Central nervous system prophylaxis with intrathecal liposomal cytarabine in a subset of high-risk patients with diffuse large B-cell lymphoma receiving first line systemic therapy in a prospective trial.

The dissemination in the central nervous system (CNS) is an uncommon but fatal complication occurring in patients with diffuse large B-cell lymphoma (DLBCL). Standard prophylaxis has been demonstrated to reduce CNS relapse and improve survival rates. Intrathecal (IT) liposomal cytarabine allows maintaining elevated drug levels in the cerebrospinal fluid for an extended period of time. Data on the efficacy and safety of liposomal cytarabine as CNS prophylaxis in patients with DLBCL are still insufficient. The objective of the present study was to evaluate the effectiveness and safety of the prophylaxis with IT liposomal cytarabine in prevention of CNS relapse in high-risk patients with DLBCL who were included in a trial of first line systemic therapy with 6 cycles of dose-dense R-CHOP every 14 days. Twenty-four (18.6 %) out of 129 patients were identified to have risk factors for CNS involvement, defined as follows: >30 % bone marrow infiltration, testes infiltration, retroperitoneal mass ≥10 cm, Waldeyer ring, or bulky cervical nodes involvement. Liposomal cytarabine (50 mg) was administered by lumbar puncture the first day of the 1st, 2nd, and 6th cycle of R-CHOP14 scheme. Among 70 IT infusions, grade 3-4 adverse events reported were headache (one patient) and nausea/vomiting (one patient). With a median follow-up of 40.1 months, no CNS involvement by DLBCL was observed in any patient. In conclusion, IT liposomal cytarabine is safe, feasible, and effective for CNS prophylaxis, causing few associated risks and little discomfort to patients with DLBCL.

Bendamustine as salvage treatment for patients with relapsed or refractory mantle cell lymphoma patients: a retrospective study of the Spanish experience.

Patients with mantle cell lymphoma (MCL) have an adverse outcome after relapse. Bendamustine has demonstrated a good efficacy and toxicity profile in previously reported trials. In this study, we present a retrospective analysis of the Spanish experience in relapsed/refractory MCL treated with bendamustine in combination or alone with the objective of knowing the efficacy and toxicity profile of this treatment in our current clinical practice. Fifty eight patients were registered: 67 % male with median age of 71 years, and 2 is the median number of previous lines. The most frequent bendamustine regimen was bendamustine plus rituximab (83 %). The median number of cycles was 5 (range 1-8). The overall response rate was 84 % with 53 % of complete response/unconfirmed complete response (CR/uCR). Median progression-free survival (PFS) was 16 months (95 % confidence interval (CI) 13.3-18.8), and for patients who achieved CR/uCR, it was 33 months (95 % CI 11.1-54.2). Median overall survival (OS) was 30 months (95 % CI 25.6-34.9). For PFS, only blastoid histology and not achieving CR after bendamustine had a significant negative impact on the univariate and multivariate analyses (p < 0.05). Nevertheless, for OS, only an elevated lactate dehydrogenase (LDH) had negative impact on both, univariate and multivariate analyses (p < 0.05). Only one case of treatment-related mortality in a 79-year-old patient with very bad performance status was reported. In 280 cycles, 12 (4 %) hospitalizations for febrile neutropenia were reported. In our population, bendamustine has been a good salvage treatment with a favorable toxicity profile in a non selected and heavily pretreated population of patients with MCL.

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The genetic interaction between VKORC1 c1173t and calumenin a29809g modulates the anticoagulant response of acenocoumarol.

BACKGROUND: The efficacy of oral anticoagulant therapy is largely conditioned by both environmental and genetic factors. OBJECTIVES: To attempt to define the genetic profile involved in the response to this treatment. PATIENTS AND METHODS: We selected 100 men younger than 75 years, with non-valvular atrial fibrillation, who started anticoagulation with acenocoumarol following the same protocol: 3 mg for three consecutive days. Then, doses were individually adjusted to achieve a steady International Normalized Ratio (INR). The basal plasma level and the level after 3 days were obtained, and the INR was determined. We studied five functional polymorphisms: FVII -323 Del/Ins, CYP2C*9, VKORC1 c1173t, calumenin (CALU) R4Q and CALU a29809g. The dose required for a steady INR was also recorded. RESULTS: Only the VKORC1 genotype had significant impact on the efficacy of therapy. Carriers of the 1173t allele were significantly more sensitive to therapy for 3 days [INR 2.07 (1.59-2.87) vs. 1.74 (1.30-2.09); P = 0.015] and they needed lower acenocoumarol doses to stabilize their INR (15.8 +/- 5.6 vs. 19.5 +/- 6.0 mg week(-1); P = 0.004). Its effect was exacerbated by combination with the CALU a29809g polymorphism. Carriers of both variants (27% of the sample) achieved the highest INR [2.26 (1.70-3.32)] and required the lowest dose (14.1 +/- 5.1 mg week(-1)). This genetic profile was particularly relevant in patients with INR >or= 3.5 at the start of therapy (P = 0.005; odds ratio = 6.67, 95% confidence interval = 1.32-37.43). CONCLUSIONS: Our results suggest that CALU a29809g might be a new genetic factor involved in the pharmacogenetics of anticoagulant therapy, and confirm that specific genetic profiles defined by different polymorphisms will determine the initial response and dose required to achieve a stable and safe INR.

[Enterovesical fistula in Crohn disease. An infrequent presentation]. / Fístula enterovesical en enfermedad de Crohn. Una presentación poco frecuente.

Herein we describe a case of enterovesical fistula in a patient with Crohn's disease that presented exclusively as urinary symptoms. The patient had no known history of GI disorders. The clinical features, natural history and treatment of enterovesical fistula in Crohn's disease are discussed.

[Biliary ileus: enterolithotomy only or radical surgery?]. / Ileo biliar: sólo enterolitotomía o cirugía definitiva?

Eleven patients, 8 women and 3 men, mean age 69.9 years (range 54-81) were operated with a gallstone ileus during a seven years period. Echography and barium study of small bowel were made in 8 and 2 patients, and gave a diagnostic rate of 37% and 100%, respectively. A preoperative diagnosis was made in 72.2% of cases, simple enterolithotomy was made in 8 cases and in three cases a definitive treatment of biliary pathology was added. There was no mortality and a major complication was observed in 1 patient without biliary surgery (evisceration and recurrence of biliary ileus); no major complications were seen in patients with primary biliary surgery. With a careful, selection, surgery can be made without mortality nor morbidity.

[3 cases of postpartum acquired factor VIII inhibitor]. / Tres casos de inhibidor del factor VIII adquirido postparto.

Three cases of postpartum acquired factor VIII inhibitors were seen in our hospital between 1981 and 1989. The clinical picture, which was mild in one patient and severe in two, began several months after delivery (four to nine). After treatment with methylprednisolone, good clinical response was obtained in the three cases. However, normal values of factor VIII:C were obtained more easily with the higher doses of steroids. A new pregnancy and delivery in one of our patients did not induce the reappearance of the inhibitor after several years of follow-up.

[Surgical management of polycystic liver]. / Manejo quirúrgico de la poliquistosis hepática.

Three patients with polycystic liver disease, needing surgical treatment, are reported. In two cases surgical indication was continuous pain and compressive symptoms from an abdominal mass, and in the third case was an infection of the cyst. All patients were treated by fenestration combined with resection of cysts. The postoperative course was uneventful in two patients, but hepatic failure developed in the third case, needing hepatic transplantation. This patient died during this operation. The complications of the disease and its surgical management are revised.

[Hepatic mesenchymal hamartoma]. / Hamartoma mesenquimal hepático.

A case is presented of a 10-year-old female twin with a cystic liver mass that debuted as a painless epigastric mass. The lesion was excised by hepatectomy of segments II and III, confirming in the review of the cavity the presence of a common mesentery with cecocolonic malposition. The postoperative course was normal and clinical and echographic study of her twin sister disclosed no anomalies. The anatomopathologic study of the lesion revealed a tumor of difficult filiation that presented features of mesenchymal hamartoma together with others of biliary cystadenoma. The amount and nature of the stromal component, together with the patient's age at appearance, made us classify the case as mesenchymal hamartoma. The morphologic findings observed seem to support the histopathologetic theory of a congenital origin.

Results of fundic patch operation for severe stricture of the esophagus.

Eighteen patients ranging in age from 32-82 years with benign distal esophageal stricture underwent and survived fundic patch operation. Twelve of these patients had undergone esophageal dilatation but without success. Five had had surgery for hiatal hernia using Hill, Belsey or Lortat-Jacob techniques. Middle laparotomy was done in five and left thoracotomy in thirteen. A fundic patch with a 270 degrees fundoplication was performed in seven and a fundic patch with 360 degrees fundoplication in the remaining eleven. The average hospital stay was 12.3 days. Dysphagia disappeared in seventeen and persisted for eight months in one patient. Three patients required instrumental dilatation for a few months. Endoscopic examination, pH study and X-ray fluoroscopy were done. Gastroesophageal reflux was nil in patients treated with Nissen's 360 degrees fundoplication and three of these 7 patients without Nissen's fundoplication had gastroesophageal reflux. Epithelialization of the patched esophageal wound was evident 6 months after the operation.