Anti-CCR7 therapy exerts a potent anti-tumor activity in a xenograft model of human mantle cell lymphoma.

BACKGROUND: The chemokine receptor CCR7 mediates lymphoid dissemination of many cancers, including lymphomas and epithelial carcinomas, thus representing an attractive therapeutic target. Previous results have highlighted the potential of the anti-CCR7 monoclonal antibodies to inhibit migration in transwell assays. The present study aimed to evaluate the in vivo therapeutic efficacy of an anti-CCR7 antibody in a xenografted human mantle cell lymphoma model. METHODS: NOD/SCID mice were either subcutaneously or intravenously inoculated with Granta-519 cells, a human cell line derived from a leukemic mantle cell lymphoma. The anti-CCR7 mAb treatment (3 × 200 µg) was started on day 2 or 7 to target lymphoma cells in either a peri-implantation or a post-implantation stage, respectively. RESULTS: The anti-CCR7 therapy significantly delayed the tumor appearance and also reduced the volumes of tumors in the subcutaneous model. Moreover, an increased number of apoptotic tumor cells was detected in mice treated with the anti-CCR7 mAb compared to the untreated animals. In addition, significantly reduced number of Granta-519 cells migrated from subcutaneous tumors to distant lymphoid organs, such as bone marrow and spleen in the anti-CCR7 treated mice. In the intravenous models, the anti-CCR7 mAb drastically increased survival of the mice. Accordingly, dissemination and infiltration of tumor cells in lymphoid and non-lymphoid organs, including lungs and central nervous system, was almost abrogated. CONCLUSIONS: The anti-CCR7 mAb exerts a potent anti-tumor activity and might represent an interesting therapeutic alternative to conventional therapies.

[Laparoscopic excision of retroperitoneal ganglioneuroma through anterior transperitoneal approach]. / Extirpación de un ganglioneuroma retroperitoneal por vía laparoscópica a través de un abordaje transperitoneal anterior.

BACKGROUND: Retroperitoneal ganglioneuromas are rare entities. Their treatment is complete surgical resection. Due to the proximity to major vessels, variable location and unknown malignant status, surgeons are often reluctant to use a laparoscopic approach for the resection of retroperitoneal masses. To our knowledge, only five cases of laparoscopic resection of retroperitoneal ganglioneuroma have been previously reported. CLINICAL CASE: We present the case of a 53-year-old woman who complained of intense, diffuse, stabbing, intermittent, nonradiating abdominal pain sharpest in both flanks during the preceding 6 months. A contrast-enhanced CT scan showed a well-defined, homogeneous 4-cm mass located in the retroperitoneum, extending from the exit of the inferior mesenteric vessels up to the renal veins. A laparoscopic anterior transperitoneal approach was performed with infraumbilical Hasson trocar and two 10-mm trocars in both iliac fossas. Operation time was 90 min. The patient was discharged on the second postoperative day. Histopathology reported a retroperitoneal ganglioneuroma. After 12 months follow-up, the patient is alive and disease-free. CONCLUSIONS: For digestive surgeons not used to the retroperitoneal access through the lateral position, the anterior transperitoneal approach can be a safe alternative for the resection of retroperitonal neoplasms.

Identification of prognostic factors in pancreatic cancer.

BACKGROUND: Surgical resection is the only potentially curative treatment for pancreatic cancer, but it is associated with high complication rates. Outcome is poor, even in those resected cases. Identification of prognostic factors preoperatively may help to improve treatment of these patients, based on the expected response. METHODS: A retrospective study of clinical variables of 59 patients with histological diagnosis of pancreatic carcinoma at University Hospitals Ramon y Cajal and La Princesa (Madrid, Spain) between 1999 and 2003 was performed. RESULTS: We analyzed 59 patients (32 males and 27 females) with a mean age of 63.76 years. All patients were operated on, performing palliative surgery in 32% and tumor resection in 68%, including pancreaticoduodenectomy in 51% and distal pancreatectomy in 17%. Median overall survival was 14 months (range: 1-110 months). We observed that the presence of abdominal pain (p = 0.042) and back pain (p = 0.004) at diagnosis, palpation of abdominal mass at physical examination (p = 0.012), preoperative levels of hemoglobin <12 g/dl (p = 0.0006) and serum albumin <2.8 g/dl (p = 0.021), perineural infiltration (p = 0.025), lymph node affection (p = 0.004), stages II, III, and IV (p = 0.001), and presence of residual tumor (R+) (p = 0.008) are all associated with poor survival. CONCLUSIONS: Abdominal and back pain, palpation of abdominal mass at physical examination, preoperative levels of hemoglobin <12 g/dl and serum albumin <2.8 g/dl, perineural infiltration, lymph node affection, stages II, III, and IV, and the presence of residual tumor are associated with poor outcome.

Influencia de la quimioterapia preoperatoria en el parénquima hepático y en la evolución posquirúrgica de pacientes sometidos a hepatectomía por metástasis de carcinoma colorrectal / Influence of pre-surgical chemotherapy on liver parenchyma and post-surgical outcome of patients subjected to hepatectomy due to colorectal carcinoma metastases

Introducción: El objetivo del estudio fue valorar la relación entre la administración preoperatoria de regímenes de quimioterapia basados en irinotecán u oxaliplatino con el desarrollo de enfermedad hepática grasa no alcohólica (EHGNA) o el síndrome de obstrucción sinusoidal (SOS) y la influencia de estas alteraciones histológicas sobre la evolución de los pacientes tras la intervención quirúrgica. Pacientes y método: Estudio prospectivo en el que se incluyeron 45 pacientes sometidos a intervención quirúrgica por metástasis hepáticas de cáncer colorrectal entre mayo de 2005 y julio de 2009. Se recogieron variables demográficas, preoperatorias, de la intervención quirúrgica y de la evolución postoperatoria. Se obtuvo una muestra de la pieza de resección para su análisis histológico siguiendo los parámetros de clasificación de la EHGNA (índice NAS) y del SOS. Resultados: En 22 casos se administró quimioterapia neoadyuvante previa a la resección (grupo de estudio) y 23 pacientes formaban parte del grupo control (no quimioterapia). En 4 de los 7 pacientes (57,2%) en los que se administró de forma preoperatoria irinotecán, se observó esteatohepatitis borderline o diagnóstica (p=0,001). Siete de los 15 pacientes tratados con oxaliplatino (46,7%) desarrollaron un SOS moderado o grave (p=0,002). No hubo diferencias en cuanto a la morbimortalidad en función del grado de EHGNA, pero sí hubo una mayor tasa de complicaciones hepáticas y mayor estancia media en los pacientes con SOS moderado/intenso (p=0,004 y p=0,021 respectivamente). Conclusiones: La administración de irinotecán se relacionó de forma significativa con un aumento en la incidencia de esteatohepatitis, sin que esto aumentara la morbimortalidad. Los pacientes tratados con oxaliplatino tuvieron una mayor incidencia de SOS y existió un aumento de las complicaciones hepáticas y de la estancia media (AU)

Introduction: The aim of the study was to evaluate the relationship between the pre-surgical administration of a chemotherapy regime based on irinotecan or oxaliplatin and the development of non-alcoholic fatty liver disease (NAFLD) or sinusoidal obstruction syndrome (SOS), and the influence of these histological changes on the outcome of patients after surgical intervention. Patients and method: A prospective study which included 45 patients surgically intervened due to colorectal cancer liver metastases between May 2005 and July 2009. Demographic data and the variables before during and after the operation were collected. A specimen of the resection was obtained for histological analysis following the classification parameters of the NAFLD (NASH index) and SOS scale. Results: Neoadjuvant chemotherapy was given before the resection in 22 cases (study group) and 23 patients made up the control group (no chemotherapy). Borderline or diagnostic steatohepatitis was observed in 4 of the 7 patients (57.2%) who were given preoperative irinotecan (P=0.001). Seven of the 15 patients (46.7%) treated with oxaliplatin developed a moderate or severe SOS (P=0.002). There were no differences in morbidity or mortality associated to the NAFLD grade, but there was a higher rate of liver complications and longer mean hospital stay in patients with moderate/severe SOS (P=0.004 and P=0.021, respectively). Conclusions: Treatment with irinotecan was significantly associated with an increase in the incidence of steatohepatitis, but did not increase the morbidity or mortality. Patients treated with oxaliplatin had a higher incidence of SOS, an increase in liver complications and a longer mean hospital stay (AU)

Breast cancer stem cell hypothesis: clinical relevance (answering breast cancer clinical features).

The cancer stem cells hypothesis arises from observation of normal tissue hierarchy and the demonstration of stem cells in normal tissues. Scientists continue to debate whether the putative cancer cells derive from the transformation of normal tissue stem cells or from more differentiated cells. The existence of a subpopulation of tumour cells with stem-cell-like characteristics, including very slow replication and resistance to standard chemotherapy, posses a novel therapeutic challenge. This review summarises the state of development of normal and cancer breast cells and the clinical and therapeutic relevance.

Distal cholangiocarcinoma associated with papillitis with viral CMV inclusions.

Cytomegalovirus (CMV) infections are usually described in immunodeficient patients. In immunocompetent patients active infection is uncommon, consisting usually of a mononucleosis-like syndrome. Numerous reports show that CMV is a potential pathogen in the gastrointestinal tract, even in immunocompetent patients, where it can produce lesions from the mouth to the anus. We report herein an uncommon association of chronic inflammation of the papilla and viral CMV inclusions with distal cholangiocarcinoma in a 72-year-old woman who presented jaundice, choluria, acholia and generalized pruritus. At laparotomy, dilatation of the bile ducts and an enlarged head of the pancreas were found. Pancreatoduodenectomy was performed. Pathology revealed an enlarged papilla, due to chronic inflammation with CMV inclusions. Histological analysis revealed moderately differentiated ductal adenocarcinoma of the distal bile tract.