Long-course preoperative chemoradiation versus 5 × 5 Gy and consolidation chemotherapy for clinical T4 and fixed clinical T3 rectal cancer: long-term results of the randomized Polish II study.

BACKGROUND: This trial evaluated whether preoperative short-course radiotherapy and consolidation chemotherapy (CCT) were superior to chemoradiation in rectal cancers with clinical (c)T4 or fixed cT3. Previously, we reported early results showing no differences in the radical surgery rate (primary end point). In the short-course/CCT group, we observed lower acute toxicity of preoperative treatment and better overall survival (OS). We updated results to determine whether the benefit in OS was sustained and to evaluate late complications. PATIENTS AND METHODS: Patients with cT4 or fixed cT3 rectal cancer were randomized either to preoperative 5 × 5 Gy and three cycles of FOLFOX4 or to chemoradiation (50.4 Gy with bolus 5-Fu, leucovorin and oxaliplatin). RESULTS: Patients (N = 515) were eligible for analysis, 261 in the short-course/CCT group and 254 in the chemoradiation group. The median follow-up was 7.0 years. The difference in OS was insignificant [hazard ratio (HR) 0.90; 95% confidence interval (CI) 0.70-1.15; P = 0.38). However, the difference in early OS favouring short-course/CCT previously reported was observed again, being 9% at 3 years (95% CI 0.5% to 17%). This difference disappeared later; at 8 years OS was 49% in both groups. There was no difference in disease-free survival (HR 0.95; 95% CI 0.75-1.19; P = 0.65) at 8 years 43% versus 41% in the short-course/CCT group versus the chemoradiation group, respectively. The corresponding values for cumulative incidences of local failure and distant metastases did not differ and were HR = 1.08, 95% CI 0.70-1.23, P = 0.60, 35% versus 32% and HR = 1.10, 95% CI 0.68-1.23, P = 0.54, 36% versus 34%, respectively. The rate of late complications was similar (P = 0.66), grade 3+ being 11% versus 9% in the short-course/CCT group versus the chemoradiation group, respectively. CONCLUSION: The superiority of preoperative short-course/CCT over chemoradiation was not demonstrated. CLINICAL TRIAL NUMBER: The trial is registered as ClinicalTrials.gov number NCT00833131.

Lobectomy vs. segmentectomy. A propensity score matched comparison of outcomes.

BACKGROUND: Segmentectomy has emerged as a lung parenchymal sparring alternative to the gold standard lobectomy in non-small cell lung cancer (NSCLC) patients. We hypothesized that there is parity between functional, local recurrence and survival outcomes. PATIENTS AND METHODS: Parenchymal sparring procedures including anatomical segmentectomies were propensity score matched 1:1 with lobectomies (n = 64). The primary outcomes included survival, functional and oncological outcomes. The oncological outcomes were: post-operative histology, clear margins and local recurrence rates. Kaplan Meier survival curves were used to compare the survival. Oncological and functional variables were assessed by Fischer exact test and t-test. RESULTS: The pre-operative performance status, ASA grade, lung function, risk factors, surgical approach and tumour histology were similar between the groups. The tumour size was significantly higher for lobectomies (32.4 ±â€¯17 vs. 24.6 ±â€¯12 mm, p = 0.01). The tumour staging in the segmentectomy group was similar to the lobectomy group (Ia; 50 vs. 34%; Ib: 29 vs. 37%; IIa 11 vs. 9.3%; IIb 5 vs. 14%; IIIa 5 vs. 4.6%, p = 0.83). The loco-regional recurrence was lower in the segmentectomy group (1.5 vs. 3.1%, p = 0.69). The up-staging and down-staging post-surgery was similar in both groups, while neo-adjuvant therapy was used in 5 lobectomy and 3 segmentectomy cases. The survival was similar at 1 year between the groups (88 vs. 92%, p = 0.65). Between 4 and 5 years, the survival reduced in the parenchymal sparing group to 39% vs. 68% in the lobectomy group (p = 0.04). CONCLUSION: Surgical selection bias could be an important confounder in the selection of patients undergoing segmentectomy. Similar up and down staging were demonstrated in the two groups. This is one of the first studies to investigate the results of segmentectomy versus lobectomy in stage II/IIIa NSCLC tumours. No significant differences were found in functional outcomes, but the survival decreased after 4 years in the segmentectomy group, which could be explained by lower survival in the stage II/IIIa tumours treated with segmentectomy.

Postimpoundment time course of increased mercury concentrations in fish in hydroelectric reservoirs of northern Manitoba, Canada.

Mercury (Hg) concentrations in fish in boreal reservoirs have been shown to be increased for up to 3 decades after impoundment. However, the time course of increased concentrations is not well known. The purpose of this study was to determine the evolution of Hg concentrations in fish in the boreal reservoirs of northern Manitoba, Canada, and its relationship with severity of flooding. We determined total Hg concentrations in three species of fish for up to 35 years after impoundment in 14 lakes and lake basins. Postimpoundment trends depended on fish species and reservoir. In the benthivorous lake whitefish (Coregonus clupeaformis), Hg concentrations increased after flooding to between 0.2 and 0.4 microg g(-1) wet weight compared with preimpoundment concentrations between 0.06 and 0.14 microg g(-1) and concentrations in natural lakes between 0.03 and 0.06 microg g(-1). Hg concentrations in lake whitefish were usually highest within 6 years after lake impoundment and took 10 to 20 years after impoundment to decrease to background concentrations in most reservoirs. Hg concentrations in predatory northern pike (Esox lucius) and walleye (Sander vitreus) were highest 2 to 8 years after flooding at 0.7 to 2.6 microg g(-1) compared with preimpoundment concentrations of 0.19 to 0.47 microg g(-1) and concentrations in natural lakes of 0.35 to 0.47 microg g(-1). Hg concentrations in these predatory species decreased consistently in subsequent years and required 10 to 23 years to return to background levels. Thus, results demonstrate the effect of trophic level on Hg concentrations (biomagnification). Peak Hg concentrations depended on the amount of flooding (relative increase in lake surface area). Asymptotic concentrations of approximately 0.25 microg g(-1) for lake whitefish and 1.6 microg g(-1) for both walleye and northern pike were reached at approximately 100% flooding. Downstream effects were apparent because many reservoirs downstream of other impoundments had higher Hg concentrations in fish than would be expected on the basis of flooding amount.

Anticoagulant drugs increase natural killer cell activity in lung cancer.

BACKGROUND: In preclinical studies in animal models and in initial clinical trials, anticoagulation drugs have been shown to be effective in the prevention and treatment of haematogenous metastasis, and in the prolongation of survival in animal models. However, only a few studies have been performed on the direct influence of anticoagulation drugs on the immune system. OBJECTIVE: The purpose of this study is to determine the effect of warfarin, unfractioned heparin, low molecular weight heparins (LMWHs), and acetylsalicylic acid anticoagulants on the functional activity of natural killer (NK) cells. PATIENTS AND METHOD: Cytotoxic activity in patients with early, operable stages of non-small-cell lung cancer was compared with healthy volunteers. Cytotoxic studies were also carried out in tumor-bearing animals. RESULTS: Lung-cancer patients were characterized by significantly lower NK cell cytotoxicity (7.07 +/- 3.15) than healthy donors (44.12 +/- 10.62, P < 0.001). NK cell activation was found in both in vitro experiments using peripheral blood mononuclear cells (PBMC) from healthy donors and ex vivo in lung carcinoma patients after treatment with unfractionated heparin and fraxiparine. Similarly, potentiation of NK cell activity in Lewis lung carcinoma-bearing mice was found after therapy with unfractionated heparin. NK cell activity is lower in lung cancer patients than in normal subjects. CONCLUSIONS: NK cell activation was increased by LMWHs. Other anticoagulants augment the effector function of NK cells in cancer patients and in an animal model of lung cancer. This is a novel effect of these compounds, which were thought previously to exert their effect only via their anticoagulant properties.

Manipulation of antioxidant status fails to improve fertility of lactating cows or survival of heat-shocked embryos.

Experiments were conducted to test whether enhancement of antioxidant status could improve fertility and milk yield in dairy cows and resistance of cultured embryos to heat shock. Three experiments in three herds were performed to evaluate the effect of multiple intramuscular injections of 500 mg of vitamin E and 50 mg of selenium at 8 to 21 d before expected calving and at 30 and 80 d postpartum on reproduction of lactating Holstein cows. Vitamin E and selenium injections did not improve reproductive function or milk yield in any of the studies. The predicted 305-d milk yield (averages of least-squares means across treatments) were: 9478, 7073, and 10,204 kg projected 305-d milk for experiments 1, 2, and 3, respectively. Percentages of cows pregnant at first service were 30, 16, and 24% in experiments 1, 2, and 3, respectively. Three studies were performed to test whether vitamin E improved development of cultured bovine embryos exposed to heat shock. Heat shock of 41 degrees C at the two-cell stage reduced development to the blastocyst stage, but culture with 100 microM vitamin E did not reduce effects of heat shock on impaired development. For example, 9 h at 41 degrees C reduced blastocyst development from 51.2 +/- 3.3% to 3.4 +/- 3.3% in the absence of vitamin E and from 54.0 +/- 3.3% to 5.2 +/- 3.3% in the presence of vitamin E. Development of morulae to the blastocyst stage was not compromised by culture at 41 degrees C for 9 h. Additionally, there was no overall effect of vitamin E on morula development. In conclusion, multiple injections of vitamin E and selenium at the administered levels did not improve postpartum fertility nor milk yield of lactating Holstein cows in three different herds, and there was no direct thermoprotective effect of vitamin E for cultured, heat-shocked embryos.

Genetic divergence in cellular resistance to heat shock in cattle: differences between breeds developed in temperate versus hot climates in responses of preimplantation embryos, reproductive tract tissues and lymphocytes to increased culture temperatures.

The detrimental effects of heat stress on fertility in cattle are less pronounced in heat-tolerant breeds. Although these genetic differences reflect differences in thermoregulation, cells from heat-tolerant breeds are less adversely compromised by increased temperature (that is, heat shock) than cells from heat-sensitive breeds. Experiments were performed to test the hypothesis that cells and tissues from two thermotolerant breeds (Brahman and Senepol) are better able to survive and function after exposure to increased temperature than cells and tissues from two thermosensitive breeds (Holstein and Angus). Exposure of embryos at>eight-cell stage at day 5 after insemination to heat shock of 41.0 degrees C for 6 h decreased development to the blastocyst stage and the number of cells per embryo. However, the deleterious effect of heat shock on blastocyst formation and the number of cells per embryo was less pronounced for Brahman than for Holstein and Angus breeds. Embryos from Senepol cows had very low development and it was not possible to determine heat shock effects in this breed. In contrast to the sensitivity of embryos to heat shock, there was no effect of a 41.0 degrees C heat shock on [(3)H]leucine incorporation into proteins secreted by oviductal or endometrial explants. Lymphocytes from Brahman and Senepol cows were more resistant to heat-induced apoptosis than lymphocytes from other breeds. Heat shock reduced lymphocyte glutathione content but the magnitude of the decrease was not affected by breed. In conclusion, embryos from Brahman cows are more resistant to heat shock than embryos from Holstein or Angus cows. Genetic differences are also present in thermotolerance for apoptosis response in lymphocytes, with Brahman and Senepol cattle being more resistant to heat shock than Angus and Holstein breeds. It is likely that the evolutionary forces that led to the Brahman and Senepol breeds being adapted to hot climates resulted in the selection of genes controlling resistance to cellular heat shock.

Progesterone inhibits rejection of xenogeneic transplants in the sheep uterus.

OBJECTIVES: One of the proposed roles of progesterone is to prevent maternal immunological destruction of the allogeneic conceptus. Here, it was demonstrated that progesterone allows survival of a xenotransplant placed in the uterine lumen. METHODS: Ovariectomized ewes, surgically prepared to have ligatures around each uterine horn, were given daily subcutaneous injections of 50 mg progesterone or vehicle (sesame oil). After 30 days of treatment, mouse hybridoma cells were transplanted to one ligated uterine horn and phosphate-buffered saline was injected into the other horn. The uterus was flushed after an additional 14 days of treatment and hybridoma cells were identified by immunofluorescence. RESULTS: Overall, hybridoma cells were recovered from 4 of 5 progesterone-treated ewes and 1 of 5 vehicle-treated ewes. Immunohistochemical analysis of intercaruncular endometrium using antibodies towards CD8, gammadelta, and CD45R lymphocyte markers revealed that local presence of hybridoma cells caused a significant increase in CD8+ cells in all tissue compartments. While not significant, the numbers of CD8+ cells in the luminal and glandular epithelium were lower for progesterone-treated ewes. Progesterone tended to increase gammadelta T cell numbers in the glandular epithelium. CONCLUSIONS: Results demonstrate that xenograft rejection in the uterus is associated with an increase in CD8+ cells in the endometrium and that progesterone can inhibit uterine tissue graft rejection responses sufficiently to allow survival or delay rejection of xenograft tissue.

Local versus systemic control of numbers of endometrial T cells during pregnancy in sheep.

Pregnancy in sheep is associated with changes in numbers of specific T-lymphocyte populations in the uterine endometrium. These changes probably contribute to evasion by the conceptus of maternal immunological rejection and indicate a possible role for T cells in placental growth, parturition and post-parturient uterine defence against infection. The purpose of the present experiment was to evaluate the relative importance of systemic signals (i.e. those present throughout the uterus or from the circulation, including conceptus hormones secreted into the maternal blood) versus locally acting conceptus signals for regulating changes in numbers of endometrial lymphocytes during pregnancy. The approach taken was to surgically confine pregnancy to one uterine horn and compare differences in lymphocyte numbers between the two uterine horns as well as between both horns of pregnant ewes with those of ovariectomized ewes. As compared with ovariectomized ewes, there was a decline in numbers of CD45R+ lymphocytes within glandular epithelium and an increase in gammadelta T-cell number within the luminal epithelium. These changes occurred in both the pregnant and non-pregnant uterine horns of unilaterally pregnant ewes. Moreover, there were no significant differences in lymphocyte numbers between the two uterine horns of unilaterally pregnant ewes. Expression of CD25 was absent in tissues from both uterine horns. In conclusion, changes in numbers of endometrial lymphocytes during pregnancy, rather than due to locally acting signals of conceptus origin, are the result of hormonal signals of maternal or conceptus origin that either act directly on endometrial lymphocytes or stimulate the uterine endometrium to induce synthesis of regulatory molecules that affect lymphocyte dynamics.

High frequency oscillatory ventilation.

We at Virginia Baptist Hospital feel that the Sensor Medics 3100A high frequency oscillatory ventilator to be an effective and safe ventilator for the treatment of RDS and PIE. This ventilator appears to offer a gentler form of mechanical ventilation which is potentially of greatest value to the smallest premature infants.

[The treatment of uterine carcinomas. A report on the cure results at the Hannover Medical College]. / Die Behandlung der Uteruskarzinome. Bericht über die Heilungsergebnisse an der Medizinischen Hochschule Hannover.

From 1971 to 1980, 639 patients with carcinoma of the cervix and 271 patients with endometrial cancer were treated in the Division of Radiation Therapy of the Medical School Hannover. In 606 patients radical radiation therapy was followed by routine surgery, 304 patients have been irradiated primarily due to the local spread of the tumor. The radiation therapy consisted of a combination of external beam and intracavitary therapy. In patients with carcinoma of the cervix the five-year survival was 92% for stage Ia, 78% for stage Ib, 67% for stage IIa, 47% for stage IIb, 20% for stage III and 7% for stage IV. In patients with endometrial cancer the five-year survival was 91% for stage I, 71% for stage II, 60% for stage III and 0% for stage IV. Severe complications, i.e., ureteral stricture or fistula occurred in 1% to 1.5% of the patients with cervix cancer and in 0.5% to 1% of the patients with endometrial cancer.

Evaluation of early diagnostic criteria for ankylosing spondylitis in a 10 year follow-up.

A set of early diagnostic (ED) criteria comprising clinical data, ESR, radiological spinal signs, and the risk factor HLA B27 was evaluated after 5 and 10 years in a follow-up of 54 patients with an initial diagnosis of possible ankylosing spondylitis (AS). After 10 years 32 patients (59%) had developed definite AS according to the New York criteria, 10 individuals (19%) had possible or undifferentiated spondylarthropathy (SA), whereas in 12 patients (22%) other diagnoses were stated. ED criteria had a high discriminatory significance for the development of AS after 5 and 10 years (P less than 0.005, P less than 0.001 respectively). In this respect they were more valuable than B27 determination alone (P less than 0.01) or the ED criteria without HLA B27 (P less than 0.05). Furthermore, patients with still possible or undifferentiated SA had a higher mean score at the first examination than individuals with other final diagnosis (P less than 0.05). Thus, the ED criteria were useful for the identification of patients developing definite AS and of individuals in the AS related group of possible or undifferentiated SA.

[Magnetic resonance tomography using gadolinium-DTPA in the diskectomy syndrome--a reliable method of identifying a recurrent prolapse in scar tissue]. / Die Kernspintomographie mit Gadolinium-DTPA beim Diskektomie-Syndrom--eine zuverlässige Methode zur Identifizierung eines Rezidivprolapses im Narbengewebe.

The non invasive diagnostic possibilities of MR have resulted in better diagnosis of degenerative spinal diseases. Twenty-one patients with failed back surgery syndrome (postdiscectomy syndrome) were studied to evaluate the possibility of 1-Tesla magnetic resonance (MR) imaging with gadolinium diethylene triamine pentaacetic acid (Gd-DTPA) in differentiating post operative scar tissue from recurrent disc herniation. The enhanced MR studies correctly depicted the character of abnormal epidural tissue in all patients. We conclude that MR with GD-DTPA might be the method of choice to differentiate reliably postoperative epidural fibrosis from recurrent disc prolapse.

Radio-opaque liposomes for the improved visualisation of focal liver disease by computerized tomography.

Liposomes laden with radio-opaque agents (ROA) were prepared by the reverse phase evaporation method. The liposome solutions--containing 1.7-2.5 mg iodine per mg lipid--were injected into Wistar rats. 60 min post injection the rats were scanned in a Siemens CT scanner. Following the injection of 260 mg encapsulated iodine per kg bodyweight--less than half the iodine of the normal ROA bolus injection--there was a long lasting arise in liver enhancement of 40 Hounsfield units (HU). In animals with liver tumours induced by nitrosamine lesions of 2-3 mm in diameter could be detected.

Use of a modified needle in antegrade transfemoral arterial approach for diagnostic and interventional procedures.

A modified needle for the antegrade transfemoral approach in diagnostic and interventional procedures is described that simplifies access to the superficial femoral artery, and that can easily be manufactured from standard puncture needles.

[Comparison of raster mammography and real time sonography with histology in carcinoma of the breast]. / Vergleich der Rastermammographie und der Real-time-Sonographie mit Histologie bei Karzinomen der Brustdrüse.

In a retrospective study, the results of real-time sonography and grid mammography in 161 patients with histologically confirmed breast cancer were analyzed and compared with the histopathologic characteristics of the tumours to assess the diagnostic accuracy of these preoperative image-producing methods. The results showed the determination of the tumour size as obtained by the image-producing methods to correlate closely with the histopathologic findings. Furthermore, both real-time sonography and mammography yielded certain indications allowing prognostically valuable conclusions in respect of malignancy and invasiveness of the carcinomas. Taking into account the different but complementing diagnostic results of both methods, the combination of grid mammography and real-time sonography must be considered as the presently most reliable preoperative diagnostic procedure.