Relapse-free Survival Rates In Patients Research Articles

Effect of Wnt5a on drug resistance in estrogen receptor-positive breast cancer

BackgroundPreviously, we reported that Wnt5a-positive breast cancer can be classified as estrogen receptor (ER)-positive breast cancer; its prognosis is worse than that of Wnt5a-negative breast cancer. This study aimed to investigate the mechanisms underlying the poor prognosis in Wnt5a-positive breast cancer patients.MethodsIn total, 151 consecutive ER-positive breast cancer patients who underwent resection between January 2011 and February 2014 were enrolled. DNA microarray and pathway analyses were conducted using MCF-7 cells stably expressing Wnt5a [MCF-7/Wnt5a (+)]. Based on the outcomes, cell viability/drug sensitivity assays, and mutation analysis were performed using cell cultures and breast cancer tissues. The relationship between Wnt5a and the PI3K–AKT–mTOR signaling pathway was also examined.ResultsThe relapse-free survival rate in patients with Wnt5a-positive breast cancer was significantly lower than that in patients with Wnt5a-negative breast cancer (P = 0.047). DNA microarray data suggest that only the cytochrome P450 (CYP) pathway was significantly upregulated in MCF-7/Wnt5a (+) cells (P = 0.0440). Additionally, MCF-7/Wnt5a (+) cells displayed reduced sensitivity to the metabolic substrates of CYP, tamoxifen (P < 0.001), paclitaxel (P < 0.001), and cyclophosphamide (P < 0.001). Of note, PIK3CA mutations were not associated with the expression of Wnt5a in breast cancer tissue and culture cells.ConclusionsIn ER-positive breast cancer, Wnt5a upregulates the CYP metabolic pathway and suppresses tamoxifen, paclitaxel, and cyclophosphamide resistance, all of the three, standard treatment methods for ER-positive breast cancer. Wnt5a is thus potentially involved in the poor prognosis of ER-positive breast cancer independently of the PI3K–AKT–mTOR signaling pathway.

Anti-fibrotic properties of an adiponectin paralog protein, C1q/TNF-related protein 6 (CTRP6), in diffuse gastric adenocarcinoma.

Patients with advanced gastric cancer, especially diffuse-type gastric cancer, which is often accompanied by stromal fibrosis, commonly exhibit a poor prognosis. This study was designed to unravel the potential roles of C1q/TNF-related protein 6 (CTRP6) in the fibrotic cancer microenvironment of diffuse-type gastric adenocarcinoma. A total of 49 diffuse-type gastric cancer samples were evaluated in this study, and 23 of these samples exhibited focal CTRP6 immunoreactivity. CTRP6 immunoreactivity was found to be correlated with favorable survival outcomes, in terms of both overall and relapse-free survival rates, but this trend did not reach significance (P = 0.15). By contrast, CTRP6 immunoreactivity was significantly correlated with relapse-free survival rates in patients with diffuse-type gastric cancer at a distal site (P = 0.028). Notably, most gastric cancer cells at the cancer invasive front were CTRP6 negative, especially in areas of robust fibrosis. Double immunohistochemical staining demonstrated an inverse expression profile for CTRP6 and the activated fibroblast marker alpha smooth muscle actin (α-sma) in stromal and gastric cancer cells at the cancer invasion front. The addition of recombinant CTRP6 protein attenuated the TGF-β-induced α-sma expression in cultured human fibroblasts but did not alter the proliferation rate or Matrigel-invasion activity of the cultured gastric cancer cells. In addition, CTRP6 did not affect the viability of normal human gastric epithelial cells. This study suggests that CTRP6 may have potential application in combating stromal fibrosis in diffuse-type gastric cancers.

Comparison of survival and perioperative outcome of the colonic stent and the transanal decompression tube placement and emergency surgery for left-sided obstructive colorectal cancer: a retrospective multi-center observational study \u201cThe CODOMO study\u201d

PurposeAdvances in endoscopic technology have led to the reevaluation of self-expandable metallic stent (SEMS) placement as a bridge-to-surgery (BTS) in patients with obstructive colorectal cancer. In Japan, after inclusion of SEMS placement as a BTS in the medical insurance coverage in 2012, this procedure has been increasingly performed. However, a transanal decompression tube (TADT) placement has been used as a BTS. We aimed to retrospectively evaluate the optimal strategy for obstructive left-sided colorectal cancer (OLCRC) by comparing SEMS and TADT placement with emergency surgery.MethodsWe included 301 patients with stage II and III OLCRC from 27 institutions. The study patients were divided into Surgery group (emergency surgery, n = 103), SEMS group (BTS by SEMS, n = 113), and TADT group (BTS by TADT, n = 85). We compared the survival and perioperative outcomes of patients in the Surgery group as a standard treatment with those in the SEMS and TADT groups.ResultsThe 3-year relapse-free survival rate in patients in the Surgery group was 74.8%, while that in patients in the SEMS group and TADT group were 69.0% (p = 0.39) and 55.3% (p = 0.006), respectively. The technical success rate was not statistically different, but the clinical success rate was significantly higher in the SEMS group than in the TADT group (p = 0.0040). With regard to postoperative complications after curative surgery, the SEMS group had significantly lower of complications (≥ grade 2) than the Surgery group (p = 0.022).ConclusionPatients who underwent SEMS placement for OLCRC had similar oncological outcomes to patients who underwent emergency surgery.

The impact of surgery induced immune-nutritional change on the outgrowth of micrometastasis after potentially curative resection for gastric cancer.

e16581 Background: Whereas radical resection for gastric cancer is only life-saving option, resulting host response have been suggested to trigger the outgrowth of previously disseminated foci at distant anatomical sites via alteration of anti-tumor immunity. The prognostic nutrition index (PNI) which was calculated as 10 × serum Alb concentration (g/dL) + 0.005 × peripheral total lymphocyte count (/µL) is a surrogate marker of inflammation related nutritional decline and the imbalance of T lymphocyte differentiation. The aim of study was to evaluate the impact of perioperative change of PNI. Methods: The medical record of 567 gastric cancer patients who matched with the following inclusion criteria, R0 resection between 2006 and 2018, no preoperative anticancer treatment, pStage IB-IIIC according to UICC TNM classification and no other organ cancer at surgery, was identified from the prospectively maintained database. The postoperative laboratory data was routinely evaluated at POD 1, 3, 7 and first visit after discharge (AD). The PNI was compared through the perioperative course. Then the predictive value of low PNI-AD which defined as PNI &lt; 40 on the relapse free survival (RFS) after surgery was estimated by COX proportional hazards analysis. Results: The median value of PNI at base line, 1, 3, 7 POD and AD was 51.0, 35.9, 34.0, 38.3 and 48.2, respectively. The PNI as significantly decreased at 1, 3 and 7 POD. Though the PNI at AD had a proclivity to recover, which was still significantly lower than that at base line. During observation period after surgery, the recurrence was encountered in 80 patients. The 5-year RFS rate in patients of pStage IB (n = 164), II (n = 228) and III (n = 175) was 97.4%, 88.9% and 64.7%, respectively. The multivariate analysis identified female gender (HR: 1.715, 95%CI; 1.018-2.890, p = 0.04), pT3-4 (HR:3.620, 95%CI; 2.011-6.518, p &lt; 0.01), pN1-3 (HR:2.741, 95%CI; 1.428-5.263, p = 0.02), vessel invasion (+) (HR:2.666, 95%CI; 1.681-4.229, p &lt; 0.01), PNI-AD &lt; 40 (HR:1.833, 95%CI; 1.002-3.352, p = 0.04) were independent predictors of recurrence. The low PNI-AD was significantly related to the recurrence in the population of pStage III, but not in pStage IB and II. Conclusions: The retardation of postoperative recovery of PNI might evoke the distant metastasis.

Oncogenic Roles Of A Histone Methyltransferase SETDB2 In AML1-ETO Positive AML.

IntroductionAML1-ETO produced by t(8;21) abnomality has multiple effects on the leukemogenesis of acute myeloid leukemia (AML). SET domain, bifurcated 2 (SETDB2) can mediate gene silencing by trimethylation of the ninth lysine residue of histone H3 protein (H3K9) of the promoter and has been confirmed as an oncogene in many cancers. The role of SETDB2 in AML1-ETO positive AML is not clear.MethodsQuantitative reverse transcription PCR was performed to measure SETDB2 expression in bone marrow from AML patients and healthy people. Kaplan-Meier analysis was performed to investigate the effect of SETDB2 on prognosis of AML patients. Dual luciferase reporter gene assay, chromatin immunoprecipitation were performed to investigate the regulatory mechanism of AML1-ETO on SETDB2. CCK-8 and colony formation assay were performed to measure the effect of SETDB2 on leukemic cells.ResultsSETDB2 is highly expressed in AML1-ETO positive AML. The overall survival, event-free and relapse-free survival rate of patients with high SETDB2 expression was lower than those of patients with low SETDB2 expression. SETDB2 is epigenetically upregulated by AML1-ETO fusion protein. Downregulation of SETDB2 expression significantly inhibits the proliferation and clonality of leukemic cells and promotes the sensitivity of leukemic cells to an epigenetic inhibitor JQ1.ConclusionAML1-ETO/SETDB2 is a novel epigenetic pathway of leukemogenesis and SETDB2 is a potential therapeutic target of t(8;21) AML.

MicroRNA-9-5p-CDX2 Axis: A Useful Prognostic Biomarker for Patients with Stage II/III Colorectal Cancer.

A lack of caudal-type homeobox transcription factor 2 (CDX2) protein expression has been proposed as a prognostic biomarker for colorectal cancer (CRC). However, the relationship between CDX2 levels and the survival of patients with stage II/III CRC along with the relationship between microRNAs (miRs) and CDX2 expression are unclear. Tissue samples were collected from patients with stage II/III CRC surgically treated at Kyoto University Hospital. CDX2 expression was semi-quantitatively evaluated by immunohistochemistry (IHC). The prognostic impacts of CDX2 expression on overall survival (OS) and relapse-free survival (RFS) were evaluated by multivariable statistical analysis. The expression of miRs regulating CDX2 expression and their prognostic impacts were analyzed using The Cancer Genome Atlas Program for CRC (TCGA-CRC). Eleven of 174 CRC tissues lacked CDX2 expression. The five-year OS and RFS rates of patients with CDX2-negative CRC were significantly lower than those of CDX2-positive patients. Multivariate analysis of clinicopathological features revealed that CDX2-negative status is an independent marker of poor prognosis in stage II/III CRC. miR-9-5p was shown to regulate CDX2 expression. TCGA-CRC analysis showed that high miR-9-5p expression was significantly associated with poor patient prognosis in stage II/III CRC. In conclusion, CDX2, the post-transcriptional target of microRNA-9-5p, is a useful prognostic biomarker in patients with stage II/III CRC.

Impact of Preoperative Skeletal Muscle Mass and Quality on the Survival of Elderly Patients After Curative Resection of Colorectal Cancer.

Objective: Skeletal muscle loss (sarcopenia) is a prognostic factor in patients undergoing gastrointestinal surgery. However, the influence of muscle quality on prognosis remains unclear. We retrospectively examined preoperative skeletal muscle quantity and quality impact on survival of elderly patients undergoing curative resection of colorectal cancer. Methods: We examined data from 142 patients aged ≥75 years who underwent curative resection of colorectal cancer between 2007 and 2012. We determined the size and quality of skeletal muscles, represented by the psoas muscle mass index (PMI) and intramuscular adipose tissue content (IMAC), respectively, using a preoperative computed tomography image. Overall survival (OS) and relapse-free survival (RFS) rates were determined according to values of PMI, IMAC, and other prognostic factors. Results: OS and RFS rates in patients with low PMI were lower than those in patients with normal PMI. The OS and RFS rates in patients with high IMAC were also lower than those in patients with normal IMAC. PMI and IMAC were independent prognostic factors for OS (hazard ratio [HR], 3.81, and 3.04, respectively); IMAC was an independent factor for RFS (hazard ratio [HR], 3.03). Conclusion: Preoperative sarcopenia, indicating low quality and size of skeletal muscle, predicts mortality after curative resection of colorectal cancer in the elderly.

Effect Modification of Vitamin D Supplementation by Histopathological Characteristics on Survival of Patients with Digestive Tract Cancer: Post Hoc Analysis of the AMATERASU Randomized Clinical Trial.

Some coauthors of this study previously performed the AMATERASU randomized, double-blind, placebo-controlled trial of postoperative oral vitamin D supplementation (2,000 IU/day) in 417 patients with stage I to III digestive tract cancer from the esophagus to the rectum who underwent curative surgery (UMIN000001977). We conducted a post-hoc analysis of the AMATERASU trial to explore the effects of modification of vitamin D supplementation by histopathological characteristics on survival. Among patients with poorly differentiated adenocarcinoma, the 5-year relapse-free survival rate of patients supplemented with vitamin D was 91% compared with 63% in the placebo group (hazard ratio [HR], 0.25; 95% confidence interval [CI], 0.08 to 0.78; P = 0.017; P for interaction = 0.023). Similarly, the 5-year overall survival rate was 92% in the vitamin D group compared with 72% in the placebo group (HR, 0.25; 95%CI, 0.07 to 0.94; P = 0.040; P for interaction = 0.012). In contrast, there were no significant effects in other histopathological characteristics between vitamin D and placebo groups. These findings generated the hypothesis that oral vitamin D supplementation may improve both relapse-free survival and overall survival in a subgroup of patients with poorly differentiated adenocarcinoma.

The impact of posthepatectomy liver failure on long-term survival after hepatectomy for colorectal liver metastasis

BackgroundPostoperative complications affect both the short-term and long-term outcomes. The aim of this study was to identify specific prognostic factors among complications after hepatectomy for colorectal liver metastasis (CRLM). MethodsBetween 2002 and 2014, 427 patients underwent initial hepatectomy for CRLM. The clinicopathological parameters including postoperative complications were evaluated to identify the prognostic factors for the overall (OS) and relapse-free survival (RFS). ResultsOne hundred and forty-nine patients (34%) developed postoperative complications, including surgical site infection (n = 49, 11.4%), bile leakage (n = 41, 9.6%), posthepatectomy liver failure (PHLF) (n = 26, 6.0%), and pulmonary complication (n = 20, 4.6%). The independent predictors of RFS included primary nodal metastasis, abnormal CA19-9 levels, extrahepatic metastasis, bilateral CRLMs, ≥5 CRLMs, preoperative chemotherapy, lack of adjuvant chemotherapy and PHLF. The 5-year RFS rates in patients with and without PHLF were 8% and 32%, respectively (P < 0.001). The independent prognostic factors for OS included primary nodal metastasis, abnormal CA19-9 levels, extrahepatic metastasis, positive surgical margins, preoperative chemotherapy, lack of adjuvant chemotherapy and PHLF. The 5-year OS rates in patients with and without PHLF were 31% and 63%, respectively (P = 0.004). ConclusionsAmong the complications, only PHLF was associated with decreased long-term survival after hepatectomy for CRLM as well as tumor-specific prognostic factors.

Central Nervous System Failure in Korean Breast Cancer Patients with HER2-Enriched Subtype: Korean Radiation Oncology Group 16-15 Multicenter Retrospective Study.

PurposeThe purpose of this study was to evaluate the risk of central nervous system (CNS) failure in Korean patients with human epidermal growth factor receptor 2 (HER2)-enriched breast cancer treated with surgery followed by postoperative radiotherapy (RT).MethodsA total of 749 patients from eight institutions were enrolled in this study. All of them underwent surgery followed by postoperative RT from 2003 to 2011; 246 (32.8%) received neoadjuvant chemotherapy and 649 (81.7%) received adjuvant chemotherapy. Adjuvant trastuzumab was administered to 386 patients (48.6%).ResultsThe median follow-up duration was 84 (range, 8–171) months. The 7-year disease-free and overall survival rates were 79.0% and 84.2%, respectively. On multivariate analysis, mastectomy, nodal involvement, and presence of lymphatic invasion were correlated with poor overall survival (p = 0.004, 0.022, and 0.011, respectively), whereas T stage and lymphatic invasion were associated with disease-free survival (p = 0.018 and 0.005, respectively). Regarding CNS failures, 30 brain metastases, 2 leptomeningeal metastases, and 8 brain and leptomeningeal metastases were noted. The 7-year CNS relapse-free survival rates in patients receiving and not receiving trastuzumab were 91.2% and 96.9%, respectively (p = 0.005). On multivariate analysis, the administration of adjuvant trastuzumab was the only prognostic factor in predicting a higher CNS failure rate (hazard ratio, 2.260; 95% confidence interval, 1.076–4.746; p = 0.031).ConclusionAdjuvant trastuzumab was associated with higher CNS failure rate in Korean patients with HER2-enriched breast cancer. Close monitoring and reasonable approaches such as CNS penetrating HER2 blockades combined with the current standard therapy could contribute to improving intracranial tumor control and quality of life in patients with CNS metastasis from HER2-enriched breast cancer.

Clinical features of poorly differentiated thyroid papillary carcinoma

ObjectiveTo investigate the clinical feature of the poorly differentiated thyroid papillary carcinoma. MethodsWe investigate retrospectively 276 thyroid papillary carcinoma patients who underwent initial treatment at our Department who underwent initial treatment at our Department during the 13-year period from 2000 to 2012. We examine the pathological samples of papillary carcinoma retrospectively to investigate the prevalence of a poorly differentiated component in the tumor. Then the disease-specific survival rate, metastasis-free survival rate, and relapse-free survival rate were compared between patients with or without a poorly differentiated component. In addition, well differentiated carcinoma and poorly differentiated carcinoma were compared in relation to the age, sex, TNM stage, and recurrent laryngeal nerve infiltration. ResultsIt was considered appropriate to define tumors with a poorly differentiated component of 10% or more as poorly differentiated carcinoma. There was a significant difference of the T classification but not the N classification between well and poorly differentiated thyroid papillary carcinomas. The disease-specific survival rate, metastasis-free survival rate, and relapse-free survival rate of patients with poorly differentiated carcinoma was significantly lower than that of patients with well differentiated carcinoma, and we considered that this might be due to the higher frequency of local infiltration in patients with poorly differentiated tumors. ConclusionThe higher relapse rate compared with well differentiated carcinoma suggests that careful postoperative follow-up of patients with poorly differentiated carcinoma is important, particularly surveillance of distant metastasis.

Prognostic value of gross tumor regression and plasma Epstein Barr Virus DNA levels at the end of intensity-modulated radiation therapy in patients with nasopharyngeal carcinoma

PurposeTo assess gross tumor regression and plasma Epstein–Barr virus (EBV)-DNA levels at the end of intensity-modulated radiation therapy (IMRT) and its prognostic impact on patients with nasopharyngeal carcinoma (NPC). Participants and MethodsIn total, 397 patients with non-metastatic, histologically confirmed NPC were retrospectively examined. All patients underwent magnetic resonance imaging of the nasopharynx and neck, and plasma EBV DNA assays before treatment and at the end of IMRT. ResultsThe estimated 5-year loco-regional, local and regional relapse-free survival rates for patients with complete response (CR) and non-CR of the total tumor, primary tumor and metastatic lymph nodes at the end of IMRT were 94.9% vs. 85.8%, 96.6% vs. 87.3%, and 98.7% vs. 89.8%, respectively (P < 0.05). The estimated 5-year loco-regional relapse-free survival (LRRFS) rates for patients with persistent tumor with and without boost irradiation were 95.3% vs. 83%, respectively (P = 0.034). The estimated 5-year overall survival (OS), failure-free survival (FFS) and distant metastasis-free survival (DMFS) rates for patients with negative and positive plasma EBV DNA at the end of IMRT were 83.1% vs. 50.3%, 81.5% vs. 49.3%, and 87.6% vs. 61.5%, respectively (P < 0.001). Multivariate analyses indicated that regression of the total tumor and boost irradiation was an independent predictor of LRRFS, and plasma EBV DNA levels were independent predictors of OS, FFS and DMFS. ConclusionsGross tumor regression and plasma EBV DNA levels at the end of IMRT served as predictors of poor prognosis for patients with NPC. The patients with persistent tumor and/or positive plasma EBV DNA might require timely strengthening treatment.

Initial Experience of Single-port Laparoscopic Multivisceral Resection for Locally Advanced Colon Cancer.

The aim of this study was to evaluate the safety and feasibility of single-port laparoscopic multivisceral resection (SLMVR) for locally advanced colon cancer invading or adhering to neighboring organs. A prospectively collected database was collated of all patients undergoing SLMVR from January 2011 to December 2014. Short-term and long-term oncologic outcomes were evaluated. Thirty consecutive patients who underwent SLMVR were identified and the completion rate was 90%. The R0 resection rate of the primary tumor was 100%. The postoperative complication rate was 23.3%. The 3-year relapse-free survival rates of patients with stage II (n=11) and stage III (n=12) disease were 80.8% and 54.6%, respectively. The 5-year overall survival rates of patients with stage II and stage III disease were 75.8% and 75.0% over a median follow-up of 42 months, respectively. SLMVR for locally advanced colon cancer is safe and feasible in selected patients.

Single-Incision Laparoscopic Colectomy for Colon Cancer: Experiences with 308 Consecutive Cases

Single-incision laparoscopic surgery (SILS) has been developed with the aim to further reduce the invasiveness of conventional laparoscopy. Our experiences with more than 300 consecutive patients with SILS for colon cancer are reviewed, and its outcomes are evaluated to determine the midterm clinical and oncologic safety of SILS for colon cancer in a community hospital. A single surgeon's consecutive experience of SILS for colon cancer is presented. Three hundred and eight patients were treated with the SILS procedure for colon cancer between December 2010 and March 2015. Data were analyzed according to intention to treat. Of these 308 patients, 19 (6.2%) were converted to laparotomy. Intraoperative injury occurred in five patients. Postoperative complications occurred in 19 patients (6.2%). The 2-year relapse-free survival rates of patients with Stage I, Stage II, and Stage III were 97.8, 92.2, and 80.4 per cent, respectively, and the 2-year overall survival rates of patients with Stage I, Stage II, Stage III, and Stage IV were 100, 95.7, 93.0, and 74.4 per cent, respectively. Our initial experiences showed that SILS colectomy for cancer can be performed safely and with good short-term oncologic outcomes by a skilled surgeon.

Progression level of extracapsular spread and tumor budding for cervical lymph node metastasis of OSCC.

The progression level of extracapsular spread (ECS) for cervical lymph node metastasis of oral squamous cell carcinoma (OSCC) was previously divided into three types, and their relationships with the prognosis of patients were re-examined. The Kaplan-Meier method was used to examine overall survival (OS) and relapse-free survival (RFS) curves. Prognosis factor for recurrence was analyzed with univariate and multivariate analysis. ECS was detected in 216 cases of OSCC and analyzed. The 5-year overall survival and RFS rates of patients with type C, which was microscopically defined as tumor invasion to perinodal fat or muscle tissue, were significantly poor at 40.6 and 37.8%, respectively. The results of a univariate analysis suggested that the prognosis of ECS in OSCC patients is associated with its progression level, particularly type C. The 5-year RFS rate of type C with tumor budding was significantly poor at 31.5%. Type C with tumor budding correlated with local and regional recurrence as well as distant metastasis. In a multivariate analysis, tumor budding was identified as an independent prognostic factor. These results suggest that the progression level of ECS and tumor budding are useful prognostic factors in OSCC patients. This study indicated that the progression level and tumor budding of ECS for cervical lymph node metastasis were useful prognostic factors in OSCC patients.

Impact of splenic hilar lymph node metastasis on prognosis in patients with advanced gastric cancer.

Background:Impact of splenic hilar LN dissection during total gastrectomy for proximal advanced gastric cancer is controversial. The objective of this study was to assess the impact on prognosis of splenic hilar lymph node(LN) metastasis compared to that of metastasis to other regional LN groups.Study DesignPatients who underwent total gastrectomy with D2 LN dissection from 2000 to 2010 were reviewed retrospectively. The clinicopathologic characteristics and long-term results of patients with splenic hilar LN metastasis were compared to those of patients with only metastasis to other extraperigastric LNs (stations #8a, #9, #11, or #12a). To investigate the survival benefit of performing splenic hilar LN dissection, the estimated therapeutic index for the procedure was calculated by multiplying the incidence of metastases in the hilar region by the survival rates for individuals with nodal involvement in that region.ResultsOf 602 patients, 87(14.5%) had hilar LN metastasis. The 5-year overall and relapse-free survival rates for patients with hilar LN metastasis were 24.1% and 12.1%, respectively. These rates were similar to those for patients with metastasis to other extraperigastric LNs (P > 0.05), with similar recurrence patterns. Overall survival in the hilar LN metastasis group was better than that for patients with distant metastasis(P < 0.05). The estimated therapeutic index of splenic hilar LN dissection was 3.5, which was similar to index values for LN dissection at other extraperigastric LNs.ConclusionsDissection of splenic hilar LNs during total gastrectomy for advanced gastric cancer allows for a prognosis similar to that achieved with dissection of extraperigastric LNs.

Aberrant methylation of the promoter regions of the SOX7 and p15INK4b genes and Wnt signaling pathway antagonists in patients with acute myeloid leukemias

to investigate the methylation status of the SOX7 and p15NK4b genes and Wnt signaling pathway antagonists in patients with acute myeloid leukemia (AML) in order to assess the association of the rate of aberrant methylation (AM) with the morphological variant and pattern of chromosomal aberrations, as well as the impact of the methylation status on survival. The data of 57 AML patients aged 20 to 79 years were analyzed. The methylation status of the genes was studied by methylation-specific polymerase chain reaction. The signs of the AM of ≥1 gene were detected in 52 (91.2%) of the 57 patients. The most common finding was AM of simultaneously 2 or 3 genes: in 29.8 and 21.1% of the patients, respectively. Concurrent methylation of 3-5 genes proved to be a more frequent finding in AML patients with myelodysplasia: in 7 (70%) of 10 patients. The proportion of patients with methylation of 5 genes was considerably higher in a group of patients with a complex karyotype: 50% versus 8.3% among other patients (odds ratio: 11.0; 95% confidence interval 2.0 to 61.6; p=0.01). There were no differences in the median overall and relapse-free survival rates in patients with a normal karyotype and without FLT3 and NPM mutations, who received induction therapy, in relation to the number of genes with AM. AM of the p15NK4b and SOX7 genes and Wnt signaling pathway antagonists is detected in the majority of patients with AML, which allows hypomethylating agents to be recommended for the treatment of patients who cannot use intensive cytostatic therapy for different reasons. The detection of a large number of genes with the aberrant methylation status in most AML patients with myelodysplasia or a complex karyotype serves as the basis for initiating trials to evaluate the efficiency of a combination of 5-azacytidine and cytostatics.

Long-term prognostic impact of circulating tumour cells in gastric cancer patients.

AIMTo analyse the long-term prognostic impact of circulating tumour cells (CTCs) in gastric cancer patients who underwent surgery.METHODSA 7.5-mL peripheral vein blood sample was obtained from each patient with treatment-negative gastric adenocarcinoma before surgery. OBP-401, a telomerase-specific, replication-selective, oncolytic adenoviral agent carrying the green fluorescent protein gene, was used to label CTCs. Correlations between the number of CTCs and clinical end points were evaluated.RESULTSThe median follow-up period of the surviving patients with gastric cancer was 60 mo. The CTC number tended to increase concomitantly with disease progression. The overall survival of patients with more than five CTCs in 7.5-mL of peripheral blood was lower than that of patients with five or less CTCs, although the difference was not significant (P = 0.183). A significant difference in relapse-free survival was found between patients with more than five and those with five or less CTCs (P = 0.034).CONCLUSIONA lower number of CTCs was correlated with higher relapse-free survival rates in patients. Detection of CTCs using OBP-401 may be useful for predicting prognosis in gastric cancer.

An accelerated hypofractionated radiotherapy regimen in patients after organ-sparing surgery for stages I–IIA breast cancer

Objective: to assess the results of accelerated hypofractionated radiotherapy and to comparatively analyze it with the standard radiotherapy in patients with stages I–IIA breast cancer (BC) after organ-sparing surgery. Materials and methods. A total of 203 patients with stages I–IIA BC underwent radiotherapy after organ-sparing surgery. A control group of 91 patients received the standard radiotherapy (the single focal dose (SFD) was 2 Gy 5 times a week, 25 fractions; the total focal dose (TFD) was 50 Gy for 5 weeks). A study group of 112 patients had accelerated hypofractionated radiotherapy (SFD 3 Gy 5 times a week, 13 fractions; TFD 39 Gy for 2.3 weeks). Results. Local recurrences were not detected in any patient after the hypofractionated radiotherapy regimen and were diagnosed in 3.3 % of the patients after the standard regimen. There were no statistically significant differences between the groups in 5-year overall and relapsefree survival rates. Further observation revealed a statistically significant difference in 6-year overall survival rates in the study and control groups: 99.1 and 70.4 %, respectively (p ≤ 0.046). The 6-year relapse-free survival rates in patients who had received the accelerated hypo-fractionated radiotherapy regimen were also significantly higher than in those who had the standard radiotherapy regimen: 97.9 and 71.3 %, respectively (p ≤ 0.043). The rate of post-radiation normal tissue damages after the hypofractionated radiotherapy regimen was significantly lower (15.2 %) than that after the standard regimen (27.5 %). Good and excellent cosmetic results of treatment were achieved in most (95.1 %) patients and did not differ in their frequency after different radiotherapy regimens. Conclusion. The accelerated hypofractionated radiotherapy regimen showed a high efficiency and a favorable toxicity profile in patients with stages I–IIA BC.

Immunohistochemical Expression and Clinical Significance of Suggested Stem Cell Markers in Hepatocellular Carcinoma.

Background:Increasing evidence has shown that tumor initiation and growth are nourished by a small subpopulation of cancer stem cells (CSCs) within the tumor mass. CSCs are posited to be responsible for tumor maintenance, growth, distant metastasis, and relapse after curative operation. We examined the expression of CSC markers in paraffin-embedded tissue sections of hepatocellular carcinoma (HCC) and correlated the results with clinicopathologic characteristics.Methods:Immunohistochemical staining for the markers believed to be expressed in the CSCs, including epithelial cell adhesion molecule (EpCAM), keratin 19 (K19), CD133, and CD56, was performed in 82 HCC specimens.Results:EpCAM expression was observed in 56% of the HCCs (46/82) and K19 in 6% (5/82). EpCAM expression in HCC significantly correlated with elevated α-fetoprotein level, microvessel invasion of tumor cells, and high histologic grade. In addition, EpCAM expression significantly correlated with K19 expression. The overall survival and relapsefree survival rates in patients with EpCAM-expressing HCC were relatively lower than those in patients with EpCAM-negative HCC. All but two of the 82 HCCs were negative for CD133 and CD56, respectively.Conclusions:Our results suggest that HCCs expressing EpCAM are associated with unfavorable prognostic factors and have a more aggressive clinical course than those not expressing EpCAM. Further, the expression of either CD133 or CD56 in paraffin-embedded HCC tissues appears to be rare.