Recommendations on the use of azole antifungals in hematology-oncology patients.

The administration of antifungals for therapeutic and, especially, prophylactic purposes is virtually a constant in patients requiring hematology-oncology treatment. Any attempt to prevent or treat Aspergillus or Mucor infections requires the administration of some drugs in the azole group, which include voriconazole, posaconazole and isavuconazole, noted for their activity against these pathogens. One very relevant aspect is the potential risk of interaction when associated with one of the antineoplastic drugs used to treat hematologic tumors, with serious complications. In this regard, acalabrutinib, bortezomib, bosutinib, carfilzomib, cyclophosphamide, cyclosporine A, dasatinib, duvelisib, gilteritinib, glasdegib, ibrutinib, imatinib, nilotinib, ponatinib, prednisone, ruxolitinib, tacrolimus, all-transretinoic acid, arsenic trioxide, venetoclax, or any of the vinca alkaloids, are very clear examples of risk, in some cases because their clearance is reduced and in others because of increased risk of QTc prolongation, which is particularly evident when the drug of choice is voriconazole or posaconazole.

[Causes of conversion in laparoscopic surgery for gastroesophageal reflux disease: an analysis of our experience]. / Causas de conversión en la cirugía laparoscópica de la enfermedad por reflujo gastroesofágico: análisis de nuestra experiencia.

BACKGROUND: since its introduction in 1991 laparoscopic antireflux surgery has gained great success and popularity among surgeons, and now it is the gold standard for the treatment of gastroesophageal reflux disease (GERD). AIM: to identify and evaluate the causes of conversion in the laparoscopic surgery of GERD and hiatus hernia. MATERIAL AND METHODS: since January 1993 to August 2007 606 laparoscopic antireflux procedures were performed in our hospital. There were 296 women and 310 men with a median age of 53.5 years. The main indication for surgery was evidence of intractable or recurrent GERD symptoms after adequate medical treatment with associated hiatal hernia. The preoperative workup included manometry, pH-metry, oral endoscopy, and barium swallow. The surgical technique was mainly the Nissen-Rossetti procedure. RESULTS: mean postoperative hospital stay was 2.7 days. The operation had to be converted to an open procedure in 43 cases (7%). Conversions were more frequent in the first decade of the learning curve (26 vs. 17, p < 0.016), and fewer among the group of experts in advanced laparoscopic surgery (15 vs. 28, p < 0.017). In 17 cases conversions were due to an intraoperative complication whereas in 26 cases a conversion was done because of technical difficulties. Esophageal perforation and pneumothorax rates were 0.8 and 1%, respectively, and mortality and morbidity rates were 0.1 and 12%. CONCLUSION: the rate of conversion is acceptable and significantly decreases with surgeon experience.

Endoscopic treatment of oesophageal leiomyoma: four new cases.

BACKGROUND AND STUDY AIMS: The advent of endoscopic techniques in the last decades has produced a change in the approach of the oesophageal leiomyoma. The aim of the study is to explain our experience in the laparoscopic surgery of the oesophageal leiomyoma. MATERIALS AND METHODS: We realised a retrospective study of the oesophageal leiomyoma operated on in our centre by the endoscopic approach between 2001 and 2004. There were two females and two males. All were symptomatic and pyrosis was the most frequent symptom. The preoperative study was an oral endoscopy and barium swallow. In all the cases enucleation was performed, two by thoracoscopy and two by laparoscopy approach. RESULTS: The mean operating time was 230 min. No deaths or intraoperative complications occurred and there were no cases of conversion to open surgery either. The mean postoperative hospital stay was 3.25 days (range 2-4 days). There was no case of recurrence. CONCLUSIONS: The enucleation is an easier procedure and constitutes the therapy of choice of the oesophageal leiomyoma. We think that muscle borders should be closed after enucleation and that biopsy is not indicated preoperatively.

Long-term results and complications related to Crurasoft® mesh repair for paraesophageal hiatal hernias.

PURPOSE: The application of mesh-reinforced hiatal closure has resulted in a significant reduction in recurrence rates in comparison with primary suture repair. However, the use of meshes has not completely extended in all the cases of large paraesophageal hiatal hernias (LPHH) due to the complications related to them. The aim of this study is to present our long-term results and complications related to Crurasoft® mesh (Bard) for the treatment of LPHH. METHODS: From January 2004 to December 2014, 536 consecutive patients underwent open or laparoscopic fundoplication for gastroesophageal reflux disease or LPHH at Ramón y Cajal University Hospital. Primary simple suture of the crura and additional reinforcement with a Crurasoft® mesh (Bard) was performed in 93 patients (17.35 %). Radiologic hiatal hernia recurrence and mesh-related complications were investigated. RESULTS: Of the 93 patients undergoing mesh repair, there were 28 male and 65 female with a mean age of 67.27 years (range 22-87 years). Laparoscopic surgery was attended in 88.2 % of the cases, and open surgery in the rest 11.8 %. Mean operative time was 167.05 min (range 90-370 min). Median postoperative stay was 4.79 days (range 1-41 days). Conversion rate was 8.53 % (7 patients). Intraoperative complications were described in 10.75 % (10 patients), but all of them, except in one case, could be managed laparoscopically. Overall postoperative complications rate was 28 %. Early postoperative complications occurred in 11 patients (12 %), respectively, for grades 2 (6 cases), 3b (1 case) and 5 (4 cases) according to the Clavien-Dindo classification. Late postoperative complications occurred in 15 patients (16 %), respectively, for grades 1 (7 cases), 2 (2 cases), 3b (5 cases) and 5 (1 case) according to the Clavien-Dindo classification. Thirty day-mortality rate was 4.3 %. Mortality rate specific associated with the mesh was 1 %. Reoperation rate was 5.4 %. After a median follow-up of 76.33 months (range 3-130 months), 8 patients (9 %) developed a recurrent hiatal hernia. Mesh was removed in three cases (3.22 %). CONCLUSIONS: In our experience, the recurrence rate in patients with a Crurasoft® (Bard) is acceptable. However, the rate of postoperative complications and mortality is excessive. The use of meshes in the hiatus keeps on being controversial due to the severe complications related to them. It would be advisable to compare our results in the non-mesh group in terms of recurrences and complications, to determine if meshes in the hiatus should be given in these patients due to its high rate of complications.

Surgical treatment of esophageal leiomyoma: an analysis of our experience.

INTRODUCTION: leiomyoma is the most common benign esophageal neoplasm. Surgical treatment (enucleation) has traditionally been the therapy of choice. The advent of minimally invasive techniques has produced an increase in endoscopic approaches to the detriment of open surgery. OBJECTIVE: the aim of this study was to compare the results obtained with open surgery and with laparoscopic surgery in this kind of pathology. MATERIAL AND METHODS: we performed a retrospective study of all leiomyomas operated for in our center between 1986 and 2004, and obtained 9 cases of esophageal leiomyoma. Four were women and five men, between the ages of 40 and 70, with a mean age of 53.5 years. The most frequent symptoms were heartburn (5 cases), dysphagia (3 cases), and retrosternal pain (3 cases). Surgery was in all the cases an enucleation. An open approach was performed in 5 cases (3 thoracotomies and 2 laparotomies), and an endoscopic approach in 4 (2 thoracoscopies and 2 laparoscopies). RESULTS: the mean postoperative hospital stay was 5.12 days (range 2-8 days). This was shorter for endoscopic approaches versus open surgery (3.25 vs. 7 days). There was no case of esophageal mucosal perforation or reconversion. No death, intraoperative complication, or tumor relapse was described. Only 2 patients had complications: post-surgical thoracic pain, and intestinal obstruction by adhesions 8 years after surgery. CONCLUSION: enucleation is an easier procedure and constitutes the therapy of choice for esophageal leiomyoma. This approach has to be laparoscopic. We think that muscle borders should be closed after enucleation, and that biopsy is not indicated preoperatively.

20 years experience in the management of Zenker's diverticulum in a third-level hospital.

Zenker s diverticulum arises in the posterior wall of the pharynx, above the cricopharyngeal muscle, secondary to a functional cricopharyngeal disorder. We describe our experience with the management of Zenker s diverticulum from 1985 to this day in a third-level hospital. We review clinical data from 27 patients (78% males) with a mean age of 60.4 years. The most common clinical manifestations were dysphagia, regurgitation, syalorrhea, cough, and weight loss. All cases were diagnosed using an esophagogram. A diverticulectomy with cricopharingeal myotomy was performed in 74% of patients. Complications developed in 5 cases (21%), and the recurrence rate was 4% (1 of 3 cases, where myotomy was not performed).

Native valve endocarditis due to Candida parapsilosis: a late complication after bone marrow transplantation-related fungemia.

A case of Candida parapsilosis endocarditis observed 16 months after BMT is reported. The patient, a 35-year-old female with CML, suffered from Candida parapsilosis fungemia on day +22 after BMT. In spite of treatment with amphotericin B, fluconazole and catheter withdrawal, the same yeast was isolated > 1 year later from a vegetation on an old rheumatic mitral valve. Although the patient remained in complete cytogenetical and hematological remission, in vitro tests showed reduced phagocytic and chemotactic capacity of neutrophils and monocytes. This case stresses the need of prolonged therapy for patients with candidemia after BMT.

Autologous peripheral blood progenitor cell transplantation with <2 x 10(6) CD34(+)/kg: an analysis of variables concerning mobilisation and engraftment.

INTRODUCTION: This study analyses the factors affecting mobilisation and engraftment in autologous peripheral blood progenitor cell transplantation according to the number of CD34(+) re-infused. MATERIALS AND METHODS: A total of 190 patients underwent mobilisation with G-CSF alone (n=113) or in combination with chemotherapy (n=77). A total of 116 patients (61%) were autografted with <2 x 10(6) CD34(+) cells/kg and 74 patients were transplanted with >2 x 10(6) CD34(+) cells/kg. Rates of granulocyte and platelet recovery were estimated using the product-limit method of Kaplan-Meier and compared using a log-rank test. The Cox regression model was used for the multivariate analysis of factors influencing engraftment. Differences between cohorts were evaluated by one-way ANOVA or Mann-Whitney tests, and multivariate analysis was performed using a stepwise lineal regression. RESULTS: Neutrophil and platelet engraftment was significantly longer with <2 x 10(6)/CD34(+)/kg (12 vs 10 days, P=0.014 and 16 vs 13 days, P=0.0001 respectively). Platelet recovery was affected by exposure to alkylating agents (P=0.04), refractory disease (P=0.02) and AML (P=0.0001), but only the last two variables remained significant in Cox regression (P<0.01). Granulocyte engraftment was longer in CML (univariate, P=0.04) and in refractory disease (multivariate, P=0.02). In patients re-infused with >2 x 10(6)/CD34(+)/kg, the Cox model did not identify prognostic factors for haematopoietic recovery. CONCLUSION: Although mobilisation schedules and disease status influenced not only the yield of progenitor cells, but also the engraftment kinetics, the number of CD34(+) re-infused was the main predictor of haematopoietic recovery. While engraftment succeeded in most of the cases, the re-infusion of >2 x 10(6)/CD34(+)/kg resulted in significantly shorter recovery times.

Acute lymphoblastic leukemia in an XYY male.

A case of acute lymphoblastic leukemia (ALL) in a 16-year-old male with a 47,XYY karyotype is reported. This chromosome aneuploidy was found in both bone marrow (BM) cells and mitogen-stimulated lymphocytes. Immunologic profile of leukemic cells showed a null phenotype. To our knowledge, this is the fifth case reported in the literature.

[Immunologic reconstitution of peripheral blood lymphocytes in patients treated by bone marrow transplantation]. / Reconstitución inmunológica de los linfocitos de sangre periférica en pacientes tratados con trasplante de médula ósea.

BACKGROUND: Lymphocyte subset reconstitution was studied in 65 patients undergoing allogeneic and autologus bone marrow transplantation (BMT). PATIENTS AND METHODS: The expression of molecules on the membrane of lymphocyte subsets was assessed by two-colour flow cytometry and a direct immunofluorescence assay. The functional capacity of the patient's T lymphocytes following transplantation was identified by stimulation whit peripheral blood lymphocytes; B cells from BMT recipients were tested for their ability to respond, in vitro, to pokeweed (PWD) mitogen. RESULTS: 1) The proportion of CD8+ T lymphocytes was higher than the CD4+ T lymphocytes until 1 1/2 year after-BMT, with high percentage of immature T cells (CD3+, CD8+, HLA-DR+, CD25-) in the first nine months post-transplant. Moreover, a large proportion of T lymphocytes lacked CD5 expression in the first year following BMT. 2) T-cell proliferative response to PHA was low with subsequent recovery until normality. 3) Low numbers of B cells in the first two months with a significant increase since then until 1 1/2 year after-BMT; the phenotype of these B cells was mainly CD19+, CD5+. 4) High in vitro spontaneous immunoglobulin production by peripheral blood B lymphocytes and an impaired response to PWM was observed. 5) Increased percentage of cells with natural killer (CD56) cell phenotype was seen during the 2nd and 3rd months after the graft infusion. After 1 1/2 year postgrafting, this percentage returned to normal level. CONCLUSIONS: Taken together, these data indicate the existence of numerous abnormalities in several subsets of peripheral blood lymphocytes after BMT and suggest a slow kinetics of immune recovery after human marrow transplantation being complete between 18 and 24 months following BMT.

[Reconstitution of peripheral blood lymphocytes in patients treated with bone marrow transplantation: comparison between allogeneic and autologous transplantation]. / Reconstitución de los linfocitos de sangre periférica en pacientes tratados con trasplante de médula ósea: comparación entre el trasplante alogénico y el autólogo.

BACKGROUND: This study compares the immune reconstitution of total T cells, CD4 and CD8 cell subsets, activated T cells, NK cells and B cells in 66 patients who underwent allogeneic or autologous bone marrow transplantation (BMT). PATIENTS, MATERIAL AND METHODS: The reconstitution of peripheral lymphocytes subsets was studied using two-color flow cytometry. The study group consisted of 39 patients who received allogeneic BMT compared with 27 patients who received autologous BMT. Peripheral blood was examined at different time intervals. As a measure of immune function, the response to the mitogen phytohemaglutinin (PHA) was determined. RESULTS: The pattern of recovery of CD3+, CD4+ and CD8+ T cells, as well as the PHA response, was similar for each type of transplant. CD3+CD5- cells were significantly higher following autologous BMT than after allogeneic BMT and during more time. An overexpression of DR on T cells following autologous or allogeneic BMT demonstrates an increasing degree of T-lymphocyte activation. This activated T-cell subset was more stable in patients transplanted with allogeneic BM than in patients treated with autologous BM. The levels of total B cells and CD19+CD5+ B-cells were increased during 2 to 12 months following autologous MBT, remaining normal afterwards; in contrast, the levels of CD19+ lymphocytes and CD19+CD5+B-cells remained higher than normal ranges until 36 months in patients transplanted with allogeneic BM. The percentage of NK cells was significantly increased following both autologous and allogeneic BMT. The highest percentage of NK cells were detected about 2 and 6 months post-transplant in patients treated with autologous or allogeneic BM, respectively. CONCLUSIONS: Allogeneic BMT appears to induce a slight delay recovery of B and NK cells in comparison to autologous BMT. In contrast, T-cells recovery was similar for each type of transplant, although a higher percentage of CD3+CD5- T cells and a faster recovery of activated CD3+DR+ cells to normal levels were observed in patients transplanted with autologous BM.

[Clinical and functional results after Laparoscopic fundoplication. Prospective evaluation]. / Resultados clínicos y funcionales después de funduplicatura laparoscópica. Evaluación prospectiva.

OBJECTIVE: To prospectively assess the medium- and long-term clinical and functional results in consecutive patients undergoing laparoscopic procedures for gastroesophageal reflux. PATIENTS AND METHOD: The series included the interventions performed or assisted by the first author in 325 patients referred for surgical evaluation between December 1992 and June 2000. Forty patients were excluded from the study because they did not fulfil the inclusion criteria for laparoscopic surgery. A further 20 patients who underwent laparoscopic surgery were excluded because they required conversion to open surgery. Thus, 265 patients were included in the study. One hundred ninety-six total fundoplications (Nissen-Rossetti) and 69 partial fundoplications(42 posterior-Toupet and 27 anterior-Dor) were performed. The surgical technique employed was a slight modification of that described by Dallemagne et al with five-trocars. Preoperative evaluation was established by clinical features, endoscopy with biopsy, barium contrast radiography, esophageal manometry and esophageal pH monitoring. RESULTS: The mean follow-up was 47.1 3.3 months (range: 4-92 months). Heartburn, regurgitation, and dysphagia were relieved in 92.5%, 97.7%, and 88.1% of patients respectively. Complete relief of symptoms was achieved in all patients who presented preoperative respiratory symptoms as a complication of gastroesophageal reflux. Esophagitis healed in 98.2% of patients with preoperative esophagitis. Correction of lower esophageal sphincter pressure and lower esophageal sphincter length were statistically significant compared with preoperative status (p = 0.006 and p = 0.003, respectively). Pre- and postoperative differences in the percentage of patients with a pH < 4 in 24-hour ambulatory esophageal pH monitoring were also significant (p = 0.005), confirming correction of acid reflux. Morbidity appeared in 6.7% of patients and there was no mortality. Conversion to open procedures was required in 7.5%. The mean operative time was 115 6.3 minutes. CONCLUSIONS: These preliminary results suggest that when performed by experienced surgeons laparoscopic fundoplication provides an excellent alternative in selected patients with gastroesophageal reflux. Both medium- and long-term clinical and functional results, as well as morbidity, were satisfactory and were similar to those of open fundoplication.

[Reconstructive surgery with polypropylene mesh associated with kidney transplant]. / Cirugía reconstructiva con malla de polipropileno asociada al trasplante renal.

OBJECTIVE: There is very little literature on hernial complications of the abdominal wall in association to renal transplantation. The present report aims to evaluate their incidence and type, as well as the intervention carried out and its results. MATERIAL AND METHOD: A retrospective analysis of a series of 650 renal transplantations has been carried out between 1978-1996 in our centre. A braided polypropylene mesh (Prolene) was used to repair abdominal wall defects and/or diagnosed hernias in 8 (1.2%) cases: 5 eventrations, 1 inguinal hernia and one combination of both: the last case required extensive debridement of the abdominal wall due to necrotizing fascitis. Mean time to eventration was 47.3 months (range 1-106). RESULTS: In all cases, the mesh was placed in the pre-peritoneal space. Two patients developed complications (one haematoma and one wound infection), though graft removal was not necessary in any case. Follow-up was 33.1 months (range 6-78) with no findings of hernial relapse. One patient started successful chronic ambulatory peritoneal dialysis (CAPD) 30 days after the intervention. CONCLUSIONS: The polypropylene mesh is a sound alternative in the treatment of hernial complications associated to renal transplantation, with acceptable morbidity, and efficacy rates that in our series reached 100%.

[Bone marrow transplantation in malignant diseases in childhood using reverse isolation technics: evaluation of results]. / Trasplante de médula ósea en enfermedades malignas en la edad pediátrica con aislamiento inverso convencional: valoración de resultados.

Between July 1985 and March 1990, 31 pediatric patients with neoplastic diseases underwent bone marrow transplantation (22 allogenic and 9 autologous). Routine reverse isolation techniques with sterilization of the gastrointestinal tract were used in all cases. Of these patients, 55% had fever and 32% had a documented infection. In allogenic bone marrow transplants, 23% developed graft-versus-host disease, grade I-IV. The incidence of infection and graft-versus-host disease compares favorably with other published reports from centers utilizing laminar air flow rooms during bone marrow transplantation. This suggest that standard reverse isolation techniques may be used without increasing the morbidity and mortality in these patients.

Quinidine-induced agranulocytosis of abrupt onset.

Drug-induced agranulocytosis is a clinical entity characterized by a selective reduction of circulating neutrophils, usually to a level less than 0.2 x 10(9)/l in relation to the administration of the drug. Quinidine is an antiarrhythmic agent widely used on an outpatient basis with some well-known hematological side effects. Its midterm administration has been related to a few cases of agranulocytosis. Herein, we describe the case of a 60-year-old man with atrial fibrillation who presented quinidine-induced agranulocytosis of abrupt onset only 3 days after the exposure to the drug, recovering normal levels of neutrophils during the 3rd hospitalization day. Pathogenic mechanisms are discussed.