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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., (© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Introduction: Bortezomib (Velcade) is a proteasome inhibitor that has shown important clinical efficacy either as a single agent or in combination with other cytostatic agents in multiple myeloma (MM). In the present protocol, bortezomib was combined with other active substances like bendamustine and prednisone (BPV), in order to assess the efficacy and toxicity of the combination therapy in patients with relapsed or refractory MM., Methods: Between January 2005 and December 2011, 78 patients with relapsed or refractory MM were treated with bendamustine 60 (-120) mg/m(2) on days 1 and 2, bortezomib 1.3 mg/m(2) on days 1, 4, 8 and 11, and prednisone 100 mg on days 1, 2, 4, 8 and 11. The median number of prior therapies was 2 with a wide range of 1-9. Thirty-three patients had pre-existing severe thrombocytopenia and/or neutropenia (WHO grade 3 or 4)., Results: A median number of two (range 1-7) BPV treatment cycles were given to the patients. The majority of the patients (n = 54; 69 %) responded after at least one cycle of chemotherapy with 3 CR, 10 nCR, 10 VGPR and 31 PR. Median PFS and OS for patients without severe hematological toxicities due to previous treatments (n = 45) were 11 and 50 months, respectively. Outcome for these patients was significantly better than that for patients with severe hematological toxicities (grade 3 or 4, n = 33) with a PFS, and OS of 3 months (p < 0.05) and 5 months (p < 0.001), respectively. The regimen was well tolerated with few significant side effects in patients without severe hematological toxicities due to previous treatments. These results indicate that the combination of bortezomib, bendamustine and prednisone is well tolerated in patients with relapsed or refractory MM.

Purpose: This study aimed to prove the usefulness of the diagnostic plot, using the haemoglobin content of reticulocytes as a measure of functional iron deficiency (FID) and the ferritin index as a measure of iron availability, to customise anaemia treatment in cancer patients., Methods: Based on results of this plot, cancer patients fulfilling practice guideline criteria to receive erythropoiesis-stimulating agents (ESAs) were allocated to treatment with ESAs alone, iron alone or the combination of both. Primary endpoint was the percentage of patients identified to require iron in addition or as an alternative to ESA therapy., Results: Out of 303 patients screened, 286 were allocated to treatment: 204 patients were normochromic and iron replete and treated with ESAs alone, 22 had both FID and anaemia of chronic disease and were treated with ESAs and parenteral iron, and 60 were iron-depleted and treated with iron only. After 8 weeks, a haemoglobin increase >1 g/dL from baseline was shown by 56% of patients treated with ESAs alone, by 100% of patients receiving the combination, by 50% of normochromic and by 73% of hypochromic iron-depleted patients receiving iron only. Acute phase reaction did not diminish the response rate to ESAs., Conclusions: The diagnostic plot was superior to transferrin saturation and ferritin in predicting iron availability in hypochromic patients treated with ESAs and proved useful to select treatment for anaemia in cancer patients.

Although chronic lymphocytic leukemia (CLL) is a disease of elderly patients, subjects older than 65 years are heavily underrepresented in clinical trials. The German CLL study group (GCLLSG) initiated a multicenter phase III trial for CLL patients older than 65 years comparing first-line therapy with fludarabine with chlorambucil. A total of 193 patients with a median age of 70 years were randomized to receive fludarabine (25 mg/m(2) for 5 days intravenously, every 28 days, for 6 courses) or chlorambucil (0.4 mg/kg body weight [BW] with an increase to 0.8 mg/kg, every 15 days, for 12 months). Fludarabine resulted in a significantly higher overall and complete remission rate (72% vs 51%, P = .003; 7% vs 0%, P = .011). Time to treatment failure was significantly shorter in the chlorambucil arm (11 vs 18 months; P = .004), but no difference in progression-free survival time was observed (19 months with fludarabine, 18 months with chlorambucil; P = .7). Moreover, fludarabine did not increase the overall survival time (46 months in the fludarabine vs 64 months in the chlorambucil arm; P = .15). Taken together, the results suggest that in elderly CLL patients the first-line therapy with fludarabine alone does not result in a major clinical benefit compared with chlorambucil. This trial is registered with www.isrctn.org under identifier ISRCTN 36294212.

An infection with Bartonella henselae transmitted from domestic cats to humans by scratching normally leads to cat-scratch disease. When the human host has severe immunosuppression or HIV infection, the potentially life-threatening disease bacillary angiomatosis can develop. A 79-year-old man presented with livid-erythematous, angioma-like skin lesions. We considered a cutaneous infiltrate from his known chronic lymphocytic leukemia, Merkel cell carcinoma, cutaneous metastases of internal tumors, cutaneous sarcoidosis, mycobacterial infection and even atypical herpes simplex infection. The correct diagnosis was proven histologically and by PCR. Because of increasing numbers of immunosuppressed and HIV-positive patients, as well as an infection rate of 13% for B. henselae in domestic cats in Germany, one must be alert to the presence of bacillary angiomatosis.

Salvage therapy for patients with mantle cell lymphoma (MCL) remains a challenge. The clinical course is characterised by increasing resistance to conventional chemotherapy and a dismal long-term outcome. On the basis of studies demonstrating synergy in vitro, eight heavily pretreated patients (median age 65 years) with advanced stage MCL were individually treated with a novel combination protocol consisting of the proteasome inhibitor bortezomib (1.5 mg/m(2); Days 1 and 4), high-dose cytarabine (750-2000 mg/m(2); Days 2 and 3) and dexamethasone (40 mg daily; Days 1-4). Rituximab (375 mg/m(2)) was added in patients not refractory to prior rituximab-containing regimens. Treatment was repeated in 3-week intervals or postponed until hematologic recovery for up to four planned cycles. Toxicity consisted mainly of Grade 3/4 hematotoxicity, which occurred in all patients. Median treatment interval was 31 days. Objective responses were observed in four (50%) of eight patients, including two complete remissions. Median progression free and overall survival were 5 and 15.5 months, respectively. The combination of bortezomib and a high-dose cytarabine-containing regimen has activity in heavily pretreated patients with relapsed or refractory MCL.

Thalidomide is an effective agent for advanced refractory or relapsed multiple myeloma (MM), although dose-limiting toxicity (DLT) may limit its use. This Phase I study found that a combination of low-dose thalidomide with bendamustine and prednisolone (BPT) maintained or increased efficacy, whilst avoiding DLT in 28 patients with MM that was refractory or that had relapsed after conventional chemotherapy or high-dose therapy with stem-cell support. BPT comprised fixed doses of bendamustine (60 mg/m(2)) and prednisolone (100 mg), and escalating doses of thalidomide (50, 100, 200 mg). Treatment cycles were repeated every 28 d until the occurrence of maximum response, DLT, or disease progression. Twenty-four patients responded after at least two cycles (four complete remission, six very good partial remission, 14 partial remission). Median progression-free and overall survival for all patients was 11 and 19 months respectively. Only mild/moderate non-haematological side effects were observed and no patient developed dose-limiting haematotoxicity. Transient grade 3-4 neutropenia was reported in 12 patients, and grade 3-4 thrombocytopenia occurred in two patients. We conclude that BPT therapy was well tolerated in patients with relapsed or refractory MM, with a response rate higher than 80%. The maximum tolerated dose of thalidomide was not reached in this study.

This study of first-line treatment in advanced-stage follicular lymphoma patients analysed the effects of MCP (mitoxantrone, chlorambucil and prednisolone) chemotherapy alone or in combination with rituximab (R-MCP) on circulating lymphoma cells (CLC) and assessed the prognostic value of a quantitative monitoring of CLC. CLC numbers were determined by quantitative polymerase chain reaction (PCR) for the t(14;18)-translocation or by allele-specific PCR for rearranged immunoglobulin heavy chain genes. We analysed blood samples from 43 patients treated in a randomized trial comparing eight cycles of MCP versus R-MCP. Clearance of CLC at the end of therapy was achieved in 21/25 patients (84%) treated with R-MCP compared with 0/18 after MCP alone (P < 0.0001). A > or = 2 log CLC reduction was associated with a favourable clinical response (P = 0.0004) and prolonged event-free survival (P = 0.02). In R-MCP patients, stable CLC numbers or consistently PCR-negative blood samples were associated with a continuing clinical remission whereas in two patients a relapse was preceded by a > or = 2 log CLC increase. This study demonstrated that R-MCP led to a rapid and sustained eradication of CLC and a > or = 2 log CLC reduction was associated with a superior quality and duration of the clinical response.

Purpose: Rituximab has been shown to be active in follicular lymphoma (FL), both as monotherapy and in combination with chemotherapy. We conducted a randomized trial comparing mitoxantrone, chlorambucil, and prednisolone (MCP) chemotherapy plus rituximab with MCP alone., Patients and Methods: Previously untreated patients with stage III or IV CD20+ indolent or mantle cell lymphoma were randomly assigned to either eight 28-day cycles of MCP plus rituximab (R-MCP; n = 181) or eight cycles of MCP alone (n = 177). All patients who achieved a complete or partial remission were treated with interferon maintenance until relapse. Herein, we report the results from the primary analysis population of patients with FL, who constituted the majority of patients (56%) recruited to the trial (n = 201; R-MCP, n = 105; MCP, n = 96)., Results: Rates of overall and complete response were significantly higher in the R-MCP arm than the MCP arm (overall response, 92% v 75%, respectively; P = .0009; complete response, 50% v 25%, respectively; P = .004). With a median follow-up time of 47 months, median event-free survival (EFS) and progression-free survival (PFS) times were significantly prolonged with R-MCP compared with MCP (EFS, not reached v 26 months, respectively; P < .0001; PFS, not reached v 28.8 months, respectively; P < .0001), and overall survival (OS) was significantly improved with R-MCP compared with MCP (4-year OS rate, 87% v 74%, respectively; P = .0096)., Conclusion: The R-MCP regimen significantly improves complete and overall response rates, EFS, PFS, and OS in patients with previously untreated advanced FL, without a clinically significant increase in toxicity.

In follicular lymphoma (FL) and mantle cell lymphoma (MCL) the monoclonal antibody rituximab may improve the prognosis when combined with chemotherapy. This was investigated in a prospective randomized study in patients with relapsed disease. A total of 147 patients were randomized to receive 4 courses of chemotherapy with 25 mg/m(2) fludarabine on days 1 to 3, 200 mg/m(2) cyclophosphamide on days 1 to 3, and 8 mg/m(2) mitoxantrone on day 1 (FCM), alone or combined with rituximab (375 mg/m(2); R-FCM). Of 128 evaluable patients, 62 were randomized for FCM and 66 for R-FCM. R-FCM revealed an overall response rate of 79% (33% complete remission [CR], 45% partial remission [PR]) as compared with 58% for FCM alone (13% CR, 45% PR; P = .01), with similar results in a subgroup analysis of FL (94% vs 70%) and MCL (58% vs 46%). In the total group, the R-FCM arm was significantly superior concerning progression-free survival (PFS; P = .0381) and overall survival (OS; P = .0030). In FL PFS was significantly longer in the R-FCM arm (P = .0139) whereas in MCL a significantly longer OS was observed (P = .0042). There were no differences in clinically relevant side effects in both study arms. Hence, the addition of rituximab to FCM chemotherapy significantly improves the outcome of relapsed or refractory FL and MCL.

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.

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.

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)

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.

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.

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.

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.

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.