsies were obtained from the tumour and analysed with flow cytometry. This procedure provides a rapid calculation of qualitative parameters such as ploidy and quantitative parameters such as the in vivo S-phase fraction labelling index which indicates the percentage of cells that have entered into the cycle, the duration of S-phase (Ts) and the potential tumour doubling time (Tpot). RESULTS: Thirty-eight colorectal carcinomas were studied without prior chemotherapy or radiation therapy (group 1) and ten rectal carcinomas were studied following radiation therapy (group 2). In diploid tumours, the labelling index was significantly lower in the post-radiotherapy group than in the pre-radiotherapy group (2.7 +/- 1.1% versus 6.4 +/- 4.2%, respectively; P= 0.01), and the Tpot was significantly longer after radiotherapy (group 2) (22.0 +/- 7.0 days versus 8.6 +/- 6.0 days, P = 0.002). Standard fractionated radiation therapy also appears to result in a longer Tpot in diploid adenocarcinomas of the colon and rectum. This effect was not observed in aneuploid tumours. CONCLUSIONS: The effectiveness of hyperfractionated schedules of radiation therapy for aneuploid rectal tumours with short Tpot warrants further investigation in a larger patient population.

[Extrarenal nodular nephrogenic blastema in the inguinal canal: report of two cases]. / Blastème néphrogène nodulaire extrarénal de siège inguinal: à propos de deux cas.

Two observations of extrarenal nephrogenic nodule in inguinal canal are reported. We underline the difficulties in differential diagnostic with true Wilms' tumor, and in sparing these pediatric cases from more aggressive treatment. The main morphological arguments in favor of non-tumoral nephrogenic nodular remnants are: the size of the lesion, the association with a congenital inguinal hernia suggesting a congenital abnormality, and the organoid organization of blastemic tissue surrounding the cavities lined with "hobnail" epithelium evoking a mesonephrogenic origin.

[Pseudomyxoma extraperitonei. Report of 3 cases]. / Le pseudomyxome extrapéritonéal. A propos de 3 observations.

The authors report three additional cases of pseudomyxoma extraperitonei and describe the modalities of occurrence and evolution. Pseudomyxoma extraperitonei arises from spontaneous or accidental implantation of mucosal cells of the primary site. This inoculation is accompanied by the modification of glandular cells which survive by adapting themselves to the interstitial connective tissue environment, raising thus the ability of extensive involvement and tumor-like invasive behavior.

A European de facto standard for image folders applied to telepathology and teaching.

Since 1980, French pathologists at ADICAP (Association pour le Développement de l'Informatique en Cytologie et en Anatomie Pathologique) have created a common language code allowing the use of computers for routine applications. This code permitted the production of an associated exhaustive image bank of approximately 30,000 images. This task involved many specialists necessitating the definition of specific processes for security and simplicity of data handling. In particular, it has been necessary to develop image communication. To achieve that goal, it was necessary to define a folder, associating textual information to images. That was done through several industrial software providers contribution. Consequently, this folder, using a common packaging standard, allowed any pathologist access to images, codified data and clinical information. Accessing folders has been made easy by launching a Web server at CRIHAN under the supervision of ADICAP. An ADICAP software user may not only browse through the folder but may also import them into their own system and produce new folders. Today more than a hundred users in France and in foreign countries are able to provide diagnostic advice and also referential products useful for further education and quality control. The next challenge is the development of this preliminary de facto approach toward an internationally admitted standard suited for morphological image exchange.

Taenia crassiceps invasive cysticercosis: a new human pathogen in acquired immunodeficiency syndrome?

A fluctuant, painful, subcutaneous, and intermuscular tumor developed in a 38-year-old man with severe acquired immunodeficiency syndrome (AIDS) in which immunodeficiency was severe. Surgery revealed lesions that formed a multilocular pouch embedded in deep tissues in the forearm filled with tapiocalike material containing a viscous fluid, granules, and cysticercilike small vesicles. Pathologic and parasitologic evaluation showed cysticerci embedded in a fibrocollagen reaction with inflammatory granulomatous reaction. Each cysticercus contained an invaginated scolex with two rows of small (i.e., 80 microm) and large (i.e., 114 microm) rostellar hooks, identical to larva of Taenia crassiceps. All clinical, parasitologic, and pathologic features of these cysticerci were very different from those of all other larval cestode (i.e., Taenia solium cysticercosis, coenurosis, sparganosis, cysticercosis due to Taenia saginata [Cysticercus bovis], primary and secondary hydatidosis [Echinococcus species]). T crassiceps cysticerci usually develop in subcutis and pleuroperitoneal cavities of rodents, whereas the adult tapeworm is commonly found in the digestive tract of foxes. Biologic properties of T crassiceps cysticerci and epidemiologic characteristics of pandemic human immunodeficiency virus (HIV) could eventually indicate new potential cases of T crassiceps cysticercosis in humans.

Comparison between endoscopic and surgical sampling for the measurement of potential doubling time in colorectal cancer.

In colorectal cancer, tumoral kinetic parameters could influence the therapeutic strategy. The aim of this study was to test the validity of a preoperative assessment of tumoral kinetics on biopsies obtained from endoscopic sampling. After infusion of 250 mg of bromodeoxyuridine (BrdUrd), tumor samples were taken. The following kinetic parameters were evaluated by Begg's method: labeling index (LI) of BrdUrd, duration of the S phase (Ts), and potential doubling time (Tpot). We compared the findings in preoperative endoscopic samples (t1), endoscopic samples (t2), and macrobiopsies of the tumor after surgical resection (t3) to test the effect of time, surgical procedures, and sampling mode on results. Eight diploid and 11 aneuploid colorectal cancers were studied. In diploid tumors, no difference in Tpot, Ts, or LI values was found among the three time intervals. In aneuploid tumors, Tpot value at t1 was lower than t3: 2.9 +/- 1.2 versus 4.5 +/- 1.4 days (P = 0.02). This difference seemed to be independent of sampling type but related instead to the time interval between BrdUrd infusion and biopsy and to the changes due to the surgical condition. On the other hand, LI seemed to be the most stable kinetic parameter. With a cutoff value of 4 days for Tpot and of 10% for LI to differentiate slow and fast growing tumors, the positive predictive values of LI were 90% at t1, 80% at t2, and 50% at t3 in aneuploid tumors.

Selective resection of the phrenic nerve roots in rabbits. Part I: Cartography of the residual innervation.

Partial unilateral diaphragmatic paralysis remains poorly understood. This study evaluates the residual innervation of the diaphragm after selective resection of one or several roots of the right phrenic nerve in rabbits. Forty-seven animals were operated on according to five root resection modalities. Seven animals served as control. Eight weeks after surgery, the different regions of each hemidiaphragm were analyzed. Electromyographic activity was measured during quiet inspiration and the following histomorphometric parameters were studied: mean fiber area, fiber area dispersion, and ratio large diameter over small diameter. The results obtained from the two measurements were similar. When the accessory phrenic nerve was spared, the crural diaphragmatic region was preserved; denervation was encountered in anterior and lateral parts of the hemidiaphragm. When the highest root of the right phrenic nerve was resected, denervation denervation was limited to the sternal region. When resection of the two highest roots was performed, partial denervation was observed in each region, with residual innervation in the posterior hemidiaphragm. When resection of both the lowest roots was performed, denervation was maximal in the costal region; sternal region remained intact. No contralateral innervation was observed. We conclude that in rabbits: 1) resection of a single root of the phrenic nerve preserves consistent residual innervation. 2) somatotopy of the diaphragm innvervation follows an anteroposterior distribution.

Transforming growth factor alpha (TGF-alpha) expression correlates with DNA replication in regenerating rat liver whatever the hepatectomy extent.

Liver regeneration is a physiological mechanism that leads to restoration of the hepatic parenchyma following hepatectomy or toxic injury. As a two-third hepatectomy is the usual model to analyse this phenomenon, few studies have compared liver regeneration after minor vs major hepatectomy. We have used a quantitative RT-PCR technique to study the hepatic transcription of the TGF-alpha gene in rats submitted to 30% or 80% hepatectomy and we have correlated this transcription with the regenerative response assessed by flow cytometry and Ki-67 expression. The level of TGF-alpha expression and the regenerative response were different, according to the volume of liver removed, and were statistically correlated (r = 0.679, p = 0.002). TGF-alpha expression and phase S peaked at day 2 vs 6 in the 80% vs 30% hepatectomized rat groups, respectively. Ki-67 expression occurred at 2 h post-hepatectomy in the two groups of rats and was observed until day 14 mainly in the 80% hepatectomy group. Our results indicate that TGF-alpha expression in regenerating liver is strongly correlated with hepatocyte mitosis, that a delayed regenerative response occurs following 30% hepatectomy and that the course of regeneration differs between minor vs major hepatectomy.

Digestive manifestations in an immunocompetent adult with varicella.

A case of varicella with pancreatic pain as a first manifestation, a typical papulovesicular rash, pulmonary and hepatic and esophageal localizations occurring in an immunocompetent adult is reported. Treatment with intravenous acyclovir resulted in a prompt improvement and recovery in less than 4 days.

Antenatal exposure to atenolol and retroperitoneal fibromatosis.

We present a case of retroperitoneal fibromatosis in a fetus whose mother took atenolol during pregnancy. A 25-year-old obese woman was treated for hypertension with 100 mg atenolol daily from the second month until the end of pregnancy. At 29 weeks, echography disclosed a retroperitoneal mass and at 37 weeks, a boy was delivered. A biopsy of the tumor showed a fibromatosis with medullary compression, treated by antimitotics until 3 months of age. At the age of 4, the mass had disappeared but severe scoliosis was present. This in utero exposure to atenolol drew our attention because the retroperitoneal localization of the tumor is similar to that of fibroses reported in adults after exposure to atenolol and for other reasons: transplacental carcinogenesis has been demonstrated in humans, at least for diethylstilboestrol, atenolol crosses the placental barrier, the drug was taken during nearly the whole pregnancy, and retroperitoneal fibromatosis is exceptional as a neonatal tumour.

Hepatosplenic gamma/delta T-cell lymphoma: a report of two cases in immunocompromised patients, associated with isochromosome 7q.

Two cases of peripheral T-cell lymphoma, characterized by hepatosplenic presentation and gamma/delta T-cell receptor phenotype on malignant cells, are reported. Little is known about the chromosomal changes in these peculiar lymphomas. We report the cytogenetic analysis of these two patients. Isochromosome 7q and trisomy 8 were observed. These abnormalities were reported previously in five cases of gamma/delta T-cell lymphoma. These two patients had lymphomatous infiltration of the spleen, liver, bone marrow, and (in one case) lymph nodes. These abnormalities occurred in immunocompromised patients (i.e., immunosuppressive therapy for kidney transplantation and chemotherapy for Hodgkin's disease), without Epstein-Barr virus infection stigmata in tumor cells.

[Gallbladder involvement in Crohn disease]. / Atteinte vésiculaire au cours de la maladie de Crohn.

We report the case of a young woman with Crohn's disease involving the entire digestive tract and with associated lesions of the liver, pancreas and gallbladder. This latter lesion led to acute cholecystitis which required cholecystectomy. The histo-pathological examination showed granulomas with multinucleated giant cells in the lamina propria. This observation illustrates a severe and extended form of Crohn's disease involving the entire digestive tract as well as the liver, the pancreas and the gallbladder.