Synchronous lesions detected by autofluorescence bronchoscopy in patients with high-grade preinvasive lesions and occult invasive squamous cell carcinoma of the proximal airways

The cancerization field concept implies that lung cancer multicentricity may be a frequent event and primary studies using white-light bronchoscopy (WLB) have reported a high prevalence of multicentricity in patients with roentgenographically occult lung cancer. We have used autofluorescence bronchoscopy (AFB) to reassess the prevalence of synchronous lesions in patients referred for the staging and/or treatment of occult lesions initially detected during WLB. All the patients referred with high-grade preinvasive lesions (severe dysplasia, DYS S and carcinoma in situ, CIS) and occult invasive squamous cell carcinoma (CIV) of the bronchus initially detected during WLB at other centers, underwent AFB. Data were prospectively collected and retrospectively analyzed to assess the prevalence of synchronous occult lesions. From January 1996 to December 2001, 28 patients (26 males, 2 females; mean age: 65 +/- 11) were assessed. After re-evaluation, in two cases, the referred lesions corresponded only to metaplasia and were discarded from analysis. The 26 other patients were referred for 28 lesions (3 DYS S, 19 CIS and 6 CIV; 2 patients were referred with two synchronous lesions). AFB revealed, in these 26 patients, six additional lesions (1 DYS S, 4 CIS and 1 CIV). Multicentricity in this group, initially estimated to amount to 7% with WLB alone, raised to 23% by using AFB. The high prevalence of synchronous lesions in this series of patients with occult DYS S, CIS and occult CIV suggests that AFB may be a useful adjunct in the pretreatment evaluation.     

Primary cutaneous large B-cell lymphoma: the relation between morphology, clinical presentation, immunohistochemical markers, and survival

The histogenesis, morphology, immunophenotype, and clinical behavior of cutaneous large B-cell lymphomas (CLBCL) are largely a matter of controversy. We performed an investigation to determine whether CLBCL have features that differentiate them from other large B-cell lymphomas and whether CLBCL is itself a heterogeneous group. To this end, we reviewed the main characteristics of a series of 32 cases of LBCL found in the skin. We reviewed the clinical findings and paraffin sections of the tumors from these 32 patients. The immunohistochemical study performed included p53, MIB1, Bcl2, Bcl6, and CD10 markers. We carried out statistical analysis of these data (univariate and multivariate), seeking an association between the features of the tumors and clinical outcome, as defined by failure-free survival time. Only one patient died as a consequence of the lymphoma. Nevertheless, the accumulated probability of survival without failure at 48 months was 0.46. The number, type, and localization of the lesions were not associated with variations in either survival or failure-free survival. The expression of p53 was negative in this group of CLBCL, whereas Bcl-2 expression or localization in the lower leg did not relate to any other significant feature. Histologic examination of the cases disclosed three different groups: Grade III follicular lymphomas (FLs), monomorphous large B-cell lymphomas (LBCL type I), and LBCL with an admixed component of small B-lymphocytes (LBCL type II). Grade III FL (11 cases) tended to be found in the head and neck and showed CD10 expression in a majority of cases. A higher probability of lymph node relapses was associated with cases located in the head and neck and with CD10+ tumors. Cutaneous large B-cell lymphomas are indolent tumors, but follow an insidious course. Our data support the interpretation that CLBCL is a heterogeneous condition; comprises some LBCL derived from CD10+ germinal center cells which manifests more frequently as tumors in the head and neck region, with an increased probability of relapse in lymph nodes [1] and has some distinctive morphologic features. The existence of a component of small B-cells within the other CLBCL could lend support to the theory that some of these tumors, more than arise de novo, may have originated in preexistent small B-cell lymphomas, but no firm evidence of this is provided in this study.     

Combination radiotherapy and chemotherapy in cancer of the pancreas. Review of the literature and prospects

Overall prognosis of pancreatic adenocarcinoma is still very poor with median survival around 10 months after radical surgery in operable patients, or after full-dose radiation therapy in non-surgical candidates. In metastatic disease, multidrug chemotherapy regimens give a response rate of around 30% with median survival of 10 months. Random trials conducted by the GITSG in inoperable cases have shown improved results for chemoradiation with 5-FU for radiotherapy alone and a doubling of median survival with a 1-year survival of 40% vs 10%. Incorporation of Adriamycin in these combined modality protocols does not improve the results in terms of survival. Chemoradiation also shows improved results compared with chemotherapy alone. In patients amenable to radical surgery, adjuvant post-operative treatment with chemoradiation gave superior results over surgery alone with a doubling of median survival and a significant improvement of a two-year survival rate (42% versus 15%). Intra-operative radiation therapy leads to better local control but without a significant improvement in survival. With a better understanding of radio-chemotherapy interactions and mechanisms of radiosensitization through continuous infusion of fluorouracil and/or cisplatinum, these encouraging results should be confirmed within the next few years.     

Motor cortex activation in Parkinson's disease: dissociation of electrocortical and peripheral measures of response generation.

This study investigated characteristics of motor cortex activation and response generation in Parkinson's disease with measures of electrocortical activity (lateralized readiness potential [LRP]), electromyographic activity (EMG), and isometric force in a noise-compatibility task. When presented with stimuli consisting of incompatible target and distractor elements asking for responses of opposite hands, patients were less able than control subjects to suppress activation of the motor cortex controlling the wrong response hand. This was manifested in the pattern of reaction times and in an incorrect lateralization of the LRP. Onset latency and rise time of the LRP did not differ between patients and control subjects, but EMG and response force developed more slowly in patients. Moreover, in patients but not in control subjects, the rate of development of EMG and response force decreased as reaction time increased. We hypothesize that this dissociation between electrocortical activity and peripheral measures in Parkinson's disease is the result of changes in motor cortex function that alter the relation between signal-related and movement-related neural activity in the motor cortex. In the LRP, this altered balance may obscure an abnormal development of movement-related neural activity.     

Clinimetric quality of the fire fighting simulation test as part of the Dutch fire fighters Workers' Health Surveillance

Background  

Clinimetric data for the fire fighting simulation test (FFST), a new test proposed for the Workers' Health Surveillance (WHS) of Dutch fire fighters, were evaluated.     

Vegetable oil based versus wood based stanol ester mixtures: effects on serum lipids and hemostatic factors in non-hypercholesterolemic subjects

A pine wood based stanol ester mixture-composed of sitostanol (92%) and campestanol (8%) effectively lowers cholesterol absorption and consequently LDL-cholesterol concentrations. It has been postulated that the less absorbable plant sterols reduce cholesterol absorption more effectively. As sitostanol is absorbed less than campestanol, we decided to examine if a vegetable oil based stanol ester mixture with 68% sitostanol and 32% campestanol is less effective than the wood based stanol ester mixture. For this, 112 non-hypercholesterolemic men and women consumed for 4 weeks a rapeseed oil (LEAR) based margarine and shortening. For the next 8 weeks, 42 subjects continued with these products, while the other subjects received products with a vegetable oil (n=36) or a pine wood based stanol ester mixture (n=34). Consumption of 3.8 g vegetable oil based stanols (2.6 g sitostanol plus 1.2 g campestanol) lowered LDL cholesterol 14.6+/-8.0% (-0.37 mmol/l; vs. the control group; P<0.001; 95% CI for the difference, -0.22 to -0. 51 mmol/l). Four grams pine wood based stanols (3.7 g sitostanol plus 0.3 g campestanol) showed a comparable decrease of 12.8+/-11.2% (-0.34 mmol/l; P<0.001; 95% CI-0.18 to-0.51 mmol/l). Decreases in LDL cholesterol were not different between the two experimental groups (P=0.793), while apoE genotype did not have a major impact on this hypocholesterolemic response. Serum HDL cholesterol and triacylglycerol concentrations were not changed. The decreases in apo B in both experimental groups differed significantly (P<0.001) from changes in the control group. Coagulation and fibrinolytic parameters were not affected. We therefore conclude that vegetable oil and wood based stanol ester mixtures, with a different sitostanol/campestanol ratio, have similar LDL cholesterol lowering effects in a non-hypercholesterolemic population.     

Association of homozygous variants of STING1 with outcome in human cervical cancer

DNA‐sensing receptor Cyclic GMP–AMP Synthase (cGAS) and its downstream signaling effector STimulator of INterferon Genes (STING) have gained significant interest in the field of tumor immunology, as a dysfunctional cGAS‐STING pathway is associated with poor prognosis and worse response to immunotherapy. However, studies so far have not taken into account the polymorphic nature of the STING‐encoding STING1 gene. We hypothesized that the presence of allelic variance in STING1 would cause variation between individuals as to their susceptibility to cancer development, cancer progression, and potential response to (immuno)therapy. To start to address this, we defined the genetic landscapes of STING1 in cervical scrapings and investigated their corresponding clinical characteristics across a unique cohort of cervical cancer patients and compared them with independent control cohorts. Although we did not observe an enrichment of particular STING1 allelic variants in cervical cancer patients, we did find that the occurrence of homozygous variants HAQ/HAQ and R232H/R232H of STING1 were associated with both younger age of diagnosis and higher recurrence rate. These findings were accompanied by worse survival, despite comparable mRNA and protein levels of STING and numbers of infiltrated CD8⁺ T cells. Our findings suggest that patients with HAQ/HAQ and R232H/R232H genotypes may have a dysfunctional cGAS‐STING pathway that fails to promote efficient anticancer immunity. Interestingly, the occurrence of these genotypes coincided with homozygous presence of the V48V variant, which was found to be individually associated with worse outcome. Therefore, we propose V48V to be further evaluated as a novel prognostic marker for cervical cancer.