Efficacy and Feasibility of Allogeneic Hematopoietic Stem-Cell Transplantation in the Treatment of Refractory Acute Myeloid Leukemia

Background

Refractory acute myeloid leukemia (AML) includes AML includes failure of disease to respond to standard induction chemotherapy, relapse within 6 months after first CR, and 2 or more relapses. The outcome of these patients is usually very poor; only a small proportion can be rescued by allogenic hematopoietic stem-cell transplantation (allo-HSCT). The aim of this study was to evaluate the efficacy and feasibility of allo-HSCT in patients with refractory AML.

Homozygous microdeletion of chromosome 4q11-q12 causes severe limb-girdle muscular dystrophy type 2E with joint hyperlaxity and contractures

Microdeletion syndromes are commonly transmitted as dominant traits and are frequently associated with variably expressed pleiotropic phenotypes. Nonlethal homozygous microdeletions, on the other hand, are very rare. Here, we delineate the fifth and so far largest homozygous microdeletion in nonmalignancies of approximately 400 kb on chromosome 4q11-q12 in a large consanguineous East-Anatolian family with six affected patients. The deleted region contains the beta-sarcoglycan gene (SGCB), the predicted gene SPATA18 (spermatogenesis associated 18 homolog) and several expressed sequence tags. Patients presented with a severe and progressive Duchenne-like muscular dystrophy phenotype, a combination of hyperlaxity and joint contractures, chest pain, palpitations, and dyspnea.     

Hemorrhagic shock and encephalopathy syndrome in infancy and childhood

After a few days of prodromal illness with diarrhea and fever there was an abrupt onset of coma, seizures, severe shock, and hyperpyrexia in two infants; they than developed bleeding, pancytopenia, and impairment of liver and renal function. Both infants survived with major neurologic sequelae. The clinical symptoms and laboratory parameters were compatible with hemorrhagic shock and encephalopathy syndrome which was first described in 1983. The clinical course and biochemical features of this disease and its differential diagnoses are described, and etiology and pathogenesis are discussed. Furthermore it will be discussed, whether the hemorrhagic shock and encephalopathy syndrome is actually a "new" disease or just a new label for a known disorder.     

Colon cancer with isolated metastasis to the kidney at the time of initial diagnosis

Blood-borne metastases to the kidneys from solid tumors have received little attention in the medical literature because they usually occur in a setting of advanced systemic disease, and renal involvement is a elatively minor cause of symptoms. Although the frequency of metastases to the kidney in cancer patients is 7–13% in large autopsy series, incidental discovery of a renal metastasis as the first manifestation of a primary tumor is a very rare event. The most common primary malignancy to involve the kidney is bronchogenic carcinoma, followed by breast and gastrointestinal cancers. In this article, we report a patient with left colon cancer and isolated metastasis to the right kidney at the time of initial diagnosis. Left hemicolectomy and right nephrectomy were performed. Adjuvant systemic chemotherapy consisting of 5-fluorouracil (5-FU) and folinic acid (FA) was given. 5-FU and FA were stopped after four cycles because metastases to the lung and liver occurred about 3 mo after the surgery during adjuvant chemotherapy. Capecitabine was started. The patient died 9 mo after the discovery of the isolated renal metastasis. Nephrectomy is more for diagnostic clarification in the setting of synchronous primary because it has no effect on survival and its effect on quality of life is minimal; as seen in our case, the other organ metastases rapidly occur and the survival is limited. Nephrectomy may also compromise the choice of chemotherapy agents that require renal clearance, thus a careful evaluation of renal functions is necessary if a nephrectomy is performed. In the matter of a decreased renal clearance, the doses of these drugs should be decreased or the choice should be reevaluated.     

Complications of gynaecological laparoscopy--a retrospective analysis of 3572 cases from a single institute.

Three thousand, five hundred and seventy-two laparoscopic procedures were analysed retrospectively from a single institution between 1996 and 2003. Operations were classified into four groups as diagnostic laparoscopy (386, 10.8%), minor (1092, 30.5%), major (1866, 52.4%) and advanced (228, 6.5%) laparoscopic procedures. Overall, 67 (1.88%) complications occurred. The complication rates were 1.81%, 1.37%, 1.82% and 4.82% in the respective groups. One death (0.03%) occurred due to aortic injury during insertion of the principal intraumbilical trocar. Complications during insertion of the Verres needle, principal and accessory trocars were noted in 25 cases (38.2%) and were comparable among the four groups. Intraoperative complications occurred in 32 patients (47.8%) encountered mainly in the major and advanced groups. Overall, acute postoperative complications occurred in 10 (14.9%) patients. Despite advanced technology and experience, complications during the installation phase of laparoscopy remain a major cause of significant morbidity and most operative complications occurred in advanced operative procedures. Complications associated with all types of laparoscopic procedures should not be underestimated.     

Increased bioaccumulation of urethane in CYP2E1-/- versus CYP2E1+/+ mice.

Urethane is a fermentation by-product and a potent animal carcinogen. Human exposure to urethane occurs through consumption of alcoholic beverages and fermented foods. Recently, CYP2E1 was identified as the primary enzyme responsible for the metabolism of [(14)C]carbonyl-labeled urethane. Subsequently, attenuation of urethane-induced cell proliferation and genotoxicity in CYP2E1-/- mice was reported. The present work compares the metabolism of single versus multiple exposures of CYP2E1-/- and CYP2E1+/+ mice to (14)C-ethyl-labeled urethane. Urethane was administered as a single 10 or 100 mg/kg gavage dose or at 100 mg/kg/day for 5 consecutive days. CYP2E1+/+ mice administered single or multiple doses exhaled 78 to 88% of dose as (14)CO(2)/day. CYP2E1-/- mice eliminated 30 to 38% of a single dose as (14)CO(2) in 24 h and plateaued after day 3 at approximately 52% of dose/day. The concentrations of urethane-derived radioactivity in plasma and tissues were dose-dependent, increased as a function of the number of doses administered, and were significantly higher in CYP2E1-/- versus CYP2E1+/+ mice. Whereas urethane was the main chemical found in the plasma and tissues of CYP2E1-/- mice, it was not detectable in CYP2E1+/+ mice. In conclusion, multiple dosing led to considerable bioaccumulation of urethane in mice of both genotypes; however, greater retention occurred in CYP2E1-/- versus CYP2E1+/+ mice. Furthermore, greater bioaccumulation of (14)C-ethyl-labeled than [(14)C]carbonyl-labeled urethane was observed in mice. Comparison of the metabolism of ethyl-versus carbonyl-labeled urethane was necessary for tracing the source of CO(2) and led us to propose for the first time that C-hydroxylation is a likely pathway of urethane metabolism.     

Prognostic factors that affect survival after the treatment of early stage cervical carcinoma

The aim of this study was to investigate the presence of risk factors for predicting survival and to evaluate the efficacy of the radical surgery in patients with early stage cervical carcinoma. A total of 200 women who underwent radical hysterectomy and bilateral pelvic lymph node dissection for early stage cervical carcinoma were retrospectively analysed. We found that lymph node involvement (P <0.0015) and lymphovascular invasion (P <0.05) were the best prognostic factors for disease-free survival in our cases. The depth of cervical invasion, lymphovascular invasion and parametrial spread were closely related with lymph node involvement. Parametrial spread was shown in 38 patients (19%), assessed as stage Ia-IIa pre-operatively. Seventy-six stage Ib patients, at high-risk of recurrence, received adjuvant radiotherapy. Although there was some local tumour recurrence in the control group, adjuvant radiotherapy did not improve the overall survival in stage Ib patients. As a consequence, primary surgery would be definitive in estimating survival from histopathological evaluation. This study demonstrates that lymph node involvement and lymphovascular space infiltration were the best predictor factors for survival.