Dendritic cell immunizations alone or combined with low doses of interleukin-2 induce specific immune responses in melanoma patients.

Dendritic cell (DC)-based therapy has proved to be effective in patients with a variety of malignancies. However, an optimal immunization protocol using DCs and the best means for delivering antigens has not yet been described. In this study, 20 patients with malignant melanoma in stages III or IV were vaccinated with autologous DCs pulsed with a melanoma cell lysate, alone (n = 13) or in combination with low doses of subcutaneous (s.c.) interleukin (IL)-2 injections (n = 7), to assess toxicity, immunological and clinical responses. Monocyte-derived DCs were morphological, phenotypic and functionally characterized in vitro. Peripheral blood mononuclear cells (PBMC), harvested from patients either prior to and after the treatment, were analysed using enzyme-linked immunosorbent spot (ELISPOT). After vaccination, 50% of the patients tested (seven of 13) from the first group and (three of seven) from the second, showed an increase in interferon (IFN)-gamma production in response to allogeneic melanoma cell lines but not to controls. Four of five tested human leucocyte antigen (HLA)-A2(+) patients with anti-melanoma activity also showed specific T cell responses against peptides derived from melanoma-associated antigens. Delayed type IV hypersensitivity reaction (DTH) against melanoma cell lysate was observed in six of 13 patients from the group treated with DC vaccines only and four of seven from the group treated with the combination of DCs and IL-2. Significant correlations were found between DTH-positive responses against tumour lysate and both disease stability and post-vaccination survival on the stage IV patients. There were no toxicities associated with the vaccines or evidence of autoimmunity including vitiligo. Furthermore, no significant enhancement was observed as a result of combining DC vaccination with IL-2. Our data suggest that autologous DCs pulsed with tumour lysate may provide a standardized and widely applicable source of melanoma specific antigens for clinical use. It is safe and causes no significant side effects and has been demonstrated to be partially efficient at triggering effective anti-melanoma immunity.

Avances en inmunoterapia celular contra el melanoma maligno / Advances in cellular immunotherapy for malignant melanoma

An alternative strategy for cancer treatment is the manipulation of the immune system, denominated cancer immunotherapy. The immunotherapeutical use of cells of the immune system, like dendritic cells (DC), is being explored in different clinical protocols. Recently, we finalized a clinical phase I protocol, for the treatment of malignant melanoma, using DCs loaded with tumor lysates. Our results indicate that the subcutaneous application of DCs do not produce adverse effects. We also observed an increase of tumor specific T lymphocytes precursors in the blood, associated to hypersensitivity reactions (DTH) in 60% of the treated patients. In most cases, an stability in the disease was observed, although without a significant association between vaccination and survival. Additionally, therapies based on Interleukin-2 (IL-2) have been used with relative success in the treatment of some kind of tumors since 1985. However, problems associated to the toxicity of IL-2 still restrict its massive use. Our direct experience with the use of IL-2, indicates that low doses and its subcutaneous application, maintains the beneficial effects for patients, eliminating the adverse effects. Based on the accumulated evidence during last the five years, we decided to implement an optimized clinical protocol, which alternatively combines dendritic cells vaccines with the use of low doses of IL-2 for the reinforcement of the immunological system.

[Deciduosis of the appendix as cause of acute abdomen in pregnancy]. / Deciduosis apendicular como causa de abdomen agudo en el embarazo.

Ectopic decidua reaction or deciduosis is a physiological phenomenon of pregnancy due to a progesterone induced metaplasia of the pluripotential cells of the subcelomic mesenchyma. Usually it is an incidental finding that has not been associated with clinical symptoms. Isolated cases of ectopic decidua have been reported with symptoms simulating appendicitis. We are reporting a case of deciduosis localized in the appendix with abdominal pain during the last period of pregnancy.

[Enteroendocrine cells modifications in Helicobacter pylori gastritis]. / Modificaciones de las células enteroendócrinas en gastritis por Helicobacter pylori.

OBJECTIVE: The aim of the present study was to analyze the modifications in the number and distribution of enteroendocrine cells (EEC) in antrum of patients with Helicobacter pylori (HE) gastritis. We also wanted to demonstrate their possible participation in the immune response. MATERIAL AND METHODS: Twenty-six (26) biopsies of gastric antrum from patients between the ages of 40 and 60 were used. Slides were stained with H&E, Giemsa for HP, and chromogranin A to visualize EEC. Five (5) patients were normal controls. Eleven (11) patients had antral chronic gastritis (ACG) with different grades of activity, and ten (10) patients had multifocal atrophic gastritis (MAG), both groups associated to HP. EEC were quantified in relation to 100 epithelial cells. Results were statistically compared. RESULTS: In the normal control group, EEC were sparsely distributed, deep in antral glands, with an average 19.51 EEC/100 epithelial cells. In ACG there were 12.01/100. Besides EEC were irregularly distributed, close to inflammatory areas, or near lymphoid follicles. CONCLUSION: The decrease in EEC is probably due to degranulation and later to a disappearance or inhibition of stem cells by inflammatory products in HP gastritis. The proximity of EEC to prominent inflammatory zones may indicate EEC modulate the immune response. They produce and excrete peptides that interact with membrane receptors found in T lymphocytes and macrophages.

Deciduosis apendicular como causa de abdomen agudo en el embarazo. / [Deciduosis of the appendix as cause of acute abdomen in pregnancy]

Ectopic decidua reaction or deciduosis is a physiological phenomenon of pregnancy due to a progesterone induced metaplasia of the pluripotential cells of the subcelomic mesenchyma. Usually it is an incidental finding that has not been associated with clinical symptoms. Isolated cases of ectopic decidua have been reported with symptoms simulating appendicitis. We are reporting a case of deciduosis localized in the appendix with abdominal pain during the last period of pregnancy.

Modificaciones de las células enteroendócrinas en gastritis por Helicobacter pylori. / [Enteroendocrine cells modifications in Helicobacter pylori gastritis]

OBJECTIVE: The aim of the present study was to analyze the modifications in the number and distribution of enteroendocrine cells (EEC) in antrum of patients with Helicobacter pylori (HE) gastritis. We also wanted to demonstrate their possible participation in the immune response. MATERIAL AND METHODS: Twenty-six (26) biopsies of gastric antrum from patients between the ages of 40 and 60 were used. Slides were stained with H&E, Giemsa for HP, and chromogranin A to visualize EEC. Five (5) patients were normal controls. Eleven (11) patients had antral chronic gastritis (ACG) with different grades of activity, and ten (10) patients had multifocal atrophic gastritis (MAG), both groups associated to HP. EEC were quantified in relation to 100 epithelial cells. Results were statistically compared. RESULTS: In the normal control group, EEC were sparsely distributed, deep in antral glands, with an average 19.51 EEC/100 epithelial cells. In ACG there were 12.01/100. Besides EEC were irregularly distributed, close to inflammatory areas, or near lymphoid follicles. CONCLUSION: The decrease in EEC is probably due to degranulation and later to a disappearance or inhibition of stem cells by inflammatory products in HP gastritis. The proximity of EEC to prominent inflammatory zones may indicate EEC modulate the immune response. They produce and excrete peptides that interact with membrane receptors found in T lymphocytes and macrophages.

[Analgesic response and secondary effects in patients with osteoblastic metastasis, treated with Samarium 153 ethylenediaminotetramethylenephosphate]. / Respuesta analgésica y efectos secundarios en pacientes con metástasis osteoblásticas tratados con Samario-153 etilendiaminotetrametilenfosfato.

BACKGROUND: Samarium153 EDTMP, a beta and gamma emitter, is used in the palliative therapy of painful bone metastases. AIM: To evaluate the analgesic effects and myelotoxicity of Samarium153 EDTMP in patients with prostate, breast and renal carcinoma. PATIENTS AND METHODS: Twenty patients with bone metastases (11 males), aged 65 years old as a mean, received a 1 to 2 mCi/kg intravenous dose of Samarium153 EDTMP, produced in Chile. Patients were followed thereafter during 4 to 40 weeks. Pain was assessed using a visual analogue scale. RESULTS: Pain decreased from a score of 6.4 prior to treatment, to 2.7 at the fourth week of therapy and the effect lasted a mean of 12.5 weeks. Myelotoxicity was observed in 68% of cases (WHO stage I in 21%, stage II in 37%, stage III in 11% and no patients in stage IV). Platelets were the most affected series and neutrophils the least affected. Cell counts returned to normal between the sixth and eighth week. Seventy nine percent of patients decreased their basal analgesic therapy at the sixth week and 88% did so at the eighth week. Forty one percent of these patients discontinued all analgesics. CONCLUSIONS: Samarium153 EDTMP is effective in the treatment of pain in patients with bone metastases and its myelotoxicity is low to moderate. It should be considered as a therapy for this type of pain, with the precaution of performing periodical bood counts.

[MALT lymphoma of the bladder: report of a case]. / Linfoma MALT de vejiga. Informe de un caso.

Primary malignant lymphomas of the bladder are infrequent. We report a 70 year old woman presenting with hematuria, dysuria, malaise and a 5 kg weight loss. Pelvic ultrasound examination showed a 8 x 8 x 8 cm solid and cystic mass adjacent to the bladder and uterus. Cystoscopic biopsy disclosed a low grade B cell non Hodgkin lymphoma. She was treated with 6 cycles of chemotherapy with disappearance of the mass. Two years after admission, the patient is free of disease.

[Tropisetron for the prevention of nausea and vomiting during chemotherapy: multicenter clinical study]. / Tropisetron en la prevención de náuseas y vómitos por quimioterapia. Estudio clínico multicéntrico.

The antiemetic effect of tropisetron was studied in 97 cancer patients (67 men, 30 women) receiving cisplatin in doses of 75 mg/m2 or higher. On 279 chemotherapy cycles studied (max 6 per patient) 5 mg of tropisetron was administered once a day i.v on day 1 and p.o. on days 2 to 6. Efficacy preventing vomiting and nausea was measured in 24 hour period as: complete control O episodes, major control 1 to 2 episodes, minor control 3 to 4 episodes and no control 5 or more episodes. Satisfactory vomiting control (complete and major) was 69%, 63%, 82%, 88%, 96% and 96% in days 1 to 6 of cycle 1. Satisfactory nausea control (complete and major) for the same days was 70%, 66%, 72%, 85%, 92% and 97%. Similar data was obtained for the subsequent cycles. Complete vomiting control was obtained in 47%, 35%, 56%, 72%, 81% and 84% and for nausea in 42%, 39%, 48%, 64%, 81% and 87%. 19 patients presented adverse effects (19.6%). Only 2 headache episodes had a definite relation with the antiemetic drug. 12 patients discontinued the medication; 6 due to drug inefficacy, 2 to illness unrelated to the drug, 1 to lack of collaboration, and 3 due to other reasons. We conclude that tropisetron allows satisfactory control of acute and delayed vomiting in a high percentage of patients treated with high doses of cisplatin. The drug does not have significant secondary effects. Tropisetron administration in only one daily dose implies an evident advantage and a treatment cost reduction.

[Uterine lipoma localized in the myometrium. Report of a case, and review of the literature]. / Lipoma uterino de localización miometrial. Presentación de un caso, con revisión de la literatura.

Lipomatous benign neoplasms of uterus are very rare entities in women. The present paper presents a case of uterine lipoma. The diagnosis is easily made at the time of surgery or at autopsy, but before this, they may lead to many problems in the differential diagnosis with another uterine tumors. Recent papers suggest the possibility of a preoperative diagnosis made by computed tomography and magnetic resonance imaging. Cytogenetic analysis of this benign tumor have established chromosomal abnormalities in sites that may control cell proliferation.

[Dietary carotene intake and lung cancer among men from Santiago]. / Carotenos dietarios y cáncer pulmonar en hombres de Santiago.

Aiming to assess the association between carotenes and vitamin A intake and lung cancer, a case control study was performed. Sixty one male subjects with lung cancer and 61 controls paired for age, sex and smoking habits from 6 hospitals in Santiago were analyzed. Based on a consumption tendency enquiry, the mean weekly intake of food groups, carotenes and vitamin A was calculated, considering seasonal variations. Results showed that cases consumed less "winter" vegetables than controls (chard, beet, chicory, spinach and cabbage) but no differences between groups in carotene and retinol consumption. It is concluded that patients with lung cancer have a lower consumption of carotene rich vegetables.

Carcinoma transicional de vejiga: evaluación de factores pronósticos / Transitional carcinoma of the bladder: evaluation of prognostic factors

Se analizan factores pronósticos en 25 pacientes con carcinoma transicional (CT) de vejiga con un seguimiento mínimo de 2 años. Histológicamente correspondían a 12 tumores grado I, 10 pacientes grado II y 3 grado III. De acuerdo con el estadio eran 11 pacientes estado O, 8 estadio A, 3 estadio C. Se investigó la presencia de gonadotrofina corónica subunidad beta (HCGB) por métodos inmunohistoquímicos, en 18 casos, 8 negativos y 10 positivos y de los isoantígenos de grupo sanguíneo (IGS) en 18, resultando 8 positivos y 10 negativos. La ploidía nuclear fue estudiada con un analizador de imágenes en los extendidos citológicos de los 25 casos, resultando 5 diploides y 20 aneuploides estableciéndose el grado de malignidad el que varió entre 0,100 y 2,689. Se demostró la relación pronóstica adversa de un estadio clínico avanzado y de un grado histológico III, teniendo los I y II una evolución similar entre ellos pero mejor que el grado III. La presencia de HCGB, aneuploidía y grado de malignidad creciente fueron parámetros pronóstico III, teniendo los I y II una evolución similar entre ellos pero mejor que el grado III. La presencia de HCGB, aneuploisía y grado de malignidad creciente fueron parámetros pronósticos desfavorables estadísticamente significativos. Lo mismo ocurrió, pero sin significación estadística para los IGS. Estas determinaciones son de utilidad en la evaluación de CT de vejiga en especial en las lesiones grado histológico bajo (AU)

Carcinoma transicional de vejiga: evaluación de factores pronósticos / Transitional carcinoma of the bladder: evaluation of prognostic factors

Se analizan factores pronósticos en 25 pacientes con carcinoma transicional (CT) de vejiga con un seguimiento mínimo de 2 años. Histológicamente correspondían a 12 tumores grado I, 10 pacientes grado II y 3 grado III. De acuerdo con el estadio eran 11 pacientes estado O, 8 estadio A, 3 estadio C. Se investigó la presencia de gonadotrofina corónica subunidad beta (HCGB) por métodos inmunohistoquímicos, en 18 casos, 8 negativos y 10 positivos y de los isoantígenos de grupo sanguíneo (IGS) en 18, resultando 8 positivos y 10 negativos. La ploidía nuclear fue estudiada con un analizador de imágenes en los extendidos citológicos de los 25 casos, resultando 5 diploides y 20 aneuploides estableciéndose el grado de malignidad el que varió entre 0,100 y 2,689. Se demostró la relación pronóstica adversa de un estadio clínico avanzado y de un grado histológico III, teniendo los I y II una evolución similar entre ellos pero mejor que el grado III. La presencia de HCGB, aneuploidía y grado de malignidad creciente fueron parámetros pronóstico III, teniendo los I y II una evolución similar entre ellos pero mejor que el grado III. La presencia de HCGB, aneuploisía y grado de malignidad creciente fueron parámetros pronósticos desfavorables estadísticamente significativos. Lo mismo ocurrió, pero sin significación estadística para los IGS. Estas determinaciones son de utilidad en la evaluación de CT de vejiga en especial en las lesiones grado histológico bajo

Rapid karyotyping in ectopic pregnancies.

The aim of this study was to determine the feasibility of karyotyping ectopic Fallopian tube pregnancies utilizing dividing cytotrophoblast cells. Villi from 78 ectopic conceptuses were processed by the direct chromosome technique and cytogenetic diagnosis was successful in 60 cases (76.9 per cent). The amount of villi obtained, as well as villus morphology, was correlated with cytogenetic success rate. Histological examination of the Fallopian tube was also carried out. A total of 47 cases were chromosomally abnormal (78.3 per cent), which is the highest frequency of cytogenetic abnormalities reported to date.

[Transitional carcinoma of the bladder. Evaluation of prognostic factors]. / Carcinoma transicional de vejiga. Evaluación de factores pronósticos.

This study evaluates prognostic factors in 25 patients with transitional cell carcinoma (TCC) of the bladder with a minimum follow up of two years. Histologically there were 12 patients with grade I tumors according to the Mostofi's classification, 10 patients with grade II lesions and 3 grade III. The course of the grade I and II tumors was similar and the grade III worse. According to stage, there were 11 patients stage 0, 8 stage A, 3 stage B and 3 stage C. Patients with all stages recurred but only those with stage B and C died of their disease. In 18 patients the expression of the beta subunit of HCG and of the blood group isoantigens was demonstrated by immunohistochemistry. There were 8 negative cases and 10 positive for the beta subunit of HCG and 10 negative and 8 positive for the blood group isoantigens. DNA analysis was done with an image analyzer on cytological smears of the urine in the 25 cases after decolorization of the smears and Feulgen staining. There were 5 diploid and 25 aneuploid cases. The DNA malignancy grade was determined with a range between 0.100 and 2.689 and the number of events more than 5c (5N). The presence of HCG, aneuploid tumors, a malignancy grade higher than 0.500 and the presence of events more than 5c were statistically significant unfavorable prognostic factors. The presence of blood group isoantigens was associated with a better evolution of the tumor but did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma transicional de vejiga. Evaluación de factores pronósticos. / [Transitional carcinoma of the bladder. Evaluation of prognostic factors]

This study evaluates prognostic factors in 25 patients with transitional cell carcinoma (TCC) of the bladder with a minimum follow up of two years. Histologically there were 12 patients with grade I tumors according to the Mostofis classification, 10 patients with grade II lesions and 3 grade III. The course of the grade I and II tumors was similar and the grade III worse. According to stage, there were 11 patients stage 0, 8 stage A, 3 stage B and 3 stage C. Patients with all stages recurred but only those with stage B and C died of their disease. In 18 patients the expression of the beta subunit of HCG and of the blood group isoantigens was demonstrated by immunohistochemistry. There were 8 negative cases and 10 positive for the beta subunit of HCG and 10 negative and 8 positive for the blood group isoantigens. DNA analysis was done with an image analyzer on cytological smears of the urine in the 25 cases after decolorization of the smears and Feulgen staining. There were 5 diploid and 25 aneuploid cases. The DNA malignancy grade was determined with a range between 0.100 and 2.689 and the number of events more than 5c (5N). The presence of HCG, aneuploid tumors, a malignancy grade higher than 0.500 and the presence of events more than 5c were statistically significant unfavorable prognostic factors. The presence of blood group isoantigens was associated with a better evolution of the tumor but did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

[Medical oncology: notions for a new specialty]. / Oncología médica: ideas para una nueva especialidad.

The higher incidence and mortality rates of cancer require an increasing concern of the medical community regarding this disease. In the last decade the management of advanced stages of the disease has progressed significantly. The contributions of basic research, and improvements in diagnostic methods, chemotherapy, hormonal therapy and bio-therapy has made this possible. The internist is the most competent specialist to take over the diagnosis and management of this disease; therefore he should be trained in the different disciplines which will enable him to become a medical oncologist. The training program for this new specialty should be designed by post-graduate schools with the support of the universities, the Ministry of Health and even private institutions. In Chile, as in other developed countries, there are training programs which have been suited to satisfy the growing needs of different specialties.

[Immunoscintigraphy in stomach neoplasms with anti-CEA BW 431/26 monoclonal antibodies marked with Tc 99 m]. / Inmunocintigráfia en cáncer gástrico con anticuerpo monoclonal anti-CEA BW 431/26 marcado con TC 99 M.

A 57 year old female had a tubular gastric adenocarcinoma confirmed by endoscopy and radiologic studies. Echotomography of the abdomen revealed multiple adenopathies. Immunoscintigraphy with 99mTc labeled anti-CEA BW 431/26 monoclonal antibody was performed. Images obtained at 6 and 24 h showed a significant uptake at the primary lesion and at periaortic adenopathies both in conventional gamma-camera and single emission photon tomography. This immuno-scintigraphic technique may be helpful in the management of patients with gastric cancer.