Gemcitabine combined with the monoclonal antibody nimotuzumab is an active first-line regimen in KRAS wildtype patients with locally advanced or metastatic pancreatic cancer: a multicenter, randomized phase IIb study.

BACKGROUND: This randomized study was designed to investigate the superiority of gemcitabine (gem) plus nimotuzumab (nimo), an anti-epidermal growth factor receptor monoclonal antibody, compared with gem plus placebo as first-line therapy in patients with advanced pancreatic cancer. PATIENTS AND METHODS: Patients with previously untreated, unresectable, locally advanced or metastatic pancreatic cancer were randomly assigned to receive gem: 1000 mg/m2, 30-min i.v. once weekly (d1, 8, 15; q29) and nimo: fixed dose of 400 mg once weekly as a 30-min infusion, or gem plus placebo, until progression or unacceptable toxicity. The primary end point was overall survival (OS), secondary end points included time to progression, overall response rate, safety and quality of life. RESULTS: A total of 192 patients were randomized, with 186 of them being assessable for efficacy and safety (average age 63.6 years). One-year OS/progression-free survival (PFS) was 34%/22% for gem plus nimo compared with 19%/10% for gem plus placebo (HR = 0.69; P = 0.03/HR = 0.68; P = 0.02). Median OS/PFS was 8.6/5.1 months for gem plus nimo versus 6.0/3.4 mo in the gem plus placebo group (HR = 0.69; P = 0.0341/HR = 0.68; P = 0.0163), with very few grade 3/4 toxicities. KRAS wildtype patients experienced a significantly better OS than those with KRAS mutations (11.6 versus 5.6 months, P = 0.03). CONCLUSION: This randomized study showed that nimo in combination with gem is safe and well tolerated. The 1-year OS and PFS rates for the entire population were significantly improved. Especially, those patients with KRAS wildtype seem to benefit. The study was registered as protocol ID OSAG101-PCS07, NCT00561990 and EudraCT 2007-000338-38.

Clinical experience with ferric carboxymaltose in the treatment of cancer- and chemotherapy-associated anaemia.

BACKGROUND: Intravenous (i.v.) iron can improve anaemia of chronic disease and response to erythropoiesis-stimulating agents (ESAs), but data on its use in practice and without ESAs are limited. This study evaluated effectiveness and tolerability of ferric carboxymaltose (FCM) in routine treatment of anaemic cancer patients. PATIENTS AND METHODS: Of 639 patients enrolled in 68 haematology/oncology practices in Germany, 619 received FCM at the oncologist's discretion, 420 had eligible baseline haemoglobin (Hb) measurements, and 364 at least one follow-up Hb measurement. Data of transfused patients were censored from analysis before transfusion. RESULTS: The median total iron dose was 1000 mg per patient (interquartile range 600-1500 mg). The median Hb increase was comparable in patients receiving FCM alone (1.4 g/dl [0.2-2.3 g/dl; N = 233]) or FCM + ESA (1.6 g/dl [0.7-2.4 g/dl; N = 46]). Patients with baseline Hb up to 11.0 g/dl and serum ferritin up to 500 ng/ml benefited from FCM treatment (stable Hb ≥ 11.0 g/dl). Also patients with ferritin >500 ng/ml but low transferrin saturation benefited from FCM treatment. FCM was well tolerated, 2.3% of patients reported putative drug-related adverse events. CONCLUSIONS: The substantial Hb increase and stabilisation at 11-12 g/dl in FCM-treated patients suggest a role for i.v. iron alone in anaemia correction in cancer patients.

Bisphosphonate-related jaw necrosis--severe complication in maxillofacial surgery.

Bisphosphonates are used as potent inhibitors in metastatic bone lesions. They can reduce skeletal burden and prevent bony metastases. They are integral in the treatment of some tumours like breast cancer, prostate cancer and multiple myeloma. As a side effect, these drugs also may cause severe jaw necrosis. Twenty-four patients with bisphosphonate-related jaw necrosis were analyzed in a clinical study. These necroses mostly appeared after administration of aminobisphosphonates. Recurrent avascular necroses were found after changing from Pramidronate to Zoledronate. All patients were treated by resection of necrotic bone. Repeated surgical interventions were required with about 25% of the patients. The management of patients with bisphosphonate-related jaw necrosis remains extremely difficult and includes surgical procedures as well as the eradicating of the necrotic bone including antibiotic therapy. The prevention of such complications consists in a minimization of dental surgical interventions and an avoidance of ulcers by dental prosthesis.

[Cytochemical demonstration of phenoloxidase in peripheral blood leukocytes]. / Zytochemischer Nachweis von Phenoloxidase in Leukozyten des peripheren Blutes.

A comparative application of phenoloxidase-demonstration and Pappenheim staining allows a sure differentiation of phenoloxidase-positive cells to be made, which can be found in the peripheral blood with different activity and different pattern of response. While eosinophils, neurophils, monocytes and lymphocytes contain phenoloxidase, basophiles do not.

[Lymphogranulomatosis and pregnancy]. / Lymphogranulomatose und Schwangerschaft.

A long period of full remission after successfully treated Hodgkin's disease set more and more in our concern problems of pregnancy and parturition in these patients. There are no exact informations about an unfavourable influence of pregnancy on the course of Hodgkin's disease. Although in cases of severe disease the treatment of the mother goes first we will restrain from therapeutical activities in patients with favourable histology and missing B-symptoms. It is reported on 3 cases of Hodgkin's disease with succeeding pregnancy and delivery. The stage IV of Hodgkin's disease in one patient is apparently followed by an uncomplicated course of pregnancy and lack of recurrent disease.

[Clinical aspects and prognosis of highly malignant non-Hodgkin's lymphomas]. / Klinik und Prognose der Non-Hodgkin-Lymphome hoher Malignität.

Clinical data and courses of the disease of 56 patients with non-Hodgkin-lymphomas of high malignancy were demonstrated. The age-depending summit of the frequency was between the 51st and 60th year of age, the age median was about 48 years. The initial remission rate three months after the beginning of the therapy was 66%. Out of the responders in 44% relapsed, in which cases 70% of the relapses developed in the first year after the beginning of treatment. After twelve months the survival rate was 0.52 and after 48 months 0.32. Patients with initial remission, with localized stages I and II (Ann Arbor) as well as with primarily extranodal manifestation and with histology of centroblastoma had a clear prognostic advantage. Initial B-symptomas, an advanced stage of the disease and a histology of immunoblastoma and lymphoblastoma as well were negatively correlated to the prognosis.

Remarks on gastroenterologic diagnostics of amoebic liver abscess, peritoneal tuberculosis and tropical splenomegaly.

The amoebic liver abscess, the peritoneal tuberculosis and the "tropical splenomegaly" belong to diseases which are frequent in warm countries but single cases appear also in moderate climate by intercontinental communications. False diagnoses especially in the first both can lead to severe rsp. fatal consequenses. Therefore experiences are dealed with, which have been gained within nearly one year in Ethiopia and which shall illustrate the diagnostic procedures under field conditions in warm countries as well as under conditions of modern hospitals in moderate climates. Amoebic liver abscess is quickly detected and confirmed by sonography and immunodiagnostic. Contrary to it in the fields there is the puncture by means of a i. v.-needle often not only the sole diagnostic but also the first and sometimes life-saving therapeutic procedure in advanced cases. It allows X-ray in double contrast technique if equipment is available. In suitable cases such approved technique shall be used also in modern clinics disposing of methods like sonography and computerized tomography. Concerning peritoneal tuberculosis our examinations agreed with the opinion of literature that the laparoscopy seems to be the most suitable method for quickly detection and safe discrimination from decompensated portal hypertension in liver cirrhosis. By the way the "cope needle" are mentioned which is distributed in warm countries for searching for peritoneal tuberculosis by performance of a blind peritoneal biopsy. It is easier than laparoscopy but not so efficient. - In this connection 31 cases examined by laparoscopy are presented in a table in order to give an impression on further indications to laparoscopy existing in such areas of warm countries.(ABSTRACT TRUNCATED AT 250 WORDS)

[Megakaryocytic pseudomyelosis with severe thrombocytosis]. / Megakaryozytäre Pseudomyelose mit hochgradiger Thrombozytose.

A 66-year-old female patient complained of loss of body weight and fatigue. The clinical examination revealed a thrombocytosis with a maximum count of 3.200 . 10(9) platelets and a leukocytosis with maximally 25 . 10(9) white cells in the peripheral blood. The bone marrow showed a large increase of megakaryocytes. Under the diagnosis of megakaryocytic myelosis a chemotherapy with 186 mg busulfan was performed. In the course of this treatment the clinical picture of a sepsis occurred which could not be controlled by antibiotics. The patient died four months after her admission to the clinic. The essential findings in autopsy were a caseous tuberculosis of the lymph nodes with haematogenic generalization which appeared as a septic tuberculosa gravissima ("typhobacillosis" Landouzy). The bone marrow was atrophic. Spleen liver and lymph nodes were without evidence for a myeloproliferative disorder. Thus, the initial diagnosis had to be changed to a megakaryocytic pseudomyelosis with massive thrombocytosis as a reaction to the tuberculous infection. The differential diagnosis of megakaryocytic myelosis, other disorders of the myeloproliferative syndrome, and the reactive thrombocytosis are discussed.

[Growth hormone secretion in growth retarded children and adolescents]. / Untersuchungen zur Wachstumshormonausschüttung minderwüchsiger Kinder und Jugendlicher.

In 119 children and adolescents with restricted growth whose secretion of growth hormone (hGH) was investigated in the insulin hypoglycaemia test, different hGH-secretion patterns were found. 52.1% of the investigated persons showed a prestimulatory stress-conditioned hGH-secretion. There were no relations to age or to sex. The hypoglycaemia-conditioned secretion of hormone following this spontaneous release has quantitatively no relation to the size of the decrease of blood sugar. However, it is also determined by the trend of secretion in the pretest-phase. Different modes of synthesis and release are the cause for this behaviour. High spontaneous hGH-levels decrease the hypoglycaemia effect of the intravenously applied insulin. In 33.9% of the cases the levels of the growth hormone are lower during the proper test phase or only as high as in the preparation time. Twelve times the poststimulatory values simulated a hyposomatotropism. The eventual importance of the secretion patterns remains up to now unclear for the longitudinal growth.

Effects of type of information (abstract-concrete) and field dependence on asymmetry of hand movements during speech.

Asymmetry of object-focused (gestural) and body-focused (self-touching) movements was investigated in a sample of 14 field dependent and 14 field-independent right-handed male college students. The data were obtained from standardized, videotaped interviews which consisted of an abstract and a concrete communicative task. Significant right-hand asymmetry was found for gestures which depict or represent (motor primary movements,p less than .01) but not for nonrepresentational speech primacy movements. In general, field-independents had greater right-hand asymmetry than field-dependents for object-focused movements, whereas field-dependents showed more left-hand asymmetry of self-touching. Results are discussed in terms of a possible relationship between extent of movements asymmetry and the use of visual imagery in verbal encoding.

Physiological concomitants (I131 uptake) of field dependence.

Radioactive iodine uptake levels of two matched groups 11 field dependent and 11 field independent male euthyroid medical students were compared at the 7th, 24th, and 48th hr and at the 7th day. Significantly higher levels were observed in the field dependent group at all points except the 48th hr. These findings may reflect individual differences in adaptive psychoendocrine functioning.