Median Recurrence-free Survival For Patients Research Articles

Prognostic factors in patients with hepatocellular cancer with progression after liver transplantation

Introduction. Hepatocellular cancer is the most frequent primary malignant neoplasm of the liver, developing against the background of viral hepatitis, alcohol abuse, metabolic disorders, cirrhosis. Most often hepatocellular cancer is diagnosed at late stages of the disease, when patients are no longer subject to specific treatment. The priority method of treatment of early stages remains surgical. In the absence of cirrhosis or with compensated cirrhosis the best option is liver resection, in other cases orthotopic liver transplantation is performed. However, when hepatocellular cancer is diagnosed, most patients fall outside the Milan criteria, and the bridge to orthotopic liver transplantation is down-stage therapy. Bridge therapy is used to treat hepatocellular cancer while awaiting liver transplantation and aims to prevent stage progression. The probability of progression of hepatocellular cancer after orthotopic liver transplantation within the first two years is about 75% and about 10% is detected after the fourth year. Progression of hepatocellular cancer remains the main factor limiting the life expectancy of patients after orthotopic liver transplantation.The aim of the study: to evaluate the results of antitumor treatment of patients with hepatocellular cancer progression after liver transplantation.Materials and methods. We evaluated the results of treatment of 50 patients with hepatocellular cancer progression after orthotopic liver transplantation, who were treated on the basis of FGBU NMI Center of Oncology named after N.N. Blokhin. N.N. Blokhin Oncology Center in the period from 2009 to 2020. We analyzed and evaluated overall and recurrence-free survival depending on the bridge therapy, type of treatment, presence of vascular invasion and portal vein thrombosis.Results. According to the results of bridge therapy, hepatocellular cancer stage progression was observed in 9 patients, stabilization - in 17 patients, partial/complete response – in 9 patients. The median recurrence-free survival of patients who received bridge therapy and down-stage therapy was 23.6 months; among patients who did not, it was 35.6 months. The median overall survival with surgical treatment was 79.8 months, whereas with radiation therapy it was 17.2 months. Conclusions. In the studied group of patients the treatment was tolerated satisfactorily. Optimization of immunosuppression protocol and modification of dose regimens of systemic therapy is considered as a condition for treatment, which leads to improvement of long-term treatment results (overall and relapse-free survival).

Survival outcomes in patients with muscle-invasive bladder cancer receiving neoadjuvant chemotherapy stratified by number of cycles.

4586 Background: Neoadjuvant cisplatin-based chemotherapy (NAC) prior to radical cystectomy is the standard of care for patients with muscle invasive bladder cancer (MIBC). Three or more cycles of NAC are commonly administered based on outcomes in prior prospective trials, however many patients are intolerant of 3 cycles of NAC due to toxicity. The prognosis of patients receiving fewer than 3 cycles of NAC has yet to be elucidated. Methods: This is a retrospective single-center study to quantify pathologic response, recurrence-free survival (RFS), and overall survival (OS) from time of first NAC in patients treated with < 3 cycles of NAC compared to patients treated with ≥3 cycles of NAC. Inclusion criteria include: diagnosis of MIBC between 2004-2017, ≥5 years of follow up, deceased or had recurrence prior to 5 years follow up but with adequate follow-up data. Patients were excluded from the study if they were found to have metastatic disease prior to initiation of NAC, lost to follow up prior to 5 years with no evidence of recurrence or death, or had progression of disease during NAC. The primary objective of this study was to determine RFS and OS in patients stratified by cycles of NAC. Patient characteristics were compared using chi-square tests, Fisher’s exact tests, and Wilcoxon rank sum tests. Kaplan Meier curves and log-rank tests were used to compare RFS between subgroups, and Cox proportional hazards models were used to compare RFS adjusting for ECOG performance status, baseline GFR, stage, type of NAC regimen, and patient age at first dose of NAC. 5-year OS was calculated as a percentage of patients surviving at 5 years. Results: A total sample of 195 patients were treated with NAC for MIBC, of which 30 (15.3%) patients received < 3 cycles and 165 (84.6%) patients received ≥3 cycles of NAC. 53 patients received gemcitabine and cisplatin (GC) and 142 patients received methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC). Complete pathologic response (ypT0N0) was observed in 7.4% of patients receiving < 3 cycles and in 26.8% of patient receiving ≥3 cycles of NAC (p = 0.024). Significant pathologic response ( < ypT2) was obtained in 22.2% of patients receiving < 3 cycles of NAC and in 41.8% of patients receiving ≥3 cycles (p > 0.05). Median RFS in patients with < 3 cycles of NAC was 8.8 months (95% CI 6.51, 13.4) and 54.5 months with ≥3 cycles of NAC (95% CI 29.8, 111.9). Based on a log-rank test there is a statistically significant difference in unadjusted RFS between the two groups (p < 0.001). The 5-year OS in patients receiving < 3 cycles of NAC was 13.3%, and the 5-year OS in those receiving ≥3 cycles was 53.3%. Conclusions: Early cessation of chemotherapy due to intolerance had significant implications on pathologic response, RFS and OS. Clinicians should prioritize administering at least 3 cycles of cisplatin-based chemotherapy when feasible to optimize outcomes.

CT-Guided Percutaneous Cryoablation for Lung Metastasis of Colorectal Cancer: A Case Series.

This study aimed to evaluate the efficacy of computed tomography (CT) guided percutaneous cryoablation (CA) for the management of lung metastases in patients with metastatic colorectal cancer (mCRC). Retrospective analysis was performed on 38 mCRC patients with lung metastases, who underwent CT-guided percutaneous CA at our center from May 1, 2020 to November 1, 2021. The technical success rate, 1-year local control (LC) rate, recurrence-free survival (RFS) and treatment-related complications were analyzed. The CA procedure was successfully performed in all patients, with a technical success rate of 100%. The 1-year LC rate was 94.7% (36/38), while 16 patients experienced new distant lung metastases during the follow-up period. The median RFS was 20 months (95% CI: 13.0-27.0). The median RFS of patients with and without extrapulmonary metastasis was 15 and 23 months, respectively. Complications were reported in 18 (47.4%) patients following the CA procedure. Pneumothorax was discovered in 15 (39.5%) patients, and five of these patients (13.2%) required chest tube intubation. Two patients (5.3%) presented with hemoptysis during the CA procedure. One patient developed subcutaneous emphysema as detected in the post-procedure follow-up imaging. All patients tolerated the peri-procedural pain well under local anesthesia, and the mean visual analog scale (VAS) score was 2.8. Lung CA is a safe and well-tolerated treatment with a satisfactory local control rate for patients with lung metastases derived from mCRC.

Early discontinuation of adjuvant chemotherapy in patients with early-stage pancreatic cancer correlates with inferior survival: A multicenter population-based cohort study.

BackgroundThe current study aimed to determine the association between timing and completion of adjuvant chemotherapy and outcomes in real-world patients with early-stage pancreatic cancer.MethodsIn this multi-center cohort study patients with early-stage pancreatic cancer who were diagnosed from 2007–2017 and underwent complete resection in the province of Saskatchewan were examined. Cox proportional multivariate analyses were performed for correlation with recurrence and survival.ResultsOf 168 patients, 71 eligible patients with median age of 69 years and M:F of 37:34 were identified. Median time to the start of adjuvant therapy from surgery was 73 days. Of all patients, 49 (69%) patients completed adjuvant chemotherapy and 22 (31%) required early treatment discontinuation. Median recurrence-free survival of patients who completed treatment was 22 months (95%CI:15.8–28.2) vs. 9 months (3.3–14.7) if treatment was discontinued early (P<0.001). Median overall survival of those who completed treatment was 33 (17.5–48.5) vs. 16 months (17.5–48.5) with early treatment discontinuation (P<0.001). In the multivariate analysis, treatment discontinuation was significantly correlated with recurrent disease, hazard ratio (HR), 2.57 (1.41–4.68), P = 0.002 and inferior survival, HR, 2.55 (1.39–4.68), P = 0.003. No correlation between treatment timing and survival was noted.ConclusionsEarly discontinuation but not the timing of adjuvant chemotherapy correlates with inferior outcomes.

2010 versus the 2000 consensus criteria in patients with normalised insulin-like growth factor 1 after transsphenoidal surgery has high predictive values for long-term recurrence-free survival in acromegaly.

The present study investigated the factors associated with recurrence during long-term follow-up in acromegaly and compared the recurrence rate between patients in remission with 2010 vs 2000 consensus criteria. We retrospectively recruited 133 adult acromegalic patients who had undergone transsphenoidal surgery (TSS) from January 2013 to December 2014 and assessed their clinical characteristics, surgical outcomes and recurrence. Surgical remission was defined as normalised insulin-like growth factor 1 (IGF-1) with nadir growth hormone (GH) during an oral glucose tolerance test (OGTT) <1μg/L no less than 3months after TSS without adjuvant therapy. Recurrence was defined as persistently reelevated IGF-1 after surgical remission. Cox regression analysis and Kaplan-Meier survival analysis were performed to evaluate the factors associated with recurrence. Remission was achieved in 77 cases (57.9%) after TSS alone. Recurrence was seen in five cases (6.5%) at 12, 12, 12, 36 and 54months, respectively, after surgery. Cox regression analysis showed that a nadir GH<0.4μg/L (vs 0.4-1.0μg/L) at surgical remission (odds ratio [OR]=0.106; 95% confidence interval [CI]=0.017-0.645; P=0.015) and Ki-67 index (OR=2.636; 95% CI=1.023-6.791; P=0.045) were independent factors influencing recurrence. Kaplan-Meier survival analysis showed that the median recurrence-free survival was 36months (95% CI=20-52) for patients with nadir GH 0.4-1.0μg/L at surgical remission. The median recurrence-free survival for patients with nadir GH<0.4μg/L at surgical remission was much longer (ie, required further follow-up to estimate). A failure of GH suppression under 0.4μg/L during an OGTT in patients with normalised IGF-1 and a higher Ki-67 index are independent predictors of recurrence after surgical remission in GH-secreting pituitary adenomas. Compared to patients with nadir GH<0.4μg/L, those with nadir GH 0.4-1.0μg/L appear to have a significantly higher risk of recurrence.

Weight gain during neoadjuvant therapy is associated with improved recurrence-free survival for patients undergoing pancreatectomy for pancreatic ductal adenocarcinoma

Presenter: Jonathan Hue MD | Case Western Reserve University School of Medicine Background: Weight loss commonly precedes the diagnosis of pancreatic ductal adenocarcinoma (PDAC). There is growing emphasis on neoadjuvant treatment for patients with localized disease. The severity and impact of weight loss during neoadjuvant therapy is not well studied. We hypothesized that weight loss during neoadjuvant chemotherapy would be associated with poor short- and long-term outcomes. Methods: We performed a single institution retrospective cohort study of patients with histologically confirmed PDAC who received neoadjuvant chemotherapy (with or without radiotherapy) and underwent a pancreatectomy between 2009-2021. We abstracted patient weights within 1 year preceding diagnosis, as well as at diagnosis, chemotherapy start, and before pancreatectomy. Patients were categorized based on weight change from start of chemotherapy to surgery: weight gain (≥5%), stable ( < 5% gain to < 5% loss), and weight loss (≥5%). The association between weight change and pathologic, perioperative, and long-term outcomes was analyzed. Results: A total of 127 patients received neoadjuvant therapy followed by pancreatectomy during the study period, of whom 95 had raw weights recorded at the specified time points and were included in the analysis. The median weight loss prior to diagnosis was 7.9% (range: 0.5% gain to 24.1% loss). Thirty patients (31.6%) lost weight during neoadjuvant chemotherapy, 56 (59.0%) had stable weight, and nine (9.5%) gained weight. Patients who lost weight were more likely to have locally advanced disease compared to patients with stable weight or weight gain (26.7% vs 8.9% vs 11.1%, p=0.12). CA19-9 levels were similar at the time of diagnosis and prior to pancreatectomy across groups. There was no difference between the three groups in the number of chemotherapy cycles administered, chemotherapeutic regimens, rate of neoadjuvant radiotherapy, or the time from initiation of chemotherapy to surgery. There was no difference in pathologic (tumor size, lymph node positivity, margin positivity, pathologic response to therapy) or perioperative (in-hospital complication rate, length of stay, discharge disposition) outcomes based on degree of weight loss during therapy. Utilization of adjuvant chemotherapy and adjuvant radiotherapy was also similar between groups. Median overall survival of patients who gained weight during neoadjuvant therapy was longer than that of patients with stable weight or weight loss (38.4 vs 25.8 vs 26.7 months, p=0.58), but this did not reach statistical significance. Median recurrence-free survival of patients who gained weight during neoadjuvant therapy was longer than that of patients with stable weight or weight loss (29.5 vs 9.6 vs 14.0 months, p=0.07, Figure). After controlling for clinical and treatment factors as well anatomic stage, weight gain was associated with improved recurrence-free survival benefit compared to weight loss (HR=0.15, 95% CI 0.03-0.81). A similar association was not identified when analyzing overall survival (HR=1.17, 95% CI 0.28-4.80). Conclusion: Weight trends during neoadjuvant therapy are variable, but the majority of patients maintain weight or lose weight. Patients who gain weight during neoadjuvant therapy may have improved recurrence-free survival. The association between weight and overall survival is less clear. Future studies may validate weight as a predictor of survival among patients receiving neoadjuvant therapy for localized PDAC.

Cytomegalovirus and systemic inflammation at time of surgery is associated with worse outcomes in serous ovarian cancer

Objectives: Cytomegalovirus (CMV) is a common infection that establishes latency in healthy people. CMV has been associated with alterations of the immune compartment leading to improved responses, while inflammation has been shown to adversely impact outcomes. We investigated whether CMV serostatus predicts outcomes in ovarian cancer in the presence or absence of inflammation.Methods: A total of 106 patients with serous ovarian cancer from 2006 to 2009 were analyzed. CMV and systemic inflammation was measured using CMV immunoglobulin G (IgG) and C-reactive protein (CRP), respectively, in serum collected prior to cytoreduction. Patients were stratified by CMV IgG (non-reactive, reactive/borderline) and CRP (≤10, >10 mg/L) status. Overall survival (OS) and recurrence-free survival (RFS) were compared by group using log-rank tests and Cox proportional hazards regression models adjusting for age at surgery.Results: Of 106 eligible patients, 40 (37.7%) were CMV+/CRP+, 24 (22.6%) CMV+/CRP-, 19 (17.9%) CMV−/CRP+, and 23 (21.7%) CMV−/CRP−. CRP+ had higher CA-125 levels (P = 0.05) and higher rates of suboptimal debulking (P = 0.03). There were no other significant differences in demographic, surgical, or pathologic factors between groups. CMV+/CRP+ patients median RFS and OS were 16.9 months (95% CI: 9.0–21.1) and 31.7 months (95% CI: 25.0–48.7), respectively, with a significantly worse RFS (aHR: 1.85, 95% CI: 1.05–3.24, P = 0.03) and OS (aHR: 2.12, 95% CI: 1.17–3.82, P = 0.01) compared to CMV−/CRP− (RFS = 31.2 months (95% CI: 16.0–56.4) and OS = 63.8 months (95% CI: 50.7–87.0)). CMV+/CRP− group displayed the longest OS (89.3 months).Conclusions: Previous exposure to CMV and high CRP at surgery portended worse RFS and OS compared to women who tested negative. The CMV+/CRP− group had the longest OS, indicating that CMV status alone, in the absence of inflammation, may be protective.

Patients' prognosis of intrahepatic cholangiocarcinoma and combined hepatocellular‐cholangiocarcinoma after resection

Combined hepatocellular‐cholangiocarcinoma (cHCC‐CC) and intrahepatic cholangiocarcinoma (ICC) are classified into one category, but comparison of prognosis of the two carcinomas remains controversial. The aim of the current study was to investigate surgical outcomes for patients with ICC or cHCC‐CC who underwent resection in order to elucidate whether the classification of ICC and cHCC‐CC is justified. Subjects were 61 patients with ICC and 29 patients with cHCC‐CC who underwent liver resection from 2001 to 2017. Clinic‐pathological data from the two groups were compared. Tumor number and vascular invasion were independent risk factors for recurrence‐free survival (RFS) in both groups (P < .001 for both). Of note, for patients with ICC, tumor cut‐off size of 5 cm showed statistical significance in median RFS (>5 cm vs ≤5 cm, 0.5 years vs 4.0 years, P = .003). For patients with cHCC‐CC, tumor cut‐off size of 2 cm showed statistical significance in median RFS (>2 cm vs ≤2 cm, 0.6 years vs 2.6 years, P = .038). The median RFS of patients with cHCC‐CC was 0.9 years (95% confidence interval: 0.3‐1.6), which was poorer than that of patients with ICC (1.3 years, 0.5‐2.1) (P = .028); the rate of RFS at 5 years was 0% and 37.7% respectively. Our study supports the concept of classifying ICC and cHCC‐CC into different categories because of a significant difference in RFS between the two.

Clinicopathological values of NBS1 and DNA damage response genes in epithelial ovarian cancers.

Epithelial ovarian cancers (EOCs) are highly lethal gynecological malignancies with a high recurrence rate. Therefore, developing prognostic markers for recurrence after chemotherapy is crucial for the treatment of ovarian cancers. As ovarian cancers frequently respond to DNA-damaging agents, we assessed the clinicopathological significance of key double-strand DNA break (DSB) repair genes, including BRCA1, BRCA2, BARD1, ATM, RAD51 and NBS1 in EOC cell lines and paraffin-embedded tissue sections from 140 EOC patients treated with cytoreductive surgery, followed by platinum-based chemotherapy. These samples were analyzed for the clinicopathological impact of DSB genes by western blot analysis, immunohistochemistry and quantitative real-time PCR. Of the DSB repair genes, BRCA1, ATM and NBS1, which are involved in the homologous recombination-mediated repair pathway, were related to aggressive parameters in EOC. When survival analysis was performed, NBS1 expression exhibited an association with EOC recurrence. Specifically, increased NBS1 expression was found in 107 out of 140 cases (76.0%) and correlated with advanced stage (P=0.001), high grade (P=0.001) and serous histology (P=0.008). The median recurrence-free survival in patients with positive and negative expression of NBS1 was 30 and 78 months, respectively (P=0.0068). In multivariate analysis, NBS1 was an independent prognostic factor for the recurrence of EOC. Together, these results suggest that NBS1 is a marker of poor prognosis for the recurrence of EOC and is associated with aggressive clinicopathological parameters.

Desmoid-type fibromatosis-associated Gardner fibromas: prevalence and impact on local recurrence

Although Gardner fibroma is a precursor lesion of desmoid tumor, the prevalence and prognostic importance of Gardner fibroma associated with desmoid tumors has not been systematically studied in adults. From 129 patients with desmoid-type fibromatosis, 170 specimens were re-examined for the presence of an associated Gardner fibroma. Clinicopathologic features of Gardner fibroma-associated desmoid-type fibromatosis were compared to desmoid tumors without associated Gardner fibroma. Recurrence-free survival was compared using multivariate Cox proportional hazard regression to account for known confounding factors. Of 104 evaluable primary desmoid tumor resections, 25 (24%) had an associated Gardner fibroma. When previous incisional biopsies and resection specimens of locally recurrent desmoid tumors were also examined, the overall prevalence of associated Gardner fibroma was 37%. Desmoid tumors arising in high risk anatomic sites (extremities or deep soft tissues of the back and chest wall) were more often associated with Gardner fibroma than tumors at other sites. Median recurrence-free survival for patients with Gardner fibroma-associated desmoid-type fibromatosis was 3.2 years, whereas median survival for patients without associated Gardner fibroma was >25 years (hazard ratio 2.8; P = 0.001). Although the presence of Gardner fibroma had no impact on the recurrence rate of desmoid tumors arising at high risk anatomic sites, associated Gardner fibroma increased the risk of recurrence 4-fold for desmoid tumors at low risk anatomic sites. Associated Gardner fibroma is under-recognized in desmoid-type fibromatosis and increases the risk of local recurrence for a subgroup of patients.

Improving the clinical risk score: An analysis of molecular biomarkers in the era of modern chemotherapy for resectable hepatic colorectal cancer metastases

The prognostic relevance of variations in expression of specific tumor genes in colorectal cancer liver metastases (CRCLMs) in patients treated with resection and modern chemotherapy is not known. Patients submitted to liver resection for CRCLM between January 2000 and October 2007 were studied. A clinical risk score (CRS; range, 0-5) was calculated for each patient. RNA was extracted from histologically confirmed tumor isolates, and using real-time polymerase chain reaction (PCR) studies, we assessed the quantitative expression of 12 genes with potential importance in chemotherapy resistance and tumor progression, including thymidylate synthase (TS; 5-fluorouracil), excision repair cross complementing gene-1, and xeroderma pigmentosum groups A through G (oxaliplatin), topoisomerase-I (irinotecan), c-met, and hepatocyte growth factor. Primary outcomes were recurrence-free survival (RFS) and disease-specific survival (DSS) after hepatic resection. One-hundred fifty-five patients with good quality tumor mRNA were identified. Median follow-up was 32 months for survivors, and the median CRS was 2. Eighty-seven patients (56%) received preoperative chemotherapy, and 124 (80%) received postoperative chemotherapy. Median RFS for all patients was 13 months, and 3-year DSS was 69%. Median RFS and 3-year DSS for patients with an increased CRS (3-5) was lower (7 vs 18 months [P < .0001] and 50% vs. 80% [P < .0001], respectively). Of the 12 genes studied, only increased TS expression was associated with a lower RFS (hazard ratio, 1.16; 95% confidence interval, 1.0-1.3; P = .03) and DSS (hazard ratio, 1.25; 95% confidence interval, 1.0-1.5; P = .03). Median RFS and 3-year DSS for patients with increased TS expression was decreased (9 vs. 15 months [P = .03] and 48% vs. 82% [P = .001], respectively). TS expression had prognostic value that was independent of CRS on multivariate analysis. In patients with hepatic CRCLM treated with resection and modern chemotherapy, increased expression of TS improves outcome stratification and appears to be a useful biomarker.

Pattern of recurrence in patients with ruptured primary gastrointestinal stromal tumour

This study assessed the outcomes of patients with a gastrointestinal stromal tumour (GIST) that ruptured before or during resection. The records of 23 patients (8 women, 15 men; median age 54 years) with ruptured primary non-metastatic GIST were retrieved from a database of 554 patients. The written surgical and pathology reports were analysed. Review pathology was performed in all 23 cases, and mutational analysis of KIT and platelet-derived growth factor α (PDGFRA) genes was performed in 21 patients. Median follow-up was 52 months. Tumour rupture was spontaneous in 16 patients, following abdominal trauma in two and occurred during resection in five. Primary tumour location was the stomach in six patients, duodenum in one and small bowel in 16. Mean tumour size was 10·2 (range 4-28) cm. According to the Miettinen and Lasota risk classification, the distribution of very low-, low-, intermediate- and high-risk cases was one, two, five and 15 respectively. One patient remained disease-free at 83 months. Fifteen of 16 patients who did not receive adjuvant therapy developed tumour recurrence after a median of 19 months. Median recurrence-free survival in patients with KIT mutations involving codons 557-558 was 11 months. Patients with a rupture of GIST into the abdominal cavity have a risk of recurrence of nearly 100 per cent. In patients with deletion mutations involving codons 557-558, recurrence-free survival was less than 1 year. All patient groups are clear candidates for adjuvant drug therapy.

Gemtuzumab ozogamicin as first‐line treatment in patients aged 70 years or older with acute myeloid leukemia

Elderly patients with acute myeloid leukemia (AML) are generally unable to withstand the rigors of intensive induction chemotherapy and its attendant complications. Gemtuzumab ozogamicin (GO) is an immunoconjugate that had demonstrated activity in recurrent AML. The objective of the current study was to determine the prognostic factors for achievement of complete remission (CR) in newly diagnosed elderly AML patients treated with GO as initial induction therapy. A retrospective study was performed of efficacy and toxicity associated with GO therapy, and factors potentially predictive of response were assessed in 49 previously untreated AML patients. CR was achieved in 14% of all treated patients. Among the patients with an intermediate-risk karyotype, the CR rate was 30%, compared with none with an unfavorable karyotype. The median duration of overall survival was 3.7 months (95% confidence interval [95% CI], 1.4-6.9 months), and the median recurrence-free survival in patients who achieved CR was 11.8 months (95% CI, 5.0-ind months). These data suggest that GO should be considered as a first-line treatment option in older patients with AML with intermediate-risk cytogenetics who cannot tolerate high-dose induction chemotherapy.

Overexpression of stathmin1 in the diffuse type of gastric cancer and its roles in proliferation and migration of gastric cancer cells.

Background:Stathmin1 is a microtubule-regulating protein that has an important role in the assembly and disassembly of the mitotic spindle. The roles of stathmin1 in carcinogenesis of various cancers, including prostate and breast cancer, have been explored. However, its expression and roles in gastric cancer have not yet been described.Methods:Stathmin1 expression in paraffin-embedded tissue sections from 226 patients was analysed by immunohistochemistry. Roles of stathmin1 were studied using a specific small interfering RNA (siRNA).Results:The expression of stathmin1 was positively correlated with lymph node metastasis, TNM stages and vascular invasion, and negatively with recurrence-free survival, in the diffuse type of gastric cancer. The median recurrence-free survival in patients with a negative and positive expression of stathmin1 was 17.0 and 7.0 months, respectively (P=0.009). When the expression of stathmin1 was knocked down using siRNA, the proliferation, migration and invasion of poorly differentiated gastric cancer cells in vitro were significantly inhibited. Moreover, stathmin1 siRNA transfection significantly slowed the growth of xenografts in nude mice.Conclusion:These results suggest that stathmin1 can be a good prognostic factor for recurrence-free survival rate and is a therapeutic target in diffuse-type gastric cancer.

BubR1 as a prognostic marker for recurrence-free survival rates in epithelial ovarian cancers

Background:Epithelial ovarian cancer is one of the most lethal malignancies, and has a high recurrence rate. Thus, prognostic markers for recurrence are crucial for the care of ovarian cancer. As ovarian cancers frequently exhibit chromosome instability, we aimed at assessing the prognostic significance of two key mitotic kinases, BubR1 and Aurora A.Methods:We analysed paraffin-embedded tissue sections from 160 ovarian cancer patients whose clinical outcomes had been tracked after first-line treatment.Results:The median recurrence-free survival in patients with a positive and negative expression of BubR1 was 27 and 83 months, respectively (P<0.001). A positive BubR1 expression was also associated with advanced stage, serous histology and high grade. In contrast, Aurora A immunostaining did not correlate with any of the clinical parameters analysed.Conclusion:BubR1, but not Aurora A, is a prognostic marker for recurrence-free survival rates in epithelial ovarian cancers.

E‐cadherin promoter polymorphism (C‐160A) and risk of recurrence in patients with superficial bladder cancer

Tumor recurrence is a hallmark of superficial bladder cancer. Currently, a molecular marker for bladder cancer recurrence is lacking. E-cadherin plays an important role in epithelial development and in the establishment and maintenance of cell-cell adhesion and tissue architecture. The purpose of this study is to investigate the association of an E-cadherin promoter polymorphism (CDH1c-160a) with the risk of bladder cancer recurrence. This study included 302 patients with superficial bladder cancer. Genomic DNA was extracted from peripheral blood lymphocytes and genotyping was performed using Taqman assay. Clinical data were collected by medical chart review. Cox proportional hazard model was used to estimate the hazard ratios (HRs) associated with genotypes while adjusting for age, gender, smoking status, tumor stage and grade where appropriate. During a median follow-up of 27.65 months, 151 patients experienced disease recurrence. Subsequent analyses were restricted to Caucasians only due to the small sample size of other ethnic groups (13 in recurrence group and 15 in non-recurrence group). Among the 274 Caucasian patients, 138 developed recurrence during the same length of follow-up time. In Caucasian patients, having at least one variant A allele conferred a 32% reduction in recurrence risk (adjusted HR: 0.68; 95% CI: 0.48-0.96). The median recurrence-free survival for patients carrying at least one variant A allele was significantly longer than that for patients with a homozygous CC genotype (40.4 vs 12.5 months, p=0.04). Our findings suggest that the E-cadherin promoter polymorphism may be a valuable molecular marker for bladder cancer recurrence.

Association of Time to Recurrence With Thymidylate Synthase and Dihydropyrimidine Dehydrogenase mRNA Expression in Stage II and III Colorectal Cancer

Patients with International Union Against Cancer (UICC) stage IIb and III colon cancer and stage II and III rectal cancer may receive adjuvant chemotherapy with 5-fluorouracil (5-FU). High levels of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) have been associated with resistance to 5-FU in advanced colorectal cancer. The aim of this study was to investigate the association of TS and DPD mRNA levels with recurrence-free survival in patients with colorectal cancer who are receiving adjuvant 5-FU–based chemotherapy. TS and DPD mRNA quantitation was retrospectively performed in primary colorectal cancer specimens from patients receiving adjuvant 5-FU using a reverse transcription– polymerase chain reaction technique. The median TS mRNA level in patients with a recurrence (n = 142) was 0.68, and in patients without a recurrence (n = 206) the median level was 0.80 ( P < 0.01). Patients with a recurrence who had a low TS level (TS ≤ 0.9; n = 102) had a median recurrence-free survival of 18 months (range 3.0 to 54 months), and those with a high TS level (TS > 0.9; n = 40) had a median recurrence-free survival of 11 months (range 1.7 to 53 months; P = 0.0024). There was no difference in the median recurrence-free survival of patients with low and high DPD mRNA levels. The TS mRNA level may be a useful marker to predict the time to recurrence in patients with colorectal cancer who are receiving adjuvant 5-FU treatment. ( J Gastrointest Surg 2002;6:331–337.)

Prognostic value of p27Kip1 and p21WAF/Cip protein expression in muscle invasive bladder cancer.

Two genes, namely p27Kip1 and p21WAF/Cip1 that reveal distinct structural homology, have been identified as inductors of cell cycle arrest at the G1-checkpoint to prevent entry of somatic cells into the S phase of the cell cycle when substantial DNA damage has occurred. It was demonstrated that the p21WAF/Cip1 gene is induced by pathways dependent and independent from a functionally intact p53 tumour suppressor protein. It has been suggested that decreased expression both of the p21WAF/Cip1 and p27Kip1 protein may contribute to the development of human malignancies due to loss of critical antiproliferative mechanisms. So far, the role of altered p21WAF/Cip1 and mainly of a decreased p27Kip1 protein expression in patients with muscle invasive bladder cancer has not been investigated. In the present study, 50 tumour specimens from 50 patients undergoing radical cystectomy (T2-T4) were investigated for different biological and clinical characteristics as possible prognostic factors: age, depth of tumour infiltration (T-stage), histological grading (G), lymph node status as well as immunohistochemical staining for the p21WAF/Cip1 and p27Kip1 proteins. The median recurrence-free survival for patients with and without retained p21WAF/Cip1 protein expression was 54 months (3-86 months) and 13 months (1-40 months), respectively (p=0.07). During univariate analysis, loss of p21WAF/Cip1 protein expression (p=0.02), T-stage (p=0.02) and histological grading (p=0.03) were significant prognostic factors for survival, among which a negative reaction for the p21WAF/Cip1 protein (p=0.02) as well as T-stage (p=0.005) remained independent significant predictors during multivariate analysis. Loss of p27Kip1 protein expression was not correlated with the recurrence-free or the overall survival of the patients. Prospective studies are needed to confirm the independent prognostic potential of cell-cycle associated proteins such as p21WAF/Cip1 in patients with muscle invasive bladder cancer. The availability of more refined prognostic factors should assist decision making regarding the value of more aggressive treatment options, such as adjuvant or neoadjuvant chemotherapy, for defined subgroups of patients.