ESMO Consensus Guidelines for management of patients with colon and rectal cancer. a personalized approach to clinical decision making.

Colorectal cancer (CRC) is the most common tumour type in both sexes combined in Western countries. Although screening programmes including the implementation of faecal occult blood test and colonoscopy might be able to reduce mortality by removing precursor lesions and by making diagnosis at an earlier stage, the burden of disease and mortality is still high. Improvement of diagnostic and treatment options increased staging accuracy, functional outcome for early stages as well as survival. Although high quality surgery is still the mainstay of curative treatment, the management of CRC must be a multi-modal approach performed by an experienced multi-disciplinary expert team. Optimal choice of the individual treatment modality according to disease localization and extent, tumour biology and patient factors is able to maintain quality of life, enables long-term survival and even cure in selected patients by a combination of chemotherapy and surgery. Treatment decisions must be based on the available evidence, which has been the basis for this consensus conference-based guideline delivering a clear proposal for diagnostic and treatment measures in each stage of rectal and colon cancer and the individual clinical situations. This ESMO guideline is recommended to be used as the basis for treatment and management decisions.

[Evolution and revolutionary events in oncology in the end of XX - beginning of XXI century].

This review highlights major achievements of the Russian oncology in the past decades, such as works of N.N. Petrov, L.A. Zilber, N.N. Blokhin, E.E. Pogosyants. Revolutionary shift in the understanding of the malignization process have become possible after decoding of human genome, as well as genome of several tumors such as breast cancer, acute myeloblastic leukemia, several brain tumors, testicular cancer and other neoplasms. The issue of stem cells being possible ancestors of tumor cells is also discussed in the review. Also the author observes main modern therapeutic approaches towards cancer treatment. It is specially highlighted that XXI century molecular biology achievements made it possible to start personal tumor treatment based on its' specific genotype.

[Alcohol withdrawal delirium: What's new for an old disease?] / Delirium tremens : quoi de neuf pour une vieille maladie ?

The management of alcohol withdrawal syndrome is a frequent work in both community medicine and hospital wards. One of the most severe complications of alcohol withdrawal is Delirium Tremens (DT). The purpose of this development is to update knowledge on this complication in terms of diagnosis, evaluation and therapeutic approaches. It also proposes a reflection on the trajectory of care during and after DT.

Delayed lower extremity paresis following iliosacral screws: Atypical complication and treatment.

Percutaneous iliosacral screw placement has become the technique of choice for treating injuries to the posterior pelvis. However, the technique requires an understanding of the anatomy surrounding the bone corridors to avoid complications and detect them early if they occur. We present the clinical case of a patient with a U-shaped fracture of the sacrum that evolves with gluteal pain and left foot equine paresis after percutaneous fixation with iliosacral screws. Angio-CT of the pelvis shows active arterial bleeding from the superior gluteal artery associated to extensive hematoma in the thickness of the gluteus medius muscle. Emergency embolization is performed by installing coil and gelatin. Successful control of bleeding is achieved. To avoid this complication, a complete imaging study is recommended in planning the surgery and to avoid multiple repositioning of the guide or screw. Arterial injury should be suspected in case of increasing pain despite analgesia, functional impairment or neurological deficit and the angiographic study and resolution by selective embolization of the bleeding vessels must be performed.

A prognostic model in patients treated for metastatic gastric cancer with second-line chemotherapy.

BACKGROUND: This retrospective study was carried out to evaluate the prognostic significance of clinical factors in patients treated for metastatic gastric cancer with second-line chemotherapy. PATIENTS AND METHODS: We evaluated the prognostic significance of various clinical factors in 126 patients, who were treated with second-line chemotherapy. RESULTS: Median progression-free and overall survival (OS) for second-line chemotherapy were 3.3 and 5.3 months, respectively, with an overall response rate of 11.1%. Multivariate analysis identified three independent prognostic factors: performance status: Eastern Cooperative Oncology Group zero to one [hazard ratio (HR) 2.3, 95% confidence interval (CI) 1.7-5.4], hemoglobin (Hb) level: >/=10 g/dl (HR 2.2, 95% CI 2.1-2.4) and time-to-progression (TTP) under first-line therapy: >/=5 months (HR 0.5, 95% CI 0.3-0.8). From the obtained data, a prognostic index was constructed, dividing the patients into three risk groups: good (n = 40), intermediate (n = 36) and poor risk group (n = 56). The median survival for good, intermediate and poor risk groups were 13.5, 6.0 and 2.9 months, respectively, whereas the 1-year OS rates were 50.2%, 14.2% and 2.6%, respectively (P = 0.00001). CONCLUSIONS: With inadequate data from randomized controlled trials at the moment, our report indicates that second-line chemotherapy is effective and beneficial in patients with good performance status, higher Hb level along with higher TTP under first-line therapy.

Morphological abnormalities of the hip in acetabular fractures.

Poor prognosis factors in surgical treatment of acetabular fracture-dislocations have been well established but there is little information about how morphological abnormalities of the hip may affect the surgical outcome. Hip anatomy has a wide range of variations. Morphological abnormalities of the hip can also be observed in patients with acetabular fractures. We present a case of a complication in a patient with a complex acetabular fracture, acetabular retroversion and femoroacetabular impingement. A 31-year old male patient was transferred to our trauma center following a high speed road traffic accident. Trauma series CT revealed cerebral contusion, subdural hematoma, aortic dissection and a left transverse plus posterior wall acetabular fracture. The left hip was reduced and the acetabular fracture was treated with a Kocher Langenbeck approach in prone position. The pelvic X- ray evidenced an anatomic reduction and signs of acetabular retroversion with positive posterior wall sign and crossover sign. CT scan evidenced increased alpha angle in the femoral head neck junction. During the follow up, 2 months after the acetabular fixation, patient suffered a posterior left hip dislocation and a total cementless hip arthroplasty was performed. Patients with acetabular retroversion and femoroacetabular impingement (CAM lesion) may be at risk of posterior dislocation. The influence of acetabular version and impingement may be also closely involved in how challenging the determination of hip stability can be in patients with posterior wall acetabular fractures. Acetabular retroversion and FAI may be related to the dislocation of unstable patterns with small fragments (wall sizes less than 20%). In this case postoperative precautions were not enough. We believe capsular reattachment with anchors and bracing may be useful in these selected cases. As these patients are not candidates for retroPAO (the recommended treatment for acetabular retroversion) maybe arthroscopic anterior wall riming and CAM resection should be performed at an early stage to decrease or avoid fulcrum.

[Targeted drugs for the treatment of disseminated colonic cancer].

5-Fluorouramcil has been the medicine of choice for systemic treatment of metastatic colonic cancer for the last 35 years. Objective positive results of this therapy were documented in 30% of the cases, it delayed the development of active disease by 4 months, and ensured a 6 month survival. Introduction of irinotecan, oxaliplatin, capecitabine, S = 1, and other drugs into clinical practice improved overall efficiency of therapy to 40-50%, increased time till progression of the disease to 6 months and survival to 15 months. Targeted drugs (bevacizumab, cetuximab) combined with the known chemotherapeutic programs (FOLFOX, FOLFIRI, XELIRI, XELFOX, etc.) showed even higher therapeutic effect, i.e. overall efficiency 50-60%, time to progression 10 months and survival of more than 1.5 years. Panitumumab is an active agent to be used in the third-line therapy.

[Docetaxel in the treatment of metastatic gastric cancer].

Since the late 1990s, docetaxel (Dtx), an antitubular drug, has been studied as a tool for the treatment of GC. Maximum effectiveness of docetaxel as monotherapy amounted to 24%, with a median survival of 7 months. Two-drug combinations were developed containing docetaxel with 5-fluorouracil (DF) and docetaxel with cisplatin (DC). They proved effective in 43 and 33% of the cases respectively and ensured a similar median survival of 9-10 months. Clinical studies of a three-component combination containing docetaxel, 5-fluorouracil and cisplatin (DCF) as first-line therapy of metastatic GC were carried out in the XXIst century and showed its efficacy in 50% of the cases with a median survival of 10-12 months. The DCF regimen may be considered as a new standard for the treatment of patients with metastatic GC and satisfactory health status (ECOG 0-1). The combination is being modified to improve its toxicity profile by substituting oxaliplatin for cisplatin and oral fluoropyrimidines for i.v. 5-fluorouracil.

Aqueous, solid and gaseous partitioning of selenium in an oxic sandy soil under different microbiological states.

The aim of this study was to investigate the role of microorganisms on the behaviour of selenium in natural soil maintained under strictly aerobic conditions. Six-day batch experiments were performed with soils constrained to different microbiological states, either by sterilisation or by adding organic substrates. Selenium was added to the soil as selenite. The distribution of selenium in the gaseous, liquid and solid phases of the batch was measured. Selenium partitioning between the various solid phases was investigated by chemical sequential extractions. Active microorganisms played major effects on the distribution of selenium within the soil. On the one hand, microorganisms could promote selenium volatilisation (in relatively small amounts), leading to the spreading of selenium compounds outside the soil. On the other hand, microbial activities increased both amount of selenium retained by the soil and the strength of its retention (less exchangeable selenium), making selenium less susceptible to remobilisation.

An overview of BORIS: Bioavailability of Radionuclides in Soils.

The ability to predict the consequences of an accidental release of radionuclides relies mainly on the level of understanding of the mechanisms involved in radionuclide interactions with different components of agricultural and natural ecosystems and their formalisation into predictive models. Numerous studies and databases on contaminated agricultural and natural areas have been obtained, but their use to enhance our prediction ability has been largely limited by their unresolved variability. Such variability seems to stem from incomplete knowledge about radionuclide interactions with the soil matrix, soil moisture, and biological elements in the soil and additional pollutants, which may be found in such soils. In the 5th European Framework Programme entitled Bioavailability of Radionuclides in Soils (BORIS), we investigated the role of the abiotic (soil components and soil structure) and biological elements (organic compounds, plants, mycorrhiza, and microbes) in radionuclide sorption/desorption in soils and radionuclide uptake/release by plants. Because of the importance of their radioisotopes, the bioavailability of three elements, caesium, strontium, and technetium has been followed. The role of one additional non-radioactive pollutant (copper) has been scrutinised in some cases. Role of microorganisms (e.g., K(d) for caesium and strontium in organic soils is much greater in the presence of microorganisms than in their absence), plant physiology (e.g., changes in plant physiology affect radionuclide uptake by plants), and the presence of mycorrhizal fungi (e.g., interferes with the uptake of radionuclides by plants) have been demonstrated. Knowledge acquired from these experiments has been incorporated into two mechanistic models CHEMFAST and BIORUR, specifically modelling radionuclide sorption/desorption from soil matrices and radionuclide uptake by/release from plants. These mechanistic models have been incorporated into an assessment model to enhance its prediction ability by introducing the concept of bioavailability factor for radionuclides.

Variation of the distribution coefficient (Kd) of selenium in soils under various microbial states.

This study aimed to (i) evaluate whether the K(d) value of selenium is dependent upon the soil microbial activity and (ii) define the limitation of the use of the K(d) concept to describe selenium behaviour in soils when assessing the long-term radiological waste disposal risk. K(d) coefficients, as well as information on selenite speciation in the soil-solution, were derived from short- and long-term batch experiments with a calcareous silty clay soil in various microbial states. Soil microbial activity induced (i) an increase of the K(d) value from 16 l kg(-1) in sterile conditions to 130 l kg(-1) when the soil was amended with glucose and nitrate, and (ii) changes in selenium speciation both in the solution (presence of seleno-species other than free Se(IV)) and in the solid phase (Se linked to microorganisms). Although the K(d) coefficient adequately reflects the initial fractionation between soil-solid and soil-solution, it does not allow for speciation and microbial processes, which could affect reversibility, mobility and the long-term accumulation and uptake into crops.

Identifiability of sorption parameters in stirred flow-through reactor experiments and their identification with a Bayesian approach.

This paper addresses the methodological conditions -particularly experimental design and statistical inference- ensuring the identifiability of sorption parameters from breakthrough curves measured during stirred flow-through reactor experiments also known as continuous flow stirred-tank reactor (CSTR) experiments. The equilibrium-kinetic (EK) sorption model was selected as nonequilibrium parameterization embedding the Kd approach. Parameter identifiability was studied formally on the equations governing outlet concentrations. It was also studied numerically on 6 simulated CSTR experiments on a soil with known equilibrium-kinetic sorption parameters. EK sorption parameters can not be identified from a single breakthrough curve of a CSTR experiment, because Kd,1 and k- were diagnosed collinear. For pairs of CSTR experiments, Bayesian inference allowed to select the correct models of sorption and error among sorption alternatives. Bayesian inference was conducted with SAMCAT software (Sensitivity Analysis and Markov Chain simulations Applied to Transfer models) which launched the simulations through the embedded simulation engine GNU-MCSim, and automated their configuration and post-processing. Experimental designs consisting in varying flow rates between experiments reaching equilibrium at contamination stage were found optimal, because they simultaneously gave accurate sorption parameters and predictions. Bayesian results were comparable to maximum likehood method but they avoided convergence problems, the marginal likelihood allowed to compare all models, and credible interval gave directly the uncertainty of sorption parameters θ. Although these findings are limited to the specific conditions studied here, in particular the considered sorption model, the chosen parameter values and error structure, they help in the conception and analysis of future CSTR experiments with radionuclides whose kinetic behaviour is suspected.

Am-241 remobilization in a calcareous soil under simplified rhizospheric conditions studied by column experiments.

The effects of simplified rhizospheric conditions on the leaching of (241)Am from a calcareous soil, freshly contaminated, were investigated in batch and column experiments. Glucose and/or citrate were used as artificial exudate solutions at concentrations ranging from 10(-4) to 10(-2)moldm(-3). Am desorption, expressed in terms of distribution coefficients, varied from K(d)>10(4)dm(3)kg(-1) corresponding to a majority of experimental conditions, to K(d)/=10(-2)moldm(-3). Soil columns revealed successive steady states coupled with transitory episodes, the latter represented up to 90% of the total Am release. (241)Am fractions with different behaviours were thus highlighted in columns whereas batch only accounted for highest Am mobile fractions. The implications of the different processes are discussed in terms of modelling approach and risk assessment.

Pediatric sinogenic epidural and subdural empyema: The role of endoscopic sinus surgery.

AIM: To analyze the indications and outcomes of open neurosurgical approaches (ONA) and endoscopic transnasal approaches (ETA) in the surgical management of pediatric sinogenic subdural and epidural empyema. MATERIAL AND METHODS: Retrospective single-center study design within a tertiary care referral center setting. Children less than 18 years of age consecutively operated on between January 2012 and February 2014 for drainage of a sinogenic subdural empyema (SE) or epidural (EE) empyema were included. MAIN OUTCOME MEASURES: success of first surgical procedure, persistent symptoms and sequelae at the end of the follow-up period. RESULTS: Nine SE (53%) and 8 EE (47%) were observed. Neurological symptoms, especially seizures, were more frequent in the SE group. Perioperative pus samples were positive in 67% of the SE group and in 75% of the EE group. The most frequently isolated bacteria belonged to the Streptococcus anginosus group. CT or MR imaging showed that most empyema probably originated from the frontal sinus. However, two cases resulted from an ethmoiditis and one case from a Pott's puffy tumor, without any direct contact with the paranasal sinus. In cases of SE, the most effective surgical technique was ONA with craniotomy. Associated endoscopic sinus drainage was useful for the purpose of bacteriological diagnosis. In cases of EE, effectiveness was noted in both ONA and ETA techniques. In two cases of EE, the ETA procedure encompassed direct drainage of the empyema through the posterior wall of the frontal sinus (Draf III approach). The number of patients successfully treated after a single surgical procedure was higher in the EE group (p=0.05). Regarding outcomes, no mortalities were observed. Persistent disorders at the end of the follow-up period, especially headaches, cognitive, concentration or schooling problems, tended to be more frequent in the SE group than in the EE group (67% vs 29%), and were more commonly observed in cases requiring several surgical procedures (75% vs 12.5%) (p=0.05). DISCUSSION: Endoscopic sinus surgery plays a critical role in the surgical management of pediatric sinogenic SE and EE. In cases of small volume EE, the endoscopic approach associated with antibiotherapy may be sufficient to treat the infectious process.

Long term results of treatment in patients with extragonadal germ cell tumours.

From 1979 to 1991 56 patients with extragonadal germ cell tumours (EGCT) received cisplatin based chemotherapy. From 16 patients with seminomatous EGCT 13 achieved complete remission (CR) with chemotherapy alone, 2 with additional radiotherapy with final CR rate of 94%. 5 (31%) patients developed relapses and at a median follow-up of 38 (5-103) months 11 (69%) are alive and 10 (62%) have no evidence of disease (NED). Only 7 patients with non-seminomatous EGCT reached CR with chemotherapy alone and 8 more with additional chemotherapy or surgery. Overall CR was 37% and 3 (20%) relapses have been observed. At a median follow-up of 26 (3-114) months 14 (35%) are alive and remain free of disease, 26 (65%) have died. By univariate analysis seminomatous EGCT patients had a significantly greater likelihood of achieving a CR, for non-seminomatous EGCT BEP induction chemotherapy was superior to VAB-6, and NSEGCT patients with serum levels > 2000 ng/ml had worse prognosis. Current staging systems are insufficient to predict the treatment outcome in EGCT.

Paclitaxel and cisplatin as salvage treatment in patients with non-seminomatous germ cell tumour who failed to achieve a complete remission on induction chemotherapy.

The purpose of this study was to evaluate the efficacy and toxicity of paclitaxel and cisplatin combination chemotherapy as salvage treatment in patients with non-seminomatous germ cell tumour. Sixteen patients with histologically proven germ cell tumour, measurable disease and/or elevated serum tumour markers were eligible for the protocol. All patients had previously not achieved a complete remission (CR) to platinum-based induction chemotherapy and cytoreductive surgery. The treatment consisted of paclitaxel 175-225 mg/m2 as a 3-hour infusion, followed by cisplatin 100 mg/m2, repeated every 3 weeks for up to four cycles. Seven patients achieved a marker-positive partial remission (PR) by the end of the cisplatin-based induction chemotherapy; the remainder had disease progression at the start of the paclitaxel plus cisplatin treatment. One (6%) CR and 3 (19%) PRs were achieved, with an overall response rate of 25% (90% confidence interval 7-43). The duration of the CR is currently 9+ months; two PRs lasted 2 months. One patient with a PR has been lost to follow-up. During a median follow-up of 8 months (range 1-11), 12 patients died from the disease progression. The median survival for the whole group was 7 months. Toxicity was moderate, with neutropenia grade 3 occurring in 29% of patients, thrombocytopenia grade 1-3 in 29%, creatinine > 130 mmol/l in 36%, peripheral neuropathy grade 1-2 in 50%, and nausea and vomiting in 43%. Paclitaxel plus cisplatin showed modest activity, with an overall response rate of 31% in patients with poor prognosis who had not achieved a CR on induction chemotherapy.

Efficacy of combination chemotherapy including Platidiam in the treatment of malignant testicular tumors.

Thirty-seven patients were treated for advanced malignant testicular tumors with combined chemotherapy including cis-platinum (Platidiam). A complete regression was achieved in 23 patients (62%). No severe side effects were observed. Also in this study the effectivity of cis-platinum in the treatment of testicular tumors was proved.

Drug dose delivery and treatment outcome relationship in standard bleomycin, etoposide and cisplatin combination chemotherapy in nonseminomatous germ cell tumor patients.

This study retrospectively evaluated the influence of drug dose delivery components (DDDC) of bleomycin, etoposide and cisplatin chemotherapy for metastatic nonseminomatous germ cell tumors on treatment outcome (NSGCT). Between December 1987 and January 1995, 75 NSGCT patients were treated with a median of 4 cycles (range 3-8) of cisplatin 120 mg/m2 on day 1, etoposide 100 mg/m2 on days 1 through 5 and bleomycin 30 U on days 1, 3, and 5 every 3 weeks. DDDC, such as cumulative dose, cumulative dose in mg/m2, dose intensity (DI), relative dose intensity (RDI), dose intensity products, and relative dose intensity products by drug, were calculated and tested as possible predictors of treatment outcome in patients classified according to Indiana University (IU), and International Germ Cell Cancer Cooperative Group (IGCCCG) classifications. Overall complete response (CR) rate was 64%, and 3-year progression-free survival (PFS) was 59%. By IU classification there were statistical differences in CR and survival between moderate (89-81%) and advanced disease (42-40%) (p < 0.005), while for patients classified according to IGCCCG criteria, statistical differences in CR and PFS there were not registered. DI (mg/m2/week) and RDI values for the entire group were: cisplatin 33-0.82; etoposide 133-0.80 and bleomycin 11-0.37. We did not observe a statistically significant difference in drug dose delivery components for treatment outcome between patients who achieved a CR and incomplete response when analyzed by either extent of disease or whole group. Extent of disease was the most important predictor of treatment outcome.

Phase I/II trial of carboplatin dose escalation in combination chemotherapy with etoposide, bleomycin and GM-CSF support for poor prognosis nonseminomatous germ cell tumors patients.

To determine the maximum tolerated dose (MTD), and therapeutic efficacy of carboplatin (CBDCA) in combination with etoposide and bleomycin (CEB) as initial chemotherapy for poor prognosis germ cell tumors, a CBDCA dose escalation supported with GM-CSF had been performed. Twenty four untreated patients were treated with CBDCA 400 mg/m2 on day 1, etoposide 100 mg/m2 on days 1 to 5 and bleomycin 30 mg on days 1, 3, 5. Four cycles were scheduled at 21-day interval. The first cohort of 6 patients received only initial chemotherapy regimen. In the subsequent cohorts of six patients, the CBDCA dose was increased by 100 mg/m2. A fixed dose and schedule of GM-CSF at 5 micrograms/kg subcutaneously was given on days 6 through 15. Myelosuppression, with neutropenic fever and hemorrhages, was the dose-limiting toxicity at the 600 mg/m2 dose level. The recommended dose of CBDCA is 500 mg/m2. Overall complete response (CR) rate was 71% and with median follow up of 25 (16-34) months, 58% of patients are alive and have no evidence of disease (NED). A higher number of CR was achieved with CBDCA dose higher than 400 mg/m2 compared with CBDCA dose of 400 mg/m2 (92 vs. 50%, p = 0.03), as well as a higher proportion of patients who are alive and with NED (75 vs. 42%, p = 0.1). Despite GM-CSF support, the MTD of CBDCA could not be increased beyond 500 mg/m2 (50% of the dose escalation), due to severe myelosuppression. The treatment outcomes obtained with CEB in our study are no better than the standard cisplatin-based chemotherapy. Further studies of this regimen, where CBDCA dose should be calculated according to the patients glomerular filtration rate are warranted.

[Therapeutic effect of blastolysin in athymic mice with transplanted strains of human tumors]. / Terapevticheskii éffekt blastolizina u bestimusnykh myshei s perevivnymi shtammami opukholei cheloveka.

9 transplanted strains were used for the evaluation of antitumour effect of blastolysin. The short-term inhibition of the tumour growth was observed on the following models: breast cancer, stomach cancer, kidney cancer and chorionepithelioma.