Validation of modular endoscopic medial maxillectomies for inverted papilloma of the maxillary sinus.

BACKGROUND: Treatment of inverted papilloma of the maxillary sinus (IPMS) has a lower success rate compared to other IPs. As such, its correct management generally needs trans-nasal endoscopic medial maxillectomy (EMMs) for adequate resection. The aim of this manuscript is to describe outcomes and major prognostic factors of a cohort of patients with IPMS who were treated with EMM. METHODOLOGY: In this multicentric study, patients affected with IPMS and treated with EMMs were included. The site of origin of the IPMS were studied as well as the type of EMM performed. The histological features (IP vs dysplasia), type of mucosal resection (total vs. pedicle oriented), and post-operative complications were analyzed. RESULTS: 310 patients were included (212 primary and 98 recurrent cases). After a mean follow-up of 45.4 months, 15 patients experienced recurrence (4.8%) due to the application of EMMs tailored to the surgical insertion point. Dysplasia was significantly associated with a higher risk of recurrence. The rates of early and late complications were 11.6% and 11.9%, respectively. CONCLUSIONS: IPMS resection via tailored EMM is associated with excellent disease control, thus excluding the systematic use of extended EMMs, which can however be justified in case of dysplastic IPMS given its significant impact on recurrence.

Does advanced age affect treatment of early glottic carcinoma?

AIMS: Early glottic carcinoma is currently managed by radiation therapy or endoscopic surgery. Both are effective in elderly patients, but their respective indications are poorly determined. The present study assessed our management of very elderly patients with early glottic carcinoma. MATERIAL AND METHODS: A retrospective single-center study included all patients aged 75 years and older at diagnosis, treated by radiation therapy or endoscopic surgery with curative intent for T1 or T2 glottic carcinoma between 2004 and 2018. RESULTS: Records of 33 patients (27 men and 6 women; mean age, 82.2 years (range, 76.1-93.1 years)) were reviewed. 24 patients received radiation therapy and 9 endoscopic resection. The only factor for choice of treatment was anterior commissure involvement. Overall survival was 87% at 2 years and 62% at 5 years. 19% of patients relapsed within 5 years and had to undergo further treatment. There were no treatment-related deaths. Radiation therapy was associated with more acute local complications, with two temporary treatment interruptions and one uncompleted treatment. Surgical treatment was more likely to result in dysphonia, found in 80% of cases. CONCLUSION: Treatment of early glottic cancer in elderly subjects can consist in either radiotherapy or endoscopic surgery. Age should not affect management. Surgical treatment is shorter and better tolerated, although with poorer vocal outcome, and may be preferred in the most comorbid patients.

Pathology underrates colon cancer extranodal and nodal metastases; ex vivo radioimmunodetection helps staging.

PURPOSE: Colorectal carcinoma is frequently accompanied by small lymph nodes metastases that often escape pathologic examination. We evaluated whether ex vivo radioimmunodetection with the Affinity Enhancement System (AES) could improve detection of mesocolonic metastases. EXPERIMENTAL DESIGN: A bivalent 111In-labeled hapten was injected (16 patients) 4 days after a bispecific antibody (anticarcinoembryonic antigen, antihapten). Surgery was done 1 to 3 days later, and radioactive uptake in the mesocolon was recorded. Extensive pathologic examination of the mesocolon (reference method) was done after fat dissolution. This method visualizes all lymph nodes but is not in routine use. RESULTS: The reference method disclosed 705 nodes. There was no significant difference between the number of node metastases detected by AES or by the reference method (16 versus 17). Better detection would have been obtained by AES than by routine pathology (P<0.01). In addition 12 extranodal metastases were found in this study of which eight were detected by AES. The prognostic importance of such extranodal metastases has been underlined in the literature. Routine pathology combined with AES would have disclosed all node metastases and 86% of total metastases versus 35% by routine pathology alone. CONCLUSIONS: Ex vivo radioimmunodetection could improve nodal and extranodal metastases detection in patients with colorectal cancer. Its value for improving pathologic analysis, together with the effect of these small metastases on prognosis, should be further evaluated. The benefit of adjuvant chemotherapy for patients upstaged with radioimmunodection should also be assessed because adjuvant chemotherapy improves the 5-year survival of stage III patients.

Changes in AIDS-related lymphoma since the era of highly active antiretroviral therapy.

HIV infection is associated with a high incidence of AIDS-related lymphomas (ARLs). Since the use of highly active antiretroviral therapy (HAART), the incidence of AIDS-defining illnesses has decreased, leading to a significant improvement in survival of HIV-infected patients. The consequences of HAART use on ARL are under debate. This study compared the incidence and the characteristics of ARL before and after the use of HAART in a large population of HIV-infected patients in the French Hospital Database on HIV (FHDH) and particularly in 3 centers including 145 patients with proven lymphoma. Within the FHDH, the incidence of systemic ARL has decreased between 1993-1994 and 1997-1998, from 86.0 per 10 000 to 42.9 per 10 000 person-years (P < 10(-30)). The incidence of primary brain lymphoma has also fallen dramatically between the periods, from 27.8 per 10 000 to 9.7 per 10 000 person-years (P < 10(-11)). The analysis of 145 cases of ARL in 3 hospitals showed that known HIV history was longer in the second period than in the first period among patients with systemic ARL (98 versus 75 months; P <.01). Patients had a higher number of CD4 cells at diagnosis during the second period (191 versus 63/microL, P = 10(-3)). Survival of patients with systemic ARL also increased between the periods (from 6 to 20 months; P =.004). Therefore, the profile of ARL has changed since the era of HAART, with a lower incidence of systemic and brain ARL. The prognosis of systemic ARL has improved.

Chronic use of non-steroidal anti-inflammatory drugs does not alter colonic mucosa of patients without diarrhoea.

BACKGROUND: Several types of colitis can be NSAID-induced, but whether chronic use of NSAIDs alters colonic mucosa in patients without diarrhoea is not known. PATIENTS AND METHODS: Biopsy specimens of rectal mucosa were taken in six patients with rheumatoid arthritis without diarrhoea receiving NSAIDs (group 1, n=6). Patients with rheumatoid arthritis without diarrhoea not receiving NSAIDs (group 2, n=9), and patients undergoing surveillance colonoscopy (group 3, n=23) served as controls. In all patients from the three study groups, intraepithelial lymphocyte count and apoptotic cell count were assessed, and sub-epithelial collagen band thickness was measured. Leucocyte population of lamina propria was evaluated semi-quantitatively. HLA-DR and CD25 expression of mucosal cells was appreciated by immunohistochemistry. RESULTS: Intraepithelial lymphocyte count was in the normal range in all three group patients, and not statistically different between groups. Apoptotic epithelial cell count was not different between groups. Sub-epithelial collagen band thickness was normal in all the patients. No patient had a marked infiltration of lamina propria by leucocytes, and HLA-DR and CD25 were normally expressed in all patients. CONCLUSION: These results from a small sample of patients suggest that patients without diarrhoea receiving NSAIDs on a long-term basis do not develop microscopic or inflammatory colitis.

In situ hybridization determination of the heterophagocytic origin of type 2B prostate epithelial lipochrome pigment granules: histochemical and ultrastructural correlates.

UNLABELLED: Morphologically, polymorphic prostatic lipochrome pigment has been classified and subclassified in the last few years. Type 2B lipochrome pigment granules (LPGs) are frequently found in prostatic epithelium in patients who had died of AIDS. Intensive apoptosis is observed in the same epithelium which lends support to the hypothesis of heterophagocytic (apoptotic) origin of type 2B pigment granules. Detection of nuclear chromatin material is necessary for the differentiation of an autophagosomal from a heterophagosomal structure in the cellular cytoplasm. OBJECT OF THE STUDY: Application of in situ hybridization (ISH) for elucidating the origin of subtype 2B LPGs in the prostate epithelial cells of patients who had died of AIDS. METHODS: ISH was used on routine necropsic prostate epithelial samples from three patients who had died of AIDS. A DNA probe raised against total human DNA was employed. RESULTS: Multiple hybridization signals were detected in type 2B LPGs which shows the presence of nuclear material in those structures. The chromatin material localized to the periphery of pigment granules. CONCLUSION: Type 2B LPGs have a heterophagocytic origin and represent phagocytosed apoptotic bodies in the phase of phagolysosomal degradation. They can be used as a morphologic tissue marker of intensive epithelial apoptosis.

Are complicated forms of celiac disease cryptic T-cell lymphomas?

We assessed the clonality of duodenal mucosal T cells in patients with celiac disease and controls. Fifteen adult patients were studied. Four patients had a complicated celiac disease, 3 did not respond to a gluten-free diet, and 2 had an ulcerative jejunitis (including 1 patient with nonresponsive celiac disease). Seven patients had an untreated celiac disease responsive to a gluten-free diet. Histological examination of duodenal biopsies of these 11 patients showed benign-appearing celiac disease without evidence of lymphoma. Four patients with nonulcer dyspepsia and normal duodenal biopsies served as controls. TCRgamma gene rearrangements were analyzed by multiplex polymerase chain reaction on DNA extracted from duodenal biopsies. Major clonal rearrangements of the T-cell receptor were found in 4 cases, all with complicated celiac disease. Monoclonality was confirmed by DNA sequencing of the junctional region in 3 cases and by hybridization with clone-specific oligoprobes. Patients with celiac disease responsive to gluten-free diet had mainly a polyclonal pattern, with 1 of them having an oligoclonal rearrangement. An oligoclonal pattern was also observed in 2 control patients. Three patients with complicated celiac disease evolved to T-cell lymphoma with liver (n = 2) or bone marrow (n = 1) invasion. Identical clones were found in the enteropathic duodenojejunum and peripheral blood in the patient with large-cell lymphoma with bone marrow invasion. This study suggests that complicated celiac disease is a cryptic T-cell lymphoma.

An autopsy study of the prostate in acquired immunodeficiency syndrome: evidence for excessive apoptosis and intracytoplasmic epithelial inclusions.

We describe a combination of epithelial cell apoptosis and intracytoplasmic inclusions in prostatic epithelium in 6 patients who died from the acquired immunodeficiency syndrome. Two different types of apoptosis were detected: simple cell shrinkage and exploding glandular cells. No intracellular or extracellular viral particles were detected, either ultrastructurally or immunohistochemically. Intracytoplasmic inclusions are apoptotic bodies in a state of degradation and in close association with lipofuscin. The cell degeneration we observed confirms the theory that increased apoptotic cell depletion is responsible for weight loss in the acquired immunodeficiency syndrome. In the prostate itself, the combination of excessive apoptosis and active phagosomal digestion of apoptotic bodies presents a "human model" of postcastration rat ventral prostate, under the conditions of severe immune deficiency.

Definition and diagnosis of cytomegalovirus colitis in patients infected by human immunodeficiency virus.

The definition and routine diagnosis of cytomegalovirus (CMV) colitis in patients infected by human immunodeficiency virus (HIV) are controversial. In 100 consecutive HIV-infected patients who underwent colonoscopy for the investigation of diarrhea, we compared the yields of routine diagnostic tools for CMV infection and assessed the risk of further CMV organ disease in subgroups of patients with the following features: full evidence of CMV colitis (group 1), colonic CMV infection but no endoscopic lesions (group 2), and no evidence of colonic CMV infection (group 3). All biopsies taken during colonoscopy were examined immediately by routine hematoxylin and eosin (H&E) staining and viral culture and then pooled for second-line H&E staining and immunohistology. Among the 15 diagnoses of CMV colitis (group 1), two were missed during initial H&E examination, and both patients developed further CMV organ disease during follow-up. Of the 12 group 2 patients 11 were not receiving anti-CMV drugs at the time of initial colonoscopy. CMV organ disease was not significantly more common in these patients than in group 3 during follow-up. We conclude that routine H&E staining of colonic biopsy specimens for CMV inclusions is not 100% sensitive for CMV colitis. The favorable outcome of colonic CMV infection without endoscopic lesions suggests that only patients with full evidence of CMV colitis warrant specific antiviral therapy.

Thrombotic microangiopathy and cytomegalovirus disease in patients infected with human immunodeficiency virus.

Thrombotic microangiopathy (TMA) can occur during the course of human immunodeficiency virus (HIV) infection. Clinical and pathological data for 29 patients with TMA and HIV infection were recorded. In a retrospective case-control study, we analyzed the link between opportunistic infections or drug therapies and TMA. Twenty-five patients (mean CD4+ cell count +/- SD, 71.9 +/- 18.3/mm3) had renal impairment, and four had neurological dysfunction. In one-half the cases, the disease was progressive with isolated fragmentation anemia appearing several months before the clinical symptoms. The diagnosis of TMA was confirmed by histological examination of kidney biopsy specimens (18 cases). Endothelial cytomegalovirus (CMV) inclusions were associated with TMA in nine of 18 cases, whereas histological examination did not detect CMV in any control specimens (P < .001). The case-control study demonstrated a link between TMA and clinical CMV infection (odds ratio, 3.9; 95% confidence interval, 1.1-14). We conclude that TMA is a late complication of HIV infection and can be associated with systemic CMV infection in this setting.

[Sclerosing peritonitis. A series of 10 cases and review of the literature]. / Péritonite encapsulante. Une série de 10 observations et revue de la littérature.

OBJECTIVE AND METHODS: The aim of this study was to describe the main features of sclerosing peritonitis, using a retrospective study in 10 patients. RESULTS: The main causes of sclerosing peritonitis were continual ambulatory peritoneal dialysis (n = 3), peritoneal chemotherapy (n = 2) and liver cirrhosis (n = 2). Sclerosing peritonitis was revealed by acute or chronic bowel obstruction (n = 8). Small bowel X-rays and abdominal tomodensitometry showed a small bowel dilatation with a normal mucosa (n = 7), ascites (n = 5) as well as agglutination and fixation of small bowel loops within a cocoon (n = 3). Surgical viscerolysis was performed in 9 patients and allowed prolonged clinical remission in 4; 3 patients died postoperatively (1 had a cirrhosis and 2 were treated with continuous ambulatory peritoneal dialysis), 1 patient had a complicated postoperative course with recurrent enterocutaneous fistulae. CONCLUSION: Sclerosing peritonitis may be suspected in a patient who presents a combination of bowel obstruction, small bowel dilatation without mucosal disease and ascites. Surgical viscerolysis is a dangerous operation associated with high mortality in patients with renal failure or cirrhosis.

Principal cell-specific antigen and hormonal regulatory network in RC.SVtsA58 cell line.

We used a dual immunomorphological and physiological approach to demonstrate that the RC.SVtsA58 rabbit cortical cell line exhibits features of highly differentiated cortical collecting tubule (CCT) principal cells (PC). First, we raised monoclonal antibodies against RC.SVtsA58 cells and screened their reactivity with the rabbit kidney: three were specific for the basolateral domain of CCT PC and bound to 100% of RC.SVtsA58 cells. Second, we showed that bradykinin, atrial natriuretic peptide, and prostaglandin E2 increased intracellular Ca2+, guanosine 3',5'-cyclic monophosphate, and adenosine 3',5'-cyclic monophosphate (cAMP), respectively. In addition, 10 nM bradykinin inhibited desmopressin-elicited cAMP production by > or = 40%; this effect was suppressed by 10 microM of indomethacin and was reproduced with 1 nM of prostaglandin E2, indicating the conservation of arginine vasopressin-related regulatory loops described in microdissected CCT and freshly isolated cells. However, RC.SVtsA58 cells also express intercalated cell markers even after repeated cloning, which suggests that tsA58, a temperature-sensitive strain of simian virus-40, has transformed a multipotent type of PC in keeping with the cell interconversion hypothesis.

Dramatic changes of sulfated proteoglycans composition in a tumorigenic SV-40-transformed renal proximal-tubule cell line.

To characterize the sulfated proteoglycans (PGs) alterations associated with malignant transformation of epithelial cells in vitro, the localization, charge, size, and composition of cell-associated and secreted sulfated PGs have been compared in rabbit renal proximal-tubule cells in primary culture (Ronco et al., 1990) and in a derived SV-40 transformed cell line (RC.SV1) exhibiting a proximal phenotype and high tumor-inducing ability (Vandewalle et al., 1989). Both normal and transformed cells incorporated PGs into a thick basement membrane layer as shown by ruthenium red staining and immunodetection with a monoclonal antibody raised against the core protein of the bovine basement membrane heparan sulfate-PG (HS-PG). In primary cultures of normal cells, cell-associated PGs were almost identical to those extracted from renal tubule fractions in vivo by their size (Kav = 0.27 vs. 0.26 on Sepharose CL-6B) and composition characterized by the exclusive presence of heparan sulfate glycosaminoglycan (HS-GAG) chains. In addition, the cells secreted a HS-PG with similar biochemical characteristics (Kav = 0.29; 100% HS-GAG chains). The SV-40-transformed RC.SV1 cells also synthesized and secreted a unique PG with the same charge and Kav values and apparently the same core protein (35 kDa) as in nontransformed cells, but three major differences were observed: (i) an increased proportion of PG-associated [35S]sulfate radioactivity released into the culture medium (36 vs. 21%), (ii) the emergence of free GAG chains unincorporated into PGs and detected only in the cell-associated fraction, and (iii) a dramatic change in the composition of GAG chains in which chondroitin sulfate replaced heparan-sulfate. The latter finding is in keeping with the known chondroitin sulfate increase and heparan-sulfate decrease in epithelial tumors. The alterations of PGs observed in this study may play a role in the acquisition and/or maintenance of the malignant phenotype.

Coexpression in humans by kidney and fetal envelopes of a 280 kDa-coated pit-restricted protein. Similarity with the murine target of teratogenic antibodies.

Experimental studies performed in the rat over the last three decades have shown that antibodies raised against kidney or yolk sac, which, in the rat, surrounds the embryo and serves as a placenta during the major part of pregnancy, induced fetal resorptions or malformations. It is generally considered that the teratogenic antibodies decrease internalization and degradation of maternal proteins by yolk sac epithelial cells leading to an inadequate supply of nutriments to the embryo. These observations demonstrating the pathogenic role of antibodies to fetal envelopes are of great potential interest in clinical pathology since most cases of fetal malformations in humans are of unknown cause. The authors have recently shown that the key teratogenic antibodies in the murine system were directed against a 280 kDa-coated pit protein (gp280) specific for the brush border of epithelial cells lining the renal proximal tubule and the yolk sac. This observation allows for the unique opportunity to search for a similar system in humans. In this study, the presence in humans of a protein closely related to murine gp280 is shown, as indicated by extensive immunologic crossreactivity, close apparent molecular weights, strong homology of bidimensional peptide maps, and restricted distribution at the organ and subcellular level. In addition to kidney and yolk sac, human gp280 was also detected within the coated pits of the placental syncytiotrophoblastic cells. When introduced in an in vitro rat embryo culture system, antibodies to human gp280-induced developmental anomalies in a dose-dependent manner. These observations indicate that the antigenic component of the murine model is present in humans and can give rise to heterologous antibodies that cause developmental anomalies, suggesting that the experimental model might be of significance in human pathology.

Detection and typing of human papillomaviruses in cervical smears by an original application of the polymerase chain reaction.

The detection and typing of human papillomaviruses on cervical smears were performed by means of a new application of the polymerase chain reaction allowing easier and faster detection of the amplification product. This application consisted of a combination of two series of amplifications and the use of primers labelled with biotin and with 125 iodine on a reporter group for the second amplification. The final amplification product was detected by counting the radioactivity after incubation of the media in avidin-coated tubes. This test was compared with conventional methods of detection by electrophoresis and Southern blot and its specificity was confirmed. The study of a series of 52 patients demonstrated a higher prevalence of type 16 in relation to type 6/11 and 18 and a correlation between the degree of dysplasia and the frequency of oncogenic types 16 and 18. This new application could facilitate studies of the prevalence of HPV in large series of cervical smears.

Histological and urinary reactivity of monoclonal antibody 1BE12 in bladder carcinoma. Purification of the antigen from urine.

We have previously reported the production of monoclonal antibody (MAb) 1BE12, which recognizes a glycoprotein in breast-cancer cells. In the present work, 1BE12 reactivity was tested by immunohistochemistry in bladder carcinoma (92 cases) and in non-tumoral bladder samples (15 cases). In 71% of bladder tumors, more than 30% of cells were intensely stained by 1BE12. The percentage of reactive cells was higher in cancers invading the muscle than in more superficial tumors (p = 0.039). In non-tumoral bladder, immuno-staining, when present, was usually confined to the superficial layers with a low number of cells stained (less than 30%) in 13/15 cases. Slot blots, performed on urine samples from 43 bladder-cancer patients and 21 healthy controls, were quantified by densitometry scanning. We found higher optical density (OD) values in urine from muscle-invasive-cancer patients than in urine from more superficial tumors and healthy controls, with a significantly different distribution (p = 0.005). The urinary antigen was detected by immunoblotting with 1BE12 as high-molecular-weight species (greater than 150 kDa). The reactive glycoprotein could thus be purified by immunoaffinity and FPLC filtration from the perchloric-acid-soluble fraction of urine from patients with invasive bladder carcinoma. The availability of purified antigen will allow us to quantitate our assay, in order to evaluate its potential use as a prognostic indicator in bladder-cancer patients.

Polarized membrane expression of brush-border hydrolases in primary cultures of kidney proximal tubular cells depends on cell differentiation and is induced by dexamethasone.

To analyze the influence of cell differentiation and the effects of hormones on the subcellular distribution of apical antigens in polarized epithelial cells, we have compared the localization of three brush border (BB) hydrolases [neutral endopeptidase (ENDO), aminopeptidase N (APN), and dipeptidylpeptidase IV (DPPIV)] in primary cultures of renal proximal tubule cells grown in various culture media. The degree of cell differentiation modulated by medium composition was estimated by measuring proximal functions, including glucose transport, specific enzymatic activities, and PTH responsiveness. In the dedifferentiated state observed in cells grown in 1% fetal calf serum (FCS)-supplemented medium, the three hydrolases are abnormally concentrated in a cytoplasmic vesicle compartment with weak expression on both membrane domains. By contrast, in serum-free hormonally defined medium (DM: insulin, 5 microgram/ml; dexamethasone, 5 x 10(-8) M), which markedly enhances morphological and functional cell differentiation, the distribution of hydrolases parallels that observed in the normal tubule. When added to the DM devoid of hormones, insulin has little polarizing effect, whereas dexamethasone dramatically increases the apical expression of the hydrolases, which then almost disappear from the basolateral membrane and cytoplasmic vesicular compartments. This glucocorticoid hormone augments the amount of immunoreactive antigen detectable on the apical domain in paraformaldehyde-fixed cells but does not change the total enzymatic activity. This suggests the presence in tubular cells of a dexamethasone-dependent polarizing machinery that requires de novo RNA and protein synthesis, and probably acts mainly by targeting a storage cytoplasmic pool of enzyme to the apical domain.

Maintenance of proximal and distal cell functions in SV40-transformed tubular cell lines derived from rabbit kidney cortex.

This paper reports the preparation and describes the properties of three renal tubular cell lines derived using SV40 infection of primary cultures of rabbit kidney cortical cells, enriched in proximal cells. RC.SV1 was initially derived from cultures grown in the presence of fetal calf serum exhibiting a low degree of proximal differentiation. The cells were subsequently adapted to grow in serum-free hormonally defined medium and display basic properties of proximal tubule cells including well-developed apical microvilli, strong expression of brush-border hydrolases, Na+-coupled glucose uptake, and increased cyclic AMP production when exposed to PTH. The other two cell lines were derived from cultures in serum-free hormonally defined medium and propagated in the same medium. They are characterized by some common properties including rare and short microvilli, low expression of apical hydrolases, and low or undetectable Na+-dependent glucose uptake, but differ by their abilities to respond by an increase in cAMP to various hormonal stimuli. RC.SV2 cells are sensitive to calcitonin and to a lesser extent to isoproterenol and PTH, suggesting that they may originate from the thick ascending limb of Henle's loop and the bright portion of the distal tubule. RC.SV3 responds essentially to isoproterenol and arginine vasopressin, suggesting a more distal origin (late distal and initial collecting tubule). Emergence of distal cell lines from cultures exhibiting proximal characteristics may be related to distal cell overgrowth as suggested by analysis of growth kinetics and increased Na+/H+ exchanger activity in RC.SV2 compared with RC.SV1.