Daily oxygen supplementation to the incubator at different stages of embryonic development alters the activity of antioxidant enzymes in the lung tissue of broiler chicks at a high altitude.

1. Pulmonary hypertension, associated with mitochondrial function in the lung tissue of broilers, can occur at hypoxic high altitudes. The present research examined the impacts of O2 supplementation at different embryonic stages on broiler organ development and antioxidant enzyme activities.2. In total, 360 eggs from Ross 308 broiler breeders at sea level were divided into a control group (O2 non-supplementation group) and three experimental groups daily 1 h 23.5% O2 supplementation from days 0 to 11 (O0-11), from days 12 to 21 (O12-21), and from days 18 to 21 (O18-21) of embryonic age.3. The lung, heart, right ventricular (RV), and left ventricular (LV) + septum of newly hatched and seven day old chicks from every group were dissected and weighed. Antioxidant enzyme activities were examined in their lung tissue.4. The lung weight did not change in any group. At hatching, the heart weight (g and %) was higher in the O12-21 and O18-21 groups than in the O0-11 and control groups, but the relative heart weight was the highest in the O18-21 group in comparison with the O12-21 group.5. Superoxide dismutase (SOD) activity increased in all experimental groups at both ages, but glutathione peroxidase (GPx) activity increased only in seven day old chicks. Catalase (CAT) exhibited high activity in the O12-21 and O18-21 groups at hatching. In the seven day old chicks, while the CAT activity did not change in the O18-21 group, it decreased in the O0-11 group and increased in the O12-21 group.6. Glutathione reductase (GR) activity did not change in the O18-21 group, but GR exhibited low activity in the O0-11 group and high activity in the O18-21 group in newly hatched chicks. The GR activity only decreased in the O18-21 group of seven day old chicks.7. The results indicated that oxygen supplementation to the incubator caused alterations in the antioxidant enzyme activities in the lungs of broiler chicks, and this may have been in response to oxidative stress.

Isolated tumor cells in stage I & II colon cancer patients are associated with significantly worse disease-free and overall survival.

BACKGROUND: Lymph node (LN) involvement represents the strongest prognostic factor in colon cancer patients. The objective of this prospective study was to assess the prognostic impact of isolated tumor cells (ITC, defined as cell deposits ≤ 0.2 mm) in loco-regional LN of stage I & II colon cancer patients. METHODS: Seventy-four stage I & II colon cancer patients were prospectively enrolled in the present study. LN at high risk of harboring ITC were identified via an in vivo sentinel lymph node procedure and analyzed with multilevel sectioning, conventional H&E and immunohistochemical CK-19 staining. The impact of ITC on survival was assessed using Cox regression analyses. RESULTS: Median follow-up was 4.6 years. ITC were detected in locoregional lymph nodes of 23 patients (31.1%). The presence of ITC was associated with a significantly worse disease-free survival (hazard ratio = 4.73, p = 0.005). Similarly, ITC were associated with significantly worse overall survival (hazard ratio = 3.50, p = 0.043). CONCLUSIONS: This study provides compelling evidence that ITC in stage I & II colon cancer patients are associated with significantly worse disease-free and overall survival. Based on these data, the presence of ITC should be classified as a high risk factor in stage I & II colon cancer patients who might benefit from adjuvant chemotherapy.

Discrete improvement in racial disparity in survival among patients with stage IV colorectal cancer: a 21-year population-based analysis.

PURPOSE: Recently, multiple clinical trials have demonstrated improved outcomes in patients with metastatic colorectal cancer. This study investigated if the improved survival is race dependent. PATIENTS AND METHODS: Overall and cancer-specific survival of 77,490 White and Black patients with metastatic colorectal cancer from the 1988-2008 Surveillance Epidemiology and End Results registry were compared using unadjusted and multivariable adjusted Cox proportional hazard regression as well as competing risk analyses. RESULTS: Median age was 69 years, 47.4 % were female and 86.0 % White. Median survival was 11 months overall, with an overall increase from 8 to 14 months between 1988 and 2008. Overall survival increased from 8 to 14 months for White, and from 6 to 13 months for Black patients. After multivariable adjustment, the following parameters were associated with better survival: White, female, younger, better educated and married patients, patients with higher income and living in urban areas, patients with rectosigmoid junction and rectal cancer, undergoing cancer-directed surgery, having well/moderately differentiated, and N0 tumors (p < 0.05 for all covariates). Discrepancies in overall survival based on race did not change significantly over time; however, there was a significant decrease of cancer-specific survival discrepancies over time between White and Black patients with a hazard ratio of 0.995 (95 % confidence interval 0.991-1.000) per year (p = 0.03). CONCLUSION: A clinically relevant overall survival increase was found from 1988 to 2008 in this population-based analysis for both White and Black patients with metastatic colorectal cancer. Although both White and Black patients benefitted from this improvement, a slight discrepancy between the two groups remained.

Molecular staging of lymph node-negative colon carcinomas by one-step nucleic acid amplification (OSNA) results in upstaging of a quarter of patients in a prospective, European, multicentre study.

BACKGROUND: Current histopathological staging procedures in colon carcinomas depend on midline division of the lymph nodes with one section of haematoxylin & eosin (H&E) staining only. By this method, tumour deposits outside this transection line may be missed and could lead to understaging of a high-risk group of stage UICC II cases, which recurs in ∼20% of cases. A new diagnostic semiautomated system, one-step nucleic acid amplification (OSNA), detects cytokeratin (CK) 19 mRNA in lymph node metastases and enables the investigation of the whole lymph node. The objective of this study was to assess whether histopathological pN0 patients can be upstaged to stage UICC III by OSNA. METHODS: Lymph nodes from patients who were classified as lymph node negative after standard histopathology (single (H&E) slice) were subjected to OSNA. A result revealing a CK19 mRNA copy number >250, which makes sure to detect mainly macrometastases and not isolated tumour cells (ITC) or micrometastases only, was regarded as positive for lymph node metastases based on previous threshold investigations. RESULTS: In total, 1594 pN0 lymph nodes from 103 colon carcinomas (median number of lymph nodes per patient: 14, range: 1-46) were analysed with OSNA. Out of 103 pN0 patients, 26 had OSNA-positive lymph nodes, resulting in an upstaging rate of 25.2%. Among these were 6/37 (16.2%) stage UICC I and 20/66 (30.3%) stage UICC II patients. Overall, 38 lymph nodes were OSNA positive: 19 patients had one, 3 had two, 3 had three, and 1 patient had four OSNA-positive lymph nodes. CONCLUSIONS: OSNA resulted in an upstaging of over 25% of initially histopathologically lymph node-negative patients. OSNA is a standardised, observer-independent technique, allowing the analysis of the whole lymph node. Therefore, sampling bias due to missing investigation of certain lymph node tissue can be avoided, which may lead to a more accurate staging.

Carbon dioxide insufflation in colonoscopy is safe: a prospective trial of 347 patients.

Available evidence suggests that the use of CO(2) insufflation in endoscopy is more comfortable for the patient. The safety of CO(2) use in colonoscopy remains contentious, particularly in sedated patients. The objective of the present prospective trial was to assess the safety of CO(2) colonoscopies. Methods. 109 patients from our previous randomized CO(2) colonoscopy study and an additional 238 subsequent consecutive unselected patients who had a routine colonoscopy performed in a private practice were enrolled from April 2008 through September 2008. All but 2 patients were sedated. All patients were routinely monitored with transcutaneous CO(2) measurement. Volumes of CO(2) administered were correlated with capnographic measurements from transcutaneous monitoring. Results. Of the 347 patients examined, 57% were women; mean (SD) age of participants was of 60.2 years (12.8). Mean propofol dosage was 136 mg (64 mg). Mean CO(2) values were 34.7 mm Hg (5.3) at baseline, 38.9 mm Hg (5.5) upon reaching the ileum, and 36.9 mm Hg (5.0) at examination's end. Mean maximum increase of CO(2) was 4.5 mm Hg (3.6). No correlation was observed between volume of CO(2) administered and increase in level of CO(2) (correlation coefficient: 0.01; P value: 0.84). No complications were observed. Conclusions. The present prospective study, which was based on one of the largest sedated patient sample reported to date in this setting, provides compelling evidence that CO(2) insufflation in colonoscopy is safe and unassociated with relevant increases in transcutaneously measured levels of CO(2).

Elevated preoperative CEA is associated with worse survival in stage I-III rectal cancer patients.

BACKGROUND: The objective of this investigation was to assess whether preoperative carcinoembryonic antigen (CEA) level is an independent predictor of overall survival in rectal cancer patients. METHODS: All patients (n=504) undergoing a resection for stage I-III rectal cancer at the Kantonsspital St Gallen were included into a database between 1991 and 2008. The impact of preoperative CEA level on overall survival was assessed using risk-adjusted Cox proportional hazard regression models and propensity score methods. RESULTS: In risk-adjusted Cox proportional hazard regression analyses, preoperative CEA level (hazard ratio (HR): 1.98, 95% confidence interval (CI): 1.36-2.90, P<0.001), distance from anal verge (<5 cm: HR: 1.93, 95% CI: 1.11-3.37; P=0.039), older age (HR: 1.07, 95% CI: 1.05-1.09; P<0.001), lower body mass index (HR: 0.94, 95% CI: 0.89-0.98; P=0.006), advanced tumour stage (stage II HR: 1.41, 95% CI: 0.85-2.32; stage III HR: 2.08, 95% CI: 1.31-3.31; P=0.004), R 1 resection (HR: 5.65, 95% CI: 1.59-20.1; P=0.005) and chronic kidney disease (HR: 2.28, 95% CI: 1.03-5.04; P=0.049) were all predictors for poor overall survival. CONCLUSION: This is one of the first investigations based on a large cohort of exclusively rectal cancer patients demonstrating that preoperative CEA level is a strong predictor of decreased overall survival. Preoperative CEA should be used as a prognostic factor in the preoperative assessment of rectal cancer patients.

Carbon dioxide insufflation in routine colonoscopy is safe and more comfortable: results of a randomized controlled double-blinded trial.

Many patients experience pain and discomfort after colonoscopy. Carbon dioxide (CO(2)) can reduce periprocedural pain although air insufflation remained the standard procedure. The objective of this double-blinded, randomized controlled trial was to evaluate whether CO(2) insufflation does decrease pain and bloating during and after colonoscopy compared to room air. Methods. 219 consecutive patients undergoing colonoscopy were randomized to either CO(2) or air insufflation. Propofol was used in all patients for sedation. Transcutaneous CO(2) was continuously measured with a capnograph as a safety parameter. Pain, bloating, and overall satisfaction were assessed at regular intervals before and after the procedure. Results(data are mean ±SD). 110 patients were randomized to CO(2) and 109 to room air. The baseline characteristics were similar in both groups. The mean propofol dose was not different between the treatments, as were the time to reach the ileum and the withdrawal time. pCO(2) at the end of the procedure was 35.2 ± 4.3 mmHg (CO(2) group) versus 35.6 ± 6.0 mmHg in the room air group (P > .05). No relevant complication occurred in either group. There was significantly less bloating for the CO(2) group during the postprocedural recovery period (P < .001) and over the 24-hour period (P < .001). Also, patients with CO(2) insufflation experienced significantly less pain (P = .014). Finally, a higher overall satisfaction (P = .04 ) was found in the CO(2) group. Conclusions. This trial provides compelling evidence that CO(2) insufflation significantly reduces bloating and pain after routine colonoscopy in propofol-sedated patients. The procedure is safe with no significant differences in CO(2) between the two groups.

Negative appendicectomy and perforation rates in patients undergoing laparoscopic surgery for suspected appendicitis.

BACKGROUND: Despite widespread use of imaging technologies including ultrasonography and computed tomography, rates of negative appendicectomy and perforated appendicitis remain high. This trend analysis examined whether rates of negative appendicectomy and perforated appendicitis have decreased over time, and sought to evaluate clinical predictors associated with negative appendicectomy and perforated appendicitis. METHODS: This analysis was based on the prospective database of the Swiss Association of Laparoscopic and Thoracoscopic Surgery (SALTS). All patients aged 12 years and over undergoing emergency laparoscopic appendicectomy between 1995 and 2006 were included. Unadjusted and risk-adjusted logistic regression analyses were performed. RESULTS: A total of 7964 patients underwent laparoscopic appendicectomy, of whom 7452 (93.6 per cent) had acute appendicitis and 512 (6.4 per cent) had a macroscopically normal appendix. Perforation occurred in 1230 (16.5 per cent) of those with appendicitis. In multivariable analysis, younger age (12-18 years), female sex, absence of local or generalized peritonitis and an early point during the study period were significant predictors of negative appendicectomy. For perforated appendicitis, significant predictors included age over 36 years, presence of localized or generalized peritonitis, and high American Society of Anesthesiologists grade. The rate of negative appendicectomy decreased from 12.7 per cent in 1995 to 2.8 per cent in 2006, there being a significant reduction in both unadjusted and risk-adjusted analyses (P < 0.001 for trend). In adjusted analyses, the rate of perforated appendicitis did not increase significantly over time. CONCLUSION: The rate of negative appendicectomy decreased over time, without an accompanying increase in perforated appendicitis. The risk of having a negative appendicectomy was highest in girls aged 12-18 years without local or generalized peritonitis during the early study period, whereas perforation was associated with age over 36 years, presence of localized or generalized peritonitis, and greater co-morbidity. Copyright © 2011 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Population-based trend analysis of laparoscopic Nissen and Toupet fundoplications for gastroesophageal reflux disease.

BACKGROUND: The Nissen and Toupet fundoplications are the most commonly used techniques for surgical treatment of gastroesophageal reflux disease. To date, no population-based trend analysis has been reported examining the choice of procedure and short-term outcomes. This study was designed to analyze trends in the use of Nissen versus Toupet fundoplications, and corresponding short-term outcomes during a 10-year period between 1995 and 2004. METHODS: A trend analysis was performed of 873 patients (Toupet: 254 patients, Nissen: 619 patients) prospectively enrolled in the database of the Swiss Association for Laparoscopic and Thoracoscopic Surgery. RESULTS: The frequency of the performed techniques remained stable during the observation period (p value for trend 0.206). The average postoperative and total length of hospital stay both significantly decreased during the 10-year period from 5.6 to 4.0 days and 6.8 to 4.8 days, respectively (both p values for trend <0.001). The average duration of surgery decreased significantly from 141 minutes to 121 minutes (p value for trend <0.001). There was a trend towards less complications in later years (2000-2004) compared to early years (1995-1999, p = 0.058). Conversion rates were significantly lower in later years compared with early years (p = 0.004). CONCLUSIONS: This is the first trend analysis in the literature reporting clinical outcomes of 873 prospectively enrolled patients undergoing Nissen and Toupet fundoplications during a 10-year period. The proportion of laparoscopic Nissen versus Toupet fundoplications remained stable over time, indicating that literature reports of the advantages of one procedure over the other had minimal influence on surgeons' choice of technique. Length of hospital stay, duration of surgery, morbidity, and conversion rate decreased over time, reflecting the learning curve. Clearly, patient outcomes have much improved during the 10-year observation period.

Population-based trend analysis of 2813 patients undergoing laparoscopic sigmoid resection.

BACKGROUND: The use of laparoscopic sigmoid resection for diverticular disease has become increasingly popular. The objective of this trend analysis was to assess whether clinical outcomes following laparoscopic sigmoid resection for diverticular disease have improved over the past 10 years. METHODS: The analysis was based on the prospective database of the Swiss Association of Laparoscopic and Thoracoscopic Surgery. Some 2813 patients undergoing elective laparoscopic sigmoid resection for diverticular disease from 1995 to 2006 were included. Unadjusted and risk-adjusted analyses were performed. RESULTS: Over time, there was a significant reduction in the conversion rate (from 27.3 to 8.6 per cent; P(trend) < 0.001), local postoperative complication rate (23.6 to 6.2 per cent; P(trend) = 0.004), general postoperative complication rate (14.6 to 4.9 per cent; P(trend) = 0.024) and reoperation rate (5.5 to 0.6 per cent; P(trend) = 0.015). Postoperative median length of hospital stay significantly decreased from 11 to 7 days (P(trend) < 0.001). CONCLUSION: This first trend analysis in the literature of clinical outcomes after laparoscopic sigmoid resection, based on almost 3000 patients, has provided compelling evidence that rates of postoperative complications, conversion and reoperation, and length of hospital stay have decreased significantly over the past 10 years.

Sentinel lymph node biopsy is associated with improved survival compared to level I & II axillary lymph node dissection in node negative breast cancer patients.

OBJECTIVE: The few long-term follow-up data for sentinel lymph node (SLN) negative breast cancer patients demonstrate a 5-year disease-free survival of 96-98%. It remains to be elucidated whether the more accurate SLN staging defines a more selective node negative patient group and whether this is associated with better overall and disease-free survival compared with level I & II axillary lymph node dissection (ALND). METHODS: Three-hundred and fifty-five consecutive node negative patients with early stage breast cancer (pT1 and pT2< or =3 cm, pN0/pN(SN)0) were assessed from our prospective database. Patients underwent either ALND (n=178) in 1990-1997 or SLN biopsy (n=177) in 1998-2004. All SLN were examined by step sectioning, stained with H&E and immunohistochemistry. Lymph nodes from ALND specimens were examined by standard H&E only. Neither immunohistochemistry nor step sections were performed in the analysis of ALND specimen. RESULTS: The median follow-up was 49 months in the SLN and 133 months in the ALND group. Patients in the SLN group had a significantly better disease-free (p=0.008) and overall survival (p=0.034). After adjusting for other prognostic factors in Cox proportional hazard regression analysis, SLN procedure was an independent predictor for improved disease-free (HR: 0.28, 95% CI: 0.10-0.73, p=0.009) and overall survival (HR: 0.34, 95% CI: 0.14-0.84, p=0.019). CONCLUSIONS: This is the first prospective analysis providing evidence that early stage breast cancer patients with a negative SLN have an improved disease-free and overall survival compared with node negative ALND patients. This is most likely due to a more accurate axillary staging in the SLN group.

Caveats in the interpretation of the surgical literature.

The ability to appraise research literature critically is an invaluable tool in the era of evidence-based medicine. The objective of this educational article is to highlight certain caveats that are important to those who seek to interpret the surgical literature. These caveats are illustrated with intuitive examples drawn from the field of surgery. It is hoped that the article will help surgeons to recognize the common pitfalls encountered when interpreting scientific reports. This is important if research findings are to be transferred appropriately into the realm of clinical practice.

Early introduction of laparoscopic sigmoid colectomy during residency.

BACKGROUND: Laparoscopic sigmoid colectomy for benign diseases is becoming the standard of care. However, few residency programmes incorporate the procedure. This study evaluated the safety and feasibility of the early introduction of laparoscopic sigmoid colectomy during residency. METHODS: From a database of consecutive laparoscopic sigmoid colectomies collected prospectively over 6 years, those for cancer and primary open sigmoid colectomies were excluded. Surgeons were categorized into five levels of experience in colonic surgery. Patient demographics, operative data, complications and conversion rates were assessed. RESULTS: A total of 262 sigmoid colectomies were performed by 13 surgeons. American Society of Anesthesiologists grade and diverticular disease classification were similar across the five experience levels. There were no significant differences in morbidity, mortality or readmission rates between experience levels. However, operative time (230 versus 145 min, P < 0.001) intraoperative blood loss (200 versus 100 ml, P < 0.001) and conversion rate (13.6 versus 2.1 per cent, P = 0.002) all decreased with increasing surgical experience (trainee versus trainer). CONCLUSION: It is safe and feasible to introduce laparoscopic sigmoid colectomy to a structured residency.

Expression of MAGE-A cancer/testis antigens in esophageal squamous cell carcinomas.

BACKGROUND: Although the diagnosis and therapy of esophageal cancer have improved over the past decade, the prognosis remains dismal. Since MAGE-A cancer/testis antigens (CTA) are potential targets for immunotherapy, this study was aimed at evaluating their expression in these patients and its prognostic value. MATERIALS AND METHODS: Using 57B monoclonal antibody, MAGE-A CTA expression was analyzed in paraffin-embedded tumor specimens of 98 patients with esophageal squamous cell carcinoma or adenocarcinomas who had undergone surgical resection. For all patients, a postoperative follow-up of at least 4 years was available. The expression was quantified using a scoring system considering intensity and homogeneity of the immunostaining. The prognostic relevance of MAGE-A expression was analyzed in univariate analyses as well as Cox proportional hazard regression analysis. RESULTS: 57B positivity could be detected in 38 tumors (38.8%). Positive staining was observed in five out of 32 adenocarcinomas (15.2%) and in 33 out of 66 (50%) squamous cell carcinomas. MAGE-A expression did not correlate with the TNM classification, grading or age of the patients. Both univariate (p=0.88) and multivariate analyses (p = 0.82) revealed that MAGE-A expression lacked prognostic significance in esophageal carcinomas. CONCLUSION: MAGE-A was expressed in half of the squamous cell carcinomas of the esophagus, but rarely in adenocarcinomas. Although its immunodetection was insufficient for prognostic evaluation, the high expression rate suggests MAGE-A as a potential target for immunotherapy in the first group with the ability for pretherapeutic testing.

Propensity scores and the surgeon.

BACKGROUND: Evidence-based surgery has been established as a cornerstone of good clinical practice, promising to improve the treatment of patients and the quality of surgical education. However, evidence-based surgery requires dedicated clinicians trained to perform methodologically sound clinical investigations. Statistical knowledge is therefore invaluable. Surgical studies often cannot be randomized. Propensity scores offer a powerful alternative to multivariable analysis in the assessment of observational, non-randomized surgical studies. Unfortunately, many surgeons are unaware of this important analytical approach that has gained increasing stature in medical research. Thus, propensity score analyses are not used often in surgical studies. OBJECTIVE: The purpose of this paper is to provide a comprehensive overview of propensity score analysis, allowing the surgeon to understand the role, advantages and limitations of propensity scores, boosting their development in surgical investigations.

Long-term outcomes of breast cancer patients after endoscopic axillary lymph node dissection: a prospective analysis of 52 patients.

BACKGROUND: Reports on long-term outcomes after endoscopic axillary lymph node dissection (ALND) of breast cancer patients are still lacking in the medical literature. The objective of this prospective study was to assess the oncological and functional outcomes in breast cancer patients after endoscopic ALND. METHODS: Fifty-five breast cancer patients were prospectively enrolled, of whom 52 were available for follow-up with a median of 71.9 months (range 11-96). The following oncological and functional endpoints were evaluated during follow-up at several time points: occurrence of local, axillary and distant metastases, seroma or infection, shoulder mobility (range of motion), numbness, pain, presence of lymphoedema as well as restriction in activities of daily living. RESULTS: In 52 patients endoscopic ALND of level I and II was successfully performed. Two port-site metastases (2/52, 4%) occurred, one of which in a patient with negative axillary lymph nodes. The same patient suffered from the only axillary recurrence (1/52, 2%). Three patients (3/52, 6%) developed lymphoedema. No other functional adverse events (shoulder mobility, pain, numbness, hypertrophic scar) were noticed at the end of the observation period. CONCLUSION: The present investigation with long-term follow-up after endoscopic ALND--the first one in the literature--reveals minor morbidity, good functional and cosmetic results. In contrary to conventional surgery, the endoscopic procedure is associated with the occurrence of port-site metastases, not seen in the open approach. Axillary recurrences do not appear more frequently when compared with results after conventional ALND. In the meantime the less invasive sentinel lymph node (SLN) biopsy is the established standard technique in evaluating the axillary lymph node status.

Phase I/II clinical trial of a nonreplicative vaccinia virus expressing multiple HLA-A0201-restricted tumor-associated epitopes and costimulatory molecules in metastatic melanoma patients.

We performed a phase I/II clinical trial in metastatic melanoma patients with an ultraviolet (UV)-inactivated nonreplicating recombinant vaccinia virus enabling the expression, from a single construct, of endoplasmic reticulum-targeted HLA-A0201-restricted Melan-A/MART-1(27-35), gp100(280-288), and tyrosinase(1-9) epitopes, together with CD80 and CD86 costimulatory proteins. Corresponding soluble peptides were used to boost responses and granulocyte-macrophage colony-stimulating factor was used as systemic adjuvant. Safety and immunogenicity, as monitored with in vitro-restimulated peripheral blood mononuclear cells by cytotoxic T lymphocyte precursor (CTLp) frequency analysis and tetramer staining, were specifically addressed. Of 20 patients entering the protocol, 2 had to withdraw because of rapidly progressing disease. Immune responses were evaluated in 18 patients (stage III, n = 5; stage IV, n = 13) and increases in specific CTLp frequencies were observed in 15. In 16 patients responsiveness against all 3 antigens could be analyzed: 7 (43%), including all stage III cases, showed evidence of induction of CTLs specific for the three epitopes, and 2 (12%) and 4 (25%), respectively, showed reactivity against two or one tumor-associated antigen. In three stage IV patients no specific CTL reactivity could be induced. Increases in CTLp frequency were detected mostly after viral vaccine injections. However, in a majority of patients final CTLp levels were comparable to initial levels. Tetramer characterization of Melan-A/MART-1(27-35)-specific CTLs during the protocol also suggested preferential expansion after recombinant virus administration. Vector-specific humoral responses, frequently undetectable in stage IV patients, did not appear to prevent tumor-associated antigen-specific CTL induction. Aside from a single occurrence of transient grade 3 leukopenia, no major clinical toxicity was reported. Seventeen of 18 patients completed the 3-month trial (one patient died before the last delayed-type hypersensitivity test). Three displayed regression of individual metastases, seven had stable disease, and progressive disease was observed in seven patients. This is the first report on the administration of a UV-inactivated recombinant vaccinia virus coexpressing five transgenes in cancer patients. The results described here, in terms of safety and immunogenicity, support the use of this reagent in active specific immunotherapy.

Perioperative detection of disseminated tumour cells is an independent prognostic factor in patients with colorectal cancer.

BACKGROUND: The objective of the present investigation was to assess the prognostic significance of disseminated tumour cells in peritoneal lavage, and peripheral and mesenteric venous blood in patients undergoing curative resection of colorectal cancer. METHODS: The prognostic impact of perioperative cytological and immunocytochemical detection of disseminated colorectal cancer cells was evaluated prospectively. Peritoneal lavage fluid, and peripheral and mesenteric venous blood from 53 consecutive patients undergoing curative surgery for colorectal cancer were analysed. The dichotomous results (positive versus negative) from the cytological and immunocytochemical analysis were used as a predictor along with other co-variates in proportional hazard regression models of disease-free and overall survival. RESULTS: Disseminated colorectal cancer cells were found in 13 of 53 patients (25 per cent) using cytology (CYT) and/or immunocytochemistry (ICC). The median follow-up at the time of the analysis was 37 months. In multivariate proportional hazard regression models CYT/ICC status was a significant predictor for disease-free (P = 0.002) and overall (P = 0.006) survival. CONCLUSION: Disseminated tumour cells detected by CYT and ICC represent an independent prognostic factor in patients undergoing surgery for colorectal cancer and may identify patients at high risk of recurrence.