Contribution of plasminogen activators and their inhibitors to the survival prognosis of patients with Dukes' stage B and C colorectal cancer.

Despite the advances in pre-, peri- and post-operative medical care of colorectal carcinoma patients, the prognosis has improved only marginally over recent decades. Thus, additional prognostic indicators would be of great clinical value to select patients for adjuvant therapy. In previous studies we found that colorectal carcinomas have a marked increase of the urokinase-type of plasminogen activator (u-PA), and the inhibitors PAI-1 and PAI-2, whereas the tissue-type plasminogen activator (t-PA) is found to be decreased in comparison with adjacent normal mucosa. In the present study we evaluated the prognostic value of several plasminogen activation parameters, determined in both normal and carcinomatous tissue from colorectal resection specimens, for overall survival of 136 Dukes' stage B and C colorectal cancer patients, in relation to major clinicopathological parameters. Uni- and multivariate analyses indicated that a high PAI-2 antigen level in carcinoma, a low t-PA activity and antigen level and a high u-PA/t-PA antigen ratio in adjacent normal mucosa are significantly associated with a poor overall survival. A high ratio of u-PA antigen in the carcinomas and t-PA antigen in normal mucosa, i.e. u-PA(C)/t-PA(N), was found to be predictive of a poor overall survival as well. All these parameters were found to be prognostically independent of the clinicopathological parameters. Multivariate analysis of combinations of these prognostically significant plasminogen activation parameters revealed that they are important independent prognostic indicators and have in fact a better prognostic value than their separate components. Based on these combined parameters, subgroups of patients with Dukes' stage B and C colorectal cancer could be identified as having either a high or a low risk regarding overall survival. In conclusion, these findings emphasize the relevance of the intestinal plasminogen activation system for survival prognosis of patients with colorectal cancer and, in the future, might constitute a patient selection criterion for adjuvant therapy

Over de grens: Nederlands extreem geweld in de Indonesische onafhankelijkheidsoorlog, 1945-1949

Op 17 augustus 1945, twee dagen na de Japanse capitulatie, verklaarde Indonesië zich onafhankelijk. Nederland erkende dit niet en trachtte met geweld zelf de regie te voeren over het onvermijdelijke proces van dekolonisatie. Dit leidde tot vier jaren van moeizame onderhandelingen en bittere oorlogvoering. In 2005 verklaarde de Nederlandse regering dat Nederland die oorlog niet had moeten voeren. Over het geweld dat de Nederlandse militairen tijdens deze oorlog hadden toegepast, staat echter nog altijd het regeringsstandpunt uit 1969 overeind: er waren wel ‘excessen’, maar de krijgsmacht had zich in de regel ‘correct’ gedragen.Naarmate de aanwijzingen van extreem Nederlands geweld zich opstapelden, bleek dit officiële standpunt steeds moeilijker vol te houden. De Nederlandse regering besloot daarom in 2016 tot financiering van een groot onderzoeksprogramma. De belangrijkste conclusies daarvan zijn in dit boek te vinden. De auteurs maken aannemelijk dat de Nederlandse krijgsmacht op structurele basis extreem geweld toepaste en dat dit toen en ook lang daarna op allerlei manieren werd toegedekt. Dit alles past slecht bij een rooskleurig nationaal zelfbeeld – zoals eigenlijk de hele koloniale geschiedenis met dat zelfbeeld schuurt.Colonial and Global Histor

Predicting incomplete resection in non-small cell lung cancer preoperatively: a validated nomogram

Background: Patients who are surgically treated for stage I to III non-small cell lung cancer (NSCLC) have dismal prognosis after incomplete (R1-R2) resection. Our study aimed to develop a prediction model to estimate the chance of incomplete resection based on preoperative patient-, tumor-, and treatment-related factors. Methods: From a Dutch national cancer database, NSCLC patients who had surgical treatment without neoadjuvant therapy were selected. Thirteen possible predictors were analyzed. Multivariable logistic regression was used to create a prediction model. External validation was applied in the American National Cancer Database, whereupon the model was adjusted. Discriminatory ability and calibration of the model was determined after internal and external validation. The prediction model was presented as nomogram. Results: Of 7156 patients, 511 had an incomplete resection (7.1%). Independent predictors were histology, cT stage, cN stage, extent of surgery, and open vs thoracoscopic approach. After internal validation, the corrected C statistic of the resulting nomogram was 0.72. Application of the nomogram to an external data set of 85,235 patients with incomplete resection in 2485 patients (2.9%) resulted in a C statistic of 0.71. Calibration revealed good overall fit of the nomogram in both cohorts. Conclusions: An internationally validated nomogram is presented providing the ability to predict the individual chance of incomplete resection in patients with stage I to III NSCLC planned for resection. In case of a high predicted risk of incomplete resection, alternative treatment strategies could be considered, whereas a low risk further supports the use of surgical procedures

Diaphragm muscle fiber function and structure in humans with hemidiaphragm paralysis.

Item does not contain fulltextRecent studies proposed that mechanical inactivity of the human diaphragm during mechanical ventilation rapidly causes diaphragm atrophy and weakness. However, conclusive evidence for the notion that diaphragm weakness is a direct consequence of mechanical inactivity is lacking. To study the effect of hemidiaphragm paralysis on diaphragm muscle fiber function and structure in humans, biopsies were obtained from the paralyzed hemidiaphragm in eight patients with hemidiaphragm paralysis. All patients had unilateral paralysis of known duration, caused by en bloc resection of the phrenic nerve with a tumor. Furthermore, diaphragm biopsies were obtained from three control subjects. The contractile performance of demembranated muscle fibers was determined, as well as fiber ultrastructure and morphology. Finally, expression of E3 ligases and proteasome activity was determined to evaluate activation of the ubiquitin-proteasome pathway. The force-generating capacity, as well as myofibrillar ultrastructure, of diaphragm muscle fibers was preserved up to 8 wk of paralysis. The cross-sectional area of slow fibers was reduced after 2 wk of paralysis; that of fast fibers was preserved up to 8 wk. The expression of the E3 ligases MAFbx and MuRF-1 and proteasome activity was not significantly upregulated in diaphragm fibers following paralysis, not even after 72 and 88 wk of paralysis, at which time marked atrophy of slow and fast diaphragm fibers had occurred. Diaphragm muscle fiber atrophy and weakness following hemidiaphragm paralysis develops slowly and takes months to occur.1 augustus 201

Extended lymph-node dissection for gastric cancer

BACKGROUND: Curative resection is the treatment of choice for gastric cancer, but it is unclear whether this operation should include an extended (D2) lymph-node dissection, as recommended by the Japanese medical community, or a limited (D1) dissection. We conducted a randomized trial in 80 Dutch hospitals in which we compared D1 with D2 lymph-node dissection for gastric cancer in terms of morbidity, postoperative mortality, long-term survival, and cumulative risk of relapse after surgery. METHODS: Between August 1989 and July 1993, a total of 996 patients entered the study. Of these patients, 711 (380 in the D1 group and 331 in the D2 group) underwent the randomly assigned treatment with curative intent, and 285 received palliative treatment. The procedures for quality control included instruction and supervision in the operating room and monitoring of the pathological results. RESULTS: Patients in the D2 group had a significantly higher rate of complications than did those in the D1 group (43 percent vs. 25 percent, P <0.001), more postoperative deaths (10 percent vs. 4 percent, P= 0.004), and longer hospital stays (median, 16 vs. 14 days; P <0.001). Five-year survival rates were similar in the two groups: 45 percent for the D1 group and 47 percent for the D2 group (95 percent confidence interval for the difference, -9.6 percent to +5.6 percent). The patients who had R0 resections (i.e., who had no microscopical evidence of remaining disease), excluding those who died postoperatively, had cumulative risks of relapse at five years of 43 percent with D1 dissection and 37 percent with D2 dissection (95 percent confidence interval for the difference, -2.4 percent to +14.4 percent). CONCLUSIONS: Our results in Dutch patients do not support the routine use of D2 lymph-node dissection in patients with gastric cance