A Two-Step Diagnostic Approach for NTRK Gene Fusion Detection in Biliary Tract and Pancreatic Adenocarcinomas.

BACKGROUND: It is of interest to determine the incidence and molecular characteristics of NTRK gene fusions in patients with bilio-pancreatic cancers, because of possible treatment with TRK inhibitors for advanced tumors. The aim of the present study was to apply the guidelines for NTRK testing algorithm to a series of patients with bilio-pancreatic cancers. METHODS: Immunohistochemistry screening was applied on formalin-fixed paraffin-embedded archival blocks from surgical resections, biopsies, or cytological samples of biliary tract and pancreatic adenocarcinomas. The presence of at least a weak staining in rare tumor cells led to testing by 2 RNA-based NGS panels. RESULTS: For biliary tract tumors, 153 samples have been selected. A total of 140 samples were suitable to perform IHC, and 17 samples were IHC positive. RNA NGS testing of the 17 IHC-positive samples revealed a single NTRK3 gene fusion (ETV6(4)-NTRK3(14)) that was detected by both NGS panels. In this perihilar cholangiocarcinoma, IHC performed on a biopsy showed a weak focal cytoplasmic and nuclear staining. No other NTRK fusion was detected on the 16 other samples with both panels. Overall in the patients screened by IHC and confirmed by NGS, the percentage of NTRK fusions was 0.7%. For pancreatic cancers, 319 samples have been selected and 297 were suitable to perform IHC. Nineteen samples were IHC positive. No fusion was detected by NGS. CONCLUSION: NTRK gene fusions are rare in bilio-pancreatic cancers but testing is of high interest due to possible treatment with specific TRK inhibitors.

Cyclophosphamide, Thalidomide, and Dexamethasone as Initial Therapy for Patients With Newly Diagnosed Multiple Myeloma in a Middle-Income Country: 7-Year Follow-Up.

PURPOSE: Major progress has occurred in multiple myeloma (MM) treatment in recent years, but this is not seen in low- and middle-income countries. MATERIALS AND METHODS: We retrospectively assessed the efficacy and safety of cyclophosphamide, thalidomide, and dexamethasone (cyclophosphamide 400 mg/m2 for 5 days, thalidomide 100 mg once daily, if tolerated, and dexamethasone 40 mg once weekly; in 28-day cycles) in patients with newly diagnosed MM treated at our institution between April 2008 and December 2012. Survival outcomes were estimated by the Kaplan-Meier method. RESULTS: Fifty-nine patients were found to meet the selection criteria. Median age was 56 years (27-78). Fifty-nine percent (n = 35) were male. International Staging System three was found in 24%. The median number of treatment cycles was 11 (range 4-12). After a median of 81-month follow-up (range 5-138 months), the overall response rate was 69.5%. The complete response and very good partial response were 5% and 32%, respectively. Median progression-free survival (PFS) was 35 months (95% CI, 18 to 41). The 3-year PFS was 47.4% (95% CI, 34.5 to 59.6) and 5-year PFS was 24.9% (95% CI, 14.4 to 36.9). The median of overall survival (OS) was 81 months (95% CI, 33 to not reached). The 3-year OS was 63.4% (95% CI, 49.2 to 74.6), and 5-year OS was 57.5% (95% CI, 43.2 to 69.4). The most common adverse event was neutropenia (grade 3 and 4, 30.5%). Out of 23 patients eligible for stem-cell transplantation, 10 (43.5%) proceeded with autologous transplantation. Treatment-related deaths occurred in four patients (6.7%). CONCLUSION: Cyclophosphamide, thalidomide, and dexamethasone achieves good response rates with tolerable toxicity, especially in patients age 65 years or younger representing a feasible approach for patients with MM in low-income health care settings.

New Algorithms Improving PML Risk Stratification in MS Patients Treated With Natalizumab.

Overview: We assessed the role of age and disease activity as new factors contributing to establish the risk of progressive multifocal leucoencephalopathy in multiple sclerosis patients treated with natalizumab in 36 University Hospitals in Europe. We performed the study in 1,307 multiple sclerosis patients (70.8% anti-John Cunninghan virus positive antibodies) treated with natalizumab for a median time of 3.28 years. Epidemiological, clinical, and laboratory variables were collected. Lipid-specific IgM oligoclonal band status was available in 277 patients. Factors associated with progressive multifocal leucoencephalopathy onset were explored by uni- and multivariate logistic regression. Results: Thirty-five patients developed progressive multifocal leucoencephalopathy. The multivariate analysis identified anti-John Cunninghan virus antibody indices and relapse rate as the best predictors for the onset of this serious opportunistic infection in the whole cohort. They allowed to stratify progressive multifocal leucoencephalopathy risk before natalizumab initiation in individual patients [area under the curve (AUC) = 0.85]. The risk ranged from <1/3,300 in patients with anti-John Cunninghan virus antibody indices <0.9 and relapse rate >0.5, to 1/50 in the opposite case. In patients with lipid-specific IgM oligoclonal bands assessment, age at natalizumab onset, anti-John Cunninghan virus antibody indices, and lipid-specific IgM oligoclonal band status predicted progressive multifocal leucoencephalopathy risk (AUC = 0.92). The absence of lipid-specific IgM oligoclonal bands was the best individual predictor (OR = 40.94). The individual risk ranged from <1/10,000 in patients younger than 45 years at natalizumab initiation, who showed anti John Cunningham virus antibody indices <0.9 and lipid-specific IgM oligoclonal bands to 1/33 in the opposite case. Conclusions: In a perspective of personalized medicine, disease activity, anti-lipid specific IgM oligoclonal bands, anti Jonh Cunninghan virus antibody levels, and age can help tailor natalizumab therapy in multiple sclerosis patients, as predictors of progressive multifocal leucoencephalopathy.

Synovial chondromatosis and soft tissue chondroma: extraosseous cartilaginous tumor defined by FN1 gene rearrangement.

A fusion between fibronectin 1 (FN1) and activin receptor 2A (ACVR2A) has been reported previously in isolated cases of the synovial chondromatosis. To analyze further and validate the findings, we performed FISH and demonstrated recurrent FN1-ACVR2A rearrangements in synovial chondromatosis (57%), and chondrosarcoma secondary to synovial chondromatosis (75%), showing that FN1 and/or AVCR2A gene rearrangements do not distinguish between benign and malignant synovial chondromatosis. RNA sequencing revealed the presence of the FN1-ACVR2A fusion in several cases that were negative by FISH suggesting that the true prevalence of this fusion is potentially higher than 57%. In soft tissue chondromas, FN1 alterations were detected by FISH in 50% of cases but no ACVR2A alterations were identified. RNA sequencing identified a fusion involving FN1 and fibroblast growth factor receptor 2 (FGFR2) in the case of soft tissue chondroma and FISH confirmed recurrent involvement of both FGFR1 and FGFR2. These fusions were present in a subset of soft tissue chondromas characterized by grungy calcification, a feature reminiscent of phosphaturic mesenchymal tumor. However, unlike the latter, fibroblast growth factor 23 (FGF23) mRNA expression was not elevated in soft tissue chondromas harboring the FN1-FGFR1 fusion. The mutual exclusivity of ACVR2A rearrangements observed in synovial chondromatosis and FGFR1/2 in soft tissue chondromas suggests these represent separate entities. There have been no reports of malignant soft tissue chondromas, therefore differentiating these lesions will potentially alter clinical management by allowing soft tissue chondromas to be managed more conservatively.

Plasma lactate and leukocyte mitochondrial DNA copy number as biomarkers of insulin sensitivity in non-diabetic women.

High plasma lactate levels have been associated with reduced mitochondrial respiratory capacity and increased type 2 diabetes risk, while mitochondrial DNA (mtDNA) copy number has been proposed as a biomarker of mitochondrial function linked to glucose homeostasis. The aim of this study was to evaluate the association between circulating lactate levels and leukocyte mtDNA copy numbers with insulin secretion/sensitivity indexes in 65 Chilean non-diabetic women. mtDNA copy numbers were measured in leukocytes using qPCR and digital-droplet PCR. A 75-g Oral Glucose Tolerance Test (OGTT) was performed to calculate systemic and tissue-specific insulin sensitivity indexes, as well as insulin secretion surrogates based on plasma c-peptide. An intravenous glucose tolerance test (IVGTT; 0.3 g/kg) was also carried out. Disposition indexes were calculated as the product of insulin secretion × sensitivity. Plasma levels of leptin, adiponectin, TNF-α, MCP-1, and non-esterified fatty acids were also determined. Fasting plasma lactate shows a significant association with a wide range of insulin sensitivity/resistance indexes based on fasting plasma samples (HOMA-S, adipose IR index, Revised-QUICKI, leptin-adiponectin ratio, TyG index, McAuley index and TG-to-HDL-C ratio), as well as OGTT-based measures such as the Matsuda index, the hepatic insulin resistance index, and the disposition index. Fasting plasma lactate was also positively associated with the circulating adipokines TNF-α and MCP-1. We also detected a direct association between fasting plasma lactate with leukocyte mtDNA copy numbers. The above results support the use of fasting plasma lactate, and possibly leukocyte mtDNA copy numbers, as biomarkers of reduced oxidative mitochondrial capacity, decreased hepatic insulin sensitivity, and future diabetes risk.

Primary cutaneous T-cell lymphoma: experience from the Peruvian National Cancer Institute.

BACKGROUND: Primary cutaneous T-cell lymphomas constitute a heterogeneous and rare group of diseases with regional particularities in Latin America. OBJECTIVE: To determine the clinicopathological features, relative frequency and survival among patients from a Peruvian institution. METHODS: Primary cutaneous T-cell lymphomas were defined based on the absence of extracutaneous disease at diagnosis. Classification was performed following the 2008 World Health Organization Classification of Neoplasms of the Hematopoietic and Lymphoid tissues. Risk groups were established according to the 2005 World Health Organization-EORTC classification for cutaneous lymphomas. Data of patients admitted between January 2008 and December 2012 were analyzed. RESULTS: 74 patients were included. Mean age was 49.5 years. In order of frequency, diagnoses were: mycosis fungoides (40.5%), peripheral T-cell lymphoma not otherwise specified (22.95%), adult T-cell lymphoma/leukemia (18.9%), CD30+ lymphoproliferative disorders (6.8%), hydroa vacciniforme-like lymphoma (5.4%), extranodal NK/T-cell lymphoma (4.1%) and Sézary syndrome (1.4%). Predominant clinical patterns were observed across different entities. Mycosis fungoides appeared mainly as plaques (93%). Peripheral T-cell lymphoma not otherwise specified and adult T-cell lymphoma/leukemia presentation was polymorphic. All patients with hydroa vacciniforme-like lymphoma presented with facial edema. All cases of extranodal NK/T-cell lymphoma appeared as ulcerated nodules/tumors. Disseminated cutaneous involvement was found in 71.6% cases. Forty-six percent of patients were alive at 5 years. Five-year overall survival was 76.4% and 19.2%, for indolent and high-risk lymphomas, respectively (p<0.05). High risk group (HR: 4.6 [2.08-10.18]) and increased DHL level (HR: 3.2 [1.57-6.46]) emerged as prognostic factors for survival. STUDY LIMITATIONS: Small series. CONCLUSION: Primary cutaneous T-cell lymphomas other than mycosis fungoides or CD30+ lymphoproliferative disorders are aggressive entities with a poor prognosis.

Primary cutaneous T-cell lymphoma: experience from the Peruvian National Cancer Institute

Abstract: Background: Primary cutaneous T-cell lymphomas constitute a heterogeneous and rare group of diseases with regional particularities in Latin America. Objective: To determine the clinicopathological features, relative frequency and survival among patients from a Peruvian institution. Methods: Primary cutaneous T-cell lymphomas were defined based on the absence of extracutaneous disease at diagnosis. Classification was performed following the 2008 World Health Organization Classification of Neoplasms of the Hematopoietic and Lymphoid tissues. Risk groups were established according to the 2005 World Health Organization-EORTC classification for cutaneous lymphomas. Data of patients admitted between January 2008 and December 2012 were analyzed. Results: 74 patients were included. Mean age was 49.5 years. In order of frequency, diagnoses were: mycosis fungoides (40.5%), peripheral T-cell lymphoma not otherwise specified (22.95%), adult T-cell lymphoma/leukemia (18.9%), CD30+ lymphoproliferative disorders (6.8%), hydroa vacciniforme-like lymphoma (5.4%), extranodal NK/T-cell lymphoma (4.1%) and Sézary syndrome (1.4%). Predominant clinical patterns were observed across different entities. Mycosis fungoides appeared mainly as plaques (93%). Peripheral T-cell lymphoma not otherwise specified and adult T-cell lymphoma/leukemia presentation was polymorphic. All patients with hydroa vacciniforme-like lymphoma presented with facial edema. All cases of extranodal NK/T-cell lymphoma appeared as ulcerated nodules/tumors. Disseminated cutaneous involvement was found in 71.6% cases. Forty-six percent of patients were alive at 5 years. Five-year overall survival was 76.4% and 19.2%, for indolent and high-risk lymphomas, respectively (p<0.05). High risk group (HR: 4.6 [2.08-10.18]) and increased DHL level (HR: 3.2 [1.57-6.46]) emerged as prognostic factors for survival. Study limitations: Small series. Conclusion: Primary cutaneous T-cell lymphomas other than mycosis fungoides or CD30+ lymphoproliferative disorders are aggressive entities with a poor prognosis.

Cáncer colorrectal en los jóvenes: factores pronósticos y características clínico patológicas en un instituto del cáncer de Perú.

OBJECTIVE: To determine clinicopathological features and prognostic factors among young colorectal cancer (CRC) patients in a Peruvian Cancer Institute. METHODS: Data of patients 40 years or younger, admitted between January 2005 and December 2010, were analyzed. RESULTS: During the study period, 196 young patients with CRC were admitted. The tumor was located in the rectum, left colon and right colon in 45.9%, 28.6% and 25.5% of cases. Family history of CRC was found in 13.2% and an autosomal pattern of inheritance, in 8.6% of the cases. The most common symptoms were pain (67.9%) and bleeding (67.3%). The majority (63.1%) of colon cancer cases and more than a third (34.4%) of rectal cancer cases were diagnosed in stage III or IV. The histologic type was tubular, mucinous and signet ring cell adenocarcinoma in 73.5%, 14.8% and 8.6%, respectively. The depth of invasion was T3 in 21.4% and T4 in 53%. Nodal involvement was detected in 44.5%. Five-year overall survival (OS) was 44.3%. In the multivariate analysis, only the stage resulted an independent prognostic factor for survival. CONCLUSIONS: CRC in Peruvian young patients is mostly sporadic. It presents more often in the distal colon or rectum and at advanced stages of the disease. Mucinous and signet ring cell carcinoma were requent histological types. Five-year OS stage by stage is similar to that reported in the literature for older patients. Stage was the only independent prognostic factor for survival.

Final 5-Year Study Results of DASISION: The Dasatinib Versus Imatinib Study in Treatment-Naïve Chronic Myeloid Leukemia Patients Trial.

PURPOSE: We report the 5-year analysis from the phase III Dasatinib Versus Imatinib Study in Treatment-Naïve Chronic Myeloid Leukemia Patients (DASISION) trial, evaluating long-term efficacy and safety outcomes of patients with chronic myeloid leukemia (CML) in chronic phase (CP) treated with dasatinib or imatinib. PATIENTS AND METHODS: Patients with newly diagnosed CML-CP were randomly assigned to receive dasatinib 100 mg once daily (n = 259) or imatinib 400 mg once daily (n = 260). RESULTS: At the time of study closure, 61% and 63% of dasatinib- and imatinib-treated patients remained on initial therapy, respectively. Cumulative rates of major molecular response and molecular responses with a 4.0- or 4.5-log reduction in BCR-ABL1 transcripts from baseline by 5 years remained statistically significantly higher for dasatinib compared with imatinib. Rates for progression-free and overall survival at 5 years remained high and similar across treatment arms. In patients who achieved BCR-ABL1 ≤ 10% at 3 months (dasatinib, 84%; imatinib, 64%), improvements in progression-free and overall survival and lower rates of transformation to accelerated/blast phase were reported compared with patients with BCR-ABL1 greater than 10% at 3 months. Transformation to accelerated/blast phase occurred in 5% and 7% of patients in the dasatinib and imatinib arms, respectively. Fifteen dasatinib-treated and 19 imatinib-treated patients had BCR-ABL1 mutations identified at discontinuation. There were no new or unexpected adverse events identified in either treatment arm, and pleural effusion was the only drug-related, nonhematologic adverse event reported more frequently with dasatinib (28% v 0.8% with imatinib). First occurrences of pleural effusion were reported with dasatinib, with the highest incidence in year 1. Arterial ischemic events were uncommon in both treatment arms. CONCLUSION: These final results from the DASISION trial continue to support dasatinib 100 mg once daily as a safe and effective first-line therapy for the long-term treatment of CML-CP.

Cáncer colorrectal en los jóvenes: factores pronósticos y características clínico patológicas en un instituto del cáncer de Perú / Colorectal cancer in the young: clinicopathologic features and prognostic factors from a cancer institute in Peru

To determine clinicopathological features and prognostic factors among young colorectal cancer (CRC) patients in a Peruvian Cancer Institute. Methods: Data of patients 40 years or younger, admitted between January 2005 and December 2010, were analyzed. Results: During the study period, 196 young patients with CRC were admitted. The tumor was located in the rectum, left colon and right colon in 45.9%, 28.6% and 25.5% of cases. Family history of CRC was found in 13.2% and an autosomal pattern of inheritance, in 8.6% of the cases. The most common symptoms were pain (67.9%) and bleeding (67.3%). The majority (63.1%) of colon cancer cases and more than a third (34.4%) of rectal cancer cases were diagnosed in stage III or IV. The histologic type was tubular, mucinous and signet ring cell adenocarcinoma in 73.5%, 14.8% and 8.6%, respectively. The depth of invasion was T3 in 21.4% and T4 in 53%. Nodal involvement was detected in 44.5%. Five-year overall survival (OS) was 44.3%. In the multivariate analysis, only the stage resulted an independent prognostic factor for survival. Conclusions: CRC in Peruvian young patients is mostly sporadic. It presents more often in the distal colon or rectum and at advanced stages of the disease. Mucinous and signet ring cell carcinoma were frequent histological types. Five-year OS stage by stage is similar to that reported in the literature for older patients. Stage was the only independent prognostic factor for survival...

Determinar las características clínicopatológicas y factores relacionados con el pronóstico del cáncer colorrectal (CCR) en los pacientes jóvenes del Instituto Nacional de Enfermedades Neoplásicas (INEN). Material y métodos: Se analizaron retrospectivamente los datos de los pacientes de 40 o menos años admitidos entre enero del 2005 y diciembre del 2010. Resultados: Se incluyeron 196 pacientes. La localización correspondió al recto, colon izquierdo y colon derecho en 45,9%, 28,6% y 25,5%. En 13,2% hubo antecedentes familiares de CCR y en 8.6%, un patrón de herencia autosómico dominante. Los síntomas más frecuentes fueron dolor (67,9%) y sangrado (67,3%). El 63,1% de los casos de cáncer de colon y el 34,4% de los casos de cáncer de recto, se diagnosticaron en estadio clínico (EC) III o IV. El tipo histológico correspondió a adenocarcinoma tubular, mucinoso y de células en anillo de sello en 73,5%, 14,8% y 8,6%, respectivamente. La profundidad de la invasión fue de T3 en 21,4% y de T4 en 53%. En 44,5% de los casos hubo compromiso ganglionar. La sobrevida global (SG) a 5 años fue de 44,3%. En el análisis multivariado, el estadio resultó ser un factor pronóstico independiente. Conclusiones: El CCR en jóvenes es en su mayoría esporádico, se presenta con mayor frecuencia en el colon distal o recto y en estadios avanzados. El carcinoma mucinoso y de células en anillo de sello fueron tipos histológicos frecuentes. La SG comparada por estadios es similar a la reportada en la literatura. El EC fue el único factor pronóstico independiente para sobrevida...

[Adjuvant chemo radiotherapy after gastrectomy and D2 lymphadenectomy in patients with gastric cancer in the National Institute of Cancer, Lima, Peru]. / Tratamiento adyuvante con quimioterapia y radioterapia luego de gastrectomía y disección ganglionar D2 en pacientes con cáncer gástrico en el Instituto Nacional de Enfermedades Neoplásicas, Lima, Perú

INTRODUCTION: Adjuvant chemo radiotherapy is the standard treatment in Western countries in gastric cancer patients submitted to curative resection. INT0116 pivotal trial established adjuvant chemo radiation as the standard care for resected high risk adenocarcinoma of the stomach in US however was hampered by suboptimal surgery. There is controversial data about efficacy of this adjuvant therapy in patients who have undergone D2 lymphadenectomy predominantly. In our hospital D2 lymphadenectomy is standard surgery for gastric cancer. OBJECTIVE: To prove that chemo and radio therapy post gastrectomy and D2 linphadenectomy in patients' with gastric cancer is effective. MATERIAL AND METHODS: Retrospective study with gastric adenocarcinoma patients stage II to IV M0 who underwent curative resection at INEN (Instituto Nacional de Enfermedades Neoplasicas) Lima-Peru between 2001 and 2006. Standard treatment at institution is D2 lymphadenectomy. Chemo radiotherapy according to INT0116 was given like adjuvant therapy. Survivalcurves were calculated according to Kaplan-Meier method and compared with log-rank test. RESULTS: 84 patients were included 60.7% male and 39.3% female. Mean age was 49.5 years old. The pathologic stages were T1-T2 (15.5%), T3- T4 (84.5%), N0-N1 (10.7%), N2-N3 (89.3%). D2 lymphadenectomy was performed in all patients. The 3-year DFS was 17% and 3-year overall survival was 23.9%. However when we analyzed by subgroups the overall survival, was in group N1 (66.7%) and in group N2 (58.9%) and N3 (18.3%) and 3 years DFS by subgroups were N1 (100%), N2 (51.9%) and N3 (16.3%). CONCLUSIONS: Adjuvant chemo radiotherapy decreased risk of death and relapse to three years mainly in patients with node positive N1-N2, who underwent curative resection with D2 lymphadenectomy, but recurrence was most frequent in N3 node positive, maybe is necessary improve the chemotherapy in this group of patients for decrease the rate of relapse.

Tratamiento adyuvante con quimioterapia y radioterapia luego de gastrectomía y disección ganglionar D2 en pacientes con cáncer gástrico en el Instituto Nacional de Enfermedades Neoplásicas, Lima, Perú / Adjuvant chemo radiotherapy after gastrectomy and D2 lymphadenectomy in patients with gastric cancer in the National Institute of Cancer, Lima, Peru

Introducción: La quimio radioterapia adyuvante es una alternativa de tratamiento especialmente para pacientes con cirugías inferiores a D2. El estudio INT016 estableció la quimio radioterapia adyuvante como el cuidado estándar para adenocarcinoma resecado de alto riesgo del estómago en Estados Unidos, sin embargo, se vio obstaculizado por la cirugía sub óptima. Existe controversia acerca de la eficacia de esta terapia adyuvante en pacientes sometidos a linfandenectomía D2. En nuestra institución la linfandenectomía D2 es la cirugía estándar para cáncer gástrico. Objetivo: Demostrar que la terapia adyuvante de quimio y radioterapia en pacientes con cáncer gástrico sometidos a gastrectomía y disección ganglionar D2 es efectiva. Materiales y métodos: Estudio retrospectivo de pacientes con adenocarcinoma gástrico estadío II a IV M0 quienes se sometieron a resección curativa en el Instituto Nacional de Enfermedades Neoplásicas, Lima-Perú en el periodo 2001 a 2006. El tratamiento estándar en la Institución es la linfandenectomía D2 y quimio radioterapia adyuvante de acuerdo al INT016. Las curvas de sobrevida fueron estimadas con el método Kaplan-Meier y comparadas con la prueba logrank. Resultados: 84 pacientes fueron incluidos 60,7% hombres y 39,3% mujeres. La edad media fue 49,5 años. Los estadios patológicos fueron T1-T2 (15,5%), T3-T4 (84,5%), N0-N1 (10,7%), N2-N3 (89,3%). Linfandenectomía D2 fue desarrollada en todos los pacientes. Encontramos una sobrevida libre de enfermedad a 3 años de 17% y una sobrevida global de 23,9%. Cuando se analiza por subgrupos, la sobrevida global en los grupos N1, N2 y N3 fueron 66,7%, 58,9% y 18,3%, respectivamente y la sobrevida libre de enfermedad fue 100%, 51,9% y 16,3%, respectivamente. Conclusiones: La quimio radioterapia adyuvante podría ser una alternativa para disminuir el riesgo de muerte y recaída a tres años principalmente en pacientes con ganglios positivos N1-N2, quienes se sometieron a resección curativa con linfandenectomía D2, pero la recurrencia fue más frecuente en ganglios positivos N3, la quimioterapia en este grupo de pacientes podría ser una alternativa para disminuir la tasa de recaída.

Introduction: Adjuvant chemo radiotherapy is the standard treatment in Western countries in gastric cancer patients submitted to curative resection. INT0116 pivotal trial established adjuvant chemo radiation as the standard care for resected high risk adenocarcinoma of the stomach in US however was hampered by suboptimal surgery. There is controversial data about efficacy of this adjuvant therapy in patients who have undergone D2 lymphadenectomy predominantly. In our hospital D2 lymphadenectomy is standard surgery for gastric cancer. Objective: To prove that chemo and radio therapy post gastrectomy and D2 linphadenectomy in patients’ with gastric cancer is effective. Material and methods: Retrospective study with gastric adenocarcinoma patients stage II to IV M0 who underwent curative resection at INEN (Instituto Nacional de Enfermedades Neoplasicas) Lima-Peru between 2001 and 2006. Standard treatment at institution is D2 lymphadenectomy. Chemo radiotherapy according to INT0116 was given like adjuvant therapy. Survival curves were calculated according to Kaplan-Meier method and compared with log-rank test. Results: 84 patients were included 60.7% male and 39.3% female. Mean age was 49.5 years old. The pathologic stages were T1-T2 (15.5%), T3-T4 (84.5%), N0-N1 (10.7%), N2-N3 (89.3%). D2 lymphadenectomy was performed in all patients. The 3-year DFS was 17% and 3-year overall survival was 23.9%. However when we analyzed by subgroups the overall survival, was in group N1 (66.7%) and in group N2 (58.9%) and N3 (18.3%) and 3 years DFS by subgroups were N1 (100%), N2 (51.9%) and N3 (16.3%). Conclusions: Adjuvant chemo radiotherapy decreased risk of death and relapse to three years mainly in patients with node positive N1-N2, who underwent curative resection with D2 lymphadenectomy, but recurrence was most frequent in N3 node positive, maybe is necessary improve the chemotherapy in this group of patients for decrease the rate of relapse.

Addition of amifostine to the CHOP regimen in elderly patients with aggressive non-Hodgkin lymphoma: a phase II trial showing reduction in toxicity without altering long-term survival.

BACKGROUND AND OBJECTIVES: We report the 8-year follow-up of 34 patients aged ≥69 years old with NHL included in a phase IIb open-label randomized parallel groups study to evaluate the effectiveness of amifostine in preventing the toxicity of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP regime) . PATIENTS AND METHODS: Patients were randomized to receive classical CHOP (cyclophosphamide 750 mg/m(2), doxorubicin 50 mg/m(2), vincristine 1.4 mg/m(2) [maximum 2 mg] on day 1 and prednisone 100 mg/day for 5 days) or CHOP plus amifostine (6 cycles of amifostine 910 mg/m(2) on day 1). Efficacy (time to progression, TTP; disease-free survival, DFS; overall survival, OS) and toxicity endpoints were evaluated. RESULTS: Thirty-four patients were randomized to A-CHOP (n=18) or CHOP (n=16). Patients with A-CHOP vs CHOP had significantly lower toxicity; neutropenia grade 4 ocurred in 13/92 (13%) vs 23/85 (27%, P=0.007) cycles, febrile neutropenia in 3/92 A-CHOP (3%) vs 8/85 (10%, P=.056) CHOP cycles, hospitalization for toxicity in 4/92 (4%) A-CHOP vs 11/85 (13%, P=.05) CHOP cycles. Median hospitalization stay for toxicity was 5 days with A-CHOP vs 8 days with CHOP (P=.05). There were no significant differences at 8 years in TTP (A-CHOP, 48.9% vs CHOP, 36.3%; P=.65), DFS (A-CHOP, 72.9% vs CHOP 55.6%; P=.50) and OS (A-CHOP, 44.3% vs CHOP, 54.4%). There was no long-term toxicity of clinical interest. The only prognostic factor identified to 8 years was the International Prognostic Index (IPI low/low intermediate risk vs high intermediate/high risk; HR=2.98; CI 95%:1.01-8.77; P=.048). CONCLUSION: These results show that amifostine can be added to the standard CHOP treatment schedule with less acute toxicity and without influencing the outcome.

Phase III, open-label, randomized study comparing concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin versus concurrent cisplatin and radiation in patients with stage IIB to IVA carcinoma of the cervix.

PURPOSE: To determine whether addition of gemcitabine to concurrent cisplatin chemoradiotherapy and as adjuvant chemotherapy with cisplatin improves progression-free survival (PFS) at 3 years compared with current standard of care in locally advanced cervical cancer. PATIENTS AND METHODS: Eligible chemotherapy- and radiotherapy-naive patients with stage IIB to IVA disease and Karnofsky performance score ≥ 70 were randomly assigned to arm A (cisplatin 40 mg/m(2) and gemcitabine 125 mg/m(2) weekly for 6 weeks with concurrent external-beam radiotherapy [XRT] 50.4 Gy in 28 fractions, followed by brachytherapy [BCT] 30 to 35 Gy in 96 hours, and then two adjuvant 21-day cycles of cisplatin, 50 mg/m(2) on day 1, plus gemcitabine, 1,000 mg/m(2) on days 1 and 8) or to arm B (cisplatin and concurrent XRT followed by BCT only; dosing same as for arm A). RESULTS: Between May 2002 and March 2004, 515 patients were enrolled (arm A, n = 259; arm B, n = 256). PFS at 3 years was significantly improved in arm A versus arm B (74.4% v 65.0%, respectively; P = .029), as were overall PFS (log-rank P = .0227; hazard ratio [HR], 0.68; 95% CI, 0.49 to 0.95), overall survival (log-rank P = .0224; HR, 0.68; 95% CI, 0.49 to 0.95), and time to progressive disease (log-rank P = .0012; HR, 0.54; 95% CI, 0.37 to 0.79). Grade 3 and 4 toxicities were more frequent in arm A than in arm B (86.5% v 46.3%, respectively; P < .001), including two deaths possibly related to treatment toxicity in arm A. CONCLUSION: Gemcitabine plus cisplatin chemoradiotherapy followed by BCT and adjuvant gemcitabine/cisplatin chemotherapy improved survival outcomes with increased but clinically manageable toxicity when compared with standard treatment.

Less invasive fixation of an interthrocanteric fracture in an ankylosed hip with cannulated screws: a case report.

A 68-year-old woman presented following a road accident with an undisplaced intertrochanteric fracture affecting an ankylosed hip and an ipsilateral calcaneal fracture. The interthrocanteric fracture was fixed with four 7.0 mm cannulated screws. The calcaneal fracture was fixed with K wires and immobilized in a plaster. Because of this combination of injuries, although she was allowed to mobilize non weight bearing from the first week, sitting and progressive weight bearing were not permitted for six weeks. Radiographs taken at the one year showed consolidation of the hip fracture without complications. Final functional indices showed an EQ-5D VAS score of 40, EQ-5D health state index adapted to Spanish value sets of 0.493 and an Oxford Hip Score of 31. Screw fixation of an undisplaced intertrochanteric fracture in an ankylosed hip may be sufficient in some instances provided the patient remains non weight bearing for long enough.

Extranodal NK/T-cell lymphoma, nasal type: study of clinicopathologic and prognosis factors in a series of 78 cases from Peru.

It is well known that extranodal NK/T-cell lymphoma (NK/TCL) nasal type clusters in Asian countries. A large series of 78 cases of nasal NK/TCL from Peru is analyzed in the present study. Two histologic groups 1 (monomorphic) and 2 (polymorphic), were segregated according to the proportion of large cells (above and below 30%, respectively). Catalyzed signal amplification technique was performed for enhancement of immunohistochemistry reactivities. Epstein-Barr virus (EBV) sequences and types were investigated using polymerase chain reaction. Clinical characteristics, stage, outcome, and response to treatment were evaluated in both groups. Fourteen cases (18%) and 64 cases (82%) corresponded to groups 1 and 2, respectively. Except for nasal obstruction, more common in group 2, all other symptoms were similar in both groups. Local extension and staging were also comparable. Both groups showed CD3c+ CD2+ CD56+ CD3s- CD20- immunophenotype. All cases were positive for EBV. In this series type-2 EBV was found more frequent than type-1 EBV, contrarily to that observed in Asian series. However, about one-third of cases simultaneously harbored both viral types. Both groups received an average of 50-Gy dose of radiation therapy (RT), with or without chemotherapy. Complete therapeutic response was achieved in 89% of group 1 and in 74% of group 2, but this difference was not statistically significant. There were no significant differences between the groups regarding disease-free survival, failure-free survival, relapse, and overall survival. The overall survival, in both groups, was longer for patients treated with RT alone compared with those treated with combined RT therapy and chemotherapy. The present study has shown that dividing nasal NK/TCL in monomorphic and polymorphic variants, according to frequency of large cells, does not correlate with clinical and prognostic factors.

Low sensitivity of histology to predict the presence of microorganisms in suspected aseptic loosening of a joint prosthesis.

Intraoperative histology has a high specificity and sensitivity when a septic prosthesis loosening is suspected. However, its usefulness to predict the presence of microorganisms when aseptic loosening is suspected is not well defined. Intraoperative histology and cultures from periprosthetic tissue of 61 revision arthroplasties performed owing to suspected aseptic loosening were retrospectively reviewed. Frozen sections were evaluated following Mirra's criteria (adapted by Feldman). Culture was considered positive when the same microorganism was isolated in at least two samples. The cultures were positive in 12 cases and coagulase-negative staphylococci were the most common microorganisms (11 cases). In six out of 12 cases (50%), the histology revealed more than five polymorphonuclear leukocytes per high-power field. The sensitivity, specificity, positive and negative predictive value of histology to detect the presence of microorganisms was 50, 81, 40 and 86%, respectively. In conclusion, intraoperative histology using Mirra's criteria had a low sensitivity to predict the presence of microorganisms in samples from suspected aseptic prosthetic loosening.

Infección por el virus de inmunodeficiencia humana en niños de Valencia: 17 años de experiencia / Human immunodeficiency virus infection in children of Valencia: 17 years of experience

Describir la experiencia de 17 años de manejo de niños infectados por virus de inmunodeficiencia humana, determinando el impacto de la terapia antirretroviral en su morbimortalidad. Estudio retrospectivo, descriptivo, obteniéndose las características demográficas, clínicas y terapéuticas de las historias médicas de niños infectados, presentándose la información en quinquenios (< 92 93-97 98-2002). 171 niños fueron evaluados, estando infectados por VIH 62 (36,2 por ciento); 3 de 5 (60 por ciento) al principio y 26 de 96 (27 por ciento) en el último quinquenio. La distribución por sexo fue similar; 54,8 por ciento menores de 2 años. La mayoría llegaron en estadio C, principalmente antes del 92, pero después 33 por ciento en estadios N o A. Desde 1993 los niños reciben mono o biterapia y en 1998, triterapia. Nuestros hallazgos sugieren que la terapia antirretroviral no sólo disminuyó la mortalidad de 60 por ciento en 1992 a 18,7 por ciento, el porcentaje de infecciones oportunistas (de 60 por ciento a 20 por ciento) y hospitalización (41,6 por ciento a 16,8 por ciento), sino que también modificó el tipo de severidad de las infecciones comunes; neumonía y otitis crónica en sin terapia antirretroviral vs piel y tejidos blandos en los tratados, bajando la neumonía al noveno lugar. Tuberculosis, herpes zóster y citomegalovirus fueron las infecciones oportunistas más frecuentes. Se observó un incremento de los casos, principalmente después de 1998, donde se diagnosticaron el 61,3 por ciento de los mismos. La terapia antirretroviral de alta eficacia generó un gran impacto en la disminución de la morbimortalidad, hospitalización e infecciones oportunistas.

Coccidioidomicosis diseminada: manifestación inicial de sida en residente de área no endémica / Disseminated coccidioidomycosis: initial manifestation of AIDS in a non-endemic area resident

La coccidioidomicosis es causada por Coccidioides immitis, hongo muy virulento cuyo hábitat natural se restringe a la región geográfica situada en el noroeste de la República Mexicana y el suroeste de Estados Unidos de América del Norte. La mayoría de las veces cursa en forma asintomática. El padecimiento suele presentarse en forma localizada (40 por ciento), limitado al aparato respiratorio. Raramente (0.5 por ciento) causa afección multiorgánica y se constituye en la forma diseminada. Aun en áreas endémicas, la enfermedad en su forma diseminada se presenta con igual prevalencia en pacientes con infección por el virus de la inmunodeficiencia humana (VIH), que en sujetos inmunocompetentes. Sin embargo, conforme aparece y avanza el deterioro de la inmunidad celular consecutivo a la infección por VIH se puede presentar la reactivación del hongo en pacientes que lo adquirieron previamente. En la coccidioidomicosis diseminada la afección de corazón, tiroides, hígado, bazo, intestino y encéfalo es poco común, incluso en pacientes con síndrome de inmunodeficiencia humana. Se informa de un paciente residente en un área no endémica, en el cual la coccidioidomicosis diseminada se presentó como reactivación de la infección y constituyó la manifestación inicial de sida.