Dynamic soluble changes in sVEGFR1, HGF, and VEGF promote chemotherapy and bevacizumab resistance: A prospective translational study in the BECOX (GEMCAD 09-01) trial.

Despite initial responsiveness, acquired resistance to both bevacizumab and chemotherapy in metastatic colorectal cancer is universal. We have recently published that in vitro, chronically oxaliplatin resistance upregulates soluble vascular endothelial growth factor receptor 1, downregulates vascular endothelial growth factor, and also promotes c-MET, b-catenin/transcription factor 4, and AKT activation. We tested whether variation in three serum biomarkers such as the natural c-MET ligand (hepatocyte growth factor), soluble vascular endothelial growth factor receptor 1, and vascular endothelial growth factor-A was associated with efficacy in metastatic colorectal cancer patients treated in the prospective BECOX study. Serum levels of vascular endothelial growth factor-A165, soluble vascular endothelial growth factor receptor 1, and hepatocyte growth factor were assessed by enzyme-linked immunosorbent assay method basally and every 3 cycles (at the time of computed tomography evaluation) in a preplanned translational study in the first-line BECOX trial in metastatic colorectal cancer patients treated with CAPOX plus bevacizumab. Response was evaluated by routine contrast-enhanced computed tomography by RECIST 1.1 by investigator assessment and by three blinded independent radiologists. Ratios between soluble vascular endothelial growth factor receptor 1/vascular endothelial growth factor-A and hepatocyte growth factor/vascular endothelial growth factor-A were established and variations through time were related to RECIST 1.1 by investigator assessment and independent radiologist. The BECOX trial included 68 patients, and 27 patients were analyzed in the translational trial. A total of 80 RECIST 1.1 evaluations were done by investigator assessment and 56 by independent radiologist. We found that a 3.22-fold increase in soluble vascular endothelial growth factor receptor 1/vascular endothelial growth factor-A by investigator assessment and a 3.06-fold increase in soluble vascular endothelial growth factor receptor 1/vascular endothelial growth factor-A by independent radiologist from previous determination were associated with responses compared with 1.38-fold increase by investigator assessment and 1.59 by independent radiologist in non-responders (p = 0.0009 and p = 0.03, respectively). Responders had a 3.36-fold increase in hepatocyte growth factor/vascular endothelial growth factor-A from previous determination by investigator assessment and 3.66-fold increase in hepatocyte growth factor/vascular endothelial growth factor-A by independent radiologist compared with 1.43-fold increase by investigator assessment and 1.53 by independent radiologist for non-responders (p = 0.002 and 0.003, respectively). In conclusion, a decrease in vascular endothelial growth factor-A and an increase in soluble vascular endothelial growth factor receptor 1 during chemotherapy and bevacizumab exposure can contribute to both chemotherapy (due to c-MET/b-catenin activation) and bevacizumab (due to low vascular endothelial growth factor requirements) resistance. Because hepatocyte growth factor levels decrease also during acquired resistance, alternative strategies to hepatocyte growth factor-ligand inhibition should be investigated.

[PET/CT-guided salvage surgery protocol. Results with ROLL Technique and PET probe]. / Protocolo de cirugía de rescate guiada por PET/TAC. Resultados con técnica ROLL y sonda PET.

OBJECTIVE: To assess the value of intraoperatory radioguided probe detection to guide surgical resection of malignant lesions previously detected by (18)F-FDG PET-CT. MATERIAL: Twelve consecutive patients with suspected tumor recurrence detected by (18)F-FDG PET-CT considered resectable were enrolled in the study. Ultrasound guided fine needle aspiration (FNA) before surgery was performed in 6 patients and CT guided biopsy was performed in 1 patient. In 5 patients with accessible lesions, a radioguided occult lesion localization (ROLL) technique was performed after injection of (99m)Tc-colloid (1.7-2.4 mCi) inside the lesion under ultrasound or CT guidance, pre-operatively. Radioguided surgical detection was then carried out 19-24 hours afterwards using the gamma probe. In 7 patients with non-accessible needle lesions or multiple lesions, 9.5-10.5 mCi of (18)F-FDG were injected 3-5 hours before radioguided surgery using a PET-dedicated probe (Gamma locator DXI-GF&E). RESULTS: ROLL technique: All lesions injected with nanocolloid were resected (6 lesions in 5 patients, 1 patient with 2 lesions), and recurrence was histologically confirmed. PET probe: Fourteen out of 16 hypermetabolic lesions detected on the PET-CT were resected. One cervical and one mediastinal lymph node in different patients could not be excised. Histological recurrence was confirmed in 12 out of 14 lesions. In one patient, the 2 lymph nodes excised were inflammatory. CONCLUSIONS: (18)F-FDG PET-CT can be key in deciding surgical approach and appropriate radioguided protocol. When lesions are solitary and easily accessible, ROLL technique seems the method of choice. PET probe is more adequate for less accessible lesions.

Value of FDG-PET for monitoring treatment response in patients with advanced GIST refractory to high-dose imatinib. A multicenter GEIS study.

AIM: The aim of this study was to evaluate the utility of positron emission tomography with 18F-fluorodeoxyglucose (FDG-PET) in monitoring response in refractory GIST. METHODS: This multicenter study prospectively evaluated 21 patients with locally advanced and/or metastatic GIST refractory to with high-dose imatinib (800 mg/day) treated with doxorubicin 15-20 mg/m2/weekly for 4 cycles, followed by imatinib maintenance (400 mg/day). CT and FDG-PET were performed at baseline and after completion of therapy. RESULTS: Mean baseline tumor size on CT was 5.9 cm. Median progression-free survival (PFS) was 219 days (range 62-1108). Three out of 21 patients (14%) had partial responses (PR) under RECIST criteria, 12 patients (57%) remained stable (SD) and 6 showed progression (PD) of the disease during treatment (29%). Six patients had PR by FDG-PET, 15 showed SD (n=9) or PD (n=6) based on EORTC criteria. Patients with a PFS <6 mo showed a significantly higher ∑SUVmax at baseline (26.04±13.4) than those with PFS≥6 mo (9.82±5.0) (P<0.05). A correlation was found between PET response and PFS: PR 14±6.1 mo, SD 5.5±0.8 mo and PD 3.5±4.1 mo (P<0.05). A residual SUVmax <5 after treatment correlated with improved PFS (314±315 days vs 131±91 days) (P<0.01). Survival curves showed a significant association between PET response and PFS (P<0.05). Patients with wild-type genotype KIT (KIT-WT) showed a significantly lower baseline SUVmax (5.36±1.4) than non-WT KIT (8.40±3.6) (P<0.05). CONCLUSION: FDG-PET is useful in assessing response of GIST refractory to imatinib and correlates with the presence of KIT-WT. Baseline ∑SUVmax can predict response to treatment in this series.

Role of magnetic resonance imaging and cause of pitfalls in detecting myometrial invasion and cervical involvement in endometrial cancer.

OBJECTIVE: To determine the diagnostic accuracy of magnetic resonance imaging (MRI) in detecting myometrial invasion and cervical involvement in endometrial cancer. STUDY DESIGN: Seventy two consecutive patients with endometrial carcinoma underwent preoperative MRI. We compared the MRI results with the final histopathological findings. We classify myometrial invasion as <50 or>or=50% and cervical involvement as positive or negative. Standard statistical calculations were used. RESULTS: The sensitivity, specificity, and accuracy of MRI for the detection of myometrial invasion>or=50% were 71, 86, and 58%, respectively. Positive and negative predictive values are 77 and 83%, respectively. The sensitivity, specificity, and accuracy of MRI for the detection of cervical invasion were 41, 97, and 46%, respectively. Positive and negative predictive values are 71 and 89%, respectively. The possible causes of misdiagnosis included a tumor isointense with the myometrium, polypoid tumor, myometrial thinning, exceedingly irregular myometrium, presence of adenomiosis, and presence of leiomyomas. CONCLUSION: MRI assists in planning the surgical treatment of endometrial cancer with an acceptable accuracy and a good specificity, although sensitivity is suboptimal.

[Diagnosis and staging of carcinoma of the pancreas (I)]. / Diagnóstico y estadificación del carcinoma de páncreas (I).

Carcinoma of the pancreas is a neoplasm with a poor prognosis that is diagnosed in the advanced stages in most patients. Given that surgical resection is the only potentially curative treatment for this disease, it is of the utmost importance to appropriately select the group of patients with initial stage pancreatic tumors that have not extended and can therefore be resected. Several different imaging techniques can be used for this purpose: ultrasonography (US), computed tomography (CT), magnetic resonance (MR), as well as the recent additions of endoscopic ultrasonography (EUS) and positron emission tomography (PET). Other techniques, such as laparoscopy and laparoscopic ultrasonography, also play a role in the diagnosis and staging of these patients. Continual technological developments in each of the above-mentioned techniques have led to reiterated updates in the scientific literature throughout the last two decades. This review aims to evaluate each of these techniques and present diagnostic algorithms reflected in the literature in order to achieve the greatest diagnostic accuracy in determining the extent of the disease so that unnecessary surgery can be avoided in cases not susceptible to resection.

Diagnóstico y estadificación del carcinoma de páncreas (I) / Diagnosis and staging of carcinoma of the pancreas (I)

El carcinoma de páncreas es una neoplasia de mal pronóstico que se diagnostica en fases avanzadas de la enfermedad en la mayoría de los pacientes. Dado que la resección quirúrgica es la única terapéutica potencialmente curativa de la enfermedad, resulta de máximo interés seleccionar adecuadamente el grupo de pacientes con tumor pancreático en fase inicial, no extendida, y por ello resecable. Son varias las técnicas de imagen de que disponemos para llevar a cabo este propósito: ultrasonografía (US), tomografía computarizada (TC), resonancia magnética (RM), más recientemente se ha incorporado la ultrasonografía endoscópica (USE) y por último la tomografía por emisión de positrones (PET). Otras técnicas como la laparoscopia asistida o no mediante ecografía, también intervienen en el proceso diagnóstico y de estadificación de estos pacientes. El continuo desarrollo tecnológico de cada una de las técnicas mencionadas hace que estén siendo evaluadas de forma reiterada en la literatura científica a lo largo de las dos últimas décadas. La presente revisión tiene por objetivo evaluar cada una de las técnicas y presentar algunos algoritmos de diagnóstico reflejados en la literatura con el propósito de obtener la mayor precisión diagnóstica y de extensión de la enfermedad para evitar así una cirugía innecesaria en casos no susceptibles de ser resecados

Carcinoma of the pancreas is a neoplasm with a poor prognosis that is diagnosed in the advanced stages in most patients. Given that surgical resection is the only potentially curative treatment for this disease, it is of the utmost importance to appropriately select the group of patients with initial stage pancreatic tumors that have not extended and can therefore be resected. Several different imaging techniques can be used for this purpose: ultrasonography (US), computed tomography (CT), magnetic resonance (MR), as well as the recent additions of endoscopic ultrasonography (EUS) and positron emission tomography (PET). Other techniques, such as laparoscopy and laparoscopic ultrasonography, also play a role in the diagnosis and staging of these patients. Continual technological developments in each of the above-mentioned techniques have led to reiterated updates in the scientific literature throughout the last two decades. This review aims to evaluate each of these techniques and present diagnostic algorithms reflected in the literature in order to achieve the greatest diagnostic accuracy in determining the extent of the disease so that unnecessary surgery can be avoided in cases not susceptible to resection

Diagnóstico y estadificación del carcinoma de páncreas (II) / Diagnosis and staging of carcinoma of the pancreas (II)

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[Living donor kidney transplantation: helical CT evaluation of candidates]. / Trasplante renal de donante vivo: evaluación de los candidatos mediante TC helicoidal.

OBJECTIVES: Computed tomography (CT) is a diagnostic tool that has won acceptance in the past years for the vascular evaluation of living renal donor (LRD) candidates. We show the findings observed in a series of 102 candidates consecutively evaluated in our centre and present the correlation with the surgical data obtained in those individuals finally operated. METHODS: From May 1995 to June 2005, 102 LRD candidates were evaluated with CT. Eighteen were also studied with digital subtraction angiography (DSA). Fifty-eight donors underwent nephrectomy. Prevalence of arterial and venous variants found on CT exams were analyzed, as well as the correlation with surgical and DSA data when they were obtained. RESULTS: Forty-four percent candidates showed multiple renal arteries at least in one kidney. Seventy-one percent of right kidneys and 76% of left kidneys had a single arterial pedicle. Early branching was observed in 7.8% and 15.7% in right and left kidneys respectively. Venous variants were present in 17.5% and the 13.7% in right and left sides respectively. Sensitivity, specificity and accuracy of CT to detect accessory arteries were 89%, 100% and 97% respectively when it was compared to DSA. Correlation with surgical data raised 93% for the presence of arterial variants. CONCLUSIONS: Vascular variants in renal pedicle showed a high prevalence. Helical CT can effectively achieve all the information required prior to surgery as a sole imaging procedure in LRD candidates.

Preoperative and intraoperative assessment of myometrial invasion and histologic grade in endometrial cancer: role of magnetic resonance imaging and frozen section.

The objective of this study was to determine the value of myometrial invasion by magnetic resonance imaging (MRI), histologic typing and grading by endometrial biopsy, and the intraoperative evaluation of both parameters by frozen section in the evaluation of endometrial cancer. The preoperative and intraoperative records of 180 patients with endometrial cancer were used to compare the preoperative endometrial biopsy, the myometrial invasion by MRI, and the intraoperative frozen sections, with the final histopathologic findings. The preoperative endometrial biopsy gave us the tumor histologic type and grade. MRI gave us the depth of myometrial invasion. The evaluation of intraoperative frozen sections gave us the tumor histologic type, the tumor grade, and also the myometrial invasion. Patients were classified as low risk (grade 1 and 2, and myometrial invasion <50%) and high risk (grade 3 or myometrial invasion >50%). Standard statistical calculations were used. Evaluation of the tumor grade by preoperative biopsy has a sensitivity and a specificity of 75% and 95%, respectively. Evaluation of the tumor grade by intraoperative biopsy has a sensitivity and a specificity of 40% and 98%, respectively. Evaluation of the depth of myometrial invasion with MRI has a sensitivity and a specificity of 79% and 82%, respectively. Evaluation of the depth of myometrial invasion with intraoperative frozen sections has a sensitivity and a specificity of 74% and 95%, respectively. Evaluation of all four of the parameters together has a sensitivity and a specificity of 80% and 82%, respectively with a kappa of 0.621. In our opinion, the combination of preoperative biopsy and intraoperative frozen section is the best way to decide whether a lymphadenectomy is necessary with a low rate of understaging patients. MRI would have a fringe benefit in these patients.

Trasplante renal de donante vivo: evaluación de los candidatos mediante TC helicoidal / Living donor kidney transplantation: helical CT evaluation of candidates

Introducción y objetivos: La tomografía computarizada (TC) ha ganado aceptación en los últimos años en la evaluación vascular de los candidatos a donante vivo de riñón (DVR). Presentamos los hallazgos observados en una serie consecutiva de 102 candidatos y la correlación hallada con los datos quirúrgicos en los individuos que fueron intervenidos. Métodos: Desde Mayo de1995 hasta Junio de 2005 fueron evaluados mediante TC 102 candidatos a DVR. En 18 de ellos se realizó también angiografía por sustracción digital (ASD). Cincuenta y ocho candidatos fueron finalmente nefrectomizados para la donación. Se han analizado la prevalencia de variantes arteriales y venosas en los estudios TC realizados, así como su correlación con los datos de la ASD y la cirugía. Resultados: El 44% de los candidatos presentaron arterias renales supernumerarias en al menos un riñón. El 71% de riñones derechos y el 76% de riñones izquierdos tenían pedículo único. La presencia de bifurcaciones precoces fue del 7,8% y del 15,7% en cada lado y la de variantes venosas en el 17,5% y en el 13,7% en cada lado respectivamente. La sensibilidad de la TC en relación a la ASD para detectar pedículo arterial múltiple fue del 89%, la especificidad del 100% y la precisión diagnóstica del 97%. La correlación observada entre la cirugía y la TC en cuanto a la presencia de variantes arteriales fue del 93%. Conclusiones: Las variantes de la normalidad en el pedículo vascular renal tienen elevada prevalencia. La TC helicoidal permite obtener toda la información morfológica necesaria para la cirugía con elevada efectividad y en una sola sesión en los candidatos a DVR

Objectives: Computed tomography (CT) is a diagnostic tool that has won acceptance in the past years for the vascular evaluation of living renal donor (LRD) candidates. We show the findings observed in a series of 102 candidates consecutively evaluated in our centre and present the correlation with the surgical data obtained in those individuals finally operated. Methods: From May 1995 to June 2005, 102 LRD candidates were evaluated with CT. Eighteen were also studied with digital subtraction angiography (DSA). Fifty-eight donors underwent nephrectomy. Prevalence of arterial and venous variants found on CT exams were analyzed, as well as the correlation with surgical and DSA data when they were obtained. Results: Forty-four percent candidates showed multiple renal arteries at least in one kidney. Seventy-one percent of right kidneys and 76% of left kidneys had a single arterial pedicle. Early branching was observed in 7.8% and 15.7% in right and left kidneys respectively. Venous variants were present in 17.5% and the 13.7% in right and left sides respectively. Sensitivity, specificity and accuracy of CT to detect accessory arteries were 89%, 100% and 97% respectively when it was compared to DSA. Correlation with surgical data raised 93% for the presence of arterial variants. Conclussions: Vascular variants in renal pedicle showed a high prevalence. Helical CT can effectively achieve all the information required prior to surgery as a sole imaging procedure in LRD candidates

Port-site metastasis after laparoscopic surgery for endometrial carcinoma: two case reports.

BACKGROUND: Although studies have reported good results with laparoscopic-assisted vaginal hysterectomy (LAVH) to treat endometrial cancer, it has been associated with recurrent disease at trocar insertion sites. Long-term follow-up is necessary to detect possible adverse effects of this technique. CASES: We present two case reports of stage IIB endometrial cancer with port-site metastasis 39 and 48 months after initial surgery with LAVH. CONCLUSION: Although LAVH is a good technique to treat patients with endometrial cancer, port-site metastasis is a possible complication and should be taken into consideration until a randomized study shows the long-term benefits and risks of laparoscopic over standard treatment.

[Hospital registry of pancreatic tumors. Experience of the Hospital Clínic in Barcelona (Spain)]. / Registro hospitalario de tumoraciones pancreáticas. Experiencia del Hospital Clínic de Barcelona.

OBJECTIVE: To describe the characteristics of patients included in the pancreatic tumor registry of the Hospital Clínic of Barcelona. PATIENTS AND METHOD: All patients with pancreatic tumors attended between July 1990 and March 2003 were registered. Data collection included: age, gender, date of diagnosis, diagnosis, histology, size, location and tumor stage, and treatment. The correlation between tumor stage and age, date of diagnosis, and tumor location was also evaluated. RESULTS: Six hundred thirty patients with pancreatic tumors were included, representing an incidence of 60 patients/year. The mean age was 66 years and the male-to-female ratio was 1,18:1. The most frequent lesion was malignant tumor of the pancreas (92%), and the most frequent histological type was pancreatic ductal adenocarcinoma (73%). The most frequent location was the head of the pancreas (64%). In 28% of the patients, pancreatic cancer was diagnosed in stage I and II. Resection was performed in 31% of patients, whereas 48% of the patients received no treatment. The ratio between local (stage I)/disseminated (stage IV) disease was 0,34. The ratio between stage I/IV increased with age, diagnosis prior to 1994, and tumor location in the head of the pancreas. CONCLUSION: Hospital tumor registries can be used to define the profile of the attended population, which can help to delineate the best diagnostic-therapeutic strategy and can be useful in clinical research.

[Evaluation of the efficacy and efficiency of a multidisciplinary unit for the treatment of patients with colorectal cancer]. / Evaluación de la eficacia y eficiencia de una unidad multidisciplinaria para la atención de pacientes con cáncer colorrectal.

INTRODUCTION: Because of the increased complexity of the diagnostic-therapeutic approach to colorectal cancer (CRC), these patients should be managed in specialized multidisciplinary units. The aim of this study was to evaluate the efficacy and efficiency of a CRC unit (CRCU) in the diagnostic-therapeutic management of these patients. PATIENTS AND METHODS: Two groups of 50 patients with colon cancer treated in our center before and after the implementation of the CRCU were selected. Fulfillment with the protocol in terms of tumoral staging, surgical and adjuvant treatment, follow-up, interval until treatment, hospital stay, morbidity and early mortality, and the overall duration of the diagnostic-therapeutic process was analyzed. In addition, clinical workload was evaluated and a cost-minimization analysis was performed. RESULTS: The CRCU reduced the interval until surgery (20.3 12.0 vs 28.0 20.4 days; p = 0.05), hospital stay (9.8 7.7 vs 14.5 9.3 days: p = 0.01), the time to the start of adjuvant treatment (29.4 10.2 vs 39.7 19.8 days; p = 0.03) and the overall duration of the process (60.4 23,8 vs 82.1 46.1 days; p = 0.05), representing a saving of 978.85 E per patient. This improvement took place despite an increase in clinical workload (24% in 5 years in relation to the number of admissions) and had no effect on morbidity (26 vs 24%; NS) or immediate mortality (6 vs 4%; NS). CONCLUSION: Specialized multidisciplinary units increase the efficacy and efficiency of the management of patients with CRC.

Imported histoplasmosis in Spain.

Histoplasma capsulatum is a dimorphic fungus endemic in the American continent but not in Europe, where cases are usually imported. Its favorite habitat is in warm humid soils. Guano from birds and bats enhance the sporulation of the mycelial phase.1 Man acquires H. capsulatum through inhalation of spores. Most people infected by this fungi remain asymptomatic, but around 10-50% can start an illness ranging from acute pulmonary histoplasmosis to chronic histoplasmosis. In both, there is close clinical resemblance to pulmonary tuberculosis. Immunodepressed patients undergo a more severe form of the disease, usually presenting in the acute disseminated form. We present seven immunocompetent patients with histoplasmosis acquired after traveling to several American countries.

Atypical retroperitoneal fibrosis: MRI findings.

A case of retroperitoneal fibrosis with an unusual perirenal involvement diagnosed at MR imaging is reported. Other conditions, such as metastatic disease or lymphoma, may be considered especially when the initial presentation is not typical. Imaging modalities in this condition are discussed.

[Obstructive apnea syndrome during sleep secondary to a pharyngeal lymphoma. Improvement with continuous pressure treatment of the upper airway]. / Síndrome de apneas obstructivas durante el sueno (SAOS) secundario a un linfoma faríngeo. Mejoría con tratamiento con presión continua de la vía aérea superior (CPAP).

Obstructive sleep apnea syndrome (OSAS) is characterized by multiple episodes of upper airway (UA) obstruction during sleep. Patients experience daytime hypersomnia, sluggishness and inability to concentrate; snoring at night is common. We report the case of a man with Hodgkin's lymphoma without full remission and with pharyngeal recidivism leading to OSAS. He experienced marked diurnal hypersomnia accompanied by behavior disorders. Examination revealed flow-volume OSAS, suggesting UA instability. Cervical computed tomography showed a prevertebral lymphomatous mass in the pharynx causing significant UA compression. UA size increased considerably after use of continuous positive airway pressure (CPAP), which normalized sleep and produced significant relief of symptoms. Later, after chemotherapy, OSAS resolved and the patient was able to abandon CPAP treatment.

[Hepatic mesenchymatous hamartoma presenting in an adult patient]. / Hamartoma mesenquimatoso hepático de presentación en la edad adulta.

Mesenchymatous hamartoma is a benign liver tumor characteristically found in childhood, particularly during the first two years of life. A case of mesenchymatous hamartoma detected in a 23-year-old female during a study for non specific abdominal disturbances is presented. Imaging techniques showed a large mass in the right hepatic lobe with hypodense areas of cystic appearance. Pathologic study demonstrated the characteristic mixoid mesenchymatous component with areas of cyst formation and rests of liver tissue inside the tumor. Despite its rarity in adults this case demonstrates the need to consider mesenchymatous hamartoma in the differential diagnosis of hepatic masses in adults, particularly when radiologic examination demonstrates cystic components.