Stage II Research Articles

New Study on the Effect of Scopoletin and Silver Nanoparticles of Fenugreek Extract as Pancreatic Cancer Inhibition Agents

Pancreatic cancer is a highly aggressive and lethal form of cancer with limited treatment options. Therefore, exploring novel therapeutic strategies is crucial to improve patient outcomes. Researchers are currently investigating the potential therapeutic effects of scopoletin and silver nanoparticles on various diseases, including pancreatic cancer. Specifically, they have synthesized and characterized silver nanoparticles using fenugreek extract and tested different concentrations of these nanoparticles and scopoletin to determine their anti-cancer and anti-angiogenic properties. The aim is to identify the most effective dose that can reduce the levels of cyclooxygenase-2 (COX-2) and lactate dehydrogenase (LDH), which are markers associated with cancer progression. The study was performed in a laboratory setting, dividing the samples into three separate groups. The first group, known as the control group, consisted of 30 samples from healthy individuals of both genders, aged between 23 and 45 years. The second group included 30 male and female patients aged between 45 and 65 years, with stage II pancreatic cancer. Lastly, the third group comprised 30 male and female patients with stage III pancreatic cancer, aged between 52 and 79 years. This study found that, compared to the control group, patients with stage IΙ and stage IΙΙ pancreatic cancer experienced the greatest decrease in enzyme concentration at the concentration of the nanoparticle solution 2 ppm where the Cyclooxygenas-2 enzyme concentrations values were 2.43±0.22ng/ml, 3.04±0.31ng/ml and 1.59±0.06ng/ml, respectively. As for the concentration of the enzyme Lactate dehydrogenase, it was 1.20±0.02ng/ml, 1.14±0.02ng/ml and 0.85±0.18ng/ml respectively. Also, as compared to the control 1.97±0.17ng/ml, 1.72±0.10ng/ml, and 1.22±0.07ng/ml, the concentration of the scopoletin compound solution 8ppm results in the best reduction in COX-2 enzyme concentration As for the concentration of the enzyme LDH, it was 0.93±0.07 ng/ml, 0.97±0.11 ng/ml and 0.71±0.10 ng/ml In individuals with stage IΙ and stage IIΙ PC. The results of this research demonstrate that scopoletin compounds and Ag-NPs derived from Fenugreek extract function as anti-cancer and anti-angiogenesis agents by reducing the levels of cyclooxygenase-2 (COX-2) and lactate dehydrogenase (LDH) enzymes in the blood serum of individuals with stage II and stage III pancreatic carcinoma in Iraq.

Stage II oesophageal carcinoma: peril in disguise associated with cellular reprogramming and oncogenesis regulated by pseudogenes

IntroductionPseudogenes have been implicated for their role in regulating cellular differentiation and organismal development. However, their role in promoting cancer-associated differentiation has not been well-studied. This study explores the tumour landscape of oesophageal carcinoma to identify pseudogenes that may regulate events of differentiation to promote oncogenic transformation.Materials and methodDe-regulated differentiation-associated pseudogenes were identified using DeSeq2 followed by ‘InteractiVenn’ analysis to identify their expression pattern. Gene expression dependent and independent enrichment analyses were performed with GSEA and ShinyGO, respectively, followed by quantification of cellular reprogramming, extent of differentiation and pleiotropy using three unique metrics. Stage-specific gene regulatory networks using Bayesian Network Splitting Average were generated, followed by network topology analysis. MEME, STREME and Tomtom were employed to identify transcription factors and miRNAs that play a regulatory role downstream of pseudogenes to initiate cellular reprogramming and further promote oncogenic transformation. The patient samples were stratified based on the expression pattern of pseudogenes, followed by GSEA, mutation analysis and survival analysis using GSEA, MAF and ‘survminer’, respectively.ResultsPseudogenes display a unique stage-wise expression pattern that characterizes stage II (SII) ESCA with a high rate of cellular reprogramming, degree of differentiation and pleiotropy. Gene regulatory network and associated topology indicate high robustness, thus validating high pleiotropy observed for SII. Pseudogene-regulated expression of SOX2, FEV, PRRX1 and TFAP2A in SII may modulate cellular reprogramming and promote oncogenesis. Additionally, patient stratification-based mutational analysis in SII signifies APOBEC3A (A3A) as a potential hallmark of homeostatic mutational events of reprogrammed cells which in addition to de-regulated APOBEC3G leads to distinct events of hypermutations. Further enrichment analysis for both cohorts revealed the critical role of combinatorial expression of pseudogenes in cellular reprogramming. Finally, survival analysis reveals distinct genes that promote poor prognosis in SII ESCA and patient-stratified cohorts, thus providing valuable prognostic bio-markers along with markers of differentiation and oncogenesis for distinct landscapes of pseudogene expression.ConclusionPseudogenes associated with the events of differentiation potentially aid in the initiation of cellular reprogramming to facilitate oncogenic transformation, especially during SII ESCA. Despite a better overall survival of SII, patient stratification reveals combinatorial de-regulation of pseudogenes as a notable marker for a high degree of cellular differentiation with a unique mutational landscape.

The order of surgery and chemotherapy matters: Multimodality therapy and stage-specific differences in survival in gastric cancer.

Multimodality treatment improves survival for gastric cancer (GC). However, the effect of treatment sequence by stage remains unclear. We aim to compare outcomes between patients receiving neoadjuvant(neoadj) and adjuvant chemotherapy (adj). Nonmetastatic GC patients with clinical stage ≥ T2N0 who underwent both resection and neoadj or adj were identified using the National Cancer Database (2005-2014). Multivariable Cox regression analyses were performed on propensity score-matched (PSM) cohorts stratified by stage to compare overall survival (OS). We identified 11 984 patients; 55% stage I (SI), 76% stage II (SII) and 57% stage III (SIII) received neoadj. Unadjusted analysis showed worse survival among SI neoadj patients (hazard ratio [HR] 1.195, confidence interval [CI] 1.04-1.38) and improved survival for SII (HR 0.93 CI 0.87-0.998) and SIII (HR 0.75, CI 0.68-0.84). After PSM, SI patients with neoadj had worse OS with increased risk of death compared to Adj (HR 1.186, CI 1.004-1.402). SII patients had no difference in OS (HR 0.98, CI 0.91-1.07) and SIII patients had improved OS (HR 0.78, CI 0.69-0.90). In patients who received surgery and chemotherapy, the benefit of neoadj was limited to SIII with worse survival for SI. A clinical trial to examine the optimal sequence of chemotherapy is warranted.

Comparative study of open thoracotomy and thoracoscopy on the efficacy of treatment and complications of patients with stage ΙΙ thoracic empyema

Background. Thoracic empyema is an inflammatory condition of the pleura that can cause many complications and can even threaten people's lives. So, choosing the right treatment method from all available methods can improve the prognosis, reduce costs and post-treatment complications, thus improving the health of patients after the disease. Video-assisted thoracoscopic surgery (VATS) and open thoracotomy are the most commonly used surgical methods. In this study, these two surgical methods have been investigated, in terms of duration of hospitalization, postoperative pain level and the possibility of air leakage (as postoperative complications). Methodology. Patients with thoracic empyema stage II referred (between 2011 and 2020) to the Poursina and Razi Hospital Medical Center, Rasht, Iran were included in a retrospective cohort study. SPSS software and other statistical tests such as the Shapiro-Wilk test, Mann-Whitney non-parametric test, and Chi-square test were used for statistical analysis, and a P-value of less than 0.05 was considered an acceptable value. Results. The investigation on different qualitative and quantitative factors and complications after surgery showed that patients who underwent a VATS procedure had a shorter hospital stay (5.09±1.67 vs. 7.61±2.03), had a lower pain level (4.81±2.22 vs. 8.24±2.39), and the possibility of air leakage as a postoperative complication (41% vs. 56%) was lower than in the case patients who have undergone open thoracotomy. Conclusions. It can be concluded that choosing the VATS method instead of the open thoracotomy can reduce postoperative complications (such as length of hospital stay, pain level and possibility of air leakage) and can reduce the costs of treatment and the degree of health system use, especially during Covid-19 pandemic.

Mesothelin expression has prognostic value in stage ΙΙ/ΙΙΙ colorectal cancer.

Mesothelin (MSLN) is a cell-surface glycoprotein present on mesothelial cells and in many cancers, where expression is generally associated with an unfavorable prognosis. The clinical significance and pathological characteristics of MSLN expression were evaluated by immunohistochemical staining of tissues from 530 stage ΙΙ/ΙΙΙ colorectal cancer (CRC) patients with R0 resection. Eighty-eight (16.6%) were MSLN-positive; 33 (37.5%) showed a luminal staining pattern whereas 55 (62.5%) showed a non-luminal staining pattern. MSLN expression, including the luminal and non-luminal staining patterns, was associated with shorter cancer-specific survival (CSS) period in stage ΙΙ (n = 314, P = 0.024) and stage ΙΙΙ (n = 216, P = 0.0002) CRC patients. The non-luminal staining pattern was correlated with poor prognosis in stage ΙΙ (P = 0.0006) and III (P < 0.0001) CRC, but a luminal staining pattern was not significantly correlated with prognosis. Cox's multivariate analysis revealed that a non-luminal staining pattern was associated with CSS independently of other conventional parameters in stage II (P = 0.040, hazard ratio (HR) = 2.92) and III (P = 0.020, HR = 2.13) CRC patients. Immunohistochemical evaluation of MSLN expression was helpful in the prediction of patient prognosis in stage II/III CRC.

Current Season Photoassimilate Distribution in Sweet Cherry

Sweet cherry (Prunus avium) tree canopies comprise three types of leaf populations: fruiting spur (FS), nonfruiting spur (NFS), and extension shoot (ES) leaves. The contribution of each leaf population as sources of photoassimilate synthesis and distribution for sweet cherry fruit development has not been described previously. To determine how carbon fixed by different leaf populations is distributed to reproductive and vegetative sinks during fruit development, fruiting branches of 7-year-old ‘Ulster’ sweet cherry trees grown on ‘Gisela®6’ (Gi6) (Prunus cerasus × Prunus canescens) rootstock at Michigan State University’s Clarksville Research Center (Clarksville, MI) were exposed to 13CO2 labeling on five dates in 2003 [25, 40, 44, 56, and 75 days after full bloom (DAFB), which occurred on 30 Apr.], comprising the period from late Stage I (SI) to late Stage III (SIII) of fruit development. Forty-eight hours after labeling, whole branches were removed and separated into different organs for 13C analysis by gas chromatography–mass spectrometry (GC-MS). The organs analyzed included: FS leaves, NFS leaves, ES leaves, fruit, and wood + bark from the segment of the branch corresponding to each leaf population. Relative distribution of C from each leaf population source to each sink varied during fruit development. Overall, the proportion of 13C recovered in the fruit was highest for the FS leaf population (which included fruit exposure to 13CO2), followed by the NFS leaves, then ES leaves. From SI to SIII, ≈60% of the 13C recovered in the FS portion of the branch was found in the fruit, except during the exponential growth of fruit in mid-SIII (56 DAFB) when this proportion was nearly 80%. About 30% of the 13C fixed by NFS leaves was found in the fruit during Stage II (SII) (40 DAFB) and early (44 DAFB) and late (75 DAFB) SIII, with higher proportions at SI (45% at 25 DAFB) and mid-SIII (70%). About 25% of the 13C fixed by ES leaves was found in the fruit during SI, SII, and late SIII, with a lower proportion (17%) at early SIII when shoot growth was exponential, and a higher proportion (nearly 60%) at mid-SIII. The proportion of 13C fixed and translocated to ES growth was minimal from FS and NFS leaves throughout the sampling dates, but that by the ES leaves was significant, peaking at early SIII. The results illustrate the dynamics of C contribution from each leaf population between vegetative and reproductive sinks during growth in sweet cherry orchards, which provides useful physiological information for canopy pruning and crop load regulation.

574P - Risk of Recurrence in Patients with Colon Cancer Stage Ii and Iii: a Systematic Review of Recent Literature

ABSTRACT Aim: Adjuvant chemotherapy is established routine therapy for colon cancer (CC) patients with radically resected stage III and “high-risk” stage II disease. The decision on recommending adjuvant chemotherapy, however, is based on data from older patient cohorts not reflecting improvements in pre-operative staging, surgery, and pathological examination. The aim of this study is to review the current risk of recurrence in stage II and III patients adequately staged, operated by colorectal cancer specialized surgeons, the surgical specimen investigated according to modern standards, and adequately followed-up, and secondly, to estimate the relative importance of routinely assessed clinico-pathological variables. Methods: The PubMed/MEDLINE and the Cochrane databases were systematically searched for randomized controlled studies and observational studies published after 1.1.2005 with patients included after January 1995 on prognosis in surgically treated patients with CC stage II and III. Results: Of 2596 studies identified, 37 met the inclusion criteria and 25 provided data for meta-analysis. The total patient sample size in the 25 studies reporting either disease-free or recurrence-free survival (DFS) was 15,785 in stage II and 18,425 in stage III. Five-year DFS for stage II patients operated without subsequent adjuvant chemotherapy was 81.4% (95% confidence interval (CI) 75.4-87.4; in studies with good/very good quality of reporting it was 82.7%, (95%CI 80.8-84.6)), and for stage III 49.0% (95%CI 23.2-74.8). For stage II patients treated with adjuvant chemotherapy, the 5-year DFS was 79.3% (95%CI 75.6-83.1), and for stage III 63.6% (95%CI 59.3-67.9). The prognostic impact of commonly investigated clinico-pathological parameters, i.e. pT-stage, pN-stage, differentiation, number of lymph nodes studied, MMR-status, and emergency surgery was confirmed. Conclusions: There are several reasons to regard the presented DFS results as an under-estimation of what is achieved at high-quality centres today. The effects of ongoing efforts towards optimized patient management on recurrence rates should be further evaluated in prospective population-based studies, and the results published Disclosure: All authors have declared no conflicts of interest.

569P - Giv As a Novel Prognostic Marker in Stage Ii Colon Cancer

ABSTRACT Aim: There is an evident unmet need to better define recurrence risk for patients with stage II colon cancer (CC), particularly those with mismatch repair proficient (pMMR) tumors, to determine the subgroup of patients that may benefit from adjuvant chemotherapy. GIV/Girdin is a novel metastasis associated protein that triggers tumor cell invasion by enhancing PI3K/AKT signaling downstream of multiple oncogenic receptors. We explored the potential of GIV as a prognostic marker in stage II CC. Methods: A MMR antibody panel and a GIV specific antibody were developed by Ventana and evaluated by immunohistochemistry (IHC) on a cohort of stage II CC from Melbourne (n = 192), enriched for patients with recurrent disease (n = 44, 25%). Log rank test was used to assess the association of GIV IHC expression status with the recurrence risk. Evaluation of alternative GIV scoring algorithms, combining staining intensity and percent staining, and statistical predictive modeling including the analysis of distant recurrence free survival (DRFS) was undertaken for the chemo-naive cases, stratified by MMR and AJCC tumor (T) status. The association between GIV IHC status and standard histopathologic criteria was also assessed. Results: The distribution of deficient MMR (dMMR) vs pMMR cases were 20.8% and 79.2%, respectively. Within the chemo-naive population (n = 103), expected associations between pathologic features and DRFS were observed, including pMMR vs dMMR (HR 4.12, p = 0.052), T4 vs T3 (HR 2.39, p = 0.055) and lymphovascular invasion (LVI) vs no LVI (HR 2.62, p = 0.021). GIV positivity, defined as >10% of tumor cells stained or any staining of 3+ intensity, was present in 45 (44.0%) of pMMR chemo-naive cases. For T3 pMMR chemo-naive cases (n = 91), GIV positivity was associated with significantly reduced DRFS (HR 2.49, p = 0.022). Adding LVI as an additional parameter to the algorithm for this group increased the HR to 4.74 (95% CI 1.90-11.85). Conclusions: GIV IHC expression status has been found to be associated with T3 disease, pMMR, and DRFS in an initial cohort of stage II CC. This exploratory diagnostic algorithm currently undergoes validation in two independent clinical stage II CC cohorts, with promising preliminary data. Disclosure: P. Waring: received research grant funding from F. Hoffmann-La Roche; B. Lafleur, A. Muranyi, S. Singh and P. Brunhoeber: Employee of Ventana Medical Systems, Inc., a member of the Roche Group; S. Hu, V. Teichgraber, U. Rohr, R. Ridder:. and K. Shanmugam: Employee of F. Hoffmann-La Roche Ltd. All other authors have declared no conflicts of interest.

658P - A Retrospective Analysis of the Relation Between Durations of Adjuvant Chemotherapy with Its Effects on Overall Survival and Relapse Free Survival in Stage Ii or III Gastric Cancer

ABSTRACT Aim: This study was conducted to propose the optimal duration of adjuvant chemotherapy in stage II or III gastric cancer regardless of treatment regimens, which had been introduced from the oral fluoropyrimidine derivatives to the intravenous fluoropyrimidine combined with platinums. Methods: We retrospectively analyzed data from 2198 patients with histologically confirmed gastric cancer who underwent curative gastrectomy with D2 lymphadenectomy between 2005 and 2012. 1347 patients (61.3 %) were treated by surgery alone due to early stage or patients' refusal of chemotherapy and 851 patients (38.7%) of stage II or III gastric cancer were treated with diverse durations and various kinds of adjuvant chemotherapy. The duration of adjuvant chemotherapy less than 6 months [Group 1] was 343 patients (40.3%), from 6 months to less than 12 months [Group 2] was 179 patients (21.0%), from 1 year to less than 2 years was [Group 3] 240 patients (28.2%) and over 2 years [Group 4] was 89 patients (10.5%). Results: Overall survival (OS) and relapse free survival (RFS) were analyzed according to durations of adjuvant chemotherapy. Median follow-up duration was 3.82 years. Each median OS in Group 1, 2, 3, and 4 was 3.07 years (reference), 3.24 years (hazard ratio [HR] 1.019, 95% CI, 0.520 to 1.997, p-value 0.956), 4.06 years (HR 0.485 95% CI, 0.243 to 0.966, p-value 0.040*) and 4.87 years (HR 0.368, 95% CI, 0.128 to 1.058, p-value 0.064). Each median RFS in Group 1,2,3 and 4 was 2.68 years (reference), 3.06 years (HR 0.948, 95% CI, 0.484 to 1.854, p-value 0.875), 4.02 years (HR, 0.494 95% CI, 0.248 to 0.985, p-value 0.045*) and 4.76 years (HR, 0.392 95% CI, 0.136 to 1.127, p-value 0.082). * p Conclusions: We concluded that a prospective cohort study should be performed to figure out the longer period of adjuvant chemotherapy in gastric cancers could obtain much higher OS and RFS. Disclosure: All authors have declared no conflicts of interest.

214P - Hypermethylation of O6-Methylguanine-Dna Methyltransferase (Mgmt) Promoter As a Prognostic Biomarker for Stage Ii, III and Iv Colorectal Cancers

ABSTRACT Aim: The present study aimed to discover novel epigenetic biomarkers that could permit identification of CRC patients who are at high-risk of developing tumor recurrence following curative surgery and who are at high-risk of imminent tumor progression following treatments for unresectable cancer. Methods: Given that previous studies have clearly shown that microsatellite stable (MSS) CRC with BRAF mutations have worse outcomes compared to other subgroups, in the initial discovery phase we analyzed a 17-gene methylation biomarker panel consisting of differentially methylated loci in BRAF mutant (V600E) CRCs with microsatellite instability (MSI) and MSS. In the validation phase, we analyzed an independent cohort of 255 stage II/III CRCs that underwent curative resection and 103 stage IV CRCs. Results: We identified that among the 17-genes methylation panel; only MGMT methylation levels were predictive of disease recurrence in CRC. Extensive methylation of the MGMT promoter region was observed in 22% of stage II/III and 16% of stage IV CRCs, and this was significantly associated with relapse -free survival (RFS) (p = 0.03 by Wilcoxon test), but not with overall survival (p = 0.96 by Wilcoxon test) in stage II/III CRC following curative resection. By using Cox proportional hazards regression, for all stage II and III cases, the relative risk ratio for RFS was 2.2 (95%CI; 1.1 to 5.6, p = 0.0359) in MGMT unmethylated vs. methylated CRCs and was 0.62 (0.034 to 3.2, p = 0.627) in MSI vs. MSS CRCs. Of 103 stage IV CRCs, 69(68%) patients were diagnosed as unresectable (unresectable group) cases and 32 (32%) were resectable (resectable group). MGMT methylation was significantly improved overall survival in unresectable group (HR = 0.43 (0.17 to 0.94), p = 0.03, Cox proportional hazards regression). Conclusions: Our data firstly highlight the importance of MGMT methylation status as one of the promising predictive biomarkers that can robustly identify patients who are at risk for disease recurrence in patients following curative surgery in stage III CRC patients and predict the outcomes of stage IV CRC patients with unresectable disease lesions at the time of diagnosis. Disclosure: All authors have declared no conflicts of interest.

575P - Adjuvant Chemotherapy and Overall Survival in High Risk Stage Ii Colon Cancer

ABSTRACT Aim: Patients with stage II colon cancer are considered high risk in case of pathological T4 (pT4), poor or undifferentiated grade, emergency surgery, Methods: All patients with high risk stage II colon cancer diagnosed in the area of the Eindhoven Cancer Registry between 2008-2012 were included. Vascular invasion was not included. Multivariable logistic regression was used to assess the association between high risk factors and CT administration. 3-year OS according to CT was based on Kaplan-Meier curves and Cox regression was used to discriminate the independent effect of CT on the risk of death. A subsample was created using propensity score matching (PSM) in which patients who did not receive CT were matched to patients who did. Results: 922 patients were identified of whom 151 (16%) received CT. In multivariable analysis, patients were more likely to receive CT in case of a pT4 tumor (n = 188) (pT4 vs. pT3 30 vs. 11%, OR 4.82, 95% CI 3.04-7.65), Conclusions: Most high risk factors were associated with increased use of CT, although the absolute proportion of CT given was low. In this observational study CT receipt was associated with improved OS. Future studies should focus on how quality of life is affected by CT and what influence this has on choice of treatment. Disclosure: All authors have declared no conflicts of interest.

Adjuvant chemotherapy for stage II and stage III colon cancer—What is happening in routine practice?

e15046 Background: Randomised studies have defined adjuvant chemotherapy as standard treatment for stage III colon cancer (SIIICC), with multiple options available. For stage II (SII) disease, the selection of patients for adjuvant treatment remains controversial. There remains limited data on clinician decision making regarding adjuvant chemotherapy in routine clinical practice. Methods: A review of patients treated with SII &amp; IIICC at 4 hospitals, utilising data from BioGrid Australia, where clinician choice and rationale were prospectively documented. Results: 372 patients (37%) with SII and 307 (30%) with SIIICC were identified from 1015 CC patients treated from January 2003 till November 2008. Median age was 68 years, 51% were male; 49% female. 66 (25%) of patients with SIIICC were not offered chemotherapy, predominantly due to advanced age or co-morbidity. Since oxaliplatin and capecitabine became widely available in 2005, 66% of treated patients have received oxaliplatin based therapy, 15% bolus 5-FU alone and 19% capecitabine. For SII disease, overall 81 (26%) pts received adjuvant chemotherapy. Age was the dominant influence on treatment choice with 41% aged 70 (p&lt;0.001) receiving treatment. Patients with high risk features were also more likely to receive adjuvant therapy. (p= 0.006 for those with lymphovascular invasion and p= 0.0068 for those with T4 tumours). Dose reductions and completion rates were similar for SII and III disease, and for older and younger patients. Conclusions: Over 25% of patients with SIIICC do not receive adjuvant chemotherapy in routine practice, with physicians basing non-treatment recommendations predominantly on patient age and co-morbidity. Where treatment is used, oxaliplatin-based therapy is the dominant regimen, except in older patients. In SIICC, adjuvant chemotherapy is used in one in four patients, more frequently in younger patients and those with high risk features. No significant financial relationships to disclose.

Stage-specific prognostic value of molecular markers in colon cancer: Results of the translational study on the PETACC 3-EORTC 40993-SAKK 60–00 trial

4002 Background: We compared the incidence of molecular markers in stage II (SII) and III (SIII) colon cancer and tested their prognostic value per stage, using PETACC 3, an adjuvant trial with 3,278 patients. We included expression of P53, SMAD4, thymidylate synthetase (TS) and hTERT, mutations of KRAS and BRAF, microsatellite instability (MSI) and 18qLOH. Methods: 1,564 formalin fixed paraffin embedded tissue blocks were prospectively collected and DNA from normal and tumor tissue was extracted after macrodissection. High P53, TS and hTERT expression and SMAD4 loss were assessed by immunohistochemistry. MSI was studied with 10 markers. KRAS exon 2 and BRAF exon 15 mutations were analyzed by allele specific real time PCR. 18qLOH was studied by pyrosequencing 7 SNPs. Prognostic value of the markers was analysed per stage by Cox regression for Relapse Free Survival (RFS). Results: marker frequencies and stage specific p-values in prognostic models in 420 SII and 984 SIII patients are listed in the table . Significant differences in frequency per stage were found for all markers except KRAS and BRAF. An interaction test for differences between marker prognostic value for SII and SIII was significant for MSI (p=0.04) and 18qLOH (p=0.04) in SII. Multivariate analysis including markers, T stage, N stage (for SIII), Tu grade, age &lt;60, sex, treatment arm, and Tu site found T stage (p=0.0001) and MSI (p=0.02) as independently significant clinical predictors in SII; N stage (p&lt;0.0001), T stage (p&lt;0.0001), SMAD4 (p&lt;0.0001) and P53 (p=0.01) in SIII. Conclusions: Molecular markers in colon cancer have a stage specific prognostic value. The possibility that the stages represent different diseases, rather than sequential steps in the evolution of a single disease, needs to be considered. [Table: see text] [Table: see text]

Radiation therapy combined with cis-diammine-glycolatoplatinum (nedaplatin) and 5-fluorouracil for Japanese stage Ii–Iv esophageal cancer compared with cisplatin plus 5-fluorouracil regimen: a retrospective study

To evaluate the treatment outcome of radiotherapy combined with cis-diammine-glycolatoplatinum (nedaplatin) plus 5-fluorouracil (5-FU) for esophageal cancer. From January 2000 to December 2004, a total of 12 esophageal cancer patients with locally advanced and metastatic esophageal cancer (stages II-IVB) were treated with radiation therapy (50.4 Gy) combined with nedaplatin (80 mg/m(2), bolus infusion) and 5-FU (800 mg/m(2)/24 h, continuous infusion for 4 days) (NDP group). We compared the data with those of patients during the same period receiving a different chemotherapy regimen consisting of cisplatin (75 mg/m(2), bolus infusion) and 5-FU (1000 mg/m(2)/24 h, continuous infusion for 4 days) (n = 29, CDDP group) combined with the same radiation therapy. The median survival period was 11.5 months in the NDP group and 13.1 months in the CDDP group. The overall survival rates at 1-, 2-, and 3-years were 40%, 13%, and 13% in the NDP group and 56%, 42%, and 8% in the CDDP group (P = 0.2472), respectively. Grade III and IV leukocytopenia was observed in six (50%) and none of the patients in the NDP group and 14 (48%) and seven (24%) in the CDDP group, respectively. Grade III thrombocytopenia was observed in three (25%) in the NDP group and four (14%) in the CDDP group. Radiation combined with nedaplatin and 5-FU is a safe and effective method for treating esophageal cancer. We recommend that NDP should be used rather than dose-reduction of CDDP combined with 5-FU in patients with impaired renal function as indicated by low creatinine clearance value (40-60 mL/min).

Comparación entre el efecto de lactobacillus casei y el de una vacuna comercial en pollos contra la coccidiosis

This study was carried out to determine a possible protective effect of Lactobacillus casei against Eimeria spp. infection in broilers. In Stage I (SI), 165 broilers were used to isolate Eimeria spp. in commercial farms and to determine the number of oocysts to be used per bird in a challenge. In Stage II (SII), 300 broilers were distributed at random into five groups, each with three replicates (20 birds/replicate). Birds in group A were treated with a commercial vaccine, orally 15 d before the challenge (b.c.). Each bird in group B was inoculated intraperitoneally (i.p.) with viable L. casei organisms 7 d b.c. Animals in group C were inoculated i.p. with a supernatant from L. casei growth media seven d b.c. Birds in group D acted as non-treated infected control and those from group E performed as non-treated uninfected control. Protection was assessed through the anticcocidial index (Al). In SI a combination of Eimeria acervulina (125,000), E. tenella (100,000) and E. maxima (100,000) oocysts per bird was used as an inoculum in the challenge. The AI obtained in SII for groups A, B, C, D, and E was 189 (adequate), 177 (moderate), 86 (bad), 65 (bad) and 200 (good), respectively. On d 33 a.c. mean weight of broilers treated with the vaccine and of those inoculated with L. casei was similar. These results suggest that L. casei could be considered as an alternative for coccidiosis control in broilers.

Gynecologic abnormalities in surgically treated women with stage II or III rectal cancer.

The objective of this article is to review the incidence and management of gynecologic abnormalities in women undergoing surgery for rectal cancer. We performed a retrospective chart review utilizing the Johns Hopkins Tumor Registry and Pathology database. Eighty-six female patients who underwent abdominal surgery between 1985 and 1996 for Stage II or Stage III rectal cancer were identified. Data gathered included: patient demographics, history, intraoperative findings and complications, cancer stage and histology, adjuvant treatments, and followup. Specific attention was focused on the diagnosis, management, and followup of concurrent gynecologic problems. At the time of surgery, nineteen women (22%) had previously undergone hysterectomy and bilateral salpingo-oophorectomy. Of the remaining 67 patients, 25 (37%) were found to have gynecologic abnormalities at the time of surgery, 15 (22%) underwent adnexectomy or hysterectomy or both. Forty-two women (63%) had normal internal genitalia. Of the 61 peri- and postmenopausal women, nine underwent bilateral oophorectomy for therapeutic reasons. No prophylactic oophorectomies were performed in any of the patients. Incidental pathologic findings necessitating gynecological procedures are common in patients undergoing surgery for rectal cancer. These findings are frequently suboptimally assessed and managed in the pre-, intra-, and postoperative periods. Colorectal surgeons operating on women with Stage II and III rectal cancer should be cognizant of the high likelihood of identifying incidental gynecologic pathology and be prepared for definitive management of the pathology. The utilization of prophylactic oophorectomy in postmenopausal women undergoing surgery for rectal cancer is currently not optimal; preoperative discussion should address this option.

The efficacy of postoperative vaginal irradiation in preventing vaginal recurrence in endometrial cancer.

Between 1960 and 1985 hysterectomy was performed on 811 FIGO stage I and 116 stage II endometrial cancers which were divided into three groups: low-risk stage Ii (grade 1 and 2 lesions confined to the inner third of the myometrium; high-risk stage Iii (grade 3 and/or invading to the middle third of the myometrium or beyond); and FIGO stage II tumors (also high-risk). Hysterectomy was the only treatment in 492; in 145 the vaginal vault alone was radiated and in 290 the whole vagina, in each instance by an intracavity dose of 60Gy; in 34 of the latter high-risk tumors the pelvis received an additional 46Gy by external beam therapy. Forty isolated vaginal recurrences were detected; 10 in 308 low-risk and 22 in 184 high-risk tumors treated by surgery alone, and two and five in 40 low and 105 high-risk patients, respectively, who received adjuvant vault irradiation. No recurrences followed irradiation of the whole vaginal mucosa in 163 stage Ii low-risk and 40 stage II lesions and one, 9 years later, in 87 high-risk stage Iii tumors. Nearly 45% of patients with vaginal recurrence died from cancer within 1 year, 77% within 5 years and only 10% survived their recurrence 10 years. Total vaginal irradiation eliminated vaginal recurrences in low risk and reduced the incidence to 2.1% at 20 years after high-risk tumors.