Does the addition of oxaliplatin to preoperative chemoradiation benefit cT4 or fixed cT3 rectal cancer treatment? A subgroup analysis from a prospective study.

BACKGROUND: Whether there is any benefit derived from adding oxaliplatin to fluoropyrimidine-based preoperative chemoradiation is currently unknown in cases of advanced cT3 or cT4 tumours. Our aim was to evaluate this issue by analysing a randomized trial, which compared two schedules of preoperative treatment (chemoradiation vs. 5 × 5 Gy with 3 cycles of consolidation chemotherapy) for cT4 or fixed cT3 rectal cancer. PATIENTS AND METHODS: Delivery of oxaliplatin was mandatory to the first part of the study. For the second part, its delivery in both treatment-assigned groups was left to the discretion of the local investigator. We analysed a subgroup of 272 patients (136 in the oxaliplatin group and 136 in the fluorouracil-only group) from institutions that had omitted oxaliplatin in the second part of the study. RESULTS: Circumferential resection margin negative (CRM-) status rate was 68% in the oxaliplatin group and 70% in the fluorouracil-only group, p = 0.72. The pathological complete response rate (pCR) was correspondingly 14% vs. 7%, p = 0.10. Following multivariable analysis, when comparing the CRM- status in the oxaliplatin group to the fluorouracil-only group, the odds ratio was 0.79 (95 CI 0.35-1.74), p = 0.54; there being no interaction between concomitant chemoradiation and 5 × 5 Gy with consolidation chemotherapy; pinteraction = 0.073. For pCR, the corresponding results were 0.47 (95 CI 0.19-1.16), p = 0.10, pinteraction = 0.84. CONCLUSION: No benefit was found of adding oxaliplatin in terms of CRM nor pCR rates for either concomitant or sequential settings in preoperative radiochemotherapy for very advanced rectal cancer.

Long-course oxaliplatin-based preoperative chemoradiation versus 5 × 5 Gy and consolidation chemotherapy for cT4 or fixed cT3 rectal cancer: results of a randomized phase III study.

BACKGROUND: Improvements in local control are required when using preoperative chemoradiation for cT4 or advanced cT3 rectal cancer. There is therefore a need to explore more effective schedules. PATIENTS AND METHODS: Patients with fixed cT3 or cT4 cancer were randomized either to 5 × 5 Gy and three cycles of FOLFOX4 (group A) or to 50.4 Gy in 28 fractions combined with two 5-day cycles of bolus 5-Fu 325 mg/m(2)/day and leucovorin 20 mg/m(2)/day during the first and fifth week of irradiation along with five infusions of oxaliplatin 50 mg/m(2) once weekly (group B). The protocol was amended in 2012 to allow oxaliplatin to be then foregone in both groups. RESULTS: Of 541 entered patients, 515 were eligible for analysis; 261 in group A and 254 in group B. Preoperative treatment acute toxicity was lower in group A than group B, P = 0.006; any toxicity being, respectively, 75% versus 83%, grade III-IV 23% versus 21% and toxic deaths 1% versus 3%. R0 resection rates (primary end point) and pathological complete response rates in groups A and B were, respectively, 77% versus 71%, P = 0.07, and 16% versus 12%, P = 0.17. The median follow-up was 35 months. At 3 years, the rates of overall survival and disease-free survival in groups A and B were, respectively, 73% versus 65%, P = 0.046, and 53% versus 52%, P = 0.85, together with the cumulative incidence of local failure and distant metastases being, respectively, 22% versus 21%, P = 0.82, and 30% versus 27%, P = 0.26. Postoperative and late complications rates in group A and group B were, respectively, 29% versus 25%, P = 0.18, and 20% versus 22%, P = 0.54. CONCLUSIONS: No differences were observed in local efficacy between 5 × 5 Gy with consolidation chemotherapy and long-course chemoradiation. Nevertheless, an improved overall survival and lower acute toxicity favours the 5 × 5 Gy schedule with consolidation chemotherapy. CLINICAL TRIAL NUMBER: The trial is registered as ClinicalTrials.gov number NCT00833131.

Cathelicidin related antimicrobial peptide, laminin, Toll-like receptors and chemokines levels in experimental hypersensitivity pneumonitis in mice.

INTRODUCTION: Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by unresolved inflammation and tissue repair pathologies triggered by repeated organic dust exposure. The aim of the study was to investigate changes in levels of the cathelicidin related antimicrobial peptide (CRAMP), laminin (LAM-A1), selected Toll-like receptors (TLR) and chemokines in experimental HP in mice. MATERIALS AND METHODS: Three and 18-month-old female C57BL/6J mice underwent inhalations of the saline extract of Pantoea agglomerans cells, Gram-negative bacterium common in organic dust and known for its pathogenic impact. The inhalations were repeated daily (28 days). ELISA was used for measuring in lung tissue homogenates concentration of CRAMP, LAM-A1, TLR2, TLR4, TLR8, CXCL9 (chemokine [C-X-C motif] ligand) and CXCL10. RESULTS: Levels of TLR2, TLR4 and CXCL9 were significantly higher in both young and old mice lungs already after 7 days of inhalations, while significant increase of LAM-A1 and CXCL10 was noted after 28 days, compared to untreated samples. TLR8 level was significantly augmented only in young mice. Only CRAMP level significantly declined. Significantly higher TLR8 and CXCL9 concentration in untreated samples were noted in old animals compared to young ones. CONCLUSION: Significant alterations of the examined factors levels indicate their role in HP pathogenesis.

Preliminary studies on the relationship between Ixodes ricinus activity and tick-borne infection among occupationally-exposed inhabitants of eastern Poland.

Relative density (activity) of the tick Ixodes ricinus was determined in five districts of the Lublin region (eastern Poland) by vegetation flagging. Tick activity values were compared to the determined by ELISA tests seroprevalence to tick-borne encephalitis virus (TBEV) and Borrelia burgdorferi in forestry workers and farmers from the same areas. A significant correlation between tick activity and seroprevalence to both TBEV and B. burgdorferi antigen was found in farmers and in the total examined population.

[The risk factors of Toxocara canis infestation in population of patients from the Lublin region]. / Czynniki ryzyka zarazenia sie Toxocara canis w populacji pacjentów z makroregionu lubelskiego.

The risk factors of Toxocara canis infestation were assessed among population of patients from the Lublin region. Sera from 151 patients suspected of toxocarosis were tested on the presence of the specific antibodies by ELISA (Biokema-Bordier, Switzerland). Sera from 74 women and 77 men were collected (mean: 24 years; range: 0-74 years). Women sera were found positive in 27 cases (36.5%) and men in 34 cases (44.2%). Positive results were found in the following age groups: young people up to 15 years--34 positive from 71, people from 16 to 30 years old--7 from 33, people from 31 to 45 years old--9 from 24 and people older than 45 years--11 from 23. Patients suspected of ocular larva migrans were found serologically positive in 37 cases from 98. Among patients with eosinophilia 8 positive cases were found from 17 (47.1%). Rural inhabitants were found positive in 41 cases from 73, whereas inhabitants of small towns in 17 cases from 55 and inhabitants of Lublin city (population nearly 400,000) in 3 cases from 23. This relationship was statistically significant (p<0.01). The difference between the group of living in a house (52% positive cases) compared to those living in flats (18% positive cases) was also statistically significant (p<0.001).

[Risk of tick-borne encephalitis (TBE) virus infection among people occupationally exposed to tick bites]. / Ocena narazenia na zakazenie wirusem kleszczowego zapalenia mózgu osób zawodowo eksponowanych na kontakt z kleszczami.

The paper presents the results of seroepidemiologic studies concerning tick-borne encephalitis (TBE) in 1583 persons (1261 forestry workers and 233 farmers) from the Lublin region (eastern Poland) occupationally exposed to ticks and in 130 healthy blond donors (a control group). The mean percentage of seropositive reactions in forestry workers amounted 19.8% and in farmers 32.0%. Based on 5-year research (1994-1998) conducted in 5 districts of the Lublin region, an existence of endemic foci of TBE was detected in the district of Biala Podlaska, on the areas of Radzyñ Podlaski and Parczew, where the percentage of seropositive reactions in forestry workers exceeded 50%. Statistical analysis showed that the frequency of seropositive reactions in forestry workers and farmers was significantly greater compared to control group (p<0.001 and p<0.05, respectively). It indicates that these groups are occupationally exposed to TBE wirus. Totally, in the years 1994-98 nine clinical cases of TBE (acute neuroinfection) in forestry workers and fourteen clinical cases in farmers were confirmed serologically. The effectiveness of specific immunization against TBE was proved on the brie of 100% seroconversion in 56 earlier seronegative forestry workers. The obtained results proved that forestry workers and farmers in Poland are under increased risk of infection with TBE virus.

Seroepidemiologic study on tick-borne encephalitis among forestry workers and farmers from the Lublin region (eastern Poland).

The paper presents the results of seroepidemiologic studies concerning tick-borne encephalitis (TBE) in 1,583 persons (1,261 forestry workers and 233 farmers) from the Lublin region (eastern Poland) occupationally exposed to ticks and in 130 healthy blood donors (a control group). The mean percentage of seropositive reactions in forestry workers amounted to 19.8% and in farmers 32.0%. Based on 5-year research (1994-1998) conducted in 5 districts of the Lublin region, the existence of endemic foci of TBE was detected in the district of Bia a Podlaska, on the areas of Radzyn Podlaski and Parczew, where the percentage of seropositive reactions in forestry workers exceeded 50%. Statistical analysis showed that the frequency of seropositive reactions in forestry workers and farmers was significantly greater compared to control group (p < 0.001 and p < 0.05, respectively). It indicates that these groups are occupationally exposed to TBE virus. In the years 1994-98, a total of nine clinical cases of TBE (acute neuroinfection) in forestry workers and fourteen clinical cases in farmers were confirmed serologically. The effectiveness of specific immunization against TBE was proved on the basis of 100% seroconversion in 56 earlier seronegative forestry workers. The obtained results proved that forestry workers and farmers in Poland are under increased risk of infection with TBE virus.

Tolerability and efficacy of GM-CSF [Leucomax] in patients with small cell lung cancer treated with intensive chemotherapy.

The aim of this study was to evaluate tolerability and efficacy of Leucomax (Sandoz/Schering Plough) used for neutropenia in patients with small cell lung cancer (SCLC) treated with etoposide and cisplatin. The potential influence of granulocyte-macrophage colony stimulating factor (GM-CSF) on chemotherapy relative dose intensity (RDI) was also evaluated. The chemotherapy used was the following, cisplatin 50 mg m-2 i.v. 1 and 7 day, etoposide 170 mg m-2 i.v. 3-5 days, q 3-4 weeks. Patients received a median of six cycles (range 2-8) over 4-36 weeks (median: 20). Thirty-two consecutive patients were treated, six were excluded. Eleven patients received GM-CSF 5 micrograms kg-1 s.c. due to absolute neutrophil count (ANC), 1000/mm3 until recovery (ANC > 2000 mm3) or during 7 days, and thereafter prophylactically 24 hours post subsequent chemotherapy cycles for 7 days. Four patients received single GM-CSF course during the terminal disease phase. In 11 patients, there was no neutropenia requiring GM-CSF during the whole treatment course. Toxicity of chemotherapy was high, including thrombocytopenia, neutropenia, anaemia, mucositis, fever and hypotension. GM-CSF toxicity was the following, first dose reaction-one patient, local erythema-two patients, arthralgia-one patient, hypotension, chills, fever requiring GM-CSF discontinuation one patient RDI of cisplatin/etoposide was 0.77/0.62 in GM-CSF group, and 0.90/ 0.80 in patients who didn't receive Leucomax. Overall objective response rate to chemotherapy and complete response rate were 80% (21/26), 26% (7/26) and median survival of all patients was 10 months. Median disease free survival was 8 months. Four patients are alive, two patients lost during progression, 20 died. Administration of GM-CSF did not appear to improve RDI of chemotherapy, overall response rate (RR) nor survival in this phase I/II clinical study. RDI of chemotherapy was reduced in patients receiving GM-CSF due to thrombocytopenia and/or extrahaematologic toxicity of chemotherapy.

[Early results of chemotherapy in patients with non-small cell lung cancer]. / Wczesne wyniki leczenia chemicznego chorych na niedrobnokomórkowego raka pluca.

59 patients with non-small cell lung cancer were treated with cisplatin (60 mg/m2) on day 1 and etoposide (60 mg/m2) on days 1-5. The results of the treatment were evaluated after 4th course. Remissions were seen in 27 patients, 17 patients had stabilization and 15-progression. The response rate in stages I and II was 70%, in stage III-40% and in stage IV-23%. In squamous cell carcinoma the response rate was 55%, in large cell carcinoma-25% and in adenocarcinoma-12%.

[Cadmium content in daily food rations of rural school-age children]. / Zawartosc kadmu w calodziennych racjach pokarmowych dzieci wiejskich w wieku szkolnym.

Cadmium was determined in 230 daily food rations of children aged 8-9 years and 12-13 years. The study was carried out in spring and in autumn during three successive days. Daily meals were collected from the households selected in the area of five villages. Cadmium was determined by the extraction ASA method, after dry mineralization at about 450 degrees C. The level of cadmium in the examined food rations varied from 6 to 569 micrograms/person/day, with the mean value of 43.5 +/- 52.6 micrograms/person/day, and the median of 31.3 micrograms. In 93% of food rations the amount of cadmium was below the upper limit--the dose permitted by the WHO for adults i.e. 57-71 micrograms/day. Considering the children's smaller body weight the daily cadmium intake in food rations was converted into the daily cadmium intake per 1 kilogram body weight. In the group of children aged 8-9 years cadmium intake was 0.3-15 micrograms, with the mean value of 1.7 micrograms, and in the group of 12-13-years-old children it was 0.1-13.9 micrograms, with the mean of 1.3 micrograms. Only 36% of food rations in the group of younger children and 58% of food rations in the older group contained the amount of cadmium below the tolerable value of 1 microgram/kg body weight/day. The weekly cadmium intake was calculated for each child based on its amount in daily food rations during the successive three days. The mean value was 12.3 micrograms/kg body weight, with the median of 8.1 micrograms, within the range of values 2.1-58.8 micrograms.(ABSTRACT TRUNCATED AT 250 WORDS)

Urinary excretion of protein and non-protein hydroxyproline in patients with sarcoidosis and interstitial pulmonary fibrosis.

The determination of total hydroxyproline (Hyp) with separation into protein and non-protein fractions was carried out in 24-hour urine samples of healthy persons, patients with sarcoidosis and patients with interstitial pulmonary fibrosis (i.p.f.). In the group of sarcoidosis Hyp excretion was evaluated taking into account progression of pulmonary changes and disease activity. It was found that total and non-protein Hyp excretion correlated positively in healthy persons as well as in those with sarcoidosis, and interstitial pulmonary fibrosis. An increased excretion of total and non-protein Hyp occurred in 24% of the patients with sarcoidosis while excretion of protein Hyp remained within the normal range. In 30% of the patients with interstitial pulmonary fibrosis increased excretion of total and non-protein Hyp was demonstrated. The excretion of protein Hyp in these patients did not deviate from normal values. The results of our study indicate that determination of total and nonprotein Hyp in urine may be useful in the evaluation of fibrotic changes in the pulmonary diseases mentioned above. However, these parameters are not usefull in differentiation between sarcoidosis and interstitial pulmonary fibrosis.

[Two cases of tuberculous pericarditis--diagnostic difficulties]. / Dwa przypadki gruzliczego zapalenia osierdzia--trudnosci diagnostyczne.

Some difficulties etiological diagnosis were presented in an example of two clinical cases. In the first patient with exudative pericarditis tuberculosis was determined in histopathological examination of lymph node (caseous necrosis). After antituberculotic treatment the majority of clinical symptoms was disappeared. In the second patient with chronic constrictive pericarditis the tuberculous etiology was accepted according to highly positive tuberculin reaction and signs of pericardial calcification. Patient was qualified to pericardiectomy.

[Castleman tumor]. / Guz Castlemana.

A case of a mediastinal benign tumor in a 56 year old male is presented. The tumor was detected during a routine chest radiographic examination. The patient was asymptomatic. During thoracotomy two tumors were found. One was localized in the middle mediastinum the other in the posterior mediastinum. Both tumors were removed completely. Basing on the results of the clinical examination, of the laboratory data and the histopathological examination of the resected tumors a diagnosis of Castleman's tumor of the plasma-cell type was made.

[Ofloxacin in the treatment of pulmonary changes caused by Mycobacterium avium and Mycobacterium xenopii]. / Ofloksacyna w leczeniu zmian w plucach wywolanych przez Mycobacterium avium i Mycobacterium xenopii.

Two cases of atypical mycobacterial infections are reported. The first caused by Mycobacterium avium in a patient with silicosis, the second by Mycobacterium xenopii in a subject with evidence of extensive post-tuberculosis pulmonary lesions. Both were treated with ofloxacin with good results.

The usefulness of serum angiotensin-converting enzyme test in the diagnosis of sarcoidosis.

Angiotensin-converting enzyme (ACE) was determined in blood serum of 110 patients with sarcoidosis and 80 healthy persons. Taking into account the advancement of pulmonary changes as well as disease activity the behaviour of this enzyme was estimated. It was found that ACE activity is significantly higher in patients with sarcoidosis than in control group. The rise of ACE activity took place in 90% of patients with active sarcoidosis and almost in 50% with inactive sarcoidosis.

[Prognostic value of measuring serum angiotensin I-converting enzyme (ACE) in patients with sarcoidosis]. / Prognostyczna wartosc oznaczania enzymu konwertujacego angiotensyne I (ACE) w surowicy chorych na sarkoidoze.

Serum ACE (s-ACE) activity were determined in 112 sarcoid patients and 60 healthy volunteers. The mean s-ACE activity in sarcoid patients were 39.5 +/- 14.1 U. and in healthy volunteers 22.1 +/- 3.6, U. Significant increase of s-ACE was seen in active sarcoidosis 51.2 +/- 13.7 U. Serum ACE activity increased twice or more in comparison with control values imply activity of the process. Serum-ACE determination may be of use as a prognostic factor in sarcoidosis.

[Post-traumatic chylothorax]. / Pourazowy wylew chlonki do jamy oplucnej (chylothorax).

A case of post-traumatic chylothorax in a 84 year old man with ILD is presented. The chylothorax was successfully treated after 6 months, which was confirmed at post-mortem, during which a solitary plasmocytoma of the left kidney was also diagnosed.

Effect of hydrazide cysteine on T cells. II. Human autologous rosette forming cells belong to two subpopulations differing with respect to the sensitivity to hydrocortisone and hydrazide cysteine.

In our studies on healthy individuals and patients suffering from chronic spastic bronchitis we demonstrated that autologous rosette forming cells in peripheral non-B lymphocytes belong to two subpopulations: HC-sensitive and HC-resistant. In about 50% of individuals there exists only one subpopulation of ARFC-HC-resistant. Treatment of individuals, whose non-B lymphocytes are 100% resistant to HC, with HC, did not cause any alteration in the ability to form rosettes. On the other hand, injection of HC into the individuals whose non-B lymphocytes are partially resistant to HC causes significant reduction of the autologous rosette formation. Similar results were obtained in the in vitro studies. Hydrazide cysteine converts HC-sensitive lymphocytes into HC-resistant which do not form rosettes. The mechanism of action of HC and HD on the cells forming autologous rosettes is discussed.