[Medical Rehabilitation in Gastrointestinal Oncology]. / Onkologische Rehabilitation bei gastrointestinalen Tumorerkrankungen.

BACKGROUND: The demographic change of the human population comes along with an increasing aging, a rise of chronic diseases, particular carcinosis, as well as the need for prolonged working life times. This causes big challenges for the public health systems, primarily in the field of surgery. In this respect, oncological rehabilitation has an important supporting function. Its mission is to reintegrate the patient after surgery back into domestic, social and professional life. This article covers the most significant questions for rehabilitation of gastrointestinal oncology. PURPOSE: The aim of this study is to illustrate the legal foundations and routes to access oncological rehabilitation as well as to provide a survey of the contents of oncological rehabilitation with a special emphasis on gastrointestinal tumours. METHOD: We surveyed experience in clinical rehabilitation by means of an appropriate literature search. Key Findings and Conclusions: Oncological rehabilitation is anchored in social legislation. The terms of reference are different from those of an acute hospital. Apart from the treatment of numerous specific somatic problems, both psycho-oncological care and social-medical consultation and evaluation are centrally important tasks.

Fast imaging of laboratory core floods using 3D compressed sensing RARE MRI.

Three-dimensional (3D) imaging of the fluid distributions within the rock is essential to enable the unambiguous interpretation of core flooding data. Magnetic resonance imaging (MRI) has been widely used to image fluid saturation in rock cores; however, conventional acquisition strategies are typically too slow to capture the dynamic nature of the displacement processes that are of interest. Using Compressed Sensing (CS), it is possible to reconstruct a near-perfect image from significantly fewer measurements than was previously thought necessary, and this can result in a significant reduction in the image acquisition times. In the present study, a method using the Rapid Acquisition with Relaxation Enhancement (RARE) pulse sequence with CS to provide 3D images of the fluid saturation in rock core samples during laboratory core floods is demonstrated. An objective method using image quality metrics for the determination of the most suitable regularisation functional to be used in the CS reconstructions is reported. It is shown that for the present application, Total Variation outperforms the Haar and Daubechies3 wavelet families in terms of the agreement of their respective CS reconstructions with a fully-sampled reference image. Using the CS-RARE approach, 3D images of the fluid saturation in the rock core have been acquired in 16min. The CS-RARE technique has been applied to image the residual water saturation in the rock during a water-water displacement core flood. With a flow rate corresponding to an interstitial velocity of vi=1.89±0.03ftday(-1), 0.1 pore volumes were injected over the course of each image acquisition, a four-fold reduction when compared to a fully-sampled RARE acquisition. Finally, the 3D CS-RARE technique has been used to image the drainage of dodecane into the water-saturated rock in which the dynamics of the coalescence of discrete clusters of the non-wetting phase are clearly observed. The enhancement in the temporal resolution that has been achieved using the CS-RARE approach enables dynamic transport processes pertinent to laboratory core floods to be investigated in 3D on a time-scale and with a spatial resolution that, until now, has not been possible.

Evidence for pluripotent stem cell origin of idiopathic myelofibrosis: clonal analysis of a case characterized by a N-ras gene mutation.

Three cases of idiopathic myelofibrosis were screened for the presence of mutations at codon 12, 13, or 61 of the ras gene family by a rapid method based on polymerase chain reaction and hybridization to mutation-specific oligonucleotides. PB cells of one patient showed a point mutation at codon 12 of the N-ras oncogene. This molecular genetic hallmark was used to investigate the clonal relationship of different cell lineages by cell separation analysis. Presence of the N-ras 12 mutation in granulocytes, monocytes, B cells, and T lymphocytes, as well as erythroblasts, indicates that idiopathic myelofibrosis originates from a pluripotent stem cell, at least in this patient.

Clonal analysis of chronic myeloproliferative disorders using X-linked DNA polymorphisms.

Restriction fragment length polymorphisms of the X-chromosome genes phosphoglycerate kinase and hypoxanthine phosphoribosyl transferase were used to study clonality in peripheral blood leukocytes from 48 women with chronic myeloproliferative disorders (c-MPD). A total of 50% of patients were heterozygous for one or both of the polymorphic loci. These included 17 cases with polycythemia vera, four patients with essential thrombocythemia (ET), and three cases with idiopathic myelofibrosis (IMF). A clear-cut monoclonal X-inactivation pattern was observed in 17 of 24 cases including all IMF patients. Only one patient with PV exhibited a nonclonal composition of her leukocytes, while six cases demonstrated a predominantly clonal pattern in peripheral blood cells. Among the latter category reckoned three of four ET patients. Cell separation analyses were performed in one ET and three PV patients. In all four cases a monoclonal pattern of the granulocyte fraction could be established, while T lymphocytes of these patients were of nonclonal origin. These data suggest that the vast majority of c-MPDs arise from multipotent hematopoietic stem cells. Moreover, this type of clonal analysis might be of help in discriminating between primary MPD and reactive processes.

Deletion of c-fms sequences in the 5q- syndrome.

Southern blot analyses demonstrated hemizygosity of c-fms sequences in three cases of the 5q- syndrome, cytogenetically characterized by del(5)(q13;q35) or del(5)(q31;q35). In situ hybridization studies revealed a deletion of this oncogene from the 5q- chromosome in two cases; moreover, we localized c-fms to region 5q31-33.

Stem cell defects after cytoreductive therapy in man.

The study of stem cell defects in man after cytoreductive therapy appears to be of particular importance since hematotoxicity represents the major limiting side effect in many instances. On the other hand, such studies are met by difficult methodological problems. In particular, bone marrow sampling in man cannot be done on a quantitative basis. Furthermore, ethical considerations restrict the sampling of serial bone marrow specimens. We have studied the reaction of hematopoiesis including stem cells in man with the available methods, in particular CFU-GM (CFU-C), CFU-E, and BFU-E in bone marrow (BM) and peripheral blood (PB) during the course of various cytostatic regimens given for adjuvant and palliative chemotherapy of human cancer. Major findings of these studies were The acute reaction of BM stem cells and differentiated BM precursor pools corresponds to the mechanisms known to be effective in animal experiments. The PB CFU-GM may be of particular importance in man in demonstrating long-term derangements. In an attempt at quantification of human BM data, an index was developed from BM spicule morphometry and from standardized BM aspirate cellularity. Stem cell defects in BM and PB were observed that did not show up in the PB counts, in particular after nitrosoureas. Indication of prolonged derangements in stem cells up to five years after chemotherapy were observed after adjuvant therapy for breast cancer. From these data, it appears advisable to study stem cell data in man for newly developed chemotherapeutic regimens in order to minimize early and late side effects on hematopoiesis.

Involvement of chromosome 9 in variant Ph1 translocation.

Cytogenetic analysis of a patient with chronic myelocytic leukemia revealed a translocation (21; 22) (q 22; q 11) without a detectable involvement of chromosome 9. By in-situ hybridization studies, however, we demonstrate a reciprocal translocation of sequences from chromosome 9 (c-abl) to Ph1 and chromosome 22 (bcr) to 9, respectively. These observations suggest a consistent participation of chromosome 9 in the Ph1 translocation, regardless of the cytogenetic subtype.

[Progressive pulmonary fibrosis due to combined treatment with BCNU, cyclophosphospahmide and cytosin-arabinoside (author's transl)]. / Progrediente Lungenfibrose unter der Kombinationstherapie mit BCNU, Cyclophosphamid und Cytosin-Arabinosid.

Two patients treated for acute leukaemia with BCNU, cyclophosphamide and cytosin-arabinoside are reported, in whom pulmonary fibrosis developed and progressed during therapy. The development of lung fibrosis during combined treatment, together with serological exclusion of other diseases known to be associated with pulmonary fibrosis, make a causal connection between the treatment and the fibrosis very probable.

Multiresidue chromatographic method for the determination of macrolide residues in muscle by high-performance liquid chromatography with UV detection.

A high-performance liquid chromatographic (HPLC) method for the simultaneous determination of tilmicosin, tylosin, spiramycin, and its major metabolite neospiramycin was developed that is suitable for porcine, bovine, and poultry muscles. Macrolide residues were extracted from muscle with acetonitrile, fat was removed by liquid-liquid extraction with isooctane, and the extract was then cleaned on Bond Elut C18 cartridges. The HPLC separation was performed on an Inertsil ODS3 C18 column (150 x 4 mm) with 0.05% trifluoroacetic acid-acetonitrile in a gradient mode. Two different chromatographic gradients were used for tilmicosin-tylosin and spiramycin-neospiramycin, and the detection wavelengths were 287 and 232 nm, respectively. The method was validated from 1/2 the maximum residue limit (MRL) to 4 times the MRL with pork muscle samples. Mean recoveries were 60, 63.5, 51, and 42% for tilmicosin, tylosin, spiramycin, and neospiramycin, respectively. The detection limits are 15 micrograms/kg for tilmicosin and tylosin, 30 micrograms/kg for spiramycin, and 25 micrograms/kg for neospiramycin. Linearity, precision, and accuracy of the method were also tested.

Mouse monoclonal IgM antibody against human lung cancer line SK-LC-3 with specificity for H(O) blood group antigen.

Spleen cells from mice immunized with the human lung cancer line SK-LC-3 were fused with mouse NS-1 myeloma cells. One of the hybrid clones produced a monoclonal IgM antibody (designated F-3), detected with antimouse Ig-MHA and hemagglutination assays. This antibody was completely absorbed by O red cells and completely inhibited by low concentrations of H(O) glycoproteins and hog mucin (A + H). Bombay (Oh) red cells completely failed to absorb F-3 activity even after treatment with neuraminidase. A1, A2, A1B, A2B, and B red cells and A- and B-glycoproteins were less effective in absorbing or inhibiting F-3 activity. Other glycoproteins (including those having Lea or blood group precursor structures) showed little or no inhibitory activity. Serum from nude mice carrying F-3 hybridoma agglutinated O and A2 red cells at a titer of 1:40,000 and 1:640, respectively. A1, A1B, A2B, and B red cells were agglutinated with titers of 1:80 or less. Monoclonal antibody F-3 is, therefore, highly specific for H(O) blood group determinants.

Daunomycin, cytosin-arabinoside and VP-16 (DAV) for myeloid blast crisis of CML.

Nine patients with myeloid blast crisis of Philadelphia chromosome-positive chronic myelocytic leukemia received 1-3 courses of intensive induction chemotherapy with DAT (daunomycin, cytosin-arabinoside and 6-thioguanin) or DAV (daunomycin, cytosin-arabinoside and VP-16). Eight patients responded with clearing of blasts from peripheral blood giving a response rate of 89%. However, bone marrow aplasia with less than 5% blasts was seen in only 2 patients. These 2 patients subsequently received an allogeneic bone marrow transplant and achieved complete remissions of 3 and 6 month duration. All patients died due to progression of blast crisis. Median survival of the group was 164 days. These results were compared to a historical control group of 31 patients with myeloid blast crisis treated with vincristine and prednisone. Despite a significantly better response rate with DAV or DAT (8 of 9 versus 9 of 31, p = 0.01) survival was not significantly different than that of the control group.

Polycythemia vera. A clinical study of 141 patients.

The clinical course of 141 unselected patients (64 m, 77 f, median age 59) with polycythemia vera (PV), treated during the period 1967 to 1986 was analyzed to study prognostic factors and the correlation between treatment strategies and complication rates. Therapy was performed according to a prospectively defined treatment protocol. Primary control of the disease was achieved by phlebotomy. Marrow suppression by radioactive phosphorus or low dose busulphan was used only as a second-line therapy or to lower high platelet counts. The clinical course of the patients was characterized by a low rate of acute leukemia (4%) and a high rate of thromboembolic complications (40%). Myelofibrosis developed in 17 patients (12%). Median survival of the patents was 9.4 years. The prognostic influence of several parameters at the time of diagnosis was tested: age, sex, spleen size, percentage of blood blasts + promyelocytes, leucocyte count, platelet count, hemoglobin, hematocrit, reticulocyte count and the values of the lactate-dehydrogenase (LDH) and the alkaline neutrophil phosphatase (ANP) all had no significant influence on the length of survival. The prognosis of PV patients with atypical disease presentation at diagnosis was not different from patients with typical disease.

Budd-Chiari syndrome and thrombosis of other abdominal vessels in the chronic myeloproliferative diseases.

Of 501 patients with chronic myeloproliferative diseases (c-MPD) 18 developed thrombosis of major abdominal vessels including 6 with hepatic vein thrombosis (Budd-Chiari syndrome). The complication was seen in 14 of 140 (10%) patients with polycythemia vera (PV), 3 of 23 (13%) patients with essential thrombocythemia (ET), 1 of 106 (1%) patients with idiopathic myelofibrosis (IMF), and none of 232 patients with chronic myelogenous leukemia (CML). Leading symptoms and signs were abdominal pain, progressive splenomegaly, widening abdominal girth, ascites, venous collaterals, and nausea and vomiting. The diagnostic modalities with highest specificity were angiography and explorative laparotomy. A causal relationship between the thrombotic event and hematocrit, thrombocyte count, or hemostatic abnormalities at the time of diagnosis could not be established. Detailed laboratory tests of platelet function and coagulation and fibrinolytic parameters of 5 surviving patients did not show any specific defect. Despite medical and surgical intervention, 39% of the patients died within 2 months after diagnosis of the thrombosis. The majority of the survivors developed further complications like liver cirrhosis with portal hypertension and esophageal varices or the short bowel syndrome after extensive bowel resection for mesenterial infarction.

Blast crisis of Philadelphia chromosome-positive chronic myelocytic leukemia (CML). Treatment results of 69 patients.

We have studied the clinical courses of 69 patients with blastic crises of Philadelphia chromosome positive CML to identify parameters that were associated with an increased response rate or survival. Cytogenetic analysis at the time of blastic transformation revealed additional chromosome changes in 70% of the patients tested. Bone marrow fibrosis was detected in 58% of evaluable patients. Lymphoblastic transformation was seen in 28% of the patients tested with cell surface marker analysis. The value of 5'-nucleotidase as a marker for distinguishing lymphoid from non-lymphoid blast crisis was confirmed. Of 57 evaluable patients, 23 (40%) responded to therapy (CR/PR longer than 14 days). Median survival was 75 days. Longer survival was related to the following factors: Ph1-chromosome as the only detectable cytogenetic abnormality; lymphoblastic transformation; no bone marrow fibrosis; high percentage of blasts and promyelocytes in the bone marrow, and response to therapy. No prognostic significance was associated with age, sex, Tdt, LDH, spleen size, duration of the chronic phase of the disease, white blood cell count, Hb, platelet count and percentages of basophils, eosinophils, erythroblasts and blasts and promyelocytes in the peripheral blood. These data confirm the poor prognosis of patients with blastic crisis of CML treated by conventional chemotherapy.

Blood group change in a patient with blastic transformation of a myelodysplastic syndrome.

Loss of certain red blood cell antigens has been described in patients with acute myelocytic leukemia (AML). This paper describes the loss of blood group A antigen in a patient with AML. The acute leukemia in this patient was preceded by a myelodysplastic syndrome for several months. At the time of diagnosis the patient's red cells showed the 0 Rh(D)+ phenotype. After induction of complete remission with two courses of Daunorubicin, Cytosin-arabinosid, and Etoposid his blood group reverted to A2. Serological studies including saliva analysis revealed that the original blood group was very likely A.

T lymphocytes lack rearrangement of the bcr gene in Philadelphia chromosome-positive chronic myelocytic leukemia.

To study the possible involvement of T lymphocytes in Philadelphia chromosome (Ph)-positive chronic myelocytic leukemia (CML) we analyzed the arrangement of the bcr gene in T cell and non-T cell samples of 12 CML patients. Although all the patients showed bcr rearrangements in non-T cell fractions, T cell populations lacked respective gene recombinations. Moreover, by Southern blot analyses using T cell receptor beta chain sequences our data indicate polyclonality of T cell samples from 11 of 12 cases; in one patient a clonal T cell population could be identified. These results suggest that T lineages of most Ph-positive CML patients are not derived from pluripotent stem cells involved in leukemogenesis and thus confirm previous investigations based on cytogenetic or glucose-6-phosphate dehydrogenase analyses. The demonstration of polyclonal T cell populations may reflect persistence of stem cells committed to differentiate only into T cells.

Idiopathic thrombocytopenic purpura and autoimmune hemolytic anemia in Hodgkin's disease.

Idiopathic thrombocytopenic purpura (ITP) and Coombs' positive hemolytic anemia (AIHA) were found, respectively, in 5 (1%) and 1 (0.2%) of 492 patients with Hodgkin's disease (HD). 33 cases of ITP associated with HD reported in the literature are reviewed. Of our cases, ITP was coincident with the diagnosis of HD in 1 patient. In another patient ITP preceded the diagnosis of HD by 41 months and in the remaining 3 patients the diagnosis of ITP was established after they had been successfully treated for HD. A herpes zoster infection preceded ITP by 1 month in 1 patient and another had herpes zoster at the time of diagnosis of ITP. AIHA had preceded the diagnosis of HD by 8 months in 1 case. In patients with ITP the prognosis seems to be related only to the status of the underlying HD.

Low-dose Ara-C in the treatment of acute leukemia. Cytotoxicity or differentiation induction?

The differentiation inducing effect of low-dose Ara-C on human myeloid leukemic cells was studied in two patients with subacute myelocytic and subacute myelomonocytic leukemia in vivo and in vitro. By continuous i.v. administration of 10 mg Ara-C/m2 over 12 h daily for 12 or 20 days complete remissions were obtained in both patients with normalization of the incidence of the committed progenitor cells BFU-E and CFU-C in the marrow while the incidence of pluripotent CFU-GEMM remained subnormal. Parallel cultures of the patients' bone marrow cells in diffusion chambers (DC) implanted in mice demonstrated a clear cytotoxic effect of low-dose Ara-C. The greater increase of granulopoietic cells within DC in the Ara-C exposed group than in control mice after the end of drug administration is, in addition, an indication for differentiation induction by this kind of Ara-C therapy.

Idiopathic myelofibrosis: a retrospective study of 103 patients.

The clinical course of 103 patients (50 males, 53 females; median age 59 years) with idiopathic myelofibrosis (IMF) seen at our hospital between 1967 and 1986 was analyzed retrospectively. Common symptoms and signs at the time of diagnosis were: myelofibrosis (96%), splenomegaly (84%), anemia (81%), osteosclerosis (45%), malaise (41%) and leukocytosis (41%). It was possible to follow the majority of patients without treatment or with transfusion therapy only for prolonged periods of time. The use of cytostatic drugs and radiotherapy was restricted as much as possible. Probably due to this treatment strategy the incidence of acute leukemia was low (5%). Major thromboembolic complications were seen in 19% of the patients. Median survival of the patients was 4.3 years. The prognostic influence of several disease parameters determined at the time of diagnosis was tested: age, sex, leukocytes, platelets, hemoglobin, reticulocytes, LDH, ANP-score, spleen size and percentage of peripheral blood blasts + promyelocytes had no significant influence on the length of survival. Osteosclerosis, a presumed sign of advanced disease, was not correlated with survival either.

Cell-surface antigens of human lung tumors detected by mouse monoclonal antibodies: definition of blood-group- and non-blood-group-related antigenic systems.

The pattern of antigen expression in human non-small-cell cancers of various histological subtypes has been studied. Mouse monoclonal antibodies (MAbs) were generated following immunizations with cell lines of squamous, adeno- and anaplastic large-cell carcinomas of the lung. Seven non-blood-group-related antigens were defined in addition to 5 antigens related to blood-group determinants. Detailed specificity was established with a large panel of cultured cell lines and normal and neoplastic tissues. MAb F-18 reacted in direct tests with the immunizing squamous lung carcinoma cell line, with 5 out of 5 choriocarcinoma cell lines, but with no other cell lines. No expression of F-18 antigen was observed in any normal or malignant tissue examined. The other 6 non-blood-group-reactive MAbs (F-7, F-8, F-11, F-15, F-16 and F-17) could be distinguished by their reactivity on a panel of cultured cells and tissues. One MAb in this group (F-17) reacted strongly with 19/35 lung tumor cell lines, 32/76 other tumor-derived cell lines, cultured normal kidney cells and fetal lung fibroblasts. This antibody did not react with any normal adult tissues examined, but did react with several cancer tissues including 1/17 lung tumors, 2/4 ovarian cancers and 1/5 colon tumors. Immunoprecipitation tests revealed that 5 of the antigens were glycoproteins: F-18 (Mr greater than 200,000), F-15 (Mr 44,000), F-16 (Mr 90,000), F-17 (Mr 95,000) and F-8 (Mr 95,000). Four MAbs detected Y blood-group antigen (Le(y)), only 2 of which were able to agglutinate O erythrocytes. Another antibody detected X blood-group antigen (Le(x)).