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.

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.

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.

[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.

[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.

[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.

Scanning electron microscopy of the initial lymphatics of the skin after use of the indirect application technique with glutaraldehyde and MERCOX as compared to clinical findings.

Certain phenomena in the region of the initial lymphatics during clinical examination (indirect lymphography and microlymphography)--namely build-up and course and filling and diffusion--have still to be elucidated. The glutaraldehyde and MERCOX methods were used to simulate indirect application conditions in clinical procedures in skin specimens (human and pig) which were then examined by scanning electron microscopy. The results presented include novel findings on the microtopography of these lymph vessels and the typology of filling refluxes which are of importance when indirect imaging techniques are employed. Various speeds of application were used and the function of the opening apparatus with previously undescribed structures (endothelial bridges and connective tissue trabeculae) was taken into consideration. Recommendations aimed at standardizing the nomenclature of parietal structures and sections of the lymphatics have been incorporated in the report.

[Experiences with selective catheter embolization of the internal iliac artery in life-threatening hemorrhage from uterine cancers]. / Erfahrungen mit der selektiven Katheterembolisierung der Arteria iliaca interna bei lebensbedrohlich blutenden Uteruskarzinomen.

Patients with heavily bleeding cervical or endometrial carcinomas were treated by embolisation. A catheter was placed into the internal iliac artery via the femoral artery. By the use of Gianturco-Anderson-Wallace springs, selective embolisation was performed distally to the superior gluteal or iliolumbar artery. Five patients between the age of 42 to 86 years (four cervical carcinomas, one endometrial carcinoma) were treated by embolisation. In four patients bleeding stopped after treatment. One patient died after further haemorrhage. Only minor side effects were seen. Thus, surgical ligature of the internal iliac arteries seems to be a thing of the past. Nevertheless, catheter embolisation should be performed only after alternative methods had been tried.

[Roentgen diagnosis of colorectal endometriosis]. / Zur Röntgendiagnostik der kolo-rektalen Endometriose.

Preoperative diagnosis of symptomatic colorectal endometriosis is often difficult. Hence, the x-ray findings of eight woman patients with confirmed affection of the colon with endometriosis foci were evaluated together with the clinical, surgical and histological findings. In 50% of the cases rectal haemorrhages were the most frequently occurring sign. In three-quarters of the cases the colon sigmoideum was involved. Radiologically it was possible to prove in 37.5% each of the cases that there was a polypoid lesion and an irregular concentric stenosis of the intestinal lumen. In 25% of the cases we found a complete stenosis of the intestinal lumen combined with ileus. X-ray sign pattern of colorectal endometriosis, however, is not pathognomonic.

[Hand arteriography. Surgical indications and results]. / Handarteriographie. Chirurgische Indikationen und Ergebnisse.

Based on experience in arteriography of the hand in 108 patients the authors present in a retrospective study the surgical indications (trauma, tumour, angiodysplasia, malformation and embolic lesion) and results of this method. The diagnostic value of arteriography of the hand is shown by means of results and examples.

[Results of real-time sonography and raster mammography of 200 breast cancers]. / Ergebnisse der real-time-Sonographie und Rastermammographie bei 200 Mammakarzinomen.

The article reports on 200 patients with histologically verified carcinomas of the breast in whom both real time mammasonography and grid mammography were performed. The indications for additional use of real time sonography in the diagnosis of malignant diseases of the female breast were a palpable node or a suspicious finding in mammography. All patients were examined with a high resolution realtime scanner with a 7.5 MHz transducer. The diagnostic criteria of sound deep to the mass (type I-IV), the regularity of the conteur of the mass, and the presence or absence of internal echoes. The typical sonographic features of histologically different types of carcinoma of the female breast are demonstrated by means of case examples. Mammasonography offers a high degree of accuracy in preoperative differential diagnostic assessment of tumour status in malignant processes of the breast. The combined mammographic-sonographic evaluation is the method of choice in clinical evaluation of masses of the female breast.

[Therapy and results of the treatment of vulvar cancer. A review of 234 cases 1951-1976]. / Therapie und Behandlungsergebnisse beim Vulvakarzinom. Eine Ubersicht über 234 Fälle der Jahre 1951-1976.

From 1951 to 1976 234 patients with invasive carcinoma of the vulva were treated at the Department of Obstetrics and Gynaecology, Medical School Hannover. 53.3% of these patients underwent simple vulvectomy. Radical vulvectomy and lymphadenectomy was performed in 17.9%. 45.7% received postoperative radiotherapy. -213 patients were followed up 5 years or more. After surgery alone the 5-year-survival rate was 56.9%, after operation and radiotherapy 43.4%, after exclusive radiation 14.2%. The 5-year-survival rate of all patients was 42.7%.

[Therapy and results of the treatment of breast cancer. A report on 1,003 cases 1970 to 1978]. / Therapie und Behand-lungsergebnisse beim Mammakarzinom. Ein Bericht über 1003 Fälle der Jahrgänge 1970 bis 1978.

1003 women with invasive breast carcinoma were treated in the Department of Obstetrics and Gynecology, Medical School Hannover, between 1970 and 1978. In 787 patients modified radical mastectomy was combined with postoperative radiation therapy. In 797 patients, who were observed for at least 5 years, the 5 year survival rate was 63.0%, depending on tumor stage. In spite of intensive loco-regional treatment, local recurrence occurred in 18.0%. For us, that was one among other reasons to discontinue routine postoperative radiation therapy.