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.

The current application of ACOSOG Z0011 trial results: Is further implementation of sentinel lymph node intra-operative histopathological examination mandatory in breast cancer patients - a single-centre analysis.

The main objective of the ACOSOG Z0011 trial was to determine the impact of abandoning complete axillary lymph node dissection (ALND) on survival of breast cancer patients with sentinel node lymph (SLN) metastasis in whom breast conserving therapy (BCT) had been performed. The aim of our study was to assess the clinical value of intra-operative histopathological examination of SLN. Our study comprised 1284 invasive breast cancer patients in whom sentinel lymph node biopsy (SLNB) was carried out. SLN intra-operative histopathological assessment was routinely performed in patients treated within the first period (07.2013-06.2014). However, the decision regarding intra-operative assessment was made by the surgeon for the patients who underwent this evaluation in the later period 07.2014-06.2015 and were submitted for BCT. BCT was performed in 72.4% of patients. In total, 316 patients (24.6%) developed SLN-metastasis. Within the period 07.2014-06.2015, SLN intra-operative microscopic evaluation was performed in 20.8% of patients submitted for BCT. ALND was omitted in 27.5% of patients demonstrating SLN metastasis, in comparison with 15.5% of the group from the previous period (p=0.0094). The proportion of patients demonstrating macrometastasis in SLN who received conservative treatment to the axilla increased from 5.4% to 23.1% (p=0.0007). The choice of SLN final histopathological assessment may allow for deferral of decision on more extensive surgery of the axilla in patients submitted for SLNB. The omission of routinely-performed SLN intra-operative histopathological evaluation has led to a statistically significant increase in the proportion of patients in whom complete ALND was avoided.

Prospective assessment of the quality of life in patients treated surgically for rectal cancer with lower anterior resection and abdominoperineal resection.

INTRODUCTION: Rectal cancer is the most common malignant neoplasm of the gastrointestinal tract. The aim of the study was to assess the quality of life in patients undergoing surgical treatment for the rectal cancer, either lower anterior or abdominoperineal resection. MATERIALS AND METHODS: 100 patients suffering from rectal cancer were selected for a prospective study (50-APR, 50-LAR). The quality of life was assessed two times: at the admission to the Department and 6 months following surgery. For assessment of the quality of life, two standard questionnaires were used, EORT QLQ-C30 and EORTC QLQ-C29. RESULTS: The studied groups were not different with respect to demographic factors. The patients who underwent LAR spent less time in hospital (p = 0.00001). The patients undergoing APR scored less with respect to physical ability (p = 0.0434), cognitive (p = 0.0363) and emotional state (p = 0.0463) and on symptom scale (nausea and vomiting - p: 0.0199, diarrhea - p: 0.0000, constipation (p = 0.0018)); however, the patients who were treated with LAR scored less on pain scale (p = 0.0189). The QLQ-C29 questionnaire revealed impaired functioning of patients 6 months following APR in terms of life chances (p = 0.0000) and problems with body weight (p = 0.0212). In both groups, the quality of life improved 6 months after surgery. CONCLUSIONS: LAR is a chance for better quality of life for many patients. Six months after surgery, the quality of life of patients improves regardless of the operating method (APR, LAR).

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.

Management and results of treatment of breast cancer patients having sentinel lymph node micrometastases.

According to current therapeutic guidelines, finding micrometastases in the sentinel node (SLN) of a patient with non-advanced breast cancer is not an absolute indication for adjuvant axillary lymph node dissection (ALND). This work presents our experiences regarding this clinical problem. 1071 breast cancer patients were referred for sentinel node biopsy between January 2004 and December 2011. Metastases were found in 245 of the removed lymph nodes. In 49 patients lymph node changes turned out to be micrometastases or isolated tumor cells (ITC). ALND was performed in 38 cases of sentinel node micrometastases or ICTs. In three patients involvement of other axillary lymph nodes was found in the studied tissue material (7.9% vs. 37.9% for metastases >2mm). The remaining patients with micrometastases in the SLN (11/49) were treated conservatively. No local axillary recurrences or neoplastic metastases were found in this group of patients with SLN micrometastases. Mean follow-up period in patients who had undergone ALND was 18.0 months (4 to 60 months) and 21.4 months (9-40 months) in patients without ALND. Non-radical surgical treatment in the presence of SLN micrometastases in patients with non-advanced breast cancer does not lead to therapeutic failure (local axillary recurrences, distant metastases). Obtaining favorable outcomes of conservative treatment in the analyzed group of patients does not require additional modification of the adjuvant therapy.

The 'sleeve' anastomosis method for hemodialysis shunts: an eleven-year follow-up study.

PURPOSE: The problem of long form fistula for hemodialysis is well known among vascular surgeons because of frequent thromboses in anastomotic place. One of the pro-thrombotic factors is suture in the vessel's lumen. Since the 'sleeve' method prevents this, the patency rate should improve. METHODS: One hundred and eighty-two (182) patients were operated using the "sleeve" method. The operation was done under local anaesthesia and the first step was the dissection of the cephalic vein and the radial artery. Using Prolene 7-0 the artery and the vein were connected as follows: the first suture was placed intramuraly about 5 mm from the artery edge to the vein edge. The second suture (placed in the same way) was on the opposite side. The end of the radial artery was placed into the lumen of the cephalic vein and the sutures were tied. Two additional sutures were placed between them. Finally, four sutures were added to keep the artery in the vein. RESULTS: In our hands the patency rate of 'sleeve' arterio-venous fistulas was high: 95% after one month, 86% after one year, 64% after 5 years and 57% after 10 and 11 years. Every 'sleeve' fistula provided adequate blood flow, which increased during the follow-up period. CONCLUSIONS: The authors consider the "sleeve" fistula method as the primary choice because of its simplicity and excellent long-term patency.

[Interpretation of diagnostic data exemplified by tests for identification of Helicobacter pylori in gastric mucosa]. / Interpretacja danych diagnostycznych na przykladzie testów dla identyfikacji Helicobacter pylori w blonie sluzowej zoladka.

Seven diagnostic tests were employed to detect the infection of gastric mucosa with the H. pylori bacteria, among patients with epigastric pain and dyspeptic complains. The tests' results were compared to the bacteriologic culture. For each test the following criteria were taken into consideration: sensitivity, specificity, positive and negative predictive values. The tests' accuracy was compared with the agreement expected by chance and beyond chance (kappa). For each test the likelihood ratio was calculated for its positive and negative results. The construction of so called diagnostic decision tree was presented, which allows on the evaluation of the diagnostic test and its utility. The best result were obtained from the test, in which the identification of bacteria took place in the histopathologic specimen after its Gram staining. The interpretation of clinical significance of diagnostic data is simplified with the use of likelihood ratio calculated for a positive test result.

[Use of 4 microbiological methods to detect Helicobacter pylori]. / Wykorzystanie 4 metod mikrobiologicznych w wykrywaniu Helicobacter pylori.

The presence of Helicobacter pylori (HPY) was confirmed in 90% of a group of 76 patients with gastric disorders. The methods included the direct urease test, a preparation directly stained by the Gram method, culture and serological study using Cobas Core Anti-H. pylori EIA. High levels of IgG HPY antibodies were found in the serum of patients with gastritis chronica and ulcus duodeni. Urease activity can be observed even after 48 hours. Nevertheless such interpretation of test results requires confirmation by other microbiological methods applied simultaneously. HPY was obtained in 50% of culture. Already one hour after the test started, it was possible to confirm this species on the basis of Rapidec pylori. The presented procedure can be used and performed in a laboratory cooperating effectively with a gastroenterologist.

DNA base modifications in chromatin of human cancerous tissues.

Free radical-induced damage to DNA in vivo is implicated to play a role in carcinogenesis. Evidence exists that DNA damage by endogenous free radicals occurs in vivo, and there is a steady-state level of free radical-modified bases in cellular DNA. We have investigated endogenous levels of typical free radical-induced DNA base modifications in chromatin of various human cancerous tissues and their cancer-free surrounding tissues. Five different types of surgically removed tissues were used, namely colon, stomach, ovary, brain and lung tissues. In chromatin samples isolated from these tissues, five pyrimidine-derived and six purine-derived modified DNA bases were identified and quantitated by gas chromatography/mass spectrometry with selected-ion monitoring. These were 5-hydroxy-5-methylhydantoin, 5-hydroxyhydantoin, 5-(hydroxymethyl)uracil, 5-hydroxycytosine, 5,6-dihydroxycytosine, 4,6-diamino-5-formamidopyrimidine, 8-hydroxyadenine, xanthine, 2-hydroxyadenine, 2,6-diamino-4-hydroxy-5-formamidopyrimidine, and 8-hydroxyguanine. These compounds are known to be formed typically by hydroxyl radical attack on DNA bases. In all cases, elevated amounts over control levels of modified DNA bases were found in cancerous tissues. The amounts of modified bases depended on the tissue type. Lung tissues removed from smokers had the highest increases of modified bases above the control levels, and the highest overall amounts. Colon cancer tissue samples had the lowest increases of modified bases over the control levels. The results clearly indicate higher steady-state levels of modified DNA bases in cancerous tissues than in their cancer-free surrounding tissues. Some of these lesions are known to be promutagenic, although others have not been investigated for their mutagenicity. Identified DNA lesions may play a causative role in carcinogenesis.

[Psychosocial conditions of psychotropic drug poisoning of patients treated in the Gdansk Toxicology Center]. / Psychospoleczne uwarunkowania zatruc lekami psychotropowymi u chorych leczonych w Gdanskim Osrodku Toksykologicznym.

The purpose of the study was in analysis of both causes and social conditioning leading to attempts of self-intoxications by the use of psychotropic drugs. The study included 234 patients treated in the Gdansk Toxicological Center during years 1982-1987. In a majority, the intoxications referred to young subjects up to 30 year of age, more frequently women than men. Only 10% of subjects studied have had university education. The alcohol or drug dependence and various psychiatric disturbances has been noted in a majority of cases studied. The lack of real suicidal determination was characteristic pattern of group observed.

Acute silver poisoning through inhalation.

The paper presented a case of acute occupational poisoning with silver vapours. The course of the ailment was very serious. The clinical picture corresponded to the syndrome of the "shock lung"--with extreme respiratory insufficiency. The treatment included administration of steroids, heparin, antibiotics and controlled respiration with a positive endexpiratory pressure (PEEP). The patient was completely cured and fully regained physical fitness. Our observation seems to shake the hitherto predominant view of non-toxicity of metallic silver or its vapours.