Early complete donor hematopoietic chimerism in peripheral blood indicates the risk of extensive graft-versus-host disease.

Achievement of complete donor hematopoietic chimerism (CC) is the goal of allogeneic stem cell transplantation (allo-SCT). Persistence of recipient hematopoiesis augments the risk of relapse, which is one of the main reasons for mortality after allo-SCT. Another main reason for morbidity and mortality is severe extensive chronic graft-versus-host disease (cGvHD). We examined chimerism in peripheral blood of 54 allogeneic stem cell recipients using multiplex STR-PCR method and compared it with the timing and severity of cGvHD. In total, 25 patients achieved early CC (by day 100 post transplant) at a median time of 60 days. In total, 21 of them developed extensive cGvHD. In those patients CC uniformly preceded emergence of cGvHD by a mean of 85 days. A total of 26 patients obtained late CC at a median time of 270 days post transplant. Of this group, only eight patients developed extensive disease. Development of cGvHD in those patients preceded achievement of CC in 10 of 13 cases by a mean of 100 days. The difference between early and late CC groups as to the frequency of the extensive cGvHD was statistically significant (P<0.001). Also, there was a significant correlation of the time of CC and time between CC and cGvHD. Additionally, patients with early CC developed significantly more severe cGvHD measured by the need of three-drug treatment to control the disease (P<0.005). It can be concluded that achievement of early complete donor hematopoietic chimerism in peripheral blood is strongly predictive of severe extensive GvHD.

Imatinib therapy prior to myeloablative allogeneic stem cell transplantation.

It is unknown whether imatinib prior to myeloablative haematopoietic stem cell transplantation (HSCT) increases transplant-related toxicity. Among the side effects induced by imatinib, myelosuppression and liver injury might worsen HSCT outcomes. We retrospectively analysed engraftment, liver toxicity, acute graft-versus-host disease (aGVHD) incidence and 100-day mortality in 30 patients with BCR/ABL-positive leukaemias who received imatinib before HSCT and compared results of 48 age-matched controls who did not receive preceding imatinib. Both neutrophil and platelet engraftment occurred more rapidly among imatinib patients but the differences adjusted for Gratwohl scale were not statistically significant (P = 0.18 and 0.22, respectively). The adjusted hazards of having liver function tests (LFTs) >1.5 normal increased and the adjusted durations of elevated LFTs were not significantly different. The estimated adjusted difference in mean peak bilirubin values was also not significantly different (P = 0.48). However, the adjusted hazard of increased creatinine >1.5 normal was significantly higher in the imatinib group (HR = 4.09, P = 0.02). The adjusted odds of grades II-IV aGVHD were similar in both groups (OR = 0.86, P = 0.78), and while the adjusted odds of 100-day mortality were lower among imatinib patients, the difference was not significant (OR = 0.65, P = 0.60). These data do not provide any evidence that imatinib preceding HSCT increases acute transplant-related toxicities.

Surgery alone in the curative treatment of localised oesophageal carcinoma.

AIM: To document the results of surgery alone in patients with localised oesophageal carcinoma. METHODS: Between January 1982 and 2002, 179 consecutive patients who underwent curative oesophagectomy for stage 0, I or II oesophageal carcinoma, without neo-adjuvant treatment, were analysed retrospectively. RESULTS: Postoperative mortality and morbidity rates were 2.8 and 30.7%, respectively. The overall actuarial survival rate at 5 years was 59%. No patients with more than four invaded lymph nodes survived 5 years. A lymph node ratio more than 0.2, more than four invaded lymph nodes and an advanced pTNM stage were predictors of poor prognosis. CONCLUSION: Long-term survival after surgery alone for localised oesophageal carcinoma can be achieved in some 2/3rds of patients. These results should be considered before designing neo-adjuvant therapeutic regimen or embarking into exclusive treatment alternate to oesophagectomy.

Extent of oesophageal resection for adenocarcinoma of the oesophagogastric junction.

AIMS: The optimal extent of oesophageal resection and surgical approach in patients treated for adenocarcinomas of the oesophagogastric junction (OGJ) are still uncertain. We report the correlations between resection margin involvement and outcome. METHODS: Patients with positive proximal resection margin (PPRM) and those with negative proximal resection margin (NPRM) were compared. RESULTS: Of 94 patients with macroscopically complete resection, eight were PPRM. There was no difference between the two groups in postoperative mortality or morbidity rates, in anastomotic leakage or in recurrence rates. The median survival in the PPRM group was 11.1 months compared with 36.3 months in the NPRM group (P=0.02). No infiltration was observed in patients whose proximal margin exceeded 7 cm. The extended transthoracic approach was the only prognostic factor for tumours type II (P=0.03, RR=1.4, 95% CI: 1.1-1.8). CONCLUSION: Histologic infiltration of oesophageal resection margin influences 5-year survival rate. In adenocarcinomas of the OGJ that can be treated curatively, a transection with a 8 cm oesophagectomy above the tumour in fresh specimen should be performed, and by thoracoabdominal approach for tumours type I and II.

[Preoperative prognostic factors for squamous cell carcinomas of the thoracic esophagus]. / Facteurs pronostiques préopératoires des cancers épidermoïdes de l'oesophage thoracique.

AIM OF THE STUDY: To identify preoperative survival prognostic factors in patients with resectable squamous cell carcinoma of the thoracic esophagus. POPULATION: From January 1982 to September 1999, 868 patients underwent surgery for esophageal carcinoma in our department, including 493 for squamous cell carcinoma of the thoracic esophagus. The following parameters were retrospectively included in univariate and multivariate analysis: age, sex, undernutrition, dysphagia, tumor diameter and nodal involvement on the CT-scan, preoperative treatment, surgical technique, curative resection, pTNM classification, histologic type and postoperative complications. The actuarial survival was determined. RESULTS: Survival prognostic factors were dysphagia, nodal involvement on CT-scan and depth of tumor invasion at pathological examination. Three groups of patients were identified on the two preoperative variables: group 1: patients without dysphagia (n=102), group 2: patients with dysphagia but without nodal involvement on the CT- scan (n=244), group 3: patients with dysphagia and with nodal involvement on the CT- scan (n=147). The median survivals were 62.4, 19.1 and 14.4 months in groups 1, 2 and 3, respectively, and 5-year actuarial survivals were 50%, 21% and 11% (P<0.009). CONCLUSION: Our study confirms that dysphagia and nodal involvement on the CT-scan are simple preoperative prognostic factors in patients with resectable squamous cell carcinoma of the thoracic esophagus.

[Oesophageal cancer in patients with head and neck cancers: therapeutic implications]. / Association cancers de l'oesophage et des voies aérodigestives supérieures : implications thérapeutiques.

AIM OF THE STUDY: To determine therapeutic and prognostic implications of an associated head and neck primary cancer in patients undergoing oesophagectomy for squamous cell carcinoma of the oesophagus. PATIENTS AND METHODS: Between 1982 and 2000, 868 patients with oesophageal cancer were operated in our institution, including 78 (9%) who underwent oesophagectomy for associated oesophageal and head and neck cancers; the latter was synchronous (n = 52) or anterior metachronous (n = 26). Influence of head and neck cancer on the treatment of oesophageal carcinoma was analysed retrospectively in terms of surgical therapeutic strategy and survival. RESULTS: Oesophageal resection consisted of oeso-pharyngolaryngectomy (n = 14, 17.9%), subtotal oesophagectomy (n = 62, 79.5%) and cervical oesophagectomy (n = 2, 2.6%). Radical resection (R0) was obtained in 85% of cases. Postoperative mortality rate was 5 % (4/78). Main complications were pulmonary (18% = 14/78) and anastomotic leaks (14% = 11/78), all of them cervical. Follow-up (mean = 25 +/- 27 months) was complete for all 78 patients. Five-year survival after R0 resection was 25%. Survival pronostic factors were denutrition, complete resection, and pT status of oesophageal tumor. CONCLUSION: In patients with associated carcinomas of oesophagus and head and neck, agressive treatment -including an oesophagectomy- allowed a 5-year survival rate more than 25% without increased mortality or morbidity rates, compared with patients operated on for isolated oesophageal carcinoma.

[Patients surviving 5 years after curative oesophagectomy for oesophageal cancer]. / Patients vivants à 5 ans après oesophagectomie curative pour cancer.

AIM OF THE STUDY: To analyse the clinical and pathological parameters of 5-year survival patients after curative oesophageal resection for cancer and to identify factors predictive of long-term survival. METHODS: The data of 370 patients who underwent oesophagectomy with curative intent from January 1982 for oesophageal squamous cell carcinoma (n = 320) or adenocarcinoma (n = 50) were reviewed. After excluding postoperative deaths (n = 20), these patients were surviving (S group, n = 113) or dead (NS group, n = 237) with a 60-month follow-up. Uni- and multivariate analysis allowed comparison between the two groups. RESULTS: Postoperative mortality and morbidity rates were 4.0% and 37.6%, respectively. Parameters related to 5-year survival were: absence of preoperative malnutrition or dysphagia, transhiatal resection, no reoperation, limited tumour, histological response to neoadjuvant treatment, absence of lymph node capsular invasion, number of invaded lymph nodes < or = 4, invaded lymph node ratio < or = 0.1, absence of tumour recurrence or metachronous primary cancer. On multivariate analysis, factors predictive of 5-year survival were: absence of preoperative dysphagia (P < 0.001), stage 0-I-IIA tumour (P<0.001) and absence of metachronous cancer (P = 0.016). CONCLUSION: Complete surgical resection allows 5-year survival. Factors predictive of long-term survival assessed in preoperative evaluation, dysphagia and tumour stage, should be useful to select patients for neoadjuvant treatment.

[Reconstruction after total circular pharyngolaryngectomy: comparison between gastric interposition and free jejunal flap]. / Reconstruction après pharyngolaryngectomie totale circulaire: comparaison de la plastie gastrique et du greffon de jejunum libre.

AIM OF THE STUDY: To elucidate hospital mortality, morbidity and actuarial survival rates of patients with carcinoma of the hypopharynx and cervical oesophagus and to identify the technique of choice for reconstruction after pharyngolaryngectomy. PATIENTS AND METHODS: We reviewed the records of 209 patients who underwent total pharyngolaryngectomy between May 1982 and January 2000. The majority of patients had advanced cancer: hypopharyngeal in 131 cases and cervical oesophageal in 78 cases. Follow-up was complete for all patients. Chi 2 and log rank tests were used, with a limit of significance of 5%. RESULTS: The postoperative mortality and morbidity rates were 4.8% and 38.3%, respectively. Alimentary continuity was achieved using the stomach (127 patients), colon (5 patients), or free jejunal autograft (77 patients). The 1-year and 5-year survival rates were 62% and 24%, respectively. There was no significant difference with regard to the survival between gastric transposition and free jejunal autograft, but there were fewer complications in the gastric pull-up group with regard to the respiratory complications (33% vs 47.0%, p < 0.05), local recurrences (15.8% vs 33.8%, p = 0.004) and survival without dysphagia (76% vs 89%, p < 10(-5)). CONCLUSION: Surgical ablation is a viable option for advanced hypopharyngeal and cervical oesophageal neoplasms, and stomach interposition is the preferred method of reconstruction.

[Diaphragmatic hernia after esophagectomy: 2 case reports and review of the literature]. / Hernie diaphragmatique après oesophagectomie: à propos de deux cas et revue de la littérature.

Diaphragmatic herniation of is uncommon after esophagectomy. The aim of this study was to report two cases of transhiatal herniation following esophagectomy, to analyse the contributing factors of this complication and to expose the preventive treatment, by means of a review of the literature.

[Essential thrombocythemia as a cause of headache in young woman]. / Nadplytkowosc samoistna przyczyna bólów glowy u mlodej kobiety.

A case of severe headache in a young woman is described. The headache was not associated with additional neurological findings. In peripheral blood extremely high count of platelets was found. Additional examinations supported the diagnosis of essential thrombocythemia (ET). As a first line treatment thrombocytapheresis was performed. The introduced hydroxyurea treatment was complicated with dysmenorrhea and neutropenia. It was the reason to the use anagrelide--a new antiplatelet drug--in the therapy of ET. The treatment with anagrelide was free of previously mentioned complications. After one year of observation the platelet count was still effectively reduced.

Common factors of spontaneous self-extubation in a critical care setting.

A prospective, concurrent study was conducted of all patients who self-extubated in a mixed critical care setting during a 14-month period. The purpose of the study was to identify the incidence and common factors associated with spontaneous self-extubation (SSE). A total of 75 cases of SSE occurred in 68 patients who had an incidence of 38.5 SSEs per 100 intubated days. The analysis of common factors of the total population found the following: 60 cases (80%) were restrained; 44 cases (59%) required reintubation; 66 cases (88%) followed commands or localized painful stimuli at the time of SSE; and 67 cases (89%) elicited spontaneous eye opening or opened eyes to verbal command at the time of SSE. Only 18 cases (24%) had analgesia administered within 1 to 2 hours of SSE. Twenty-four cases (32%) had anxiolytics administered within 4 hours of SSE. Of the 56 cases of SSE that were witnessed, 43 cases (73% of those observed) were considered deliberate rather than accidental. The practice of using intravenous boluses on an "as needed" dosing frequency for administering sedation and analgesia was a common factor in SSE. Adequate doses of sedation and analgesia delivered by continuous infusion may prevent SSE in alert, intubated patients.

Overactivity of tumor necrosis factor-alpha but not interleukin 6 is associated with low natural killer cytotoxic activity in the elderly.

In this paper we asked whether the increased production of two proinflammatory cytokines-tumor necrosis factor-alpha (TNF alpha) and interleukin-6 (IL6) in the absence of the inflammatory stimulus, a phenomenon frequently occurring in the elderly, may contribute to the decrease of natural killer (NK) cytotoxic activity. NK cell activity is a part of a nonspecific immunity directed against infected and transformed cells. We measured the levels of bioactive TNF alpha and IL6 during cytotoxic NK reactions and analyzed the effect of neutralizing monoclonal antibodies anti-TNF alpha and anti-IL6 on the outcome of cytotoxic reaction. Bioactive TNF alpha was produced in higher amounts during cytotoxic reactions of the elderly with low NK activity in comparison with its production by the elderly with high NK activity. Anti-TNF alpha decreased already low cytotoxic responses of the elderly while not having an effect on the cytotoxic potential of high responders. More of the bioactive IL6 was released during cytotoxic reactions of the elderly as compared with young people. There was, however, no relation between the height of NK cytotoxic activity and the amount of IL6. Our results suggest that the increased level of TNF alpha seen in the elderly low NK responders may pose a compensatory mechanism, necessary to keep the highest possible level of NK responses. The increased bioactivity of IL6 during NK reaction of the elderly does not seem to participate in the regulation of the level of NK cytotoxic activity.

[Treatment of essential thrombocythemia--personal experience]. / Leczenie nadplytkowosci samoistnej--doswiadczenia wlasne.

The present paper summarizes 13-years our center's experience in the treatment of essential thrombocythemia (ET). We analyzed a group of 36 patients treated with busulphan (Bu), 16 with hydroxyurea (HU) and 4 with interferon alpha (INF alpha). The results of therapy were assessed using proposed self-defined criteria of ET remission. The remission of ET was achieved in 75% of the patients treated with Bu and 57% treated with HU followed for at least 2 years. In the INF alpha treated group cytoreduction was achieved only in patients in whom initial dose of INF alpha was 6 mln I.U. per day. HU seems to be the drug of choice in younger patients because of possible mutagenic effect of Bu as well as in those, in whom Bu was administered in high total dose. During the cytoreductive or maintenance therapy with HU the blood morphology should be often controlled because of relatively high frequency (40%) of leukopenia. In each case of ET cytogenetic examination is necessary. Ph-positive ET determine the choice of the treatment.

Surgical management of and long-term survival after adenocarcinoma of the cardia.

BACKGROUND: The choice of surgical strategy for patients with adenocarcinoma of the oesophagogastric junction is controversial. This study was performed to analyse the surgical results of a 20-year experience with these lesions. METHODS: From January 1981 to January 2001, 126 patients with adenocarcinoma of the cardia underwent resection in the authors' institution. The treatment of choice was oesophagectomy for type I tumours, and extended gastrectomy for type II and III lesions. Morbidity, mortality and survival were determined retrospectively. RESULTS: Fifty-six patients (44.4 per cent) had type I tumours, 44 (34.9 per cent) type II and 26 (20.6 per cent) type III. Primary resection was performed in 113 patients (89.7 per cent). Oesophagectomy with resection of the proximal stomach was carried out in 65 patients (51.6 per cent) and extended total gastrectomy with transhiatal resection of the distal oesophagus in 61 (48.4 per cent). In-hospital mortality and morbidity rates were 4.8 and 34.1 per cent respectively. The overall 3- and 5-year survival rates were 40.9 and 25.1 per cent respectively, and were not affected by the surgical approach. Survival was significantly associated with R0 resection, pathological node-positive category, postoperative complications and tumour differentiation. CONCLUSION: Postoperative mortality, morbidity and long-term survival did not appear to be affected by surgical approach. Further prospective studies are needed to confirm the equivalence between transthoracic and transabdominal approaches.

Value of endoscopic ultrasonography as a predictor of long-term survival in oesophageal carcinoma.

BACKGROUND: : Endoscopic ultrasonography (EUS) is considered to be the best locoregional staging technique for cancer of the oesophagus. This study evaluated the relationship between preoperative EUS findings, completeness of surgical resection and survival. METHODS: : Between January 1995 and July 2002, 150 patients who underwent EUS for staging of tumours of the oesophagus were analysed prospectively. All underwent surgical resection with curative intent without neoadjuvant treatment. RESULTS: : Patient survival was significantly related to tumour (EUS T), node (EUS N) and Union Internacional Contra la Cancrum classification (EUS UICC) stage according to sonographic findings (P = 0.003, P = 0.009 and P = 0.004 respectively), and the presence of stenosis determined by EUS (P = 0.004). EUS T stage was a prognostic factor for survival (relative risk 1.7 (95 per cent confidence interval (c.i.) 1.1 to 3.0); P = 0.046). Complete surgical resection (R0) was also significantly related to EUS T, N and UICC classification (P < 0.001). EUS UICC stage was a factor predictive of R0 resection (relative risk 2.6 (95 per cent c.i. 1.4 to 4.8); P = 0.003). CONCLUSION: : R0 resection and survival of patients with tumours of the oesophagus were strongly related to endosonographic findings. These results support the proposal that EUS should be performed in all patients with oesophageal cancer, not only for staging patients before therapy but also to determine prognosis.

A comparison of active and simulated chiropractic manipulation as adjunctive treatment for childhood asthma.

BACKGROUND: Chiropractic spinal manipulation has been reported to be of benefit in nonmusculoskeletal conditions, including asthma. METHODS: We conducted a randomized, controlled trial of chiropractic spinal manipulation for children with mild or moderate asthma. After a three-week base-line evaluation period, 91 children who had continuing symptoms of asthma despite usual medical therapy were randomly assigned to receive either active or simulated chiropractic manipulation for four months. None had previously received chiropractic care. Each subject was treated by 1 of 11 participating chiropractors, selected by the family according to location. The primary outcome measure was the change from base line in the peak expiratory flow, measured in the morning, before the use of a bronchodilator, at two and four months. Except for the treating chiropractor and one investigator (who was not involved in assessing outcomes), all participants remained fully blinded to treatment assignment throughout the study. RESULTS: Eighty children (38 in the active-treatment group and 42 in the simulated-treatment group) had outcome data that could be evaluated. There were small increases (7 to 12 liters per minute) in peak expiratory flow in the morning and the evening in both treatment groups, with no significant differences between the groups in the degree of change from base line (morning peak expiratory flow, P=0.49 at two months and P=0.82 at four months). Symptoms of asthma and use of 3-agonists decreased and the quality of life increased in both groups, with no significant differences between the groups. There were no significant changes in spirometric measurements or airway responsiveness. CONCLUSIONS: In children with mild or moderate asthma, the addition of chiropractic spinal manipulation to usual medical care provided no benefit.