Association of HER2DX with pathological complete response and survival outcomes in HER2-positive breast cancer.

BACKGROUND: The HER2DX genomic test predicts pathological complete response (pCR) and survival outcome in early-stage HER2-positive (HER2+) breast cancer. Here, we evaluated the association of HER2DX scores with (i) pCR according to hormone receptor status and various treatment regimens, and (ii) survival outcome according to pCR status. MATERIALS AND METHODS: Seven neoadjuvant cohorts with HER2DX and clinical individual patient data were evaluated (DAPHNe, GOM-HGUGM-2018-05, CALGB-40601, ISPY-2, BiOnHER, NEOHER and PAMELA). All patients were treated with neoadjuvant trastuzumab (n = 765) in combination with pertuzumab (n = 328), lapatinib (n = 187) or without a second anti-HER2 drug (n = 250). Event-free survival (EFS) and overall survival (OS) outcomes were available in a combined series of 268 patients (i.e. NEOHER and PAMELA) with a pCR (n = 118) and without a pCR (n = 150). Cox models were adjusted to evaluate whether HER2DX can identify patients with low or high risk beyond pCR status. RESULTS: HER2DX pCR score was significantly associated with pCR in all patients [odds ratio (OR) per 10-unit increase = 1.59, 95% confidence interval 1.43-1.77; area under the ROC curve = 0.75], with or without dual HER2 blockade. A statistically significant increase in pCR rate due to dual HER2 blockade over trastuzumab-only was observed in HER2DX pCR-high tumors treated with chemotherapy (OR = 2.36 (1.09-5.42). A statistically significant increase in pCR rate due to multi-agent chemotherapy over a single taxane was observed in HER2DX pCR-medium tumors treated with dual HER2 blockade (OR = 3.11, 1.54-6.49). The pCR rates in HER2DX pCR-low tumors were ≤30.0% regardless of treatment administered. After adjusting by pCR status, patients identified as HER2DX low-risk had better EFS (P < 0.001) and OS (P = 0.006) compared with patients with HER2DX high-risk. CONCLUSIONS: HER2DX pCR score and risk score might help identify ideal candidates to receive neoadjuvant dual HER2 blockade in combination with a single taxane in early-stage HER2+ breast cancer.

[Endovascular treatment of intracranial venous sinus stenosis in intracranial hypertension: three case reports and a discussion of the literature]. / Tratamiento endovascular de la estenosis de los senos venosos intracraneales en la hipertensión intracraneal: descripción de tres casos y discusión de la bibliografía.

INTRODUCTION: Idiopathic intracranial hypertension is an entity with an incidence of approximately 1.2: 100,000 inhabitants/year. It affects in a greater proportion obese women and women of childbearing age. Headache is the most characteristic symptom, followed by visual disturbances. In recent years, the diagnosis of dural sinus stenosis has increased in cases of intracranial hypertension resistant to conventional treatment. For this reason, the development of endovascular therapy as a therapeutic option in selected patients is booming. CASE REPORTS: We present three cases of intracranial hypertension secondary to dural sinus stenosis, diagnosed and treated in our hospital. Despite the establishment of adequate diuretic treatment and the performance of invasive procedures to bypass the cerebrospinal fluid, they persisted with neurological symptoms and visual deficits. After verifying that they fulfilled the requirements described in the literature, they underwent intracranial stenting, with satisfactory results in all of them, achieving the disappearance of the headache and recovery of visual acuity. CONCLUSION: Stenting of dural sinus stenosis as a cause of intracranial hypertension is an increasingly used technique, which has presented favorable results. Studies are necessary to know its long-term impact.

TITLE: Tratamiento endovascular de la estenosis de los senos venosos intracraneales en la hipertensión intracraneal: descripción de tres casos y discusión de la bibliografía.Introducción. La hipertensión intracraneal idiopática es una entidad con una incidencia anual aproximada de 1,2 por cada 100.000 habitantes. Afecta en mayor proporción a mujeres obesas y en edad fértil. La cefalea es el síntoma más característico, seguido de las alteraciones visuales. En los últimos años, se ha incrementado el diagnóstico de la estenosis de los senos durales en los casos de hipertensión intracraneal resistentes al tratamiento convencional. Por ello, se encuentra en auge el desarrollo de la terapia endovascular como opción terapéutica en pacientes seleccionados. Casos clínicos. Se presentan tres casos de hipertensión intracraneal secundaria a estenosis de los senos durales, diagnosticados y tratados en nuestro hospital. A pesar de la instauración del adecuado tratamiento diurético y de la realización de procedimientos invasivos de derivación del líquido cefalorraquídeo, persistían la clínica neurológica y el déficit visual. Tras comprobar que cumplían los requisitos descritos en la bibliografía, se sometieron a la implantación de stent intracraneal (stenting), con resultado satisfactorio en todos ellos, logrando la desaparición de la cefalea y la recuperación de la agudeza visual. Conclusión. El stenting de la estenosis de los senos durales como causa de hipertensión intracraneal es una técnica cada vez más utilizada que ha presentado resultados favorables. Es necesaria la realización de estudios para conocer su impacto a largo plazo.

Correlation of 18F-FDG uptake on PET/CT with Ki67 immunohistochemistry in pre-treatment epithelial ovarian cancer. / Correlación de la captación de 18F-FDG de la PET/TC con el Ki67 de la inmunohistoquímica en el cáncer epitelial de ovario pretratamiento.

OBJECTIVE: Standardised uptake value (SUV) and volumetric parameters such as metabolic tumour volume (MTV) and total lesion glycolysis (TLG) from 18F-FDG PET/CT are useful criteria for disease prognosis in pre-operative and post-treatment epithelial ovarian cancer (EOC). Ki67 is another prognostic biomarker in EOC, associated with tumour aggressiveness. The aim of this study is to evaluate the association between 18F-FDG PET/CT measurements and Ki67 in pre-treatment EOC to determine if PET/CT parameters could non-invasively predict tumour aggressiveness. MATERIAL AND METHODS: A pre-treatment PET/CT was performed on 18 patients with suspected or newly diagnosed EOC. Maximum SUV (SUVmax), mean SUV (SUVmean), whole-body MTV (wbMTV), and whole-body TLG (wbTLG) with a threshold of 30% and 40% of the SUVmax were obtained. Furthermore, Ki67 index (mean and hotspot) was estimated in tumour tissue specimens. Immunohistochemical findings were correlated with PET parameters. RESULTS: The mean age was 57.0 years old (standard deviation 13.6 years). A moderate correlation was observed between mean Ki67 index and SUVmax (r=0.392), SUVmean 30% (r=0.437), and SUVmean 40% (r=0.443), and also between hotspot Ki67 index and SUVmax (r=0.360), SUVmean 30% (r=0.362) and SUVmean 40% (r=0.319). There was a weaker correlation, which was inversely negative, between mean and hotspot Ki67 and volumetric PET parameters. However, no statistical significant differences were found for any correlations. CONCLUSIONS: SUVmax and SUVmean were moderately correlated with Ki67 index, whereas volumetric PET parameters overall, showed a weaker correlation. Thus, SUVmax and SUVmean could be used to assess tumour aggressiveness in pre-treatment EOC.

Diagnosis of gynecological pseudoaneurysms and embolization with cyanoacrylate. / Diagnóstico y embolización con cianoacrilato de pseudoaneurismas de origen ginecológico.

Pseudoaneurysms of the uterine artery are an uncommon cause of severe gynecological bleeding secondary to surgical manipulation of the pelvis or to instrumental delivery. The different imaging techniques are of vital importance in the diagnosis. Angiography is the technique used for confirmation and also for treatment in many cases. Endovascular treatment by embolizing the pseudoaneurysm has become established as the treatment of choice, making it possible to avoid hysterectomy in women of childbearing age. This article presents two cases of gynecological bleeding due to pseudoaneurysms (one secondary to surgery and one secondary to childbirth) that were embolized in a novel way using cyanoacrylate.

Sequential treatment with immunotherapy and BRAF inhibitors in BRAF-mutant advanced melanoma.

PURPOSE: Immunotherapy (IT) agents and BRAF inhibitors (BRAFi) are effective treatments for patients with advanced BRAF-mutant melanoma although the optimal sequence remains to be elucidated. The aim of this study was to compare the outcomes of two different cohorts of patients treated with BRAFi first, then IT or the reverse sequence. PATIENTS AND METHODS: This is a retrospective study on two groups of patients: a cohort was treated first with BRAFi followed by immunotherapy (BRAFi-IT) and the other cohort with the reverse sequence (IT-BRAFi). Baseline characteristics and clinical outcomes were compared between the two cohorts. RESULTS: A total of 25 patients were included in the study. Sixteen patients were given BRAFi-IT sequence and nine received IT-BRAFi sequence. No differences were observed in the characteristics of patients prior to each treatment between cohorts. Objective response rate (ORR) achieved by BRAFi were not different among groups. ORR achieved by IT was higher when administered after BRAFi (43.8 vs 0 %). Survival rates at 1-2 years were similar in both cohorts and median overall survival was not different for BRAFi-IT and IT-BRAFi (log rank test p = 0.97). CONCLUSIONS: No differences were observed in OS between the two cohorts. These results support the indistinct use of IT or BRAFi as initial treatment in patients with metastatic BRAF-mutant melanoma, although higher rate of response to IT was observed when administered after BRAFi. Prospective randomized clinical trials are needed on this issue.

Prognostic value of (18)F-FDG PET/CT volumetric parameters in recurrent epithelial ovarian cancer.

OBJECTIVE: Metabolic tumour volume (MTV) and total lesion glycolysis (TLG) from (18)F-FDG PET/CT are emerging prognostic biomarkers in various solid neoplasms. These volumetric parameters and the SUVmax have shown to be useful criteria for disease prognostication in preoperative and post-treatment epithelial ovarian cancer (EOC) patients. The purpose of this study was to evaluate the utility of (18)F-FDG PET/CT measurements to predict survival in patients with recurrent EOC. MATERIAL AND METHODS: Twenty-six patients with EOC who underwent a total of 31 (18)F-FDG PET/CT studies for suspected recurrence were retrospectively included. SUVmax and volumetric parameters whole-body MTV (wbMTV) and whole-body TLG (wbTLG) with a threshold of 40% and 50% of the SUVmax were obtained. Correlation between PET parameters and progression-free survival (PFS) and the survival analysis of prognostic factors were calculated. RESULTS: Serous cancer was the most common histological subtype (76.9%). The median PFS was 12.5 months (range 10.7-20.6 months). Volumetric parameters showed moderate inverse correlation with PFS but there was no significant correlation in the case of SUVmax. The correlation was stronger for first recurrences. By Kaplan-Meier analysis and log-rank test, wbMTV 40%, wbMTV 50% and wbTLG 50% correlated with PFS. However, SUVmax and wbTLG 40% were not statistically significant predictors for PFS. CONCLUSION: Volumetric parameters wbMTV and wbTLG 50% measured by (18)F-FDG PET/CT appear to be useful prognostic predictors of outcome and may provide valuable information to individualize treatment strategies in patients with recurrent EOC.

Efficacy and complications in the use of self-expanding colonic stents: an analysis of 15 years' experience.

OBJECTIVE: To analyze the efficacy and safety of the procedure for placing self-expanding stents in the colon. To evaluate the factors associated with complications. To analyze the dose of radiation delivered in the procedure. MATERIAL AND METHODS: This was a retrospective descriptive study of 478 procedures done at a single center to place self-expanding metallic stents in the colon. A total of 423 nitinol stents and 79 stainless steel stents were placed. We included all colonic obstructions, of which 446 had malignant causes and 8 had benign causes. We excluded patients with intestinal perforation, severe colonic bleeding, short life expectancy, or lesions located less than 5 cm from the anus. We collected the dosimetric data and analyzed the technical success, clinical success, and complications during follow-up. RESULTS: The procedure was a technical success in 92.26% of cases (n=441) and a clinical success in 78.45% (n=375); complications occurred during follow-up in 18.5% of cases. Complications occurred more frequently with the stainless steel stents than with the nitinol stents (OR: 3.2; 95% CI: 1.8-5.7). The mean value of the dose area product was 35 Gy*cm(2). When instead of being done by the interventional radiologist working together with an endoscopist the procedure was done exclusively by the interventional radiologist, the time under fluoroscopy (p=0.001), dose area product (p=0.029), and kinetic energy released per unit mass (p=0.001) were greater. CONCLUSION: The procedure for placing self-expanding colonic stents is efficacious and safe with an acceptable rate of complications. The doses of radiation delivered were low, and the radiation doses and time under fluoroscopy were lower when the procedure was done together with an endoscopist.

[Clinical management of homocystinuria: case report and review of the literature]. / Homocistinuria; curso clínico y tratamiento dietético: a propósito de dos casos.

Homocystinuria is a congenital disorder of methyonine metabolism that leads to increased plasmatic, urinary and tissue deposits of methyonine and its main metabolite: homocysteine. Homocysteine deposits are toxic for the skeletal system (osteoporosis), the eyes (lens dislocation), central nervous system (seizures, psychiatric disorders) and also induce vascular damage (stroke and other cardiovascular events). This article reports two patients with homocystinuria in two siblings, followed by a concise review on the therapeutic strategies available for this disorder.

[Laparoscopic adrenalectomy. Five-year experience]. / Suprarrenalectomía laparoscópica. Experiencia de 5 años.

OBJECTIVE: Adrenal conditions requiring surgery are uncommon and are usually seen in several surgical departments. Our experience in laparoscopic management of adrenal pathology after almost five years of use of laparoscopy for retroperitoneal conditions at our center is reported. MATERIALS AND METHODS: A total of 37 laparoscopic adrenalectomies were performed over 53 months for benign and malignant conditions. The transperitoneal approach was used in most cases (97%) because of the greater surgeon experience with this route. Pregnancy and suspected periadrenal infiltration were considered as absolute contraindications. RESULTS: Mean operating time was 90 minutes, mean intraoperative bleeding 80 ml, and mean hospital stay was 2 days. The main complication was one death. A malignancy was found in 4 patients (10%), while all other patients (90%) had a benign condition, including 8 pheochromocytomas. CONCLUSIONS: Laparoscopy is considered to be the gold standard for benign adrenal conditions. When the malignant mass is a single metastasis from a primary tumor, the laparoscopic approach appears to be reliable. When the malignant lesion is a primary adrenal tumor, laparoscopic management is more controversial, although the results reported by experienced surgeons in their series appear to be adequate.

[Postsurgical chylous ascites: case report and literature review]. / Tratamiento dietético de la ascitis quilosa postquirúrgica: caso clínico y revisión de la literatura.

Chylous ascites derives from chyle leakage into the peritoneal cavity, either due to rupture or obstruction of abdominal lymphatic vessels. The main clinical sign is abdominal distention, while diagnosis requires the presence of triglycerides in ascitic fluid. Neoplasms are the most common cause of chylous ascites, although less common causes, such as abdominal surgery, should also be considered. The mainstay of therapy is hyperproteic diet with fat restriction and middle-chain triglycerides. Parenteral nutrition is reserved for cases in which dietary treatment fails to restore an optimal nutritional status or is contraindicated, whereas surgery is considered for patients that are deemed refractory to conservative therapy. We present a case of chylous ascites secondary to retroperitoneal lymphadenectomy.

[Diabetic foot and risk factors]. / Factores de riesgo y pie diabético.

OBJECTIVE: To identify clinic and metabolic risk factors for diabetic neuropathy and peripheral arterial disease in patients evaluated in a diabetic foot unit care. METHOD: From 2000 to 2005 we evaluated the presence of diabetic neuropathy (monofilament, tuning fork and Boulton's clinic scale) and peripheral arterial disease (ankle-brachial index and toe-brachial index) in 304 diabetic patients. We classified patients in four groups: patients without pathology (normal group), with neuropathy (neuropathic group), with peripheral arterial disease (vascular group) and with both pathologies (mixed group) and we compared the characteristics of each group. We analysed other poblational characteristics: age, gender, type of diabetes, duration, microvascular and macrovascular complications, hypertension, smoking habit, antiagregation and mean HbA1c in the last year. RESULTS: Age, frequency of hypertension and coronary disease were significantly higher (p < 0.005) in vascular and mixed group than in normal group (63 +/- 13 and 65 +/- 10 vs. 55 +/- 14; 69.2 and 70.3 vs. 45.5%; 46,2% and 39.2% vs 23.8%, respectively). Frequency of retinopathy, nephropathy and HbA1c were significantly higher (p < 0.05) in neuropathic and mix group than in normal group (62.5 and 66.2 vs. 32.7%; 45.3 and 47.3 vs. 24.8%; 8.1 +/- 1.6 and 8.0 +/- 1.3 vs 7.4 +/- 1.2 respectively). CONCLUSION: This study indicates that the development of diabetic neuropathy is related with worse metabolic control and the presence of other microvascular complications; while age, hypertension and coronary disease are risk factors for peripheral arterial disease.

Increased intrahepatic cyclooxygenase 2, matrix metalloproteinase 2, and matrix metalloproteinase 9 expression is associated with progressive liver disease in chronic hepatitis C virus infection: role of viral core and NS5A proteins.

BACKGROUND: Cyclooxygenase 2 (COX-2) and matrix metalloproteinases (MMPs) have been implicated in tissue injury and fibrogenesis in animal models but little is known regarding their role in hepatitis C virus (HCV) related liver disease in humans. AIMS: To characterise the intrahepatic expression pattern of COX-2 and MMPs in chronic HCV infection and determine whether HCV core and NS5A proteins could promote their expression in cultured hepatocyte derived cell lines. PATIENTS: Thirty two anti-HCV+ and 10 anti-HCV- patients were studied. METHODS: Western blot, reverse transcription-polymerase chain reaction (RT-PCR), enzyme immunoassay, and immunohistochemistry were used to assess the expression pattern of COX-2 and MMPs in liver biopsy samples from all patients. COX-2 gene expression and MMP-9 protein levels were also determined by immunoblot, RT-PCR, and luciferase assays in core and NS5A transfected hepatocyte derived cells. RESULTS: The intrahepatic expression level of COX-2, MMP-2, and MMP-9 was significantly higher in HCV+ than in HCV- patients, increasing with the fibrotic stage of liver disease. We further demonstrated that COX-2 mRNA, protein, and activity were induced in resting and activated core and NS5A transfectants. Both viral proteins induced transcriptional activity of the COX-2 gene promoter whereas core, but not NS5A, exerted an inducer effect on MMP-9 protein levels in cultured hepatocyte derived cells. CONCLUSIONS: Intrahepatic COX-2, MMP-2, and MMP-9 overexpression is associated with progressive hepatic fibrosis in chronic HCV infection, suggesting their pathogenic role in fibrogenesis. HCV core and NS5A proteins were able to upregulate COX-2 and MMP-9 gene expression in hepatocyte derived cells, providing a potential mechanism for hepatic fibrosis during chronic HCV infection.

[Ultrasound diagnosis of salivary gland tumors]. / Diagnóstico por ultrasonidos de los tumores de las glándulas salivares.

The ultrasonic diagnosis of salivary gland tumors can give a more accurate information than clinical data alone. For example, it will help differentiate intraglandular from extraglandular tumors and benign from malignant processes. We conducted a prospective study in 39 patients with parotidal or submaxillary tumors. Patients were evaluated with a physical exam and a with ultrasound. Results indicate that only 53.86% of the physical examinations were correct in their diagnosis compared to 87.18% of the those done by ultrasound. Specificity and sensibility for malignancy was 96.43% and 81.81% respectively. These results were similar to those reported by other authors. We conclude that the use of ultrasound techniques in the study of salivary gland pathology is well justified, due to its capacity to provide high resolution, improving clinical diagnosis.

[Pseudotumoral hepatic tuberculosis]. / Tuberculosis hepática pseudotumoral.

Liver infection as a result of tuberculosis is well known; there are several histological lesions, the most important being epithelioid cell granuloma. There are 3 anatomo-clinic variants: military or micronodular type, macronodular or pseudotumoral and pericanalicular of cholestatic. A case of a 66 year old male with a diagnosis of hepatic pseudotumoral tuberculosis, confirmed by means of a laparoscopy, is presented. The rareness of this particular presentation is discussed, as well as the difficult diagnosis due to confusion with primary or metastatic tumors of the liver.

[Intestinal parasitosis of the canine population in the principate of Asturias]. / Parasitosis intestinal en la población canina del Principado de Asturias.

A study is made of coprological samples from 354 dogs, 252 of them male and 102 female. Parasitism was found in 94 dogs (26.5%), of which 14 (15%) showed two or more associated parasites. The Councils with the highest degree of parasitism were: Peñamellera Baja (77.7%), Ribadedeva (57.1%), Castropol (53.8%), Ribadesella (50%), Piloña (46.6%), and Tapias de Casariego (44.4%). The parasites most frequently isolated were: Anciostoma Caninum (19.2%), Trichuris vulpis (8.2%), Cystoisospora canis (3%), Toxocara spp. (1.1%), and Toxascaris leonina (1.1%). The difference in the degree of parasitism in females over 1 year of age (26.6%), and of males over 1 year of age (19.6%) is statistically significant (p greater than 0.05). No eggs were found of Taenia spp., which points to the positive effects of the measures taken against the hydatid cyst, based on the biannual administration of Praziquantel to the canine population.