Lenalidomide monotherapy and in combination with cytarabine, daunorubicin and etoposide for high-risk myelodysplasia and acute myeloid leukaemia with chromosome 5 abnormalities.

Patients with high risk myelodysplasia (HR-MDS) and acute myeloid leukaemia (AML) with chromosomal changes involving deletion of the long arm of chromosome 5 (del5q), especially with complex karyotype, rarely have a durable response to combination chemotherapy. In the subgroup with monosomal karyotype there are no long term survivors (Fang et al., 2011) [1]. Recent experience indicates that the incidence of del5q in AML is ~20-30%, with only 20-25% of patients achieving complete remission (CR) (Farag et al., 2006) [2]. Additionally, therapy has significant toxicity, with induction death rates ~20% even in younger patients (Juliusson et al., 2009) [3]. This lack of efficacy provides the clinical rationale for combination/sequential therapy with Lenalidomide and combination chemotherapy. Dose dependent haematological toxicity is the major safety concern with such a combination protocol. Therefore we conducted a phase 2 study, AML Len5 (ISRCTN58492795), to assess safety, tolerability and efficacy of lenalidomide monotherapy, followed by lenalidomide with intensive chemotherapy in patients with primary/relapsed/refractory high risk MDS or AML with abnormalities of chromosome 5.

A novel prognostic model in myeloma based on co-segregating adverse FISH lesions and the ISS: analysis of patients treated in the MRC Myeloma IX trial.

The association of genetic lesions detected by fluorescence in situ hybridization (FISH) with survival was analyzed in 1069 patients with newly presenting myeloma treated in the Medical Research Council Myeloma IX trial, with the aim of identifying patients associated with the worst prognosis. A comprehensive FISH panel was performed, and the lesions associated with short progression-free survival and overall survival (OS) in multivariate analysis were +1q21, del(17p13) and an adverse immunoglobulin heavy chain gene (IGH) translocation group incorporating t(4;14), t(14;16) and t(14;20). These lesions frequently co-segregated, and there was an association between the accumulation of these adverse FISH lesions and a progressive impairment of survival. This observation was used to define a series of risk groups based on number of adverse lesions. Taking this approach, we defined a favorable risk group by the absence of adverse genetic lesions, an intermediate group with one adverse lesion and a high-risk group defined by the co-segregation of >1 adverse lesion. This genetic grouping was independent of the International Staging System (ISS) and so was integrated with the ISS to identify an ultra-high-risk group defined by ISS II or III and >1 adverse lesion. This group constituted 13.8% of patients and was associated with a median OS of 19.4 months.

Human cystic and alveolar echinococcoses as indication to liver transplantation.

The human cystic and alveolar echinococcoses are zoonotic diseases caused by larval stages of the tapeworms Echinococcus granulosus and E multilocularis. In man the liver form of the diseases develops most frequently. Recent epidemiological data indicate that the distribution of E multilocularis in the central Europe is wider than was previously anticipated; more cases of human alveococcosis during the last years have also been noted in Poland. In the present paper we analyzed several cases of human echinococcoses from Poland with respect to diagnosis and treatment as well as the indications for liver transplantation.

Liver cystadenocarcinoma--case report.

A 69-year-old woman was admitted to our Department with the diagnosis of liver cyst. She had previously undergone liver cyst fenestration 10 years before. After abdominal spiral CT, the patient was qualified for laparotomy. A cystic formation was localized in the central part of the liver, in the 4th segment and was found to compress the hilar bile ducts. A 4.5 bisegmentectomy was performed. During the postoperative course, a biliary fistula was observed, which resolved spontaneously. The treatment was also complicated by myocardial infarction. The patient was discharged in good condition 30 days postoperatively. The pathological diagnosis revealed cystadenocarcinoma.

Risk factors for morbidity following liver surgery.

The aim of this study is to define risk factors for severe complications following anatomical liver resections. The study material consists of the first 50 patients (26 women, 24 men, at mean age 50.6 years) treated at 3rd Department of Surgery 2nd Faculty of Medicine, Medical University in Warsaw. The indications for resection included benign neoplasm in 19 cases and malignancy in 31 cases. All the patients underwent anatomical liver resection in accordance with Couinaund's segmental division. In order to define prognostic factors for severe postoperative complications, a multi-factor statistical analysis was conducted. The following parameters were analysed: patient's age, the levels of bilirubin, total protein, albumin, prothrombin time, kaolin-kephalin time, range of resection and blood loss during operation. Eleven patients (22%) died in postoperative period. In 8 cases the death was caused by liver failure. Statistical analysis showed that blood loss, albumin level on fifth postoperative day and kaolin-kephalin time before and after surgery are independent risk factors predisposing to the development of complications.

Liver regeneration after anatomical resections.

BACKGROUND: The authors present the results of investigation of liver regeneration after partial parenchyma resection. MATERIAL AND METHODS: 20 patients (16 females, 4 male) aged 31-67 years were operated on because of metastatic colon cancer (7 cases), cavernous hemangioma (6 cases), hepatocellular carcinoma (1), alveococcosis (2), metastases of malignant melanoma (1), gall bladder carcinoma (1), FNH (1) and mucous cystadenocarcinoma (1). The resection according to anatomical segments by Couinaud were performed. Spiral CTs including liver volumetry were taken before and 30 days after the operation. on the 7-th day after the surgery, liver biopsy was performed and the material was examined under light and electron microscope. RESULTS: There was no postoperative mortality. We observed transient elevation of transaminases, bilirubin levels and decrease of albumin level. Control spiral CT revealed increased liver volume in 15 cases (75 percent). In 16 cases (80 percent), electron microscopy investigations showed regeneration of the liver (mitotic figures). CONCLUSIONS: Our material shows that hyperplasia as well as blood vessel and bile duct neogenesis play a very important role in liver regeneration process.

Aldehyde dehydrogenase isoenzymes in tumours--assay with possible prognostic value for oxazaphosphorine chemotherapy.

A novel fluorimetric assay, allowing independent measurement of the activities of two principal cytosolic forms of human aldehyde dehydrogenase, ALDH-1 and ALDH-3 (known as a tumour-associated ALDH) was applied to estimate the activities of these isoenzymes in human liver and thyroid tumours. The assay is based on two artificial substrates, 6-methoxy-2-naphthaldehyde (MONAL-62) and 7-methoxy-1-naphthaldehyde (MONAL-71), exhibiting excellent substrate properties toward various forms of human ALDH (see Wierzchowski et al., 1997, Anal. Biochem. 245, 69-78). We have found significant differences in ALDH activities between malignant and non-malignant tissue fragments, particularly in cancerous livers. Out of 16 tumours examined, only 4 exhibited ALDH-1 activities comparable to that found in the tumour-free tissue (0.5-2.5 U/g), while in the remaining 12 this activity was at least 10-fold lower. The ALDH-3 activity was detectable in about 40% of both tumour and tumour-free liver samples (maximum value 1.5 U/g). Comparison of 13 pathological thyroid fragments revealed ALDH activities in the range of 0.02 to 0.35 U/g, with two malignant samples showing activities of 0.27 and 0.18 U/g. Both substrate specificity and kinetic behaviour of the thyroid ALDH (Km values for the fluorogenic naphthaldehydes as well as propanal inhibition profile) were similar to those of the purified ALDH-1. In 5 thyroid samples traces of ALDH-3 activity was detected, using MONAL-62 and NADP+ as substrates (maximum value 0.04 U/g). Possible prognostic value of the foregoing measurements for cyclophosphamide chemotherapy is discussed.

Clostridium difficile in a department of surgery.

The colonization and transmission of Clostridium difficile strains was investigated at the Department of Surgery. Anaerobes were isolated from fecal samples of 27 patients among 308 investigated (mean age: 59.5 years). The majority of them (22 out of 27 patients) received anti-microbial agents prior to investigation for Clostridium difficile. Eighteen of them had undergone various surgical procedures including laparotomies. Only four Clostridium difficile positive patients had diarrhea, but pseudomembranes were not observed endoscopically. The highest colonization rate of C. difficile (20/27) was found to occur in autumn. All 54 samples from medical personnel were C. difficile free. C. difficile was isolated in 7% of samples taken from hospital environment. Toxigenicity of Clostridium difficile strains isolated from fecal samples taken from patients and from environment was 78% and 80%, respectively, as determined by cytotoxicity tissue assay, or 70% and 20%, respectively, in the latex agglutination test.