Are serial CA 19-9 kinetics helpful in predicting survival in patients with advanced or metastatic pancreatic cancer treated with gemcitabine and cisplatin?

BACKGROUND: Serial kinetics of serum CA 19-9 levels have been reported to reflect response and survival in patients with pancreatic cancer undergoing surgery, radiotherapy, and chemotherapy. We prospectively studied serial kinetics of serum CA 19-9 levels of patients with locally advanced or metastatic disease treated with gemcitabine and cisplatin. PATIENTS AND METHODS: Enrolled in the study were 87 patients (female/male = 26/61; stage III/IV disease = 24/63). Patients received gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 plus cisplatin 50 mg/m(2) on days 1 and 15, every 4 weeks. Serum samples were collected at the onset of chemotherapy and before the start of a new treatment cycle (day 28). RESULTS: 77 of 87 patients (88.5%) with initially elevated CA 19-9 levels were included for evaluation. According to imaging criteria, 4 (5.2%) achieved a complete remission and 11 (14.3%) achieved partial remission, yielding an overall response rate of 19.5%. 43 (55.8%) patients were CA 19-9 responders, defined by a > or = 50% decrease in CA 19-9 serum levels within 2 months after treatment initiation. Except for one, all patients who had responded by imaging criteria (n = 14) fulfilled the criterion of a CA 19-9 responder. Despite being characterized as non-responders by CT-imaging criteria (stable/progressive disease), 29 patients were classified as CA 19-9 responders (positive predictive value 32.5%). Independent of the response evaluation by CT, CA 19-9 responders survived significantly longer than CA 19-9 nonresponders (295 d; 95% CI: 285-445 vs. 174 d; 95% CI: 134-198; p = 0.022). CONCLUSION: CA 19-9 kinetics in serum serve as an early and reliable indicator of response and help to predict survival in patients with advanced pancreatic cancer receiving effective treatment with gemcitabine and cisplatin.

[Complication rate in the treatment of inter- and subtrochanteric femur fractures with two intramedullary osteosyntheses. Comparison of a conventional nailing system and a rotation stable fixation of the head-neck-fragment, gammanail and glidingnail]. / Komplikationsraten bei der Versorgung von per- und subtrochanteren Femurfrakturen mit zwei intramedullären Osteosyntheseverfahren. Vergleich eines konventionellen Nagelsystems mit einem rotationsstabilen Verfahren im Kopf-Hals-Fragment, Gammanagel und Gleitnagel.

Aim of the study was to evaluate typical complications in osteosynthesis of inter- and subtrochanteric femur fractures with intramedullary nailing systems. In the literature screw perforation of the femoral head into the acetabulum, postoperative fracture of the femur shaft, intraoperative shaft fracture, problems in placing of distal locking screws and deep infections are mostly described. In a retrospective study the complication rate of 100 consecutive gammanail osteosyntheses (GAN) and 96 glidingnail osteosyntheses (GLN) was analysed. 93 % of GAN and 89.3 % of GLN were followed up. Cutting out rate of GAN/GLN was 7.0 %/3.1 %, postoperative shaft fractures occurred in 1.0 %/0 %, intraoperative shaft fractures in 1.0 %/2.1 %, problems with distal locking in 2.0 %/1.0 % and deep infections in 3.0 %/1.0 %. In an analysis of internationally published data on 2 241 GAN and 365 GLN the cut-out rate was 2.3 %/0.5 %, postoperative shaft fracture 2.2 %/1.4 %, intraoperative shaft fracture 1.2 %/0.3 % and deep infection 1.2 %/2.2 %. GLN shows lower complication rates with regard to femoral head perforation and late shaft fracture than GAN.

Positron emission tomography in non-Hodgkin's lymphoma: assessment of chemotherapy with fluorodeoxyglucose.

Positron emission tomography (PET) using F-18 fluorodeoxyglucose (FDG) was performed in non-Hodgkin's lymphoma (NHL), which is known to be highly responsive to chemotherapy, but also yields variable treatment results to answer the following questions: (1) What is the extent and time course of changes in FDG utilization in response to chemotherapy? (2) Are the changes of FDG uptake at early time points of chemotherapy predictive for therapy outcome? (3) Which quantitative FDG parameter provides the most sensitive measures of initial tumor response? Dynamic PET scans were performed in 11 patients at baseline and 1 and 6 weeks after initiation of chemotherapy. Based on attenuation corrected images acquired 30 to 60 minutes postinjection, standardized uptake values (SUV) were determined. Arterial input functions were estimated from vascular F-18 activity and the metabolic rates for FDG (MRFDG) were calculated using Patlak analysis. Before chemotherapy, high FDG uptake was found in all lesions (SUV[max] 13.3 +/- 4.2). Seven days after initiation of chemotherapy, tumor FDG uptake decreased 60% (SUV[max]). A further decrease of 42% was seen at day 42 resulting in a total decrease of 79% from baseline to day 42. During a follow-up of 16.0 +/- 4.2 months, six of the 11 patients continued to show complete remission. Seven days after initiation of chemotherapy, this group of patients displayed significantly lower mean MRFDG than the group of patients with relapse. At day 42, all parameters of FDG uptake showed a significant difference for both patient groups. The relative change of MRFDG from baseline to day 42, as well as from day 7 to day 42, was significantly larger as compared with SUV parameters. Standard chemotherapy of patients with NHL causes rapid decrease of tumor FDG uptake as early as 7 days after treatment, which continues to decline during therapy, indicating the sensitivity of metabolic signals to chemotherapeutic interventions. FDG uptake at 42 days after therapy was superior in prediction of long-term outcome over day 7 parameters. Dynamic data acquisition combined with Patlak analysis of FDG kinetics may provide superior information in therapy monitoring.

[High malignant B-cell non-Hodgkin lymphoma of the heart: intravital diagnosis by transesophageal echocardiography controlled biopsy]. / Hochmalignes B-Zell-Non-Hodgkin-Lymphom des Herzens: intravitale Diagnose durch transösophageale Echokardiographie-gesteuerte Biopsie.

We report about a 66-year old patient with Non-Q-wave infarction in coronary artery two-vessel disease. During an echo- and transesophageal multiplane echocardiography preoperatively before a coronary artery bypass surgery a right atrium septal tumor of unknown form was discovered. The computerized axial tomography (CAT) and nuclear magnetic resonance (NMR) scans did not demonstrate extracardiac pathologic findings. A transesophageal echocardiography-guided biopsy of the right atrial septum over the vena femoralis and the right atrium enabled intra vitam a very early diagnosis of high malignant B-cell Non-Hodgkin-lymphoma without the need for thoracotomy. The diagnosis was confirmed histopathologically and immunohistochemically and early treatment with cytostatic therapy could begin. To our knowledge the transesophageal echocardiography-guided biopsy has never been described in the worldwide literature.

Phase I-II study of interferon-gamma and eflornithine (DFMO) in patients with advanced renal cell carcinoma, malignant melanoma and colorectal carcinoma.

Eflornithine (DFMO) and interferon-gamma (IFN-gamma) are known to exert synergistic activity on inhibition of ornithinedecarboxylase (ODC) in vitro and in experimental animal tumors thereby inhibiting tumor proliferation. In this study, we prospectively investigated therapeutic effects and side effects of a combination of DFMO and IFN-gamma in 15 patients with renal cell carcinoma (RCC), 9 with malignant melanoma (MM), and 9 with colorectal carcinoma (CRC). DEMO was given orally at a dose of 3x4 g/day during the first 2 weeks of each month; IFN-gamma was administered daily subcutaneously during the DFMO administration periods and every other day during the following 2 weeks. The starting dose of IFN-gamma was 30 mu g/m(2) in the first 5 patients and 60 mu g/m(2) in the next 28. IFN-gamma dose was doubled every 4 weeks to a maximum dose of 120 mu g/m(2) and 240 mu g/m(2), respectively. Therapy was applied for three months in cases with stable disease or partial remission. In 15 patients treatment was stopped after 3 to 11 weeks after initiation of therapy because of tumor progression (14 cases) or severe side effects (1 case). In one out of 15 patients with renal cell carcinoma a partial response was observed lasting 7 months, 5 patients showed stable disease, and 9 progressed. In patients with malignant melanoma and colorectal carcinoma, stable disease was observed in one patient and progressive disease in 8 patients per group. The most frequent side effects were fever and gastrointestinal disturbances observed in 26 patients each. The results of this study indicate that DFMO combined with IFN-gamma has no significant therapeutic activity in patients with advanced renal cell carcinoma, malignant melanoma, and colorectal carcinoma.

[Angioimmunoblastic lymphadenopathy with dysproteinemia and sclerosing cholangitis]. / Angioimmunoblastische Lymphadenopathie mit Dysproteinämie und sklerosierender Cholangitis.

A 28-year-old man with recurrent swelling of both upper eyelids was found to have increased values in several liver function tests (GOT 162 U/l, GPT 356 U/l, gamma-GT 643 U/l, bilirubin 3.0 mg/dl, alkaline phosphatase 925 U/l). Abdominal ultrasonography demonstrated lymph node enlargements up to 3 cm, dilated intra- and extrahepatic bile ducts, as well as a cyst of 3 cm size in the pancreatic tail. Endoscopic retrograde cholangiopancreatography and punch biopsy of the liver revealed sclerosing cholangitis. In addition to the eyelid swellings the patient also had protrusion of the left eyeball, blood eosinophilia (800/microliter) and marked increase in polyclonal IgG (6930 mg/dl) with lymphadenopathy suggesting the diagnosis of angioimmunoblastic lymphadenopathy with dysproteinaemia (AILD, lymphogranulomatosis X), confirmed by lymphocyte surface marker analysis. However, histological examination of a lymph node was more suggestive of a T-zone lymphoma. Treatment with ursodeoxycholic acid (250 mg three times daily) and prednisolone (initially 2 mg/kg daily) quickly led to normal biochemical values and regression of the eye changes. In addition, treatment with interferon alpha-2b (initially 3 mill. U daily for 10 days) was begun. The abnormalities in the bile ducts disappeared 6 months later. The patient has been in full remission for 25 months (prednisolone dosage reduced to 12.5/7.5 mg alternating daily and interferon alpha-2b 3 mill. U three times weekly). This response makes AILD with secondary involvement of the bile ducts the most likely diagnosis.

Treatment of metastatic gastric carcinoma with a modified FAMTX chemotherapy regimen.

Fifty patients with locally far advanced or metastasizing gastric carcinoma were treated with 5-fluorouracil, adriamycin and methotrexate using a slightly modified FAMTX protocol. Complete remission was achieved in four (8%) patients, confirmed operatively, partial remission in 13 (26%) patients, two of these going into complete remission after operative removal of residual tumor. Median duration of remission for the six patients in complete remission was 21 months, for those in partial remission five months. Median survival for all 50 patients was seven months, for those in complete and partial remission 12 months, and for those without remission four months. These results indicate the possibility of a further improvement of treatment results in patients with metastasizing gastric carcinoma using this protocol of combined operation and chemotherapy.

[Individualization of chemotherapy through in vitro predictive determination of the cytostatic sensitivity of malignant tumors]. / Individualisierung der Chemotherapie durch prädiktive In-vitro-Bestimmung der Zytostatikasensitivität maligner Tumoren.

An in-vitro test was developed for predicting the efficacy of anti-tumour chemotherapy. Cell cultures were grown from freshly removed tumours and it was then demonstrated by DNA cytophotometry and immuno-cyto-chemistry whether the growing tumour cells corresponded to those of the original tumour cells. Several cytostatic agents were then tested for their efficacy of inhibiting growth at clinically customary dosage. Growing cell cultures were established in 306 of 413 submitted tumours (74%). They responded quite differently to the various drugs that were tried. The clinical course in 94 cases was observed for minimally four and a mean of eight months to obtain an in-vitro to in-vivo correlation of response, with 178 individual correlations. A discrepancy was recorded in 16% of cases, a false-positive in-vitro sensitivity result was 3.6 times more frequently associated with an in vivo resistance than the reverse. Concordance between test results and clinical tumour response occurred in 84%. The monolayer proliferation assay correctly indicated resistance in 93.8%, sensitivity in 72.8%.

[The results of a modified FAMeth chemotherapy protocol in metastatic stomach carcinoma]. / Ergebnisse eines modifizierten FAMeth-Chemotherapieprotokolls beim metastasierten Magenkarzinom.

Fifty patients with locally far progressed or metastasizing gastric carcinoma were treated with 5-fluorouracil, adriamycin and methotrexate using a slight modification of the FAMeth schema. Full remission was achieved in four patients, confirmed at a second-look operation. Partial remission was achieved in 13 patients, two of whom went into full remission after operative removal of residual tumour. Median duration of remission for the six patients in full remission was 21 months, for those in partial remission five months. Median survival of all 50 patients was seven months, of those in full and partial remission 12 months, and those without remission four months. The results indicate that this protocol of combined operation and chemotherapy can further improve the results of treating metastasizing gastric carcinoma.

Common variable immunodeficiency syndrome and nodular lymphoid hyperplasia in the small intestine.

We report on a case of nodular lymphoid hyperplasia (NLH) of the small intestine in a patient with common variable immunodeficiency (CVID) syndrome. The CVID syndrome comprises a group of heterogeneous immunological disorders. It is characterised by hypogammaglobulinemia, recurrent sinopulmonary infections, gastrointestinal disorders (including diarrhea, infestation with Giardia lamblia, chronic-atrophic gastritis and nodular lymphoid hyperplasia (NLH), and an increased risk of malignancy. NLH is frequently associated with gastrointestinal lymphomas. It has also been found in the terminal ileum of children and in adult patients with Gardner's syndrome. NLH is found in about 20% of patients with the CVID syndrome. The diagnosis of NLH requires endoscopic and bioptic-histological examinations and the determination of the immunoglobulins.

Neutrophilic leukemia accompanied by hemorrhagic diathesis: report of two cases.

Chronic neutrophilic leukemia, which may be regarded a variant of myeloproliferative disease, is associated with mature peripheral neutrophilia, hepatosplenomegaly, tissue infiltration by mature and immature granulocytes, an elevated leucocyte alkaline phosphatase score, absence of the Ph1 chromosome and elevated vitamin B12. In the few cases described up to now thrombocytopenia and bleeding complications were frequently noticed. Here we describe two patients with chronic neutrophilic leukemia in whom thrombocytopenia and/or a profound defect of platelet function were the cause of death.

[The pharmacokinetics of doxorubicin]. / Zur Pharmakokinetik von Doxorubicin.

Doxorubicin serum levels were measured with a highly specific reversed-phase HPLC-method in patients undergoing combination chemotherapy. Serum elimination kinetics of doxorubicin follow a bi- or triphasic first order pattern with a high interpatient variability. T 1/2 of the first distribution phase was 5.4 min. T 1/2 of the terminal steady-state elimination phase was 1273 min. After consecutive bolus application of 15 mg/m2 (4 times per 48 h) cumulation of doxorubicin was found in patient's serum. Serum levels 4 h after bolus injection of doxorubicin were found to be correlated with the area under the elimination curve. Therefore, 4 h serum levels after bolus injection can be used for clinical studies correlating pharmacokinetics with antineoplastic properties of doxorubicin.

[Malignant lymphoma and tuberculosis]. / Malignes Lymphom und Tuberkulose.

In 153 patients with malignant lymphoma (1981-1984) one case of simultaneous occurrence of a Non-Hodgkin lymphoma of high grade malignancy and tuberculosis of a cervical lymph node is reported. Typical morphological characteristics were absent. In the first biopsy mycobacterium tuberculosis was demonstrated in a microbiological animal trial. In a second biopsy a centroblastic lymphoma was found. It is possible that the onset of lymph node tuberculosis is promoted by the impaired immunological defence mechanism of the malignant growth. On the other hand, the malignant lymphoma might be caused by the chronic tuberculous inflammation. Independent of this question, a persistent cervical lymphoma must be identified by biopsy and microbiology. An essential factor in deciding both therapy and prognosis of the malignant lymphoma is to diagnose the presence of a tuberculous infection, for the concurrent treatment of primary and secondary disease provides the only chance of cure.

Occurrence of the common acute lymphoblastic leukemia antigen on blast cells of a patient with chronic myelomonocytic leukemia in non-lymphoid blastic phase.

Leukemias showing a conspicuous lymphoid phenotype, ie, those that are HLA-DR positive, common acute lymphoblastic antigen (cALLA) positive, terminal deoxynucleotidyl transferase (TdT) negative, as well as myeloperoxidase positive (MPO), could be considered so-called mixed leukemias. Leukemias with biphenotypic blasts have to be distinguished from cases comprising two separate subpopulations that express different lineage-associated characteristics. By use of a simple new method (Immunogold Staining) we examined a case of chronic myelomonocytic leukemia in blastic phase and demonstrated simultaneous staining for MPO/alpha-naphthyl-esterase and expression of the HLA-DR-positive, cALLA-positive, and TdT-negative phenotype. The cALL antigen was detected only on mono- and myelo-monoblasts; its expression was inversely related to the MPO positivity, and it disappeared together with these types of blasts after chemotherapy. On the basis of our findings it remains obscure whether the cALL antigen at the initial presentation was due to the immature monocytic features of the leukemic cells or disclosed on additional lymphoid differentiation pattern of the blasts.

[Prognostic value of serum CEA and therapy-induced nonspecific CEA levels in metastasizing breast carcinoma]. / Prognostische Aussage des Serum-CEA und therapiebedingte unspezifische CEA-Verläufe beim metastasierenden Mammakarzinom.

In 57 patients with metastasized breast carcinoma, serum CEA levels (CEA-Ria-Kit, Abbot) were correlated with the clinical course under endocrine or cytostatic therapy. In 20 patients, CEA was determined at intervals of 1 to 3 days over the first 4 weeks of treatment and in 21 patients at intervals of 1-3 weeks. In 16 patients, CEA was determined prior to treatment. The clinical development was judged according to the program of UICC. We found pretreatment CEA values higher than 25 ng/ml serum mostly in patients with liver involvement and in patients with progression under the following therapy. In 22 patients, progress or remission of the disease were correlated with CEA increase or decrease of more than 20% during the first 8 weeks. In 11 patients, we found no correlation between CEA and clinical course. From the remaining 8 cases, CEA levels were out of the measuring range in 6 patients, in 2 patients we were unable to interpret the clinical course doubtlessly. There were no short-termed CEA alternations after the start of the treatment rendering a possible early estimation of the therapy effect. In 5 of 23 patients treated with methylprogesteronacetate and aminoglutethimide a continuous CEA increase developed despite clinical remission. This was not found in 10 patients treated with cytostatic chemotherapy. The pretreatment CEA is a useful prognostic parameter in patients with metastasizing breast cancer. CEA should be determined weekly in patients with increasing CEA levels under therapy and monthly in patients with decreasing CEA levels. The possibility of a tumor-independent CEA rise as a side-effect of treatment must be taken into consideration.

[Possible prevention of adriamycin-induced cardiomyopathy by verapamil. Results of a pilot study]. / Mögliche Prävention der Adriamycin-induzierten Kardiomyopathie durch Verapamil. Ergebnisse einer Pilotstudie.

An increased cytoplasmatic calcium level seems to play an important role in the pathogenesis of Adriamycin (ADM)-induced cardiomyopathy. Experiments have shown that calcium channel blockers such as verapamil may prevent this type of cardiomyopathy in animals, but data are contradictory. In a clinical pilot trial, the left ventricular function of 22 patients undergoing ADM-chemotherapy in combination with verapamil was examined. M-mode echocardiograms were performed parallel to every chemotherapy course. Left ventricular function was determined by fractional shortening rate (FS) and peak fibre shortening velocity (V ef max.). Three 40-mg doses of verapamil were given p.o./day continuously. Data of these patients were compared with a control group of 61 patients treated and checked equally without additional verapamil therapy. In the course of therapy parameters of left ventricular function remained almost constant in the verapamil group but decreased significantly in the control group. In the verapamil group FS changed by -0.05 FS %/100 mg ADM/m2, V ef max. by +0.015 circ./s/100 mg ADM/m2 compared with -2.31 FS % and -0.33 circ./s in the control group (P 0.01 and 0.001, respectively). In the verapamil group no congestive heart failure occurred and no patient showed FS below 30%, whereas in the control group in 23% (14) of the cases ADM therapy had to be stopped because FS fell below 30%. One congestive heart failure was observed. These clinical results suggest that verapamil may be a useful drug for preventing ADM-induced cardiomyopathy but further investigations are necessary.

[Hyperlipoproteinaemia during additional methenolone administration in the treatment of metastasizing carcinoma of the breast]. / Hyperlipoproteinämie bei additiver Behandlung des metastasierenden Mammakarzinoms mit Metenolonönanthat.

The effect of additive administration of methenolone oenanthate (Primobolan) on lipid metabolism was studied in 28 menopausal women with metastasizing carcinoma of the breast. In ten women hyperlipoproteinaemia type IIa was demonstrated in the course of treatment, while in two there was hyperlipoproteinaemia type IIb. One of the latter patients had a myocardial infarction in the course of treatment. There was no relationship between the level of hypercholesterolaemia and the methenolone dosage. Nor was it possible to classify the type of cholesterolaemia as a bile stasis syndrome. The hyperlipoproteinaemia regressed in every case once methenolone treatment was discontinued.