Noise patterns in visceral surgical procedures: Analysis of second-by-second dBA data of 599 procedures over the course of one year.

The objective of this study is to analyze noise patterns during 599 visceral surgical procedures. Considering work-safety regulations, we will identify immanent noise patterns during major visceral surgeries. Increased levels of noise are known to have negative health impacts. Based on a very fine-grained data collection over a year, this study will introduce a new procedure for visual representation of intra-surgery noise progression and pave new paths for future research on noise reduction in visceral surgery. Digital decibel sound-level meters were used to record the total noise in three operating theatres in one-second cycles over a year. These data were matched to archival data on surgery characteristics. Because surgeries inherently vary in length, we developed a new procedure to normalize surgery times to run cross-surgery comparisons. Based on this procedure, dBA values were adjusted to each normalized time point. Noise-level patterns are presented for surgeries contingent on important surgery characteristics: 16 different surgery types, operation method, day/night time point and operation complexity (complexity levels 1-3). This serves to cover a wide spectrum of day-to-day surgeries. The noise patterns reveal significant sound level differences of about 1 dBA, with the most-common noise level being spread between 55 and 60 dBA. This indicates a sound situation in many of the surgeries studied likely to cause stress in patients and staff. Absolute and relative risks of meeting or exceeding 60 dBA differ considerably across operation types. In conclusion, the study reveals that maximum noise levels of 55 dBA are frequently exceeded during visceral surgical procedures. Especially complex surgeries show, on average, a higher noise exposure. Our findings warrant active noise management for visceral surgery to reduce potential negative impacts of noise on surgical performance and outcome.

Stenosis of the celiac trunk is associated with anastomotic leak after Ivor-Lewis esophagectomy.

Transthoracic esophagectomy with gastric tube formation is the surgical treatment of choice for esophageal cancer. The surgical reconstruction induces changes of gastric microcirculation, which are recognized as potential risk factors of anastomotic leak. This prospective observational study investigates the association of celiac trunk (TC) stenosis with postoperative anastomotic leak. One hundred fifty-four consecutive patients with esophageal cancer scheduled for Ivor-Lewis esophagectomy were included. Preoperative staging computed tomography (CT) was used to identify TC stenosis. Any narrowing of the lumen due to atherosclerotic changes was classified as stenosis. Percentage of stenotic changes was calculated using the North American Symptomatic Carotid Endarterectomy Trial formula. Multivariable analysis was used to identify possible risk factors for leak. The overall incidence of TC stenosis was 40.9%. Anastomotic leak was identified in 15 patients (9.7%). Incidence of anastomotic leak in patients with stenosis was 19.4% compared to 2.3% in patients without stenosis. Incidence of stenosis in patients with leak was 86.7% (13 of 15 patients) and significantly higher than 38.8% (54 of 139 patients) in patients without leak (P < 0.001). There was a significant difference in median degree of TC stenosis (50.0% vs 39.4%; P = 0.032) in patients with and without leak. In the multivariable model, TC stenosis was an independent risk factor for anastomotic leak (odds ratio: 5.98, 95% CI: 1.58-22.61). TC stenosis is associated with postoperative anastomotic leak after Ivor-Lewis esophagectomy. Routine assessment of TC for possible stenosis is recommended to identify patients at risk.

Epstein-Barr virus and mismatch repair deficiency status differ between oesophageal and gastric cancer: A large multi-centre study.

BACKGROUND: Oesophageal (OeC) and gastric (GC) cancer patients are treated with similar multimodal therapy and have poor survival. There remains an urgent clinical need to identify biomarkers to individualise patient management and improve outcomes. Therapy with immune checkpoint inhibitors has shown promising results in other cancers. Proposed biomarkers to predict potential response to immune checkpoint inhibitors include DNA mismatch repair (MMR) and/or Epstein-Barr virus (EBV) status. The aim of this study was to establish and compare EBV status and MMR status in large multi-centre series of OeC and GC. METHODS: EBV was assessed by EBV-encoded RNA (EBER) in situ hybridisation and MMR protein expression by immunohistochemistry (IHC) in 988 OeC and 1213 GC from multiple centres. In a subset of OeC, microsatellite instability (MSI) was tested in parallel with MMR IHC. RESULTS: Frequency of MMR deficiency (MMRdef) and MSI was low in OeC (0.8% and 0.6%, respectively) compared with GC (10.3%). None of the OeCs were EBER positive in contrast to 4.8% EBER positive GC. EBV positive GC patients were younger (p = 0.01), more often male (p = 0.001) and had a better overall survival (p = 0.012). MMRdef GC patients were older (p = 0.001) and showed more often intestinal-type histology (p = 0.022). CONCLUSIONS: This is the largest study to date indicating that EBV and MMRdef do not play a role in OeC carcinogenesis in contrast to GC. The potential clinical usefulness of determining MMRdef/EBV status to screen patients for eligibility for immune-targeting therapy differs between OeC and GC patients.

Effects of increased image noise on image quality and quantitative interpretation in brain CT perfusion.

BACKGROUND AND PURPOSE: There is a desire within many institutions to reduce the radiation dose in CTP examinations. The purpose of this study was to simulate dose reduction through the addition of noise in brain CT perfusion examinations and to determine the subsequent effects on quality and quantitative interpretation. MATERIALS AND METHODS: A total of 22 consecutive reference CTP scans were identified from an institutional review board-approved prospective clinical trial, all performed at 80 keV and 190 mAs. Lower-dose scans at 188, 177, 167, 127, and 44 mAs were generated through the addition of spatially correlated noise to the reference scans. A standard software package was used to generate CBF, CBV, and MTT maps. Six blinded radiologists determined quality scores of simulated scans on a Likert scale. Quantitative differences were calculated. RESULTS: For qualitative analysis, the correlation coefficients for CBF (-0.34; P < .0001), CBV (-0.35; P < .0001), and MTT (-0.44; P < .0001) were statistically significant. Interobserver agreements in quality for the simulated 188-, 177-, 167-, 127-, and 44-mAs scans for CBF were 0.95, 0.98, 0.98, 0.95, and 0.52, respectively. Interobserver agreements in quality for the simulated CBV were 1, 1, 1, 1, and 0.83, respectively. For MTT, the interobserver agreements were 0.83, 0.86, 0.88, 0.74, and 0.05, respectively. For quantitative analysis, only the lowest simulated dose of 44 mAs showed statistically significant differences from the reference scan values for CBF (-1.8; P = .04), CBV (0.07; P < .0001), and MTT (0.46; P < .0001). CONCLUSIONS: From a reference CTP study performed at 80 keV and 190 mAs, this simulation study demonstrates the potential of a 33% reduction in tube current and dose while maintaining image quality and quantitative interpretations. This work can be used to inform future studies by using true, nonsimulated scans.

HIF-1alpha protein expression is associated with the environmental inflammatory reaction in Barrett's metaplasia.

The oxygen-regulated transcription factor subunit hypoxia inducible factor-1alpha (HIF-1alpha) is involved in angiogenesis, energy metabolism, cell survival, and inflammation. We examined the protein expression of HIF-1alpha within the progression of Barrett's sequence as well as the type and degree of the environmental inflammatory reaction. Squamous epithelium (SE), metaplastic, low- and high-grade dysplastic lesions, and tumor tissue of 57 resection specimens from patients with Barrett's adenocarcinoma were immunohistochemically analyzed. Active and chronic inflammatory reactions were classified according to the Updated Sydney System. HIF-1alpha protein expression increased significantly from SE to Barrett's metaplasia (BM) (P < 0.0001). From metaplasia through low- and high-grade dysplasia to cancer, no further increase could be detected. Active and chronic inflammation were also significantly different between SE and BM (P < 0.0001) but not during further progression in the sequence. HIF-1alpha protein expression did not correlate with histopathologic parameters or survival. HIF-1alpha protein expression pattern resembles the active and chronic environmental inflammatory reaction. All were significantly increased in metaplasia compared to SE without further change in tumor development. HIF-1alpha protein expression appears to be associated with inflammatory processes in the development of BM.

Association of COX-2 expression with corresponding active and chronic inflammatory reactions in Barrett's metaplasia and progression to cancer.

AIMS: Risk reduction for Barrett's cancer in individuals taking non-steroidal anti-inflammatory drugs has been reported. Cyclooxygenase (COX)-2, one of the inhibited enzymes, is putatively involved in Barrett's cancer pathogenesis. The aim of this study was to examine a possible association between COX-2 protein expression and the development and progression of the Barrett's metaplasia-dysplasia-carcinoma sequence and the type and degree of associated inflammatory reaction. METHODS AND RESULTS: Squamous epithelium, metaplastic, low-grade, high-grade dysplastic lesions and tumour tissue of 49 resection specimens from patients with Barrett's adenocarcinoma were immunohistochemically analysed. Active and chronic inflammatory reactions were classified according to the Updated Sydney System. Within the Barrett's sequence, a significant progressive increase in COX-2 expression was identified (P < 0.0001). The most significant differences were detected between squamous epithelium and Barrett's metaplasia (P < 0.001) and from low- to high-grade dysplasia (P < 0.0001). Active and chronic inflammation were significantly different between squamous epithelium and Barrett's metaplasia (P < 0.0001), but not during further progression in the sequence. CONCLUSIONS: Increasing COX-2 expression in Barrett's metaplasia is significantly associated with a change in the local inflammatory reaction, but not during further progression through dysplasia to cancer. This supports the potential of a chemoprevention strategy using COX-2 inhibitors independent of the extent and type of the inflammatory reaction in Barrett's oesophagus.

Survivin mRNA in peripheral blood is frequently detected and significantly decreased following resection of gastrointestinal cancers.

BACKGROUND AND OBJECTIVES: We evaluated if mRNA expression of survivin, an inhibitor of apoptosis, can be used to detect circulating tumor cells in peripheral blood of patients with various gastrointestinal cancers and if they decrease following complete surgical resection. METHODS: Blood samples from 40 gastrointestinal cancer patients were analyzed prior and following surgical resection by direct quantitative real-time reverse transcriptase-PCR (RT-PCR) assays. RESULTS: Survivin mRNA expression was pre-operatively detected in 35 of 40 cancer patients (88%). Post-operative survivin levels were significantly lower than pre-operative levels in 59% of resected patients and were non-detectable in 38% (Wilcoxon rank test: P < 0.04). CONCLUSIONS: This is the first report showing that direct quantitative real-time RT-PCR analysis of survivin mRNA expression in peripheral blood of patients with gastrointestinal cancers is technically feasible. Survivin mRNA levels fall significantly following complete resection and might become a molecular marker for the completeness of surgical resection.

[Success and complication rate of CT-guided marking of pulmonary nodules with coil wires for video-assisted thoracoscopic surgery (VATS)]. / Erfolgs- und Komplikationsrate der CT-gesteuerten Markierung pulmonaler Rundherde mittels Spirale vor videoassistierter thorakoskopischer chirurgischer Resektion (VATS).

PURPOSE: To assess the success and complication rate of the CT-guided marking of pulmonary nodules for video-assisted thoracoscopic surgery (VATS). MATERIALS AND METHODS: Pulmonary nodules (mean diameter 9 +/- 5 mm, mean pleural distance 7 +/- 5 mm) were marked with a coil wire in 30 patients (20 males, mean age 57.6 +/- 15.5 years, 22 patients with a history of malignancy). The intended coil-nodule distance was < or = 10 mm. RESULTS: 81 % of nodules were not visible by thoracoscopy. The technical success rate of CT-guided marking was 86.7 %. The projected nodule-coil distance was achieved in 90 % of cases. The procedure had to be changed from thoracoscopy to thoracotomy in 4 patients due to coil wire marking problems: 2 x coil displacement, 1 x coil-nodule distance > 10 mm, unfavorable direction of wire. Histology was determined in all patients (70 % malignant, 30 % benign). Complications requiring therapy were not observed. CONCLUSIONS: The CT-guided marking of pulmonary nodules is a precondition for VATS if the nodule does not involve the visceral pleura in the majority of cases. The success rate is high with a low complication rate.

Is the urokinase-type plasminogen activator system a reliable prognostic factor in gastric cancer?

AIM: The aim of this prospective study was to evaluate the clinical and prognostic impact of immunohistochemically assessed uPA and PAI-1 in patients with gastric cancer. METHODS: This prospective study analyzed specimens obtained from 105 gastric cancer patients who underwent gastrectomy with extended lymphadenectomy. The immunohistochemical expression of uPA and PAI-1 was studied semiquantitatively in the tumor epithelium and was correlated with the clinicopathological features of each patient. RESULTS: Univariate analysis revealed no statistically significant association of uPA levels with pT and pN category (p=0.655 and 0.053, respectively), grading (p=0.374), depth of tumor invasion (p=0.665), UICC classification (p=0.21) and the Laurén classification (p=0.578). PAI-1 expression showed no statistically significant correlation with pT, pN and M category (p=0.589, 0.414, and 0.167, respectively), grading (p=0.273), and the Laurén classification (p=0.368). Only the UICC classification was significantly correlated with PAI-1 (p=0.016). Kaplan-Meier analysis revealed no significant association of uPA and PAI-1 with overall survival (p=0.0929 and 0.0870, respectively). CONCLUSIONS: Our results could not verify any prognostic value of uPA and PAI-1 levels in patients with gastric carcinoma. Therefore, the uPA-system as a biologically defined prognostic marker to identify high-risk gastric cancers should be applied with caution. However, considering the number of patients involved and the borderline level of significance observed in this study, a larger number of events may have resulted in significant differences.

Feasibility of sentinel node concept in gastric carcinoma: clinicopathological analysis of gastric cancer with solitary lymph node metastases.

BACKGROUND: The feasibility and diagnostic reliability of sentinel lymph node biopsy of gastric carcinoma are still unclear and controversial. PATIENTS AND METHODS: To assess the applicability of the sentinel node concept to gastric carcinoma, we retrospectively analyzed the location of metastatic lymph nodes in patients with only one or two lymph node metastases. RESULTS: A total of 135 patients, who underwent gastrectomy with D2 lymphadenectomy for primary gastric adenocarcinoma between 1997 and 2001, were enrolled in this study. An average of 39 lymph nodes were resected and analyzed for each patient. Of the 135 patients, 88 (65%) were subtyped as pN+ (with lymph node metastasis); of the latter, 15 cases (pT1-3; 17% of N+ cases) showed one or two lymph node metastases. In 14 (93%) of these patients, lymph nodes directly adjacent to the primary tumor were involved. Skip metastases were only seen in one patient with cardia carcinoma and lymph node involvement of compartment II (left gastric artery). CONCLUSION: In patients with gastric carcinoma, especially in early stage carcinoma, the phenomenon of skip metastasis is infrequent. Therefore, the sentinel node concept may be feasible in gastric cancer.

Quantitative c-erbB-2 but not c-erbB-1 mRNA expression is a promising marker to predict minor histopathologic response to neoadjuvant radiochemotherapy in oesophageal cancer.

We examined the potential of quantitative epidermal growth factor receptor (EGFR, synonym: c-erbB-1) and c-erbB-2 (synonym: HER2/neu) mRNA expression to predict minor or major histopathologic response to neoadjuvant radiochemotherapy (cis-platinum, 5-FU, 36 Gy), followed by radical surgical resection, in patients with oesophageal cancer. Tissue samples were collected by endoscopic biopsy prior to treatment. RNA was isolated from biopsies and quantitative real-time reverse transcriptase-polymerase chain reaction assays were performed to determine c-erbB-1 and c-erbB-2 mRNA expression. Relative expression (tumour/paired normal tissue ratio standardised for beta-actin) was calculated for EGFR and c-erbB-2 mRNA. Expression levels were correlated with the objective histopathologic response in resected specimens. Histomorphologic regression was defined as major response when resected specimens contained less than 10% of residual vital tumour cells, or in case a pathologically complete response was achieved. Expression of c-erbB-1 mRNA was not associated with the degree of histomorphological response. In contrast, the relative expression levels of c-erbB-2 mRNA >1 were not associated with major histopathologic responses (sensitivity 41.6%, specificity 100%), and 10 out of 36 (28%) patients could be unequivocally identified, whose tumours did not respond well to the delivered neoadjuvant radiochemotherapy (P<0.01). Quantitative expression levels of c-erbB-2, but not c-erbB-1 mRNA, in pretreatment biopsies appear to predict minor histopathologic response to our neoadjuvant radiochemotherapy protocol. This test could be used to prevent expensive, non effective and potentially harmful therapies in approximately one-fourth of our patients, and leads to a more individualised type of combined modality treatment.

Masaoka staging is of prognostic relevance in type B3 / C thymomas.

BACKGROUND: The purpose of this study was to correlate the Ki67 labelling index (LI) with the Masaoka classification and the new WHO-classification in type B3 / C thymomas. PATIENTS AND METHODS: Fourteen patients with type B3 / C thymomas were evaluated, and archived specimens were histologically reclassified according to Masaoka staging, the new WHO classification and the Ki-67 LI in a retrospective analysis. RESULTS: Four patients presented with Masaoka stage II disease (all WHO-type B3), 1 patient had stage III (WHO-type C), 6 stage IVa (3 WHO-type B3 and 3 WHO-type C), and another 3 patients stage IVb (all WHO-type C). The statistical analysis revealed a significant correlation between Masaoka staging and Ki-67 LI (II, III vs. IV; p = 0.007). As well, WHO-classification correlated significantly with Ki-67 LI (B3 vs. C; p = 0.015). Masaoka staging (II, III vs. IV) correlated significantly with survival status (p = 0.0237) in patients with type B3 / C thymoma whereas WHO-classification did not (p = 0.3266). Between survivors and non-survivors there was no statistically significant correlation concerning Ki-67 LI (p = 0.075). CONCLUSION: Our study indicated that the Masaoka staging system is of prognostic relevance in type B3 / C thymomas.

[Heterotopic gastric pancreas: a rare cause of abdominal complaints]. / Heterotopes Pankreasgewebe der Magenwand. Seltene Ursache abdominaler Beschwerden.

Heterotopic pancreas is an uncommon cause of gastrointestinal complaints such as epigastric pain, nausea, vomiting, and upper gastrointestinal bleeding. Despite the development of modern diagnostic procedures, it is still difficult to differentiate heterotopic pancreatic tissue from other benign or malignant gastric tumors. Local excision of the gastric wall is regarded as the diagnostic and therapeutic procedure of choice. We present two cases and an overview of the literature.

Chemokines and interleukin-18 are up-regulated in bronchoalveolar lavage fluid but not in serum of septic surgical ICU patients.

Our objective was to investigate the levels of chemokines (MIP1-alpha, MCP-1, and Gro-alpha), Interleukin-18 (IL-18), and Interleukin (IL-6) in bronchoalveolar lavage (BAL) fluid and serum at the onset and ongoing states of sepsis as defined by the American College of Chest Physicians/Society of Critical Care Medicine in septic surgical ICU patients. Our summary background data was to understand the significance of compartmentalized inflammatory mediator production in an immunologically active organ (lung) in comparison with levels in the systemic circulation. The study group consisted of 20 septic patients and 10 non-septic patients on surgical ICU. At the onset of sepsis, both BAL fluid and serum samples were taken and levels of MIP-1alpha, MCP-1, GRO-alpha, IL-18, and IL-6 were measured by ELISA. Furthermore, over a subsequent 8-day period, levels of these mediators were determined in serum. In some experiments, IL-18 mRNA levels were determined in peripheral blood lymphocytes (PBL) of septic and non-septic patients. At the onset of sepsis, MIP-1alpha, MCP-1, GRO-alpha, IL-18, and IL-6 levels were significantly up-regulated in BAL fluid as compared with non-septic controls. In marked contrast, with the exception of IL-18 mRNA and IL-6 peptide, there was no increase in serum levels of inflammatory mediators determined both at the onset and during the ongoing states of sepsis. Based on the present data, monitoring levels of serum chemokines and IL-18 protein as markers of sepsis might be misleading since despite their non-detection in serum, they were highly up-regulated in the lung tissue compartment. These data might underscore the role of MIP-1alpha, MCP-1, GRO-alpha, and IL-18 in the mediation of local tissue damage. Furthermore, these findings raise the notion that mediator measurement in immunologically active organs might serve as pivotal indicators of sepsis prior to the actual fulfillment of specific clinical criteria that defines the patient as being septic.

Caspase-1-inhibitor ac-YVAD-cmk reduces LPS-lethality in rats without affecting haematology or cytokine responses.

The effect of acetyl - tyrosyl-valyl-alanyl-aspartyl - chloromethylketone (ac-YVAD-cmk), an irreversible caspase-1 (IL-1beta converting enzyme, ICE) inhibitor on mortality, leukocyte and platelet counts and cytokine levels was investigated in a double-blind rat model of endotoxaemia. Intravenous (i.v.) bolus administration of lipopolysaccharide (LPS) (25-75 mg kg(-1), n=12 per group) to anaesthetized rats induced a dose dependent increase in mortality over 8 h (LD(50)=48 mg kg(-1)). During this period, animals became leukopenic and thrombocytopenic. Serum levels of IL-beta, IL-6, and TNF-alpha were highly elevated. Pretreatment of rats with ac-YVAD-cmk at a dose of 12.5 micromol kg(-1) significantly reduced mortality from 83 to 33% using Log Rank analysis. However, ac-YVAD-cmk did not modify blood cell counts or cytokine profiles as compared with the LPS-drug vehicle group. These data lay credence to the potential importance of caspase-1-inhibition in modifying the inflammatory response to endotoxin. Further investigations are warranted in understanding the relationship between caspase-1 inhibition, cytokine production and animal survival in different experimental paradigms of sepsis.

P53 mutational status improves estimation of prognosis in patients with curatively resected adenocarcinoma in Barrett's esophagus.

The incidence of adenocarcinomas in Barrett's esophagus has been rising in the last two decades in the United States and Western Europe for yet unknown reasons. We reported previously a large multi-institutional trial implicating p53 mutations as being involved in the pathogenesis of Barrett's cancer and representing an early marker for the malignant potential of Barrett's epithelium. A prospective study was performed to evaluate the prognostic impact of p53 mutations on survival in 59 patients with Barrett's cancer. Tissue for DNA analysis was obtained by endoscopic biopsy or immediately after surgical resections from the tumor, Barrett's epithelium, and normal stomach and esophagus. p53 mutation analysis was performed by PCR-single strand conformational polymorphism screening of exons 5-9 and DNA sequencing to unequivocally prove the presence of a mutation. p53 mutations were identified in 30 of 59 (50.8%) patients. The presence of a p53 mutation in the tumor had a significant impact on survival after curative resections (RO-resections) with cumulative 5-year survival probabilities of 68.8+/-9.7% for mutation-negative tumors and 24.3+/-9.9% for mutation-positive tumors (log rank: P < 0.001). By Cox proportional hazard analysis, including the parameters of gender, age, Union International Contre Cancer tumor stage, grading, and p53 mutation status, only Union International Contre Cancer tumor stage (P < 0.0001) and p53 mutation status (P < 0.02) were of significant independent prognostic importance. p53 mutation analysis by DNA sequencing is of significant independent prognostic importance next to histopathological tumor stage in patients with curatively resected (RO-resection) Barrett's cancer. It appears that p53 mutational status is a valuable parameter to define low-risk (p53 mutation-negative) and high-risk (p53 mutation-positive) groups for treatment failure after curative resections.

Multiple molecular marker testing (p53, C-Ki-ras, c-erbB-2) improves estimation of prognosis in potentially curative resected non-small cell lung cancer.

A prospective study was performed in patients with non-small cell lung cancer (NSCLC) to evaluate the prognostic importance of multiple molecular marker (p53, c-Ki-ras, c-erbB-2) testing. 103 patients with potentially curative resections (RO resection) for NSCLC in histopathological stages I-IIIA were included. SSCP analysis and DNA sequencing for p53 and c-Ki-ras genes were performed on paired tumour and normal lung tissue samples and immunohistochemistry (c-erbB-2) was done on frozen tissue sections with a specific anti-c-erbB-2 monoclonal antibody. 46/103 (44.6%) NSCLC showed p53 mutations and 17/103 (16.5%) c-Ki-ras mutations including 12/37 (32.4%) adenocarcinomas. Overexpression of c-erbB-2 (p185) was detected in 56/103 (54.4%) tumours. 24/103 (23.3%) NSCLC were negative for alterations in all 3 parameters (c-Ki-ras, p53 and p185) whereas 79/103 (76.7%) were positive for at least one of the 3 parameters. In a regression model including a multiple molecular marker parameter (negative for all 3 markers versus positive for at least one marker), histopathological stage (P<0.00001), respectively the pT (P<0.01) and pN (P<0.00001) categories and the multiple molecular marker parameter (P<0.01) were of significant prognostic importance. This study demonstrates that testing 3 molecular markers (c-Ki-ras, p53 and c-erbB-2) improves estimation of prognosis compared to single marker testing and appears to define low (82.6%+/-7.9% 5-year survival) and high risk (40.2%+/-5.5% 5-year survival) groups for treatment failure in potentially curative (RO) resected NSCLC.

Experimental low-level direct current therapy in liver metastases: influence of polarity and current dose.

Several authors recently reported on the successful local treatment of malignant disease with low-level direct current therapy. However, antitumoral effects in colorectal metastases has not been investigated experimentally. The aim of the present study was to assess the effectiveness of this therapy and the influence of polarity and current dose. Colorectal metastases were established in BD IX rats by the injection of colon cancer cells under the liver capsule. After three weeks, the liver tumor volumes were determined by magnetic resonance imaging of the liver. Low-level direct current therapy was applied via five platinum electrodes. Four different applications were used: 60 C/cm(3), anode at the center; 60 C/cm(3), cathode at the center; 80 C/cm(3), anode at the center; and 80 C/cm(3), cathode at the center. In the control group, five electrodes were placed without applying any direct current. All animals were sacrificed on postoperative day 7. Liver metastases were histologically examined for vital tumor cells. Statistical analysis was performed with chi(2)-test. The mean initial tumor diameter before treatment was 3.6 +/- 1.4 mm (volume: 25.2 +/- 9.7 mm(3)). Histological examination of the removed livers revealed significant destruction of the metastases with localized necroses in all treatment groups; 37% had a complete response rate and 63% a partial response rate. There were no significant necroses in the control group (P < 0.0001). The best treatment results were obtained in the group with an anode at the center and a current dose of 80 C/cm(3). Direct current therapy offers a new and safe method for the local treatment of liver metastases. We were able to observe that tumor damage is related to current dose but not to the polarity of the central electrode.

Local treatment of hepatic metastases with low-level direct electric current: experimental results.

BACKGROUND: Several authors have recently reported encouraging results from low-level direct current therapy in easily accessible malignant tumors. However, antitumoral effects in colorectal metastases have not been investigated experimentally. METHODS: Using an animal model with induced hepatic metastases, we analyzed the effectiveness and the tumor growth dynamics after direct current application. Three weeks after induction tumor volumes were estimated with magnetic resonance imaging (MRI). Then direct current (80 C/cm3) was applied in the treatment group by means of one anode in the tumor center and four cathodes peripherally. In the control group electrodes were placed without applying current. Tumor growth dynamics was analyzed with MRI after 3 and 5 weeks. After this all animals were killed, and the livers histologically examined. RESULTS: After 5 weeks MRI showed a 1.6-fold tumor enlargement in the treatment group versus a 2.9-fold enlargement in the control group (Student t test, P=0.0051). The histopathologic analysis of the treated livers yielded a 21% complete response rate and a 78% partial response rate. No necroses were found in the control group. CONCLUSIONS: These results confirm the effectiveness of low-level direct current application as a potential modality for the treatment of hepatic metastases.

Prognostic impact of p21/waf1/cip1 in colorectal cancer.

In addition to the tumor suppressor gene p53, Cyclin Dependent Kinases (CDK) are well known to influence the cell cycle in normal human tissues and various neoplasias as well. The purpose of our present study was to evaluate the expression of the CDK-inhibitor p21/waf1/cip1 in colorectal cancer with special emphasis on the prognostic impact. Between 1985 and 1991, 294 patients (median age, 65 years) underwent surgical operative therapy for colorectal cancer. Formalin-fixed and paraffin-embedded tumor specimens were investigated. For immunohistochemistry the Catalysed Reporter Deposition (CARD) technique was performed. The survival probability was calculated and possible prognostic risk factors were tested using multivariate analysis. The p21/ waf1/cip1 staining pattern was positive in 197 (67%) specimens and negative in 97 (33%) samples. No significant correlation could been calculated between p21/waf1/cip1 expression and other variables such as age, sex, WHO-Classification, localisation, grading, TNM-classification or UICC-stage. Patients with a positive staining reaction had a significantly better survival (p < 0.0052). Moreover, p21/waf1/cip1 was shown to be an independent prognostic parameter by multivariate analysis (p < 0.022). In contrast with these findings, the p53 tumor status had no impact on survival. P21/ waf1/cip1 appears to be an independent prognostic parameter in colorectal cancer and is associated with a favorable survival. This feature may be related to a cell cycle arrest in the G1 phase induced by p21/waf1/cip1, resulting in lower tumor cell proliferative activity.