Compromiso nodal y extranodal detectado con PET/CT en linfoma en etapificación / Nodal and extranodal involvement detected by PET/CT in staging lymphoma

Objective: To describe visible nodal and extra-nodal involvement using PET/CT in the different types and subtypes of lymphoma in staging. Patients and method: PET/CT with F18-FDG were reviewed in patients with lymphoma staging, determining frequency and location of nodal and extra-nodal involvement, and intensity of F18-FDG uptake measured by SUVmax. Results: Of the 102 patients with NHL (average SUVmax 13.0 ± 9.7), 86.3% had nodal involvement (51.9% on both sides of the diaphragm, 24.5% only above the diaphragm), and 66.7% extra-nodal compromise (42.6% bone marrow, 22.1% muscle, 16.2% renal). Of the 30 patients with HL (average SUVmax 14.6 ± 6.0), 100% had nodal involvement (63.3% only above the diaphragm, 36.7% above and below the diaphragm), and 30% had extra-nodal involvement (66.7% bone marrow, 22.2% lung). Conclusion: PET/CT is the method of choice in the staging of lymphoma, allowing the detection of nodal and extra-nodal disease in both HL and NHL.

Objetivo: Describir el compromiso nodal y extranodal visible con PET/CT en los distintos tipos y subtipos de linfoma en etapificación. Pacientes y método: Se revisaron los PET/CT con F18-FDG realizados a pacientes con linfoma en etapificación, determinando frecuencia y localización del compromiso nodal y extranodal, e intensidad de captación de F18-FDG medida mediante SUVmax. Resultados: De los 102 pacientes con LNH (SUVmaxpromedio 13,0±9,7), un 86,3% presentó compromiso nodal (51,9% a ambos lados del diafragma, 24,5% sólo sobre el diafragma) y 66,7% compromiso extranodal (42,6% médula ósea, 22,1% muscular, 16,2% renal). De los 30 pacientes con LH (SUVmax promedio 14,6±6,0), el 100% tuvo compromiso nodal (63,3% sólo sobre el diafragma, 36,7% sobre y bajo el diafragma), y 30% compromiso extranodal (66,7% médula ósea, 22,2% pulmón). Conclusión: El PET/CT es el método de elección en la etapificación del linfoma, permitiendo detectar enfermedad nodal y extranodal, tanto en LH como en LNH.

Trasplante con precursores hematopoyéticos de cordón umbilical en adultos con neoplasias hematológicas en Chile: Serie clínica / Umbilical cord hematopoietic precursors transplantation: Report of five patients

Hematopoietic precursors transplantation is a therapeutic alternative for leukemia, some metabolic diseases and some immune deficiency syndromes. In its allogeneic variety leukemia eradication is based in the conditioning prior to transplantation and the allograñ effect against leukemia. Umbilical cord blood is an alternative source of hematopoietic precursors when there are no HLA compatible relatives available. Between 2003 and 2007 we have performed five umbilical cord blood transplant in adult patients in a University hospital. All patients had malignant diseases. Conditioning protocols were ablative in all except in one patient and in all, more than one unit of umbilical cord blood was used. Hematopoietic engraftment was confirmed in all patients and the main complications registered were infectious and associated to immunosuppression.

Detección de micrometástasis por RT-PCR de citokeratina 20 y su correlación con la sobrevida global en pacientes portadores de cáncer colorrectal / Cytokeratin 20 as a marker of tumor progression or dissemination in patients with colorectal cancer

Background: Colorectal cancer relapses or metastasizes in 30 percent of cases. Cytokeratin 20 is present in 95 percent of colorectal tumors and their metastases and could be used as a marker to detect tumor cells. Aim: To assess the usefulness and prognostic value of peripheral blood and bone marrow cytokeratin 20 determinations in patients with colorectal cancer. Material and methods: Blood and bone marrow samples were obtained from 56 patients with colorectal cancer aged 26 to 77 years (31 females) before surgical procedure. They were followed for a mean of 22 months (range 2.9 to 72 months) after surgery. Blood and bone marrow from 45 patients without cancer and 35 healthy subjects were used as negative controls. Messenger RNA expression of cytokeratin 20 was studied by real time and nested polymerase chain reaction. Results: Cytokeratin 20 was detected in 6 percent of controls and 41 percent of patients. There was no relation between cytokeratin 20 expression and age, gender, overall survival, tumor relapse, progression, localization or stage. Conclusions: Cytokeratin 20 determination is not useful as a marker of tumor progression or dissemination in patients with colorectal cancer.

Alternativas terapéuticas actuales de las metástasis hepáticas: [revisión] / Current therapeutic options for liver metastasis: [review]

The liver is a common site of hematogenous metastasis, especially from gastrointestinal malignancies. Liver metastasis are generally classified as stage IV disease. Previously treatment in such patients was met with great skeptiscism. However, advances in surgical and medical therapies during the last two decades have provided effective therapeutic options for selected patients. Since major hepatic resections are now performed with acceptable morbidity and a mortality rate <3 percent, colorectal cancer metastasis to the liver are associated with 5-year survival rates of 30 percent or more. Meanwhile, a variety of new therapies have been developed, including hepatic artery infusion of chemotherapy; alcoholic, crio and radiofrequency ablation and novel strategies of systemic chemotherapy with the development of molecular targeted new products. These new therapeutic armamentarium have been used mostly in liver metastasis from colorectal cancer patients. However, liver metastasis of neuroendocrine tumors and selected cases of non colorectal cancer liver metastasis are benefited from the same strategies. This report summarizes the different therapeutic tools, their advantages and results mainly on colorectal cancer liver metastasis. These results are expected to improve even further with multimodality approaches.

Tratamiento de anemia aplásica severa adquirida en pacientes pediátricos con inmunosupresión y trasplante alogénico de precursores hematopoiéticos / Treatment of acquired severe aplastic anemia in pediatric patients with immunosupression and allogeneic stem cell hematopoyetic transplant

Background: Severe acquired aplastic anemia (SAA) is an uncommon disease of childhood. Patients with SAA receive supportive care with transfusions and timely treatment of opportunistic infections, along with specific therapies, which may be allogenic stem cell transplantation (SCT) from a matched sibling or immunosupressive therapy (IT). Aim: To report the experience in the management of SAA. Patients and methods: Twenty five children with acquired SAA were treated from July 1992 to September 2005. Patients with full matched sibling donors received allogenic SCT after conditioning with a cyclophosphamide containing regimen. The other patients received immune suppression with cyclosporine plus methylprednisolone (n= 18) plus ATG (n=17). All received supportive care until recovery of hematopoietic function. Those who had severe opportunistic infections at diagnosis or did not respond to two cycles of ATG were evaluated for unrelated donor SCT. Results: Seven patients received sibling donor SCT and 18 IT, which was repeated in six. Three patients received mismatched related (1) or unrelated (2) SCT. Nineteen patients survived with a median follow up time of 4 years, 14 with full hematologic recovery. Six patients died: four due to infections after IT or SCT, one due to intracranial hemorrhage and one with secondary myelodysplasia 12 years after IT. Conclusions: Most children with SAA can be treated successfully with sibling donor SCT or IT. Patients without a histocompatible sibling who fail to respond to IS have a worse prognosis.

Efecto de un inhibidor tirosina kinasa (imatinib) en pacientes con tumores estromales gastrointestinales metastásicos: Experiencia preliminar / Treatment of metastatic gastrointestinal stromal tumors with Imatinib: Report of four cases

Gastrointestinal stromal tumors (GIST) have mutations of the tyrosine kinase receptor. When they are localized, the treatment of choice is surgical excision, but advanced tumors have a limited response to chemo or radiotherapy. Imatinib (STI571 or Glivec®) is a selective inhibitor or tyrosine kinase proteins that has been used successfully in the treatment of advanced GIST. We report four patients (two women) with a metastatic GIST that were treated with Imatinib 400 mg day and followed for 40 months. The disease tumor stabilized in three patients and in one it had an initial reduction and progressed at the end of follow up. Therefore Imatinib can be a therapeutic alternative in patients with metastatic GIST.

Evaluación de un modelo computacional para la indicación de quimioterapia en cáncer de mama / Evaluation of a computer program in use of adjuvant chemotherapy in early breast cancer

El cáncer de mama es la segunda causa de muerte por cáncer en mujeres en Chile. El tratamiento adyuvante con quimioterapia ha demostrado disminuir la recurrencia y muerte por la enfermedad. La recomendación de usar adyuvancia en un paciente individual es compleja y depende de la evaluación del riesgo de recaída, muerte y condición del enfermo. Adjuvant! es un modelo computacional útil en la predicción de la sobrevida y beneficio de la terapia adyuvante en pacientes con cáncer de mama. El modelo Adjuvant! se estudió en nuestra población de pacientes para conocer el beneficio estimado de la quimioterapia y la relación con su prescripción. Se aplicó Adjuvant! a 125 pacientes con cáncer de mama precoz (T1N0M0) tratadas con cirugía conservadora y radioterapia, 20 (16%) recibieron quimioterapia adyuvante. Según el modelo, el beneficio absoluto en sobrevida global a 10 años con quimioterapia en este grupo es de 1.3% (0,1-11,1%) y la reducción absoluta en el riesgo de recurrencia de 6.45% (0.4-20%). Un 25% de pacientes obtendría un beneficio en sobrevida global mayor del 2% y un 58,4% (73/125) mayor al 1%. De las pacientes de nuestra serie que recibieron quimioterapia un 50% (10/20) recibirían un beneficio esperado en sobrevida global menor al 2%. La mediana de beneficio del tratamiento combinado quimioterapia / hormonoterapia en la sobrevida global es de 1,8% (2-11,1) y en la sobrevida libre de enfermedad de 10.5% (1-25,6%). En estudios clásicos, al consultar a pacientes ya tratadas, más del 50% usarían nuevamente quimioterapia por un beneficio absoluto menor al 1%.

Breast cancer is the second cause of female death in Chile. Adjuvant chemotherapy has reduced breast cancer recurrence and death. The decision to use adjuvant chemotherapy for a specific patient is complex and must consider the general condition of the patient and its risks of recurrence and death. The computer model called Adjuvant! was designed for breast cancer to predict survival and determine the benefit of adjuvant chemotherapy. The Adjuvant! model was calculated for our population of breast cancer patients to determine the predicted benefit of chemotherapy and compare it with the actual indication. The Adjuvant model was applied to 125 patients with early breast cancer, (T1N0M0), treated with breast conserving surgery and post operative radiotherapy. Adjuvant chemotherapy was use in 20 patients (16%). According to the predictive model the absolute 10-year survival benefit with chemotherapy is 1.3% (0.1-11.1%) and the absolute recurrence risk reduction is 6.45% (0.4-20%). For 25% of the patients chemotherapy would result in an overall survival benefit larger than 2% and for 58.4% (73/125) larger than 1%. In our series 50% (10/20) received chemotherapy with a predicted overall survival benefit less than 2%. The median benefit with the combination of chemotherapy and hormonal therapy in overall survival was 1.8% (0.2-11.1) and in disease free survival was 10.5% (1-25.6%). Reports from the literature indicate that more that 50% of patients treated with chemotherapy would agree to receive it again for a benefit less than 1%.

¿Es curable el cáncer de mama en etapa precoz?: Resultados del tratamiento combinado con cirugía, radioterapia y quimioterapia / Treatment results of early breast cancer: A retrospective review

Background: Breast cancer will develop in one out of ten women during their lifetime. Early diagnosis has increased in recent years. Aim: To describe a population of women with breast cancer stage T1N0M0. To analyze radiation therapy toxicity and to evaluate treatment results. Material and methods: Retrospective review of the medical records of 125 women (aged 35 to 80 years) with breast cancer T1N0M0, that were treated between January 1997 and May 2004, with breast conserving surgery and postoperative radiation therapy at an oncology center. Patients lost from follow up were contacted by telephone. Results: An abnormal screening mammography was the reason for consult in 62 percent of cases. The average tumor size was 11.6 mm. Tumors detected with screening mammogram were smaller than those detected on physical exam. The most common radiotherapy toxicity was erithema, which was severe in 2.5 percent of cases. No patient had to stop the radiation treatment due to toxicity. One patient developed arm edema. Tamoxifen was prescribed for 5 years to 80 percent of patients and 17 patients received chemotherapy. After an average follow up of 40 months, no patient has developed local breast relapse, three patients developed contralateral breast cancer and three developed distant metastasis. Two patients died from breast cancer. Disease free survival was 95 percent. Conclusions: Radiotherapy was well tolerated and had excellent local control. Screening mammography detects small tumors. Survival is excellent for early stage breast cancer.

Resultados a largo plazo del tratamiento con quimioterapia y radioterapia en linfoma no Hodgking localizado, de grados intermedio y alto / Long term results for intermediate and high grade localized non Hodgkin lymphoma, treated with chemotherapy and radiotherapy

Background: Treatment of intermediate and high grade non-Hodgkin lymphoma (NHL) includes chemotherapy with or without radiotherapy, depending on the clinical stage. The standard treatment for advanced NHL is 8 cycles of combined chemotherapy, cyclophosphamide, adriamicin, vincristine and prednisone (CHOP). Patients presenting with localized disease are treated with fewer chemotherapy cycles and involved field radiotherapy, with good results. Aim: To evaluate the treatment results including overall survival (OS) and event-free survival (EFS) in localized aggressive NHL patients treated at the Pontificia Universidad Católica de Chile, Clinical Hospital. Patients and Methods: Retrospective analysis of all patients with Ann Arbor stages I and II referred to the hematology and radiotherapy clinic between 1998 and 2003. OS and EFS analysis was made according to the Kaplan and Meier method. Log-rank and Cox methods were used for univariate and multivariate analyses, respectively. Chemotherapy and radiotherapy toxicities were scored according to World Health Organization (WHO) and Radiation Therapy Oncology Group (RTOG) scales, respectively. Results: 39 patients (20 men), aged between 20 to 85 years, were the source for this study. The average follow-up was 51 months (range 6-115). The 5 years OS and EFS were 72,4 percent and 63,3 percent, respectively. On univariate analysis, age over 60 was the only variable that affected negatively OS and EFS. Acute toxicity caused by chemotherapy and radiotherapy was uncommon. Conclusions: Age over 60 was the only independent variable associated with poor prognosis. The number of chemotherapy cycles and the drug combination did not influence the results. These results support the usefullness of a shortened chemotherapy regimen plus involved field radiotherapy.

Tratamiento endovascular del síndrome de vena cava superior / Endovascular treatment of superior vena cava syndrome

Background: Superior vena cava syndrome (SVCS) is caused by the obstruction of venous drainage from the upper portion of the body. Common clinical findings are headache and cervical, facial and upper limb edema. Occasionally, clouding of consciousness appears. Aim: to report our experience with endovascular treatment of SVCS. Material and methods: Retrospective review of all patients with SVCS subjected to endovascular treatment between 1999 and 2005. Results: Eight patients were treated, all of them with malignancies. Six had a benign obstruction due to the presence of a chemotherapy catheter located in the superior vena cava, one had obstruction secondary to radiation therapy and one a tumor compression of the superior vena cava. Two patients underwent thrombolytic therapy. Angioplasty and stenting was performed in all patients. The chemotherapy catheter was removed to all patients and installed again in one. One patient had a hemothorax secondary to a simultaneous needle lung biopsy under video thoracoscopy. No patient died in relation to the procedure. Congestive signs and symptoms subsided in all patients within 24 hours after the procedure. During follow up, only one patient had symptoms related to vena cava obstruction and three died due to their malignant tumor. Conclusions: Endovascular treatment of SVCS has a low rate of complications and provides immediate and mid-term symptom relief.

Determinación de una mutación en el gen BRCA1 en una familia que presenta cáncer de mama hereditario / Determination of a BRCA1 gene mutation in a family with hereditary breast cancer

Background: Breast cancer is the main cause of death among women between 40 and 55 years old, in whom the hereditary cases are common. Therefore, the molecular diagnosis of germ line mutations involved in breast cancer susceptibility is relevant. BRCA1 and BRCA2 have been described as the two major genes involved in familial breast/ovarian cancer. We are performing a screening of BRCA1 and BRCA2 genes, in a group of 50 high risk Chilean families for breast/ovarian cancer. We have detected a mutation, 3936 C>T, that leads to a truncated protein, in two affected women from one of the families in study. Aim: To report the results of the screening for 3936 C>T in healthy relatives of index women. Material and me-thods: The molecular diagnosis of this mutation was offered to the healthy members of this family, and 17 relatives accepted to be tested. The region of the BRCA1 gene that includes the 3936 C>T mutation, was analyzed through PCR amplification, digestion with restriction enzyme BstNI, and direct sequencing. Results: 3936 C>T DNA mutation was present in 8 relatives. Conclusions: Considering the high risk of having a mutation in the BRCA1 gene, specially in pre-menopausal women, the molecualr diagnosis, genetic and clinical counseling are highly relevant. In Chile the molecualr diagnosis is still not widely applied.

Síndrome de Munchausen: estudio de 6 casos / Munchausen syndrome: a report of 6 patients

We report 6 patients with Munchausen syndrome, a fictitious disorder with physical symptoms. There were 4 females and 2 males, the age ranged from 21 to 29 years. Abdominal pain (2), hemoptysis, schock and hypoglycemia were the prsenting symptoms. The dignosis was made after a prolonged and costly hospital course, including invasive and non invasive diagnostic procedures. Two patients were ill enough to be at risk f death. An early diagnosis may help prevent unnecessary or risky procedutres in these patients