Celecoxib: Antiangiogenic and Antitumoral Action / Celecoxib: Acción Antiangiogénica y Antitumoral

SUMMARY: Angiogenesis, a process by which new blood vessels are generated from pre-existing ones, is significantly compromised in tumor development, given that due to the nutritional need of tumor cells, pro-angiogenic signals will be generated to promote this process and thus receive the oxygen and nutrients necessary for its development, in addition to being a key escape route for tumor spread. Although there is currently an increase in the number of studies of various anti-angiogenic therapies that help reduce tumor progression, it is necessary to conduct a review of existing studies of therapeutic alternatives to demonstrate their importance.

La angiogénesis, proceso por el cual se generan nuevos vasos sanguíneos a partir de otros preexistentes, se encuentra comprometida de forma importante en el desarrollo tumoral, dado que por necesidad nutritiva de las células tumorales se generarán señales pro angiogénicas para promover este proceso y así recibir el oxígeno y los nutrientes necesarios para su desarrollo, además de ser una ruta de escape clave para la diseminación tumoral. Si bien, actualmente existe un aumento en la cantidad de estudios de diversas terapias anti angiogénicas que ayudan a reducir el avance tumoral, es necesario realizar una revisión de los estudios existentes de alternativas terapéuticas para demostrar su importancia.

Juxtaoral organ: an anatomical finding to be considered.

The juxtaoral organ (JOO) is a vestigial anatomical structure which is not usuallydescribed in lectures and classic texts of general histology and oral histology, despiteit being included in the "Terminologia Histologica: International terms for humancytology and histology". Although there is evidence about its histological structure,there are no macroscopic anatomical reports about it. We report the finding ofa structure of glandular macroscopic appearance in a horizontal section of a plastinatedhuman head belonging to the Morphology Laboratory of the Department ofBiomedical Basic Sciences at the University of Talca. Due to its location, dimensionsand anatomical relations, we determined it to be the JOO. Using a digital calliper, wemeasured the anteroposterior and transverse dimensions of the JOO and observedits anatomical relationships with neighbouring structures of clinical relevance. Weconclude that the JOO is relevant to surgical practice due to its anatomical relationswith relevant structures such as inferior third molar and lingual nerve. Its clinicalapplication lies in the differential diagnosis with invasive processes of malignantneoplasia originating in the oral cavity.

Bacteriophage performance against Staphylococcus aureus in milk is improved by high hydrostatic pressure treatments.

The combined effect of bacteriophages, vB_SauS-phi-IPLA35 (phiIPLA35) and vB_SauS-phi-IPLA88 (phiIPLA88), and high hydrostatic pressure (HHP) on Staphylococcus aureus Sa9 was evaluated in pasteurized whole milk under a simulated cold chain break, which was simulated by incubation of milk at 25°C for 48 h. Four-hundred MPa was found to be the most suitable pressure to be used in combination with these phages. Two different levels of staphylococcal initial contamination (1×10(4) and 1×10(6) CFU/mL) were tested. A synergistic effect between HHP and phages was observed in both cases. Compared to each single treatment, the combined treatment was able to reduce the initial S. aureus contamination below the detection limit (<10 CFU/mL). Bacteriophage performance in pressurize milk against S. aureus enabled milder hydrostatic pressure treatments, therefore phages can be regarded as a valuable hurdle on minimally processed food.

Empleo de coagulantes vegetales en leche de cabra murciano-granadina / Use of vegetable coagulants in Murciano-Granadina goat milk

El uso de coagulantes alternativos en la fabricación del queso favorece la obtención de productos con diferentes características a los que habitualmente encontramos en el mercado. Los coagulantes vegetales más utilizados en la actualidad son los derivados de Cynara Cardunculus, ya que permiten la elaboración de variedades de quesos con características organolépticas diferentes, que son ampliamente aceptadas por consumidores. En este trabajo se ha comparado la actividad coagulante de dos extractos vegetales de la flor de cardo (cardo silvestre: Cynara cardunculus subsp. flavescens y cardo cultivado: Cynara cardunculus subsp. cardunculus) comparándolos con coagulantes de origen animal y microbiano en leche de cabra Murciano-Granadina. Para ello se han utilizado dos métodos que definen el tiempo de coagulación: determinación visual de la aparición de los primeros flóculos (Método de Berridge) y la aplicación de sensores ópticos (CoAguLabTM). No se observan diferencias significativas en el perfil de reflectancia difusa, obtenido por el sensor CoAguLabTM entre los coagulantes vegetales y microbianos, pero si entre estos y los de origen animal con un 80% de quimosina. Los resultados obtenidos demuestran la existencia de una correlación lineal entre ambos métodos, por lo que el sensor óptico podría ser una alternativa al método de Berridge(AU)

The uses of alternative coagulants in cheese manufacture increase the products variability usually found in the market. Most of the vegetable coagulants used today are derived from Cynara cardunculus which allow the development of cheeses with different sensory characteristics. In this study, the clotting activity of two vegetable coagulants (wild cardoon: Cynara cardunculus subsp. flavescens and cultivated cardoon: Cynara cardunculus subsp. cardunculus) was compared with animal rennet and microbial coagulant in Murciano-Granadina goat milk. Two different procedures have been applied: Berridge method and optic sensor (CoAguLabTM). The corresponding means of vegetable, animal and microbial coagulant reflectance profiles obtained by CoAguLabTM were compared and no differences were found between vegetal and microbial coagulants, while differences were found between these and animal rennet (80% chymosin). Monitoring results showed the existence of a linear relationship between both methods, so that the optical sensor could be an alternative for Berridge method(AU)

Patrón de metilación génico en el cáncer de mama / Promoter methylation profile in breast cancer

BACKGROUND: Genomic DNA methylation, mutations and allelic deletions explain the inactivation of genes involved in cell proliferation and cell cycle control mechanisms. AIM: To analyze the methylation pattern of important genes related to different carcinogenic mechanisms in patients with breast cancer and the relationship with its biological behavior. MATERIAL AND METHODS: Seventy fresh-frozen breast cancer samples were selected. The methylation specific PCR (MSP) test was used to analyze promoter methylation status for genes CDKN2A (p16), hMLH1, APC, CDH1 (Cadherin E) and FHIT. RESULTS: We found methylation in at least one of the genes studied in 88% of cases and in 3 or more genes in 40.5% of cases. The frequencies of promoter hypermethylation of CDKN2A, hMLH1, APC, CDH1 and FHT were 41.4%, 11.4%, 52.9%, 70% and 42.9%, respectively. We found a relationship between CDKN2A methylatlon and better survival (p=0.002). CDH1 methylation and poor histological differentiation (p=0.007), hMLH1 methylation and non-Mapuche ethnicity (p=-0.03), APC methylation and larger tumor size (p<0.05), FHIT methylatton and lack of estrogen rectptor IHC expression (p<0.05). CONCLUSIONS: The high frequency of promoter methylation in patients with breast cancer confirms its role in breast carcinogenesis. The finding of alterations in the methylation pattern of genes studied and its association with prognostic factors is a helpful tool in the search of new criteria for clinical and therapeutic decision making.

Carcinoma subseroso de la vesícula biliar: expresión del complejo caderina-catenina / Subserous gallbladder carcinoma: expression of cadherine-catenine complex

BACKGROUND: Subserous gallbladder carcinoma is difficult to diagnose and treat. There are no tissue markers with prognostic value in this type of tumor. AIM: To study the immunohistochemical expression of E-cadherin alpha and beta catenin in subserous gallbladder carcinoma. PATIENTS AND METHODS: One hundred seventeen subjects (103 women and 14 men aged 62 and 69 years as a mean, respectively), were studied. Thirty five gallbladder samples without evidence of cancer were used as controls. Expression of markers was studied with standard immunohistochemical techniques for formalin fixed and paraffin embedded tissue. RESULTS: Ninety seven percent of tumors were adenocarcinoma. A lower or absent expression of E-cadherin, alpha catenin and beta catenin was observed in 26, 33 and 29 per cent, respectively. Actuarial five years survival was 37 per cent. No association between macroscopic features of the tumor and survival was observed. Well differentiated tumors had a 73 per cent survival, whereas less differentiated tumors had a 30 per cent survival. Tumors with a normal expression of the markers had a slightly better survival, although not significant (p = 0.06). CONCLUSIONS: Approximately 30 per cent of subserous gallbladder carcinoma have an abnormal expression of E-cadherin, alpha catenin and beta catenin. This abnormal expression has no relationship with prognosis and is probably secondary to the aberrant genic expression of the tumor.

[Findings in surgical reinterventions for cancer of the gallbladder in patients with and without preoperative chemotherapy and radiotherapy]. / Hallazgos en reintervenciones quirúrgicas por cáncer de la vesícula biliar en pacientes con y sin quimio-radiación preoperatoria.

BACKGROUND: The usefulness of surgery in the treatment of gallbladder cancer has not been clearly established. The benefits of chemo and radiotherapy are similarly dubious. AIM: To report the pathological findings in patients subjected to surgical reinterventions for gallbladder cancer. PATIENTS AND METHODS: We report 54 patients with gallbladder cancer that were subjected to a second surgical intervention for resection of liver segments IVb and V and lymph nodes corresponding to the liver hilar, portal, peripancreatic, celiac artery and periaortic territories. Thirteen of these patients were subjected to preoperative chemo-radiotherapy (4500 Gy and 5-fluouracil 500 mg/m2). RESULTS: Lymph node metastases were found in 25 and 38%, and liver metastases in 25 and 28% of patients with or without chemo-radiotherapy respectively. The most frequent pathological findings attributed to radiation in the liver were fatty infiltration in 75% of cases, vascular transformation in 83% of cases and minimal periportal lymphocyte infiltration in 40% of cases. Lymph nodes were atrophic in 67% of cases and had foci of cortical necrosis in 46% of cases. Three cases had regional lymph node and liver metastases. Most tumor cells were viable. CONCLUSIONS: No differences in the number of lymph node or liver metastases were observed between patients with and without chemo-radiotherapy. No effect of the treatment on residual tumor was observed either.

[CD44 (HCAM) expression in subserous gallbladder carcinoma]. / Expresión de CD44 (HCAM) en el carcinoma subseroso de la vesícula biliar.

BACKGROUND: HCAM or CD44 is a multifunctional cell adhesion molecule, related to cell-cell, cell-extracellular matrix interactions and involved in tumor invasion. AIM: To study the importance of CD44 expression in subserous gallbladder carcinoma. MATERIAL AND METHODS: One hundred five samples (93 female) of subserous gallbladder carcinoma and 33 non tumoral gallbladder were studied. CD44 was stained using the streptavidine-biotin technique, using human anti CD44 antibodies. Eighty subjects with carcinoma were followed for a period up to 105 months. RESULTS: Mean age of patients was 62.6 years old, all tumors were adenocarcinoma, all were silent and 13% were well differentiated. CD44 was expressed in all controls and in 91%, the expression was normal. In 57% of cancer samples, CD44 expression was abnormal, in 50% it was less expressed and in 24%, it was not expressed. No differences in CD44 expression was observed between mucosa from control samples and mucosa adjacent to the tumor or superficial or deep tumoral areas. Global five years survival was 40%. No significant differences in survival were observed in those tumors with a lower of absent CD44 expression. Six patients with a higher expression died before 18 months of follow up. CONCLUSIONS: Nearly 50% of subserous gallbladder carcinomas show an abnormal CD44 expression.

[Incipient gallbladder carcinoma. Clinical and pathological study and prognosis in 196 cases]. / Carcinoma incipiente de la vesícula biliar. Estudio clínico-patológico y pronóstico de 196 casos.

BACKGROUND: There is little information about the behavior of early gallbladder carcinoma. AIM: To report the clinical and pathological features of 196 patients with early gallbladder carcinoma. MATERIAL AND METHODS: All patients with gallbladder cancer diagnosed between 1988 and 1997 were reviewed. In 703 of 829 patients, there was information about clinical features and follow up, and were included in this study. All gallbladders were subjected to a complete mapping. When neoplastic cells involved only the mucosa or muscular layer, the tumors were considered as early. RESULTS: One hundred ninety six patients had an early carcinoma (161 women, aged 57.5 years and 35 male, aged 63.4 years). One hundred twenty eight tumors were located in the mucosa and 68 in the muscular layer. Patients with tumors involving the mucosa were younger than those with tumors involving the muscular layer. All tumors were adenocarcinomas, 66% were well differentiated and 32% moderately differentiated. Tumors were not visible macroscopically in 132 cases. Five and 10 years survival was 92%. Subjects of less than 40 years old had a 100% survival at 5 years. A hepatic and lymph node resection was done in 12 patients with tumors infiltrating the muscular layer but in only one, the tumor infiltrated the liver. No difference in survival was observed when a simple cholecystectomy or radical surgery was done. CONCLUSIONS: Nearly 25% of gallbladder carcinomas can be classified as early and its diagnosis requires a directed study. Simple cholecystectomy is curative for this type of gallbladder cancer.

Microsatellite instability, prognosis and metastasis in gastric cancers from a low-risk population.

We examined 169 cases of gastric adenocarcinoma for microsatellite instability (MSI), using a panel of 8 microsatellite markers. Of these cases, 142 were from the United States, a country of relatively low risk for gastric cancer. Comparing microdissected tumors to normal cells from the same patient, we classified tumors as being microsatellite-stable (MSS) or having a low frequency of MSI (MSI-L, up to 30% of markers different in the tumor) or a high frequency of MSI (MSI-H, 30% or more of markers different). Among our American cases, we identified 26 (18.2%) showing MSI-H and 15 (10.6%) showing MSI-L. Twenty cases were from Korean patients, and they showed no significant differences in proportions of MSI-H and MSI-L from the American cases. MSI-H tumors in the American patients were characterized by elevated frequencies of band shifts in repeat sequences of the BAX (50%), transforming growth factor-beta receptor type II (TGFbetaRII, 68.9%), beta(2)-microglobulin (21.4%) and E2F4 (51.7%) genes. Alterations in E2F4 in MSI-H tumors were always integral multiples of 3 nucleotides lost or gained, which would not cause a frameshift mutation, and within the range of normal polymorphisms for this sequence. North American patients (n = 127) with MSI-H and MSI-L tumors had a longer median survival of 541 days and 587 days, respectively, compared to 265 days for patients with MSS tumors (p = 0.027). This survival difference may result from a significantly greater tendency for metastases in the MSS group (p = 0.031).

[P53 gene mutation in gallbladder cancer]. / Mutación del gen p53 en el cáncer de la vesícula biliar.

BACKGROUND: Gallbladder cancer frequency and mortality renders it one of the most important neoplastic diseases in Chile. P53 tumor suppressor gene has been studied in most types of cancer, but there is scarce information about it in gallbladder cancer. AIM: To study the frequency of P53 gene mutation in gallbladder cancer in the ninth region of Chile. MATERIAL AND METHODS: In 25 pathological samples of gallbladder cancer, the direct amplification and sequencing of p53 gene exons 5,6,7,8-8 was possible. RESULTS: Seventeen punctual mutations were observed in 13 cases (52%). There were 10 transitions, 5 transversions, one insertion (codon 194) and one deletion (codon 186). Eight cases had mutations in exon 5, six had mutations in exon 6, two had mutations in exon 7 and one had mutations in exons 8-9. In 14 of 25 cases, gene p53 protein was positive. When immunohistochemical expression of gene p53 protein was positive in more than 20% of cells, there was a high correlation between genetic alterations and immunohistochemical expression of the protein, with a specificity, sensitivity, positive and negative predictive values over 80%. CONCLUSIONS: P53 gene mutation is observed in a high proportion of gallbladder cancers at it can be accurately detected with conventional immunohistochemical techniques. The importance of this gene in the genesis of this carcinoma should be determined studying preneoplastic lesions and early carcinomas.

[Helicobacter pylori and chronic gastritis: relationship between infection and inflammatory activity in a high risk population for gastric cancer]. / Helicobacter pylori y gastritis crónica: relación entre infección y actividad inflamatoria en población de alto riesgo de cáncer gástrico.

BACKGROUND: Helicobacter pylori has been involved in gastric epithelial cell damage and gastric gland loss or atrophy. AIMS: To evaluate role of Helicobacter pylori infection in acute and chronic changes of chronic gastritis in a high gastric cancer-risk population. MATERIAL AND METHODS: 200 patients with chronic gastritis were selected from pathological files of Temuco Hospital. A complete histopathological protocol was fulfilled considering the presence of infection by Helicobacter pylori-like-organism (HLO), acute and chronic inflammatory infiltrate, epithelial cell damage and epithelial cell regeneration. RESULTS: 82% of patients showed infection by HLO. Moreover, this infection reached a frequency of 92.7% in gastric ulcer patients and 94.4% in duodenal ulcer patients. A statistically significant positive correlation was found between HLO infection and polymorphonuclear infiltrate, lymphocytic infiltrate, mucus depletion and epithelial regenerative activity. There was not a statistical correlation between HLO infection and atrophy. Finally, 90% of patients with multifocal atrophic gastritis and 100% of patients with diffuse antral gastritis had HLO infection. CONCLUSIONS: HLO gastric infection frequently caused acute inflammatory changes in gastric mucosa with chronic gastritis. Sometimes these changes were severe, with marked polymorphonuclear migration throughout epithelium and severe epithelial cell damage. Recovery of these changes could be considered as a goal in Helicobacter pylori eradication therapy decision.

[Gastric cancer and tumor growth regulation. Study of cell proliferation markers and protein complex p53/p21WAF1/CIP1/mdm-2]. / Cáncer gástrico y regulación del crecimiento tumoral. Estudio de marcadores de proliferación celular y del complejo proteínas p53/p21WAF1/CIP1/mdm-2.

BACKGROUND: p53/p21WAF1/CIP1 and mdm-2 proteins play an important role in cell cycle regulation. The study of the pathogenesis of gastric cancer is important to understand how these tumors progress during their natural history. AIM: To study the relationship between the immunohistochemical expression of p53/p21WAF1/CIP1 and mdm-2 and cell proliferation in gastric cancer. MATERIAL AND METHODS: Fifty one gastrectomy specimens with gastric cancer were studied using immunohistochemistry for p53/p21WAF1/CIP1 and mdm-2. Cell proliferation was determined by immunolabelling with PCNA and Ki67 antigens. Mitosis figures were counted in 10 high power microscopic fields. RESULTS: Patients from whom gastric cancer specimens were obtained had a mean age of 59.3 years. Ki67 and mitosis counting showed the highest correlation index with proliferation indexes studied. No correlation was found between the expression of protein complex p53/p21WAF1/CIP1 and mdm-2 and morphological characteristics of gastric tumors. Mdm-2 protein overexpression was the only marker that showed an independent correlation with cell proliferation. Moreover, mdm-2 positive tumors showed the highest proliferation indexes when p53 was not immunohistochemically over-expressed, as determined by PCNA labelling index. CONCLUSIONS: In gastric cancer, a direct correlation between mdm-2 overexpression and cell proliferation was observed. Moreover, the fact that mdm-2 positive tumors showed the highest cell proliferation when p53 was not overexpressed, entitles us to hypothesize that mdm-2 overexpression could play a major role in gastric carcinogenesis.

[P53 tumor suppressor gene in digestive neoplasms]. / Gen supresor de tumores p53 en neoplasias digestivas.

Malignant diseases of the digestive tract cause more than 50% of deaths due to cancer in Chile. There is a high incidence of gastric and gallbladder cancer and an increasing frequency of colorectal cancer. P53 tumor suppressor gene has a great importance in carcinogenesis and its alterations are specially important in digestive tract tumors such as colorectal cancer. There is contradictory evidence about the frequency of p53 gene or protein alterations or their biological significance. There is little information about p53 in Chile and it is mostly limited to immunohistochemical studies. This revision analyzes the frequency of p53 alterations in digestive tract tumors in Chile, using immunohistochemical and molecular biology methods. A special emphasis is given to the prognostic importance of this gene.

[p53 gene mutation in cancer of the colon and rectum]. / Mutación del gen p53 en el cáncer de colon y recto.

BACKGROUND: Genetic events associated to colorectal carcinoma are well characterized, but there is scanty information about this issue in Chilean subjects. AIM: To determine the frequency and distribution of exons 5, 6, 7, 8 and 9 mutations and the immunohistochemical expression of p53 gene in biopsy samples of colorectal carcinoma. MATERIAL AND METHODS: p53 gene exons 5, 6, 7, 8 and 9 were directly sequenced in 42 biopsy samples of colorectal carcinoma. Immunohistochemical expression of p53 was determined in 35 samples. RESULTS: Thirty one discrete mutations (12 transitions, 11 transversions and 8 insertions) were observed in 21 samples (60%). Nine samples had mutations in exon 5, twelve samples had mutations in exon 6, seven samples had mutations in exon 7 and three samples had mutations in exons 8 and 9. Immunohistochemical expression of p53 protein was observed in 18 of 35 cases. There was a high correlation between the genetic alteration and immunohistochemistry, when p53 was expressed in more the 20% of cells. The positive and negative predictive values of p53 expression were 87 and 80% respectively. There was a non significant lower mortality among patients with mutations in their biopsies. CONCLUSIONS: These results confirm the involvement of p53 gene mutations in colonic carcinogenesis. Immunohistochemical methods for the detection of p53 protein have a high predictive value.

[Bcl-2 gene protein expression in salivary gland tumors]. / Expresión de la proteína del gen Bcl-2 en tumores de glándulas salivales.

BACKGROUND: Salivary gland tumors have heterogeneous pathological features. Oncogene Bcl-2 product expression inhibits apoptosis and therefore is important for tumor proliferation. AIM: To assess the immunohistochemical gene Bcl-2 protein expression in salivary gland tumors. MATERIAL AND METHODS: Twenty seven salivary gland tumors were selected from the archives of the Pathology Department of Temuco Regional Hospital. There were 20 pleiomorphic adenomas, 4 cystic adenoid carcinomas and three mucoepidermoid carcinomas. Immunohistochemical gene Bcl-2 protein expression was determined in paraffin included pathological slices. RESULTS: All pleiomorphic adenomas expressed the protein, specially in tubulo ductal structures, solid and trabecular areas. All cystic adenoid carcinomas expressed the protein in myoepithelial cells. Two mucoepidermoid carcinomas were positive, only in the epidermoid areas. CONCLUSIONS: immunohistochemical gene Bcl-2 protein was expressed in virtually all benign and malignant salivary gland tumors. This observation suggest an important role of this protein in the development of these tumors.

[Chronic sclerosing non-specific sialadenitis of the submandibular gland (Küttner tumor). Report of one case]. / Sialadenitis crónica esclerosante inespecífica de la glándula submandibular (tumor de Küttner). Caso clínico.

Chronic sclerosing unspecific sialadenitis or Küttner tumor, is an infrequent inflammatory lesion of submandibular gland. We report a 60 years old male presenting with a slowly growing, painless, bilateral submandibular tumor of two years of evolution. Pathological examinations showed marked atrophy of glandular parenchyma with increased fibrous connective tissue and an intense lymphocytic infiltration with lymphoid follicle formation. Lymphocyte population study with kappa, lambda, CD20 and CD45RO antibodies was similar to that observed in reactive lymph nodes. There was no over expression of Bcl-2 gene protein, involved in the phenomenon of apoptosis of glandular tissue, that could explain the pathogenesis of atrophy. This protein was positive only in lymphoid cells and glandular conducts. An immune etiology, with replacement of glandular tissue by lymphoid and fibrous connective tissue is suggested.

Gallbladder cancer, management of early tumors.

In spite of the fatal course associated with patients with gallbladder cancer, there is a subgroup of them in whom prognosis could be improved. Although early gallbladder cancer is considered a tumor with invasion of the mucosa or the muscular layer, in this manuscript we analyze those with invasion confined to the gallbladder. Pre-operative diagnosis of these patients is rare with cholecystectomy specimen histologic analysis being the most common way of detecting these tumors. The level of wall invasion represents a useful and practical way of dividing the patients according to their prognosis and treatment. Mucosal and muscular invasion tumors could be cured by simple cholecystectomy. Among patients with a tumor confined to the gallbladder, those with subserosal infiltration represent the largest group. Residual tumor after cholecystectomy is a common fact in these patients, thus a more aggressive procedure than simple cholecystectomy should be performed. Generally, extended cholecystectomy is the preferred approach for dealing with these patients. Unfortunately, in spite of the employment of extended and potentially curative surgery, prognosis is still poor and additional therapeutic procedures are needed. Finally, when tumors compromise the serosal layer, 5-year survival is poor irrespective of the type of therapy. However, well-selected cases deserve to undergo aggressive treatment.

Gallbladder cancer in a high risk area: morphological features and spread patterns.

BACKGROUND/AIMS: Gallbladder carcinoma is one of the most frequent malignant tumors in Chile. The aim of this paper is to show our experiences in gallbladder carcinoma. METHODOLOGY: Six-hundred-sixty-nine cases of gallbladder carcinoma were included in this prospective study; 557 females (83.5%) and 112 males (16.5%). In 466 cases (70%), diagnosis was carried out in the cholecystectomy sample, 45 cases were partial cholecystectomies and 158 cases were metastases of gallbladder carcinoma. RESULTS: Ninety-eight per cent of the cases were adenocarcinomas, and in 85% of the cases gallstones were observed. Thirty-seven per cent of the primary tumors were macroscopically inapparent. One-hundred-thirty-one cases (29%) were early carcinomas and 323 cases (71%) were advanced carcinomas. A relationship between differentiation grade and infiltration level (p=0.0001) was observed. Lymph-node metastasis was found in 18.5%, 4.5% and 3.3% in the first, second and third lymph-node barriers respectively. Muscular tumors presented no lymph-node metastasis, while in serosal tumors lymph node metastasis reached 62% (p=0.04). Hepatic tumor infiltration was observed in 11%, 19% and 38% of muscular, subserosal and serosal tumors. CONCLUSIONS: The high frequency of inapparent carcinomas, gallstones and inflammatory changes of the vesicular wall are elements that make the pre-operative diagnosis of gallbladder carcinoma difficult. Differentiation grade and infiltration level are the most reliable prognostic factors in gallbladder carcinoma. Lymph-node metastasis or liver tumor infiltration are infrequent in early gallbladder carcinoma.

Preoperative chemoradiotherapy in the treatment of gallbladder cancer.

Gallbladder cancer is generally associated with a poor prognosis, with local recurrence being the main pattern of failure. In an attempt to improve on the present status of management, we evaluated a prospective Phase II study involving preoperative 5-fluorouracil and radiation. Among 27 eligible patients with a potentially resectable gallbladder cancer detected after cholecystectomy, 18 were treated with preoperative radiation (4500 cGy; 180 cGy/fraction, 5 days/week) concurrent with a continuous infusion of 5-fluorouracil (350 mg/m2/day, days 1-5 and 21-25). Toxicity included leukopenia (8 patients) and thrombocytopenia (7 patients). Delay in surgery due to hematological toxicity was seen in 6 patients. Of the 18 patients, 15 underwent a reoperation. Resection was performed in 13 (86%). Pathologic findings after reoperation revealed residual tumor in both liver and lymph nodes in 3 patients. At a median follow-up of 24 months, 7 patients are alive. Among the patients who died after curative resection, local recurrence was demonstrated in only 1. This is the first report concerning preoperative chemoradiation in gallbladder cancer. To assess its effect on survival, a prospective randomized trial will be necessary.