Bone decay and beyond: how can we approach it better.

Osseo-degeneration is a disorder related to several factors, that may lead to the disruption of several skeletal regions providing support, such as the femur head, the vertebrae and the alveolar bone. The functional condition can be restored by means of grafting procedures, using different materials: calcium powder, xenografts, ceramics and metals. Such procedures aim at reforming an adequate bone volume and strength, that is necessary to support loading forces. Bone regeneration requires that the basic biological principles of osteogenesis, osteoinduction, osteoconduction and biocompatibility are followed. The success of regenerative procedures may depend on the inner structural, mechanical and metabolic condition of the host's bone on which implants should be inserted, on the surgical technique, and on the biomaterial used. Among these, the aging process of the patient appears to be relevant. It can be associated with metabolic disease leading to systemic functional decay, which involves a gradual steady decline of hormonal, immune function and osteo-metabolic activity. The latter can affect the positive outcomes of bone reconstruction and implant therapy. This review will analyze the biological and physiological factors involved in the bone tissue break-down, such as the influences from gut microbiome unbalance and the consequent metabolic, endocrine, immune dysfunctions, the surgery procedures and the quality of the grafting material used. The decline of bone architecture and strength should be corrected by using an appropriate clinical regenerative approach, based on a bio-endocrine, metabolic and immunologic know-how. The final characteristics of the regenerated bone must be able to support the loading forces transmitted by the implants, independent of the body location, and should be individualized according to the different condition of each patient.

A newly discovered muscle: The tensor of the vastus intermedius.

The quadriceps femoris is traditionally described as a muscle group composed of the rectus femoris and the three vasti. However, clinical experience and investigations of anatomical specimens are not consistent with the textbook description. We have found a second tensor-like muscle between the vastus lateralis (VL) and the vastus intermedius (VI), hereafter named the tensor VI (TVI). The aim of this study was to clarify whether this intervening muscle was a variation of the VL or the VI, or a separate head of the extensor apparatus. Twenty-six cadaveric lower limbs were investigated. The architecture of the quadriceps femoris was examined with special attention to innervation and vascularization patterns. All muscle components were traced from origin to insertion and their affiliations were determined. A TVI was found in all dissections. It was supplied by independent muscular and vascular branches of the femoral nerve and lateral circumflex femoral artery. Further distally, the TVI combined with an aponeurosis merging separately into the quadriceps tendon and inserting on the medial aspect of the patella. Four morphological types of TVI were distinguished: Independent-type (11/26), VI-type (6/26), VL-type (5/26), and Common-type (4/26). This study demonstrated that the quadriceps femoris is architecturally different from previous descriptions: there is an additional muscle belly between the VI and VL, which cannot be clearly assigned to the former or the latter. Distal exposure shows that this muscle belly becomes its own aponeurosis, which continues distally as part of the quadriceps tendon.

Human skin Langerhans cells are targets of dengue virus infection.

Dengue virus (DV), an arthropod-borne flavivirus, causes a febrile illness for which there is no antiviral treatment and no vaccine. Macrophages are important in dengue pathogenesis; however, the initial target cell for DV infection remains unknown. As DV is introduced into human skin by mosquitoes of the genus Aedes, we undertook experiments to determine whether human dendritic cells (DCs) were permissive for the growth of DV. Initial experiments demonstrated that blood-derived DCs were 10-fold more permissive for DV infection than were monocytes or macrophages. We confirmed this with human skin DCs (Langerhans cells and dermal/interstitial DCs). Using cadaveric human skin explants, we exposed skin DCs to DV ex vivo. Of the human leukocyte antigen DR-positive DCs that migrated from the skin, emigrants from both dermis and epidermis, 60-80% expressed DV antigens. These observations were supported by histologic findings from the skin rash of a human subject who received an attenuated tetravalent dengue vaccine. Immunohistochemistry of the skin showed CD1a-positive DCs double-labeled with an antibody against DV envelope glycoprotein. These data demonstrate that human skin DCs are permissive for DV infection, and provide a potential mechanism for the transmission of DV into human skin.

The enigmatic plasmacytoid T cells develop into dendritic cells with interleukin (IL)-3 and CD40-ligand.

A subset of CD4+CD11c-CD3- blood cells was recently shown to develop into dendritic cells when cultured with monocyte conditioned medium. Here, we demonstrate that CD4+ CD11c-CD3- cells, isolated from tonsils, correspond to the so-called plasmacytoid T cells, an obscure cell type that has long been observed by pathologists within secondary lymphoid tissues. They express CD45RA, but not markers specific for known lymphoid- or myeloid-derived cell types. They undergo rapid apoptosis in culture, unless rescued by IL-3. Further addition of CD40-ligand results in their differentiation into dendritic cells that express low levels of myeloid antigens CD13 and CD33.

Apoptosis induction and reduced proliferation in human osteoblasts by rhBMP-2, -4 and -7.

BACKGROUND: The role of bone morphogenetic proteins (BMPs) in bone healing has been demonstrated in numerous in vivo animal models. BMP-2, -4 and -7 have also been shown to stimulate the differentiation of human and animal stem cells into osteoblasts in vitro. There are, however, contradictory reports of BMPs causing apoptosis and inhibition of proliferation of osteoblastic cells. Therefore, a more complete understanding of the effects of BMP-2, -4 and -7 on human osteoblasts is required. METHODS: Cells of the immortalised human fetal osteoblastic line hFOB 1.19 were exposed to recombinant human (rh) BMP-2, -4 and -7. In addition, primary human osteoblasts were exposed to rhBMP-7. Cell proliferation was measured using a colorimetric assay. Apoptotic cells were detected using the TUNEL assay. RESULTS: The hFOB cells exposed in a dose-dependent manner to rhBMP-2, -4 and -7 had significantly lower rates of proliferation than non-treated cells, (p<0.01 for rhBMP-2, -4 and -7). The proliferation results for rhBMP-7 were replicated using primary human osteoblasts. Additionally, rhBMP-2, -4 and -7 induced a significantly higher rate of apoptosis in the hFOB cells, with a temporal and dose-dependent pattern (p<0.05), irrespective of the presence of serum growth factors. CONCLUSIONS: Despite interest in the potential clinical application of BMPs to improve bone healing, further studies are necessary to determine their full biological function before they can be used confidently in humans.

Human dermal dendritic cells process and present soluble protein antigens.

Recently, a novel type of dendritic antigen-presenting cell has been identified in the dermis of normal human and mouse skin. These dermal dendritic cells (DDC) occur in higher numbers than epidermal Langerhans cells, represent a distinct differentiation pathway of dendritic cells, and are as potent as Langerhans cells in the activation of superantigen specific T cells. As yet, nothing is known about their capacity to take up, process, and present soluble protein antigens. We used the model of tetanus toxoid (TT) driven T cell proliferation to address these questions. To test for active internalization of TT protein, gold labeled TT was incubated with Langerhans cells and DDC and could be traced to multivesicular endo-lysosomal compartments. DDC internalize TT through a receptor-mediated, clathrin-independent pathway, whereas Langerhans cells predominantly use macropinocytosis. To verify that DDC process TT by the exogenous pathway of antigen presentation, we pulsed DDC with TT protein or TT peptide after preincubation with chloroquine. Preincubation with chloroquine diminished the capacity of DDC to induce TT protein specific T cell proliferation (70-80%), but was not effective to suppress TT peptide induced T cell responses. DDC were as potent as Langerhans cells and 5-10 x more potent than plastic adherent monocytes in the presentation of TT to autologous resting T cells. Furthermore, as few as 50 DDC (stimulator:responder ratio of 1:1000) were able to induce a significant TT specific T cell proliferation. Because a subpopulation of DDC expresses low levels of CD1a, a phenotypic marker of Langerhans cells, sorting of CD1a positive and negative DDC was performed. On a per cell basis, CD1a positive and negative DDC were equally potent at mediating TT specific T cell proliferation. Thus, DDC are able to internalize, process, and present soluble protein antigens such as TT and may therefore play an important role in the regulation of skin immune responses.

Flow cytometric assessment of the reactivity of a panel of monoclonal antibodies (mAb) against two populations of human dendritic cells (DC).

BACKGROUND: The identification of antigens on human DC has been a very difficult and elusive task because of the lack of appropriate reagents. Therefore, we evaluated by flow cytometry a panel of mAb that recognize antigens on human DC, aiming to determine the kinetics of DC antigen expression at 7, 14, 21 and 28 days in (i) Dermal DC like cells (Mo-DC) and (ii) Langerhans cell like DC (Mo-LC). In addition we aimed to identify markers for DC subpopulations. RESULTS: It was found at day 7, that mAb BG6, HP-F1, BU10, RFD-1, CMRF-44 recognized <20% of Mo-DC. In contrast, 7H5, ZM3.8, CDlb/c, 55K-2, MMR1.16, MMR190.BB3 and L25 reacted with >50% of Mo-DC. Moreover, 7H5, ZM3.8, CMRF-56, CDlb/c, 55K-2, MMR1.16, MMR190.BB3 and L25 showed increased MFI reactivity against Mo-DC. mAb BG6, BU10 and CMRF-44 recognized <20% Mo-LC while RFD-1 reacted with 21% of Mo-LC. In contrast, HP-F1 showed 87% of Mo-LC positive. Also, 7H5, ZM3.8, RFD-7, MR15-2, CDlb/c, 55K-2, MMR1.16, MMR190.BB3 and L25 reacted with >50% of Mo-LC. The increase in % of positive cells was paralleled by MFI increases. At day 14, fourteen mAb recognized >50% of the Mo-DC, while five recognized 20-50% of Mo-DC. BG6 reacted with 7% of the Mo-DC. Nineteen mAb recognized >48% of Mo-LC while BG6 had negative reactivity. At day 21 and 28, all mAb reacted with >20% of Mo-DC and yielded a significant MFI with Mo-DC. Also nineteen mAb yielded significant MFI with Mo-LC while RFD-7 did not. CONCLUSIONS: The immunophenotyping assays demonstrated differences between the two DC populations as well as variations in the reactivity of the mAb at diverse time points, suggesting the existence of subpopulations within the Mo-DC and Mo-LC.

Carcinoembryonic antigen (CEA) presentation and specific T cell-priming by human dendritic cells transfected with CEA-mRNA.

The feasibility of dendritic cells (DC) for cancer immunotherapy after transfection by electroporation with mRNA encoding the human carcinoembryonic antigen (CEA) was investigated. Both, total RNA from the CEA(+) colon cancer cell line SW480 and mRNA transcribed in vitro from cDNA3.1-plasmids (pcDNA3.1+/-HisC) with a CEA-insert (ivt-CEA-mRNA, ivt-CEA/HisC-mRNA) were used. Labelled ivt-CEA-mRNA was detectable in DC by light and electron microscopy and by fluorescence-activated cell-sorting (FACS) even 15 min after electroporation. Four hours after transfection with ivt-CEA/HisC-mRNA, we detected specific expression of CEA and the histidine-tag by immunofluorescence microscopy and by FACS. CEA-specific T lymphocytes were successfully primed by transfected DC and were able to lyse CEA-expressing target cells, even from the CEA-expressing human colon adenocarcinoma cell line SW480. Thus, DC transfected by electroporation with CEA-mRNA are valuable tools for the immunotherapy of CEA(+) tumour entities.

Effects of different culture protocols on the expression of discrete T-cell receptor variable regions in human tumour infiltrating lymphocytes.

Therapeutic effects of tumour infiltrating lymphocytes (TIL) rely on T-cell receptor (TCR) engagement. In this work, the expression of five TCR alpha/beta variable (V) domains was quantitatively analysed by means of a panel of monoclonal antibodies (Mab) recognising gene products from TCR V alpha 2, V beta 5, V beta 6, V beta 8 and V beta 12 families in freshly isolated TIL and in autologous peripheral blood mononuclear cells (PBMC) from patients with neoplasms. In 3 out of 6 cases, differences in the expression of V beta 5, V beta 6, V beta 8 or V beta 12 could be detected. TIL populations were expanded by using recombinant human interleukin-2 (rhIL-2) alone or in addition to solid phase bound anti-CD3 Mab. Cultured TIL showed similar CD4/CD8 ratios and cytotoxic activity against autologous neoplastic target cells, regardless of the activation protocol. In 4 patients, the expression of TCR alpha/beta V gene products, as compared with TIL from freshly excised tumours, was found to be modified in cultured TIL, especially in cell populations activated with rhIL-2 only. These results indicate that TCR V gene usage in TIL may quantitatively differ from that in PBMC. TIL culture protocols using rhIL-2 alone or in combination with solid phase bound anti-CD3 may result in differential expression of discrete TCR V families.

Cytokine gene expression in primary brain tumours, metastases and meningiomas suggests specific transcription patterns.

To obtain an insight into the network of cytokine gene transcription in the brain tumour microenvironment, we investigated the expression of genes encoding for interleukin (IL)-1 alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-10, interferon (IFN)-gamma, granulocyte-macrophage colony-stimulating factor, tumour necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta 1, -beta 2 and -beta 3 in freshly excised brain tumour samples and autologous peripheral blood mononuclear cells. Tissue specimens from 15 primary brain tumours, three brain metastases, five meningiomas, autologous peripheral blood mononuclear cells (PBMC) and three brain tumour cell lines were tested by reverse polymerase chain reaction. Despite the presence of T-lymphocytes, cytokine gene transcripts typically detectable upon T cell receptor triggering could not be observed in central nervous system tumours of diverse histology. In primary brain neoplasms, transcription of genes encoding for the inhibitory cytokines TGF-beta and IL-10 was detectable in more than 50% of samples. IL-6 transcripts could only be detected in malignant gliomas. In brain metastases, virtually no cytokine gene transcripts could be observed. Surprisingly, TGF-beta transcripts were also detected in all meningiomas. Thus, transcription of genes encoding for inhibitory factors appears to prevail in primary brain neoplasms.

Characterisation of two human dendritic cell-lines that express CD1a, take-up, process and present soluble antigens and induce MLR.

Dendritic cells (DC) are bone marrow derived cells present in diverse tissues and organs including the skin, mucosae and blood. DC have a capital role in the afferent pathway of the immune response because of its role in up-take, processing and presenting antigens to immune cells. Human DC are usually identified by the expression of surface CD1a and HLA-DR. Despite the significant recent developments for in vitro generation of DC derived from blood by using cytokines like GM-CSF and IL-4, the studies on DC and specially on human Langerhans cells (LC) have been hampered by the laborious isolation procedure and the small yield of cells obtained by the various methods of isolation used so far. Therefore, a priority has been a search for monoclonal dendritic cell-lines with LC characteristics in order to facilitate the research in this area. The present study reports on the generation of two stable, self-replicant, adherent, dendritic, CD1a+, HLA-DR , CD45RO , CD23/FcERII+ cell-lines that up-take and process soluble antigens but also inducing MLR and antigen-dependent T-cell response.

T-cell receptor V-gene usage in neoplasms of the central nervous system. A comparative analysis in cultured tumor infiltrating and peripheral blood T cells.

The use of tumor-infiltrating lymphocytes in the treatment of central nervous system (CNS) neoplasms has met with serious obstacles due to difficulty of culture and poor characterization. Since in other tumors the therapeutic effects of tumor-infiltrating lymphocytes have been shown to rely on T-cell receptor engagement, the authors addressed the question as to whether expression of T-cell receptor variable (V) domains in cultured tumor-infiltrating lymphocytes from CNS is different from that of autologous cultured peripheral blood mononuclear cells. Infiltrating lymphocytes from CNS neoplasms, including primary malignancies, metastatic cancers, and meningiomas, were cultured in the presence of interleukin-2 and anti-CD3 monoclonal antibodies (MoAb's) in order to obtain optimum growth of T cells. Autologous peripheral blood mononuclear cells from the same patients were similarly cultured. After 4 to 5 weeks of culture, 97.3% +/- 2.6% (mean +/- standard deviation) of the resulting cell populations were CD3-positive lymphocytes. The expression of T-cell receptor V domains was then studied by using a panel of 12 MoAb recognizing gene products from T-cell receptor V-alpha 2, V-beta 5, 6, 8, and 12, V-gamma 4 and 9 families, and from two subfamilies of V-delta 2. Remarkably, in over 70% of all paired measurements, percentages of T cells expressing discrete T-cell receptor V-gene products were found to be virtually identical in tumor- and peripheral blood-derived cultured cell populations, with differences never exceeding 1%. In contrast, a different expression of individual V-gene products, concerning both alpha/beta and gamma/delta T-cell receptors, could be detected between cultured tumor-infiltrating lymphocytes and autologous peripheral blood-derived T lymphocytes in seven of 12 patients. In two cases, significant differences between the two populations were also observed in the proliferative responses obtained upon stimulation with staphylococcal enterotoxins that trigger defined V-beta T-cell receptors. Altogether, these data suggest that the T-cell receptor repertoire of cultured tumor-infiltrating lymphocytes from CNS tumors, suitable for use in adoptive immunotherapies, differs from that of autologous cultured peripheral blood mononuclear cells.

Intralipid-based short-term total parenteral nutrition does not impair small intestinal mucosa-related cellular immune reactivity in the healthy rat.

BACKGROUND: The lipid component of total parenteral nutrition (TPN) has reportedly been associated with trophic effects on the intestinal mucosa and suppressive effects on the immune system. METHODS: We have challenged these hypotheses using a 7-day TPN rodent model comparing the effects of isocaloric, isonitrogenous lipid-based (TPN-lipid, 50% of calories as long-chain triacylglycerol) and carbohydrate-based TPN (TPN-CH, 100% of calories as carbohydrates) on mucosal morphology and immune function. Enterally fed animals were included to establish a baseline for immunologic read-outs. The study was performed in healthy, metabolically stable animals to avoid interference by septic or trauma-related stress factors. RESULTS: Both TPN regimens resulted in a significantly smaller weight gain (TPN-lipid, 29.8 +/- 4.0 g; TPN-CH, 30.3 +/- 4.4 g) compared with enterally fed reference animals (49.2 +/- 3.2 g; p = .007), with no difference in nitrogen balance between the TPN groups. Mucosal sucrase activity was significantly lower in both TPN groups (TPN-lipid, 8.8 +/- 1.0 x 10(-7) katal per gram (kat/g) of protein; CH: 11.9 +/- 1.6 x 10(-7) kat/g of protein) compared with enteral feeding (17.4 +/- 0.9 x 10(-7) kat/g of protein; ANOVA: p = .0007). Morphometric analysis of the small intestine revealed no differences between the two TPN groups although a significantly depressed villus height in the TPN-lipid group could be observed in comparison to enterally fed reference rats (TPN-lipid, 0.47 +/- 0.02; TPN-CH, 0.50 +/- 0.01; enteral, 0.56 +/- 0.02 mm; ANOVA: p = .0298). Light and electron microscopy revealed a normal surface architecture in all three groups of rats. Cellular immune reactivity was evaluated using a novel specific immunization protocol: animals were immunized against OVA 4 weeks before TPN. OVA-induced lymphoproliferative responses and phenotypic data from draining popliteal and mesenteric lymph nodes were evaluated after the different regimens. Results did not differ among the three groups. CONCLUSIONS: In healthy rodents, short-term lipid-based and carbohydrate-based TPN regimens lead to limited mucosal atrophy with preserved surface architecture compared with enteral feeding. However, peripheral and mesenteric cellular immune responsiveness after both TPN regimens remained comparable to enterally fed reference animals. Therefore, mesenteric and systemic cellular immune reactivity does not appear to be impaired by lipid-based or carbohydrate-based TPN.

Glutamine peptide-supplemented long-term total parenteral nutrition: effects on intracellular and extracellular amino acid patterns, nitrogen economy, and tissue morphology in growing rats.

Glutamine (GLN) is a nonessential amino acid that is not included in current regimens for parenteral nutrition because of its chemical instability. This study tested the hypothesis that GLN supplementation during long-term total parenteral nutrition (TPN) (3 weeks) would enhance GLN availability, thereby improving nitrogen economy and growth in a growing rat model: Standard TPN delivering 300 kcal/kg per day (lipid:carbohydrate = 1.1) including 2.1 g of nitrogen per kilogram per day in an all-in-one solution was compared with an isonitrogenous, isocaloric, and isovolemic TPN regimen with 0.29 g of nitrogen per kilogram per day substituted by GLN derived from the dipeptides glycyl-GLN and alanyl-GLN (TPN GLN). Enterally fed controls were included. Analysis was confined to nonbacteremic animals with negative blood culture, in which extracellular and intracellular amino acid concentrations including GLN, nitrogen balance, serum protein concentrations, growth, and histologic sections of liver and small-bowel mucosa (light and scanning electron microscopy) were evaluated. Hepatic intracellular GLN concentrations were significantly lower, in animals receiving GLN-free TPN (11.7 +/- 1.6 nmol/mg fat-free dry and solid tissue mass, n = 9) compared with both GLN-supplemented TPN (16.0 +/- 3.0, n = 7) and enteral feeding (18.2 +/- 1.8, n = 6) (p < .001). Corresponding results were found for intracellular GLN concentrations in skeletal muscle (TPN standard 12.5 +/- 3.1, TPN GLN 14.7 +/- 3.1, enteral control 17.3 +/- 2.3, p < .05), intestinal mucosa, and spleen as well as for plasma concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

[Surgical indications in acute pseudo-obstruction of the colon (Ogilvie syndrome)]. / Indicaciones quirúrgicas en la pseudoobstrucción aguda de colon (síndrome de Ogilvie).

Acute pseudo-obstruction of the colon (APC), popularly known as Ogilvie's syndrome, has been the subject of numerous medical communications in the past two decades. In this paper three patients with APC managed surgically are presented. In two patients cecal perforation developed; in the third patient a discharge cecostomy was carried out because of a caecal diameter of 16 cm. Indications for the operative management of these patients include pneumoperitoneum, development of peritonitis in the area of the cecum, continued cecal distention after 48-72 hours of therapy with or without colonoscopy, cecal diameter greater than 12 cm, respiratory failure and uncertain diagnosis.

[Importance of surgical staging in patients with cancer of the exocrine pancreas]. / Importancia del estadiaje quirúrgico en pacientes con cáncer de páncreas exocrino.

A retrospective analysis of 64 patients with adenocarcinoma of the exocrine pancreas was carried out to determine the impact of stage of the disease and surgical treatment on survival. Significant differences (p < 0.05) were observed in the survival rates of stage I (36%), stage II (12%), stage III (15%) and stage IV (0%). Patients with pancreatectomy had better prognosis (32%) than those with palliative procedures (11%) (p < 0.025). The presence of positive lymph nodes in patients with tumor resection didn't show significant differences on survival. Survivors showed a short prodome of symptoms (< 3 weeks) and a resected neoplasm (p < 0.025).

[Villous adenoma of the appendix caused acute appendicitis]. / Adenoma velloso de apéndice causante de apendicitis aguda.

Villous adenoma of the appendix is a rare pathologic entity, the treatment is controversial. We describe the case of a patient complaining of abdominal pain that was diagnosed as acute appendicitis. Pathological examination of the surgical specimen revealed a villous adenoma of the appendix. We comment the therapeutic options and we review the literature about this pathological entity.

[Emphysematous cholecystitis. Diagnosis, clinical course, and treatment]. / Colecistitis enfisematosa. Diagnóstico, evolución y tratamiento.

Emphysematous cholecystitis is the most severe acute cholecystitis with infection by gas-producing organism. The morbidity and mortality rate are 15%. We present a retrospective study of emphysematous cholecystitis seen in our department during three years (1992-1994). Inclusion criteria were made on the basis of a characteristic history, physical examination and radiology findings. Eight patients were studied. All were men, medium age 75 years (range: 45-88). None of them was diabetic. Clinical history was typical for the disease. Radiological examinations included abdominal X-ray (none of them was demonstrative), abdominal ultrasound (carry out in five patients and diagnosis in two) and computerised tomography scanning was necessary in the others three patients. Surgery was required since complication occurred in two patients. The mean duration until surgery was 5.21 day. Only three patients had any postoperative complication and nobody death. We concluded that the treatment of choice is cholecystectomia, except for high risk patient in whom puncheon and drainage is required.

[Heterotopic gastric mucosa in the ileum with perforated ulcer]. / Mucosa gástrica heterotópica de íleon con úlcera perforada.

Heterotopic gastric mucosa (HGM) in the small bowel, other than in the Meckel's diverticulum or other congenitally anomalous bowel, is exceedingly rare. A patient with HGM of the small intestine with perforation of the ileum due to ulceration of the adjacent mucosa is presented. The authors remark the importance of the histological criteria to differentiate between true HGM from metaplastic changes, two entities with different behavior and prognostic implications.

[Carcinoma in situ of the gallbladder. The prognostic and therapeutic implications]. / Carcinoma in situ de vesícula biliar. Implicaciones pronósticas y terapéuticas.

We have studied samples from gallbladders of five patients with carcinoma in situ over a 6-year period. Two were men and three women with du age ranging between 38 and 68 years (mean age 56). The microscopic criteria employed for the diagnosis of carcinoma in situ were pseudostratification of the epithelium, nuclear crowding, loss of cell polarity, atypical mitotic divisions and absence of stromal invasion. Cholecystectomy was carried in all patients due to cholelithiasis. Signs and symptoms were those related to the presence of stones and none of the patients was the presence of carcinoma suspected clinically. All patients are alive and symptom-free 14-84 months after surgery. Authors concluded that patients with carcinoma in situ of the gallbladder usually follows a good course after cholecystectomy.