Natural history of patients with untreated liver metastases from colorectal cancer

One hundred fifty-five patients, laparotomized because of colorectal cancer, were retrospectively evaluated with special attention given to the natural course of untreated synchronous liver metastases. The median survival time for patients with synchronous liver metastases was 4.5 months. The survival time was mainly influenced by the extent of tumor involvement in the liver. Patients with elevated levels of serum-alkaline phosphatase at the time of operation had a significantly shorter survival time than those with normal values. Serum alkaline phosphatase levels are a good indication of prognosis. The incidence of synchronous liver metastases was 16 percent. This low rate is partly explained by the development of metachronous liver metastases in five patients within 1 year. Comparison with previous reports, often more than 10 years old, revels that the poor prognosis of patients with untreated liver metastases from colorectal cancer has remained unchanged.     

Sentinel lymph node biopsy staging for cutaneous malignant melanoma of the head and neck

Conclusion Sentinel lymph node biopsies (SLNBs) can be performed safely and with reasonable accuracy in HNM patients. The outcome provides important prognostic information concerning DFS and further treatment. However, one must recognize that SLNB is a multidisciplinary procedure with a learning curve for all. Objectives To evaluate efficacy of performing SLNBs in a series of consecutive patients with cutaneous head and neck melanoma (HNM)?≥?T1b from introduction of the procedure and 10 years onward. Method End-points comprised of SLNB outcome, disease-free survival (DFS), and overall survival (OS). Results SNs were harvested in 128 of 160 patients (median Breslow?=?2.0?mm, 29% ulcerated); success rate?=?80.0%, or 92.1% if excluding patients where SLNBs were omitted due to non-localization on pre-operative imaging or because of SN-location in the parotid basin. Ten patients (7.8%) had positive SLNBs and were offered early completion neck dissections. Of the 146 patients available for follow-up (median?=?27 months), 15.8% had recurrent disease. The risk of a regional nodal recurrence after a negative SLNB was 7.5%. SN-negative patients had improved DFS c.f. SN-positive patients (p?p?相似文献   

Dietary linoleate supplementation modulates formyl-peptide receptor expression and functional responses of rat neutrophils

We studied effects of dietary supplementation with the essential fatty acid (EFA) linoleic acid (LA) to see if neutrophil responses would be modulated. Neutrophils from rats maintained on a diet supplemented with EFA to 10% of the energy content--the high EFA (HEFA) group--showed a significantly higher LA concentration (but similar arachidonic acid content) compared with neutrophils from control rats maintained on a standard diet with 3% of the energy content as EFA. The HEFA group showed a significantly higher neutrophil oxidative metabolism compared with controls in response to N-formyl-methionyl-leucyl-phenylalanine (FMLP), but this response was equal to control values when stimulated by ionophore A23187, sodium fluoride, or phorbol myristate acetate. Similarly, FMLP conferred a more pronounced increase of intracellular Ca2+ in HEFA neutrophils, whereas this response to ionomycin was equal to that in controls. In contrast, HEFA rat neutrophil migration was decreased to 71% of the value in controls in response to FMLP. Similar results were observed for aggregation responses. On A23187 stimulation, HEFA and control neutrophils generated equal amounts of leukotriene B4 and other 5-lipoxygenase products as well as thromboxane B2 and 6-keto-prostaglandin F1 alpha. However, assessment of binding of FMLP labeled with tritium revealed an increase of the low affinity state of the FMLP receptor population. Thus an increased intake of one unsaturated fatty acid, LA, leading to its accumulation in neutrophils, conferred alterations in formyl-peptide-elicited responses, not associated with the formation of the assessed arachidonate-derived mediators, but most likely through the observed modulation of FMLP receptor subpopulations.     

Diagnostic delay of breast cancer – An analysis of claims to Swedish Board of Malpractice (LÖF)

Aim

Delay in the diagnosis of breast cancer may have important clinical and medico-legal implications. This study examined the decisions made by reviewers at the Swedish agency (LÖF) that handles claims of medical malpractice where claimants seek compensation for alleged suffering and/or negative clinical impacts of diagnostic delays.

Material and methods

In 1995–2006 a total of 134 women filed claims for negative effects resulting from delays in the diagnosis of breast cancer. Review of the claims led to approval of delay in the primary diagnosis for 62 women and of recurrence for 28 women. The clinical symptoms that were overlooked and other causes of delay that had any relation to therapy, prognosis and economic compensation were identified. The verdicts reached were analysed.

Results

The median delay in the diagnosis of the primary disease was 11 months and for recurrent disease 3.5 months. Delay in diagnosis of the primary disease was considered to have an impact on the therapy in 23%. The prognosis was postulated to have been adversely affected 11% of the patients for whom the delay was longer than 12 months. Delay in diagnosing the recurrence was contributing to delay in starting therapy and to unnecessary suffering in 32%. The delay in diagnosis was mainly caused by incomplete clinical or radiological examination and by misinterpretations of the examination results. Economic compensation was given in 90%. There was a warning or admonition to the responsible doctor in a third of the cases referred to the judgement court.

Conclusion

This study demonstrates that claims for compensation for delay in diagnosis of breast cancer in Sweden occur in about 1/1000 new patient. The delay in the diagnosis of the primary tumour was considered to have an impact on the magnitude of therapeutic measures in almost 25% of the women who filed claims. Economic compensation for the patients’ injuries was given in ninety percent of the cases. In women for whom there was a delay in diagnosing the recurrence there was consequently a delay in starting the palliative therapy.     

Non-nutritive sucking in sick preterm infants

BACKGROUND: Non-nutritive sucking (NNS) by the newborn infant is a fundamental behaviour and is one of the first coordinated muscular activities in the fetus. Aims: Our objective is to study the NNS pattern in prematurely born infants, who had various conditions commonly associated with immaturity. METHOD: A specially designed computer-based method that analyses and quantifies components of the NNS pattern was used. SUBJECTS: The pattern of 51 clinically stable prematurely born infants (gestational ages 26-35 weeks) making a total of 206 observations were analysed and findings were compared with those obtained from 58, healthy preterm infants. RESULTS: The rhythmic NNS pattern of alternating sucking and pauses was elicited in all examined infants, the earliest at post-menstrual age (PMA) 26 weeks. The role of PMA, the dominant predictor for several sucking variables seen in the control group, became diminished for the infants with risk factors but changes were otherwise similar. The infants' sucking activity and sucking frequency increased and the variability of the pattern declined with increased PMA and weight. Follow-up of a subgroup of infants revealed fewer sucking bursts per minute, slower sucking frequency and a greater variability of the frequency and amplitudes in those infants who developed sequelae. CONCLUSIONS: It would, thus, appear that the NNS pre-programmed rhythm generator, primarily modulated by maturation in healthy preterm infants, becomes affected by known risk associated events and in infants who later develop sequelae. Quantification of the NNS pattern in preterm infants may be a valuable future component of their evaluation.     

Effect of sulphasalazine and sulphapyridine on neutrophil superoxide production: role of cytosolic free calcium.

As the neutrophil granulocyte plays an important part in rheumatoid inflammation the effect of sulphasalazine on neutrophil function was studied. The results show that sulphasalazine, and its metabolite sulphapyridine, inhibit neutrophil superoxide production elicited by the receptor mediated stimulus N-formyl-methionyl-leucyl-phenyl-alanine (fMLP) and by the calcium ionophore A23187. This effect seems to be dependent on inhibition of intracellular Ca++ increase as both substances reduce this increase upon cell activation with fMLP and A23187. Sulphasalazine and sulphapyridine do not inhibit superoxide production after stimulation with the ester phorbol myristate acetate, a stimulus response coupling which is independent of intracellular Ca++ increase. The reported inhibition of superoxide generation may explain, at least partly, the antirheumatic property of sulphasalazine.     

Effects of local microwave hyperthermia and 5-fluorouracil in treatment of experimental liver cancer

The effect of combined treatment with local hyperthermia and i.v. infusion of 5-fluorouracil was studied in 39 Wistar rats with a transplanted adenocarcinoma inoculated in the liver. Ten to 13 days later the rats were divided into three groups. Group A1 was subjected to local microwave hyperthermia (42 degrees C) for 1 h. During the hyperthermia, an i.v. infusion of 5-FU (20 mg/kg body weight) was given. In group A2 5-FU was administered under normothermic conditions. Group A3 received saline infusion under normothermic conditions. The mortality after infusion of 5-fluorouracil and hyperthermia increased during the first week after treatment. In group A1, a significant growth retardation of liver tumor was registered seven days after treatment. This effect was not superior to that of hyperthermia alone as previously described for the same experimental model. Studies of 5-FU pharmacokinetics in plasma were performed in another 20 Wistar rats. Ten rats were given an i.v. infusion of 5-FU during local hyperthermia, while the other 10 were infused under normothermic conditions. Plasma concentration of 5-FU was determined by isotachophoretic separation. The hyperthermia caused a faster decline in serum concentration of 5-FU, probably because of accelerated catabolism of the drug.     

Phagocytosis and dynamic RES scintigraphy: an evaluation of commercial colloids in rats

Reticuloendothelial system (RES) phagocytic function or capacity can be measured by clearance studies with test substances. This study in the rat examines three commercially available 99Tcm-labelled test substances, and different methods of calculating RES capacity. Albures size 500 nm and sulphur colloid size 600 nm used for liver scintigraphic imaging and Nanocoll size 50 nm used for bone-marrow scintigraphic imaging were tested. The rats were examined under a gamma camera and the uptake by the liver, clearance from the heart and clearance from blood samples were recorded. Different amounts of substances were tested. The final uptake in different organs was recorded after the animals were sacrificed. Colloid size and stability were tested with a polycarbonate filter. (Nanocoll was found to have at least 10 times smaller colloid diameter, leading to a thousand times more particles per milligram). RES function was calculated as the uptake rate or clearance rate, k. In a logarithmic plot, the relationship between uptake or clearance and time was found to be linear between 90 and 300s and calculations of k in this interval are recommended. k-values selected from blood sample curves were 11 +/- 5 S.E.M. lower than those calculated from heart clearance curves or liver uptake curves. Increasing amounts of Nanocoll caused a decrease in uptake rate k. Albures and sulphur colloid could not be given in amounts that caused any change in k. Only Nanocoll could be given in sufficiently large amounts (above the critical dose) to challenge RES and avoid complete extraction from the circulation during first passage through RE organs. Nanocoll seems suitable for use in tests of RES function and the optimal amount was 0.03 mg per rat (0.6 X 10(12) particles).     

Influence of vasoactive drugs on blood flow in subcutaneous tumors – an experimental study in rats

Subcutaneously implanted tumors in Wistar and Lister rats were used as a model for the study of metastatic tumor blood flow and how it is affected by vasoactive drugs. Blood flow measurements were obtained using the labelled microsphere method and the reference organ technique. Microspheres (15-μm) labelled with either ⁹⁹Tc^m or ⁵¹ Cr isotopes were injected intracardially and a reference sample was drawn simultaneously at constant speed. This was performed before and after the infusion of vasoactive drugs, and (as control), saline infusion. The drugs tested (adrenaline, noradrenaline, glucagon, histamine, and vasopressin) showed profound effects on central hemodynamic parameters and on muscle and skin blood flow. The relative tumor blood flow, measured as the ratio between tumor and skin or tumor and muscle blood flow, was calculated. The results show that no enhancement of the relative tumor blood flow could be registered. In fact, a decrease in the tumor-to-muscle-blood-flow ratio was noted when noradrenaline was infused, and in the tumor-to-skin ratio when adrenaline was infused. Blood flow in subcutaneous tumors was four to five times that in muscle or skin. Tumor blood flow was also inversely related to the size of the tumor.