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A 49 year old man presented with a three months' history of symmetrical joint and muscle pain, starting in the elbow region with further extension to the whole body, and weight loss of 11 kg within four months. Laboratory investigation showed an erythrocyte sedimentation rate (ESR) of 100 mm/1st h, leucocytosis of 20.6×109/l, and a massively raised rheumatoid factor. Creatine kinase (CK) and antineutrophil cytoplasmic antibodies (ANCA) were normal. The patient had pain in elbow, wrist, knee, and ankle regions, though no joint swelling was seen. Rheumatoid arthritis was suspected and treatment with steroids and methotrexate was started. Four weeks later, an ascending numbness of the extremities occurred, starting in the left foot and subsequently spreading to both lower legs and forearms. This was accompanied by a progressive muscle weakness. The patient was then referred to our institution. On admission, the patient presented with a temperature of 38.6°C, severely reduced general condition, blood pressure of 120/95 mm Hg, and a heart rate of 120 beats/min. He had gastric cramps after food intake and could not control bowel movements and urination owing to generalised weakness. Neurological examination showed severe pain on palpation of the proximal extremities and marked impairment of sensibility of the distal extremities as well as generalised hypo/areflexia. In addition, a distally accentuated, almost complete paralysis rendered the patient unable to lift his arms, legs, or head against gravity. Laboratory investigation at that time showed an ESR of 120 mm/1st h, CK of 1425 IU/l (normal

Experimental evidence of the existence of liver-specific growth factors has been collected for more than two decades. Blood-borne growth-promoting activity of hepatocytes may be separated into plasma and platelet-derived factors. Several groups have observed the stimulation of hepatocyte growth in vitro by some platelet-associated activity, which was recently isolated from rat platelets as a 27-kDa protein called platelet growth factor (PGF). There is evidence of at least two different growth factors for hepatocytes derived from platelet-poor rat plasma, 'hepatopoietin' A and B. The partial purification of several other factors has been reported. One of these factors was prepared from the plasma of patients with fulminant hepatic failure. In addition to these 'humoral' factors, cytosolic growth-promoting activity has been partially purified by several groups. While the humoral factors described so far are only active on normal hepatocytes, the cytosolic 'hepatic stimulator substance' (HSS) also promotes the proliferation of differentiated hepatoma cells. In addition, it appears to depend on the permissive action of epidermal growth factor (EGF). None of the liver-specific growth factors except PGF has been purified to homogeneity. Thus, their significance for the control of the proliferation of normal and transformed hepatocytes is still an unsettled issue.

Fifty-nine consecutive patients with stenosing carcinoma of the upper gastrointestinal tract were entered into a prospective study defining parameters of survival during laser treatment. A total of 322 laser sessions were performed, 56% of which on an outpatient basis. Life table analysis revealed that survival was poor in the presence of metastases, and in patients under 60 years of age. Survival was statistically independent of tumor histology, location, length or previous treatment of any kind. In contrast, the degree of stenosis both before and after laser treatment was related to survival in a significant fashion. The best separation into groups was achieved with the parameter dysphagia after laser treatment. Thus, the data are compatible with an important role of adequate enteral nutrition in these debilitated patients.

Background Thymostimulin is a thymic peptide fraction with immune-mediated cytotoxicity against hepatocellular carcinoma (HCC) in vitro and palliative efficacy in advanced HCC in two independent phase II trials. The aim of this study was to assess the efficacy of thymostimulin in a phase III trial. Methods The study was designed as a prospective randomised, placebo-controlled, double-blind, multicenter clinical phase III trial. Between 10/2002 and 03/2005, 135 patients with locally advanced or metastasised HCC (Karnofsky ≥60%/Child-Pugh ≤ 12) were randomised to receive thymostimulin 75 mg s.c. 5×/week or placebo stratified according to liver function. Primary endpoint was twelve-month survival, secondary endpoints overall survival (OS), time to progression (TTP), tumor response, safety and quality of life. A subgroup analysis according to liver function, KPS and tumor stage (Okuda, CLIP and BCLC) formed part of the protocol. Results Twelve-month survival was 28% [95%CI 17-41; treatment] and 32% [95%CI 19-44; control] with no significant differences in median OS (5.0 [95% CI 3.7-6.3] vs. 5.2 [95% CI 3.5-6.9] months; p = 0.87, HR = 1.04 [95% CI 0.7-1.6]) or TTP (5.3 [95%CI 2.0-8.6] vs. 2.9 [95%CI 2.6-3.1] months; p = 0.60, HR = 1.13 [95% CI 0.7-1.8]). Adjustment for liver function, Karnofsky status or tumor stage did not affect results. While quality of life was similar in both groups, fewer patients on thymostimulin suffered from accumulating ascites and renal failure. Conclusions In our phase III trial, we found no evidence of any benefit to thymostimulin in the treatment of advanced HCC and there is therefore no justification for its use as single-agent treatment. The effect of thymostimulin on hepato-renal function requires further confirmation. Trial Registration Current Controlled Trials ISRCTN64487365.