Treatment patterns and survival in patients with hepatocellular carcinoma in the Swedish national registry SweLiv.

BACKGROUND: Consistent data on clinical features, treatment modalities and long-term survival in patients with hepatocellular carcinoma (HCC) using nationwide quality registers are lacking. This study aimed to describe treatment patterns and survival outcomes in patients diagnosed with HCC using a national maintained database. METHODS: Characteristics and treatment patterns in patients diagnosed with HCC and registered in the national register of liver and bile duct tumours (SweLiv) between 2009 and 2016 were reviewed. Overall survival (OS) was estimated using Kaplan-Meier analysis and the log rank test to compare subgroups for clinical features, treatment modalities and outcomes according to the year of treatment. RESULTS: A total of 3376 patients with HCC were registered over 8 years, 246 (7·3 per cent) of whom underwent transplantation. Some 501 (14·8 per cent) and 390 patients (11·6 per cent) had resection and ablation as primary treatment. Transarterial chemoembolization and systemic sorafenib treatment were intended in 476 (14·1 per cent) and 426 patients (12·6 per cent) respectively; the remaining 1337 (39·6 per cent) were registered but referred for best supportive care (BSC). The 5-year survival rate was approximately 75 per cent in the transplantation group. Median OS was 4·6 (i.q.r. 2·0 to not reached) years after resection and 3·1 (2·3-6·7) years following ablation. In patients referred for palliative treatment, median survival was 1·4 (0·8-2·9), 0·5 (0·3-1·2) and 0·3 (0·1-1·0) years for the TACE, sorafenib and BSC groups respectively (P < 0·001). Median survival was 0·9 years for the total HCC cohort in 2009-2012, before publication of the Swedish national treatment programme, increasing to 1·4 years in 2013-2016 (P < 0·001). CONCLUSION: The survival outcomes reported were in line with previous results from smaller cohorts. The introduction of national guidelines may have contributed to improved survival among patients with HCC in Sweden.

ANTECEDENTES: Se carece datos consistentes acerca de las características clínicas, modalidades terapéuticas y supervivencia a largo plazo en pacientes con carcinoma hepatocelular (hepatocellular carcinoma, HCC) basados en registros de calidad de ámbito nacional. El objetivo de este estudio fue describir los patrones de tratamiento y los resultados de supervivencia en pacientes diagnosticados de HCC usando una base de datos nacional. MÉTODOS: Se revisaron las características de los pacientes y los patrones de tratamiento en pacientes con un diagnóstico de HCC incluidos en el registro nacional de tumores de hígado y vías biliares (SweLiv) entre 2009 y 2016. La supervivencia global (overall sirvival, OS) se analizó mediante el método de Kaplan-Meier y test de log-rank para la comparación de subgrupos según las características clínicas de los pacientes, las modalidades de tratamiento y los resultados en función del año de tratamiento. RESULTADOS: Durante un periodo de 7 años, se incluyeron en el registro un total de 3.076 pacientes con HCC, 246 de los cuales recibieron un trasplante (7,2%). Se practicó resección y ablación como tratamiento primerio en 501 (14,8%) y 390 (11,6%) pacientes, respectivamente. La quimioembolización (TACE) y el tratamiento sistémico con sorafenib se efectuó en 476 (14,1%) y 426 (12,6%) pacientes, respectivamente; los 1.337 pacientes restantes (40,0%) fueron incluidos en la base de datos pero se derivaron para recibir el mejor tratamiento de soporte. La tasa de supervivencia a los 5 años fue del 75% en el grupo trasplantado. La mediana de OS fue de 4,6 años (rango intercuartílico, interquartile range, IQR 2,0-no alcanzado) tras la resección y de 3,1 años (IQR 2,3-6,7) tras la ablación. En los pacientes derivados para tratamiento paliativo, la mediana de supervivencia fue de 1,4 años (IQR 0,8-2,9), 0,5 años (IQR 0,2-1,2) y 0,3 años (IQR 0,1-1,0) para los grupos de TACE, sorafenib y mejor tratamiento de soporte, respectivamente (P < 0,001). La mediana de supervivencia para toda la cohorte de HCC en 2009-2012 fue de 0,9 años antes de la publicación del programa de nacional de tratamiento sueco, aumentando a 1,4 años en 2013-2016 (P <0,001). CONCLUSIÓN: Los resultados de supervivencia referidos eran consistentes con resultados previos obtenidos en cohortes más pequeñas; la introducción de guías nacionales puede haber contribuido a mejorar la supervivencia de los pacientes con HCC en Suecia.

Lowering of tumoral interstitial fluid pressure by prostaglandin E(1) is paralleled by an increased uptake of (51)Cr-EDTA.

High intra-tumoral fluid pressure (TP(IF)) may impair uptake of anticancer drugs into tumors, contributing to poor efficiency in treatment of carcinomas. Here, we demonstrate that lowering of TP(IF) parallels increased transport of (51)Cr-EDTA (m.w. 341) into tumor interstitium. Introduction of 15 microg prostaglandin E(1) (PGE(1)) -methyl ester into the s.c. tissue surrounding transplanted rat colonic (PROb) carcinomas or chemically-induced rat mammary carcinomas, lowered TP(IF) by 30%. Transcapillary transport into the interstitium of PROb tumors quantified by microdialysis increased by 39.6% after PGE(1) treatment 40 min prior to administration of (51)Cr-EDTA (n=6; p<0.05) compared to vehicle (n=10). In mammary tumors, PGE(1) increased transport into the tumors by 86.9% over controls (n=16; p<0.05). Both tumors had well developed stroma containing collagen and hyaluronan. Our data demonstrate that adjuvant treatment with PGE(1) lowers TP(IF), and enhances transport into the tumors. This principle may be of value as adjuvant therapy in treatment of solid malignancies with currently used anticancer drugs.

Blood pressure control during weight reduction in obese hypertensive men: separate effects of sodium and energy restriction.

The separate and combined effects of dietary energy and sodium restriction on regulation of blood pressure were investigated in 30 middle aged obese men with essential hypertension attending the outpatient department. In group 1 (n = 15) a basal period with no dietary restriction was followed by a period taking an energy reduced diet (5.1 MJ; 1230 kcal), the sodium intake being supplemented and hence unchanged (1:ErSn). In group 2 (n = 15) the basal period preceded a control period with no intervention, which was followed by taking a diet restricted in energy (5.1 MJ; 1220 kcal) and sodium (2:ErSr). During period 1:ErSn there were reductions in heart rate and urinary noradrenaline output but not in systolic or diastolic blood pressure. Body weight decreased by 4.9-11.7 kg and urinary sodium excretion did not change. In period 2:ErSr urinary sodium output was reduced by 81.4 (SEM 17.8) mmol(mEq)/24 h and there was a weight loss of 8.2 (SEM 0.7) kg. Systolic and diastolic blood pressures fell significantly, as did the heart rate and urinary noradrenaline excretion. These results show that in hypertensive obese men a moderate weight reducing diet decreases indices of sympathetic nervous system activity. Reduction of blood pressure to the normotensive range was observed only when there was a concomitant restriction of sodium intake.

Nitrogen balance studies in patients with uremia during treatment with protein-reduced diet and supplementation with essential amino acids or keto acids.

Nitrogen balance was studied in 4 patients with uremia during treatment with a protein-reduced diet (20 g) supplemented with either essential amino acids and histidine or a mixture of keto analogues of five of the essential amino acids and essential amino acids. 3 patients completed the study. Nitrogen balance was negative on the diet only and was improved with both forms of supplementation. However, supplementation with the keto acids did not offer any advantage over the conventional essential amino acid supplementation. 1 patient developed serious hypercalcemia during treatment with the keto acid supplementation.

Body composition during long-term treatment of uremia with amino acid supplemented low-protein diet.

The influence on body composition of prolonged treatment with low-protein diet (20 g/day) supplemented with the essential amino acids and histidine was studied in 49 patients with chronic renal failure and uremic symptoms. Total body potassium (TBK) was measured with 40K in a whole-body counter. Total body water was determined with dilution of tritiated water. Predicted values for TBK and total body water were obtained from a reference population of 476 healthy subjects. In 38 patients investigated before treatment body weight was normal while mean TBK was 91% of predicted in men and 100% in women. Mean total body water was 104% of predicted in both men and women. Thirty-one patients were investigated at 3-month intervals during treatment for up to 12 months. No significant changes in mean body weight, TBK, or total body water were found. However, in 10/13 patients TBK decreased significantly, presumably due to increased catabolism in connection with intercurrent disease or insufficient energy intake. In the absence of complications long-term treatment with a low-protein diet and essential amino acids in renal failure seems to maintain body cell mass reflected in unchanged TBK.

Studies of dietary habits in pregnancy - with special reference to the intake of iron.

The dietary habits of 94 pregnant women (median age 26 years) were studied by means of four-day dietary records. Twenty-seven women were followed longitudinally and were observed in the 10-15th, the 24-27th and the 34-37th week of gestation (L-series). The remaining 67 women comprised the A-series, of which 20, 32, and 15 made their records during the 10-15th, 24-27th, and 34-37th week of gestation, respectively. There were no significant differences between the results from these two series. The mean daily energy intake was 2360 kcal and remained unchanged during pregnancy, exceeding by 250 kcal the average intake in non-pregnant women in Gothenburg, studied earlier. The iron intake comprised 1-2 mg of haeme iron, about 10 mg of native non-haeme iron and 5-6 mg of fortificiation iron. The mean iron intake was 7.2 mg/1000 kcal, which is below the recommendation, but it was distributed over the food groups in a manner more favourable for iron absorption than in the average Swedish population. Further effects to improve the diet so as to increase the content of iron and factors known to favour iron absorption are desirable. The results justify the normal practice of prescribing supplement iron in late pregnancy.

Food iron absorption in man. Applications of the two-pool extrinsic tag method to measure heme and nonheme iron absorption from the whole diet.

A new radioisotope method to measure iron absorption from the whole diet was used in this study. The method is based on the concept that food iron is absorbed from two pools, the heme iron pool and the nonheme iron pool, which can be especially labeled with two radioiron isotopes given as hemoglobin and as an iron salt. The purpose of this study was to test the accuracy of this two-pool extrinsic tag method. The meals served were composed as an average of 6 wk consumption in the present material of 32 young enlisted men. The mean and total heme and nonheme iron absorption in all the 32 young men was 1.01+/-0.11. This figure agrees well with the mean daily losses expected for this group of subjects (1.0 mg). The conclusion can therefore be made that there are no major systematic errors of the present method to measure the total iron absorption from a mixed diet. In one series a comparison was made of the absorption of heme and nonheme iron from the meals. A significant correlation between the absorption of the two kinds of iron was found. However, a much greater fraction of the heme iron was absorbed (37%) than of the nonheme iron (5%). The absorption both from breakfast and lunch was in two series found to give a good prediction of the total daily nonheme iron absorption. One series was designed to compare the effect of two levels of iron fortification. There was a significant increase in iron absorption when the level of iron fortification of the meals was increased.